New directions for primary health care in the inner city.
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Biomedical subjects
Publications and source records attributed to M McCarthy.
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Elderly depressed patients who met the research diagnostic criteria (RDC) for major depressive illness, resistant to other types of treatment, were treated with phenelzine, a nonselective monoamine oxidase (MAO) inhibitor, for a period of 2 to 7 weeks, following 2 weeks of placebo washout period. Dosage ranged from 15-75 mg daily. Clinical status of patients as well as vital signs, EKG, and platelet MAO inhibition were measured weekly. All responders at the end of this period were followed for 1 to 2 years. Analysis of the results showed a 65% response rate as measured by Hamilton, Global, and Self-rating Scales. No significant drug effect in cognitive functioning, as measured by objective cognitive tests, was observed. Clinical improvement was sustained for all participants throughout the follow-up period with no side effects. A direct relationship between platelet MAO inhibition and clinical response was found. The majority of the responders (70%) had achieved high platelet MAO inhibition values (greater than 80%), while most of the nonresponders had platelet MAO inhibition values of less than 80%. These findings have potential clinical and research implications for treating geriatric depression, especially the ones resistant to other forms of treatment.
Intracellular nucleocapsids, virtually free of host proteins and nucleic acids, were purified from cells acutely infected with several strains of mumps virus. VIral RNA obtained from the nucleocapsids was predominantly a single 50S species, with 28S RNA occurring as a secondary peak in the RNA profile. Nucleocapsids yielded approx. 9 micrograms 50S RNA per 10(9) infected cells. The 50S RNA was partially self-complementary, indicating that mumps viral nucleocapsids include full-length plus (+) sense antigenomes. Self-annealing and competition hybridization assays with 50S RNA suggest that 28S RNA includes duplexes consisting of full-length (+) and minus (-) sense 50S RNA. Properties of the viral RNA did not vary with the method of RNA isolation, time post-infection at which nucleocapsids were harvested, nor the strain of mumps virus.
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Experiments have been carried out to examine the submandibular glands in mice with hereditary muscular dystrophy. Radioimmunoassay data confirm biological studies which show that submandibular glands in mice with muscular dystrophy contain less nerve growth factor (NGF) than glands of normal animals. Male dystrophics have half as much submandibular NGF as unafflicted mice, while females have only 10% of control levels. Gel filtration and electrophoretic studies detect no differences in the molecular properties of NGF in gland extracts from normal and dystrophic mice. Furthermore, NGF from both sources show equal activity in the sensory ganglion bioassay. Together, these results suggest that NGF deficits in submandibular glands of dystrophic mice are not due to measurement artifacts arising from alterations in the structure of the molecule. Morphological studies have uncovered a cytological basis for chemical deficits within submandibular glands of dystrophic mice. Stereological analysis of light and electron microscopic sections revealed that growth factor containing granular tubule cells (GTC) take up a smaller portion of the total gland volume, are smaller in size, and contain fewer secretory granules than comparable cells in glands from controls. Furthermore, the ultrastructure of GTC in dystrophic animals suggests that the cells are less active in producing secretory protein than GTC in glands from normal animals. These results are consistent with the idea that growth factor deficits arise from cellular abnormalities in the granular tubule segment of the gland.
Forty inpatient volunteers with diagnoses of schizophrenia were randomly assigned to treatment either with trebenzomine or thioridazine in a double-blind study of clinical antipsychotic efficacy following a 1-week placebo treatment. Psychopathology was rated using the Brief Psychiatric Rating Scale (BPRS) and Clinical Global Impression (CGI). There was a significant difference in therapeutic response to the two drugs in that psychopathology decreased significantly for the thioridazine group, but not for the trebenzomine group. Serum prolactin was elevated during treatment with thioridazine, but not with trebenzomine. Side effects were more frequently reported for the thioridazine group. These results fail to confirm previous reports of clinical antipsychotic efficacy for trebenzomine.
To determine if activity of the renal glutamate dehydrogenase (GD) pathway changes during chronic acidosis in intact dogs, we assessed the deamination of glutamate formed within renal cells during glutamine and alanine infusions. Infusing glutamine into chronically acidotic, normal and acutely alkalotic dogs enhanced renal ammonia production; more was formed as glutamine loading increased. In 4 acidotic dogs, the ratio of ammonia produced to glutamine extracted by the kidneys during exogenous glutamine loading was 1.93 compared with 0.99 for 5 alkalotic dogs and 1.23 for 2 control dogs. Little glutamate and alanine were released into the renal vein in acidotic dogs, whereas over 50% of the exogenous glutamine extracted in acutely alkalotic dogs could be accounted for as glutamate and alanine released into the renal vein. Renal glutamate concentrations were not elevated in acidosis compared with alkalosis despite greater deamidation. When glutamine infusions increased renal ammoniagenesis in acutely alkalotic and control dogs to levels seen in chronically acidotic dogs receiving no exogenous glutamine, approximately 4 to 6 times more glutamate was released from the kidneys. Infusing alanine into 7 chronically acidotic dogs enhanced ammoniagenesis significantly (p less than 0.01), but lesser augmentation was seen in 3 control dogs and no augmentation was seen in 6 acutely alkalotic dogs. The increases were secondary to enhanced glutamate deamination, not secondary to any changes in glutamine extraction and/or transaminase activity. We conclude that the glutamate dehydrogenase pathway is more active in intact acidotic dogs than it is in control and alkalotic dogs.
The "shopping list task" is a new verbal learning task with a high degree of face validity for elderly subjects. Learning and delayed recall performance were examined for three groups of subjects: young normals (n = 63, median age = 21), elderly normals (n = 44, median age = 69) and mild to moderately impaired senile dementia patients (n = 60, median age = 70). The young normal subjects performed best of the three groups in both initial learning and delayed recall measures. The elderly normals showed significant decrements in learning and recalling the list items (p less than .01). The impaired elderly showed much greater performance decrements in both learning and recall. None of the subjects showed a deficit in delayed recognition. These results suggest that both storage and retrieval difficulties occur in normal aging and dementia. The recognition test results suggest that recall deficits evidenced by both elderly groups are in large part due to faulty retrieval mechanisms. Since the shopping list task discriminated well among the three groups, it has potential for memory assessment in clinical settings.
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The growth and cytopathogenicity of five strains of mumps virus were examined in six types of cell cultures and in neonatal hamsters. These strains included the MJ and RW strains, both recent cerebrospinal fluid isolates: the neuroadapted Kilham strain; the Enders strain adapted to chick embryo; and the Jeryl Lynn vaccine strain adapted to chick cell culture. The MJ, RW, and Kilham strains all produced infectious virus without restriction in vitro, but the RW strain did not cause obvious cytopathic effect; the MJ and Kilham strains were cytopathic. The Enders and Jeryl Lynn strains adapted to chick embryo cells were cytopathic and productive in chick cell culture but were restricted in ability to grow productively in vitro on mammalian cell types, even failing to produce noninfectious particles in some cases. In vitro cytopathogenicity was a host-independent property of a specific virus strain, but the type of cytopathic effect manifest in culture (eg, fusion, cytoplasmic vacuoles) depended on both the strain and the host cell. The ability of a virus strain to invade the brain parenchyma and infect neurons in vivo appeared to correlate with the strain's cytopathogenicity and not with passage history or adaptive status.
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Recognition memory for faces was studied in 167 subjects comprised of young normals, elderly normals and elderly senile dementia patients with mild to moderate cognitive impairment. A continuous recognition paradigm was used which required an "old-new" decision to be made for each facial stimulus. The design of the stimulus sequence produced delay intervals of .5, 1, 2, and 4 min between the first and second presentations of each face, and a long delay of 40 min was also evaluated. A signal detection analysis revealed large recognition memory deficits at all delay intervals for the two elderly groups as compared to the young normals, but no differences between the normal and impaired elderly groups. In addition, there were no group differences in response criterion. The results suggest a deficit in nonverbal encoding/storage due to normal aging but no further deficit due to mild to moderate senile dementia. The data also fail to confirm an age-related increase in "cautiousness" in recognition memory tasks.
The polypeptide patterns of five strains of mumps virus have been compared under uniform electrophoresis conditions. These strains included the MJ and RW strains, recently isolated from human cerebrospinal fluid, the neuro-adapted Kilham strain and the chick embryo-adapted Enders and Jeryl Lynn strains. A similar pattern of polypeptides, featuring six common and virus-specific species, was obtained with purified virus grown in ovo, in hick embryo fibroblasts (CEF) or in Vero cells. These polypeptides have been designated VP1 (mol. wt. 200000), VP2 (mol. wt. 80000 or 75000), VP3 (mol. wt. 68000), VP4 (mol. wt. 58000), VP5 (mol. wt. 45000), VP6 (mol. wt. 39000). The virus glycoproteins were identified as VP2 and VP4; the nucleocapsid-associated proteins as VP1, VP3 and VP5. Additional polypeptides occurring both in uninfected Vero cells and in uninfected CEFs appeared in polypeptide profiles of purified mumps virus preparations, and could not be designated virus-specific polypeptides. Alhtough strain differences were minimal, we did observe (1) an extra protein, nucleocapsidassociated, in patterns from the chick-adapted Enders strain of mumps virus and (2) strain-dependent variability in the size of VP2.
The morphological heterogeneity of the chick embryo-adampted Enders strain of mumps virus was examined in relation to biological and biochemical properties of the virus. The range of virion sizes increased as multiplicity of infection (m.o.i.) increased, with virions of 800 to 1000 nm in diam. occurring in preparations grown at the higher multiplicities. There was no evidence for a distinct class of noninfectious haemagglutinating particles. Dense fractions from isopycnic gradients of virus were enriched in larger virions, but virus RNA was predominantly a single 50S species. Despite evidence that many virions were multiploid, u.v. inactivation kinetics were single-hit, suggesting only a single biologically active genome per virion.
Outside employment was obtained by 630 resident male patients who had 1447 admissions to a South London Hospital between 1963 and 1969. This "working out" group were compared with all male patients admitted to the hospital during the same period and with a national sample from the Mental Health Enquiry for 1969. The working patients had 827 spells of employment working for 742 employers, 75% of whom had employed only 1 patient for 1 spell of employment. A quarter of all male patients under 65 had worked out from the hospital over the seven years, approximately 90 out of 320 new admissions annually. This group were the younger patients admitted. The most frequent length of employment before discharge was 1--4 weeks. Patients with the diagnosis of alcoholism (the largest group in the sample) had shorter admissions and working out period than those with schizophrenia. The value of "working out" is discussed.
The welfare state has arrived and is thriving in Singapore. Mark McCarthy, a senior lecturer in community medicine at University College Hospital Medical School, London, who visited the country recently, gives his impressions of the progress being made in health services, where the emphasis is on prevention.