Quinidine plasma concentration and exertional arrhythmia.

Quinidine gluconate was used to treat arrhythmia induced with maximal exercise testing. Twenty-nine subjects who had previously developed frequent premature contractions on testing were selected for further study. After a control maximal exercise test, quinidine (10 mg. per kilogram) in solution was given orally in a single dose, and two hours later the same test was repeated. Recurrence of premature contractions was completely prevented in five of the 19 subjects tested; suppression was better than the mean value in three others, and in 11 subjects it was below the mean value. The plasma concentration at two hours was 1.68 plus or minus 0.31 ug per milliliter, which is a therapeutic level. Raising the dose to 15 mg. per kilogram eliminated the premautre contractions in six subjects whose response to 10 mg. per kilogram had not been complete, but not in two others. Lowering the dose to 5mg. per kilogram lowered the plasma level to below the therapeutic level. No differences between the responses to the drug of the otherwise healthy subject and those with symptomatic heart disease could be found. Compared with the responses to the control tests, there were small but significant changes in the second test in heart rates, blood pressure, and duration of exercise. Aerobic working capacity estimated by Vo2max was unchanged. Mild toxic effects manifested by malaise and diarrhea were a common finding with both 10mg per kilogram and 15mg per kilogram of quinidine, but not with 5mg per kilogram.


Electrophysiologic effects of isoproterenol on cardiac conduction system in man.

The effects of isoproternol (ISOP) on the functional properties of the A-V conduction system were studied in 16 patients using His-bundle recordings and the atrial extrastimulus technique. In all patients, ISOP at an infusion rate of 1 mcg. per minute resulted in sinus acceleration and enhancement of A-V nodal conduction, but had no effect on His-Purkinje conduction time. ISOP significantly decreased both functional and effective refractory periods of the A-V node. The relative refractory period of the His-Purkinje system decreased by a small amount in five patients in whom the parameter could be compared before and after the drug.


Wolff-Parkinson-White syndrome: mechanocardiographic study on the mechanical consequences of ventricular pre-excitation.

To elucidate the mechanical consequences of ventricular pre-excitation in patients with the W,W syndrome, electrical and mechanical events in the ventricles during anomalous pathway conduction and normal atrioventricular conduction were examined mechanocardiographically in 11 cases of Group A and 19 cases of Group B, in whom anomalous pathway conduction was stopped by procaine amide, resulting in normalization of conduction. Eight healthy persons were employed as a control group. In the control group, procaine amide had no significant effect on the mechanocardiographic values. In the WPW syndrome, significant prolongation of the P-X, P-J, P-T, P-C, P-I, P-Ao, and P-II intervals was induced by the drug. From the results of statistical analyses of measured values, it would appear that mechanical events in the ventricles were accelerated by ventricular pre-excitation but the extent of acceleration of the former was less than the extent of prematurity of the latter. The anomalous ventricular pre-excitation occurred earlier in cases of Group B than in those of Group A, while initiation of ventricular contraction, atrioventricular valve closure, and aortic vlave opening were accelerated more in Group A. In one case of Group B, electrical phenomena could not be related to mechanical events.


Velocity of contractile element shortening in constrictive pericarditis and the effect of pulsus paradoxus.

Force-velocity curves were constructed in nine patients with CP from a high-fidelity LV pressure tracing and its simultaneously recorded first derivative. Vmax and peak Vce (Vpm) were calculated using the 2-element (Hill) or Voigt model; the curves were also constructed and Vmax measured using the 3-element Maxwell model. The measurements were compared with those in a group of four patients with CMO and with two control subjects. Measurements of the celerity of ventricular contraction--peak LVdp/dt, Max d/IP and Vmax (2-element model)--were reduced in CP and greatly reduced in CMO. The effect of beat-to-beat variations in preload during pulsus paradoxus on the indices of ventricular celerity was studied. Peak LVdp/dt and Vpm varied with the change in LVEDP: the change in Vmax was negligible using the 2-element (Hill) or Voigt model. The 3-element (Maxwell) model failed to discriminate between the three groups of patients and seems to be invalid at high LV end-diastolic pressures.


Effects of dexamethasone on myocardial cells in the early phase of acute myocardial infarction.

Dexamethasone exerted no significant hemodynamic effect in sham-operated cats or in cats subjected to acute myocardial ischemia. However, the glucoccortcoid did normalize elevated S-T segments toward pre-ischemic values, and prevented much of the increase in plasma CPK activity following coronary artery ligation. Moreover, dexamethasone prevented loss of CPK activity and restricted the loss of lysosomal hydrolase within ischemic myocardial tissue. These data indicate that lysosomal disruption is an early consequence of myocardial ischemia and that treatment with dexamethasone prevents the loss of myocardial lysosomal and cellular enzymes as reflected in normalization of the ECG  and plasma CPK activity of ischemic cats. In this way, dexamethasone may act to retard the spread of the developing infarct within the ischemic myocardium.


Increasing the inotropic effect and toxic dose of digitalis by the administration of antikaliuretic drugs--further evidence for a cardiac effect of diuretic agents.

In prior studies, we have shown that the antikaliuretic drugs, triamterene and amiloride, through a direct cardiac effect reduce the loss of cardiac potassium induced by the administration of digitalis. Since loss of myocardial potassium is thought to underlie digitalis arrhythmias, this study was performed to determine whether triamterene and amiloride also extend the toxic dose and thus the therapeutic effect of digitalis. In twelve dogs, acetylstrophanthidin was infused (100 ug per minute) serially at 2.5-hour intervals. Trimterene (400 mg. in divided doses) was infused before the third acetylstrophanthidin infusion. This extended the dose required to produce a toxic arrhythmia by 110 per cent. In fourteen additional studies, nine dogs received 400 mg. of triamterene prior to the third acetylstrophanthidin infusion and five animals received 100 mg. of amiloride during the same period. In these fourteen studies, not only was the toxic dose of digitalis extended, but its inotropic effect (see article) (common peak developed isovolumic ventricular pressure) was also increased. These studies have demonstrated that through a cardiac effect, by reducing the digitalis-induced loss of cardiac potassium, the potassium-sparing drugs, triameterene and amiloride, extend the toxic dose of digitalis and thus permit txtension of its inotropic activity.


Lumbar punctures and meningitis.

Four patients, with an additional seven from the literature, had meningitis following a lumbar puncture (LP) that disclosed normal cerebrospinal fluid (CSF). Animal studies demonstrate that perforation of the meninges in the presence of bacteremia enhances the development of meningitis. Simultaneous blood culture should be obtained with all LPs. Regardless of the results of the initial LP, a second CSF examination is recommended in any patient whose clinical condition is deteriorating. If the initial blood culture is positive, a second LP should be strongly considered in all newborn and very young infants.


Suppuration of the submandibular salivary glands in the neonate.

Suppurative sialadenitis is rare in the neonate and usually involves the parotid glands. Two cases are reported of suppuration of the submandibular gland in the newborn. Diagnosis was made by clinical signs of infection, appearance of a unilateral, erythematous submandibular mass, and expression of pus from the orifice of Wharton duct under the tip of the tongue. Gram stain, culture, and antibiotic sensitivity studies were done on the purulent material. Staphylococcus aureus grew in both cases and was sensitive to treatment with methicillin sodium. This report discusses the management of these cases, with speculation about the possible cause. To my knowledge, these are the only two cases found in the literature of suppurative submandibular sialadenitis occuring as an isolated lesion in the neonatal period.


Cystic fibrosis and hypertrophic osteoarthropathy in children. Report of three cases.

Three patients with cystic fibrosis were noted to have swelling of knee and ankle joints during exacerbation of their lung disease. Synovial fluid was analyzed in one patient and the synovium underwent biopsy in another. These studies excluded other causes of arthritis but did not contribute any new information on the nature of secondary hypertrophic osteoarthropathy. Radiological examination of long bones confirmed the diagnosis of hypertrophic osteoarthropathy in all three patients. Since many patients with cystic fibrosis survive longer, more instances of hypertrophic osteoarthropathy are expected in the future.


Future health professional practice in America.

The changes which our health delivery system must undergo in order to respond to the health needs of our society by the year 2000 are presented. The discussion centers on two sets of forces: the necessity for institutionalization and the need for knowledge, information and understanding. Specialization as a means for division of labor among health professionals is predicted to increase.


Role of the pharmacist in primary health care.

The provision of primary health care to a rural American Indian population by a pharmacist is discussed. The training and responsibilities of the pharmacist are described. An evaluation of the care provided by the pharmacist to 393 patients is presented.


Flow rate maintenance and output of intravenous fluid administration sets.

Seven brands of intravenous fluid administration sets were studied to determine: (1)which set(s) maintained the most consistent flow rates; (2) if  the type of fluid container (open, vented or closed, nonvented) affected the flow rates of administration sets; and (3) which set(s) closely approximated the theoretical amounts of fluid to be delivered in one hour at flow rates of 60,100 and 125 ml/hour. Six samples of each brand of administration set were tested in a laboratory setting which approximatedclinical conditions. The type of fluid container had little effect on the performance of the administration sets. The ARDL set was the most accurate in terms of the average volume of fluid delivered in 24 hours. The Burron set required fewer adjustments in 24 hours to maintain a constant flow rate. The U.S. Surgical set recordedthe smallest percent change in flow rate at the end of the first hour. The U.S. Surgical set is rated superior in overall performance. Based on the results of the study,the authors make recommendations to health care personnel, the pharmaceutical industry and the U.S. Pharmacopeial Convention.


Medication errors in a multidose and a computer-based unit dose drug distribution system.

The medication error rates of a hospital's multidose and computer-based unit dose drug distribution systems were compared; in addition, the medication error rate of the unit dose system was compared to that reported for noncomputerized unit dose systems in other hospitals. Two similar adult, medical, patient care units, each serviced by a different drug distribution system, were studied for 60 days. Information about the medications administered was obtained by the disguised observation technique during intermittent periods. The observer's notations on the medications administered were compared to the physicians' orders to determine if errors had been committed. Only medication "errors of commission" were recorded. There were significantly fewer medication errors and significantly fewer medications administered at the wrong time in the unit dose system. The medication error rate associated with the unit dose system compared favorably with that of most other unit dose systems. No particular benefit, in terms of the medication error rate, was attributed to the computer element of the unit dose system.


Treatment of acute isoniazid toxicity.

The clinical symptoms and treatment of acute isoniazid toxicity are presented. The use of supportive measures and chemotherapy are discussed in detail. The pharmacology and biochemistry underlying the symptons of isoniazid poisoning are aslo presented. It is concluded that diazepam in combination with pyridoxine is the treatment of choice for the management of convulsions associated with isoniazid toxicity. Pyridoxine should be administered intravenously in amounts equal to the estimated quantity of isoniazid ingested, even if seizures have not occurred.


Journal of Clinical Computing articles on pharmacy computer applications.

A review of articles on pharmacy applications of computer-assisted data processing,published in two issues of the Journal of Clinical Computing, is presented.


Implications of certificate of need legislation for institutional pharmacy practice.

Federal certificate of need legislation (Section 1122 of Public Law 92-603)aimed at the elimination of costly, duplicative or unneeded health care expenditures is discussed. This law applies only to institutional providers receiving federal reimbursements. The key issues for pharmacy are that proposed substantial changes in service and capital expenditures of $100,000 or more must be justified to local and state comprehensive planning agencies prior to implentation. Failure to comply with the legislation can result in a reduction or withholding of federal reimbursement.


Quantitative determination of alkaloids in belladonna tincture USP.

A simplified method for the quantitative analysis of hyoscyamine hydrobromide or atropine in Belladonna Tincture USP is described. The procedure is based on the formation of an alkaloid-dye complex which can be extracted with an organic solvent and measured spectrophotometrically. The results obtained by this method compare favorably with those obtained by the USP method.


Recommended methods for compounding intravenous admixtures in hospitals.

Recommendations regarding (1)hospital receipt and storage of large-volume parenterals and (2)hospital compounding of intravenous admixtures are presented. The recommendations are presented in a stepwise manner, and a self-evaluation form is included. Also included is a pictorial illustration of a suggested dressing change for an i.v.catheter.


Quality assurance for hospital pharmacy. Part I: Basic concepts.

The basic concepts of quality assurance are discussed as they apply to hospital pharmacy practice. The terms norm, criteria, standard, structure assessment,process assessment, and outcome assement are defined. The interrelationships among the following five steps in the quality assurance cycle are reviewed: definition of quality, quality assessment, education and change, redefinition of quality, and reassessment of quality. Finally, the importance of research in the quality assurance process is discussed.


Adherence to approved drug use as a predictor of length of hospital stay.

The relationship between adherence to approved drug labeling and patient length of stay in hospitals was studied. The records of 200 patients at a 175-bed, short-term, pediatric hospital were reviewed to determine if the actual drug therapy agreed with the officially approved indications, contraindications, age restrictions and dosages. The average length of patient stay was nine days. Only 19% of the observed variation in length of stay could be correlated to the number of doses per drug per patient. The variable dose, indications, contraindications and age agreement could not be correlated to length of stay.


Assuring the quality of medications stored in patient care areas.

A program designed to improve patient care by assuring the quality of medications stored in patient care areas is described. A questionnaire covering six major areas--medication room, controlled substances, refrigerator, emergency medication kit, other storage areas and miscellaneous--designed to assist in gathering information during medication quality assurance rounds was developed. Rounds are conducted every four months by a pharmacist and a nurse. To ensure that any deficiencies are corrected, copies of the findings are sent to the appropriate pharmacy and nursing personnel.


Drug use and distribution in a pain rehabilitation center.

A 23-bed hospital unit specializing in rehabilitating patients suffering from chronic pain by (1) reducing their consumption of and dependence on medication, (2) increasing their level of daily activity and (3) discouraging pain-oriented behavior is described. In addition to aspirin or acetaminophen, four drugs--amitriptyline, diphenylhydantoin, cobra venom extract and methadone--are used to reduce pain while other therapeutic measures are used to rehabilitate the patients. Methods for reducing the amount of analgesics taken by chronic pain patients are discussed. Unit dose packaging is used because the oral solid dosage forms (including placebos) are made to look alike.


Inhibition by ice cream of the antidotal efficacy of activated charcoal.

A study was conducted to determine if ice cream and sherbet interfered with the adsorption of aspirin onto activated charcoal both in vivo and in vitro. An aqueous suspension of 20 g activated charcoal decreased the absorption of 1 g aspirin by 65%; the same dose of activated charcoal with 50 g of ice cream reduced aspirin absorption by only 42% under otherwise identical conditions. In vitro tests showed that different ice creams and sherbet decrease the adsoprtion of aspirin onto activated charcoal. Thus, although ice cream is useful for preparing palatable suspensions of activated charcoal, it decreases appreciably the antidotal efficacy of the adsorbent.


Practical pharmacokinetic techniques for drug consultation and evaluation. IV: Gentamicin blood level versus time profiles of various dosage regimens recommended for renal impairment.

The gentamicin blood level vs. time profiles of various dosage regimens recommended for renal impairment were reassessed by applying pharmacokinetic techniques to the patient data in the clinical literature. Eight dosage regimen modifications were tested in eight prototype cases of renal impairment (serum creatinine range of 0.9-12.0 mg/100 ml and creatinine clearance range of 5-100 ml/min/1.73 m-2) using simulated blood level vs. time profiles generated from the known pharmacokinetic parameters for gentamicin. Employing a one-hour intravenous infusion at dosages and dosing intervals recommended by the various blood level vs. time profiles. Methods recommending shorter dosing intervals (every 24 hours and less) generally resulted in a greater percent duration of the dosing interval above the selected "effective response concentration" (ERC) of a 4mug/ml blood level and a markedly shorter duration of sub-ERC blood levels. Methods based on creatinine clearance as an index of renal function generally achieved greater percent duration of the dosing interval above the ERC and lesser duration of blood levels below this value than methods based on serum creatinine.


Diuretics.

The use of diuretics to treat edema is reviewed. Normal salt and water metabolism is reviewed briefly. The drugs covered are the thiazide diuretics, loop diuretics(ethacrynic acid and furosemide) and distal blocking agents (spironolactone and triamterene). The sites and modes of action, indications, doses, complications and relative costs of these agents are discussed.


Specific hypotensive and antihypertensive ocular effects of d-isoproterenol in rabbits.

d-Isoproterenol (ISO) applied topically to the rabbit eye specifically lowered intraocular pressure. Thus, it effectively reduced normal intraocular pressure and inhibited intraocular pressure elevation induced by water load without causing other obvious local or systemic pharmacologic effects. By comparison, dl-ISO was pharmacologically nonspecific in that amounts required to reduce intraocular pressure also produced significant and marked tachycardia. Furthermore, maximal intraocular pressure reduction was less with dl-than with d-ISO. Accordingly, and in consideration of reported clinical experience with dl-ISO in glaucomatous man, the d-isomer should be the preferred form of ISO for treating glaucoma. d-ISO should offer advantages over any other topical medication used currently in the treatment of this condition. Toxicity studies employing large, topical doses of drug in rabbit eyes showed that d-ISO was free from ocular irritation as well as systemic toxicologic effects and should be safe for controlled studies in man.


Visual parameters associated with recovered retrobulbar optic neuritis.

Visual acuity, color vision, pupillary reaction, induced Pulfrich phenomenon, kinetic fields, static fields, afterimage testing, and ophthalmoscopic evaluation were studied in nine patients with a history of retrobulbar neuritis. The most consistently reliable test for determining the presence of an old optic nerve defect in these patients was meridional 0 to 180 degrees static perimetry. There was a uniform decrease in brightness discrimination to either side of the foveal peak.


Bulbar ligneous conjunctivitis after pterygium removal in an elderly man.

Ligneous conjunctivitis occurred unilaterally in a 74-year-old man after pterygium excision and only involved the bulbar conjunctiva. Histochemical studies confirmed the presence of mucopolysaccharides in the lesion sensitive to hyaluronidase. The patient was treated successfully with topical hyaluronidase and alpha-chymotrypsin, with no recurrence 20 months after cessation of therapy.


Absence of spontaneous head tilt in superior oblique muscle palsy.

We used the head-tilt test--based on an imbalance between the function of a paretic superior oblique muscle and its homonymous superior rectus muscle, rather than on an anomaly of cycloversion-to test three patients with superior oblique muscle palsies. Spontaneous ocular torticollis was absent if a patient had poor vision in one eye or if his vertical fusional amplitudes were of such magnitude that he was able to overcome his vertical deviation in all positions of gaze. These latter instances, though rare, may be more common than reports indicate.


Stereoacuity development in children with normal binocular single vision.

We made 344 stereoacuity determinations (Titmus Stereotest) on 321 children, ages 1 1/2 to 13 years, who had normal binocular single vision tested by other factors. The data showed a gradual improvement in stereoacuity scores with increasing age--up to age 9--when a normal stereoacuity of 40 seconds of arc was consistently found. The lower limits of stereoacuity compatible with normal binocular single vision were 3 1/2 years, 3,000 seconds; 5 years, 140 seconds: 5 1/2 years, 100 seconds; 6 years, 80 seconds; 7 years, 60 seconds; and 9 years, 40 seconds.


Genetic analysis of vergence measures in populations with varying incidences of strabismus.

Genetic parameters were contrasted for vergence amplitudes within three populations--esotropic, exotropic, and randomly selected populations-who differed in their incidence of subtypes of strabismus. In general, heritabilities for convergence exceeded those for divergence, and heritabilities for recovery points exceeded those for break points. Heritability estimates for diveregence amplitudes were significantly different for the random and esotropia populations, while convergence heritability estimates for these groups were similar. Thus, gene differences influencing divergence ability contributed to genetic variance for strabismus.


Lateral rectus muscle paralysis associated with closed-head trauma.

We examined 21 patients with closed-head trauma and resulting paralysis of the lateral rectus muscle. Clinical findings included laterally directed gaze palsy, some unconsciousness, and pseudo-duane's phenomenon suggesting a supranuclear lesion at the level of the upper pontine tegmentum, and pontine paramedial reticular formation. The surgical procedure of choice was a "midline operation," that is, the appropriate number of millimeters of recession and resection to achieve 0 to 5 degrees of exotropia in the primary position of gaze. Frequently, the medial rectus muscle must be recessed 10 nm or more and the lateral rectus muscle resected 10 nm or more to achieve this result. None of the 21 patients had diplopia after the midline procedure.


An evaluation of the role of leukocytes in the pathogenesis of experimentally induced corneal vascularization.

Studies of corneal explants in the hamster cheek pouch chamber have demonstrated that blood vessels invade the cornea only if the tissue is first infiltrated by leukocytes. In view of this observation, a comparative study of the events that precede and accompany corneal vascularization was undertaken in various experimental models. A variety of established methods were used to induce corneal vascularization, including exposure of the cornea to noxious agents, intracorneal injection of antigens into sensitized animals, as well as maintaining animals on diets deficient in vitamin A or riboflavin. In all models studied, the corneal vascularization was a manifestation of the reparative phase of the inflammatory response. A conspicuous leukocytic infiltrate of the cornea preceded and accompanied the corneal vascularization in all of the models. Although the lesions varied in several respects in the different models, all models displayed three phases with regard to vascularization: an early prevascular phase of leukocytic infiltration, a second phase where blood vessels persisted in the cornea in the absence of leukocytes. The latent period that preceded vascularization was directly related to the time of the initial leukocytic infiltration. The models in which a delay occurred in the leukocytic invasion displayed a subsequent delay in the vascular ingrowth. Conversely, in experiments where there was a rapid and extensive leukocytic invasion, there was also an early and enhanced corneal vasoproliferative response. In the various modesl investigated, the sites of the leukocytic infiltration and subsequent vascular ingrowth into the cornea paralleled each other. The data further support the hypotheses that leukocytes are a prerequisite to corneal vascularization and that leukocytes produce one or more factors which stimulate directional vascular growth.


Postmorten changes in the chemistry and histology of normal and edematous brains.

The brains of 18 patients were examined post mortem for histologic criteria of edema, and samples of white and gray matter were analyzed for water, sodium, and potassium content. In a parallel experimental study, brains of cats with unilateral freezing lesions and resulting cerebral edema were similarly examined immediately after death and up to 18 hours post mortem. In both types of material, in gray matter there was a relatively rapid (within less than 4 hours) increase in water and sodium content and fall in potassium content. In normal and edematous white matter, little change was observed post mortem. No correlation could be demonstrated in any of the material studied between water content and histologic grading for cerebral edema. It is concluded that determination of water content in the white matter postmortem could be a useful tool for the neuropathologist. Histologic assessment of cerebral edema is of little value.


Early, reversible plasma membrane injury in galactosamine-induced liver cell death.

Administration to rats of D-galactosamine (400 mg/kg) produces liver cell death that develops during the first 24 hours. Plasma membranes isolated within the first few hours from these animals show a 40% reduction in 5'-nucleotidase activity and a two-fold increase in maximum negative ellipticity determined by circular dichroism. Simultaneous administration of uridine prevents liver cell death and these early alterations in the plasma membranes. Uridine also prevents cell death if administered for up to 3 hours after galactosamine. The 5'nucleotidase activity reduced when uridine is administered for up to 2-1/2 hours after galactosamine. Changes in the liver calcium ion concentration accompany these plasma membrane alterations. Uridine will prevent and reverse the changes in calcium content in parallel to its ability to reverse the membrane alterations. The significance of these findings with respect to the mechanism of galactosamine-induced liver cell death is discussed.


Effects of ischemia on the hind limb of the rat.

The effects of ischemia, induced by a tourniquet, were investigated on 36 adult Holtzman female rates in terms of damage to the ventral horn cell of the spinal cord and tibial nerve and motor end-plate degeneration and regeneration. Clinically, the rats were tested for sensory and motor loss and recovery and these results were compared with the histological findings. Ischemic periods of 2, 4, 6, and 8 hours were used followed by survival times of 3 weeks to 9 months. Histologically, there was degeneration and regeneration found to varying degrees in the nerve and motor end-plate. There were no changes found in the ventral horn cell. There was a loss of pain sensation in all animals, except the 2 hour group, and a loss of motor function. Motor function, preceded by sensation, returned in all animals. With the absence of ventral horn cell damage it was not surprising to find adequate regeneration histologically and, therefore, a return of both sensory and motor function.


Electromyographic study of unlateral and bilateral measurement conditions of reflex, premotor, and simple reaction time to joint displacement.

The purpose of the study was to study the effects of cross-transfer on fractionated reaction time components in the unilateral and bilateral measurement conditions. Ss (N = 30) responded to a sudden arm displacement from an electromagnet by abducting the falling arm (unilateral ipsilateral trial, N = 15), by abducting the non-stimulus limb from a RT switch (unilateral contralateral trial, N = 15), or by performing both of these responses simultaneously (bilateral trial, N = 15). EMGs from the 45 randomized trials were monitored from the middle portions of the relaxed deltoideus muscles. Dependent variables were ipsilateral reflex latency (IRL), ipsilateral premotor time (IPMT), contralateral premotor time (CPMT), and contralateral reaction time (CRT). The following statistical procedures were applied to the data: an interclass correlation, a subjects-by-trials analysis of trends for each variable, and a single-groups subjects by two within-group variables analysis of variance for the six logical comparisons. IPMT was the only latency decreased by the addition of the bilateral measurement condition; however IPMT remained slower than CPMT even in the bilateral measurement condition. IRLs, CPMTs, and CRTs remained the same. The addition of a bilateral measurement condition appeared to result in less delay from the synchronous reflex volley to IPMT than in the unilateral measurement condition.


Multichannel biotelemetry systems for use in EMG studies, particularly in locomotion.

The authors describe their experience with the different types of telemetry systems, applicable for locomotion studies and other similar areas of research. They describe the differences between frequency modulation (FM) systems and time-domain multiplexing (PAM) systems. They discuss the advantages and the disadvantages of each of these systems, particularly as applied to the transmission of EMG signals.


Some observations and questions in intensive psychotherapy.

The authors discuss their observations of acute psychiatric patients in a day hospital, noting the universality of the existential concerns that arise once the patient has confronted his illness. They discuss the problem of what determins a "cure" in emotional disturbances and suggest that the primary issue is for patients to learn to live as healthy people within the limits of their individual potential.


Obstacles to utilization of prepaid mental health care.

The coverage of out-of-hospital expenses for mental health care through prepayment and insurance programs has been a major advance in removing the economic barriers to early detection, diagnosis, and treatment of mental disorders. However, obstacles to obtaining treatment block many eligible people from receiving help. The authors conducted a study among members of the United Auto Workers union to identify these roadblocks. Among the obstacles were differences in perceptions of need for treatment and in attitudes toward treatment, and lack of awareness of eligibility for benefits among three key groups - consumers, referral agents, and providers. The authors urge psychiatry to help in removing these obstacles.


"Sociopathy" and its synonyms: inappropriate diagnoses in child psychiatry.

The use of the diagnosis "sociopathy" and its synonyms hinders the search for other kinds of symptomatology, the recognition of which might lead to appropriate therapeutic intervention. The authors therefore suggest that the terms "sociopathic personality," "antisocial personality," and "acting out aggressive reaction of childhood or adolescence" be eliminated as primary diagnoses from the psychiatric nomenclature for children or adolescents. Two case reports are presented to emphasize the damage these diagnoses can cause.


The psychiatric chief residency: a preliminary training experience in administrative process.

Drawing on their experience, the authors explore the opportunity for learning administrative process that is available to the psychiatric chief resident. They categorize six models of the psychiatric chief residency and document two of them, the ward chief and the interface chief, as providing particularly rich administrative experiences. Although the chief resident's administrative experience is only a preliminary one, it can be a first step in solidifying his identity as a clinician-executive.


Comprehensive drug programs: the Dade County example.

The authors present data from a survey of four methadone maintenance programs, five outpatient clinics, six nonresidential facilities, and nine therapeutic communities affiliated with the Dade County Comprehensive Drug Program. The treatment population included more blacks but fewer Latins than the general county population. Primary drugs of abuse were narcotics in methadone clinics and "softer" drugs in outpatient and nonresidential facilities. Most patients were either self- or court referrals. Direct per patient costs, which were lowest in the outpatient clinics, averaged $1,041. The authors suggest that their data may aid other comprehensive drug treatment programs in establishing guidelines.


Manic-depressive illness and good prognosis schizophrenia.

The authors examined 88 patients with an admission diagnosis of schizophrenia for the presence of good and poor clinical prognostic signs and related their findings to the clinical presentation, response to somatic treatments, and prevalence of illness in first-degree relatives. The results augment the growing evidence that good and poor prognosis schizophrenia are different illnesses and that good prognosis schizophrenia is frequently indistinguishable from manic-depressive illness.


Delayed severe extrapyramidal disturbance following frequent depot phenothiazine administration.

The authors report the occurrence of a sever striopallidal disorder in a schizophrenic patient one week after he received fluphenazine enanthate injections on an every-other-day schedule. In view of current interest in depot psychopharmaceuticals, they recommend that careful attention be given to dosage and administration schedules and to the possibility of delayed pseudoparkinsonian symptoms. Emergency room physicians should be alerted to the possible side effects of such drugs.


The summit-annotated contract technique for hospitalized adolescents.

The author describes a technique for use with adolescents (perferably nonpsychotic, acting-out patients) in the terminal phase of psychiatric hospitalization. Patient, parents, and therapist have a summit meeting during which they write a contract which is a prerequisite of the patient's discharge. The document, which all parties sign, specifies conditions of the patient's return to family life. A case report, including a contract, illustrates the use of the technique.


Personality Characteristics of Viet Nam veterans identified as heroin abusers.

The author presents data on the Minnesota Multiphasic Personality Inventory (MMPI) characteristics of a sample of enlisted Army men returning from Viet Nam identified as heroin abusers. Although a marked heterogeneity of MMPI profile types was found, a significant percentage of the subjects showed indications of marked psychopathology, and only a minority performed within normal limits on the MMPI. Theses military subjects showed neither greater nor less psychopathology and sociopathology than previously reported samples of civilian addicts.


Psychosexual and cultural determinants of fertility choice behavior.

Although traditional societies in Oceania direct their fertility choice behavior (if any) toward spirits rather than sexual intercourse, closer observation shows that these fertility choice behaviors, while groping and magical, sometimes have empirical value. The author notes that the alternative to effective fertility control in these societies has sometimes been population regulation of the Malthusian variety (e.g., murder and starvation). Efforts aimed at spacing the family in a less savage and more effective manner deserve encouragement, the author believes.


A syndrome of depression and mutism in the Oglala Sioux.

The wacinko syndrome in the Oglala Sioux varies from a nonclinical reaction to pathological degrees of anger, pouting, withdrawal, depression, psychomotor retardation, mutism, immobility, and even to suicide. Although indigenous proctitioners recognize the syndrome as a distinctive disorder, it has not been described by non-Indian practitioners. The author presents a case report and suggests that most cases are diagnosable as reactive depressive illness.


Anatomy of the thalamoperforating arteries with special emphasis on arteriography of the third ventricle: Part I.

The thalamoperforating arteries are divided into 2 distinct groups, an anterior and a posterior. The PTPAS are retromammillary branches of the precommunicating segments of the posterior cerebral arteries. The PTPAS may be divided into interpeduncular, mesencephalic and thalamic segments and are not directly related to the third ventricle. They are primarily midbrain and thalamic arteries. The main trunk of the PTPA (mesencephalic segment) normally does not undulate, but assumes a characteristically straight configuration. The ATPAS arise from the posterior communicating arteries anterior and lateral to the mamillary bodies. The ATPAS are primarily diencephalic vessels. Interpeduncular, paraventricular (hypothalamic) and thalamic segments may be identified. The major segment of the ATPAS is para third ventricular in location at the level of the massa intermedia.


Tomographic findings of the inner ears of 24 patients with Waardenburg's syndrome.

The tomographic findings in the Stenvers' projection of inner ears of 24 patients with Waardenburg's syndrome are described. In 12 of these 48 inner ears deafness was found. The roentgenographic examination did not show any malformation of the inner ears of these patients. In the literature on this subject, the tomographic findings of the inner ears of 12 deaf patients with Waardenburg's syndrome have been described. In 8 of them malformations were reported, especially of the semicircular canals. These findings in the literature could not be confirmed by our study.


Congenital absence of bilateral vertebral arteries with occipital-basilar anastomosis.

In the present case, a patient with symptoms referable to the occipital lobe, selective angiography demonstrated evidence of occlusion of branches of the left posterior cerebral artery with collateral circulation in addition to the congenital anomaly. The congenital absence of both vertebral arteries with a large occipital-basilar anastomosis may be explained by our hypothesis that occlusion occurred at the gestation age of 32-36 days. This case is presented in the hope that it will lead to the recognition of similar anomalies and further support our hypothesis. Selective angiography is the method of choice in the study of cerebrovascular disease and brachiocephalic vessels.


B-Mode sonography as a screening procedure for asymptomatic carotid bruits.

Sixty-five B-mode carotid sonograms were obtained at random on patients undergoing cerebral arteriography. A 5 mHz transducer was used. The results were correlated with magnified cervical carotid arteriograms obtained on these patients. B-mode sonography was accurate in evaluating the carotid arteries for surgical stenosis in 72 per cent of the cases. The feasibility of using B-mode sonography as a screening test in patients with asymptomatic carotid bruits is discussed.


Hypnotherapy in the treatment of bronchial asthma.

The efficacy of hypnotherapy in aborting acute asthmatic attacks was studied in 17 children ranging in age from six to 17. All had as their primary diagnosis bronchial asthma. Prior to hypnotic induction pulmonary function was assessed, then monitored in the immediate post hypnotic period and at two intervals thereafter. The average improvement for all subjects was greater than 50% above the baseline measurement as documented by spirometry, monitored dyspnea, wheezing and subjective ratings by the subjects. It is suggested that hypnotherapy may be an important tool in ameliorating asthma, improving ventilatory capacity and promoting relaxation without recourse to pharmacologic agents. One explanation offered is that hypnosis affects an automic response, thereby diminishing bronchospasm.


Allergy epidemiology in the St. Louis, Missouri, area. I. Fungi.

1728 patients prick skin tested for eight fungi in the St. Louis, Missouri metropolitan area exhibited overall a rather low level of allergenicity as well as a general lack of cross-reactivity. Alternaria, however, elicited a high allergic reaction in both reactivity level and reaction frequency in the population. Response of pediatric patients was higher than that of adults, and the extract concentration and source varied the allergenic response only slightly.


Study of an attenuated Anaplasma marginale vaccine in Mexico natural challenge of immunity in an enzootic area.

An evaluation was made of the protection induced by an attenuated Anaplasma marginale vaccine in young purebred cattle against the challenge exposure of naturally transmitted anaplasmosis in enzootic areas of Mexico. The cattle, which were raised in isolation units free of arthropods, consisted of 10 Brown Swiss calves (1 to 13 months of age) and 8 Holstein calves (5 to 7 months of age). They were paired by breed, age, and body weight, and allotted to 2 equal groups. Calves in 1 group were vaccinated, and at 6 weeks after vaccinations were done, calves in both groups were placed in the field where they were raised for approximately 1 year. Two Holstein and 3 Brown Swiss calves of the nonvaccinated group (group 2) developed clinical anaplasmosis, and the remaining calves of this group had hematologic evidence of the disease during the 2 to 4 months after introduction to the field. The vaccinated group, which remained free of anaplasmosis, showed consistently greater weight gain than did the controls. Among the Holstein calves, the maximum weight difference in favor  of the vaccinated group was 50 kg/head at 5.5 months after field exposure, and among the Brown Swiss calves, the differences in weight gain in favor of vaccinated calves at the end of the 12-month period was between 11 and 30 percent. It is concluded that the vaccine provided a means for safe adaptation of high-quality young cattle to the tropics by protecting them against what appears to be the major obstacle to this practice, anaplasmosis.


Physiologic responses to exercise of irradiated and nonirradiated Shetland ponies: a five-year study.

Physiologic responses of irradiated and nonirradiated Shetland Ponies to controlled exercise were measured over a period of 5 years. The 5-year test began when the ponies were 3 years old and 5 months after they were exposed to 650 R of 60-Co gamma radiation. Significant differences in heart rates, respiratory rates, and rectal temperatures were demonstrated between irradiated and nonirradiated ponies when subjected to exercise and high ambient temperatures. Inthe irradiated group, heart rates were usually slower, especially during recovery immediately after exercise, and respiratory rates and rectal temperatures were higher than these rates were in the nonirradiated group when exercising in ambient temperature of 29.5 C. Exhaustive exercise did not amplify any of the differences which were apparent with moderate exercise. From a general viewpoint, the irradiated ponies performed work as efficiently as did the nonirradiated ponies. Early changes in blood-cell concentrations after irradiation were similar to those which have been observed in other large animal species. Time required for the various types of blood cells to return to base line values ranged between 3 months and 3 years.


Bile secretion in ponies with biliary fistuals.

Surgically placed bile duct cannulas allowed collection of secreted bile from nonanesthetized ponies. UNINTERRUPTED ENTEROPHEPATIC CIRCULATION WAS PERMITTED BETWEEN COLLECTIONS. Deleterious effects of cannulation were not observed. Average bile flow was 18.6 plus or minus 1.72 (standard error) mul/minute/kg, bile acid excretion was 0.179 plus or minus 0.0212 mumole/minute/kg, and bilirubin excretion averaged 1.22 plus or minus 0.136 mug/minute/kg.


A system of grading ossification in limbs of foals to assist in radiologic interpretation.

Tetracycline-labeled bones of 23 foals from 52 to 104 days old were sectioned and macroscopically examined to assess the extent of ossification or fusion of ossification centers. A grading system was devised with which to record information about the ossification centers and growth plates. The objective was to define anatomic standards which could contribute toward obtaining an accurate radiologic interpretation. Labeled limb bones of 3 neonatal foals were similarly treated, but grading of these was limited to the consideration of whether each site was still cartilaginous or had commenced to ossify.


Glossitis of military working dogs in south Vietnam; histopathologic observations.

Glossitis, known clinically as "redtongue," was studied in tissues from 34 military working dogs (MWD) in the Republic of Vietnam. This condition was manifested grossly by loss of lingual papillae on the dorsal margins of the rostral third of the tongue. Microscopically, the principal lesions consisted of loss of filiform papillae, hemorrhage and edema in the lamina propria, acanthosis, and cellular infiltration. The cause of glossitis remains unknown at this time.


Absence of sensitization to epinephrine-induced cardiac arrhythmia and fibrillation in dogs and cats anesthetized with CI 744.

Ci 744 (20 mg/kg, given intramuscularly (IM) produced a reliable level of surgical anesthesia in both dogs and cats. Animals anesthetized in this way did not have an increased sensitivity to cardiac fibrillation after they were given epinephrine. Epinephrine-induced ventricular arrhythmia observed in C1 744-anesthetized animals was eliminated in cats and was markedly reduced in dogs by bilateral vagotomy. Myocardial fibrillation was not produced by epinephrine (0.1 to 100 mug/kg, intravenously (IV) in dogs and cats anesthetized with C1 744 alone. Pentobarbital anesthesia, like C1 744 anesthesia, did not sensitize the heart, whereas a significant number of thiamylal-halothane-anesthetized animals died from cardiac fibrillation after they had been given epinephrine. Additional dogs were anesthetized with C1 744 or pentobarbital and given a series of pressor and depressor agents (isoproterenol, epinephrine, tyramine, 1, 1-dimethyl-4-phenylpiperazium iodide (DMPP) plus bilateral carotid occlusion) before and after vagotomy. The responses with either anesthetic were similar with the exception that the reflex bradycardia to pressor agents was more evident in C1 744- than in pentobarbital-anesthetized dogs.


Occurrence of infection by the cestode Grillotia in Persian Gulf fish.

A cystic condition of the peritoneum of tuna fish (Thunnus thynnus) caught from the Persian Gulf is described. Parasitologic examination established widespread infection by the cestode Grillotia. An account is given of the taxonomic position of this genus.


Activated coagulation test in normal and heparinized ponies and horses.

Activated coagulation test (ACT) was performed in 37 adult ponies and 31 adult horses. The mean ACT time  of all ponies and horses was 2 minutes 38 seconds, with a standard deviation (SD) of 29 seconds. The ACT was compared with the Lee-White clotting test in heparinized ponies. The correlation of ACT with the Lee-White test was 0.95. Anticoagulation heparinized ponies during prolonged cardiopulmonary bypass was successfully monitored with the ACT. The ACT is simple and reproducible, has a  definite end point, and would seem to be an ideal screening test for hemorrhagic diathesis in equine animals.


Further observations on the course and prognosis of chronic obstructive lung disease.

Long-term survival data are presented for 200 patients with chronic airway obstruction of uncertain etiology who were enrolled in a prospective study approximately 14 years ago. Early death rates were closely related to the initial level of ventilatory impairment. Subjects with relatively mild impairment on entry to the study had a favorable prognosis for the first 5 to 7 years of follow-up but then began to show a higher death rate; there are few long-term survivors in the total series.


Contribution of inhomogeneity of lung units to the maximal expiratory flow-volume curve in children with asthma and cystic fibrosis.

Normal children as well as those with asthma and cystic fibrosis were studied to assess the contribution of lung zones emptying at different rates to the curvilinearity of the maximal expiratory flow-volume curve. Lung volumes, maximal expiratory flow-volume curves breathing air and then breathing a helium-oxygen mixture, and single-breath nitrogen washouts were measured. Forced expiratory maneuvers from lung volumes near functional residual capacity were performed to produce transients of flow exceeding maximal flow defined by the full flow-volume curve. Normal children and those with asthma and mild cystic fibrosis had small or no transients. Those with severe cystic fibrosis had large transients as well as increased phase I on the nitrogen washout curves. These large transients were associated with increased curvilinearity of the maximal expiratory flow-volume curve and smaller than normal flow response breathing helium. In severe cystic fibrosis, the large transients suggest sequential emptying of fast and slow spaces, which influences the shape of the maximal expiratory flow-volume curve. The fast space could be due to compression of an enlarged anatomic dead space. Any time constant inequality between parenchymal units present in asthma and mild cystic fibrosis does not appear to contribute significantly tof the shape of the maximal expiratory flow-volume curve.


Tracheal mucociliary transport in patients with cystic fibrosis and its stimulation by terbutaline.

Tracheal mucous velocity was measured by observing the motion of teflon discs across the tracheal mucosa through a fiberoptic bronchoscope. The average rate of movement in 14 adult patients with cystic fibrosis was 2.6 mm per min plus or minus 3.3 SD, compared with 20.1 mm per min plus or minus 6.3 in 20 normal subjects of the same age (P less than 0.001). This failure of mucociliary transport may play a role in the pathogenesis of the pulmonary disease in cystic fibrosis. Administration of a beta-adrenergic agent, terbutaline, increased the average mucous velocity in the patients with cystic fibrosis (to 5.5 mm per min plus or minus 3.6 SD, P less than 0.001) but not in control subjects. This observation has potential therapeutic significance.


Effect of nebulized lidocaine on reactive airways.

Fourteen subjects with reversible obstructive lung disease inhaled one per cent lidocaine mist delivered by an ultrasonic nebulizer. The effect of ultrasonic nebulization per se was evaluated by a control study utilizing normal saline. After lidocaine inhalation there was a significant decrease in expiratory flow and an increase in airway resistance compared with either baseline or post-saline values. The changes were mild and do not preclude the continued use of nebulized lidocaine as an adjunct to bronchoscopy, but caution in its use is indicated.


Factors influencing the measurement of closing volume.

The various factors influencing closing volume were studied by performing the single-breath N2 test on 9 healthy nonsmokers. Time of day, day of the week, and preceding volume history had no effect on either closing volume or alveolar plateau. Slow inspiratory flow resulted in larger ratio of closing volume to vital capacity, ratio of closing capacity to total lung capacity, and change in N2 concentration than fast inspiratory flow. Voluntary regulation of the expiratory flow resulted in smaller ratios of closing volume to vital capacity and closing capacity to total lung capacity than when flow was regulated by a resistance. Prolonged breath holding of the inspired O2 led to larger ratio of closing volume to vital capacity and ratio of closing capacity to total lung capacity. To obtain uniform, comparable closing volumes, it is suggested that the subject inspire slowly, control expiratory flow (preferably voluntarily), and not pause between inspiration and expiration.


Normal values and evaluation of forced end-expiratory flow.

A new spirometric measurement was performed with 803 healthy, nonsmoking men and women. Using the forced vital capacity curves, the forced end-expiratory flow (FEF75-85%) had a negative correlation with age and a positive correlation with height. Prediction formulas and nomograms were constructed. Comparison with the forced mid-expiratory flow (FEF25-75%) showed generally larger correlation coefficients for physical characteristics and coefficients of variation for the FEF75-85%. Expressing both the FEF75-85% and FEF25-75% as ratios of forced vital capacity did not improve the coefficients. The mean flow rates of 75 male smokers were compared with 213 non-smokers 30 to 49 years of age. The FEF75-85% significantly distinguished between a group of smokers and a group of nonsmokers, but the FEF25-75% showed no significant difference. In 9 patients with presumed peripheral airways disease, FEF25-75% ranged from 70 to 110 per cent of predicted normal but FEF75-85% was 30 to 72 per cent of predicted. An extensively studied control group of 22 healthy, asymptomatic, nonsmoking subjects had FEF75-85% values of 80 to 163 per cent of predicted. Both small groups of 9 patients and 22 control subjects had FEF75-85% values within 1.65 standard error of estimate. In subgroups of 319 persons, use of 75 per cent of predicted mean for FEF75-85% was of greater value in attempting to screen normal from abnormal population than using 1.65 standard error of estimate. The FEF75-85% is suggested as a useful simple ventilatory test to detect early obstructive pulmonary disease.


Effects of ozone on pulmonary function in normal subjects. An environmental-chamber study.

Twenty healthy adults, 10 smokers and 10 nonsmokers, were exposed to 0.5 ppm of ozone for 6 hours in an environmental chamber. They engaged in two 15-min, medium-exercise stints on a bicycle ergometer during this period. The symptoms most commonly noted with exposure to ozone, dry cough and chest discomfort, were experienced by more nonsmokers than smokers. Subjects who experienced symptoms, in general, were those who developed objective evidence of decreased pulmonary function. Significant changes from control values for the group as a whole with exposure to ozone were observed for the following pulmonary function tests: specific airway conductance, pulmonary resistance, forced vital capacity, and 3-sec forced expiratory volume. No significant change was observed with respect to diffusing capacity for CO, static compliance, or the various tests derived from the N2 elimination rate. In addition, nonsmokers exhibited a significant decrease in dynamic compliance after exposure to ozone. When the smokers were considered as a separate group, no significant decrease in pulmonary function was observed, although some individual smokers showed adverse functional changes.


Biochemical characterization of hyaluronic acid from a case of benign, localized, pleural mesothelioma.

The tissue of a benign, localized, pleural mesothelioma was digested with protease, and the crude polysaccharide was fractionated by a column of Dowex-1 (Cl-form). The eluate from the column was electrophoresed and incubated with various mucopolysaccharide lysases. Based on the results of column chromatography, electrophoresis, and enzymatic digestion, it was found that hyaluronic acid was the major constituent of the glycosaminoglycans in pleural mesothelioma. The hyaluronic acid from pleural mesothelioma seemed to be identical in structure with that from human umbilical cord; however, the hyaluronic acid from mesothelioma was eluted before that from human umbilical cord when fractionated by the column of Sepharose 4B, suggesting a differnence in molecular size between the two. Also, evidence was obtained for the presence of dermatan sulfate and heparan sulfate.


Horizontal gradient in ventilation distribution due to a localized chest wall abnormality.

Horizontal gradients in the distribution of ventilation and of regional vital capacities, as well as a reversed vertical, esophageal pressure gradient, were observed in a patient with a unilateral painful chest wall lesion. The distribution abnormalities disappeared after surgical treatment. These findings suggest that the interdependency between chest wall and lungs, and within the latter, between lobes, is an important factor determining the regional distribution of ventilation and the pleural pressure gradient in man.


Prevention of radiation pneumonitis from inhaled cerium-144 by lung lavage in beagle dogs.

This study was performed to evaluate bronchopulmonary lavage and chelation therapy as a treatment method to prevent the development of radiation pneumonitis after inhalation of a radioactive aerosol. Twelve beagle dogs were exposed to an aerosol of cerium-144 in fused clay particles resulting in initial lung burdens from 47 to 64 muCi of 144-Ce per kg of body weight. Eight of the dogs were treated with a series of 10 bronchopulmonary lavages and 10 intravenous injections of calcium diethylenetriamine pentaacetate acid during the first 56 days after exposure to remove the deposited 144-Ce; the remaing 4 exposed dogs receiged no treatment. An additional 4 dogs were exposed to stable cerium and were given the course of treatment as an additional control group. Three of the 4 untreated dogs and 2 of the 8 treated dogs died 171 to 246 days after exposure with radiation pneumonitis or pulmonary fibrosis, or both. All but one of the remaining dogs were alive and apparently in good clincial health 550 dyas after exposure; the one dog had radiographic indications of pulmonary fibrosis by 365 days after exposure. The relative distribution of 144-Ce in the lungs and other major organs was similar in the treated and untreated dogs that died.


Fatal pulmonary hemorrhage after transbronchial lung biopsy through the fiberoptic bronchoscope.

A case is reported in which transbronchial lung biopsy using the fiberoptic bronchoscope was complicated by massive, fatal hemorrhage. This previously unreported complication occurred despite normal prothrombin and partial thromboplastin times and platelets of 93,000. Pathological examination revealed that a very small (0.5-mm) vessel was the source of the bleeding. Although severe complications are undoubtedly rare, this report suggests that the transbronchial lung biopsy is not a totally benign procedure. Suggestions are made to prevent future similar occurrences in very ill patients or in patients with coagulative abnormalities or blood dyscrasias.


Recurrent high altitude pulmonary edema with blunted chemosensitivity.

A young man who had had two episodes of high-altitude pulmonary edema in the absence of any respiratroy distress was noted to have a depression of his hypoxic and hypercapnic ventilatory drives. It is postulated that because of his blunted ventilaory drives, the patient progessed to coma on exposure to low ambient oxygen tensions (i.e., high altitude) without ever increasing his ventilation. The importance of including highaltitude pulmonary edema in the differential diagnosis of any patient who is admitted with coma after a sojourn at high altitude is stressed.


Lung cancer in men: a model for the relationship between age at diagnosis and smoking habits.

When studying a group of lung cancer cases in a limited period of time to determine the relationship between age at diagnosis and smoking habits, the multiplicity of birth cohorts and the small segment of the life-span distribution of cases observed are confounding and restraining conditions. A model was constructed that suggests that small observed age shifts represent large age shifts in the life-span distributions.


Daily and alternate-day corticosteroid regimens in treatment of giant cell arteritis: comparison in a prospective study.

Alternate-day corticosteroid therapy was compared with two daily corticosteroid regimens for the treatment of giant cell arteritis. In a prospective study 60 patients with this disease were randomly assigned to three treatment groups: group A, 15 mg of prednisone every 8 hours; group B, 45 mg of prednisone every morning; and group C, 90 mgof prednisone every other morning. After 1 month of treatment, the arteritis seemed to be completely suppressed in 18 patients in group A and 16 in group B but in only 6 in group C. In the 14 other patients in group C, the continuing symptoms were cyclic and developed during the day steroids were not given. By changing to a daily regimen, the arteritis was controlled in most patients in group C. Adverse reactions to prednisone were noted frequently in groups A and B but rarely in group C.


Improved computer-assisted digoxin therapy. A method using feedback of measured serum digoxin concentrations.

Automated feedback control methods were applied to a medical problem, in a computer program that used measured serum digoxin concentrations (as feedback) to predict future concentrations and to achieve desired concentrations. The system was validated by comparing its ability with the corresponding ability of physicians to regulate digoxin dosage. The prospective, randomized study included 51 patients. In the presence of varying amounts of feedback (serum digoxin concentration) information, the computer always predicted future digoxin concentrations as accurately as did physicians. For both computer and physician, the decrease in the prediction errors when two concentrations were known against that when no concentrations were known was significant: mean absolute error decreased from 0.40 to 0.25 ng/ml for the physicians and from 0.45 to 0.27 ng/ml for the computer. Thus the computer system is capable of simulating and reproducing a sophisticated aspect of physician behavior: "learning" about individual patient responses. The computer achieved desired concentrations more accurately than did physicians, especially when two or more previous digoxin concentrations were abailable (mean absolute achievement error for computer, 0.28 ng/ml; for physicians, 0.50 ng/ml).


Minimizing tuberculosis risk to hospital personnel and students exposed to unsuspected disease.

A 15-month prospective study of the personnel and students exposed to initially unsuspected active cases of tuberculosis was undertaken to define the risk of their acquiring infection. Eight of 484 (1.65%) personnel exposed to 17 initially unsuspected tuberculosis patients and 5 of 2013 (0.25%) unexposed personnel with similar risk but no known exposures developed positive tuberculin skin tests. This greater than sixfold increase in conversion rate for the exposed group was significant (chi-2=14.83; P=0.0003). Delay in making the diagnosis in these patients was associated with failure to apply a tuberculin skin test on admission in 14 patients and radiologic misinterpretation in 15. A comprehensive surveillance method involving the Employee and Student Health Departments as well as the Public Health Department is suggested to minimize the risk of undiagnosed tuberculosis.


Imported African trypanosomiasis in the United States.

Since 1967, six cases of African trypanosomiasis have been diagnosed and treated in the United States. Five patients were Americans infected with Trypanosoma rhodesiense, and the other was an African student with T. gambiense. Presenting signs and symptoms for all cases were typical of the disease, but often the diagnosis was delayed. The five Americans had spent only brief periods in endemic areas. All cases responded to therapy although one relapsed. Cases of imported sleeping sickness are few, and the risk of Americans acquiring the disease while traveling to endemic areas is low. However, the early diagnosis of sleeping sickness requires that physicians be cognizant of the possibility of imported tropical diseases.


Hereditary thrombocytopenia, deafness, and renal disease.

The syndrome of hereditary thrombocytopenia, deafness, and renal disease was manifest in at least eight members in three generations of a family. They had a lifelong history of bleeding, usually as epistaxis, bilateral sensorineural deafness starting in late childhood or the teenage years, and persistent proteinuria with varying degrees of renal dysfunction. Two members died at a young age, one from central nervous system hemorrhage, the other from chronic renal failure. Splenectomy and steroid therapy have been of transient benefit. There was dominant inheritance of the syndrome. Hematologic studies showed thrombocytopenia, large platelets, and megakaryocytic hyperplasia of the bone marrow. In contrast to a previous report, our studies showed that affected members had normal in-vitro platelet function and normal ultrastructural platelet morphology. At autopsy, histologic changes in the kidney of one affected family member were indistinguishable from those reported in classic hereditary nephritis with nerve deafness (Alport's syndrome).


Hypomagnesemic hypocalcemia secondary to renal magnesium wasting.

Two patients developed severe hypomagnesemia, hypocalcemia, and hypokalemia as a result of renal wasting of magnesium and potassium shortly after being treated with large doses of gentamicin. When therapy with gentamicin was discontinued renal loss of magnesium and potassium ceased, and serum calcium, magnesium, and potassium returned toward normal. Serum immunoreactive parathyroid hormone levels were inappropriately low during the episodes of hypocalcemia. Both patients represent examples of hypomagnesemic hypocalcemia induced by inappropriate magnesuria, possibly caused  by gentamicin. These observations suggest that serum calcium, magnesium, and potassium should be monitored during gentamicin therapy.


Myeloid, erythroid, and immune system defects in a family. A new stem-cell disorder?

Four of six siblings, offspring of Sicillian first cousins, developed a clinical disorder in early adulthood affecting the hematopoietic and immunoglobulin-producing systems. A female sibling died at age 21 with myeloid aplasia and agranulocytosis. A male sibling, at age 17, presented with erythroid and plasma cell aplasia with hypogammaglobulinemia. Two other female siblings, ages 21 and 35, had a lymphoproliferative disorder associated with hypogammaglobulinemia. In two of the affected subjects there was complete absence of the enzyme leukocyte alkaline phosphatase. Electron microscopic studies of the peripheral leukocytes from these two subjects and from one of the two asymptomatic siblings showed curious intranuclear and intracytoplasmic linear "crystalloid" structures in the mature neutrophils. It is postulated that the family contains a genetic defect, transmitted as an autosomal recessive by the heterozygous parents, that produces a stem-cell disorder manifested by myeloid, erythroid, and plasma cell aplasias, unique electron microscopic findings, and morphologic and functional abnormalities in later generations of cells.


o,p'DDD therapy in invasive adrenocortical carcinoma.

Invasive adrenocortical carcinoma was diagnosed in two patients, 3 1/2 and 69 years of age, respectively. Therapy with o,p'DDD was begun immediately, and the patients have survived 4 1/12 and 7 9/12 years, respectively. The prolonged survival represents possible "cure" of inoperable disease following early initiation of therapy.


Health manpower: numbers, distribution, quality.

Although the "health care crisis" was thought solvable by simply increasing the number of physicians, this has turned out not to be the case. The major problems in physician manpower are geographic maldistribution with a sparsity of physicians in the rural areas and the inner city and an overproduction of specialists. Certain changes in undergraduate and postgraduate medical education have contributed to this maldistribution. There is good evidence that there is an overproduction of surgeons and of medical subspecialists such as cardiologists. Much of the excess subspecialization can be laid at the foot of graduate training programs. The role of the specialty boards in affecting career choices and with them health manpower is analyzed. Some solutions to solve the geographic and specialty maldistribution problems are suggested. It is clear that more primary care physicians including general internists, family physicians, and pediatricians are needed.


Physician and nurse practitioner: conflict and reward.

Physicians and the nurse practitioners with whom they work face a number of conflicts. Conflicts develop within the individuals as they change their professional self-images. Each doctor-nurse team must develop new ways of working together and must do so against a background of long-standing professional territoriality. Comparable struggles are felt within schools and hospitals. Although governments have supported nurse practitioner programs, they have not yet enacted the fiscal and legal changes to make the role fully viable. Despite these struggles many physicians and nurses have achieved definite rewards. Research is beginning to document important successes, and educational programs are graduating significant numbers of practitioners.


Training and certifying the internist for primary care.

Internists are well prepared to offer patients continuing and comprehensive medical care of the highest quality. Residencies must include training for the provision of primary care without compromising excellence. The teaching and practice of general internal medicine are the principal functions of Departments of Internal Medicine. Modern facilities for ambulatory care and an environment conducive to the development of internists for primary care are required. Establishment of new residency positions in general internal medicine is advocated, as is appropriate funding for education in the ambulatory patient setting. Experience with disciplines such as dermatology, office gynecology, musculoskeletal medicine, ophthalmology, otolaryngology, and psychiatry should be assured. The Board will include material relevant to primary care in its Certifying Examination.


Spontaneous surface wrinkling retinopathy.

Spontaneously occurring surface wrinkling retinopathy occurreed in 17 eyes of 16 patients and was not related to pervious surgery, retinal vascular disease, or obvious ocular inflammation. Visual symptoms were not severe and follow-up suggests that the usual course of surface wrinkling is usually benign. However, 2 eyes progressed to 20/300, so that there is a chance of considerable visual deterioration in some cases. The vitreous may or may not be detached. The ophthalmoscopic features of a wrinkled shagreen, tortuous vessels pulled toward a nidus, and intraretinal hemorrhages were seen. The leakage of fluorescein into the retina is emphasized in this series and may be fairly marked. The possible causes and mechanism of wrinkling are discussed with emphasis on mild chronic ischemia and posterior vitreous collapse.


Penetrating transorbital foreign body with ocular preservation.

Large penetrating transorbital foreign bodies may initially appear to be of a devastating character to the ocular tissues. However, several reports of such large foreign bodies have proved to spare the eye. A case report of a large wooden foreign body with transorbital penetration into the right frontal lobe is reported. The globe remained intact and was only displaced, with a final visual acuity of 20/40. However, complete ophthalmoplegia and ptosis persisted. A low pressure hydrocephalus ensued following intracranial debridement.


Traumatic hyphema: surgical vs medical management.

We undertook a prospective study of traumatic hyphema during the years 1970 through 1972 to compare the effects of medical management and surgical evacuation in the more severe hyphemas. A protocol for sutdy of the two regimens enabled us to compare the results of therapy. The findings indicate that medical management is preferable for the initial 4 days in major hyphemas. Surgical intervention does not offer improvement in the poor prognosis of total hyphemas during this early period. The incidence of complications and the incidence of permanent poor visual results are higher in surgically treated patients than in those managed medically. Surgical intervention should be reserved for cases showing: (1) microscopic corneal blood staining; (2)total hyphemas with intraocular pressures of 50 mm Hg or more for 5 days (to prevent optic nerve damage); (3) hyphemas  that are initially total and do not resolve below 50% at 6 days with intraocular pressures of 25 mm Hg or more (to prevent corneal blood staining); and (4) hyphemas that remain unresolved for 9 days (to prevent peripheral anterior synechiae). A brief review of problems that may be encountered in the various forms of surgical management is included in an effort to prevent repeating similar pitfalls.


Outcome of traumatic hyphema.

One hundred and twenty-seven cases of traumatic hyphema are reviewed and discussed according to a definite system of grading. Grade iii hyphemas have definitely a poorer prognosis than Grade ii and Grade i hyphemas. Rebleeding occurs more frequently when there is a delay in treatment but does not appear to affect the outcome of a traumatic hyphema. Blood staining of the cornea could be avoided by an adequate treatment started immediately after the trauma, thus decreasing the percentage of blindness following a traumatic hyphema.


Scleral buckling with soft silicone sponge and lamellar scleral dissection.

One hundred cases of primary, nontraumatic, rhegmatogenous retinal separation were operated upon using  1/2 thickness 7.5 mp Silastic silicone sponge as a circumferential implant without an encircling element or suture tension. The use of this method has given 100% successful anatomical reattachment of the retina after a follow-up of 8 months to 3 1/2 years.


Lacrimal drainage following repair of inferior canaliculus.

Eight cases of surgically repaired lower canaliculi were studied to ascertain whether the lower canaliculus is necessary for normal lacrimal drainage and whether it is advisable to probe the superior canaliculus during inferior canalicular repair. Six of 8 patients sutdied had no epiphora despite unsuccessful surgery and a normal Schirmer"1 test. Surgery was successful on 2 pateints. These results indicate that only cosmetic repair is necessary for lacerated lower canaliculi. It is suggested that the upper canalliculus alone provides sufficient lacrimal drainage to prevent epiphora.


Blood sugar levels during routine fluid therapy of surgical patients.

The study was carried out to investigate the variations in blood sugar values during routine fluid therapy in surgical patients, when the rate of infusion often is very haphazardly adjusted. Surgical patients with normal sugar and fluid balance were divided into two groups. The glucose group (34 patients) was given 5% glucose solution as infusion fluid and the control group (the saline group, 26 patients) received 0.9% physiological saline solution. The preoperative mean value of blood sugar in the glucose group was 4.9 mmol/1 and in the saline group 4.6 mmol/1. Half an hour after the beginning of the operation the blood sugar in the glucose group rose to 7.2 mmol/1 (p smaller than 0.001) and in the saline group to 5.3 mmol/1 (p smaller than 0.01). At the end of the operation the blood sugar values in both groups had further increased significantly from the half-hour levels, in the glucose group to 7.8 mmol/1 and in the saline group to 6.1 mmol/1 (p smaller than 0.01). The difference between the groups, at each test after the initial test, was highly significant throughout (p smaller than 0.001). The result indicates to carefulness in using glucose solutions even during operations lasting 1-2 hours.


Malignant hyperpyrexia. A study of an affected family.

Our purpose was to determine whether an apparently healthy patient who died under general anaesthesia had malignant hyperpyrexia by examining her relatives and to suggest protective measures for the relatives of the deceased patient against this complication during future general anaesthetics. The family members of the deceased patient were examined systematically to determine whether or not they were prone to develop malignant hyperpyrexia. Raised serum CPK and aldolase levels, EMG changes, histopathological examination of the striated muscle, diminished muscle power during an ergometric test, and subjective symptoms revealed that other members of her family had muscular dystrophy. Our results support the theory that during general anaesthesia patients with muscular dystrophy are prone to develop malignant hyperpyrexia. Although muscular dystrophy is uncommon in Finland, affected persons should be catalogued, and preventive measures against malignant hyperpyrexia taken if they ever have to have a general anaesthetic.


Itching during pregnancy.

This retrospective study was performed in order to evaluate the frequency and the causes for itching during pregnancy. The series consists of 129 pregnant women with generalized itching, which is 1.2% of all deliveries. The most common cause for itching was hepatosis of pregnancy (83%). The other causes were pruritus of pregnancy without any liver dysfunction (12%), dermatitis (3%) and other (2%). The average time of the onset of itching was the 30th pregnancy week in hepatosis of pregnancy and the 26.5th pregnancy week in pruritus of pregnancy. The frequency of toxaemia of pregnancy varied within 24-33% in the different itching groups and that of urinary tract infection within 21-33%. The proportion of urinary tract infection was also fairly high, 23-24%, among the previous diseases. Perinatal mortality in previous pregnancies was reported by 14 patients (9.0%), 11 of them in hepatosis group (9.6%). The corresponding frequencies of perinatal mortality in the present pregnancy were 1.6% and 1.9%. The drugs most frequently used during the present pregnancy before admission were antibiotics and other chemotherapeutic agents, sulphonamide being the most common.


Hepatotis of pregnancy. A clinical study of 107 patients.

A series of 107 patients with hepatosis of pregnancy and 61 controls with normal pregnancy is reported. The delivery and the condition of the infant were the main objects of investigation. The hepatosis group was also examined for liver function, glucose tolerance, and daily urinary oestrogen. The duration of the first stage of delivery was found to be slightly shortened in the hepatosis group. Two cases (1.9%) of intrauterine death occurred in the hepatosis series, and the Apgar scores at 1 and 15 minutes were somewhat lower than in the control group. Birthweight was slightly lower in the hepatosis series, corresponding to the earlier date of delivery. 11.9% of the infants weighed less than 2.5 kg at birth. The absolute and relative weights of the placenta showed no differences. The histological examination of the placenta made on part of the series revealed maturing defects in 35%. The liver function tests confirmed the cholestatic nature of hepatosis observed earlier, yielding elevated values especially for aminotransferases, alkaline phosphatase and bilirubin. The thymol turbidity test was within the normal limits, which means that hepatitis could be excluded. Neither glucose tolerance, nor daily urinary oestrogen differed significantly from the normal. The fetal survival rate has been improved considerably by intensive care of hepatosis of pregnancy.


Epidemiology of interstitial cystitis.

Almost all the patients (95 women and 8 men) with interstitial cystitis, i.e. autoimmune cystitis, in this area with a population of about 970,000 were probably traced. The prevalence of the disease in the female members of this population was 18.1 cases per 100,000 women of all ages. The joint prevalence of both sexes together was 10.6 cases per 100,000. The annual incidence of new female cases was 1.2 per 100,000 women. The disease is not rare when mild and moderately severe cases are also diagnosed. Severe cases account for only a tenth of all cases. Only about a tenth of the patients are men and most of them had the mild form of the disease. It may begin at any age. The incidence has possibly been rising during the last 10 years. Interstitial cystitis does not as a rule progress continuously but reaches its final stage rapidly, then usually remains in the same category. With this prevalence and incidence every urologist in this area can expect to see at least one case a year.


Gastric retention following antrectomy and gastroduodenal anastomosis combined with truncal vagotomy.

A clinical series of 208 patients who had elective operations for gastroduodenal ulcer in Surgical Department II, Oslo City Hospital, has been reviewed. The study concentrates on postoperative gastric retention, comparing the frequency of this complication following antrectomy and gastroduodenal anastomosis with and without vagotomy. The patients in the nonvagotomy group had no retention problem. In the vagotomy group, 19 patients (35%) of 54 operated had troublesome postoperative retention. 7 patients (13%) had to have a further operation for this complication, all within 1 year. We no longer use the combined operation as a routine procedure for duodenal ulcer.


The proteinases and proteinase inhibitors in the peritoneal exudate during acute experimental pancreatitis in the rat.

The proteolytic activities and trypsin inhibitors of the peritoneal exudate produced by experimental acute pancreatitis in the rat were studied by fractionation with gel filtration on Sephadex G-200 and estimation of the hydrolysis of casein and synthetic substrates. The peritoneal exudate produced by injecting formalin solution into the peritoneal cavity was used as a control. The peritoneal exudate during pancreatitis revealed distinct proteolytic and ATEE hydrolysing activities and it also hydrolysed BAPNA to a lesser extent. These activities were absent from the control exudates, or only traces of them could be demonstrated with the methods used. The trypsin inhibiting capacity (TIC) in the pancreatic exudate was about half that in the control exudate. In gel filtration on Sephadex G-200 the BAPNA hydrolysing proteolytic activity was eluted with the macroprotein fraction, suggesting that the enzyme was bound to the macroproteins. TIC differed clearly in the control exudate and the pancreatitis exudate. In both of them TIC was eluted in two peaks after the macroproteins, but in the pancreatitis group the first peak was very weak, if demonstrable at all, while in the control exudate the two peaks were clearly separated and the TIC was more pronounced. These findings suggest that pancreatic enzymes are released during pancreatitis into the peritoneal cavity, where they combine with proteinase binding factors in the exudate.


Conservative surgery in acute pancreatitis.

During the years 1955-1970, 260 patients were treated for acute pancreatitis in the surgical department of the Maria Hospital. 62 of them were operated on, 44 electively, and 18 as emergency cases. The main conclusions from this series are as follows: 1) if laparotomy is required, efficient debridement and drainage are of great importance, 2) random operative decompression of the biliary duct system is statistically of little benefit, 3) in most cases purely conservative treatment or conservative surgery, taking into account individual conditions, gives good results, but obviously more radical measures are necessary for a favourable outcome in the most severe cases, as reported in the current literature, 4) in elective surgery it is important to postpone the curative operation by several weeks, preferably months, when possible, to avoid exacerbation or relapse of the disease.


Fatal pancreatitis. A clinical and post-mortem study on 24 cases of acute pancreatitis with fatal outcome, with special reference to some clinical aspects of autopsy findings.

During the years 1955-1970, 260 patients were treated in the surgical department of the Maria Hospital for acute pancreatitis. 24 of them died and went to autopsy. This study includes all these 24 patients.


Clinical diagnosis and prognosis of deep venous thrombosis.

The reliability of the diagnosis made on the basis of symptoms of deep venous thrombosis and the development of a post-thrombotic state were studied in 53 patients. Pain in the leg was present in 93% and swelling in 82% of the series, both figures are considerably higher than those reported before. The clinical diagnosis was correct in 74% of cases. The post-thrombotic state developed with unexpected rapidity: after one to three years 87% already had symptoms and/or signs of venous insufficiency, and after eight years at the latest all patients had such symptoms and/or signs.


Phosphoglucomutase types in the Asian-Pacific area: a critical reveiw including new phenotypes.

The distribution of genetic variants at the PGM1 and PGM2 loci in South and East Asia, the Western Pacific and Australasia has been surveyed on the basis of published and unpublished material comprising samples from some 33,000 persons. A critical comparsion of previously described and of new rare alleles at both loci has been undertaken. The present number for PGM1 is 14 and for PGM2 is 12. Many of these have restricted geographic or ethnic distribution.


Chromosome assignment of some human enzyme loci: mitochondrial malate dehydrogenase to 7, mannosephosphate isomerase and pyruvate kinase to 15 and probably, esterase D to 13.

Eleven independent man-mouse hybrids and 40 subclones from four to them were analysed for up to 42 enzyme markers. Nine subclones from three hybrid lines were fully karyotyped. The data presented suggest that the gene for the human enzyme MOR-M can be assigned to chromosome 7, whilst those for MPI and PK-3 are on chromosome 15. The use of a small number of well-characterized hybrids for gene assigments is discussed as well as the significance of some known human linkage relationships.


Elucidation of a pericentric inversion of a D-group chromosome in the mother of a child with Patau's syndrome.

The mother of a child with Patau's syndrome has an inversion of chromosome 13. The karyotype is designated 46, XX, inv (13) (p13q21). It is deduced that the deceased child had the karyotpye 46, XY, rec(13), dup q, inv(13) (p13q21).


A method for the storage and retrieval of laboratory data on human lymphoblastoid cell lines.

A computer-based system has been developed for the handling and retrieval of data on long-term human lymphoblastoid cell lines. It permits accurate recording of a wide range of genetic markers and other defined characteristics for the donor of each culture and for individual aliquots of any cell line. The data is recorded in relation to the in vitro age of each aliquot studied and the programme is designed to permit both the sequential examination of a single cell line and the comparison of lines of different origins. It is hoped that, by the application of this type of system, the confusion which has arisen in relation to other long-term cell lines (and which threatens to develop in relation to human lymphoblastoid cell lines) may be avoided and that the exchange of information between laboratories may be facilitated.


Total number of individuals affected by deleterious mutant genes in a finite population.

The means and standard errors of the total numbers of heterozygotes and homozygotes affected by deleterious mutant genes and the extinction time are studied by using diffusion methods. For an overdominant mutation, the effects of an increase in population size on these quantitites are much more profound than that of an increase in initial number of mutant genes whereas for a partially recessive mutation the situation is reversed. For a completely recessive mutation, the expected total number of mutant homozygotes is independent of the population size and degree of inbreeding, though the expected total number of heterozygotes and the average extinction time are dependent on these factors, particularly the population size. The effect of inbreeding on these quantitites is very similar to that of reduction in effective population size and is usally small at the prevailing level of inbreeding, except for mutations with large degrees of overdominance in large populations. The standard errors of these quantities are large. The expected total number of sickle-cell mutant homozygotes in the U.S. population has been computed.


The prior probability of autosomal linkage.

An expression is derived for the prior probability of linkage between a random trait locus and any one of m random marker loci, and this probability is computed form=1, 10, 20, 30, 50 and 100. A similar expression is derived for two trait loci, and computed for m=1, 10, 20 and 30. When one trait locus and 30 marker loci are being studied, a priori there is over a three-quarter probability that the trait locus should be syntenic with at least one of the markers, and about a one-half probability that there should be a linkage mappable from recombination frequencies. If two traits are studied, then the prior probability that at least one should be syntenic with one of the 30 markers is 0-94, and there is a three-quarter probability that such a linkage should be mappable.


Growth disorders and homocysteine metabolism.

Inherited disorders of homocysteine metabolism produce accelerated growth and arteriosclerosis with myointimal hyperplasia. The growth of cell cultures from cystathionine synthetase deficient individuals with homocystinuria is characterized by abnormal contact inhibition and production of an aggregated proteoglycan matrix which binds excess sulfate. Homocysteic acid, a precursor of sulfate ester, increases the growth rate of normal guinea pigs. Synthesis of homocysteic acid from homocysteine thiolactone is more rapid in the livers of young animals than adults, and hypophysectomy results in a pattern of homocysteine thiolactone metabolism resembling that in liver of adult animals. Homocysteine thiolactone metabolism differs in guinea pig, an herbivorous species, and in rat, an omnivorous species. Sulfate binding by cultured human cells is slightly increased when homocysteic acid is present in the culture medium. These observations suggest a relationship between homocysteic acid and somatomedin, a serum polypeptide which mediates the action of growth hormone. The growth disorders associated with homocystinuria, including arteriosclerosis and accelerated growth, are believed to result from increased conversion of methionine to homocysteine thiolactone and homocysteic acid.


On estimating the frequency of a recessive gene in a random mating population.

The maximum likelihood estimator of the frequency of a recessive gene in a random mating population is simply the square root of the proportion of recessive individuals in a random sample. However, its asymptotic variance, i.e. the inverse of Fisher's information, has an unexpected functional form, and its use may lead to incorrect inferences. An explanation for this is sought by deriving an expansion for the exact variance of the estimator. Further, a number of calculations reveal conditions under which the asymptotic variance provides a reasonable approximation to the exact variance. Lastly, the problem of setting confidence limits to the gene frequency is discussed, with a number of approximations being considered.


A note on determining measures of deviation from random mating.

Large samples results for the joint distribution of the gene frequency with the estimator for various measures of deviation from random mating are given. Also the difficulties in interpreting results for small samples are briefly discussed.


Sex ratio and the sex composition of the existing sibs.

1. It is well established that p, the probability of a male birth, declines with birth order. It is suggested here that this decline occurs within individual sibships (Poisson variation). 2. Other workers have also offered good evidence that (at least in some samples) p correlates positively between adjacent births within sibships (Markov association). 3. The present paper suggests that in addition, some couples have higher values of p than others. In other words, there is Lexis variation in p between couples. It is estimated that this Lexis variation augments the variance (contingent on the Markov process above) by a value of less than 0-002. 4. Data on sex ratio by the sex composition of the pre-existing children are interpreted to support the author's hypothesis that coital rate of parents is related to the sex ratio of their children. 5. However if the decline in sex ratio with maternal age were entirely due to the concomitant decline in coital rate, the variation in p between couples seems greater than could be accounted for by the observed variation between couples in coital rate. It is concluded that sex ratio depends on other factors besides coital rate. 6. It is noted that (when sibship size and birth rank are controlled) MF birth intervals are particularly long, and FM birth intervals particularly short, MM and FF intervals being of intermediate length.


Disk susceptibility testing of slow-growing anaerobic bacteria.

The susceptibility of 55 strains of slow-growing anaerobes to eight clinically useful or potentially useful antibiotics was determined by agar dilution and disk diffusion tests. Strains of the genera Peptococcus, Peptostreptococcus, Megasphaera, Veillonella, Eubacterium, Bifidobacterium, Clostridium, and Fusobacterium were included. All strains were susceptible to chloramphenicol, but varied in their susceptibility to penicillin, lincomycin, clindamycin, tetracyclines, and vancomycin. Correlation between minimal inhibitory concentration and inhibition zone diameters was generally good. Prediction of susceptibility based on zone diameter measurements appeared satisfactory. Although routine susceptibility testing of anaerobic bacteria is not recommended, there are circumstances where such testing is relevant to the clinical situation. For those laboratories ill-equipped to do dilution tests, a disk diffusion test would give relatively accurate preliminary information. Quantitative susceptibility tests could then be done by a reference laboratory.


Comparison of a radioimmunoassay with an enzymatic assay for gentamicin.

A radioimmunoassay and an enzymatic assay for gentamicin have been compared. The correlation coefficient for results of gentamicin assays performed by the two methods with 45 serum specimens was 0.90. A similar standard curve for the radioimmunoassay was obtained with gentamicin complex, with gentamicin Cl, Cla, or C2, or with sisomicin as ligand, but tobramycin did not compete with [(3)H]gentamicin for binding to the antiserum.


Comparison of broth and human serum as the diluent in the serum bactericidal test.

The use of serum rather than broth as the diluent in the serum bactericidal test results in a significant decrease in the test level among patients receiving highly protein-bound semisynthetic penicillins.


Broth-dilution method for determining the antibiotic susceptibility of anaerobic bacteria.

A broth-dilution method for performing antimicrobial susceptibility tests on anaerobic bacteria has been proposed. The medium used in the test was Schaedler broth, with incubation in a glove box with an atmosphere of 5% CO(2), 10% H(2), and 85% N(2), or in the GasPak system. Minimal inhibitory concentrations for selected antibiotics were determined, under these conditions, by using a conventional twofold dilution scheme for the antibiotics and a "categorization three-tube method" in which two or three clinically significant concentrations of each antibiotic were used. Minimal inhibitory concentrations obtained by both methods were very similar. The categorization method could be used routinely to test the antimicrobial susceptibility of anaerobic bacteria.