Biomedical subjects
Publications and source records attributed to L Cohen.
A case of crossed cerebellar atrophy after cranial trauma, with a 12-year neuroradiological follow-up is reported. This uncommon cerebellar degeneration has previously been reported only as an autopsic finding. It results from a lesion affecting the contralateral cerebral hemisphere. The role of different cerebro-cerebellar pathways is discussed.
Sixteen children (14 neonates less than 1 week old and 2 infants aged 3 and 6 months) had a "favorable" type of pulmonary atresia with an intact interventricular septum in which the hypoplasia of the right ventricle was mild and the cavity tripartite with a well developed infundibulum arriving in contact with a good-sized pulmonary artery from which it was separated by a totally or almost totally imperforate dome. They underwent a procedure associating an infusion of prostaglandin. E1 and an attempted pulmonary valve disobliteration by interventional catheterisation: needle puncture followed by balloon dilatation. There were 4 failed procedures (impossible puncture or dilatation), only one of which in the last 10 cases. The outcome of the 12 primary successes was related to the rapidity of recovery of right ventricular diastolic function: 7 patients were cured within a few days or weeks with prostaglandin therapy: 5 children required surgical anastomosis with a longer recovery period--3 cures but 2 deaths. Overall, there were two myocardial effractions without serious complications and 1 enterocolitis which was long-lasting but eventually cured. Two mild residual stenoses were redilated. In conclusion, the puncture-dilatation technique may be used instead of surgical valvectomy in favorable forms of pulmonary atresia with intact septum in the neonate. With experience, it was possible to remove the obstruction in 9 out of 10 cases with a minimum of complications. It is the compulsory first stage to complete cure, the probability and rapidity of which depend on recovery of right ventricular compliance.
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With a voltage-sensitive dye and an array of silicon photodiodes we monitored the action potential activity of a large fraction of the cells in the Aplysia abdominal ganglion during the gill-withdrawal reflex. This capability allowed a direct determination of the spread of sensory information within the 1,000 neurons of the ganglion. Surprisingly, approximately 30% of the neurons are activated by a light touch to a small area of siphon skin. It is likely that many other neurons also receive large synaptic potentials, either excitatory or inhibitory, and thus even a very mild and restricted stimulus will have widely distributed effects. It seems to us that these results will force a more pessimistic view of the present understanding of the neuronal basis of apparently simple behaviors.
OBJECTIVE: To report our experience in the detection of congenital heart disease using both the four-chamber view of the heart as part of the standard obstetric ultrasound examination and multiple cardiac views as part of the detailed targeted examination. METHODS: All admissions to Children's Memorial Hospital of Northwestern University Medical Center with the diagnosis of congenital heart disease between June 1988 and April 1992 were identified (N = 1947). These admissions were matched to deliveries (N = 19,321) that occurred at Prentice Women's Hospital during the same period; of these, 10,004 had at least one obstetric ultrasound examination. All fetuses were scanned either with the standard obstetric ultrasound type of examination, featuring only the four-chamber view of the heart, or by the detailed targeted imaging type of study, featuring multiple cardiac views. The type of examination performed was based on the specific request of the attending obstetrician or gynecologist. RESULTS: Thirty-three neonates who had at least one obstetric ultrasound examination were treated for congenital heart disease. An additional five pregnancies were terminated secondary to serious fetal heart defects. When only the four-chamber view was visualized, 11 of 33 fetuses (33.3%) with confirmed congenital heart disease were detected. CONCLUSIONS: Assessment of the outflow tracts is crucial for detection of many forms of congenital heart disease. However, before this is accepted as the standard of care, both the obstetric and radiologic communities should develop their skills in cardiac imaging. Only then can this sophisticated type of cardiac examination be offered to pregnant women.
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A case of hypomagnesaemia secondary to cisplatin therapy and diarrhoea had concomitant hypokalaemia. Increasing the serum potassium level from 2.8 to 3.4 mmol/litre by potassium supplementation induced tetany. Hypokalaemia in the face of hypomagnesaemia may have a membrane-stabilizing effect and preserve excitability.
CD8+ T-lymphocyte populations may be expanded in the peripheral blood of patients with chronic idiopathic neutropenia and may be involved in suppression of granulopoiesis. In this report, we have analyzed the T-cell receptor (TCR) used by the T lymphocytes of a patient with chronic severe neutropenia. Using specific oligonucleotides in the polymerase chain reaction (PCR) to amplify cDNA specific for the different families of the V alpha, V beta, and V delta TCR genes, and monoclonal antibodies (MoAbs) to examine T-lymphocyte subsets and their TCR, a persistent expansion of CD3+CD8+ T lymphocytes and a reduced repertoire of TCR V alpha and V beta genes were found in the patient's peripheral blood mononuclear cell (PBMC) preparations. A predominant portion of the T lymphocytes expressed a unique TCR structure. Thus, we found that, despite the fact that 98% of the T cells expressed alpha beta TCR on the surface membrane and less than 2% expressed tau delta TCR, nonetheless, 40% to 60% of the T cells stained positively with anti V delta 1 MoAb. Using the PCR analysis, the V delta 1 gene segment was found to be rearranged to C alpha, rather than to C delta genes. The expanded C alpha V delta 1+ cells, which are found only rarely in normal PB, expressed CD8 and were cytotoxic, and the C alpha V delta 1 receptor was functional in cytotoxicity. This constitutes the first description of an expansion of cytotoxic CD8+ lymphocytes expressing a functional "hybrid" C alpha V delta 1 gene in vivo, and suggests a pathogenic role for CD8+ C alpha V delta 1+ cells in some patients with idiopathic neutropenia.
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The NF-kappa B family of transcription proteins represents multiple DNA binding, rel related polypeptides that contribute to regulation of genes involved in immune responsiveness and inflammation, as well as activation of the HIV long terminal repeat. In this study multiple NF-kappa B related polypeptides ranging from 85 to 45 kDa were examined for their capacity to interact with the PRDII regulatory element of interferon beta and were shown to possess distinct intrinsic DNA binding affinities for this NF-kappa B site and form multiple DNA binding homo- and heterodimer complexes in co-renaturation experiments. Furthermore, using DNA templates containing two copies of the PRDII domain linked to the rabbit beta globin gene, the purified polypeptides specifically stimulated NF-kappa B dependent transcription in an in vitro reconstitution assay as heterodimers but not as p50 homodimers. These experiments emphasize the role of NF-kappa B dimerization as a distinct level of transcriptional control that may permit functional diversification of a limited number of regulatory proteins.
We have investigated several effects of verapamil (5-[(3,4-dimethoxyphenethyl)methylamino]-2-(3,4-dimethoxyphenyl)-2- isopropylvaleronitrile) on platelet structure and function. At concentrations below a threshold of approximately 4.2 x 10(7) molecules.cell-1, verapamil binds to platelets according to a typical Langmuir adsorption isotherm (i.e., binding is saturable and noncooperative). By extrapolation, we calculate that saturation would occur at 6.8 x 10(7) +/- 1.9 x 10(7) molecules.platelet-1, with one bound verapamil molecule per two membrane phospholipids. Saturation is never achieved, however, because past the threshold surface concentration, the adsorption isotherm becomes discontinuous and further adsorption becomes a linear function of the concentration of drug in solution. We attribute this discontinuity to disorganization of the membrane bilayer which is stretched beyond cohesion by insertion of too many amphiphilic molecules of a length shorter than that of the phospholipid. The partitioning of verapamil between the bulk aqueous phase and the newly created lipid phase would then account for the linear portion of the adsorption isotherm. The discontinuity of binding is accompanied by discontinuities in the verapamil-dependent swelling of platelets and the verapamil-dependent inhibition of both ADP-inducible binding of fibrinogen to, and aggregation of, platelets. In contrast, N-methylverapamil (5-[(3,4-dimethoxyphenyl)- methylamino]-2-(3,4-dimethoxyphenyl)-2-isopropylvaleronitrile), a hydrophilic quaternary amine derivative of verapamil, neither swells platelets nor inhibits the ADP-dependent processes that we investigated. From this we conclude that deprotonated verapamil is the operative species of the drug. Collectively, these data suggest that verapamil alters platelet structure and function by mechanisms involving disorganization of the platelet plasma membrane.
This paper develops a critique of international gerontology through an ethnography and analysis of gerontological practice in India. The central theme of Indian gerontology - that of an imminent demographic and social explosion of an aging population who will tax the country's slender resources - misrepresents available data and fails to signify the experience of most Indian old people. Narrative and deconstructive techniques are deployed to examine the language of crisis and the complex sources of this misrepresentation. Three sources are explored: local disjunctions of class and gender in India, neocolonial biases in the structure of knowledge on aging central to international discourse, and subaltern strategies within India for subverting Western and elite Indian imperatives of what it means to be old. A variety of textual, ethnographic, and historical materials are examined: Indian and American literature pertaining to the 1982 World Assembly on Aging, a series of sociological texts each entitled "Aging in India," and four contemporary Indian institutions designed to meet the needs of old people: a social service agency, a geriatric clinic, a retirement community, and an old age home.
Progressive polyradiculopathy is a rare, well-documented complication of the acquired immunodeficiency syndrome in man. It has been commonly attributed to a cytomegalovirus (CMV) infection. We report two HIV-infected patients with clinical and electrophysiological features of a unique, subacute, progressive polyradiculopathy. Post-mortem examination in case 1 disclosed an infiltration of the leptomeninges, the lumbar spinal cord, and the anterior and posterior roots by a B-cell immunoblastic lymphoma. Immunochemistry for HIV1 and CMV was negative in the peripheral and the central nervous system. Case 2 showed bone-marrow involvement by a Burkitt type lymphoma. Specific chemotherapy was followed by both clinical improvement of the polyradiculopathy and complete remission on a second bone-marrow biopsy. These findings may indicate that a lymphoma must also be considered a possible cause of polyradiculopathy in AIDS.
Gingival health and salivary gland function were evaluated for a period of 5 years in 14 patients who received head and neck irradiation for nasopharyngeal carcinoma (seven patients; total dose greater than 60 Gy, nasopharyngeal field) and Hodgkin's lymphoma (seven patients; total dose less than 50 Gy, "mantle" field). Plaque index (PII), bleeding index (BI), gingival recession (GR), whole saliva flow rate (WSFR), left parotid sialographic morphology, and salivary gland radioisotopic activity were assessed immediately before radiotherapy and annually thereafter. The nasopharyngeal group had perfect correlation between postradiation depression of WSFR and the sialographic and scintigraphic scores (R = -1.00 and -0.96, respectively). The degree of gland dysfunction correlated negatively with BI and the BI/PII ratio (r = -0.497) and with GR (r = 0.681). The same correlations were noted in the group with Hodgkin's lymphoma during the first 3 years of follow-up. However, recovery of parotid gland function (WSFR and scintigraphic scores) and morphology (sialographic scores) and return to the preradiation relation between WSFR and both BI/PII ratio (r = 0.75) and GR (r = -0.71) were noted in the fourth year. The differences between the nasopharyngeal and Hodgkin's lymphoma groups are attributable to the delineation of the radiation field employed in each group.
We report the purification and characterization of a unique DNA-binding protein termed TH3 that interacts with the positive regulatory domain (PRD) I and PRDIII domains of the interferon (IFN) beta promoter. In cells treated with poly rl:rC and cycloheximide, appearance of TH3 DNA-binding activity was inversely proportional to the disappearance of a constitutive complex TH1 and coincided temporally with induction of IFN-beta gene transcription. The TH3 DNA-binding protein is a small 14-kDa polypeptide that appears to be derived from the TH1 complex; TH1 in turn is related to interferon regulatory factor (IRF) 2 by immunological cross-reactivity. The TH3 protein appeared to lack the epitope required for recognition by anti-IRF-2 antisera; however, a short microsequence obtained for TH3 overlapped a sequence from the IRF-2 protein. Although TH3 binds to multimers of the AAGTGA hexamer and to PRDI, the TH3 protein alone had a predominantly neutral phenotype on PRDI-dependent transcription in vitro and lacked the negative transcriptional effect attributed to IRF-2. These results raise the possibility that specific proteolysis of a negative regulatory protein involved in silencing the IFN-beta promoter may be an important event leading to transcriptional activation of the interferon gene.
In a four-week, open label study of major depression, 15 patients who had failed to respond to a trial of fluoxetine 20 mg/day of 8-12 weeks duration were then treated with fluoxetine 40 mg/day for one week and then, if tolerated, with either 60 or 80 mg/day. The mean HAM-D-17 and CGIS scores of these 15 patients decreased significantly at the end of 4 weeks on a higher dosage of fluoxetine (60 or 80 mg/day) with respect to the beginning of the four-week study. No significant side-effects were noted.