The role of shear forces in arterial branching. A new optimality principle for the branching angles of blood vessels in the cardiovascular system is proposed: the principle of minimum drag. The results are examined in the light of general observations and compared with those obtained from the principles of minimum work and minimum volume. It is shown that in some aspects the new principle is equally consistent with observations, and, in other aspects, it is perhaps more plausible than the other two principles.


Effects of halides and bicarbonate on chloride transport in human red blood cells. Chloride self-exchange was determined by measuring the rate of 36Cl efflux from human red blood cells at pH 7.2 (0 degrees C) in the presence of fluoride, bromide, iodide, and bicarbonate. The chloride concentration was varied between 10--400 mM and the concentration of other halides and bicarbonate between 10--300 mM. Chloride equilibrium flux showed saturation kinetics. The half-saturation constant increased and the maximum flux decreased in the presence of halides and bicarbonate: the inhibition kinetics were both competitive and noncompetitive. The competitive and the noncompetitive effects increased proportionately in the sequence: fluoride less than bromide less than iodide. The inhibitory action of bicarbonate was predominantly competitive. The noncompetitive effect of chloride (chloride self-inhibition) on chloride transport was less dominant at high inhibitor concentrations. Similarly, the noncompetitive action of the inhibitors was less dominant at high chloride concentrations. The results can be described by a carrier model with two anion binding sites: a transport site, and a second site which modifies the maximum transport rate. Binding to both types of sites increases proportionately in the sequence: fluoride less than chloride less than bromide less than iodide.


Adaptation and facilitation in the barnacle photoreceptor. The barnacle photoreceptor sensitivity may either decrease (light adaptation) or increase (facilitation) after exposure to a conditioning light. The balance between adaptation and facilitation is influenced by at least three factors: initial sensitivity state of the cell, external calcium concentration, and conditioning intensity. Cells of very high sensitivity show mainly adaptation, which appears only for higher conditioning intensities and is suppressed in low-calcium media. Less sensitive cells, or those whose sensitivity is reduced by injury or metabolic decay, exhibit facilitation, expecially in low-calcium media and at intermediate conditioning intensities. Both phenomena show recovery time-courses of seconds-to-minutes. Models are proposed which relate light adaptation, as previously suggested, to increased internal calcium concentration, and facilitation either to decreased internal calcium concentration or to decreased activation "affinity" of ion-channel-blocking sites.


Phagocytosis and pinocytosis in Acanthamoeba castellanii. Endocytotic activity of Acanthamoeba trophozoites attenuates once the cells enter stationary phase in liquid culture. Phagocytosis, monitored by the ingestion of polystyrene latex beads, essentially ceases and the uptake of [3H]inulin, known to be mediated by pinocytosis, is reduced by about half. The reduced pinocytotic activity of stationary-phase cells remains sensitive to respiratory inhibitors. Preincubation of stationary-phase cells in fresh growth medium for 1-5 h before the initiation of endocytosis has no effect on phagocytosis and only marginally increases pinocytosis. This impairment of ingestion, particularly of pinocytosis, may account for the reduced contractile vacuole activity known to characterize stationary-phase cells of this organism. The unequal responses of phagocytosis and pinocytosis to the onset of stationary-phase growth suggest that they are independent processes subject to different controls.


Peptide utilization by Pseudomonas putida and Pseudomonas maltophilia. Pseudomonas putida assimilates peptides and hydrolyses them with intracellular peptidases. Amino acid auxotrophs (his, trp, thr or met) grew on a variety of di- and tripeptides up to twice as slowly as with free amino acids. Pseudomonas putida has separate uptake systems for both dipeptides and oligopeptides (three or more residues). Although the dipeptide system transported a variety of structurally diverse dipeptides it did not transport peptides having either unprotonatable N-terminal amino groups, blocked C-terminal carboxyl groups, D-residues, three or more residues, N-methylated peptide bonds, or beta-amino acids. Oligopeptide uptake lacked amino acid side-chain specificity, required a free N-terminal L-residue and had an upper size limit. Glycylglycyl-D,L-p-fluorophenylalanine inhibited growth of P. putida. Uptake of glycylglycyl[I-14C]alanine was rapid and inhibited by 2,4-dinitrophenol. Both dipeptide and oligopeptide uptake were constitutive. Dipeptides competed with oligopeptides for oligopeptide uptake, but oligopeptides did not compete in the dipeptide system. Final bacterial yields were 5 to 10 times greater when P. putida his was grown on histidyl di- or tripeptides rather than on free histidine because the histidyl residue was protected from catabolism by L-histidine ammonia-lyase. Methionine peptides could satisfy the methionine requirements of P. maltophilia. Generation times on glycylmethionine and glycylmethionylglycine were equal to those obtained with free methionine. Methionylglycylmethionylmethionine gave a generation time twice that of free methionine. Growth of P. maltophilia was inhibited by glycylglycyl-D,L-p-fluorophenylalanine.


Intracellular peptide hydrolysis by Pseudomonas putida and Pseudomonas maltophilia. Amino acids liberated by peptidase hydrolysis of di- and oligopeptides by Pseudomonas putida were measured by trinitrobenzenesulphonate assay and high voltage electrophoresis or paper chromatography followed by ninhydrin spray. Intact bacteria or periplasmic contents released by lysozyme treatment did not hydrolyse peptides. Subcellular fractionation showed that glycylmethionine peptidase activity was cytoplasmic. This enzyme had a Km of 2 mM, and was stimulated fivefold by I mM-Co2+. Crude peptidase extract did not cleave peptides with D-residues, acylated N-terminal amino groups or N-methylated peptide bonds but otherwise showed a wide specificity. Di- or tripeptides with blocked C-terminus were hydrolysed. Leucylleucine (12 mM) and leucylglycylglycine (10 mM) did not compete with glycylmethionine (1-2 mM) and glycylmethionylglycine (1-0 mM), respectively, for hydrolysis. Pseudomonas maltophilia also contained peptidase activity (0-84 mumol amino acid released from glycylmethionylglycine/min/mg protein). Peptidases of both P. putida and P. maltophilia were constitutive.


The influence of culture conditions on carotenogenesis in Streptococcus faecium UNH564P. The growth of Streptococcus faecium UNH564P and its production of triterpenoid carotenoids under a variety of culture conditions were examined. Total extractable cell lipid and carotenoid levels increased with culture age and paralleled the growth curve of the bacterium. Variations of the medium glucose concentration produced significant changes in both cell growth and carotenoid production, with the xanthophyll content decreasing at high glucose concentrations. Carotenoid degradation products were found in highly aerated cultures although a high glucose concentration appeared to have a sparing effect on oxidative degradation. Culture age appeared to have little effect on carotene:xanthophyll ratios. The significance of the production of total and individual carotenoids under the various culture conditions is discussed and related to a postulated scheme of triterpenoid carotenoid biosynthesis in the organism.


Measurement of virus antigens on the surface of HeLa cells persistently infected with wild type and vaccine strains of measles virus by radioimmune assay. Persistent states of measles virus infection have been established in HeLa cells by using Edmonston strain virus and two types of measles virus vaccine (M-VAC and Schwarz). The absolute amount of surface viral antigens expressed on these cells infected separately with the three viruses has been assessed by a newly developed method which employs [125I]-labelled Fab fragments of immunoglobulin G (IgG) from immune human sera. This method was used to determine the level of viral antigenic expression on acutely infected HeLa cells harvested at a time when 95 to 100% of cells could be lysed by antiviral antibody and complement. From our data, more than 1 X 10(6) antibody molecules must bind to each cell infected with measles virus before complement dependent lysis can occur in a homologous test system. Persistently infected cells bind 2 to 3 times less antibody than acutely infected cells and correspondingly exhibit less susceptibility to humorally-mediated immune lysis.


The replication of rodent parvovirus X14. The replication of rodent parvovirus X14 DNA has been studied in rat embryo tissue culture cells. Virus DNA was isolated from I M-NaCl-SDS-pronase supernatant fluids from 24 h after infection. The majority of this DNA was 1-7 mum in length and double-stranded, indicating that it was an intermediate in the replication cycle of this single-stranded DNA virus. Single-stranded DNA of equivalent length was isolated directly from X14 virions. The buoyant density of this DNA was 1-728 g/ml whereas the double-stranded form banded at 1-714 g/ml in caesium chloride gradients. Difficulties in detecting significant amounts of single-stranded viral DNA directly from infected cells would appear to indicate that progeny single-stranded DNA is rapidly encapsidated after synthesis.


Some cognitive, behavioral and personality correlates of maturity of moral judgment. This study was designed to test the hypothesis that maturity of moral judgment is related to moral behavior and to certain personality characteristics. The Ss, 33 fifth grade boys (approximately 10 1/2-years of age), were given the Kohlberg test of moral judgment, and scores on this test were related to a measure of general intelligence, moral conduct as judged by peers (sociometric nominations), honesty in a structured test, and certain personality variables. Maturity of moral judgment was found to be significantly correlated with general cognitive ability (intelligence test performance) and, even with intelligence partialed out, with resistance to temptation, reputation for being concerned with the welfare of others, self-confidence, and security in social relationships with peers.


Components of school anxiety: developmental trends and sex differences. Dunn's School Anxiety Questionnaire was administered to 104 third through eighth graders (Study I) and 122 eighth graders (Study II). Significant decrements in anxiety with increasing age were found for worry (but not emotionality), report card anxiety, and failure anxiety. In Study I girls scored significantly higher than boys on emotionality (but not worry) and test anxiety. Sex differences were greater in Study II, girls scoring consistently higher. In Study II a worry-emotionality questionnaire administered immediately preceding a final examination correlated highly with School Anxiety Questionnaire scores. Results are taken as generally supportive of the multidimensional approach to the study of school anxiety.


The effects of locus control and field independence-dependence on moral reasoning. This study investigated whether stages of moral reasoning vary as a function of locus of control and degree of field independence. Results, based upon 36 female undergraduates, indicated a tendency for both variables to provide some prediction of morality status when used conjointly. This derived from the fact that field independent-internal Ss has disproportionately higher scores on Kohlberg's Moral Judgment Interview than field dependent-internal, field independent-external, and field dependent-external Ss. The latter showed no appreciable differences among them.


Conservation of length and the development of a size concept. The influence of the ability to conserve length in the development of a size concept was investigated in a series of two experiments. The inability to conserve length influences the perceptual bias of young children using the linear vertical dimension of objects as a salient cue in a paired comparison task when stimulus objects do not share a common baseline. When both stimulus position and attributed functional direction are involved, the latter is more influential in serving an orienting function. Sex differences suggest that females are more field dependent than males in the use of the vertical linear dimension as a cue in the judgment of "bigger" in a paired comparison task.


Motivational effects of hunger on time estimation and delay of gratification in obese and nonobese boys. Time estimates and ability to delay gratification of obese and nonobese boys were compared by a 2x2x2 factorial experiment in which hunger and edibility of incentives were manipulated. Hunger did not affect estimates of the obese boys, while it significantly shortened estimates made by the nonobese boys when the hunger drive was made either specific or nonspecific by varying incentive conditions. Although estimates of the nonobese boys were significantly shorter in the edible than nonedible incentive condition, edibility of incentives did not affect the estiamtes of the obese, suggesting a general rather than food-specific arousal in the nonobese and a general lack of response to internal cues in the obese. Immediate rewards were chosen significantly more often by obese than nonobese Ss. However, delay gratification in both obese and nonobese was unaffected by the hunger and edibility of incentive manipulations. This was attributed to uncontrolled cognitive variables.


Comparative levels of creative ability in black and white college students. Eighty-seven black, educational psychology students from three intact, randomly selected classes at Tennessee State University were compared to ninety-four white, educational phychology students from three intact, randomly selected classes at the University of Tennessee on Torrance's Unusual Uses and Ask and Guess activities. No differences were found on the frequency of flexibility measures of either activity. No attempt was made to examine the results on this "Level II" mental ability measure on any variable except race. There were no differences based on race.


Visual discrimination in the Mongolian gerbil (Meriones unguiculatus) as a function of age. Ten young (8 weeks) and 10 old (26 weeks) male gerbils were tested for the acquisition of a visual discrimination task. Ss were given 10 daily six-trial sessions in a T-maze with a food reinforcement being associated with horizontal or vertical stripes. The older Ss failed to learn the discrimination habit, and the young Ss steadily improved over the 10 sessions.


The effect of visual angle orientation on perceived oscillatory motion. The present experiment examined  the effect of independently varying central, vertical, and horizontal visual angles (CVVA, CHVA) on proportion of perceived oscillations with rotating trapezoids. Twenty-five female undergraduates served as Ss. Diminution of the CHVA proved most effective in increasing oscillatory perception (p less than .01), although perceived oscillation was found to be inversely proportional to CVVA and CHVA (p less than .001). The data indicate that Os primarily rely on perceptual cues determined by the horizontal dimension of a trapezoid. When cue discriminability is reduced, the results suggest that O's perceptual response may be a function on individual differences in cue thresholds, and/or response criteria.


Psychological adaptation to jejunoileal bypass for morbid obesity. Psychological adaptation to jejunoileal bypass procedures in 34 morbidly obese patients was evaluated preoperatively and followed postoperatively for an average of 23 months. Preoperative emotional disturbances were mainly those of mild personality disorders with passive-aggressive, passive-dependent, and emotionally immature traits. Following discharge from the hospital, nine patients (or 24 per cent) developed psychiatric difficulties, characterized by either increased neurotic symptoms and interpersonal problems, or the emergence of psychosis. Male patients and those with the greatest weight loss were statistically more likely to have psychiatric complications. The remaining patients expressed satisfaction with the operation, noted relief from the burden of dieting, experienced less excitement associated with eating, and felt more self-confident and hopeful.


Evaluation of the initial interview in a walk-in clinic. The patient's perspective on a "customer approach". There have been different models on how to conduct the initial psychiatric interview in a walk-in clinic. A "customer approach" has been developed which stresses: a) eliciting and understanding the requests that patients have regarding how they hope to be helped; and b) negotiating a treatment plan with the patients. We evaluated this customer approach from the perspective of the patient. The first hypothesis was supported. The patient's perception of the clinician's utilization of the customer approach correlated positively and substantially with measures of outcome, especially feeling satisfied and helped. The second hypothesis was also supported. Utilization of the customer approach continued to correlate positively and substantially with outcome even when patients did not get the disposition originally wanted. We discussed the clinical significance of the customer approach especially in regard to patient objectives in the initial interview--a treatment plan vs. symptom relief.


Electrodermal response configuration as a function of rated psychopathology in children. Electrodermally labile children of schizophrenic, manic-depressive, and normal parents were identified as either uniphasic or biphasic responders, in each of three phases of a psychophysiological experiment. Psychological disturbance ratings, based upon test protocols, were determined independently. Analysis of the relationship between electrodermal response configuration and rated psychological pathology showed that biphasic responders were evaluated as more disturbed than uniphasic responders. The results were interpreted within a framework provided by Edelberg's work on the information content of the electrodermal recovery limb, and were seen as relevant to notions regarding schizophrenic information processing. It was hypothesized that in this situation, uniphasic responding reflected an adaptive defense against stimuli perceived as potentially threatening, whereas biphasic responding indicated overprocessing and inappropriate goal orientation.


Anxiety neurosis: a 5-year follow-up.

Anxiety neurosis: a 5-year follow-up. Fifty-seven patients who were seen on a psychiatric consultation service and who met criteria for the diagnosis of anxiety neurosis were followed up after 5 years. These patients presented symptoms from a variety of organ systems and appeared typical of anxiety neurotics seen in general medical practice. A favorable outcome was demonstrated in 67 per cent who were either recovered or mildly impaired. Women showed a more favorable outcome than men. Among men, age at the time of consultation was positively correlated with the degree of impairment after 5 years.


Token economies in institutional settings. Historical, political, deprivation, ethical, and generalization issues. The use of the token economy in institutional settings is examined in light of historical, political, deprivation, ethical, and generalization issues. The major points may be summarized as follows. a) The token economy may be viewed as a palliative measure to prevent the incredibly regressive effects of institutionalization. b) To achieve control in token programs in many "total institutions," an artificial state of deprivation must be achieved. c) Generalization of behaviors into the natural environment following the patient's stay in a token economy program should not be taken for granted. d) What the patient learns in a token economic system may not be what the token economy's program director probably intends.


Clinical and psychological test findings in cerebral dyspraxia associated with hemodialysis. Cerebral dyspraxia associated with hemodialysis is a progressive, fatal syndrome. Patients suffer from a combination of psychiatric and neurological signs and symptoms. Psychiatric manifestations include anxiety, depression, paranoid ideation, and a progressive dementia with impaired concentration, decreased memory, personality changes, and hallucinations. Neurological findings include deliberate speech, stuttering, dysarthria, dyspraxia of speech and movement, tremulousness, myoclonic activity, asterixis, and seizures. These symptoms are aggravated during and immediately following dialysis. Patients usually die within 6 months of its onset. The etiology is unknown. Treatment efforts have failed to reverse its course. Recognition of this syndrome is highlighted so that informed, critical decisions can be made as to whether to continue dialysis therapy.


Marital discord, sexual problems, and depression. Systematic studies of relationships among depression, sexual function, and martial discord in hemodialysis patients and their spouses arelacking; existing studies focus upon only one of these three topics, or deal with patient or spouse as individuals rather than as a couple. We studied 17 chronic, medically stable hemodialysis patients and their husbands or wives. Although couples rated their degree of marital discord as low, the investigators rated it as high, based on the number and type of specific problems reported by the couple. The couples' evaluation may not represent denial, as has been commonly assumed. Instead their evaluation may imply that the disease and its treatment overshadow marital problems, even though couples recognize and react to these problems. Couples showed a high prevalence of sexual problems--in terms of overall satisfaction, frequency of intercourse, and specific dysfunctional symptoms (difficulty becoming excited, maintaining excitement, or having orgasm). We found a strong relationship between severity of depression and severity of sexual dysfunction in patients, but not in their mates. No strong relationship existed between a patient's depression score and marital discord, although spouses showed a trend toward correlation between severity of depression and martial discord. Younger couples, especially, seem not to want intercourse when severe martial discord exists. Patients' depression scores were comparable to thoseof psychiatric patients, while spouses' depression scores resembled those of normals. While psychosocial phenomena such as marital discord, sexual dysfunction, and depression are clear, causal chains are not. Despite disadvantages inherent in using questionnaires, short, self-administered, easily scored instruments may elicit problems with sex, marriage, and mood which might otherwise be overlooked by caretaking personnel.


The fate of the untreated alcoholic. Toward a natural history of the disorder. Eighty-three male alcoholics were administered a structured interview when they appeared at a large general hospital for treatment of a variety of disorders. These represent 83 consecutive cases. None received treatment aside from brief "drying-out" but all were accepted as participants in a research program. Seventy-three (88 per cent of the sample) were located for a 3-year follow-up; five of these were not seen at the 1-year follow-up, and 10 were known to be dead. This paper focuses on 58 of the alcoholics who were seen at all three evaluations, and the 10 who were known dead. The data are presented as indicating the long term results of, at best, a mild or minimal intervention with male alcoholics. A small, but significant improvement was noted on several life-adjustment scales between the initial and 1-year evaluation (OYE), but no further improvement was seen between OYE and the 3-year evaluation (TYE); 19 percent were abstinent for 1 year and 10 per cent for the full 3-year period. The best predictor of TYE abstinence was OYE abstinence, but only for the extremes, i.e., no abstinence or total abstinence. Abstinence success was also related to a tendency to use community resources, lower number of mental hospitalizations, higher occupational status, higher global rating and, curiously, lower interpersonal adjustment rating. The group using Alcoholics Anonymous showed no better outcome than the group using no community resources at all. The mortality rate was 12 per cent over the 3 years or slightly more than 4 per cent a year. The suicide rate was about 4 per cent over the 3 years. The ratings for those dying showed a pattern of more admitted drunken arrests and heavy recent drinking superimposed on lighter overall drinking for the past year. The study demonstrates that even untreated alcoholics can be traced and effective follow-up studies completed. Results also indicate that over long time periods and left to their own devices, many alcoholics do seek out some form of help. But such assistance tends not to be sustained or intensive and a good portion of it is nonprofessional and nonmedical. Moreover, a surprisingly substantial number (31 per cent) of hospital-identified alcoholics apparently neither seek out nor receive any help at all after their initial identification; yet their self-reported life-adjustment ratings do not differ significantly from those who do seek help. The no-help receivers may be the most critical group of all to follow, as they are trule untreated. It would be important to determine how consistent in fact they are in their avoidance of help, what accounts for that behavior, and whether their ultimate fate is different from those who regularly seek assistance.


Some problems in the use of "attitude" and "atmosphere" scores as indicators of staff effectiveness in institutional treatment. Most institutional investigators have used paper-and-pencil measures of staff attitudes, opinions, and beliefs about "mental patients," "mental illness," and treatment programs or "atmosphere" to describe individual staff or aggregate staff groups. Popular scales for assessing the latter staff characteristics are noted, with a review of empirical relationships to treatment effectiveness. A review of uncontrolled and frequently confounded variables related to both effectiveness, and attitude and atmosphere scales suggests that several problems exist in the use of such measures as even indirect assessments of staff activity. Specific questions are raised for investigation which need to be answered before such scales can provide more than "demographic" description of treatment staff. Direct assessment of actual staff behavior appears to be a better alternative for determining what staff do.


Asymmetry of information processing in hallucinators and nonhallucinators. In previous work we had developed evidence suggesting that hallucinating schizophrenics differ from nonhallucinators in the pattern of errors made in a shadowing task. Non hallucinators appeared to be less willing to guess when they were unsure. The errors of the hallucinators seemed more semantically elaborate. The experiment had not been designed to study these factors and the current experiment was conducted using a technique reported by Pisoni et al. These workers had studied normal Ss in an immediate recall task, using semantically well integrated (SWI) or poorly integrated (SPI) sentences. Pisoni et al. had shown that right ear presentation produced more accurate recall of SWI as compared to SPI sentences, whereas left ear presentation failed to discriminate these sentences. Utilizing the methods of Pisoni et al., we replicated their findings in a  normal control group. The results from our hallucinating and nonhallucinating groups were different from each other, the nonhallucinators being less accurate, discriminating semantic integration level on left rather than right ear input, and making more fragmented errors. Little support could be found for attributing this pattern of performance to nonspecific aspects of the procedures. It appears that the nonhallucinators process information differently from hallucinators. These differences may reflect alterations in language development. It is speculated that such differences might be consistent with interference with the development of brain asymmetry.


Disturbed preschizophrenics. Childhood symptoms in relation to adult outcome. Adult outcome information was obtained for a sample of 45 males with a hospital diagnosis of schizophrenia. All cases had been treated at a child guidance clinic as children prior to the onset of schizophrenia as young adults. Refined outcome categories, which reflected the independent judgments of two clinical raters, led to the comparison of poor outcome with more favorable outcome cases in terms of antecedent characteristics. Five rationally derived childhood symptom scales were used. The psychotic scale was significantly related to poor outcome, while acting-out and aggressive symptom scales were related to more favorable adult outcomes. Neurotic and neurological scales were not predictive of outcome. Low childhood IQ and poor peer adjustment were significantly related to poor adult outcome. Sample limitations and comparison with results from other studies were discussed.


Psychological effects of short term cerebellar stimulation in epilepsy. The effects of short term cerebellar stimulation on integrative functions as measured by standardized psychological tests were studied. The patient group consisted of 12 epilepsy patients undergoing chronic cerebellar stimulation as treatment for intractable seizures. Three comparison groups included nonstimulated epilepsy patients, stimulated cerebral palsy patients, and stimulated stroke patients. Cerebellar stimulation resulted in some alterations in test performance. Improvements occurred from first to second test administration for both stimulated and nonstimulated subjects, as a probable practice effect. Short term stimulation of the cerebellar cortex does not result in apparent deficits. However, significant improvement in verbal output and in visual-motor performance occurred for the stimulated epilepsy group along with a small decrement in sustained concentration in a numerical task.  Preliminary hypotheses were offered to explain the results.


Craniopagus twins: surgical anatomy and embryology and their implications. Craniopagus is of two types, partial and total. In the partial form the union is of limited extent, particularly as regards its depth, and separation can be expected to be followed by the survival of both children to lead normal lives. In the total form, of which three varieties can be recognized, the two brains can be regarded as lying within a single cranium and a series of gross intracranial abnormalities develops. These include deformity of the skull base, deformity and displacement of the cerebrum, and a gross circulatory abnormality. It is considered that these and other abnormalities, unlike the primary defect, which is defined, are secondary ones; explanations for them, based on anatomy and embryology, are put forward. The implications of the various anomalies are discussed and the ethical aspects of attempted separation in these major unions considered.


Genetic associations between myasthenia gravis and the HL-A system. HL-A antigens were determined in 159 myasthenic patients, 112 of whom were females and 47 males. Fifty-seven patients were thymectomized. The relationship between 23 different HL-A antigens and myasthenia gravis (MG) with reference to sex, age at onset, clinical course of MG, thymus histology, and auxiliary diseases of the patients, as well as the significance of these antigens to 245 relatives of myasthenics, were analysed. The frequencies of HL-A1 and HL-A8 were highly significantly higher in myasthenic patients than in normal Finnish controls. The increase of HL-A1 is secondary and due to a strong linkage disequilibrium between HL-A8 and HL-A1. HL-A8 appeared most often in females with onset of MG before the age of 35 years, and inpatients with thymus hyperplasia. No significant HL-A deviations were found in males or in females with later onset of disease. In seven thymoma patients the occurrence of W10 antigen was almost significantly increased.


Serum immunogloblin levels in myasthenia gravis, polymyositis, and dermatomyositis. Analyses of serum immunoglobulin (Ig) levels were performed in patients with myasthenia gravis, polymyositis and dermatomyositis, and in normal subjects. The mean IgG levels were elevated in the disease groups and there was minimal depression of serum IgM levels in nonthymectomized myasthenic patients. There was no consistent pattern with regard to selective immunoglobulin class abnormalities, effect of thymectomy in serial studies, and no evidence of gross humoral immunological deficiency as manifested by consistent depression of serum IgA, IgG, or IgM in the disease groups.


Myasthenia gravis: clinical and histological features in relation to thymectomy. The clinical and thymic histological features of 23 patients who underwent thymectomy for myasthenia gravis have been examined and compared. Eighty-two per cent of patients with a non-neoplastic gland containing numerous germinal centres improved postoperatively, whereas 83% of patients with a non-neoplastic gland containing no germinal centres deteriorated or died. Glands with only slight involution and containing numerous germinal centres were more commonly seen in young female patients. The evidence relating thymic histological appearances with the postoperative progress of patients with myasthenia gravis is reviewed.


Transient eyelid retraction in myasthenia gravis. Three patients with myasthenia gravis had transient retraction of the upper eyelids which usually followed prolonged upgaze and which persisted for many seconds. This could result from post-tetanic facilitation, myotonia, or a transient contracture. Retraction of this type is to be distinguished from both the long-standing unilateral retraction associated with ptosis of the contralateral eyelid and the fleeting lid twitch sign.


Hypocalcaemic myopathy with paranoid psychosis. A description is given of a patient with idiopathic hypoparathyroidism and a paranoid psychosis. Changes in muscle, electromyograms, and blood enzyme levels were related to hypocalcaemia. Reference is made to the elevations of these enzyme levels found in other cases of psychosis.


Ocular bobbing with survival.

Ocular bobbing with survival. A case is described of prolonged ocular bobbing with survival after subarachnoid haemorrhage from a pontine arteriovenous malformation. Hitherto, this sign has usually been associated with a rapidly fatal outcome.


Parallel variation of ventricular CSF tryptophan and free serum tryptophan in man. Tryptophan was measured in the ventricular CSE and serum and the neutral amino acids leucine, isoleucine, valine, phenylalanine, and tyrosine were measured in the serum of two cases with ventricular drains. Samples were taken every two hours for 24 hours in one case and for 16 hours in the other. The CSF tryptophan was correlated significantly with the free--that is, non-albumin-bound--serum tryptophan but not with the total serum tryptophan. CSF tryptophan was not correlated significantly with the ratio of free serum tryptophan to the sum of the neutral amino acids. These data suggest that, in man, brain tryptophan concentrations are influenced by the free and not the total serum tryptophan and that physiological variations of the neutral amino acids do not appreciably influence the concentration of brain trytophan.


Gliomas (astrocytomas) of the brain-stem with spinal intra- and extradural metastases: report of three cases. Astrocytomas of the pons and medulla oblongata ('brain-stem gliomas') while often invasive locally, do not as a rule seed and metastasize along the spinal meninges. Three cases are here reported (two adults, one child) in whom astrocytoma of the brain-stem metastasized along the spinal cord. The dura mater itself and the spinal epidural space were invaded in two cases. The child and one adult had a pontine astrocytoma, the other adult's tumour originated in the medulla oblongata. In the two cases that came to necropsy the tumour of the brain-stem was much better differentiated than the meningeal deposits. These three cases suggest that the possibility of spinal spread of brain-stem gliomas should be considered when dealing with diagnostic and therapeutic problems of such patients.


Acute confusional states with right middle cerebral artery infarctions. Three patients presenting predominantly with acute confusional states (ACS) are shown to have infarctions in the distribution of the right middle cerebral artery. It is suggested that the main deficit in ACS is in the function of selective attention. On the basis of cortical connections of homologous areas in the monkey brain, it is argued that this deficit arises from lesions in convergence areas for association cortex.


Jaw reflexes and masseter electromyograms in mesencephalic and pontine lesions: an electrodiagnostic study. Jaw reflexes and masseter electromyograms were studied in five patients with mesencephalic and 11 patients with pontine lesions, vascular or tumorous in nature. In the former group jaw reflexes were abnormal, being delayed or absent, whereas masseter electromyograms were normal. In the latter group, both jaw reflexes and masseter EMG, showing denervation, were abnormal in six and both normal in five cases. It is suggested that the afferent limb of the human jaw reflex passes through the mesencephalic trigeminal nucleus. The methods proved to be valuable in the diagnosis of mesencephalic and pontine lesions involving the fifth cranial nerve.


Localized sympathetic overactivity: an uncommon complication of lung cancer. Direct nerve infiltration by tumour tissue usually produces pain, and loss of motor, sensory, and autonomic function. Two patients are reported in whom a major symptom of nerve infiltration was sympathetic overactivity manifested by excessive spontaneous sweating.


Pressure palsy of the ulnar nerve with prolonged conduction block. A patient is described in whom conduction block occurred in the ulnar nerve after a pressure palsy and persisted for 16 weeks. The unusually long delay in recovery is discussed.


Spatiotemporal organization of cat lateral geniculate receptive fields. Spatial and temporal properties of LGN receptive fields were studied by flashing a small bar of light across the field in 28 discrete steps. The flashes at each of the spatial positions were used to produce 28 PST histograms. These histograms were in turn displayed as a plane, with space on the chi axis, time on the psi axis, and probability of firing on the zota axis. These response planes demonstrate that the terms on, off, center, and surround do not adequately describe when the simplest LGN receptive field. We, therefore, introduce a new terminology describing the four major spatiotemporal components of LGN fields. The primary excitatory (PE) domain corresponds to the strongest excitatory response, the secondary excitatory (SE) domain corresponds to the second-strongest excitatory domain, the primary inhibitory (PI) domain corresponds to the strongest inhibitory domain and, finally, the secondary inhibitory (SI) domain corresponds to the second-strongest inhibitory domain. Based on the arrangement of these four domains, it is possible to divide LGN fields into four major categories: 1) homogeneous-on, on-center receptive fields which have a spatially homogeneous distribution of domains; 2) homogeneous-off, off-center receptive fields which have a spatially homogeneous distribution of domains; 3) heterogeneous-on, on-center receptive fields which have a spatially heterogeneous distribution of domains; and 4) heterogeneous-off, off-center receptive fields which have a spatially heterogeneous distribution of domains; 3) heterogeneous-on, on-center receptive fields which have a spatially heterogeneous distribution of domains; and 4) heterogeneous-off, off-center receptive fields which have a spatially heterogeneous distribution of domains. Using grating, it can be demonstrated that our heterogeneous/homogeneous fields correspond to X/Y fields, respectively. These data lead us to suggest that retinal PE domains generage LGN PE and SI domains, while retinal SE domains generate LGN SE and SI domains.


Interactions between cat lateral geniculate neurons. Action potentials of 31 pairs of cat LGN neurons were recorded on single electrodes. Cross-correlograms, response planes, and a new function, the logical response plane, were calculated. The cross-correlograms between these pairs revealed four interactive classes: 1) a class with a flat cross-correlogram, 2) a class with a peak in the center of the cross-correlogram seen both during spontaneous activity and during driven activity, 3) a class with an inhibitory dip in the center of the cross-correlogram seen only when the cell pairs were driven by a stimulus and predicted by the shift predictor, 4) finally, a class with an inhibitory dip in the center of the cross-correlogram seen both during driven activity and spontaneous activity and not predicted by the shift predictor. Response plane pairs calculated for the unit pairs with flat cross-correlograms showed no predictable relationship. The pairs with a dip in the center of the cross-correlograms always had response planes that were antagonistic (i.e., approximate negative images of each other). When one cell was excited, the second cell was inhibited, and vice versa. More detailed analysis, using the logical response plane, demonstrated that the majority of the antagonistic response planes had either excitatory or inhibitory overlap. That is, the cells were simultaneously excited and/or inhibited at specific spatiotemporal loci on the response plane. These data are consistent with a feed-forward inhibitory circuit in LGN. Furthermore, the data suggest that retinal centers (PE domains) produce LGN excitatory centers (PE domains) and inhibitory centers (PI domains). In turn, retinal excitatory surrounds (SE domains) produce LGN excitatory surrounds (SE domains) and inhibitory surrounds (SI domains).


Responses of cats to sudden falls: an otolith-originating reflex assisting landing. A short-latency electromyographic response has been demonstrated in the human gastrocnemius during unexpected falls (11). The hypothesis that it is a form of otolith-spinal reflex has been tested in the cat. Electromyographic activity was measured in four muscles while suddenly and unexpectedly dropping a series of six cats from 50 cm above the ground. In normal animals, electrical activation of all muscles tested occurred in two distinct phases. An early burst commenced as early as 15 ms from the instant of release, was usually spindle shaped, and often but not always disappeared by 100 ms. This burst was totally and permanently abolished by bilateral labyrinthectomy, but not by selective inactivation of the relevant semicircular canals. A later phase of muscle activity commenced 75-140 ms after release and gradually built up and then subsided, rougly centered about the movement of landing on the ground. This activity was not greatly altered by labyrinthectomy. The present results appear to confirm that the early electromyographic response to sudden falls is due to an otolith-spinal reflex. A later component is nonlabyrinthine in origin, however. Smooth landings from short falls are not possible in the absence of either phase of the response.


Trial sequence of changed unit activity in auditory system of alert rat during conditioned response acquisition and extinction. 1. The activity of units in the auditory system of alert, freely moving rats was studies during the acquisition and extinction of a tone-signaled, appetitive classically conditioned response. Responses of neurons in inferior colliculus (N = 28), medial geniculate (N = 32), posterior nucleus of thalamus (N = 28), pretectal region (N = 19), and cortex (N = 100) were studies in 74 rats across 10-trial blocks. 2. During behavioral acquisition, neurons in posterior nucleus of thalamus were the first to show response increments to CS+ onset. They were followed by neurons in cortex, pretectal region, medial geniculate, inferior colliculus and by movement behavior. 3. Prestimulus background rates during acquisition showed significant decrements in cortical neurons. These background decrements began to be evidenced in the trial series before the response increases in posterior nucleus. These data strengthened the suggestion of a previous study that posterior nucleus responses could be dependent on tonic modulation from cortex. 4. Extinction appeared to be largely a reverse of acquisition. Cortex and behavior showed response decrements first in the trial series. They were followed by medial geniculate, pretectal region, posterior nucleus, and inferior colliculus neurons. 5. The hypothesis was advanced that the auditory lemniscal adjunct afferent system may play a primary role in the early phases of auditory conditioned-response acquisition.


Responses to tones and noise of single cells in dorsal cochlear nucleus of unanesthetized cats. 1. Single-unit responses in the dorsal cochlear nucleus of unanesthetized, decerebrate cats have been divided into two categoreis. These have been differentiated on the basis of responses to best-frequency tones. Type IV units responded to best-frequency tones with excitation from threshold to about 20 or 30 dB above threshold; at higher levels, their response was inhibitory. In a few cases, the excitatory area near threshold was not seen and in a few others, the response became excitatory again at high levels. Type IV units could be divided into two groups based on the length of time that inhibition was maintained in response to long tones. Type IV units are not seen in anesthetized cats. 2. Type II/III units responded to best-frequency tones of all levels with excitation. Nonmonotonic rate versus level functions were seen in type II/III units, but they were of much less drastic character; the discharge rate of nonmonotonic type II/III units was still well above spontaneous rate for tones 50 dB above threshold. Type II/III units defined in this way were found to have, on the average, lower rates of spontaneous activity and higher thresholds than type IV units. 3. Type II/III units responded weakly to broad-band noise in comparison to auditory nerve fibers and many of them did not respond at all to noise. Type IV units, with best frequencies above 0.9 kHz, gave excitatory responses to noise. 4. The inhibitory response areas of type IV units could be divided into two areas: a central inhibitory area in the vicinity of best frequency where on- and off-discharges and afterdischarges were seen; and inhibitory side bands at higher and lower frequencies where simple inhibitory responses were seen. In four units, it was possible to show that the central inhibitory area was converted to an excitatory area after administration of an anesthetic dose of pentobarbital. 5. Most type II/III and type IV units could be excited or inhibited by stimuli in the contralateral ear. Broad-band noise was a more effective contralateral stimulus than tones at the ipsilateral best frequency. 6. On the basis of the properties of type II/III and type IV cells, it is suggested that type II/III responses are recorded from interneurons which provide a large share of the inhibitory imput to type IV cells.


Mossy fiber neck and second-order labyrinthine projections to cat flocculus. In five decerebrate cats and in two under N2O-O2 anesthesia, a bipolar electrode array was inserted into a granular layer in the rostral flocculus. At this location MF field potentials were evoked by stimulation of the ipsilateral vestibular nerve and of the C2 dorsal root ganglion. Stimulation through the array was used to fire brain stem neurons antidromically. The activity of these neurons was recorded extracellularly with glass microelectrodes. Stimulation of the C2 dorsal root ganglion evoked in the caudal lateral brain stem  a field potential caused by the arrival of impulses in primary afferent fibers. Cells projecting to the flocculus also responded to the stimulus, usually monosynaptically. These neurons were fired by stimulation of the area of the atlantoaxial joint. They did not respond to stimulation of the contralateral C2 dorsal root ganglion, and responded only rarely to stimulation of the dorsal rami of the C2 and C3 spinal nerves. Stimulation of the vestibular nerve was ineffective. Another group of cells projecting to the flocculus was fired at short latency by stimulation of the ipsilateral vestibular nerve. These neurons were usually inhibited by stimulation of the contralateral vestibular nerve. They were not affected by stimulation of any neck afferents. The location of many recording locations was identified by means of fast green dye marks. Most neurons relaying neck activity were in group x of Brodal and Pompeiano (4), a few were in the external cuneate nucleus, and one was in the descending vestibular nucleus. Neurons relaying labyrinthine activity were in the descending vestibular nucleus; one was found in the medial nucleus, in which tracks were made only rarely. There are two parallel pathways relaying neck and labyrinthine activity to the flocculus. While they are separate at the level of the brain stem, they converge in the same rostral areas of the flocculus. The neck afferent information may be required for proper performance of the flocculus in eye-movement control.


Reversal properties of climbing fiber potential in cat Purkinje cells: an example of a distributed synapse. 1. The electrophysiological properties of the EPSP generated in Purkinje cells by the activation of CFs were studies in the cat cerebellar cortex. 2. CF-EPSPs were evoked by electrical stimulation of the cerebellar white matter and recorded intracellularly from the soma of the Purkinje cells. 3. Current was injected into the Purkinje cells via the recording micropipette using a bridge amplifer in order to study the reversal properties of the EPSP. 4. The CF-EPSP reversal was biphasic with the early portion reversing first. 5. The reversed EPSP waveform was not a mirror image of the EPSP, but displayed a briefer time course. 6. A four-compartment computer stimulation showed that the reversal properities of the CF-EPSP were explicable in terms of a distributed synapse on a cable. 7. The biphasic reversal and asymmetry were shown to be due to the spatially nonuniform potential distribution created by the somatic current injection, which predominantly reversed the proximal part of the distributed synapse. Delayed rectification may also have contributed to the reversal asymmetry. 8. The advantages of a distributed synapse over a point synapse are discussed and the reversal properties of the CF-EPSP compared to those of the Ia-evoked EPSP in motoneurons.


Long spinal and pyramidal actions on hindlimb motoneurons of the marsupial brush-tailed possum, Trichosurus vulpecula. The existence of descending propriospinal reflex linkages between forelimbs and hindlimbs has been established in the brush-tailed possum (Trichosurus vulpecula). In animals under chloralose anesthesia and with intact brain stem, forelimb volleys evoked facilitation of flexor and extensor monosynaptic reflexes of both hindlimbs, more pronounced on the ipsilateral side. Powerful inhibition of briefer latency and restricted to ipsilateral flexor digitorum longus (FDL) motoneurons was also brought about by forelimb volleys; at latencies exceeding 20-30 ms, FDL inhibition was usually replaced by facilitation. Distinctness of the two long spinal actions was shown by differences in forelimb receptive fields and in threshold of the executant afferent fibers. The field for reflex inhibition was located distally in the forepaw region, that for facilitation being wider, including deep as well as superficial tissues. Threshold of afferent fibers evoking inhibition was lower than that for facilitation. The descending long spinal actions were compared with those set up by repetitive stimulation of the motor cortex contralateral to the test hindlimb reflexes. In agreement with previous work, strong facilitation of most flexor or extensor motoneurons was produced, including those of quadriceps and ankle flexors, as well as gastrocnemius and hamstring motor nuclei; inhibition consistently appeared only in the FDL motoneuron pool. Weak and inconstant inhibitory action was occasionally observed in other motor pools. Pyramidal tract section abolished the cortical inhibition of FDL, but had little effect on facilitation; both long spinal actions were unchanged. Pyramid-sparing brain stem section greatly reduced both cortical and long spinal facilitatory action, but had little or no effect on FDL inhibition from either source. Interaction experiments demonstrated facilitation of weak inhibitory actions on FDL motoneurons of forelimb and cortical stimulation when elicited together, suggesting a sharing by the two inputs of common interneuronal elements. The observation is consistent with the notion that the long propriospinal system responsible for FDL inhibition from the forepaw might provide the pathway for pyramidal inhibition of the same group of motoneurons.


Intracellular responses from granule cell layer in slices of rat hippocampus: perforant path synapse. Intracellular responses were recorded in vitro from the denate granule cell layer of hippocampal slices prepared from adult rats. Spontaneous activity of granule cells in vitro consisted of action potentials and small, graded depolarizations, presumably of synaptic origin. Granule cells could be activated by injection of depolarizing current or release of hyperpolarizing current. Individual granule cells spatially summed input from the perforant path and fired multiple action potentials in vitro following strong presynaptic volleys. Depolarization decreased and hyperpolarization increased the EPSP amplitude, which is consistent with a conductance-increase mechanism. Although we could demonstrate postexcitatory inhibition in some cells, granule cells in vitro appeared to receive less inhibitory feedback than in vivo, EPSP amplitude and spike output of granule cells showed frequency potentiation and posttetanic potentiation to perforant path stimulation. These intracellular responses in vitro complement some of the findings from field-potential analyses of the dentate gyrus in intact animals.


Role of centrifugal pathways to cochlear nucleus in determination of critical bandwidth. Atropine sulfate was applied locally to the cochlear nucleus of three unanesthetized cats in order to block the cholinergic centrifugal innervation of the nucleus. The critical bandwidth was measured behaviorally from the masked thresholds of 1-kHz tone pips in different bandwidths of masking noise. Atropine increased the critical bandwidth markedly. This suggests that normally the centrifugal pathways influence the critical bandwidth. Saline solutions alone had no effect, and if the cannula was not accurately implanted over the cochlear nucleus, atropine had no effect either.


Relationship between visual and tactile representations in cat superior colliculus. A stratified organization of visual, somatic and acoustic representations was observed in the cat SC. Cells of the superficial laminae were exclusively visual. Visual, somatic, and acoustic cells were observed in the intermediate laminae while the deeper laminae were predominantly nonvisual. A detailed examination of the tactile representation revealed a somatotopic plan which was in register with the overlying visuotopy. The magnified representation of central visual fields overlapped the magnified tactile representation of the face and, as visual RFS moved temporally, the underlying tactile RFS were displaced caudal and distal. This topographical overlap can be recognized if the visual field is depicted as a flexible sheet which is stretched over the body with the area centralis superimposed on the nose and the limbs radiating out at an acute angle. The overlapping topographies and similarities in stimulus specificity of somatic and visual cells, as well as the similar behavioral deficits previously described following SC lesions, suggests a functional parallel between modalities in the SC. The possibility that visual, somatic, and acoustic cells converge on a common delivery or distribution system, which is located in the intermediate-deeper SC strata and organizes orienting and following responses on the basis of multimodality cues, is discussed.


Fast and slow pyramidal tract neurons: an intracellular analysis of their contrasting repetitive firing properties in the cat. 1. Intracellular recordings were made from an estimated 500 neurons in the sensorimotor cortex of barbiturate-anesthetized cats. Of those which were antidromically identified from the medullary pyramids, 70 were selected which also exhibited steady repetitive firing to steps of current injected through the recording electrode; 81% were "fast" (conduction velocity greater than 20 m/s) and 19% were "slow". 2. As shown by earlier workers, the spike duration is a function of conduction velocity; a spike duration of 1.0 ms is the dividing line between fast and slow. 3. Of the 57 fast pyramidal tract neurons (PTNS), 14 exhibited double spikes during otherwise rhythmic firing patterns to a step of injected current. These very short interspike intervals (usually 1.5-2.5 ms) were first seen interspersed in a rhythmic discharge (e.g., 50-ms intervals) but, with further increases in current strength, would come to dominate the firing pattern; e.g., double spikes every 40 ms. Further increases in current would typically shorten only the long intervals; e.g., 40-30 ms, but some fast PTNS developed triple spikes, etc. 4. The extra spike appears to arise from a large hump which follows most spikes in fast PTNS; while this humplike "depolarising after-potential" can also be seen in slow PTNS, it is small. Extra spikes were seen only in fast PTNS with large postspike humps; in perhaps half of the fast PTNS, extra spikes probably contributed to "adaptation." 5. Slow PTNS often had frequency-current curves which were not repeatable; a "hysteresis" phenomenon could often be seen, where the proportionality constant relating current to firing rate decreased following high firing rates. 6. The B spike was distinguishable from the A spike in differentiated antidromic spikes in 77% of the slow PTNS, in only 14% of the fast PTNS which later exhibited double spikes during current-induced repetitive firing, and in 53% of the other fast PTNS. 7. The antidromic spike heights of doublet PTNS were not significantly different from those of other repetitively firing PTNS.


Nonketotic hyperglycemic hyperosmolar coma. Report of neurosurgical cases with a review of mechanisms and treatment. Seventy-eight critically ill patients who died while on the neurosurgical service were studied retrospectively to establish the prevalence of nonketotic hyperglycemic hyperosmolar coma (NHHC). All the patients had been comatose before death, and all underwent necropsy. Criteria for the diagnosis of NHHC included moderate-to-severe hyperglycemia with glucosuria, absence of significant acetonuria, hyperosmolarity with dehydration, and neurological dysfunction. This study revealed seven cases of unequivocal NHHC (9%), and six of hyperosmolarity but with incomplete records. Five of the seven confirmed cases of NHHC demonstrated no evidence of cerebral edema transtentorial herniation, or brain-stem damage, and showed central nervous system (CNS) lesions compatible with survival. Fatal complications of this syndrome, such as acute renal failure, terminal arrhythmias, and vascular accidents, both cerebral and systemic, were common in this series. The mechanism of coma in NHHC is believed related to shifts of free water from the cerebral extravascular space to the hypertonic intravascular space, with subsequent intracellular dehydration, accumulation of metabolic products of glucose, and brain shrinkage. It is uncertain whether injury to specific areas in the CNS is a predisposing factor to the development of NHHC. Factors documented to be significant in its development include nonspecific stress to primary illnesses, hyperosmolar tube feedings, dehydration, diabetes and mannitol, Dilantin, or steroid administration.


Possible mechanisms for observed pathophysiological variability in experimental spinal cord injury by the method of Allen. Experimental spinal cord injuries were induced in dogs by dropping calibrated weights through a vented tube onto a small impounder resting on the surgically exposed cord. The motion of the impounder and the drop-mass were recorded by high-speed photography and the resulting data were compared to those obtained from a computer simulation of the dynamics of the injury mechanism. It is concluded that this method of induced spinal cord injuries may yield markedly different degrees of cord compression depending upon the parameters of the animal material and apparatus even when the gm-cm of impact energy is maintained at a constant value. Some approaches to standardization of this injury model are suggested.


Classification of cervical spondylosis or disc protrusion by preoperative evoked spinal electrogram. Follow-up study. The evoked spinal electrogram (SEG) was studied in 11 patients with cervical spondylotic myelopathy or disc protrusion. All the patients were severely handicapped before surgery. The evoked SEG was classified in three grades before and during surgery. Periodic follow-up studies were done at 18 to 35 months, with an average of 24 months. Four of six patients were normal or slightly abnormal SEG recordings showed satisfactory improvement of the disability; however, only one patient showed any improvement when the recording was moderately or severely abnormal. Location of the cord lesion and type of surgery were similar in all patients examined, and the difference was likely ascribed to the physiological change of the intramedullary structures. The evoked SEG provides some information relative to the surgical treatment of spondylotic myelopathy or disc protrusion with cord lesion.


Chronic measurement of epidural pressure with an induction-powered oscillator transducer. An induction-powered oscillator transducer (IPOT) was designed for the chronic measurement of epidural pressure. The transducer was completely implantable so all pressure measurements were made through the intact skin. The IPOT had a linear pressure range from -50 to +200 cm H2O, was sensitive to 1 mm H2O and had a zero drift of less than 1 mm H2O/day under full load. Zero drift was minimized by using a hermetically-sealed metal bellows transducing element which was chemically treated to prevent corrosion and creep. The correlation between epidural pressure and intraventricular pressure was determined during the first 24 hours after implantation in six dogs. Epidural pressure was found to be a linear function of intraventricular fluid pressure. Epidural pressure and intraventricular pressure were essential equal provided the epidural wedge pressure was minimized by proper insertion of the transducer. The correlation between epidural pressure and intraventricular pressure was determined after chronic implantation in five dogs. Epidural pressure was a linear function of intraventricular pressure in the chronically implanted dogs, but epidural pressure was not equal to intraventricular pressure. After chronic implantation, the epidural pressure transducer was not responsive to changes in intraventricular pressure because of mechanical changes in the dura. The dura became stiff and non-compliant. Maximum correlation between epidural pressure and intraventricular fluid pressure in chronic implantations will depend on judicious material selection and mechanical design at the transducer-dura interface.


Use of epsilon aminocaproic acid (EACA) in the preoperative management of ruptured intracranial aneurysms. The authors report their experience with the use of epsilon aminocaproic acid (EACA) in the preoperative management of a series of patients with ruptured intracranial aneurysms. A similar series of patients was taken as control. They found that EACA is of definite value in preventing recurrent hemorrhage in the preoperative period. The significance of antifibrinolytic therapy in ruptured intracranial aneurysms is discussed.


Glioma of the jugular foramen. Case report. A case is presented of a jugular foramen syndrome caused by an ectopic glioma. Treatment was by intracapsular removal through a suboccipital craniectomy.


Radionuclide cisternographic evaluation and follow-up of posttraumatic subconjunctival CSF loculation. Case report. The case of a patient with massive, posttraumatic, subconjunctival cerebrospinal fluid collections is described in which diagnosis and postoperative management was simplified by serial radionuclide cisternography.


Chondrosarcoma of the cervical spine. Case report. The authors present a case of chondrosarcoma involving the lateral mass of the C-2 vertebra, treated by an apparent total removal of the tumor. A review of the literature revealed that these patients can be cured in a significant number of cases if a radical removal is accomplished.


Complication of a large cranial defect. Case report. A patient with acute subdural hematoma was successfully treated with hemicraniectomy. He developed contralateral weakness 4 months after surgery which was reversed by cranioplasty. The presumptive mechanism is a gradient between atmospheric and intracranial pressure. Early cranioplasty is suggested to prevent this phenomenon.


Cerebral arterial dolichoectasia with seizure. Case report. Cerebral angiography, performed after a seizure in a patient with a life-long history of typical hemiplegic migraine, disclosed markedly dolichoectatic anterior and middle cerebral arteries. No abnormality of the adjacent capillary or venous structures was present. A positive brain scan was attributed to ischemia induced by vasospasm rather than to the corresponding large tortuous anterior and middle cerebral arteries. There were no permanent sequelae and the patient has been free of seizures on Dilantin and phenobarbital over a 3-year follow-up period. Angiographic demonstration or description of a similar ectatic set of anterior and middle cerebral arteries could not be found in the literature. The concurrence of seizures and hemiplegic migraine adds to the peculiarity of this case.


Fatal paradoxical muscle embolization in traumatic carotid-cavernous fistula repair. Case report. A unique case of fatal paradoxical muscle embolism in a patient with a traumatic carotid-cavernous fistula is described. The muscle plug intended to occlude a left-sided fistula passed through the large fistula, bypassed the lungs by way of a patent foramen ovale, and embolized through the right carotid artery to lodge the internal carotid and middle cerebral arteries producing fatal brain infarction.


Middle cerebral artery embolectomy. Case report. A patient who developed an embolic occlusion of the right middle cerebral artery while undergoing a cerebral arteriogram was successfully operated on by removal of the embolus under the surgical microscope. Early postoperative cerebrovascular spasm was a factor in the transient deterioration of the patient's neurological condition. When the patient was last seen 2 1/2 months after surgery she was almost intact neurologically with only a mild right parietal dysfunction but with total resolution of the left hemiplegia. The literature is reviewed.


Microvascular bipolar coagulator. Technical note. A bipolar coagulator fabricated from jeweler's forceps of various sizes is described. The unit has proved very useful in microvascular neurosurgical procedures that require high magnification.


Cesium-129 myocardial scintigraphy to quantify myocardial infarction in dogs. The sizes of surgically induced acute myocardial infarctions were quantified in a study of 28 dogs. Four projections (right and left anterior oblique, anterior, and left lateral) were obtained with 129Cs myocardial scintigraphy. Control images, taken before surgery, were compared with images taken 24-72 hr after coronary artery ligation. From postmortem examination the size of the infarct was determined and expressed as a percentage of the total left  ventricle. On a standard diagram four independent observers marked the infarcted areas in each projection, expressed the severity of involvement in each area, and determined overall infarction size as a percentage of the total left ventricle. A nonlinear least-squares method was also employed to derive the size of the infarct, using the results from each observer's diagram. There were positive correlations between each observer's percentage estimate and the autopsy results. The overall accuracy of the least-squares method was similar to that of the individual observers. In this study, Observer 3 proved that acute myocardial infarcts can be quantified accurately from multiple scintigraphic projections of the myocardium, but the other three observers had difficulty in estimating infarct size. This difficulty probably resulted from the lack of well-validated criteria to aid the observer in determining the area of infarction, the severity of involvement within that area, or the total size of a myocardial infarct. Improvement in these estimates will require the development of definitive criteria, the use of optical scanners or computer processing, and combinations of radionuclides.


Lymphangitic carcinomatosis: lung scan abnormalities. Lymphangitic carcinomatosis of the lung is a late and fatal manifestation of cancer. The diagnosis is seldom made ante mortem. Four patients with breast cancer had autopsy-proven lymphangitic metastases of the lung. Of these patients, two had normal chest x-rays and three had normal ventilation lung scans. The perfusion lung scans of all four showed irregular peripheral perfusion defects. Autopsies showed permeation of the lymphatics by tumor and tumor emboli in small arteries and arterioles.


Comparison of 99mTc and 123I for thyroid imaging. Thyroid images were obtained with 99mTc and 123I, using a scintillation camera and pinhole collimator, from 85 patients selected from over 1,000 patients predisposed to the development of thyroid neoplasms by prior radiotherapy. In 66 of 85 patients 99mTc and 123I gave essentially similar information, whereas in 19 patients some thyroid-image disparity was seen. In 11 of these 19, focal areas of increased 99mTc concentration were not seen with 123I. Radioiodide images showed slightly better contrast than the 99mTc images but required a longer imaging time and usually did not provide more information; in a few cases 99mTc showed abnormalities more readily. Regardless of which radionuclide was used, oblique views were needed to define some abnormalities. Currently 123I does not provide significant advantages over 99mTc for routine thyroid imaging. However, 123I is preferred in patients with very poor thyroid function and in those with suspected retrosternal thyroid tissue. In addition, areas of increased 99mTc concentration should also be studied with 123I.


Thyroid scanning with gallium-67 and cesium-131. The roles of 131Cs and 67Ga in the evaluation of solitary thyroid nodules were investigated. Radionuclide scans were performed with 67Ga and 131I in 27 patients and with 131Cs and 131I in 43 patients. Gallium-67 detected only two of eight malignant nonfunctioning nodules and 131Cs detected one of three such nodules. The contribution of 131Cs and 67Ga to the preoperative identification of malignant thyroid lesions is of doubtful value.


Abnormal 67Ga-citrate scan of the abdomen in tuberculous peritonitis: case report. Tuberculous peritonitis in a 34-year-old alcoholic man was associated with an abnormal 67Ga-citrate scan of the abdomen. Repeated studies after thorough bowel cleansing revealed no change in the site and shape of the abnormality for 2--5 days after injection of the tracer. The inflammatory process may have been responsible for the abnormal scan.


Tumor model studies of 131I-tetracycline and other compounds. Iodine-131-tetracycline (131I-TET) was prepared by allowing tetracycline hydrochloride to react with radioiodide in acidic methanol (labeling efficiency greater than 85%). This preparation was found to be stable at--4 degrees C for at least 72 hr. Some minimal in vivo breakdown did occur. The 131I-TET, 67Ga, and several 99mTc compounds were studied in a rat hepatoma model. The incorporation of the radiopharmaceuticals into the tumor occurred rapidly, with peak levels at 0.5 and 24 hr after injection for 131I-TET and 67Ga, respectively. The clearnace of the radiopharmaceutical from nonviable tumor was slower than for viable tumor, and by 72 hr after injection the greatest concentration of radioactivity appeared in the nonviable fraction. All normal tissues showed faster clearance than did tumor tissue, regardless of viability. Decreasing the quantity of 131I-TET injected increased the percent of uptake in the nonviable tumor tissue but had no effect on the viable tumor uptake. Of the 99mTc compounds studied, the phosphates developed the highest tumor-to-background ratios. Unfortunately these ratios were not as high as those achieved for 67Ga or 131I-TET.


Circulation clearance rate of radioiodine during fibrinogen uptake tests. Scintillation counts, following administration of 125I-labeled fibrinogen, were performed on the legs of medical and surgical patients. As part of the test procedure, precordial count rates were recorded and used in calculating the fibrinogen clearance rates. A short half-time for the circulating radioiodine was found to correlate well with the detection of venous thrombosis.


Distribution and retention of 35S-sodium sulfate in man. Measurements were made of the 35S content of tissues obtained from biopsies and autopsies made during and up to 6 months after treatment of chondrosarcoma or chordoma with carrier-free Na235SO4. Usually 70--90% of an intravenous dose was excreted in the urine during the first 3 days. The major component of the blood concentration had a biologic half-time of 0.4--0.7 days. The initial uptakes in chondrosarcoma, chordoma, and red bone marrow were high and nearly equal, but the rates of loss differed greatly. Uptake in epiphyseal cartilage was comparable to that in chondrosarcoma; uptake in other types of cartilage was lower, but subsequent loss was very slow. For an administered dose of 1 mCi per kilogram of body weight, the integrated radiation doses were 2.4 rads for blood, 33 rads for red bone marrow, 155 rads for chondrosarcoma, 49 rads for chordoma, and 135 rads for normal cartilage. Doses to muscle, skin, and fibrous tissue were 7--15 rads.


A new 80-lens oscilloscope camera for routine dynamic organ scintigraphy. A simple, reliable, and cost-effective 80-lens photographic camera records dynamically from the oscilloscope of a scintillation camera without degradation of spatial resolution or data loss. Most physiologic events can be recorded completely and without interruption on a single 9 X 12-cm negative film as 40 sequential time-frames, using one of six available exposures per frame. In addition, 40 simultaneous sequential time-frames of four times the chosen duration may bracket a transient event with increased data density. The 80-lens camera has been used routinely for perfusion scintigraphy of brain, heart, liver, kidneys,and lungs with excellent results.


Radiation dosimetry of 204Bi- and 206Bi-citrates. The absorbed-radiation doses from 204Bi- and 206Bi-citrates to humans are calculated from  available nuclear and biologic data in order to evaluate the relative radiation risk of these radionuclides. The calculations reveal that the radiation dose to the kidneys is reduced by a  factor of 8 if 204Bi replaces 206Bi. This reduction suggests that 204Bi should be investigated further as a possible soft-tissue scanning agent.


"EAR" artifact in brain scans.

"EAR" artifact in brain scans. The ear closest to the camera may be imaged in high-resolution lateral views of the brain as a structure anterior to the lateral sinus. The artifact can usually be eliminated by taping the auricle down. Artifacts such as this can be expected to become somewhat more of a problem as image resolution improves.


Thyroid uptake of 131I: further comparisons of capsules and liquid preparations. Comparisons were made of thyroid uptake of three commercially available preparations of 131I, using a double-blind design, in 125 patients with normal thyroid function. Uptakes with  Squibb Iodotope Diagnostic capsules were significantly lower than those with Squibb Iodotope Oral liquid at 4 hr (p less than 0.01) and 24 hr (p less than 0.05) after ingestion in both the general population and in all patients less than 45 years of age. Uptakes of Radiocaps I-131 (Abbott Laboratories) and Iodotope Oral liquid were indistinguishable under identical conditions. Our findings indicate that interference with either absorption or metabolism of a pharmaceutical can result from the vehicle used to administer it.


Bone accumulation of 99mTc-labeled leucocytes. Leucocytes were separated from rats' blood by dextran sedimentation method and labeled with 99mTc-pertechnetate. A maximum labeling efficiency of 18.5% was achieved with the addition of 1 mg of stannous chloride. The labeled leucocytes were intact and viable and the 99mTc label  was firm. Distribution studies in rats, 3 hr after injection of 99mTc-labeled leucocytes, showed 33% concentration in the mineral part of the bone, this being slightly lower than the 36.8% concentration in the liver. Technetium concentration in the bones due to a complex formed by various ingredients used for leucocyte labeling was excluded since negligible bone uptake was noted after injection of an incubated mixture of 99mTc and all ingredients except leucocytes. Also 51Cr-labeled leucocytes showed no localization in the bone. These studies indicate that 99mTc and intact leucocytes form some sort of complex which has an affinity for bone cortex.


Comparison of inulin, iothalamate, and 99mTc-DTPA for measurement of glomerular filtration rate. Clearances of inulin, 125I-iothalamate, and 99mTc-Sn-DTPA were measured simultaneously in five mongrel dogs exhibiting a wide range of glomerular filtration rates (GFR). Standard constant-infusion inulin clearance was compared to radionuclide clearances after subcutaneous injection of the emitters mixed with aqueous epinephrine. All three substances were found to have virtually identical clearances. The accuracy, accessibility, low cost, low radiation hazard, and short half-life of 99mTc-Sn-DTPA make it an excellent substance for measuring GFR. The subcutaneous technique offers an accuracy comparable to the more difficult constant-infusion method.


Rapid radioimmunoassay of triiodothyronine on Sephadex G-25 by the Ames kit. A rapid kit method for the determination of serum triiodothyronine levels is described. The method was satisfactory in cases of thyrotoxicosis, but its lower sensitivity in euthyroid patients gave higher levels (range 2.3-3.3 nM/liter) than normally found. The kit would be of value as a rapid method (little over 3 hr) to screen patients suspected of early or T3 thyrotoxicosis.


Fluoride-selenium interaction in the hard and soft tissues of the rat. The interaction of dietary fluoride and selenium in the hard and soft tissues of rats was studied by providing drinking solutions containing 50 ppm F, as NaF, alone or plus 1 or 3 ppm Se as one of the following selenium compounds: NaSeO3, Na2SeO4, DL-selenomethionine, or DL-selenocystine. The following parameters were measured: symptoms of selenium toxicity, soft tissue uptake of fluoride and selenium, histology of liver and kidney tissues, fluoride uptake into growing femur bones, and fluoride uptake onto calcified molar enamel. No evidence was found that fluoride interacted with any of the four selenium compounds.


Studies on the 1alpha, 25-dihydroxycholecalciferol-like activity in a calcinogenic plant. Cestrum diurnum, in the chick. Cestrum diurnum (day-blooming jessamine) has been proposed to cause calcinosis in horses and cattle in Florida. The present studies investigated some physiological properties of the plant, using the chick as the experimental animal. The inclusion of dried leaf powder in a rachitogenic diet restored intestinal calcium-binding protein synthesis (CaBP) and increased calcium absorption in the cholecalciferol-deficient chick. The estimated level of cholecalciferol-equivalents in the dried leaf was about 30,000 to 35,000 IU/kg. Most of the activity was extractable with methanol:chloroform (2:1), indicating that the major cholecalciferol-like component in C. diurnum was different from the water soluble factor(s) in Solanum malacoxylon. The time course of effect of C. diurnum extract in rachitic chicks was similar to that ot 1,25-dihydroxycholecalciferol but the former had a longer lag time. The strontium fed chick, in which the kidney 25-hydroxycholecalciferol-1alpha-hydroxylase is inhibited, responded to C. diurnum extract, confirming the 1alpha,25-dihydroxycholecalciferol-like character of the Cestrum factor. The extract also appeared to interact with the intestinal 1 alpha,25-dihydroxycholecalciferol cytosol receptor although this observation is preliminary. These findings indicate that the l alpha,25-dihydroxycholecalciferol-like principle in C. diurnum many cause excessive calcium and phosphate absorption leading to calcinosis.


Hydrogen production in the rat following ingestion of raffinose, stachyose and oligosaccharide-free bean residue. Raffinose and stachyose were compared to cooked California Small White beans (CSW) containing 4% alpha-oligosaccharides (stachyose and raffinose) and to oligosaccharide-free CSW solids (residue from hexane and 70% ethanol extraction of CSW) as sources of hydrogen when ingested by rats maintained in life support systems. If the oligosaccharide content were the only hydrogen source in CSW, it would have had to be 25 times as potent as CSW, but raffinose was only five times and stachyose seven times as potent as CSW. Oligosaccharide-free residue was 0.4 to 0.5 as active as CSW. Hydrogen producing potencies of stachyose and raffinose were enhanced by feeding in combinations with residue. The increases in hydrogen production from the combinations were more than additive. Thus, CSW contains at least one 70% alcohol-insoluble substance which, in addition to the oligosaccharides, is essential to bring about quantitatively the physiological response to whole beans observed in rats.


In vivo requirement for silicon in articular cartilage and connective tissue formation in the chick. Studies were undertaken to determine further effects of silicon deficiency in the chick. The diet and experimental conditions were the same as those used in previous studies to demonstrate the essentiality of silicon for growth and development. Skeletal and other abnormalities involving glycosaminoglycans in formation of articular cartilage and comb connective tissue were found to be associated with silicon deficiency. The bones of 1 day-old deutectomized cockerels fed a silicon supplemented diet and killed at 4 weeks of age had significantly greater amounts of articular cartilage and water as compared with the silicon deficient group and also a greater proportion of hexosamine in the cartilage. The greater water content in bones of the silicon supplemented chicks coincided with a larger content of glycosaminoglycans in the articular cartilage. A similar relationship was obtained in cockerel comb. In addition to larger amounts of connective tissue and of total hexosamine in combs of the supplemented group, a higher percentage of hexosamine and a higher silicon content was found. These findings provide the first evidence for a requirement for silicon in articular cartilage and connective tissue formation and that the site of action of silicon is in the glycosaminoglycan-protein complexes of the ground substance.


In vitro uptake and metabolism of pteroylpolyglutamate by rat small intestine. The digestion and cellular uptake of 14C-pteroylheptaglutamate (14C-PG-7) was studied using an isolated cell preparation from rat small intestine and by assay of folate conjugase (EC 3.4.23.10) in whole homogenates and brush border fractions of rat small intestinal mucosa. In the cell preparation, 14C-pteroylmonoglutamate (14C-PG-1), the principal degradation product of 14C-PG-7, was concentrated earlier in the cell fraction than in the extracellular fraction, while the concentrations equalized after 15 minutes. Incubation of cells with equimolar 14C-PG-7 and 3H-PG-1 was followed by a threefold greater cellular concentration of 14C-PG-1 than 3H-PG-1. In subcellular fractionation studies, folate conjugase was minimally present in the brush border relative to the supernatant fraction. These data suggest that 14C-PG-7 is transported into the epithelial cell of the intestinal mucosa prior to its hydrolysis by intracellular folate conjugase.


Decreased absorption of calcium, magnesium, zinc and phosphorus by humans due to increased fiber and phosphorus consumption as wheat bread. During a 20 day period of high fiber consumption in the form of bread made partly from wheaten wholemeal, two men developed negative balances of calcium, magnesium, zinc and phosphorus due to increased fecal excretion of each element. The fecal losses correlated closely with fecal dry matter and phosphorus. Fecal dry matter, in turn, was directly proportional to fecal fiber excretion. Balances of nitrogen remained positive. Mineral elements were well-utilized by the same subjects during a 20-day period of white bread consumption.


Cholesterol turnover and tissue distribution in the guinea pig in response to dietary cholesterol. Cholesterol turnover and tissue cholesterol distribution were studied in guinea pigs fed either a control diet or one containing 0.1% cholesterol. Dietary cholesterol caused a significant increase in the cholesterol concentration in liver, red blood cells and small intestine, but not in plasma. Most of the increase in total body cholesterol could be accounted for as an increase in liver esterified cholesterol content. Feeding the 0.1% cholesterol-containing diet did not significantly change either the absorption of an oral dose of tracer cholesterol or the endogenous cholesterol synthesis rate. Steady state cholesterol input-output rate and total traced mass of cholesterol were significantly greater, and mean transit time was significantly longer in the animals fed the cholesterol containing diet. These data suggest that the maintenance of cholesterol homeostasis in the nonhypercholesterolemic cholesterol-fed guinea pig depends on liver accumulation of esterified cholesterol as well as on increased output of cholesterol.


Activity of L-cysteinesulfinate carboxy-lyase and persulfurase in livers of rats fed different levels of sulfate and cysteine. Activity of L-cysteinesulfinate carboxy-lyase (CSC) and persulfurase was measured in livers of rats fed 15% casein diets supplemented with (1) 0.53% cysteine, (2) 0.40% cysteine, (3) 0.40% cysteine + 0.10% sulfate, (4) 0.42% sulfate, or (5) 0.42% sulfate + 0.40% cysteine. The diets were fed to adult rats for 1 week and to weanling rats for periods of 1 and 4 weeks. At the end of each feeding period, the highest CSC activity was detected in livers from animals fed diet 4, but no differences in CSC activity were detected among livers from the other four groups. Persulfurase activity did not differ significantly among those weanling or adult rats fed the diets for 1 week but was lower among those fed diet 4 than diet 5 for 4 weeks. The acitivity patterns did not parallel those of taurine excretion or conjugation observed previously among rats fed the same diets, and may indicate that factors other than taurine synthesis and ingestion control those processes.


Vitamin A metabolism during the repletion of zinc deficient rats. The experiments reported here were designed to determine if the low plasma vitamin A levels observed in zinc deficient rats are reversible as well as to examine the time required for any response. In experiment 1, rats previously zinc deficient were repleted for 6 days with a zinc sufficient diet, fed either ad libitum, or pair-fed the amount consumed by a zinc deficient group. After repletion, plasma vitamin A concentration for the zinc sufficient group returned to within normal range while the pair-fed group had a plasma vitamin A concentration intermediate between the zinc sufficient ad libitum and zinc deficient groups. The zinc sufficient ad libitum group had a lower concentration but higher total liver content of vitamin A than the other two groups. In experiment 2, the response of zinc deficient rats to intraperitoneal zinc repletion was examined daily for 7 days. There was a 3 day lag period before plasma vitamin A began to increase significantly following zinc treatment. By the fifth day, plasma vitamin A concentration increased to within the normal range. The data suggest that adequate food intake as well as zinc appears necessary to totally reverse low plasma vitamin A concentrations in zinc deficiency. Possible mechanisms are discussed.


Effect of dietary fat on fluoride absorption and tissue fluoride retention in rats. The effect of dietary fat on fluoride toxicity was investigated in rats fed isoenergetic diets with graded levels of fat (0, 10%, 30% or 50% of energy) containing 400 ppm fluoride. Growth rate was depressed in all groups receiving fluoride but most severely in the 50% dietary fat group. Plasma, liver and femur fluoride concentrations were increased by increasing dietary fat. This was apparently due to increased absorption of fluoride, since urinary fluoride increased and fecal fluoride excretion decreased as fat intake was elevated. The enhancement of fluoride absorption by fat is believed to be due to the delaying effect of fat and fluoride on gastric emptying, thereby allowing more time for the fluoride to be absorbed from the stomach.


Standardized mortality ratios and the "healthy worker effect": Scratching beneath the surface. The age-standardized mortality ratio (SMR) is a relative index of mortality, expressing the mortality experience of the study population relative to that of a comparison ("standard") population. With the general population as the "standard", the SMR for an occupational population will underestimate the mortality experience of that latter population (since it comprises individuals necessarily healthy enough to be employable --and whose mortality risk is therefore initially lower than the general population average). However, this "healthy worker effect" does not equally to all groups within the study population. Therefore, if one attempts to adjust for this effect, the summary nature of the SMR must be recognized, and allowance must be made for variation in the healthy worker effect between different age groups, different races, different work-status groups, different causes of death, and different elapsed-time periods of observation.


Determinants of mortality in an industrial population. Many epidemiological problems are encountered in studies of mortality experience in industrial populations. The current study was undertaken to develop background data for a large chemical manufacturing company with emphasis on differentials in mortality associated with preselection factors, socioeconomic status, and general job categories. Statistically significant differences were observed in the industrial cohort with respect to socioeconomic level and job category. Differences between the industrial population and the corresponding US white male population were also noted. Findings of this study suggest additional avenues of investigative work for epidemiologists and clinicians concerned with the well being of employee groups in various industries.


Mortality among rubber workers: Relationship to specific jobs. This study has examined the ten-year mortality in a single-plant population of 6678 male rubber workers, in terms of the association of specific causes of death with a history of having worked in certain categories of jobs within the rubber industry. The work-histories of individual study subjects were analyzed, in detail, for all workers dying of selected causes of death. Comparison was made with the work-histories of a 22% age-stratified random sample of the total population. Age-adjusted exposure ratios (Tables 3 and 4) were calculated for all nine case groups in all 16 work areas, using differing exposure criteria (i.e. duration and calendar period). These ratios provide an approximation of the increased mortality risk associated with particular work areas. The risk ratios (with their associated confidence intervals), in Table 5, provide more rigorous estimates of these instances of increased mortality risk. For each cause of death studied, there were statistically significant associations with several work areas. For the cancers, the strongest associations tended to be with work areas at the front end of the production line (especially compounding and mixing), where the likelihood of contact with dusts, chemical ingredients, and vapors containing the early reaction byproducts, is high. The reclaim operation and the synthetic plant were each associated with several cancers (respiratory and bladder, and stomach and lymphato-hematopoietic cancers, respectively). The lymphatic leukemias were associated with solvent-exposure areas, especially inspection, finishing, and repair. Ischemic heart disease deaths, at ages 40-54, were strongly associated with having worked in extrusion and tread cementing, and in the synthetic plant. Deaths from diabetes mellitus were strongly associated with the janitoring-trucking category, and with jobs in the inspection, finishing and repair area. These observed associations, calculated after controlling for the variables sex and age, were apparently not due to confounding by smoking and race differences between work areas. The role of selective transfer of sick individuals (into, say janitoring or trucking) warrants further investigation. However, this mechanism is unlikely to be involved in the great majority of the observed associations. Another possible source of spurious inferences of increased risk would be correlation, within work-histories, between two job categories, one of which actually involved increased risk, while the other did not. Such associations could occur if certain job sequency trends existed within this working population. (Preliminary analyses indicate that this likelihood is not great; however, further analysis is planned.) Detailed study of specific environmental agents, historically and cross-sectionally, is currently underway, in an attempt to identify the work-environment agents responsible for the associations reported here.


Chloromethyl ethers, cigarettes, cough and cancer. Beginning in 1963 a 10-year prospective study of 125 chemical workers was carried out by periodic screening for five years and follow-up for an additional five years. Eighty-eight men were exposed to chloromethyl ethers in varying cumulative doses estimates by retrospective rating. They were divided into three groups by degree of exposure. Age distribution was similar in all groups but the proportion of current heavy cigarette smokers at the start of observation decreased with increasing chemical exposure. The prevalence of chronic cough showed a dose-response relationship to both smoking and chemical exposure. The end-expiratory flow rate was below 60% of predicted in about one-third of the exposed men compared to only 6% of unexposed men and the frequency of such low rates was dose-related to cigarette smoking. During the five-year periodic screening study the prevalence of chronic cough decreased and the prevalence of dyspnea increased while chemical exposure was falling. The 10-year incidence of lung cancer was dose-related to chemical exposure but inversely related to smoking habits. All cancers were small-cell carcinomas, occurred in men younger than 55, and had an induction-latent period of 10 to 24 years. The 10-year mortality rate in this group of workers was 2.7 times expected and lung cancer accounted for the excess number of deaths.


The pathogenesis of lupinosis in the rat. The morphological, histochemical and biochemical changes in the liver of rats challenged with a single intraperitoneal injection of the toxin of lupinosis were investigated. The resulting injury is biphasic. The initial non-specific phase lasts for a few days, affects mainly the centrilobular region and is characterised by mitochondrial swelling, lipid accummulation and autophagosome formation. In addition, the hepatic concentrations of OCT, LDH, SDH, and AST fall while that for ALP increase. This is accompanied by a rise in the serum concentration of many of these enzymes. The second phase lasts longer and is characterised by phenomena indicative of abnormalities in hepatocytic division. Normal and abnormal metaphase as well as multinucleated hepatocytes falls. The possibility that the toxin of lupinosis interferes with microtubular units is considered.


Vascular infiltration in benign breast disease. Infiltration of the walls of blood vessels by mammary epithelium was found in two cases of sclerosing adenosis. Survey of a series of cases of sclerosing adenosis and severe epitheliosis revealed a 10 per cent incidence of vascular infiltration. Usually only a single vein was involved but in the propositus an artery and two veins were infiltrated. The findings highlight the infiltrative propensities of sclerosing adenosis, already recognised as infiltrating nerve sheaths. The vascular lesions appear to be benign structurally and this is borne out by the clinical behaviour.