The turnover of mucin glycoprotein in the stomach. It is proposed that the gastric mucosa, during early stages of fasting, accumulates secreted mucin on the luminal surface of the tissue. The accumulated mucin is subsequently released from its adherent state, on precipitation by freshly secreted acid from the stimulated parietal cells, or, as an alternate mechanism, simply by the passage of ingested food. The gastric mucosa on stimulation by ulcerogenic aspirin, on the other hand, responds immediately to the insult by rapid shedding of its adherent mucin, then, within 5 minutes by an almost complete shut-down of respiration and biosynthesis, not only of glycoproteins but also of proteins and nucleic acids. However, oxygen consumption and biosynthesis quickly revive, in an endeavour to restore the mucosal tissue which has survived, with the result that the turnover of intracellular contents is augmented very much more than its normal rapid rate, illustrated in the gastric epithelial cell by Bennett in 1971 and in the non-secreting duodenal columnar cell by Bennett and Leblond (1970). 14C-Fucose was found in the Golgi apparatus, 2 minutes after injection into the animal, while within 20 minutes it had reached the surface membranes before extrusion.


Glycoprotein alterations in human colonic adenocarcinoma. A marked diminution in membrane glycoproteins containing blood group A activity was observed in colonic cancer tissues. This change was associated with a reduction of the enzyme responsible for its biosynthesis and a decreased concentration of N-acetylgalactosamine in the cancer tissues. Glycosidase activities were unchanged. In addition to the changes associated with blood group A, we also found a decrease in sugar content, alterations in other antigens, and changes in the levels of several glycosyltransferases in cancerous tissues.


Dynamic anatomy of the cervical epithelium. The surface epithelium of the cervix undergoes change at many periods during life. The changes are principally due to the occurrence of metaplastic squamous epithelium within the transformation zone. This process seems to hold the key to an understanding of the origins of neoplastic development in the cervix. Cervical mucus secretion also seems to be dramatically influenced by this process.


Neurophysiology of movement disorders.

Neurophysiology of movement disorders. The relation of the cortex, cerebellum, and basal ganglia and their participation in movement disorders is presented. Studies have shown that lesions to the cortex will produce contralateral paralysis while damage to the basal ganglia or cerebellum will result in movement abnormalities. These data provide support for the view that subcortical but not cortical structures initiate the control movement activity. It would appear that the basal ganglia and cerebellum receive signals from the auditory, visual, and somatosensory cortex integrate this information, and relay signals back to the motor cortex, which in turn sends out efferent fibers to the motor neurons of the spinal cord. The electronic and neurophysiological basis of the somatosensory evoked responses (SER) test following peripheral nerve stimulation and sensory recording in human cortex is given. Control values of SER peak to peak latency waveforms from 66 normal volunteers show the practicality of this test. Preliminary results using SER in patients are discussed from clinical case reports. The subjects had mild to marked movement disorders secondary to Parkinson's disease, vascular occlusion, multiple sclerosis, and spino-cerebellar degeneration. The potential of the SER as a clinical and experimental tool in evaluating movement abnormalities and other neuropathological conditions is presented.


The on-off effect in Parkinson's disease treated with levodopa with remarks concerning the effect of sleep. The "On-Off Effect" in levodopa treated Parkinson's disease began in a few patients during the first year of treatment. The number of patients suffering from this phenomenon increased rapidly the first three or four years with some continuing increase throughout the six years of the study. Even those whose disease had worsened would become even more incapacitated during parts of each day. One group of patients experienced their initial "On" effect upon arising at their usual hour of awakening. This would last for 1 to 3 hours and was their best time of day.


Adenylate cyclase from various dopaminergic areas of the brain and the action of loxapine. The present report is a comparative study of adenylate cyclase activity in various areas of the brain identified as dopaminergic. Low levels of dopamine were found to stimulate adenylate cyclase from the striatum, median eminence, olfactory tubercle, nucleus accumbens and amygdala. Apomorphine, known to mimic the pharmacological and physiological effects of dopamine, stimulated adenylate cyclase from these areas. Several different classes of drugs effective in the treatment of schizophrenia were potent inhibitors of the stimulation by dopamine of the enzyme from these various regions. The drugs studied included representatives of the phenothiazine, butyrophenone, dibenzodiazepine and dibenzoxazepine classes. The inhibition by the dibenzoxazepine, loxapine, which is structurally very similar to the dibenzodiazepine, clozapine, was competitive with respect to dopamine. The calculated inhibition constant (Ki) for loxapine of about 15 nM was similar to that observed for some of the more potent phenothiazines. The results, considered together with previously published data, support the possibility that the therapeutic effects as well as the extrapyramidal and endocrinological side effects, of these antipsychotic agents may be attributable to their ability to block the activation of adenylate cyclase in various select areas of the brain.


Pharmacopsychiatry and iatrogenic Parkinsonism. Through the study of the pharmacological and clinical actions of chlozapine, a new drug used in psychiatry, we are questioning one of the traditional statements on the therapeutic action of antipsychotics: the affirmation that those must have, concomitantly, antipsychotic action and intense extrapyramidal effects (drug-induced parkinsonism). Combining our own investigations and those of other authors, the generally accepted concepts on the possible biochemical mechanisms involved in the etiology of endogenous psychosis are criticized. Although there is evidence of alterations of the dopaminergic system in schizophrenia and also changes due to the action of neuroleptics, we cannot reject, given the dissociation of effects obtained with chlozapine, the possibility that the repercussion on the nigrostriatal dopaminergic system be only one of the many probably mechanisms of action of psychotropic drugs. Thus, such anatomical and neurochemical systems could be involved only in a secondary manner in the biochemical alterations typical of schizophrenia.


The Parkinsonian syndrome and its dopamine correlates. The urinary excretion of free dopamine in 37 untreated parkinsonian patients correlated negatively with the severity of rigidity and akinesia (p less than 0.025) and with total neurologic deficit (p less than 0.05). In a parallel study of psychiatric patients, those with the lowest levels of urinary free dopamine before treatment were the most vulnerable to, and developed the most severe, secondary parkinsonian rigidity (p less than 0.005), akinesia (p less than 0.05), and total deficit (p less than 0.01) when they were subsequently treated for two weeks with trifluoperazine. In neither study was there a significant correlation between free urinary dopamine and tremor. These studies directly associate the level of free dopamine in the urine with the severity of the parkinsonian syndrome. Therefore, although many peripheral sources contribute to urinary free dopamine, a small decrease in the level may actually reflect the severity of the disturbance of central dopamine metabolism and the known deficiency of dopamine in the neurons of the parkinsonian brain.


CNS compensation to dopamine neuron loss in Parkinson's disease. Postmortem studies in brains from parkinsonian patients consistently reveal a minimum loss of 75% of the nigrostriatal dopamine neurons. This indicates that over a prolonged period, before Parkinson's disease is clinically evident, there is a physiological compensation for the slow loss of dopamine neurons (i.e. compensated stage of Parkinson's disease). Only when the dopamine neuron loss is sufficiently severe (greater than 75% of nigrostriatal dopamine neurons) does the disease become clinically evident (decompensated state). Postmortem examination of Parkinson's disease brains and study of animal models indicate that the following mechanisms may contribute to this CNS compensation: 1) A decrease in striatal cholinergic activity, in an attempt to maintain a critical DA:ACh balance; and 2) A decrease in activity of GABA neurons in the striatum and substantia nigra, resulting in an increased firing rate of nigral dopamine cells. These mechanisms allow the brain to readjust to the initial dopamine cell loss in Parkinson's disease.


Brain dopamine turnover and the relief of parkinsonism. Levodopa alone or combined with a decarboxylase inhibitor elevated the concentration of homovanillic acid (HVA) in the cerebrospinal fluid (CSF). This increase correlated significantly with the dose of the drug but not with the clinical improvement, although some correlations with clinical side effects were evident. Nevertheless, the concentrations of HVA in the CSF during combined treatment were considerably lower than with therapeutically equivalent doses of levodopa alone. Obviously, a part of the HVA found in the CSF during levodopa treatment originates from the capillary walls. Treatment with dopamine receptor agonists, Piribedil or Bromocriptine decreased significantly both the basal level and probenecid- induced accumulations of HVA and CSF. But there were no changes in concentrations of 5-hydroxyindoleacetic acid (5-HIAA). Correlation analyses showed that patients who improved with both dopamine agonists used had significantly lower probenecid response of HVA in the CSF and less severe disease than those without beneficial effect. This relationship between dopamine receptor activation and improvement of parkinsonian disability suggests that the therapeutic efficacy of dopamine receptor agonists depends on the functional capacity of brain dopaminergic mechanisms.


Postmenopausal Parkinsonism: brain iron overload? Records of 11 postmenopausal parkinsonism patients were evaluated in comparison with those of 11 postmenopausal depression patients. None had a history of encephalitis, stroke, drug-induced or toxic extrapyramidal disorders, or active bleeding within six months before admission. There was no significant differences between the two groups with regard to time interval from menopause to onset of symptoms, height, weight, or age at first admission. Both groups showed normal height, hemoglobin, hematocrit, and erythrocyte counts. Parkinsonism patients were underweight and had a shorter interval from menopause to onset of symptoms (12.4 +/- 1.9 vs. 16.8 +/- 2.5 yr.). These findings are compatible with the hypothesis that in parkinsonism, hereditary predisposition to positive body iron balance may be associated with alteration of the blood-brain barrier in parkinsonism.


Failure of L-dopa to relieve activated rigidity in Parkinson's disease. Rigidity in Parkinson patients can be easily quantitated by determining net work required to passively flex and extend the forearm through an arc of 100 degrees. Rigidity thus measured can be subdivided into two very distinct types, resting and activated. Resting rigidity, measured while the patient is relaxed, responds to all effective therapeutic agents and correlates closely to degree of clinical improvement. Activated rigidity, measured during voluntary activity, is not relieved by any presently available medical treatment. It remains unchanged at pre-therapy levels even in patients who may temporarily appear to have dramatic improvement in clinical symptomatology. Longitudinal measurements made in hundreds of parkinson patients over intervals ranging from 5 to 15 years show continuing high levels of activated rigidity through the entire period of study. In marked contrast to our wide experience with parkinson patients is a single, well documented case of Wilson's disease who appears to have recovered completely both by clinical examination and by all of our machine measurements. This patient had high levels of extrapyramidal deficit, repeatedly measured over a period of four months when penicillamine therapy was being investigated. He then suddenly reverted to normal and returned to full time employment. High values of resting rigidity activated rigidity, akinesia and resting tremor all reverted to normal and have remained normal for the past 6 years. The implication of this study is that L-dopa and related treatments only mask the symptomatology of Parkinson's disease and are not retarding the underlying pathological process. Penicillamine, on the other hand, probably does relieve the destructive process in Wilson's disease and may in early cases, permanently relieve the extrapyramidal dysfunction.


New orally effective chromosome derivatives for the treatment of asthma. Two new chromone derivatives have been identified which possess oral anti-allergic activity in the rat PCA model of immediate hypersensitivity. They may have a wider spectrum of anti-allergic activity than disodium cromoglycate (SCG) since they are effective in in vitro tests involving sensitized basophils, in which SCG is inactive. Both compounds, when given orally, provide relief from experimental and clinical asthma in man.


The effect of bovine serum albumin on the in vitro inhibition of chemotaxis by anti-inflammatory agents. The anti-inflammatory agents, phenylbutazone, naproxen and niflumic acid inhibited in vitro rabbit peritoneal neutrophil chemotactic responsiveness to Escherichia coli derived chemotactic factor/s when added to cells suspended in 0.1% bovine serum albumin (BSA). Inhibition of chemotaxis by these drugs was markedly diminished as the BSA concentration was increased to 2%. Experiments with phenylbutazone demonstrated that inhibition of chemotaxis could be observed using neutrophils suspended in 2% BSA by either increasing the drug concentration or by preincubating the cells suspended in 0.1% with the drug prior to the addition of the additional BSA. These data suggest that protein binding can prevent in vitro inhibition of neutrophil chemotaxis by anti-inflammatory agents.


Prostaglandins and leucocyte migration in inflammatory reactions. The effects of a variety of particulate irritants on the prostaglandin content, protein concentration and the leucocyte counts in the exudate of implanted inert sponges and on the development of paw oedema in the rat have been studied. Variations in prostaglandin accumulation and leucocyte migration were not related but irritants causing a long-standing paw oedema increased both parameters.


The effect of drugs in established rabbit monoarticular arthritis. Established antigen-induced arthritis was produced in 264 out of 339 sensitized Old English rabbits 4-6 weeks after a single intra-articular injection of ovalbumin into one knee joint. Positive arthritis was diagnosed when the joint swelling at this time was greater than or equal to 2 mm. A positive correlation between established joint swelling and delayed hypersensitivity to ovalbumin injected intradermally 24 h prior to joint challenge was demonstrated. Groups of 5-10 arthritic rabbits were dosed orally with increasing or fixed doses of a range of drugs for a period of 3-7 weeks. Drug activity was measured on joint swelling intermittently during the test and on joint macroscopy, cell content of the synovial fluid and joint histopathology at the end of the experiment. Prednisolone sodium phosphate and ketoprofen were the most active compounds tested. Chloroquine diphosphate, cyclo phosphamide, indomethacin, naproxen, SKF 36914 and sudoxicam had some activity, while aspirin, levamisole, oxisuran and D(-)penicillamine had little or no activity.


Inhibition of arachidonic acid induced mortality in rabbits with several non-steroidal anti-inflammatory agents. The intravenous administration of arachidonic acid to rabbits is an effective in vivo model for evaluating potential anti-thrombotic drugs. Most of the non-steroidal anti-inflammatory agents (NSAIFA) inhibit this arachidonic acid induced mortality (except sodium salicylate and acetaminophen). However, there is a lack of correlation between the relative potencies from various assays (rabbit anti-thrombotic, anti-inflammatory, alalgesic, ulcerogenic and inhibition of prostaglandin synthetase evaluations). These studies imply other actions with NSAIFA than an effect solely on the prostaglandin biosynthetic pathway.


Further studies on the anti-inflammatory effect of insulin. Experiments performed on rats showed that insulin, when applied i.v. or s.c., inhibited the foot edema induced by carrageenin, thermic effect of 45.7 degrees C, compound 48/80 and 5-HT, but moderately increased the paw swelling evoked by kallikrein, a kinin-forming enzyme. The increased vascular permeability elicited by intradermal injection of histamine, 5-HT, bradykinin, PGE1, carrageenin and compound 48/80 was also suppressed. The anti-inflammatory effect was not significantly altered by propranolol and adrenalectomy on the thermal and carrageenin edema, it was variably inhibited on the skin test, and was completely abolished on the paw swelling induced by 5-HT and compound 48/80. Since insulin had little or no effect on the vascular response when given topically together with the vasoactive agents, its complex effect on the acute inflammation appears to be brought about via indirect mechanisms.


Polycystic kidney disease.

Polycystic kidney disease. This autosomal dominant disorder usually appears in middle life. The most common findings are proteinuria, abdominal pain and palpable kidneys, followed by hematuria, hypertension, pyuria, uremia and calculi. In 15% of patients, death is due to cerebral aneurysm. Family counseling and the detection of "at risk" family members are important elements of management. Statistically, half of the offspring of one affected parent will have the disease.


Performance of the piezoelectric microbalance respirable aerosol sensor. A battery-portable respirable aerosol sensor has been experimentally evaluated. Calibration procedures are described. For instruments calibrated with welding smoke, test results show agreement within +/- 15% of parallel filter samples for 10 laboratory and industrial aerosols including welding and tobacco smoke, oil mist, cotton and asbestos mill dusts, powdered metal and walnut shell dusts, and atmospheric urban aerosol in the 0.05-5.5 mg/m3 range. Results show that an average of several piezobalance measurements can accurately simulate a time-integrated filter sample in many industrial environments.


Results of a two year chronic toxicity study with hexachlorobutadiene in rats. Lifetime ingestion by rats of 0.2 mg/kg/day of hexachlorobutadiene caused no discernible ill effects. Slight degrees of primarily renal toxicity occurred with 2 mg/kg/day; 20 mg/kg/day caused multiple toxic effects, including renal tubular neoplasms.


Thermal and mechanical properties of aluminized fabrics for use in ferrous metal handling operations. Protective garments are normally worn in molten handling operations to provide some protection against molten metal splashes. These garments are also intended to provide protection against radiant heat, and they should be as heat resistant and comfortable as possible. Asbestos-based fabrics have been employed for many years, but recently some concern has been expressed over possible asbestos exposure. This program was undertaken to explore the ability of several types of fabrics to resist heat transfer during molten metal impact. A molten metal splash test, along with standard methods for determining tensile strength, flame resistance, and abrasion-flexing resistance were used to evaluate several classes of protective fabrics. The results indicate that there are materials available that offer equal or better mechanical properties and thermal protection compared to aluminized asbestos.


Application of occupational exposure limits to unusual work schedules. A one-compartment exponential models is described which predicts "equal protection", based on biological uptake rates, for unusual air contaminant exposure situations as compared to a "normal" exposure of five 8-hour days per week. This is done by equating peak body burdens resulting from a normal and an unusual exposure, in terms of an adjustment factor applied to the normal exposure limit for an air contaminant. This factor predicts the highest allowable concentration in an unusual exposure situation which will not result in a higher-than normal body accumulation of the inhaled substance. Graphs and formulae are provided for determining adjustment factors for anticipated unusual exposure schedules. The model's predictions and published data are compared.


Ergonomic principles basic to hand tool design. A survey of those features of hand tools relevant to the physical interaction between the implement and the human operator. Concepts basics to the optimization of forces are mentioned, followed by a description of some of the more common physiological problems and musculoskeletal complaints associated with improper hand tool and design and usage. An account of the distribution of contact pressures and possible consequences, if these are excessive, is followed by a description of the role of working gloves as related to ergonomic problems and their possible relationships to occupational diseases of the hand and wrist. Some aspects of anatomy and anthropometry pertinent to the optimization of posture, motion patterns and tool size precede a list of desirable features for power tools. A glossary is included as an aid to the reader. The concepts and situations described are applicable to the design and use of the vast majority of hand tools.


A new method for monitoring personal exposure to ethylene oxide in the occupational environment. A novel method for monitoring occupational exposure to ethylene oxide was developed. Ethylene oxide was collected on Columbia JXC activated carbon, desorbed with carbon disulfide, and analyzed by gas chromatography using a TERGITOL TMN or UCON LB55OX column. Several parameters such as selection of adsorbent and column; effects of humidity, sampling rate and volume; shelf-life; interference from ten contaminants; desorption technique and calibration curve were investigated. The lower detection limit of the method is 0.15 ppm in ten liters of air. The method was evaluated statistically and by conducting a round-robin interlaboratory study.


A method for evaluating the biomechanical stresses resulting from manual materials handling jobs. Manual materials handling tasks are inherent to many different jobs in industry today. The performance of such tasks exposes the worker to a variety of biomechanical hazards. This paper proposes a formalized algorithm for evaluating such hazards, and demonstrates the use of the algorithm in four different jobs. Medical data from these jobs are presented which serve to confirm the types of biomechanical stresses quantified by the biomechanical evaluations.


Noise generation in pneumatic blow-off guns. An efficiency rating system is presented to aid in the selection of hand held air guns, nozzles, and ejectors. This guide is based on noise levels, force or thrust, and air supply pressure. In addition, air consumption, blocked static air pressure, noise directivity patterns and spectra are presented. Finally, noise control techniques in the use and installation of nozzles and ejectors are reviewed.


Evaluation of Federal man tests for self-contained breathing apparatus. The transient pulmonary responses to four short duration man tests used in the Federal approval of breathing apparatus were measured. The pulmonary ventilation dropped 30 percent in the first thirty seconds in the periods assigned for samples and readings which were immediately preceded by work. A physiological deficit was incurred during the short duration man tests which meant that less O2 and ventilation were required when compared to steady state responses shown on approval tests. The scheduled man test activities for short duration breathing apparatus should be revised and made more vigorous to match the intended use of escape apparatus.


Respiratory effects of exposure to ozone plus sulfur dioxide in Southern Californians and Eastern Canadians. Volunteer subjects were exposed in an environmentally controlled chamber in Los Angeles to SO2 and O3, separately and in combination, to study the enhanced toxicity of the O3 + SO2 mixture observed in a previous study in Montreal. Toxic responses to O3 + SO2 were less severe than observed previously, and only slightly more severe than with O3 alone. Sulfur-containing aerosols formed by chemical reactions within the chamber air may have contributed to the O3 + SO2 responses in the Montreal study. Adaptation of Los Angeles residents to ambient O3 may also contribute to response variability.


Use of detector tubes under extreme conditions (humidity, pressure, temperature). Detector tubes are mainly used in a temperature range between 0 degrees C and 40 degrees. At lower temperatures systematic minus indications may occur, high temperatures cause plus indications. By utilizing simple warming-up methods or cooling devices the temperature of the gas to be tested can be adjusted to a temperature which which is suitable for detector tubes. Humidity often influences chemical reagents. In detector tubes this interfering effect can be eliminated by special drying preparations. The reading of most of the detector tubes is directly proportional to the absolute air pressure. Pressure correction can be done easily by the gas law.


An industrial hygiene calibration manifold. The industrial hygiene calibration manifold provides a continuous, stable, dynamic, reproducible vapor sample in the concentration range of fractional to thousands of parts per million. The principle of operation is the gravimetric determination of the sample diffusion or permeation rate and the measurement of total volumetric flow. The manifold consists of the following components: an organic-free air system, vapor jacketed diffusion-permeation chamber, jacketed multicomponent Venturi-type mixing manifold, exponential dilution flask and jacketed sampling manifold. This manifold can be used to validate or calibrate various industrial hygiene analyses such as charcoal and detector tube technology, impinger techniques, respirator cartridge testing, and various survey instruments.


Acute myocardial infarction with normal and near normal coronary arteries. Documentation with coronary arteriography within 12 1/2 hours of the onset of symptoms in two cases (three episodes). Three instances (in two patients) of acute myocardial infarction associated with arteriographically normal or near normal coronary arteries are reported. One patient with a lateral infarction had a normal coronary arteriogram and hypokinesia of the lateral wall. Another patient had two infarctions: (1) a transmural inferior-lateral infarction associated with occlusion of the most distal segment of the posterior descending branch of the right coronary artery, and (2) a transmural anterior-lateral-superior infarction associated with occlusion of the most distal segment of the left anterior descending coronary artery. Neither occlusion was consistent with the extent of infarction. Although coronary arteriography was performed as early as 12 1/2, 3 3/4 and 11 2/3 hours, respectively, after the onset of symptoms of infarction in these three instances, the pathophysiologic features of the infarctions are obscure. Temporary occlusion of an epicardial coronary artery by spasm or platelet aggregates, or both, is suggested as a possible mechanism of the acute event.


Left ventricular hemodynamics and function in acute myocardial infarction: studies during the acute phase, convalescence and late recovery. The left ventricular hemodynamics of 70 patients with acute myocardial infarction were determined from measurements of pulmonary arterial end-diastolic pressure, cardiac index, mean arterial pressure and heart rate during the acute phase(first study, 5 hours after admission), 4 to 6 weeks later (second study, during convalescence) and in 35 percent of all subjects 6 to 12 months after the acute infarction (third study). Serial analysis of serum creatine kinase was carried out during the acute phase. The peak CK value normalized for body surface area was used as a rough index of the extent of the acute myocardial necrosis. The condition of all survivors of the acute stage improved. Patients with only slightly reduced left ventricular performance during the acute stage recovered to nearly normal during convalescence. The condition of patients with greatly reduced left ventricular function also improved but remained impaired during convalescence. In all patients the main changes in left ventricular hemodynamics occurred within the first 4 to 6 weeks; there was almost no further alteration during the following 9 months.


Influence of excitability on the ventricular fibrillation threshold in dogs. The influence of the excitability threshold on the ventricular fibrillation threshold was studied in dogs during myocardial ischemia and potassium and aprindine infusion. Interventions that influenced excitability threshold were associated with similar changes in ventricular fibrillation threshold although the percent change in both values differed. Although it is possible that the interventions studied caused parallel but independent changes in excitability threshold and ventricular fibrillation threshold, it is likely that the excitability threshold influences the ventricular fibrillation threshold. An increase in excitability threshold could result in an increase in ventricular fibrillation threshold in spite of an increase in the actual tendency of the heart to fibrillate spontaneously. Such discordance between the "electrical stability of the heart" and the ventricular fibrillation threshold was found during myocardial ischemia.


Effectiveness of intraaortic balloon pumping without cardiac surgery for patients with severe heart failure secondary to a recent myocardial infarction. Twenty-five patients with class III or class IV left ventricular failure (Myocardial Infarction Research Unit criteria) after a recent myocardial infarction were treated with intraaortic balloon pumping between December 1, 1972 and December 1, 1976. Three patients had no improvement and died during pumping. Two patients with improvement died during at attempt at weaning from circulatory assistance. Of 20 patients successfully weaned, 6 died within 3 months, 5 of these within 10 days after the weaning procedure. Of 14 patients who survived for more than 3 months, 13 were alive on February 15, 1977. Twelve of these 13 were in functional class II and 6 had resumed professional activities. Intraaortic balloon pumping proved an effective method for treating severe left ventricular failure after an acute myocardial infarction. Even withour surgery, 14 of 25 patients survived 3 or more months after an acute infarction complicated by serious pump failure.


The sinus node.

The sinus node. This discussion of the sinus node begins with a description of its normal anatomy, particularly in the human heart, and then proceeds to a review of the several pathologic changes known to affect the sinus node. The latter include diseases of the sinus node artery, changes in the normal collagen framework of the node, pericarditis and certain infiltrative processes. The concluding section combines an examination of function and structure of the sinus node on the basis of experimental observations. Some new laws of the heart dealing with governance of normal cardiac rhythm are presented.


Echocardiographic interpretation in the presence of Swan-Ganz intracardiac catheters. Swan-Ganz balloon flotation catheters can produce strong echoes in the right heart. These echoes have variable configurations and can mimic right heart structures; their reverberations can be confused with left heart structures.


High-voltage electron microscopy of extracellular fibrillogenesis. High-voltage electron microscopy was employed to observe developing extracellular connective tissue elements in the cervical perinotochordal and perivertebral regions in the chick embryo from 2 through 15 days' incubation. During days 2 and 3, small (10 nm) and large (18-20 nm) microfibrils surrounded the notochord, becoming evident around fibroblast-like cells in day 4. Amorphous material, globular granules and microfibrillar bundles were present at this time. Microfibrillar length increased as did the total population of microfibrils. At four days microfibrils 3-5 nm in diameter arose in all directions from globular granules. During day 9 and thereafter to day 15, microfibrillar diameters increased. This growth formed unit collagenous fibrils 30 nm in diameter or greater. Axial periodicity became evident at day 14. Small microfibrils appear to be composed largely of glycoproteins and do not contain a significant amount of collagen. The globular granules and associated filaments are probably proteoglycans. The amorphous material is believed to provide molecular collagen to developing fibrils. Large microfibrils and unit collagenous fibrils contain significant amounts of molecular collagen.


Age related differences in binding of concanavalin A to plasma membranes of isolated neurons. Neurons isolated from the lateral vestibular nucleus of young adult and senescent Fischer-344 rats were incubated with fluorescamine-labelled Concanavalin A (fl-Con A) alone, or following incubation in trypsin or Vibrio cholerae neuraminidase. They were then observed and photographed. Microdensitometric analysis of fluorescence micrographs showed that senescent rat neurons were significantly more fluorescent than those from young adult rats. Additionally, either patches or caps of fl-Con A were seen on the surface of neurons from senescent rats, while most young adult rat neurons bound fl-Con A uniformly. Pretreatment with trypsin or neuraminidase had no effect on the amount of fluorescence on the surface of senescent rat neurons, and only a slight effect on the surface distribution. Trypsin and neuronal plasma membranes of young adult rats and a rearrangement of the binding pattern in the majority of neurons observed.


Fenestrations in regenerating skeletal muscle capillaries. A new observation of fenestrae with diaphragms in the endothelial wall of regenerating skeletal muscle capillaries is described in seven-day-old wounds of the cremaster muscle of adult male guinea pigs. The fenestrations were 44 nm in diameter and contained diaphragms with a central dense structure. These findings suggest an additional route for physiological exchange mechanisms in wound capillaries.


The perineural sheath in the urodele amphibian. The perineural epithelial cells of the peripheral nerve sheath in triturus are elongated flat cells with long and thin cytoplasmic processes. Structural characteristics of the processes include a relative absence of common cytoplasmic organelles of the perinuclear cytoplasm but an abundance of vesicular profiles similar to fully formed pinocytotic vesicles. Unlike pinocytotic vesicles, vesicles of the processes often contain an 8-nm thick filament attached to their cytoplasmic face. Vesicles are also interconnected by similar filaments or by tubules. In addition, almost all vehicles appear to have openings at the cell surface, a feature not seen for pinocytotic vesicles. The concentration of exogenous peroxidase in the vesicles, and the subsequent appearance of peroxidase in the endoneural fluid, myelin sheath and axon, support the notion that the vesicles function in the exchange of substances between extraneural and endoneural fluids.


The effect of vinblastine-induced microtubule loss on kidney podocyte morphology. The effect of intravenous injections of vinblastine sulfate on the renal glomerular epithelium was studied by scanning and transmission electron microscopy. Two hours after treatment with vinblastine, microtubules were almost completely lost from the podocyte cell bodies and major processes, and crystalline inclusions of a tubular nature had appeared within the cytoplasm. Coincident with this loss of microtubules, podocyte major processes at first collapsed and then became significantly thinner as they appeared to lose much of their cytoplasm to the nucleated cell body. These observations suggest that microtubules serve to maintain the shape and integrity of podocyte major processes. At no time after vinblastine treatment did we note any alteration in podocyte pedicel morphology.


Ultrastructure of the aging myocardium: a morphometric approach. Left ventricular tissue from adult and aging Syrian hamster heart was compared at the ultrastructural level, using both qualitative and morphometric electron microscopy. The aging myocardium often showed indented nuclei, lipid droplets and aggregations of dense bodies. The volume fractions of muscle cells occupied by mitochondria, lipid and lysosomes (including both primary lysosomes and residual bodies) was significantly greater in the old animals, while there was no significant difference in nuclear volume fraction or myofibrillar mass. Sarcoplasmic reticular volume and membrane surface area fell during aging. The area of mitochondrial inner membrane plus cristae per mitochondrial volume also fell. When sarcoplasmic reticular and mitochondrial area were expressed per myofibrillar volume fraction, the sarcoplasmic reticular ratio fell, while the mitochondrial parameter remained constant. Discoordinate aging of cellular components in the mammalian myocardium is proposed.


Mode of locomotion of Schwann cells migrating in vivo. The manner of locomotion of Schwann cells during normal development was studied by means of repeated observations and photomicrographs of individual cells at closely spaced time intervals and focal levels. In developing tadpole peripheral nerves, Schwann cells move sporadically with brief periods of rapid translation of the whole cell interspersed with longer intervals when the cell shows little or no overall movement. Highest rates of locomotion averaged 5 micrometer/minute with a duration of no greater than four to six minutes. Net rates of speed measured over at least 20 minutes were always considerably lower, with the average being 1.9 micrometer/minute. Rapid locomotion involves protrusion and growth of several pseudopodia, while the cell body remains in place, followed by attachment of these processes to an axonal surface, and finally detachment of the trailing portions of the cell as the entire cell hitches forward, "inchworm-style".


Dictyosome-like structures with cylindrical intersaccular connections (microtubules?) in guinea pig spermatocytes. Structures superficially resembling dictyosomes were present in guinea pig primary spermatocytes and in spermatids in late stages of development. The dictyosome-like structures (DLS) were composed of 2 to 17 saccules. Each saccule averaged about 20 nm in thickness (membranes plus lumen) and 400 nm in diameter and was separated from adjacent saccules in a stack by an intersaccular space of about 12 nm. Single saccules separated from the DLS were also present. Tubules up to 60 nm in diameter were continuous with the edges of the saccules and sometimes extended for several micrometers into the cytoplasm. The membranes of the tubules appeared similar to the saccule membranes. Some DLS saccules and tubules had coated vesicles attached to them. A distinguished feature of DLS was the presence of microtubule-like structures, about 10 nm in diameter, that bridged the inter-saccular spaces. Some of these bridging structures appeared continuous through one or more saccules. The bridging structures were often arranged in linear arrays or in clusters of three to four. The membranes of the DLS appeared tripartite but stained differently from the membranes of the endoplasmic reticulum or Golgi apparatus. The inner (luminal) leaflet of the tripartite membrane usually appeared discontinuous or globular after fixation in glutaraldehyde-osmium tetroxide. The DLS could be distinguished from all other cellular components and may represent a new organelle unique to spermatogenesis.


The morphogenetic relationship of the temporal muscle to the coronoid process in human embryos and fetuses. The purpose of this investigation was: (a) to study the developmental relationships of the temporal muscle and the coronoid process during the critical initial stages of morphogenesis and (b) to correlate the developmental stages of the muscle and the bone with data describing the functioning of the muscles of mastication in utero. The heads of 41 human embryos and fetuses, 6 to 11 weeks, estimated fertilization age, were sectioned and examined under light microscopy. The findings are described in terms of six successive stages, each characterized by a major developmental change occurring during that stage. The data indicate that the temporal and masseter muscle anlagen begin to develop prior to the skeleton to which they ultimately become attached. The coronoid process differentiates subsequently as a discrete entity within the mass of the temporal muscle anlage at an estimated fertilization age of 7 to 7.5 weeks (23-24 mm CRL). At approximately eight weeks of age, the coronoid process unites with the main portion of the mandibular ramus. The findings here presented do not support the conclusion that the coronoid process is self-differentiating as Washburn ('47) contended. Instead, the development of this feature of the human mandible represents a response that follows the differentiation of the temporal muscle. This conclusion is consistent with the observations drawn from a number of investigations concerning structural and functional development of the face.


Electron microscopy of the connective tissues between longitudinal and circular muscle of small intestine of cat. Electrotonic spread of applied potentials was observed between longitudinal and circular muscle layers of the small intestine with no rectification. Nexal junctions were demonstrated between muscle fibers of each layer. Connective tissue cells bridged between the two muscle layers. These showed structural characteristics of fibrocytes and of interstitial cells. Some nexuses were seen between connective tissue cells and between these cells and muscle fibers of each layer but in most junctions the membranes were 10-18 nm apart. Since connective tissue can serve for electrical conduction between cultured heart cells and since electrical properties of intestinal muscle permit transmission with low degrees of coupling, it is suggested that interstitial cells and fibrocytes may electrically couple longitudinal and circular muscle layers of cat intestine.


The role of movement in the development of a digital flexor tendon. D-tubocurarine was injected into the air sac of 8-day chick embryos to prevent movement of the digits of the hind limb. The embryos were paralyzed from the tenth to the eighteenth day, when the experiment was terminated. The immobilization of the flexor digitorum profundus tendons in the tarsus resulted in a loss of specialized structures around and on this tendon, as determined by light and electron microscopy. Specialized areas observed in the normal chick (synovial cavity, fibrocartilaginous area, and elastic vinculum) failed to form, as a result of the paralysis of the digit. Several authors have shown previously that movement is a requirement for the molding and maintenance of joint cavities in vivo, in ovo and in vitro (see text for references). We have shown that movement of the tendon is required to produce a functional tendon apparatus in the embryo and predict that movement is also required for regeneration after injury.


Fusion of nasal swellings in the mouse embryo: surface coat and initial contact. The nasal region of 12-day-old mouse embryos was examined with the electron microscope to determine whether a surface coat and membrane specializations are involved in epithelial fusion between the medial and lateral nasal swellings. Ruthenium red was used to examine the distribution of the surface coat. Prior to contact, a surface coat is always present over the epithelial linings of the nasal swellings in the region of presumptive fusion, and it is often heavier in the fusing than in the non-fusing regions. At the point of initial contact, the coat is present as a thin film between touching superficial cells, suggesting that it may mediate epithelial contact. The initial contact between the cells of the medial and lateral nasal swellings is made by short projections from one superficial cell to the surface of an opposing superficial cells meet. The contacting membranes, which are separated by a distance of approximately 6-10 nm and show an increased electron-density, probably provide a firm adhesion between the nasal swellings.


Effect of moderate malnutrition on concentrations of immunoglobulins and enzymes in tears and saliva of young Colombian children. The influence of moderate malnutrition on immunoglobulins and enzymes in the sera and secretions of 71 Colombian children was studied. Concentrations of immunoglobulin A, immunoglobulin G, lysozyme, albumin, and aminopeptidase were measured in the sera, tears, and saliva of 27 normal, 32 grade I, 9 grade II, and 3 grade III malnourished children. The most severely malnourished children, grades II and III, had markedly reduced immunoglobulin A concentrations and elevated immunoglobulin G concentrations in tears. Immunoglobulin A levels in whole saliva were also reduced in these malnourished children. In contrast, the concentration of immunoglobulin A in the sera of these children was significantly elevated. There was no influence of malnutrition on levels of lysozyme, albumin, total protein, and aminopeptidase in tears or saliva. These results indicate that secretory immunity may be impaired in moderately malnourished children due to decreased levels of immunoglobulin A in secretions.


Fasting (acute energy deprivation) in man: effect on blood coagulation and fibrinolysis. Blood coagulation and fibrinolysis parameters were studied during 10 days of total fasting in healthy, normal weight males. A reduction of plasma levels of factor VIII activity with a concomitant decrease in factor VIII antigen was found, without other laboratory evidence for a disseminated intravascular coagulation. The effect of 10 days' starvation on blood coagulation appears to be small but the effect of more prolonged starvation might implicate impaired hemostasis.


Effect of systemic bacterial infection on absorption rates of L-histidine and glycylglycine from the human jejunum in vivo. Jejunal absorption rates of L-histidine (from a 100 mmole/liter solution) and glycylglycine (from a 50 mmole/liter solution) were determined with a souble-lumen tube perfusion system in vivo in 12 Zambian African men; six had acute bacterial pneumonia (infection group) and six had no clinical evidence of a bacterial infection (control group). With this experimental design the mean rate of histidine absorption was significantly higher in the infection compared with the control group, but mean rates for glycine absorption from glycylglycine were not significantly different. During the glycylglycine infusions, the luminal disappearance rate of the intact peptide was significantly greater than the total glycine absorption rate. The correlation between individual histidine and glycylglycine absorption rates was significant. That is probably because after intracellular hydrolysis and efflux to the lumen, some glycylglycine is reabsorbed as free glycine by the amino-acid transfer mechanism, and the rate of that has previously been shown to be increased in subjects with systemic bacterial infections.


Effect of autoclaving of a lactose-containing diet on cholesterol and bile acid metabolism of conventional and germ-free rats. Feeding of lactose in amounts comparable to the adult human intake in developed countries (6% of diet, and in later studies 10%) had no major effect on cholesterol and bile acid metabolism of germ-free and conventional rats. However, when lactose-containing casein-starch diets were sterilized by autoclaving, changes in intestinal and/or fecal bile acids were found. Both germ-free and conventional rats demonstrated some increase in intestinal beta-muricholic acid concentrations ascribable to the mere presence of lactose in the diet. Autoclaving of the diet produced additional changes, especially in the fecal bile acid pattern of conventional rats. Here the ratio between the beta-muricholic-derived secondary bile acids hyodeoxycholic and omega-muricholic acids changed from the usual 5:3 to approximately 1:10, with omega-muricholic acid becoming the major fecal bile acid. These changes point to a notable effect of lactose-derived products, formed during steam-sterilization, on the microbial modification of intestinal bile acids in the lower gut. Similar changes have been observed after oral administration of aureomycin and other, unrelated antibiotics that inhibit growth of gram positive organisms.


Influence of diet on trans fatty acids in human milk. In two experiments on relations between diet and milk lipids, subjects recorded food intake for 1 week and saved duplicate portions of foods consumed on 3 days. Diet collections were analyzed for selected nutrients and percent fatty acids. In the first experiment, for 1 week five subjects took morning and evening milk samples for fatty acid analysis. Significant differences were found in percentages of trans- 18:1 and total trans fatty acids between subjects' milks but not between morning and evening samples. In the second experiment six additional subjects collected milk samples in the morning only. Subjects were significantly different in the percentages of trans- 18:1 and total trans acids in their milks. In nine of the 11 subjects the fluctuation of percent total trans acids in the milk appeared to follow dietary trans changes after a 12 to 36 hr lag period. A significant correlation was found for diet and evening milk of the same day. Polyunsaturated/saturated ratios of the fatty acids in the diet lipids were related to those for milk lipids from the same evening and the next morning. Although other factors are involved, diet lipids influence trans fatty acids and polyunsaturated/saturated ratios of the fatty acids in human milk.


The effect of kind of carbohydrate in the diet and use of oral contraceptives on metabolism of young women. I. Blood and urinary lactate, uric acid, and phosphorus. Six oral contraceptive (OC) users and six control subjects consumed diets in which 43% of the calories came from either sucrose or starch for 4 weeks in a cross-over design. Kind of carbohydrate in the diet had no effect on blood lactate response to a sucrose load, but lactate response of OC users was greater than that of control subjects. Kind of carbohydrate in the diet did not affect urinary lactate excretion after a sucrose load; however, OC users excreted more lactate than did controls and there was a significant interaction between dietary carbohydrate and OC use. Serum uric acid levels were significantly higher when the sucrose diet was consumed, but levels were not affected by OC use. Serum phosphorus levels were not affected by kind of carbohydrate in the diet but were higher in control subjects than in OC users and there was a significant interaction between diet and OC use. There were no significant differences in urinary uric acid and phosphorus excretions after sucrose loads or in 24-hr urinary excretions of uric acid, phosphorus, or urea due to kind of carbohydrate in the diet or OC use.


Vitamin B6 intakes and 24-hr 4-pyridoxic acid excretions of children. Vitamin B6 intake and 4-pyridoxic acid excretions of 22 children were determined. Mean intake of vitamin B6 per day was 1.10 mg +/- 0.47. Mean percentage of vitamin B6 intake excreted as 4-pyridoxic acid was 48% +/- 23. Excretion of 4-pyridoxic acid was significantly correlated to vitamin B6 intake but not to vitamin B6/protein ratios or vitamin B6/kilocalorie levels. Excretions of 4-pyridoxic acid equal to or below 0.15 mg appeared to be indicative of poor vitamin B6 intake for the children which was similar to the excretions found by others for depleted adults.


Sodium and potassium intakes and excretions of normal men consuming sodium chloride or a 1:1 mixture of sodium and potassium chlorides. Two groups of 10 healthy young men were matched on the basis of their free-choice consumptions of regular table salt. For 28 days they were then fed carefully controlled low-sodium foods. One group was permitted free-choice seasoning of these foods with regular table salt, the other with a 1:1 mixture of sodium and potassium chlorides. Intakes and urinary and fecal excretions of sodium and potassium were determined by analysis. The results were: 1) the subjects salted their food with essentially the same amounts of regular table salt as of the 1:1 mixture; 2) the sodium intake associated with seasoning at the table was reduced with the 1:1 mixture to 44 percent of the amount consumed with regular table salt; and 3) over a 28-day period there was no tendency for subjects to increase their use of a 1:1 mixture, when used in place of regular table salt, to compensate for their reduced sodium intakes. Under the conditions of this study, the use of the 1:1 mixture as a seasoning agent for foods that contained no added salt resulted in an average total intake of sodium (food plus seasoning) which was 55 percent that of the subjects using regular table salt.


Intestinal calcium-binding protein 3 months after massive small bowel resection in the piglet. Changes in intestinal calcium-binding protein and calcium binding activity were studied at resection and 3 months after 90% small bowel resection in piglets and one adult pig. A calcium-binding protein (MW congruent to 11.000) with calcium-dependent eletrophoretic mobility was partially purified from mucosal extract of proximal jejunum, mid-gut, and ileum. The concentration of calcium-binding protein and the calcium-binding activity of the intact animals were found highest in the proximal jejunal segment, lowest in the ileal segment. After resection in the four surviving animals out of nine, a significant increase in calcium-binding activity was observed in the proximal jejunum and in the distal ileal segment. The change in calcium-binding activity was much more marked in the ileum than the jejunum. These data demonstrate that pig intestinal mucosa possesses an adaptive capacity to increase the synthesis of calcium-binding protein after massive small bowel resection.


Evaluation of hair analysis for determination of zinc status using rats. Weanling male and female Sprague-Dawley rats were fed diets of graded levels of dietary zinc from 3 to 68 ppm. The zinc concentrations of hair, bone, and testes reflected the dietary intake by increasing with each increment of dietary zinc. Kidney zinc indicated the state of zinc metabolism by declining on restricted intakes and remaining constant above the requirement level. Plasma and liver zinc concentrations and enzyme activities were not related to dietary intake nor were any significant changes observed with restricted zinc intakes. Hair zinc levels decreased more rapidly with dietary zinc levels below the zinc requirement. Therefore, hair zinc analysis can be used to aid in diagnosis of a deficiency or evaluate dietary intake for the rat but can not be used to assess the state of zinc metabolism.


Clofibrate-induced changes in glucagon and insulin secretion in patients with angiographically documented coronary artery disease. This study examines insulin and glucagon secretion in the basal state and in response to clofibrate therapy in patients with angiographically proven coronary artery disease. When compared with weight matched subjects without coronary artery disease, neither insulin nor glucagon secretion were abnormal in response to L-arginine stimulation. However, in response to clofibrate, a marked reduction in insulin secretion and simultaneous elevation in glucagon secretion characterized all patients. Our data suggest the hypothesis that altered insulin and glucagon secretion in response to clofibrate therapy may participate in the reduction of new coronary events reported to occur during therapy with this drug.


Intravenous feeding of the rat with short chain fatty acid esters. I. Glycerol monobutyrate. Intravenous nutrition was investigated using butyric acid because it is oxidized independent of carnitine transport into the cell mitochondria. This carnitine independent fatty acid, in the form of water soluble monobutyrin, was continuously infused into rats for seven days at 27 g monobutyrin per kilogram of body weight per day and provided half the daily energy requirement. All experimental animals survived the alimentation in good health and were free of detectable physiological and behavioral abnormalities. The intravenous infusion depressed the test animals spontaneous food intake to half their preinfusion level. These experimental rats still demonstrated continuous weight pain in contrast to weight loss by pair-fed controls. At decapitation, the monobutyrin infused rats had hepatic glycogen levels three times that of the controls, along with lower soluble hepatic protein, and normal lipid and water content. The plasma acetoacetate was also elevated in experimental rats. It was inferred from these results that monobutyrin was hydrolyzed, and the metabolites were oxidized by the rat. It is concluded from these observations that monobutyrin produces no obvious toxic affects during short infusion periods and provides calories for the rat when given intravenously.


Nutrient intake and serum lipids in urban and rural Puerto Rican men. Dietary intake information was collected on 2,426 rural and 5,828 urban men free of coronary heart disease in the Pureto Rico Heart Health Program. Serum cholesterol and triglyceride, body weights, and related parameters were measured during a detailed cardiovascular examination. There were statistically significant differences between rural and urban values with respect to lipids, relative weight, and intake of many nutrients. Rural subjects had lower lipids and relative weights. Serum cholesterol was associated with relative weight in both rural and urban areas. In the urban areas, serum cholesterol was associated with intake of total fat, saturated fatty acids, polyunsaturated fatty acids, total carbohydrate, and starch (all measured as percent of calories). It was also related to percent carbohydrate from starch and dietary cholesterol intake, even after relative weight was taken into account. The associations were of a low order, although statistically significant. The association of fasting triglycerides with some of the carbohydrate variables was statistically significant after relative weight was taken into account in the urban area. Overall, diet and relative weight can account for at most 6% of the variability in serum cholesterol observed, with at most 2.5% of the variability due diet alone.


Assessing the anthropometric status of Hawaii's preschoolers participating in feeding programs in day care centers. A survey of low and middle income preschoolers who were exposed to similar feeding programs and physical activities showed similarity of physical growth between the two groups of children. Mean values of arm size, muscularity, triceps skinfold, and fat area were similar and signified adequate protein status and caloric reserves in both groups of children. Comparison of data from preschoolers in Oahu and on the United States mainland showed that all left arm triceps skinfold medians of preschoolers in Oahu were 1) smaller than the medians recorded for right arms in the Health and Nutrition Examination Survey and 2) greater than the values on the 50th percentile for right arms of white children of the Ten-State Nutrition Survey, which indicated that Oahu preschoolers occupied a caloric reserve intermediate between the two mainland United States populations surveyed. Medians of heights and weights were lower than the median values of the Health and Nutrition Examination Survey and were closer to the 50th percentile of while children in the Ten-State Nutrition Survey.


Parotid enlargement, forehead edema, and suppression of malaria as nutritional consequences of ascariasis. Bilateral painless enlargement of the parotids, a curiously localized edema of the forehead and relative freedom from malaria were striking findings in children of Anjouan but not of Grande Comore, two neighboring islands of the Comorro group in the Indian Ocean. Compared with those of Grande Comore, Anjouan children were heavily infested with Ascaris lumbricoides. We suggest that the clinical findings may be the nutritional consequence of severe ascariasis and that the low incidence of malaria in Anjouan children may be an example of the delicate ecological balance between the host, the Ascaris, and the plasmoidum.


Serum uric acid level of Thai individuals in comparison with the nutritional status and some other physical and biochemical parameters. Serum uric acid levels were measured in a total of 287 adults of Thai origin in Bangkok and the rural area. Mean values and range were found to exceed slightly serum uric acid concentration as reported from western countries. There was no significant difference between the Bangkok group and the group from the rural area but males and females differed significantly in their serum uric acid levels. A significant positive correlation to the ratio between weight to height as an index of the nutritional status was found.


Recurrent abdominal pain: gaining control of the symptom. The treatment of recurrent abdominal pain without organic cause requires that the families involved change their focus from organic to emotional issues. This is done during a family conference with the pediatrician, in which a positive approach to the problem is outlined. Following such a plan avoids the pitfalls of continuing an inappropriate and organically oriented response to the family's needs and also avoids threatening the family with emotionally charged personal needs too soon. When the transition period is successfully negotiated, the child's symptoms often are alleviated without further psychological intervention. In cases where further psychiatric intervention is indicated, a foundation has been laid for successful treatment. Nineteen patients have been successfully treated either by the pediatrician alone or have successfully begun psychotherapy, thus preventing unnecessary medical tests and further "doctor shopping", which characteristically accompanies such cases.


Malrotation with gastric volvulus, midgut volvulus, and pancreatitis. A 2-year-old child with intestinal malrotation had simultaneous gastric volvulus, midgut volvulus, acute pancreatitis, and gastric perforation, followed postoperatively by a temporary period of both lactosuria and sucrosuria. The gastric volvulus and midgut volvulus resulted in both proximal and distal obstruction of the duodenum, reproducing clinically a previously reported experimental model designed to produce pancreatitis. Operative reduction of the midgut volvulus and the gastric volvulus and repair of the gastric perforation was accomplished. The child has had normal growth and development during the ensuing nine years.


Incidence of Nelson's syndrome after adrenalectomy for Cushing's disease in children: results of a nationwide survey. To establish the incidence of Nelson's syndrome in children treated with total bilateral adrenalectomy (TBA) for Cushing's disease, a survey was made of members of The Lawson Wilkins Pediatric Endocrine Society. Thirty-one patients aged 10 months to 16 years had been treated with TBA for Cushing's disease; one had been treated with ortho para prime isomer of dichlorodiphenyldichloroethane alone. Postadrenalectomy hyperpigmentation was reported in 18 patients. Sella enlargement was detected in eight patients (25%) after 1 to 5.5 years (mean, three years) post-TBA. Five of these patients have had documented pituitary adenomas to date. This incidence is higher than the adult figure of 10% to 16%.


Propionic acidemia and anorectal anomalies in three siblings. Three siblings suffering from recurrent vomiting, hypotonia, hyperpnea, dehydration, and ketoacidosis were diagnosed as having ketotic hyperglycinemia secondary to propionic acidemia. They also had leukopenia and thrombocytopenia, and two of them had anorectal malformations, one an imperforate anus with rectoperineal fistula, and the other an ectopic anus. The occurrence of propionic acidemia and anorectal anomalies in three siblings out of eight children in a consanguineous marriage suggests an autosomal recessive genetic inheritance.


Simultaneous occurrence of diabetes mellitus, diabetes insipidus, and optic atrophy in a brother and sister. We report the cases of two siblings who died at age 21 and 15 years respectively. Both had optic atrophy, pitressinsensitive diabetes insipidus, and insulin-dependent diabetes mellitus, with onset occurring in early childhood. Although there are now 21 patients from 15 families with this syndrome, this is the first time that necropsy findings have become available. They include the expected atrophy of hypothalamic nuclei and degeneration of the optic nerves, chiasm and tract, as well as a totally unexpected degeneration of the pons and cerebellum.


Perinatal aspects of omphalocele and gastroschisis. Forty-one infants treated for abdominal wall defects were studied retrospectively. Using established anatomic criteria the infants were identified as having either an omphalocele or gastroschisis. They were compared for maternal and infant characteristics to determine if distinct perinatal characteristics exist between the two groups. Gastroschisis patients had lower mean maternal age, were more likely to be first born, and to be of lower birth weight. Major malformations apart from those associated with the gastrointestinal tract and the anterior abdominal wall occurred 12 times more often in omphalocele patients. Ventral defects warrant a careful anatomical and clinical differentiation, and in the case of omphalocele, a thorough search for other anomalies.


Gastric ulcer: effect of healing on gastric acid secretion and fasting serum gastrin levels. In 15 patients with uncomplicated gastric ulcers, basal and peak gastric acid outputs and fasting serum gastrin levels were studied before and after healing. The mean basal acid output [4.0 +/- 1.3 (SEM) mEq H+/hr], the mean peak acid output (29.5 +/- 5.1 mEq H+/hr), and the mean fasting serum gastrin level (80.3 +/- 16.7 pg/ml) in these patients did not change significantly with healing. Failure of gastric secretory function to change with healing suggests that mucosal resistance factors are more important than gastric acid secretion in the pathogenesis of a gastric ulcer.


Colonic-duodenal fistula in Crohn's disease. A fistula between the ascending colon and the duodenum occurs not uncommonly as a complication of Crohn's disease with primarily colonic involvement. Clinical and radiological findings in four cases are presented. In three instances the fistula served as an indication for surgical intervention; after ileosigmoidostomy, ileorectal anastomosis, and ileostomy alone, the patients improved clinically but x-ray evidence of patency of the fistula persisted. Recurrent activity of the Crohn's disease in two responded to medical treatment as it did in one patient without surgery at all. The internal fistula need not be a seriuos complication of Crohn's disease and should not serve as an indication for surgical correction for its own sake.


Experimental liver necrosis: hepatic erythrocyte sequestration as a cause of acute anemia. A prospective study was undertaken to determine the cause of the acute anemia previously observed in pigs manifesting acute liver necrosis after administration of acetaminophen in dosages in excess of the LD100. A highly significant correlation was found between the degree of anemia and increase in liver weight (P less than 0.001) and a similarly significant correlation was noted between the increase in liver weight and 51Cr activity in the liver after administration of autologous erythrocytes labeled with 51Cr. Marked hepatic erythrocyte sequestration was confirmed histologically, whereas there was minimal erythrocyte accumulation in extrahepatic tissue. Erythrocyte glutathione content was not altered by acetaminophen administration. It was concluded that hepatic sequestration of erythrocytes occurred to a sufficient extent to account for the precipitous fall in hematocrit observed.


Vitamin B12 absorption following human intestinal bypass surgery. Adaptation of vitamin B12 absorption by small intestine has been suggested by experimental and clinical studies. Five partial ileal bypass patients and ten jejunoileal bypass patients were studied for adaptation of B12 absorption following surgery. Adaptation of vitamin B12 absorption could not be demonstrated in either group. Few of the patients on an individual basis demonstrated adaptation. Parenteral B12 should be given to all patients who undergo bypass surgery unless evidence of persistent normal B12 absorption has been obtained.


Surgical vagotomy and stomach wall ATP and ADP in pylorus--ligated rats. The stomach wall ATP and ADP have been studied in rats, with and without bilateral surgical vagotomy, 24 hr after pylorus ligation. It was observed that the amounts and concentrations of ATP significantly decreased in both parts (corpus + antrum and forestomach) in pylorus-ligated rats, while the amounts and concentrations remained at a significantly higher level in pylorus-ligated + vagotomized rats. Changes in amounts and concentrations of ADP paralleled those of ATP. It has been concluded that a significant decrease of cellular ATP is necessary to produce gastric hypersecretion in ulceration in pylorus-ligated rats. This significant decrease of cellular ATP, in corpus + antrum and forestomach, can be prevented by bilateral surgical vagotomy.


Preoperative diagnosis of pancreatic carcinoma by percutaneous aspiration biopsy. Carcinoma of the pancreas and chronic pancreatitis may be extremely difficult to differentiate by standard diagnostic methods preoperatively as well as at the operating table. Operative pancreatic biopsy may have a high morbidity, rare mortality, and can be misleading. Percutaneous aspiration biopsy may be of great potential benefit. It provides additional histological material not usually available, and an accurate diagnosis of malignancy can be made. In select patients a needless laparotomy may be avoided. It appears to be a safe procedure that should be considered in the evaluation of the patient with suspected pancreatic malignancy in which a mass lesion is demonstrated by ultrasonography, computerized tomography, angiography, or retrograde pancreatography.


Mucosal lesions due to gastric distension in the rat. The pathogenesis of acute gastric mucosal lesions produced by distension of the rat stomach was studied. One hour of distension with 0.1 N HCl, but not saline, produced lesions in the glandular stomach in all rats. Histologic studies revealed marked thinning of the mucosa plus thrombus formation in the ulcerated area. Gastric distension with 8 ml HCl (per 100 g body weight) produced severe lesions, 4 ml minimal lesions and 2 ml no lesions. Intragastric pressure in the 8-ml group remained above 110 mm H2O for the first 10 min. Distension with 8 ml acid/100 g body weight for just 10 min resulted in significant lesion formation. Acid distension did not cause generalized disruption of the gastric mucosal barrier to H+ back-diffusion. It appears that an intragastric pressure of over 110 mm H2O for 10 min damages the mucosa by pressure (with thinning) and ischemia (with thrombosis), resulting in decreased resistance to acid peptic digestion and consequent acute lesion formation.


Continuous electrocardiographic monitoring with Holter electrocardiocorder throughout all stages of gastroscopy. Continuous electrocardiographic recording on magnetic tape with a Holter electrocardiocorder was performed during gastroscopy on 55 consecutive patients. ECG recording was begun before premedication and was terminated 1 hr after the withdrawal of the gastroscope. The ECG changes during the different stages of the procedure were separately analyzed: 38.18% of patients had E.C.G. changes--sinus tachycardia (20%), ST-T changes (23.6%), ventricular and atrial premature beats (20.0% and 7.27%, respectively). atrial premature beats with aberrant conduction (3.6%), and coronary sinus rhythm (1.8%). All changes disappeared spontaneously after the procedure. Although relatively safe, gastroscopy requires careful consideration of the risks, especially in severe cardiac patients.


Gallstone prevalence and biliary lipid composition in inflammatory bowel disease. Biliary cholesterol saturation has been correlated with disease variables that might effect bile acid loss in ileitis patients with (N = 9) or without (N = 8) intestinal resection having a defined prevalence of gallstones. In addition, cholesterol saturation was determined in ulcerative colitis patients (N = 7) and gallstone patients (N = 18) as well as in 5 normal controls. Biliary cholesterol saturation in ileitis patients both with and without resection was similar to that in gallstone patients yet the prevalence of gallstones was only 12%. Cholesterol saturation did not correlate with ileal resection nor the extent, duration, or activity of ileitis. Biliary cholesterol saturation was not different in ulcerative colitis patients from that in normal subjects. It is concluded that cholesterol saturation of bile alone does not account for the high prevalence of cholesterol gallstones that has been reported in ileitis patients.


Lower esophageal sphincter function in cirrhosis. Lower esophageal sphincter (LES) function in cirrhosis was evaluated using an infused manometric system. LES pressure (LESP) in 10 subjects with cirrhosis (22 +/- 1 mm Hg) (mean +/- SE) was not significantly (P greater than 0.05) different from that of 10 control subjects (21 +/- 1 mm Hg) but was significantly (P less than 0.01) greater than the LESP recorded in 5 subjects with cirrhosis and ascites (16 +/- 2 mm Hg). There was no significant difference in LES response to intravenous pentagastrin, intravenous edrophonium, or straight-leg raising in the three groups. After loss of ascitic fluid, LESP significantly (P less than 0.01) increased (deltaP : 9 +/- 3 mm Hg) and gastric pressure (GP) significantly (P less than 0.01) decreased (deltaP: 8 +/- 2 mm Hg). The changes in LESP and GP revealed a significant (R = 0.83, P less than 0.001) linear correlation. These data indicate (1) cirrhosis is associated with normal LES function, and (2) the mechanism of lowered LESP with ascites may be the inability of the LES to maintain a sustained response to chronic increases in GP.


Percutaneous aspiration liver biopsy using a large-caliber disposable needle: a preliminary report. A modification of the aspiration liver biopsy technique using a large-caliber disposable needle is described in an 18-month experience. One hundred forty liver biopsies were performed, obtaining adequate tissue in 98% of the patients. Complications occurred in 12 patients and were limited to pain at the biopsy site, epigastrium, or right shoulder; one instance of tachycardia and three of transient hypotension occurred. Thirty patients studied prospectively with liver scans and hematologic parameters failed to disclose subclinical complications. While the number of patients biopsied is still too small to provide definite conclusions , it appears that this technique is safe, similar and has a very high yield of excellent specimens. In addition, the needle offers the advantage of being disposable and easy to use by a single operator.


Roentgenographic findings in work hypertrophy of the muscularis propria of the terminal ileum. This case is presented as an uncommon example of valvulae thickening caused in part by work hypertrophy of the circular muscular layer. This normal response of smooth muscle may occur in association with progressively obstructing lesions of the colon or ileocecal valve. Recognition of a similar abnormal small-bowel appearance may suggest the presence of a more distal obstructing lesion.


The incidence of cervical cancer and duration of oral contraceptive use. In a prospective study carried out on a cohort of 17,942 women belonging to the Kaiser Foundation Health Plan and living in suburban communities of the San Francisco Bay Area, a positive association was found between the incidence of cervical carcinoma and total duration of oral contraceptive use. The association was established while controlling for the effects of age, education, and selected infections. The association persists when incident cases of dysplasia are added to those of carcinoma. A further study, in which covariates relating to sexual behavior will also be taken into account, is in progress.


Latitude, migration, and the prevalence of multiple sclerosis. Prevalence of multiple sclerosis (MS) was determined in three groups of Caucasians in King and Pierce Counties (Washington) and in Los Angeles County (California): natives (born in study state), migrants from high-risk states (North), and migrants from low risk states (South). A diagnosis of definite or probable MS (excluding migrants with onset before migration) was established in 1816 of the persons found. The prevalence in Los Angeles County natives and in migrants from the South to either Los Angeles County or King-Pierce Counties were relatively low, while prevalence in King-Pierce Counties among natives and migrants from the North were high. The prevalence in migrants from the North to Los Angeles was intermediate. The results suggest that some degree of protection is provided to migrants by residence in low-prevalence areas, either early or later in life.


Adequacy of survey data collected from substitute respondents. This study examined interview data on personal habits (smoking, drinking and dietary histories) when collected from two sources. A sample of 300 pairs of subjects (mostly husbands and wives) was obtained from an ongoing health survey in Hawaii, and both members of each pair were interviewed separately about the habits of the husband. Care was taken that the members of each pair had no opportunity to communicate with each other between the start and completion of both interviews. The results showed remarkably good agreement in overall mean values between the two groups of respondents. In general, approximately 75% of the pairs agreed within acceptable limits on most items. There was no clear association of the degree of agreement within pairs with a variety of characteristics of the surrogate group, including age, race, level of education, family income, and duration of residence of proportion of meals eaten together with the subject. These findings are encouraging for the use of surrogate respondents in studies of personal habits where direct interviews are not always feasible, or where the use of such substitutes can improve the reppresentativeness and size of the sample.


Sudden infant death and infanticide.

Sudden infant death and infanticide. The hypothesis, advanced by Asch (Mt Sinai J Med NY 35:214-220, 1968), that a majority of sudden infant death syndrome (SIDS) cases are actually infanticides, is addressed by examination of age comparable infant homicide rates (United States, 1950-1974) and consideration of current theory regarding SIDS pathogenesis. The analysis provides no support for the hypothesis.


Prevalence and epidemiologic significance of antibody to hepatitis B core antigen in Greece. The diagnostic and epidemiologic significance of antibody to hepatitis B core antigen (anti-HBc) detected by complement fixation was studied in a sample of 412 healthy persons, 0-70 years old of both sexes living in the Athens area. The prevalence of hepatitis B virus (HBV) infections was found to be very high (26.5%) and the hepatitis B surface antigen (HBsAg) carrier rate (4.1%) among the highest in Europe. Anti-HBc was detected in 63 (15.3%) of the examined infection. The prevalence of anti-HBc (without HBsAg or anti-HBs) increased with age, while the HBsAg carrier rate declined in older age groups. It was also found that the frequency of anti-HBc persists for a shorter period than the anti-HBs after HBV infection. These data stress the importance of anti-HBc testing in increasing the sensitivity of the detection of potentially infective HBV carriers as well as in studying various epidemiologic aspects of HBV infection.


The epidemiology of hepatitis B infections in a poly-ethnic population. Hepatitis B antigen (HBsAg) was found in 5% and hepatitis B antibody (anti-HBs) in 33% of male blood donors from different ethnic groups in Paramaribo, Surinam. Among these ethnic groups only blood donors of Indonesian origin had a higher prevalence of both HBsAg and anti-HBs. The Indonesian donors may acquire this antigen and antibody at an earlier age than donors of Creole origin or of the Mixed ethnic group.


Bloom's syndrome. VI. The disorder in Israel and an estimation of the gene frequency in the Ashkenazim. An effort was made to identify all individuals with Bloom's syndrome living in Israel between September 1971 and September 1972. Each of the eight individuals located were Jewish and could readily be classified Ashkenazic. The frequency of the Bloom's syndrome gene in Ashkenazim was estimated to be .0042 (minimum), implying a heterozygote frequency greater than 1 in 120. A striking distortion of the sex ratio (M/F = 7.0) may have been due to underascertainment of affected females. One of the affected individuals ascertained during the survey subsequently has died from cancer, which is in keeping with the recognized cancer proneness of this condition. Four of the affected have married, but no conception is known to have occurred, which suggests that sub- or infertility is a feature of the syndrome.


Intrafamilial correlation analysis for IgM serum levels. The IgM serum level was determined in the members of 29 healthy families. The IgM mean concentrations between fathers and mothers and between sons and daughters were significantly different (P less than .01), with higher serum IgM levels in females than in males. Simple linear regression analysis was done for the following intrafamilial combinations: son-father, daughter-father, son-mother, and daughter-mother. Significant correlation coefficients (P less than .05) were obtained in all four combinations, which does not support the X-linked gene hypothesis (i.e., that the X chromosome carries quantitative genes for immunoglobulin M). An alternative explanation for the differences between sexes for IgM serum concentration is considered.


Detection of genetic variation with radioactive ligands. I. Electrophoretic screening of plasma proteins with a selected panel of compounds. To detect new genetic variation in human plasma proteins, a panel of 63 radioactive substances were screened as potential radioligands using polyacrylamide gel electrophoresis (PAGE) and autoradiography. Vitamins, hormones, drugs, amino acids, purines, pyrimidines, sugars and lipids labeled with 14C or other radionuclides were among those substances tested. A majority bound to albumin and a smaller fraction to prealbumins and lipoproteins. Several vitamins and hormones bound to specific alpha and beta globulins. (1) Electrophoretic polymorphisms of vitamin D-binding protein (group-specific component), a vitamin B12-binding protein (transcobalamin II), and thyroxine-binding alpha-globulin are described elsewhere. (2) Testosterone-binding beta-globulin (TeBG) showed an electrophoretic polymorphism in Caucasians and a possible deficiency allele. (3) Transcortin showed an electrophoretic doublet in all persons tested but no electrophoretic variation. (4) A protein binding derivative of norepinephrine or epinephrine was identified as transferrin. (5) A nonpolymorphic protein running cathodal to albumin and binding a derivative of riboflavin was tentatively identified as a fraction of albumin with mobility altered as a result of interaction with the ligand.


Maternal effects in human cleft lip and palate. To look for a persistent maternal effect of CL(P) and CP, 8,000 pedigrees were screened for half sibships, and data were pooled from 16 investigators. After excluding known genetic or cytogenetic diagnoses from the probands with facial clefts, a recurrence risk of .011 was obtained for CL(P) based upon 342 maternal half sibs. This was nearly identical to the risk of .014 based upon 210 paternal half sibs. CP proband frequencies of .004 for maternal half sibs and .009 for the paternal counterparts were also found. The lack of significant maternal effects in this data supports previously reported data from twin studies and from interracial crosses from Hawaii. The lack of maternal effect in human CL(P) and CP is in contrast to genetic data on clefting in mice.


Congenital deficiency of human R-type binding proteins of cobalamin. A family expressing the congenital absence of the R-type binders of cobalamin (Cbl), vitamin B-12, was restudied. The capacity to bind Cbl to R type binders was absent from serum, saliva, cerebrospinal fluid, gastric juice granulocytes, and granulocyte output of the propositus. Serum R did not carry Cbl in vivo. There was no immunological R binder in his saliva, but cross reacting material was detected in his serum. Evidence of a partial expression of the defect was observed in offspring of two affected persons. There were no obvious clinical consequences of the defect.


Segregation analysis of thalassemia in Ferrara. Segregation analysis of 996 families in which the gene for beta-thalassemia was segregating showed no distortion of expected Mendelian ratios. No appreciable frequency of sporadic cases was detected. It was suggested that segregation distortion is not a mechanism which contributes to the maintenance of polymorphism in the beta-thalassemia system in the population of the Ferrara area.


Studies on African pygmies. V. Red cell acid phosphatase polymorphism in Babinga pygmies: high frequency of ACPR allele. A group of Babinga Pygmies from the Central African Republic have been analyzed for the acid phosphatase polymorphism with special reference to the ACPR allele. The frequency of this allele (17%) is one of the highest observed in Africa and is comparable only with those reported for the Khoikhoi and the San.


Effect of refrigeration on bactericidal activity of four preserved multiple-dose injectable drug products. The influence of refrigeration on the bactericidal capability of preservative systems in multiple-dose injectable drug products was studied. Commercially available multiple-dose injectable drug products containing preservatives--atropine/phenol, lidocaine/methylparaben, cyanocobalamin/benzyl alcohol and diphenhydramine/benzethonium chloride--were divided into two groups, one to be maintained under refrigeration (5C) and the other to be maintained at room temperature (25C). In separate tests the multiple-dose vials (MDVs) were individually inoculated with the following organisms: Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, and Serratia marcescens, and cultured to establish bacterial concentrations at 0, 1, 2, 4, 8 and 24 hours. Bacteria in the preservative systems tested remained viable significantly longer under refrigeration. (Data for diphenhydramine/benzethonium were not obtainable with the methodology used.) It is recommended that sterile medications maintained in preserved MDVs be stored at romm temperature after initial use (i.e., after exposure to possible contamination) unless drug stability considerations dictate otherwise.


Pharmacist-manned drug information centers in the United States. Pharmacist-manned drug information centers (DICs) were surveyed in early 1976 to obtain current information concerning the status, availability and scope of their services. Eight-six institutions believed to be active in disseminating drug information were surveyed; 74 responses were usable. Descriptive information on the respondents is tabulated. It appears that DICs make constructive contributions to enhancing drug therapy. Respondents at 63 of the centers believed, and 31 DICs said they have demonstrated, that physicians who used their services often changed their drug therapy based on answers supplied by the centers.


Pharmacy program for monitoring diabetic patients. Pharmacist involvement in a program for monitoring and treating diabetic patients in a 58-bed Indian Health Service hospital is described. Using guidelines established in conjunction with the medical staff, pharmacists interviewed patients to determine the status of their disease, evaluated laboratory data, and decided whether to dispense refills or have the patient evaluated by a physician. The pharmacist also provided patient education concerning the disease, treatment and self-care. During a 19-month period, 50% of 193 diabetic patients were monitored primarily by pharmacists. The increased involvement of the pharmacists has resulted in better use of their abilities and has freed more time for physicians to spend with patients who have complications.


Effect of plasma exchange on circulating immune complexes and antibody formation in patients treated with cyclophosphamide and prednisone. A patient with systemic lupus erythematosus (SLE) and a patient with an immune complex disease resembling Goodpasture's syndrome were treated with cyclophosphamide, prednisone and repeated plasma exchanges. Circulating immune complexes decreased, and symptoms of central nervous system disease remitted for up to 15 to 20 days after plasma exchange in the patient with SLE. In vitro lymphocyte blastogenic responses to antigens were also transiently increased on two occasions following treatment. In the second patient, decreases in circulating immune complexes and clinical improvement were ascribed chiefly to immunosuppressive drug treatment. Serum antibody to keyhole limpet hemocyanin was relatively unaffected by plasma exchange in both patients. These results suggest that plasma exchange may help to deplete circulating immune complexes or alter the equilibrium between soluble antigen and antibody which causes complexes to form and circulate. It may be less effective in reducing circulating antibody levels in patients who continue to produce new antibody.


Investigation of a new parameter in chronic lymphocytic leukemia: the percentage of large peripheral lymphocytes determined by the Hemalog D. Prognostic significance. The number of large peripheral lymphoid cells and the ratio of these large unstained cells to the total number of peripheral lymphocytes was determined by means of the Hemalog D in 57 patients with chronic lymphocytic leukemia (CLL) and in 100 control subjects. Although the absolute number of large unstained cells/mm3 is simply a reflection of peripheral lymphocytosis, the ratio large unstained cells to total lymphocyte count was shown to correlate with clinical staging. In control subjects, this ratio ranged from 3.2 per cent to 11¿per cent. In those with CLL it was less than 11.2 per cent in 43 patients and greater than 11.2 per cent in 14 patients. These 14 patients corresponded statistically to patients with advanced disease in our clinical staging system (stages III and IV). An increase in the large unstained cells to total lymphocyte ratio is therefore a statistical criterion of poor prognosis.


Penicillamine-associated myasthenia gravis, antiacetylcholine receptor and antistriational antibodies. Myasthenia gravis with thymic hyperplasia developed in a patient with Wilson's disease after eight years of penicillamine treatment. Four months prior to the onset of myasthenia, penicillin hypersensitivity was observed. Immunofluorescence on the excised thymus revealed immunoglobulin and complement deposition, but the myasthenia persisted after thymectomy and continuation of penicillamine therapy. Increased antiacetylcholine receptor antibody was demonstrable throughout. This patient subsequently became pregnant, enabling studies to be performed on the transplacental transfer of the immunoglobulin G (IgG) class antiacetylcholine receptor antibody. Eleven cases of rheumatoid arthritis with penicillamine-associated antistriational antibodies have also been observed; in three of these cases there was evidence of myasthenia gravis. These observations extend earlier reports of the association of penicillamine with myasthenia gravis and suggest that antistriational antibody, antiacetylcholine receptor antibody and thymic hyperplasia may be independent effects of penicillamine therapy.


Effects of corticosteroids in the treatment of patients with gastric aspiration. Forty-three of 88 patients suspected of having aspirated gastric contents met stringent criteria for the diagnosis of aspiration of gastric contents. One group of 25 patients was treated with corticosteroids and a second group of 18 patients was treated without corticosteroids. The two groups were clinically well matched according to all variables except that the patients who did not receive corticosteroids had greater hypoxemia and a higher incidence of infiltration on chest roentgenogram which would indicate that these patients had received greater pulmonary injury from aspiration of gastric contents. Thirty-two per cent of the patients who received steroids died compared to 28 per cent of those who did not receive steroids. Although the mortality rate difference was not statistically significant, the occurrence of gram-negative pneumonia five days after aspiration was more frequent in the patients treated with steroids.


The effect of the interaction of pyrazinamide and probenecid on urinary uric acid excretion in man. Complex interactions occur between pyrazinamide (PZA) and probenecid in man involving both the metabolism and distribution of the drugs, and their effects on renal tubules. Pretreatment with PZA prolonged the half-life (T 1/2) of probenecid without changing its plasma-binding. As the rate of probenecid metabolism is decreased, its uricosuric action tends to be prolonged and the effect of PZA lessened. The PZA-suppressible urate level is increased to values well above control after the administration of probenecid; it is less after alkalinization of urine, although still larger than the value for PZA-suppressible urate after the administration of PZA alone. Urinary probenecid excretion is much greater when urine is alkalinized. These observed drug interactions, plus the known effect of probenecid to block secretion of PZA, have to be considered in evaluating the effect of the two drugs given together, compared to the effect of each drug given separately.


Intestinal tuberculosis: experience at a Canadian teaching institution. Thirteen cases of inflammatory bowel disease suspected to be intestinal tuberculosis are analyzed. In nine, the diagnosis was established from such criteria as caseation necrosis, positive acid-fast stains or cultures of the diseased tissue. In four others, enteric tuberculosis remained a diagnostic possibility as judged by the following criteria: coexistence of the bowel lesion with established tuberculosis elsewhere, a clear response to antituberculous chemotherapy, or typical features on roentgenographic, surgical or histologic examination. The patients with intestinal tuberculosis were not necessarily recent immigrants or poor, nor did they have coexistent active pulmonary disease. Although most exhibited classic features of intestinal tuberculosis, the diagnosis was rarely considered at first. A greater awareness of the entity is needed to avoid confusion between intestinal tuberculosis and Crohn's disease.


Chlorpropamide-induced hypoglycemia: successful treatment with diazoxide. A healthy adolescent boy was treated on two occasions for an overdose of chlorpropamide (Diabinese). Glucose therapy alone was not sufficient to control the hypoglycemia, but the administration of glucose plus diazoxide raised the blood sugar to supranormal levels. A bolus of intravenous glucagon briefly raised the blood sugar level to within normal limits, increased the blood ketones but also augmented insulin secretion. An overdose of sulfonylurea may cause prolonged and fatal hypoglycemia. Rational therapy, both in diabetic and normal persons, is glucose plus an "insulin antagonist." The administration of diazoxide was effective in our patient, substantially reducing the plasma insulin level; this agent may be the "insulin-antagonist" of choice for use in sulfonylurea-induced hypoglycemia.


Left ventricular myxoma: echocardiographic diagnosis and review of the literature. A 33 year old man with the findings of mild aortic stenosis had an echocardiographic diagnosis of left ventricular myxoma prolapsing through the aortic valve during each ventricular systole. The M-mode echocardiogram, B-scan ultrasonogram and angiograms of this patient are presented. The clinical characteristics in all the reported cases of left ventricular myxomas are reviewed.


Trichinosis causing extensive ventricular mural endocarditis with superimposed thrombosis. Evidence that severe eosinophilia damages endocardium. Clinical and morphologic observations are described in a 46 year old woman with fatal trichinosis. Attention is called to the occurrence of extensive ventricular endocardial damage with superimposed thrombosis; Evidence is presented to indicate that the most likely cause of the endocardial damage is the associated eosinophilia. The mechanism by which eosinophils damage endocardium, however, remains obscure.