[Initial stage of cardiac insufficiency as a complication of a past myocardial infarct]. An instrumental and roentgenological examination was conducted in 164 patients who had survived myocardial infarction 1 to 10 years before the examination and having been free of any clinically manifest signs of congestive heart failure. The investigation included a study of the inotropic and pump function of the myocardium of the left ventricle, the electric and mechanical activity of the left atrium, the pulmonary haemodynamics under bicycle tests of growing power, and under identical conditions after premedication with cardiac glycosides (0.00036 mg/kg of body weight of Strophanthin K). Proceeding from the study of the readaptation of the circulation system and its transit to the initial stage of cardiac insufficiency the authors developed criteria of the onset of therapy for latent cardiac failure in patients with postinfarction cardiosclerosis.


[Therapy and prevention of different forms of ventricullar fibrillation in myocardial infarct]. Data on 80 cases of myocardial infarction complicated by different forms of ventricular fibrillation (VF)--primary, secondary and recurrent--are analysed. VF was shown to be accompanied by distinct disorders in respiration, metabolism and haemodynamics. Metabolic disorders are characterized by acid-base and electrolyte balance changes, increased activity of the adrenal glands, and increased release of catecholamines and glucocorticoids into the blood. The latter proves that VF increases the stress reaction of the body caused by acute myocardial infarction. The success of prevention and treatment of VF depends on the early hospitalization of acute myocardial infarction patients in specialized intensive care and resuscitation units where emergency reanimation measures can be taken, controlled therapy rendered, and VF prevented by influencing the altered metabolism and stress state. Special attention is paid to repeated VF for which the authors employ, along with routine therapy, Glucagon that produces an antiarrhythmic and cardiotonic effect.


[Recurrent necrosis as a complication of the subacute period of myocardial infarct]. Recurrent myocardial infarction was observed in 105 among 656 myocardial infarction patients (16.1%). The recurrence developed more often after macro-focal infarction, especially when complicated by cardiogenic shock and/or pulmonary oedema. The clinical pattern of a recurrence was characterized by a significant increase of the incidence of the arrhythmic and gastralgic variants of myocardial infarction. Among those surviving acute myocardial infarction for over 72 hours recurrent necrosis was the leading cause of death in 78%. A faster hospital rehabilitation of the myocardial infarction patients did not result in any increase of the incidence of recurrent myocardial infarction.


[Evaluation of the external respiratory and lesser circulatory function in acute postinfarct cardiac aneurysm]. The function of pulmonary respiration was studied in 28 patients with acute postinfarction aneurysms of the heart, in 20 normal individuals and in 25 patients with transmural myocardial infarction non-complicated by by cardiac aneurysm. A comparative analysis of the obtained data has shown that patients with acute postinfarction aneurysms of the heart have more severe pulmonary respiration disorders than those with transmural myocardial infarctions. The degree of these disorders grows in accordance with the degree of circulation insufficiency. The authors believe the main cause of such pulmonary respiration disorders in cardiac aneurysms to consist in a reduced contractile capacity of the heart muscle with subsequent disturbances in the intracardiac haemodynamics and the development of pulmonary hypertension. The authors recommend to take into account the degree of pulmonary respiration disorders when determining the vital and occupational prognosis, as well as the indications for a surgical management of this complication of myocardial infarction.


[Blood kinin system in acute myocardial infarct treated with thrombolytic preparations]. The treatment of patients with acute myocardial infarction by thrombolytic agents affects several indices characterizing the pathological process. The effect of thrombolytic therapy was studied with reference to the activation of the blood kinin system. The data on a activating effect of myocardial infarction upon the state of the kinin sys tem were proved. When thrombolytic agents (streptoliase, streptase and fibrinolysin) and heparin are given, the kinin system is activated still further which clearly correlates with an elevated fibrinolytic activity of the blood. Under fibrinolytic therapy the most sensitive component of the kinin system proves to be kallikreinogen. The possible effect of the activation of the blood kinin system by thrombolytics upon the state of myocardial infarction patients is discussed.


[Prevalence of ischemic heart disease depending on the extent of manifestation of certain risk factors]. A comparative assessment is presented for the significance of some risk factors (systolic and diastolic pressures, blood serum cholesterol and triglycerides, fasting blood sugar level and blood fibrinogen level) for the spreading of ischaemic heart disease with reference to their severity. When the method of parametric discriminative analysis was used, most of the examined indices displayed a growing extent of ischaemic heart disease from the lower values towards the higher ones, and a decreasing importance of the factor with the growing age. The multidimentional analysis of the spreading of ischaemic heart disease illustrates its increasing spreading along with the accumulation of the amount of some risk factors. These data proved the necessity of a differentiated approach to the study of preventive measures in different age groups with certain risk factors.


[Platelet morphology and physical stress (author's transl)]. The morphology of thrombocytes of 45 volunteers in varying conditions of training was analysed under physical stress. The probands were divided in three groups of 15 each. Group X (aged 20-26 years) had occasional gymnastics training. Group Y (aged 44-52 years) was without any physical training, and Group Z consisted of athletes (aged 22-25 years) in good training condition. By means of the platelet aggregation test (PAT), thrombocyte changes were classified in 5 stages: solitary stage (I), accumulation stage (II), degranulation stage (III), fibrin forming stage (IV), irreversible aggregation stage (V). The probands were subjected to ergometer stress in exact dosage. With the exception of the athletes, all blood smears showed a decrease in stage I (solitary), and considerable increase in stages II-V. 5, 30, or 60 min after stress, the return of irreversible aggregates (PAT V), of platelet changes in the fibrin-forming stage (PAT IV), and in the degranulation stage (PAT III), was markedly delayed in Group Y (untrained older persons) when compared with the group of well-trained athletes. The observation may offer an explanation for some cases of acute thrombotic cardiac death among trained athletes. On the other hand, it may prove the better adaptation of the thrombocytic system during physical stress when athletes are in good physical condition.


[The regulation of serum albumin in physiological and pathological conditions (author's transl)]. 12 g of albumin are synthesized daily by the bound polyribosomes of all human liver cells together, corresponding to 10% of the intravascular albumin mass. The cell is producing a precursor albumin. During secretion albumin is liberated by splitting of a small peptide. Only 40% of the total body albumin is located intravascularly. 12g of albumin are degraded or excreted daily, 30% of it by the liver, the kidneys and the gastrointestinal tract. The main site of albumin catabolism is unknown. Albumin with a half-life of about 20 days is degraded at a constant fractional catabolic rate. The absolute rate of degradation varies depending on the plasma content. This mechanism allows an effective regulation of the serum albumin level. The fractional catabolic rate, however, is not completely fixed. It is slowly reduced if the serum albumin content is markedly reduced as in protein deficiency, the blind loop syndrome, cirrhosis, nephrosis, and diseases of the gastrointestinal tract. Infusion of albumin increases the fractional catabolic rate slowly. This must be taken in consideration substitution albumin in chronic diseases. The shift from the extravascular to the intravascular compartment is a short-term regulatory mechanism. The regulation of synthesis and degradation are independent from each other. The molecular mechanism of regulation of synthesis and degradation are unknown, partially due to inadequate methods.


[The pathogenesis of oral contraceptive hypertension (author's transl)]. Simultaneous administration of estrogen and progestogen accelerates Goldblatt-type hypertension in rats. Neither estrogen nor progestogen alone alters arterial blood pressure. In the hormonal combination the hypertensive effect of estrogen can be replaced by epsilon-amino-capronic acid and the hypertensive effect of progestogen by desoxycorticosterone acetate. Estrogen is the only substance increasing plasma renin activity. There exists no correlation between the increase of the blood pressure and the plasma renin activity in the various groups of experimental animals receiving the different hypertensive preparations. Because of this, oral contraceptive hypertension may be supposed not to result from a stimulation of the renin-angiotensin system but may easily be seen in a combination of endothelial lesions and sodium retention, the former being caused by the estrogen's effect on blood coagulation, the latter produced by the synthetic progestogen.


[Behaviour of plasma renin activity during long-term treatment with propranolol (author's transl)]. 17 patients (40 +/- 9 years) with essential hypertension were included in the study. A monotherapy of 120, 160 or 240 mg propranolol per day was administered orally according to the antihypertensive effect. Four weeks after treatment, blood pressure and heart rate showed a statistically significant decrease and remained unchanged over a period of six months. Plasma renin activity decreased significantly from 5.7 +/- 6.3 ng/ml/h at the beginning of the study to 1.8 +/- 1.3 ng/ml/h after 4 weeks. 5 months later however plasma renin activity increased again to 5.0 +/- 0.9 ng/ml/h. The difference was statistically significant. From 17 patients 7 (41%) had lower levels of plasma renin activity after 6 months treatment when compared with pretreatment  values. In only 3 patients (18%) was plasma renin activity lower after 6 months than after four weeks. We conclude that the increase in plasma renin activity is a reactive mechanism to the reduced blood pressure under long-term conditions. The decrease of plasma renin activity in short-term treatment of essential hypertension is not a mechanism responsible for the antihypertensive effect of propranolol during long-term treatment.


[Effect of bradykinin on muscular glucose uptake in man (author's transl)]. Glucose metabolism of the human forearm was studied in 4 healthy volunteers by monitoring arterial deepvenous glucose concentration differences and by the determination of muscle blood flow, using 133xenon as a tracer, during 25 min intra-brachial-arterial infusion of bradykinin (13.3 ng per min). During the infusion of the kinine the forearms glucose uptake rose continuously from 0.64 +/- 0.11 micronmoles up to 1.68 +/- 0.22 micronmoles per 100 g x min after 25 min of the infusion (p less than 0.005). The enhancement of glucose uptake was partly due to the prompt small acceleration of muscle blood flow and partly to the continuously increasing glucose extraction of the forearm. From these data it is evident that besides insulin there is another physiological agent able to enhance glucose entry into the muscle cell.


[Favourable erythrocyte rheology in patients with glucose-6-phosphate dehydrogenase deficiency (author's transl)]. The rheological properties of erythrocytes of 6 patients with glucose-6-phosphate dehydrogenase deficiency were studied. A method of filtration and measurements of viscosity of erythrocyte suspensions with a hematocrit of 80% were used. The erythrocytes of all patients were more flexible than the erythrocytes of healthy controls. The erythrocytes of the patients passed the polycarbonate filters with a pore diameter of 5 micron more rapidly and showed a lower viscosity of erythrocyte suspensions. The increased flexibility of erythrocytes was due to a lower hemoglobin content which was measured in isolated ghosts. After incubation of the cells with acetylphenylhydrazine, Heinz bodies formed in the erythrocytes of controls. The flexibility of these cells decreased markedly. Though more Heinz bodies were found in the erythrocytes of the patients when the cells were incubated under identical conditions, even these erythrocytes became less rigid than the erythrocytes of controls. From these results we condlude that the more flexible erythrocytes of the patients could pass the splenic sinus even when they contain Heinz bodies. The rheological properties of the erythrocytes explain why splenectomy is not efficient in glucose-6-phosphate dehydrogenase deficiency.


The efficacy of cueing techniques in Broca's aphasia. Twenty Broca's aphasia patients were stimulated with four cues in a picture-naming task. Among the severe aphasics in the group, presentation of a word to be imitated was the most effective cue and presentation of the initial syllable of the word ranked second. Sentence completion and printed word cues were equally effective and ranked third. Mild aphasic patients responded equally well to all four classes of cues. Reliability measures indicated that the order of potency of cues for the severe group was stable over time. Oral apraxia did not appear to contribute significantly to the severity of Broca's aphasia in any of these subjects. Possible explanations are presented for the effectiveness of cues studied.


Judgments of grammaticality by normal and language-disordered children. Fifteen linguistically normal children and 15 linguistically deviant children were presented with three types of agrammatical sentences. The subjects were asked to judge the sentences as right or wrong and to change the sentences judged as wrong, rendering them correct. The three types of agrammatical sentences represented rule violations of syntactic agreement (Type A), lexical restrictions (Type B), and word order (Type C). The two groups of children were compared in terms of the number of sentences of each type that were agrammatical. Those productions which represented the child's correction of agrammatical sentences were subjected to descriptive analyses (percentages) with specific reference to the number of attempted changes and the number of those changes which demonstrated corrections of the specific deviation from well formedness. Results indicated that the two groups of subjects were significantly different in their ability to recognize grammatical errors in sentence Types A and C, but did not differ in their ability to recognize errors in sentence Type B. The descriptive comparison of the groups' verbal corrections reflected this trend, in that the language-disordered subjects made corrections  specific to the error on more of the Type B sentences (for example, "The dog writes the food.") than on Types A (for example, "She will pick some flowers last week.") or C (for example, "Get and come your dinner."1.) Linguistically normal children accurately corrected 90.7% of the sentences judges as agrammatical; this percentage did not vary more than 1% across sentence types.


On facilitating spontaneous talking in young children. Encouraging spontaneous talking in children requires quite different techniques from those used in highly structured language skill training. Data are reviewed demonstrating that certain behaviors commonly used by clinicians may actually decelerate spontaneous talking in the child because they function as constraints on the child's behavior. This dilemma is interpreted in terms of pragmatics, the effects of communication on behavior. On this basis, techniques for encouraging spontaneous talking which emphasize the interpersonal aspects of clinical work with language-delayed children are discussed.


Communicative and cognitive deterioration in dialysis dementia: two case studies. We studied the cognitive and communicative deterioration of two patients who were treated by maintenance dialysis and developed a fatal progressive encephalopathy, "dialysis dementia." Detailed language, speech, and psychological evaluations support the contention that this neurologic syndrome is in fact a dementia. Stuttering and intermittent mutism characterize the disorder and may be valuable in the differentiation of dialysis dementia from other neuropsychiatric syndromes. Some of the speech and language defects are not explicable on the basis of intellectual deterioration and probably represent involvement of the cortical language centers.


Effect on phoneme duration control of three utterance-length conditions in an apractic patient. Phoneme duration control in utterances of various lengths was investigated in one apractic subject. Results indicate a loss of segment duration control and a speeding of intrasyllabic articulatory rates in apraxia. Findings are related to a theory of apractic speech dysfunction.


The assessment of pitch discrimination ability in young children. This study tested the hypothesis that some tasks used in assessing pitch discrimination ability may instead by assessing children's ability to deal with relational language. Five tasks were given to 36 normal children who were equally divided into three age groups, six to six and one-half years, seven to seven and one-half years, and eight to eight and one-half years of age. Task 1 involved a training procedure to assess the children's ability to hear the differences in the pitch of two tones, which were an octave apart. A simple motor response was required. Task 2 assessed the children's ability to label these tones as high or low. Task 3 assessed their ability to compare two tones and label the second as higher or lower than the first. Task 4 examined their ability to label as high or low the position of a man on a ladder. Task 5 examined their ability to compare the positions of two men on two ladders and say whether the second man was higher or lower than the first. Results indicated that children who make pitch discriminations as demonstrated by nearly perfect scores on Task 1 often fail to demonstrate those discriminations on tasks requiring relational language. A comparison of Tasks 2 and 3 to Tasks 4 and 5 suggests that children in the age range studied are less proficient in applying high-low and higher-lower to pitch than to spatial relations.


Aphasia: a divergent semantic interpretation. The present paper reinterprets aphasia relative to the divergent and convergent components of Guilford's model of behavior. It suggests that some aphasiologists have defined aphasia as a convergent semantic disorder. They have determined the presence or absence of an aphasic impairment on the basis of each individual's ability to recognize and reproduce previously learned material and to converge upon  one correct answer. The present analysis also shows that there are a number of theoretical models of aphasia which indicate that aphasia involves more than a convergent semantic impairment. Aphasia, interpreted according to Guilford's model, appears to have a divergent component. Aphasia involves a decrease in an individual's ablilty to provide ideas in situations where a proliferation of ideas on some topic is required, or to extend the boundaries of what he already knows. The individual who is impaired in his ability to produce a number of relevant ideas and a variety of different kinds or categories of responses has a divergent semantic impairment.


Adaptive abilities of hospitalized alcoholics and matched controls. The brain-age quotient. Comparison of alcoholics' and controls' Brain-Age Quotients and performance on various educational and problem-solving variables indicated that the alcoholics were comparable to the controls in verbal ability but were deficient in problem-solving ability.


Defensive style in alcoholics and nonalcoholics. After testing with the Controlled Repression-Sensitization Scale, 38 alcoholics were found to place greater reliance on sensitizing defenses than nonalcoholics. A test of the Defense Mechanism Inventory found no differences between alcoholics and controls.


Treatment termination variables, MMPI scores and frequencies of relapse in alcoholics. MMPI scores failed to predict treatment completion in alcoholics, but successful completion of treatment was related to lower relapse rates.


Describing alcohol consumption. A comparison of three methods and a new approach. The Absolute Alcohol-Quantity-Pattern index, a new method of measuring alcohol consumption, is described and compared with three other measurement systems.


Drinking, driving, and the attribution of responsibility. Among 112 students asked to attribute responsibility in 8 hypothetical traffic accident stuations, the state of alcohol intoxication affected both the degree of responsibility and the magnitude of financial sanctions assessed a potentially responsible driver involved in a road accident.


Three heritable responses to alcohol in a heterogeneous randomly mated mouse strain. Inferences for humans. Alcohol-induced heart-rate change, open-field activity changes and sleeping time were found to be significantly heritable in mice. Heart rate and sleeping time may have parallels in man and mouse in their alcohol responses and genetics.


Pharyngogastrostomy for treatment of severe caustic stricture of the pharynx and esophagus. Four cases of combined pharyngeal and esophageal stricture were managed by pharyngogastrostomy 4 months to 42 years after injury. The stomach was brought up to the neck via the posterior mediastinum after the esophagectomy. A thoracotomy was not used. The results were suprisingly good in 3 patients followed to 3 years. A fourth patient died 6 months after the operation. In those patients benefiting from the operation, regurgitation was minimal when a few precautions were observed. The patients have normal hunger pains and appetite. They are able to eat a full-sized meal. The advantages of stomach compared to colon replacement of the esophagus are discussed.


Topical cardiac hypothermia for myocardial preservation. We compared moderate (29 degrees C.) and profound (5 degrees C.) (ice chips) cardiac hypothermia for myocardial preservation during aortic cross-clamping for 30 or 60 minutes in a canine right heart bypass preparation. Ventricular function deteriorated significantly at 29 degrees C. but not at 5 degrees C. Maximum dp/dt declined only after 60 minutes of ischemia at 29 degrees C., and Vmax decreased after one hour at either temperature. Lactate and pyruvate washout were greater after 29 degrees C., and pyruvate production persisted after 60 minutes of ischemia at 29 degrees C. Reactive hyperemia was greater after 30 minutes of ischemia at 29 degrees C. Reactive hyperemia was greater after 30 minutes of ischemia at 29 degrees C., and total coronary flow remained elevated after 60 minutes of ischemia at 29 degrees C. Coronary flow distribution was not altered by hypothermia. Ultrastructural changes were primarily time dependent and not temperature dependent. Ice-induced subepicardial injury was not evident in the ultrastructure or by flow distribution. Sixty minutes of profound topical cardiac hypothermia is moderately well tolerated by the canine heart, but functional and structural alterations are evident.


Valve replacement in children and adolescents. Replacement of diseased heart valves has become the treatment of choice in many adults. Valve replacement in older children and adolescents has been done in our institution only when other procedures are ineffective. Over the past 10 years, 24 patients have received 28 artificial valves. Thirteen (54 per cent) had rheumatic heart disease; the remainder had congenital or acquired valvular abnormalities. The Björk-Shiley valve was most commonly used in the aortic position and the Beall prosthesis in the mitral position. Sixteen patients (67 per cent) survived operation and have been followed from 3 to 79 months, averaging 27 months. All are free of cardiac symptoms. Hemarthrosis occurred once in 2 survivors (13 per cent). Eight patients died (33 per cent), 5 immediately postoperatively and 3 within a year after the operation. The mortality rate has declined to 21 percent during the past 3 years. Our experience in the pediatric age group suggests that valve replacement is a serious undertaking with higher mortality rate than in adults. The operation should be reserved for those patients in whom valvuloplasty or valvulotomy is expected to be ineffective.


Management of patients with severe, coexistent coronary artery and peripheral vascular disease. The coexistence of severe coronary artery and peripheral vascular lesions is not uncommon. Although diagnostic and sequential therapeutic techniques are standardized, the priority of surgical treatment is unresolved. Eight cases are reported in which simultaneous surgical correction of coronary atherosclerosis and carotid atherosclerosis, abdominal aortic aneurysm, or aortoiliac atherosclerosis was accomplished with success. Two additional cases demonstrate the complications which can occur when coexistent lesions are not corrected simultaneously. The surgical techniques employed are discussed. Because of these results, a further clinical trial seems warranted.


Bronchoplastic procedures for lung cancer. Twenty patients with lung cancer have undergone bronchoplastic procedures September, 1965, to June, 1976 in our hospital. Bronchoplastic procedures are considered to be indicated for early cases of hilar lung cancer rather than for somewhat advanced cases. Endoscopic examination and roentgenograms of the bronchial arteries are needed to delineate resectional lines of bronchus, the former for deciding the mucosal extent and the latter the intrabronchial extent of the tumor. The bronchoplastic procedures we adopted were free from the risks and dangers generally accompanying the operation, and there were no postoperative deaths. For the prevention of postoperative complications, careful attention to suture technique is needed, and postoperative bronchoscopic suction of intrabronchial secretions is absolutely necessary. These procedures assure good quality of life postoperatively and improvement in the survival rate by preserving pulmonary function, enhancing curability, and increasing the operative indications. These advantages warrant high evaluation of the operation.


Cricotracheal disruption owing to strangulation. A report of two cases with successful surgical repair. Two patients with cricotracheal disruption resulting from accidental strangulation of the neck were treated. The first patient had severe respiratory obstruction. In the second patient, a fascial tube maintained airway continuity between the separated larynx and trachea, and she had no difficulty breathing. A preoperative diagnosis of tracheal injury was based on the findings of respiratory obstruction, bloody secretions in the endotracheal tube, and subcutaneous emphysema in the neck. In both cases, an endotracheal tube was easily passed and entered the distal tracheal lumen. This relieved the respiratory obstruction in the first case and allowed administration of general anesthesia and control of ventilation during the operation. Prompt repair with cricotracheal anastomosis was followed by excellent results in both cases.


Lymphedema: results of surgical treatment in 64 patients (1936-1964). Patients with peripheral lymphedema are usually treated without operation. In some, however, operations are required in order to reduce swelling, ensure comfort, and improve function and appearance. Because new surgical approaches are available for the treatment of peripheral lymphedema, we reviewed our previous operative experiences for these conditions at the Mayo Clinic to provide a reference to which the newer procedures may be compared. Sixty-four patients underwent operation for peripheral lymphedema between 1936 and 1964. Follow-up information was obtained on 56 patients. Seventeen patients required three procedures to alleviate the swelling in an extremity. Morphologic aspects of the excised tissue were also evaluated in these cases. Results were considered excellent in 13, good in 22, fair in 8, and poor in 13. Complications of operation consisted primarily of wound infections, hematomas, and necrosis of skin flaps.


Influence of protein content upon the electrolyte composition of lymph and plasma. The concentration of Na+ and Cl' is higher in renal hilar lymph (HL) than in arterial (P) or renal venous plasma or thoracic duct lymph (TDL).  The purpose of the present study was to test the theory that this is the consequence of differences in protein content of lymph and plasma rather than a reflection of renal function.  Samples of P, HL and TDL were obtained from dogs and analysed for Na+, Cl', K+ and Ca++.  The samples were then centrifuged through an ultrafiltration membrane to remove the protein and reanalysed for electrolyte content.  Ca++ concentrations were reduced by 30-40% in the (protein-free) filtrate.  This was attributed to protein binding.  Na+ and Cl' concentrations were raised minimally (2.0 mEq/L and 5.0 mEq/L respectively) in protein-free filtrate of plasma, but not in protein-free filtrate of lymph.  It was concluded that the relative protein concentration in lymph and plasma are not an important influence on Na+ and Cl' concentrations.


Immune complexes (IgG and C3) at the motor end-plate in myasthenia gravis: ultrastructural and light microscopic localization and electrophysiologic correlations. Although there is strong evidence that myasthenia gravis (MG) is caused by an autoimmune reaction to the nicotinic postsynaptic acetylcholine receptor (AChR) protein, immune complexes have never been directly demonstrated at the end-plate by immunocyto-chemistry or immunoelectron microscopy. Staphylococcal protein A (which binds to the Fc region of human IgG subclasses 1, 2, and 4) and rabbit anti-human C3 conjugated with peroxidase were used for the ultrastructural (5 patients) and light microscopic (12 patients) localization of IgG and C3, respectively, at MG end-plates. Both IgG and C3 were localized on segments of the postsynaptic membrance and fragments of degenerating junctional folds in the synaptic space. In nonmyasthenic control patients no immune complexes were evident at the end-plate. As judged by morphometric analysis of electron micrographs, the immune complexes were more abundant in the less severely affected MG patients than in the more severely affected ones. A linear correlation was demonstrated between the length of the postsynaptic membrance binding immune complexes and the amplitude of the miniature end-plate potential. The less intense reaction for immune complexes in the more severely affected MG patients can be attributed to the smaller quantity of AChR remaining at their end-plates. The findings provide unambiguous evidence for a destructive auto-immune reaction involving the postsynaptic membrance in MG. Immunopharmacologic blockade of AChR and IgG-induced modulation of AChR may also contribute to the AChR deficiency at the MG end-plates.


New aspects of aldosterone regulation.

New aspects of aldosterone regulation. Evidence is presented that points to an important role of the COOH-terminal heptapeptide fragment of angiotensin II, (Des-Asp) angiotensin II, in the regulation of aldosterone biosynthesis. In favor of this view are the demonstrations that (1) the heptapeptide is as effective as angiotensin II in stimulating aldosterone secretion, (2) heptapeptide antagonists are potent and specific inhibitors of angiotensin II-induced steroidogenesis, and (3) the heptapeptide can be generated readily in plasma and locally in tissues. The concept of specific adrenal cortical receptors for the heptapeptide also allows a possible explanation for the observation that arterial pressure-angiotensin II-aldosterone inter-relations often are inconsistent.


Aldosterone regulation in essential hypertension: altered adrenal responsiveness to angiotensin II. Adrenal responsiveness to angiotensin II was evaluated in patients with "normal-renin" hypertension. Plasma aldosterone, plasma renin activity, and angiotensin II levels were determined, in the supine and, after 21/2 hours in the upright position, in 70 patients with essential hypertension who were on a diet containing 10 meq of sodium and 100 meq of potassium. The increment of plasma aldosterone between supine and upright positions, divided by the increment in plasma renin activity (deltaPA/deltaPRA), was used as an estimate of adrenal sensitivity to angiotensin II. Fifty-seven patients had deltaPa/deltaPRA ratios within the range observed for a normotensive control population; 13 had low ratios. The low ratios suggested subnormal aldosterone responsiveness to angiotensin II. To further test this hypothesis, angiotensin II was infused into 19 of the 70 patients. In those patients with normal deltaPA/deltaPRA ratios, the plasma aldosterone response was similar to that observed in normotensive controls. On the other hand, in those patients with low ratios, a significant increase in plasma aldosterone levels did not occur even with a dose of angiotensin II 10 times higher than that producing an increase in the normally responsive group. In a separate study, the adrenal response to infused angiotensin II was determined in 12 hypertensive patients who were on a sodium intake of 200 meq. These patients were previously known to have normal renin levels after sodium restriction and upright posture. Under these conditions, the hypertensive patients as a group had a significantly greater plasma aldosterone increment to infused angiotensin II than did sodium-loaded normotensive control subjects. Thus, some patients with normal-renin essential hypertension may have either enhanced or reduced adrenal responsiveness to angiotensin II, depending on the conditions of dietary intake of sodium.


Role of 18-hydroxy-11-deoxycorticosterone and 16 alpha, 18-dihydroxy-11-deoxycorticosterone in hypertension. Excess secretion of 18-hydroxy-11-deoxycorticosterone (18-OH-DOC) occurs in more than 10% of hypertensive patients with suppressed plasma renin activity, but it also is reported to occur in essential hypertension without impairment of the renin system. Preliminary studies measuring plasma 18-OH-DOC by radioimmunoassay support the idea that 18-OH-DOC secretion is elevated in some patients with essential hypertension. Interpretation of these data must take into account endogenous ultradien and circadian variations in plasma 18-OH-DOC, however. 18-OH-DOC serves as a precursor of another steroid secretory product. Conversion of labeled 18-OH-DOC to a new structure, 16alpha, 18-dihydroxy-11-deoxycorticosterone (16alpha, 18-diOH-DOC), was demonstrated to be greatly accelerated by the adrenal tissue in low-renin patients as compared with those with normal adrenal tissue (70 to 80% versus 15% conversion). Hypersecretion of 16alpha, 18-diOH-DOC occurred in each. This steroid exerted no effect on sodium metabolism in adrenalectomized rats or in the toad bladder assay, but it markedly enhanced activity of subthreshold doses of aldosterone in reducing sodium excretion in urine of adrenal-ectomized rats. Because of the unique activity of this steroid, we have concluded that excessive 16alpha, 18-diOH-DOC secretion may be important in the genesis of suppressed renin in some patients with hypertension.


Decision rules for hypertension screening: application in a poor community with endemic hypertension. Data from a hypertension screening project involving 4,272 black residents of a rural southern community were analyzed to determine the effects of a set of admission-decision rules on the case load of a proposed hypertension clinic. Four decision rules were investigated: conjunctive (diastolic high or systolic high); disjunctive (diastolic and/or systolic high); additive (sum of diastolic and systolic high); and systolic only. Most information relevant to admission to treatment came from knowledge of systolic blood pressures, even though knowledge of the diastolic pressure is essential in individual diagnosis. Incremental increases in the minimum blood pressure necessary for admission to treatment from 140/90 mm Hg to 160/95 mm Hg resulted in a one-third reduction in the number of patients treated, a 24% reduction in personnel utilization per patient, and a 34% reduction in drug costs; but in an estimated 14% increase in the attack rate for morbid events in men.


The Charlottesville blood pressure survey: the role of the physician in hypertension case finding. The population of a community of 29,608 adults was screened door-to-door for elevated blood pressure. A questionnaire was administered and analyzed to profile the hypertensive person who is most likely to be unaware of his problem. One hundred and one people with  documented sustained hypertension were "unaware" of their problem. Of these, 58% had a diastolic blood pressure consistently greater than 100 mm Hg. Sixteen per cent of all hypertensive males were unaware of their problem compared to 5% of hypertensive females. Of those less than 35 years old, 38% of males were unaware compared with 4% of females. White (11%) persons were more apt to be unaware than non-white persons (6%). No person with a positive family history of hypertension was unaware. Ninety-one per cent of all unaware hypertensives had a regular physician. Sixty per cent had consulted a physician within 18 months, and 92% had consulted a physician within 60 months of the survey. The screening process was completed on only 21% of all adults in the target community. These data suggest that the young, white, hypertensive male with no family history of hypertension is most likely to be unaware of his problem. Routine measurement of blood pressure by physicians may be more efficient than door-to-door surveys in contacting the unaware hypertensive person.


Foreign medical graduates in rural primary care: the case of western New York State. To determine whether foreign medical graduates (FMGs) provide a disproportionate and increasing share of primary care in some rural areas, changes in physician distribution in a rural section of upstate New York over a 20-year period (1953-1973) were evaluated by country of medical education and type of practice. A contiguous urban area was examined for comparison. In 1953, FMGs accounted for a higher proportion of primary care physicians in rural areas (11%) than in urban practice (6%) (p less than 0.01). By 1973, this distribution had increased to 26% rural and 14% urban (p less than 0.001). During the two decades, the number of U.S. medical graduates in primary care declined by 15% in the rural areas but increased by 13% in the urban center. The number of primary care FMGs in this same period increased 88% in the rural area. With a 10% decline in (rural) FMGs trained in developed countries, this net increase in FMGs was accounted for by physicians from developing countries. Primary care physicians trained in the U.S. or in developed countries increased more in the urban center, while physicians from developing countries increased more in rural (53%) than urban (47%) practices. Finally, by 1973, rural primary care physicians were more likely than urban primary care physicians to be from developing countries (p less than 0.001).


[Prevalence of penumoconiosis in a steel-plant (author's transl)]. Chest X-rays of 483 steel workers employed in the same factory were examined by the authors and classified according to the ILO U/C 1971 classification for pneumoconiosis. The prevalence of pneumoconiosis was found to be 8.4%. The majority of the positive cases were detected among the furnace workers and then among presse and rolling-mill workers. Only one positive case was found among the workers of the other foremen. It is stated that the furnace is the main source of pollution and that the lack of protective systems spreads the risk also to the surrounding working sites. No significant differences were found as for the opacity features.


Exercise-induced bronchospasm-a review.

Exercise-induced bronchospasm-a review. The nature, causes and treatment of exercise-induced bronchospasm (E.I.B.) are reviewed. The condition is common, particularly in children. The spasm affects mainly the large airways; it appears a few minutes after effort, peaks in 10-15 minutes, and commonly resolves spontaneously in 40-60 minutes. The origin is probably multifactorial, with reflex stimulation of tracheal receptors, altered sympathetic neural discharge, prostaglandins and mast-cell sensitization being involved on different occasions. Effective treatments are equally varied, including selective beta agonists, theophylline and cromolyn glycate. For the sports physician, the best current approach seems the use of the Cromolyn drugs about one hour prior to competition.


Factors in delayed muscle soreness.

Factors in delayed muscle soreness. The possible causes of delayed muscle soreness which occur 24 to 48 hr after exercise were examined from three different approaches, each designed to test an existing hypothesis. Surface electromyograms were used to evaluate the muscle spasm theory; the possibility of actual muscle cell damage was monitored by the presence of myoglobinuria, while the ratio of hydroxyproline/creatinine (OHP/Cr) in 24 hr urine collection was used as a marker for connective tissue involvement. In the first study, although all volunteers developed muscle soreness 24 and 48 hr after exercise, no change in the EMG activity of the sore muscles was observed. Myoglobin excretion was found in 88% of the subjects who developed soreness. However, in a second study, 92% of the subject who performed both moderate and heavy exercise but did not develop muscle soreness had myoglobinuria. In contrast, during a third experiment subjects on gelatin-free diets showed an increase (P less than .1) in the OHP/Cr between control (.020+/-.001) and 48 hr post-exercise (.002+/-.001, X+/-SE). Soreness resulted in all cases. When the OHP/Cr value is taken for the day of maximal soreness, the post-exercise mean increases to .024+/-.001 and the level of significance rises (P less than .005). These observations support the concept that exercise induced soreness may be related to disruption of the connective tissue elements in the muscle and/or their attachments.


Muscle strength and fiber composition in athletes and sedentary men. Members of Swedish national teams in track and field events (sprinting and jumping), downhill skiing, race walking, orienteering, and a group of sedentary men were studied to examine the relationship between muslce fiber characteristics in needle biopsy samples form m. vastus lateralis and muscle strength measured as peak torque during isokinectic knee extensions. In comparison with the sedentary group the following differences were found: a) percentage fast twitch fibers was lower in the endurance athetes, b) fast to slow twitch muscle fiber area ratio was higher in the track athletes, c)track athletes and downhill skier attained higher peak torque values at all angular velocities examined. The track athletes had, however, higher torque values at the fastest angular velocity as compared to the downhill skiers, whereas there was no differnce under isometric conditions. The proportion of fast twitch fibers was related to torque produced, especially at high motion velocity. The training also appeared to affect the force-velocity relationship.


Effects of frequency and duration of training on attrition and incidence of injury. Eighty-seven male inmates from a state prison and 70 inmates from a county jail volunteered as subjects. The subjects, age 20 to 35 yrs, were assigned randomly into a control or exercise group. Their Vo2max and treadmill performance values were determined before and after a 20 week jogging program. Training intensity was between 85 and 90 percent of maximum heart rate and involved workouts 3 days/week for 15, 30, or 45-min duration at the state prison and for 30-min 1, 3, or 5 days/week at the country jail. Cardiorespiratory fitness improved in direct proportion to frequency and duration of training. Injury, occurred in 22%, 24% and 54% of the 15, 30, and 45-min duration groups and in 0%, 12%, and 39% of the 1, 3, and 5-day/week groups, respectively. Attrition resulting from injury occurred in 0%, 0%, and 17% and in 0%, 4%, and 6% of the same respective groups. Attrition due to lack of interest was similar for all training groups (25%), but was significantly lower in the control groups (10%). Although the results showed a greater increase in cardiorespiratory fitness for the 45-min duration and 5-day/week groups, these programs are not recommened for beginning joggers because of the significantly greater percent of injuries.


Oxygen cost of running in trained and untrained men and women. The purpose of this study was to compare the oxygen cost of running as it relates to speed of running among the following four groups: trained male distance runners, trained female distance runners, untrained but active men and women. Each subject was given a series of treadmill tests during which Vo2 was measured at submaximal work loads. The linear regression equation was utilized to compute the relationship between Vo2 and running speed for each groups. The results indicated that the rate of increase in Vo2 for a given increase in running speed could be represented as a straight line and was the same for all groups (P greater than .05). The trained male runners had a significantly lower Vo2 (P less than .05) than those of the other three groups at any measured speed. The trained females and untrained males had significantly lower Vo2s than the untrained females (P less than .05) at any of the given range of speeds. No significant differences were observed between the untrained mean and trained women (P greater than .05). It was concluded that there were differences in the oxygen cost of running not only between the trained and untrained groups but also between males and females.


[Frequency transducer for magnetic recording of bioelectrical processes]. In conducting electrophysiological and medical investigations, in registration of bioelectric processes in particular, various types of converters permitting notation of bioelectric signals can be used with an ordinary tape recorder instead of costly magnetic registrators. A frequency converter with whose help it is possible to register bioelectric processes in a frequency range of 0.1 to 10(3) Hz with a conversion error of not more than 1.5 per cent is proposed.


[Cold sterilization of medical wares made of plastic]. To many objects and articles made of polymeric materials the traditional methods of sterilization are inapplicable. This has given rise to the need for devising new methods and means, for sterilization with chemical solutions. Pertinent investigations have ascertained that with the use of the preparation "Desoxon-1" the physico-mechanical properties of polymeric materials remain practically unchanged. With an exposure of 15 min there could be achieved complete sterilization of the study objects made of the cast acrylate material "Dacryl-4", copolymer of ethylene with vinylacetate, of a high-pressure polyethylene, copolymer of styrene, and of other materials.


[Self-contained neurosurgical cryoprobe]. A cryoprobe with an interchangeable container (vessel) holding the cryoprobe has been designed, this enabling it to dispense with the use of hoses to deliver the coolant to and remove it from the Dewar vessel and the vacuum pump. The cryogenic action provided for by a single ampoule lasts 5 minutes. The small diameter of the cryoprobe makes for a minimal traumatization of the surrounding structures, while the absence of connecting hoses makes for its easy handling.


Familial hemochromatosis: characteristics of the precirrhotic stage in a large kindred. Ffty asymptomatic members of a kindred with familial hemochromatosis were studied in an effort to clarify some of the physiologic abnormalities present in the pre-cirrhotic or latent stage of the disease. Using excess hepatic iron as a marker for inheritance of hemochromatosis, results of liver biopsies on 31 family members suggest an auto-somal dominant mode of inheritance with incomplete expressivity. In addition to a relationship between alcohol intake and excess liver iron, there was a strong association between the level of alcohol intake and the presence of hepatic fibrosis in those subjects with excess iron stores. Both serum iron and transferrin saturation were significantly higher in family members with iron overload than in those who were not affected. Only transferrin saturation was significantly correlated with the severity of hepatic iron deposition. Studies of glucose tolerance (OGTT, IVITT, glucose clamp studies) demonstrated a defect in carbohydrate metabolism associated with deficient insulin secretion and insulin resistance, both of which were related to the degree of hepatic iron depostion. In this kindred we have found no evidence for a contribution of inheritance to the carbohydrate intolerance of hemochromatosis. Iron overload was not related to activity of hepatic collagen proline hydroxylase or urinary excretion of peptide-bound hydroxyproline. Serum ferritin, previously thought to be a reliable marker of reticuloendothelial iron stores, was normal in 19 of 20 family members with iron overload.


[Device for determining oxygen tension in biological objects using a pulse method]. An apparatus designed by the authors for measuring oxygen tension in biological objects is described. An electronic commutator allows it to close the inlet of the recording system at the instant of interval, to accomplish separate and smooth adjustment of the pulse and interval duration within a wide range. This makes it possible to electively establish the electrodes polarization and depolarization conditions depending upon the electrochemical characteristics of the electrodes, the nature of the biological object and the purposes of investigations, which represents the advantage of the unit over the other known apparatus.


Systemic capillary leak syndrome and monoclonal IgG gammopathy; studies in a sixth patient and a review of the literature. The clincical and laboratory features of a sixth patient with periodic systemic capillary leak syndrome are reported. During an attack metabolic studies demonstrated a marked shift of plasma (10 to 70%) from the intravascular to the extravascular space resulting in hemoconcentration (highest hematocrit of 82). At the termination of the attack there was a return of the electrolytes, water and proteins to the intravascular compartment. The cardiovascular, renal and endocrine compensation was appropriate to this insult and no underlying abnormalities were demonstrated in these systems. The effector pathways of coagulation, complement, bradykinin generation, prostaglandins and histamine metabolism did not appear to be responsible for the altered capillary permeability. The patient was not missing inhibitors of these same pathways. The only persistently abnormal finding was a monoclonal IgG gammopathy. However, further studies of this paraprotein did not uncover a link between it and the abnormal capillary permeability. Five similar cases are reviewed; at least four and possibly all of these patients also had an IgG paraprotein. Treatment of these attacks was unsuccessful. Attemps to prevent the episodes with a wide variety of therapeutic agents failed. Treatment of the acute attacks with administration of intravenous fluids, did not maintain an adequate intravascular volume and may lead to fluid overload upon return of normal capillary integrity. Pressor agents were of no apparent value and may cause increased cardiac irritability. Although the clinical features and pathophysiology of the capillary leak syndrome have been defined, the etiology remains unknown.


[Mechanized system for planning technological processes]. A mechanized system for the production processes planning involving the use of an electronic code device for data preparation on a punched tape of the "EPECT-IT" type, at the base of which there are classifiers of standard operations and transitions to individual design members, is considered. A fragment of the classifier and a skeleton diagram of the system are presented. It is pointed out that the use of the system helps improve the quality of the design work, as well as to yield considerable economic advantages. The system is in operation at some enterprises of the medical engineering industry.


Metabolic and endocrine studies in a case of lipoatrophic diabetes. A 20-yr-old female with congenital lipoatrophic diabetes was studied, with the following findings: (1) Serum insulin levels increased after both oral glucose and intravenous arginine administration; there was no growth hormone response to the latter. (2) The infusion of insulin (0.1 units and 0.5 units/kg) during the fed state and following at 110-hr fast produced only minimal changes of various fuels measured, with the exception of a decrease in the branched-chain amino acids. (3) There was a minimal production of ketones during the 110-hr fast. (4) Matabolic expenditure was markedly increased during the postabsorptive state (65-75 kcal/hr/sg m); it fell into the normal range during the 110-hr fast (31-35 kcal/hr/sq m). (5) Following meals, the patient experienced complaints ranging from cold and shivering to feeling hot with gross diaphoresis. These findings were associated with intermittent lability of her skin temperature,  which varied 1 degree - 2 degrees F during a 3-hr period. (6) Progressive increases in doses of regular insulin before each meal resulted in up to a total of 9000 units/day being required before normal blood glucose levels were achieved. (7) A 2-wk therapeutic trial of pimozide provided no significant changes in a variety of hormones and fuels in the basal state or following insulin perturbations. (8) A variety of pituitary hormones and pituitary target organ hormones were studied in both the hypothyroid (Hashimoto's thyroiditis) and euthyroid state (following thyroid replacement). All the hormone responses were normal except that growth hormone did not rise during the slow wave sleep in either thyroid state.


[Use of titanium alloys for medical instruments]. On the ground of an analysis into properties of titanium and its alloys the fields of their possible utilization for making various medical instruments are proposed. Because of their insufficient hardness and wear-resistance the titanium alloys cannot be recommended for making medical instruments with thin cutting edges. For the reasons of their insufficient strength, low wear-resistance and substandard modulus of elasticity, it is inexpedient to use titanium alloys in making many types of clamping medical instruments. Nor is it advisable to employ titanium alloys in handles of the instruments, for this may lead to a contact corrosion of their working parts. The use of titanium alloys is recommended for making bone-joining members, retracting medical instruments, of the spatula and speculum types, some kinds of non-magnetic pincers and ultrasonic medical instruments.


Renal effects on serum gastric inhibitory polypeptide (GIP). Fasting and meal-stimulated serum immunoreactive gastric inhibitory polypeptide (GIP) concentrations were measured in normal subjects and in uremic patients undergoing chronic hemodialysis. Mean fasting GIP was higher in the uremic patients (1006 +/- 145 (SE) pg/ml) than in the normal control subjects (132 +/- 31 pg/ml, p less than 0.001). Also, postcibal absolute and incremental serum GIP concentrations between 15 and 180 min were greater (p less than 0.05) in the uremic patients than in the control subjects; in the former they failed to return to fasting levels 180 min after the meal. In a second study, using anesthetized normal dogs, simultaneous renal arterial and venous serum GIP concentrations were measured during an intraduodenal perfusion of glucose. The renal arterial-venous (A-V) GIP gradient became greater as serum arterial GIP concentrations increased. The correlation between renal A-V GIP gradient and renal arterial GIP concentration was quite good (r = 0.85), with a 39% maximum mean A-V reduction in serum GIP concentrations observed across the kidney. This large renal A-V GIP gradient observed under nonsteady conditions suggests that the kidney may be an important site for the removal of GIP from the circulation. Thus, the higher than normal fasting and stimulated serum GIP concentrations observed in uremic patients can be attributed, at least in part, to a loss of the renal extraction mechanism for GIP.


[Machine for washing hospital laboratory vessels]. To improve washing laboratory vessels a selection of effective detergents was made and the technology of washing has been worked out. These data formed a groundwork for the construction of the washing machine, model BII-200, whose pilot unit has passed technical and medical tests and is recommended for batch production. The capacity of the machine with the use of the synthetic detergent "Trias" (per cycle): 252 test tubes, 96 microscope slides, 30 Petri dishes. The duration of the washing cycle is 27 min.


Antibacterial and inducer activities for tetracycline resistance by its derivates and analogues. Antibacterial and inducer activities of thirteen TC derivates were investigated for tetracycline (TC) resistance in staphylococcus aureus. Four compounds of the TC derivatives were not able to induce the resistance to TC in Staphylococcus aureus MS3937 rms7 (TC) + harboring an inducible TC resistance determinant located on a plasmid. The 12a-hydroxy position seems to be essential for the inducer activity.


[Comparative study of the growth parameters of methanotropic bacteria]. Growth parameters and their interrelationship were determined for two mixed and seven pure cultures of methanotrophic bacteria. The specific growth rate, the rate of methane assimilation, and the economic coefficient changed significantly in the course of cultivation of the methanotrophic cultures in the periodic regime, the changes being of the extremem character. Therefore, mean values of the growth parameters of these cultures determined under identical conditions were compared. These parameters were found to be dependent on the taxonomy of the cultures and on the conditions of their growth. No considerable differences had been found in the growth parameters between mixed and pure methanotrophous cultures. Portions of the carbon of methane expended for synthesis of the biomass, carbon dioxide, and exometabolites was different among methanotrophic cultures belonging to different genera.


[Cholesterol-degrading capacity of several strains of Actinomyces lavendulae]. Forty eight strains of Actinomyces lavendulae were studied. Morphological and physiological differences between the strains were found during growth on a liquid glucose-asparagine medium. In short-term experiments, the mycelium of 17 cultures of actinomycetes decomposed over 50% of cholesterol during two hours. The strains with a high activity of cholesterol decomposition (from 0.86 to 1.47-10(-2) conventional units of the specific activity) in short-term experiments were found: 556, 6959, 12348, 6960, 9840, and 10979. Introduction into the medium of such inductors as cholesterol, cortisone, cortisone acetate, and acetate of substance S had different effect on growth of the cells and their cholesterol decomposing ability.


[Effect of humus and microbial inoculates on yield and nitrogen uptake by agricultural plants]. The application of humus had a positive effect on grain and straw yield of paddy and the yield increased with the increasing concentration of humus. The highest dose ((0,05%) corresponding to 1120 kg humus/ha significantly increased the grain and straw yield by 85 and 30 per cent over control. The efficiency of algal inoculation was enhanced in the presence of humus and recorded 41 per cent increase in yield over algae. The nitrogen uptake was also appreciably increased by grain and straw due to humus application. Humus at 0,05 per cent along with algae significantly increased the nitrogen uptake by paddy over algae alone. Root nodulation, growth and yield of gram crop were appreciably increased due to humus application. The grain and straw yield were increased due to humus (0,05%) application showing 32 and 41 per cent increase over control. The efficiency of Rhizobium inoculation was also improved in the presence of humus and the grain and straw yield was significantly increased.


[Bacterial destruction of algal organic matter with glucose formation]. The increase in the number of bacteria, the rate of destruction of organic matter, and the rate of glucose assimilation with analysis according to Wright and Hobbie were determined during 205 days in two bottles containing water from the Rybinsk Reservoir; one of the bottles contained also 25 mg of dry algal cells per one litre. During this period in the control, 39% of the initial amount of the organic matter was destructed (12 mg C per litre), and 4.6% of glucose was formed from this quantity. In the experimental series, 85.6% of the initial amount of the organic matter underwent destruction (from 12.5 mg C per litre), and 48.5% of glucose was formed from this amount.


[Clarifying the systematic position of Actinomyces erythraeus Waksman et Curtis 1916 and its transfer to the genus Proactinomyces]. Cell walls of Actinomyces erythraeus RIA-1387 were found to contain m-diaminopimelic acid, arabinose, and galactose (type IV of cell walls). The mycelium undergoes fragmentation during superficial and submerged growth, and is not susceptible, or only mildly sensitive, to the action of lysozyme. The colonies of Act. erythraeus have no horizontal layers. These data suggest that the organism was erroneously classed as belonging to the Actinomyces genus. It should be transferred to the Proactinomyces genus under the name of Proactinomyces erythraeus (Waksman et Curtis) comb. nov.


[Photosynthetic development of purple sulfur bacteria during illumination with green light]. The photosynthetic purple sulphur bacterium Chr. vinosum grows by assimilating carbon dioxide at the account of the energy of light of different spectral composition. Short wavelengths of physiological radiation, blue and green, the region of carotenoid absorption, as well as white light, are used by the bacterium for assimilation of carbon dioxide, biosynthesis of biomass, protein, and pigments. Therefore, the possibility of utilization of the energy of green light for bacterial photosynthesis was shown for the first time. Blue light is more favourable for growth of the bacterium than green light is, provided the energy (in ergs or incident quanta) is the same. An increase in the intensity both of long and short wavelength radiation activates biomass accumulation and CO2 assimilation. Photosynthetic growth of the bacterium during its illumination with wavelengths of 464, 497, and 535 nm etc. which are similar to the absorption maxima of carotenoid pigments, suggests the participation of the latter in the uptake of energy that is necessary for photosynthesis.


[Ultrastructural changes in the mycelia of Actinomyces hygroscopicus var. var. enhygrus--a proteolytic enzyme producer--during submerged fermentation]. Ultrastructural changes were found to occur in the mycelium of Actinomyces hygroscopicus, strain 33x, which produced an exocellular proteolytic enzyme during submerged fermentation, in both laboratory and semiindustrial conditions (in 100-1 fermenters). In the course of the enzyme accumulation, numerous vacuoles appeared in the hyphae, some hyphae became wider, and the cell walls were more loose. The greatest structural changes were found in the intracytoplasmic membrane systems. The ultrastructural changes of the mycelium are not presumably connected with the accumulation of the enzyme, but are the result of the differentiation of cellular structures during aging of the cells and their transition to the stage of autolysis.


[Frequency of formation of mutants resistant to nystatin in polyploid strains of Candida scottii]. Polyploid strains of Candida scottii differ by their susceptibility to the action of nistatin. Haploid strain is most resistant, diploid strain is less resistant than haploid strain, and triploid strain is more susceptible than diploid strain. UV-treatment resulted in mutants which were 1.5--2 times more resistant to the action of nistatin than parent forms. The frequency of nistatin-resistant mutants increases with the ploidity of the cultures and with the doses of UV-irradiation.


[Influence of carbon sources on the development of Thermus ruber at different temperatures]. The obligate thermophilic bacterium Thermus ruber was found to grow better at 55-65 degrees C on media containing organic acids rather than sugars as a sole source of carbon. In these conditions, the morphology of the cells changes: they are rod-shaped whereas, during growth on lactose which is the best carbon source as compared to other sugars, the cells have the shape of rods in the first hours of growth but later acquire the shape of long threads. Malate and pyruvate are the best carbon sources at 60-65 degrees C of growth; the biomass accumulated in this case is 1.5 times greater than on the medium containing lactose. Apparently, salts of organic acids, being more oxidized substrates as compared to sugars, are easier assimilated by the bacterium at higher temperatures when oxygen solubility in the medium decreases.


[Effect of colchicine and other polyploidogenic factors in contact with the deep vegetative mycelium of the fungus Trichothecium roseum--producer of the antibiotic trichothecin and proteolytic enzymes]. Colchicine, boric acid, and camphor were used to produce viable cultures of Trichothecium roseum actively producing the antibiotic, by treating the submerged vegetative mycelium of the fungus with these compounds. Colchicine (0.5--1.0%), boric acid (0.25--2.00%), and camphor (0.25--1.50%) were added to the nutrient medium before it was inoculated with conidia or vegetative mycelium; later, the submerged mycelium was transferred to slanted agar. The cultures were characterized by a high number of the nuclei in the conidia, a low ratio of the plasma to the nuclei, a high rate of growth, and a high antibiotic activity. In sharply varying conditions of nutrition, such polynuclear forms had an adaptive advantage as compared to the parent forms. The polynuclear cultures are regarded to be biologically equal to polyploid forms.


[Attempt to establish genome similarity between Alcaligenes faecalis and several Gram-negative bacteria using the method of molecular hybridization of DNA to DNA]. The technique of DNA-DNA molecular hybridization was used to demonstrate the absence of genome similarity between Alcaligenes faecalis and gram-negative bacteria belonging to the genera Pseudomonas, Enterobacterium, Comamonas producing alkalis, and vibrions. Some similarity in the polynucleotide sequences was found between the DNA of the reper strain of Alcaligenes faecalis 45 (5--10% of homology) and the DNA of the culture belonging to the Achromobacter genus; therefore, the two genera may belong to one and the same family.


Prosthetic valves 1977: a retrospective analysis and a look to the future. Experimental and clinical studies that we published in 1972 indicated that the ability of man to extend tissue inward from the valve attachment site is limited to few millimeters, and that the cardiovascular wall/valve body spatial relationships are critically important in prevention of thrombotic complications. Since 1972, clinical observations have supported these conclusions. Cloth-covered valve prostheses in man have failed to become completely covered by tissue. The tilting disc valve (Björk-Shiley) has proved to be an advance over the ball design. However, for maximum hydraulic efficiency, the 60 degrees opening of the prosthesis must be augmented by positioning the valve in harmony with the tilt of the annulus into which is implanted. Currently, we are studying the functional significance (gradient and turbulence) of various positional relationships of the opened disc to the tilt of the anatomic valve annulus. Changing the orientation of the Björk-Shiley mitral prosthesis, for instance, can mean a difference in functional opening ranging from 30degrees to 90degrees, and from 45degrees to 75degrees for the aortic valve.


Cigarette smoking in Sydney schoolchildren aged 12 to 13 years: 1971 to 1975. The cigarette smoking prevalence of schoolchildren aged 12 to 13 years in 1975 was compared with that in an age-matched sample interviewed in 1971. Identical methods were used to collect the smoking prevalence data. There was an increase in smoking prevalence over the years 1971 to 1975, with 22-5% of boys smoking one or more cigarettes per week in 1975 compared with 14% in 1971 and with 19-1% of girls smoking this number in 1975 compared with 4-6% in 1971. Alternative strategies to attack the problem of smoking among children are needed.


A method for measuring the mean pressure gradient across prosthetic heart valves under in vitro pulsatile flow conditions. A method is described for measuring the mean pressure gradient that occurs across a prosthetic heart valve over the forward flow phase in a simulated cardiac pumping cycle. The procedure is to simultaneously gate both the pressure signal and a manually controlled reference voltage of opposite polarity. The gated pressure signal is used to charge up a capacitor, while at the same time the gated reference signal is used to remove charge from the capacitor. The reference voltage is equal to the mean value of the pressure gradient voltage when there is zero net voltage on the capacitor. The gating procedure is simple and straightforward. Sample results for the system, which has been used extensively to study valve performance in vitro, are given.


Petrol vendors, capillary blood lead levels and contamination. It was recently claimed in a Tasmanian study that the mean blood lead level of 48 petrol vendors in Hobart, Tasmania, was 32-9 microng/100 ml, compared with 14-3 microng/100 ml for controls, and that seven individuals had blood lead levels above 40 microng/100 ml. In the present study, the blood lead levels of 20 service station workers in Melbourne and 20 controls were determined, both capillary and venous samples being used. The results obtained on capillary samples were similar to those of the Tasmanian study. However, the venous samples gave much lower results; the mean venous blood lead level of the service station workers was 18-2 microng/100 ml and that of the control group was 10-9 microng/100 ml. It was concluded that the blood lead levels obtained in the Tasmanian study were falsely high, because of contamination of the capillary samples, and that the blood lead levels of service station workers in Melbourne are not above the accepted "level of concern".


Biomedical instrumentation in the Soviet Union. By utilizing biomedical instrumentation from other nations, and by designing and fabricating instrumentation in several institutes under the control of the Medical Industries Ministry and the U.S.S.R. Academy of Medical Sciences, the Soviet Union has attempted to a bridge a 20 to 30-year technology gap. The lack of interagency cooperation and sophisticated manufacturing capability, combined with a system not directed to recognizing or exploiting innovation from within, suggests continued dependence on other countries. The Soviet system in these regards serves well as an example of a bureaucracy and system limiting technologic advancement. It is hoped that future actions in this country, in response to the U.S. Food and Drug Administration's direct regulatory control over U.S. medical devices, will not lead to a similar stifling of technology development.


Procaineamide blood levels after administration of a sustained-release preparation. Procaineamide is now available as a sustained-release preparation. This preparation was administered in an eight-hourly regime to 26 patients, and therapeutic blood levels were obtained for the duration of the 56-hour study period in 20 patients. No side effects were observed. Inadequate blood levels may be predicted from a single blood level eight hours after the first dose, which could allow for dosage adjustment.


Heart valve prostheses: who protects our patients, and from what? Phenomenal advances in the development of cardiac valve prostheses have taken place in less than two decades. However, the currently prevailing atmosphere of consumer protectionism in existence 20 years ago probably would have made such developments impossible. Recent passage of the Medical Device Amendments of 1976 (P.L. 94-295) will not only make future development extremely difficult, but also may force the field of cardiac valve replacement back into the era of the 1950s. Regulations implementing  this legislation may be even more disastrous. It is time for someone to protect patients from their so-called protectors.


Cardiothoracic surgery in Australia: future manpower needs. A survey has been made of cardiothoracic surgeons in Australia, and of trainees in the speciality. Analysis of the results suggests that too many surgeons are being trained in this field. Remedial measures are suggested.


The quest for the perfect prosthetic heart valve. Thirty years have elapsed since the introduction of the first artifical heart valves. Since that time, many improvements have been made in the design and fabrication of prosthethic valves, but the perfect valve remains elusive. After experience with clinical implantation of more than 5000 artificial valves of all types, we designed a new prosthesis which we believe incorporates the best features of the earlier models and reflects our concepts of the best configuration of an artificial valve. Thus far we have implanted over 2500 Cooley-Cutter valves and the results have been gratifying. The valve has a full-orifice design with the metallic frame milled from a single block of medical-grade titanium, has a pyrolite occluder in a double-cone configuration, and Teflon sewing rings to conform to the aortic and mitral annuli. A major problem with prostheses made from synthetic materials is the need for prolonged anticoagulation. The incidence of thromboembolic complications with this valve has been very low and excellent late results encourage us to use this prosthesis routinely except in unusual circumstances.


Development of a cardiac valve substitute: the Smeloff-Cutter prosthesis. Several criteria were used for the development of the Smeloff-Cutter prosthesis: (a) the valve must permit adequate pulsatile forward flow with minimal gradients and regurgitation; (b) materials used must be inert or compatible with tissue and blood; (c) the prosthesis must be durable; (d) attachment must be easy and secure; (e) the valve must be nonhemolytic and nonthrombogenic; (f) its geometry must not impinge on surrounding structures; (g) testing must be in vitro as well as in vivo; and (h) its use must result in an acceptable long-term clinical response. Application of these criteria to the design of the Smeloff-Cutter valve is described.


Polyacrylamide gel as a medium for DNA dissociation and reassociation. Several properties of thermal denaturation and renaturation of DNA in polyacrylamide gels were investigated: (1) Following electrophoresis the DNA band was scanned and shown to increase in absorbance with increasing temperature. The increase was proportioned to DNA concentration across the peak. (2) The dependence of the Tm on salt concentration over a hundred fold range was similar to that found for DNA in free solution. (3) Denaturation of several DNA samples ranging in G + C content from 26 to 71% was compared in gels and free solution. The relationship between Tm and % G + C was virtually identical for both sets of DNAs. (4) The kinetics of DNA renaturation in the gel was followed. Reassociation of bacteriophage T4 DNA was 2nd order and proceeded more rapidly in polyacrylamide gels than in free solution.


Digestion of chromatin with deoxyribonuclease II. The action of DNAse II on DNA in chromatin was studied. The formation of acid-soluble products followed a two-phase kinetic curve. At the end of the first more rapid phase about 25% of DNA was degraded. Early in the degradation process DNA was converted into double stranded fragments, whose sizes were multiples of about 180 base pairs. As the degradation proceeded these fragments were reduced in size. After denaturation DNA from digested chromatin was resolved into discrete single stranded fractions, exact multiples of a ten-nucleotide length, forming a pattern very similar to that observed with DNAase I.chkova LV


Isolation and partial purification of ceruloplasmin messenger RNA from rat liver. Partially purified ceruloplasmin mRNA was isolated using indirect immunoprecipitation of rat liver polysomes and poly(U)-Sepharose chromatography of polysomal RNA. This RNA programmed the synthesis of ceruloplasmin polypeptides in a cell-free system from mitochondria. Immunochemical analysis of the translation products revealed a 40-fold enrichment of the ceruloplasmin mRNA activity. The purified ceruloplasmin mRNA migrated as a major homogeneous component with an apparent molecular weight about 1 X 10(6) daltons in polyacrylamide gels containing sodium dodecyl sulfate. The immunoprecipitated products of the cell-free translation had molecular weights in the range 4.5--5.4 X 10(4) daltons as estimated by gel-electrophoresis under denaturating conditions. These values approach the weight of the half-molecule of native ceruloplasmin.


A comparative study on the two classes of heterogeneous nuclear ribonucleoprotein particles separated in metrizamide density gradient, by electrophoresis of proteins and chase experiments. Evidence for two distinct subfractions of HnRNP in mammalian nuclei. Heterogeneous nuclear ribonucleoprotein particles (HnRNP) were separated in metrizamide density gradients, into two fractions migrating to 1.31 g ml-1 and 1.18 g ml-1, respectively. Proteins associated with each of these fractions were analysed by SDS-acrylamide gel electrophoresis. It is shown that the whole proteins extracted from these two metrizamide fractions exhibit clearly different electrophoretic patterns: 1.31 HnRNP particles contain as major polypeptide chains molecules with molecular weights ranging from 40,000 to 65,000, while major polypeptides of 1.18 HnRNP are banding in the 30,000-40,000 molecular weight region of the gels. Both fractions contain numerous other associated polypeptide chains whose molecular weights are above 65,000. A possible kinetic relationship between these two HnRNP classes was investigated in vivo by performing chase experiments. No clear evidence for a precursor-product relationship was found. Implications arising from these structural and kinetic observations, and problems relating to nuclear maturation of pre-messenger RNA, are discussed.


[Effect of increased feeding of oligosaccharides on serum bilirubin levels in newborns (author's transl)]. Previous trials to improve bilirubin elimination in newborns by increased feeding of breastmilk, formula or carbohydrate, especially glucose, gave different if not controversial results. Oligsaccharide solutions with low osmolarity and therefore good compatibility nowadays allow the administration of comparatively high amounts of carbohydrates to term and preterm newborn babies. With this mind a prospective study in 55 newborns, 26 males and 29 females, with birthweights ranging between 1980--3800g, was started. 30 infants got 25% solution of oligosaccharides (DEXTRO neonat), 50 ml/kg and day, during the first 6 days after birth, in addition of normal milk formula. 25 control infants got 5% solution of glucose instead of the oligosaccharide solution. Development of weight (Table 1) and haematokrit (Table 2) of both groups showed (perhaps interesting but) no significant differences. The oligosaccharide  group showed significant elevation of blood glucose at the 2nd and several other days (Table 3), and significant lowering of serum bilirubin at the 4th, 5th and 6th day (Table 4, Fig. 1). Changes of amount or distribution of body water are (see Table 1 and 2) not likely for explanation. Other possible explanations are discussed. Further investigations would be of interest. Prophylactic and therapeutic use in postnatal hyperbilirubinaemia seems possible.


[Pharmacokinetical comparison of glucose and oligosaccharides for oral glucose tolerance test (author's transl)]. Oral loading with 5 to 10% glucose-solution for oral glucose tolerance tests gave reproducable curves of blood sugar levels. The relatively large amount of fluid administered was a factor of disturbance. Stronger solutions of glucose, e.g. 50%, altered the course of the curve and gave a delay of enteral absorption, obviously by osmotic reaction. The 25% Malto-Oligosaccharide-solution DEXTRO O.G-T. was well tolerated, gave well reproducable curves, and is recommended for oral glucose tolerance tests in children.


The pituitary-testicular axis in men with chronic renal failure. We studied the effects of uremia on the pituitary-testicular axis in 35 men with creatinine clearances less than 4 ml per minute per 1.7m(2). We found significant elevation (p less than 0.001) of plasma luteinizing hormone and follicle-stimulating hormone (p less than 0.005) and subnormal levels of testosterone (p less than 0.005). Testicular histology revealed severe spermatogenic damage. Human chorionic gonadotropin produced a subnormal testosterone response. The initial response of plasma luteinizing hormone and follicle-stimulating hormone to luteinizing-hormone-releasing hormone was normal, but their subsequent decline was prolonged. The suppression of plasma luteinizing hormone levels by testosterone propionate was normal, but the nadir occurred late; the elevated plasma luteinizing hormone level was due to reduced metabolic clearnace and increased production. Chronic renal failure interferes with testicular steroid production and spermatogenesis.


Shattuck lecture--The general medical journal: for readers or repositories? General medical journals seek newsworthiness but face obstacles because of their usually slow publication schedules and because of contents that readers find either obscure or contradictory to long held beliefs. In addition, since medical news has become "big news," general medical journals find themselves in competition with both the lay press and the medical giveaways. One effect of the escalating public interest in medical news is that general medical journals that are reliable and have maintained their newsworthiness are increasingly cited. These journals thus eventually transmit research findings to the public as well as to the health-care professions. To help prevent exaggeration and misinterpretation by the lay press and by the public, general medical journals must evaluate submissions in a broader than traditional context. Nevertheless, newsworthiness is an appropiate goal for such journals.


Associations of hepatitis B surface antigenemia with HLA locus B specificities. To test whether HLA histocompatibility phenotypes might be associated with circulating hepatitis B surface antigen (HBsAG), we performed chisquare and Scheffé analyses on findings in 144 renal patients with known HLA types and HBsAg status. A significant relation between locus B HLA type (or types) and HBS antigenemia was demonstrated (P = 0.01, adjusted for dual testing) with positive associations suggested between Bw15, Bw17 and Bw35 types and transient or persistent (or both) antigenemia. The latter associations individually were statistically significant only if multiple testing was disregarded, but the contrast by the Scheffé method between the three implicated specificities and all other specificities was significant, even after adjustment for multiple testing (P less than 0.02). Associations of genetically determined HLA specificities with hepatitis B infection may constitute the basis for previously observed population differences in HBS Ag prevalences, and suggest that susceptibility to hepatitis B infection may be in part genetically determined.


Effect of surveillance on the number of hysterectomies in the province of Saskatchewan. In  1972 the College of Physicians and Surgeons of Saskatchewan appointed a committee to study hysterectomies because the Saskatchewan Department of Health had data showing that the annual number of hysterectomies carried out in the province had increased by 72.1 per cent between 1964 and 1971, whereas the number of women over 15 years of age had increased by 7.6 per cent. The committee compiled a list of indications for hysterectomy. Any hysterectomy carried out for one of these reasons was classified as justified, and the remainder as unjustified. Five hospitals were reviewed in 1970 and a further two in 1973. In 1974, all seven hospitals were reviewed again. In these hospitals, the average proportion of unjustified hysterectomies had dropped from 23.7 per cent at the time of the first review to 7.8 per cent in 1974. The total number of hysterectomies in the province dropped by 32.8 per cent between 1970 and 1974.


Effects of diabetes mellitus on cholesterol metabolism in man. In view of the reported excess prevalence of atherosclerosis and cholelithiasis in diabetes, we investigated several aspects of cholesterol metabolism under metabolic ward conditions in six Pima Indians with maturity-onset diabetes mellitus. Cholesterol balance (13.5 versus 11.0 mg per kilogram per day, P less than 0.05), fecal bile acid excretion (415 versus 261 mg per day, P less than 0.05), bile acid pool size (3150 versus 1950 mg, P less than 0.05), fasting plasma cholesterol (193 versus 160 mg per deciliter, P less than 0.05) and plasma triglycerides (251 versus 150 mg per deciliter, P less than 0.05) were higher during uncontrolled hyperglycemia than during relative euglycemia on insulin. The increased plasma lipid levels and total cholesterol synthesis during hyperglycemia may contribute to the acceleration of atherosclerosis in diabetes mellitus. Gallbladder bile was significantly more saturated with cholesterol (181 per cent versus 114 per cent, P less than 0.05) during insulin treatment than during uncontrolled hyperglycemia. Bile lipid composition was thus more favorable to cholesterol precipitation and gallstone formation during insulin treatment than in the untreated diabetic state.


Nucleotide sequence of bacteriophage phi X174 DNA. A DNA sequence for the genome of bacteriophage phi X174 of approximately 5,375 nucleotides has been determined using the rapid and simple 'plus and minus' method. The sequence identifies many of the features responsible for the production of the proteins of the nine known genes of the organism, including initiation and termination sites for the proteins and RNAs. Two pairs of genes are coded by the same region of DNA using different reading frames.


DNA sequences coding for the H2B histone of Psammechinus miliaris. Starting from restriction enzyme cleavage sites of known topologies the DNA sequences coding for two thirds of the H2B histone protein, together with some 3 inch extracistronic sequences, have been determined for the sea urchin Psammechinus miliaris. This unambiguously identifies this gene and further reveals its 5 inch-3inch polarity and accurate map position in a cloned histone DNA repeat unit.


Is dopamine a neurohormone of the adrenal medulla?  Studies with morphine stimulation. Dopamine (da) concentrations in rat adrenals, plasma and brain were variably elevated 1 h after a large parenteral dose of morphine. In adrenals, unlabelled DA increased 2-fold and labelled DA, synthesized from 3H-tyrosine, increased more than 4-fold. The increases could be prevented by inhibition of DA-synthesizing enzymes and spinal cord transection, respectively. Labelled DA in plasma increased 2.7-fold after morphine in intact rats but did not increase in those with spinal cord transection. It is concluded that: (1) morphine stimulates the adrenal by increasing nerve impulse flow, (2) increased nerve impulse flow increases DA synthesis and levels, and (3) the increased DA levels result in increased release of DA into the bloodstream.


Effects of peripheral and local administration of picrotoxin on the release of newly synthesized 3H-dopamine in the caudate nucleus of the cat. The release of 3H-DA was estimated in superfusates of a superfusion cannula introduced into the caudate nucleus of "encéphale isolé" cats. 3H-DA was continuously formed from L-3,5-3H-tyrosine introduced into the superfusion medium. Injected at the periphery, picrotoxin (2.5 mg/kg, i.p.) markedly enhanced the release of 3H-DA, the effect being particularly pronounced 90 min after the drug injection. The effects of the local introduction of picrotoxin into the substantia nigra and into the caudate nucleus on 3H-DA release were also examined to ensure the specificity of the result. Picrotoxin (10(5) M) added into the superfusing medium of a second superfusion cannula introduced in to the substantia nigra enhanced by 2 to 5 times the release of 3H-DA during the drug application. No effect could be seen when the tip of the superfusion cannula was not exactly localized into the substantia nigra. Although less pronounced, a stimulation of 3H-DA release was also seen when picrotoxin(10(6) M) was added directly into the superfusion medium of the cannula introduced into the caudate nucleus. These results suggest that some gabaergic neurons are involved in the control of DA release by acting on dopaminergic cell bodies or dendrites into the substantia nigra. Other gabaergic neurons may directly or indirectly act on dopaminergic terminals within the caudate nucleus.


Convulsions induced by hyperbaric oxygen: inhibition by phenobarbital, diazepam and baclofen. 1. The anticonvulsive potencies of diazepam, phenobarbital and baclofen against convulsions induced by oxygen under high pressure (OHP), by isoniazid and by strychnine were investigated in mice and rats. 2. The anticonvulsive potency of diazepam was much higher than that of phenobarbital and baclofen against all three types of convulsions. 3. The selective activity of diazepam against isoniazid induced convulsions in rats (dose ratio ED50 phenobarbital/ED50 diazepam: 400) could not be confirmed in mice (dose ratio ED50 phenobarbital/ED50 diazepam: 20-40), where diazepam was equipotent against all three types of convulsions. 4. Baclofen which does not inhibit strychnine induced convulsions was equipotent in inhibiting convulsions evoked by isoniazid and OHP in mice. 5. The results are in agreement with the postulated GABA-inhibitory mechanism of OHP induced convulsions, whereas they make a glycine inhibitory mechanism very unlikely. Although the results do not allow further conclusions about the mode of action of diazepam, a clinical trial of diazepam in OHP-induced convulsions should be considered.


Distribution pharmacokinetics of warfarin in the rat, a non-linear multicompartment model. Preliminary analysis and linear two-compartment solutions of warfarin plasma concentrations recorded in the rat after intravenous bolus injections of 1, 2, 8 and 40 mg/kg of sodium warfarin revealed marked non-linearities. The half-life of total warfarin concentration in the plasma from 1-12h remained unchanged with all the doses used, but that of free warfarin was shorter with 40 mg/kg, possibly as the result of an increase in the binding of the drug to plasma proteins as the high total warfarin concentration decreased. The apparent volume of distribution generally increased with increasing dose, and differed according to the method used for its calculation.  Liver warfarin data could be solved with Langmuir type saturation kinetics, but the saturation phenomena were slight in the concentration range studied. A non-linear multicompartment model was constructed, the physiological spaces of which were plasma, interstitial fluid and tissue. The binding of free warfarin to plasma proteins, interstitial fluid proteins and tissue structures was assumed to occur instantaneously, with saturable binding to plasma and interstitial fluid proteins, and a constant binding to tissues. The fluxes between the free warfarin pools of plasma and interstitial fluid as well as elimination were assumed to be linear. Following parameters were simulated simultaneously, using an analog hybrid computer: two for the above-mentioned fluxes, four for zero time drug mass distribution between plasma and interstitial fluid, and one for tissue binding. According to the best fits, warfarin is preferentially distributed into plasma, interstitial fluid and highly perfused tissues. The solution suggests that non-linearities in the pharmacokinetics of warfarin, a highly plasma protein-bound drug, first occur in plasma and interstitial fluid. Therefore, it is believed that the quantitative non-linear multicompartment approach presented in this paper might be useful in studying the kinetic behaviour of other highly plasma protein-bound drugs, too.


Effects of polymer-linked sulfonylurea derivatives on insulin release. In order to elucidate whether polymerlinked sulfonylurea derivatives may serve as tools to locate the sulfonylurea receptor site, an easily detectable sulfonylurea was synthetized and coupled to cyanogen-bromide activated dextran. The conjugate proved to be unstable and to release sufficient amounts of free agent to explain its insulinotropic activity. Based on these findings previous results claiming that dextran-linked sulfonylureas retain biological activity may be questioned. A stable conjugate was obtained when the acrylyl derivative of the sulfonylurea was co-polymerized with acrylamide. Both a high (greater than 50000) and a low (1500) molecular weight fraction of this conjugate failed to stimulate insulin release from the perfused rat pancreas, questioning the ability of macromolecular conjugates to combine with the sulfonylurea receptor site.


The effect of clonidine on gastric acid secretion in rats and dogs. The effect of clonidine on gastric acid secretion was investigated using rats and dogs. In the stomach lumen perfused rat basal gastric acid secretion was increased by clonidine in the anaesthetized rat but inhibited in the conscious animal. Clonidine also reduced the basal gastric acid secretion in rats with chronic gastric fistula, (ED50 12 microng/kg p.O.). In addition, gastric secretion stimulated by insulin hypoglycaemia was inhibited by clonidine in anaesthetized stomach lumen perfused rats and in conscious dogs with gastric fistula. In the rat gastric secretion stimulated by electrical vagus stimulation was inhibited as well. However, clonidine had no effect on the gastric acid secretion stimulated by carbachol in stomach lumen perfused rats and in dogs with denervated fundic pouch. These results suggest that the inhibition of gastric acid secretion by clonidine probably is due to an inhibition of acetylcholine release at the vagus nerve endings. Additional central gastric antisecretory effects can, however, not be excluded by this study.


Influence of prostaglandins on connective tissue cell growth and function. Prostaglandins (PGs) are synthesized by cultured fibroblasts. PGs regulate specific cellular functions by influencing cyclic nucleotide levels. PGE1 increases cAMP levels, thus enhancing glycosaminoglycan (GAG) synthesis and reducing proliferation. Exogenous cyclic nucleotides, on the other hand, affect PG formation. Glucocorticoids (GCs) decrease cAMP content, GAG synthesis and PG formation in fibroblasts, the latter effect occurring only after prolonged incubations. The decrease in endogenous PG levels causes a sensitization of the cells to exogenous PGE1, thus counteracting the initial inhibitory effect of GCs on cAMP content and GAG synthesis. Cell proliferation shows an inverse relationship to PG-induced changes in cAMP levels.


Participation of prostaglandins in pathogenesis of aspirin-sensitive asthma. Recent evidence suggests that the induction of bronchoconstriction in aspirin-sensitive patients by analgesics is due to the inhibition of PG biosynthesis in their respiratory tract. PGEs might play the main defensive role in the bronchi of aspirin-sensitive asthmatics. Removal of this potent bronchodilator by PG synthetase inhibitors leaves the effects of spasmogens unopposed, and possibly promotes the release of histamine from its stores.


[Transformation of an afferent tactile signal into a motor command in the cat motor cortex]. The activity of 112 units of the cat precruciate motor cortex was studied simultaneously with the performance of a placing reaction of the foreleg to tactile stimulation of its distal parts. The response latency to the tactile stimulation of the foreleg was 30-40 ms for the electromyographic response of m. biceps brachii and 20 +/- 10 ms for the earliest-responses of the motor cortical neurons. The electrical reaction of m. biceps brachii occured 5-10 ms after the termination of the electrical stimulation of the cortex by a puls series (the series duration was 25 ms, the pulse duration 0.2 ms, frequency 400 per s). Two different types of excitatory reactions of the motor cortex units were found: the sensory (s) ones occured at each tactile stimulus and did not depend on the presence or absence of the foreleg motion; the motor (m) type of reactions developed simultaneously with the motor placing reaction of the foreleg only. The minimal latency of cortical m- and s-type discharge was 20 +/- 10 ms. Electrical stimulation (5-25 micronA) through the microelectrode placed in the locus of neuronal activity which increased during active flexion of the foreleg, provoked in 70% of cases the electrical response in m. biceps brachii.