Biomedical subjects
Publications and source records attributed to M Rosenthal.
Although the relation between the virus of condyloma acuminatum and carcinoma of the cervix has been suspected, in the patient whose report follows, the presence of the viral lesion in the cervix next to an area of carcinoma in situ was demonstrated histologically.
The long term effects of specific noradrenergic denervation of rat cerebral cortex were considered in parallel studies of in vitro noradrenergic receptor binding and isoproterenol-induced adenosine 3':5'-monophosphate (cycle AMP) generation and of in vivo oxidative metabolism. Noradrenergic denervation was achieved by the local, unilateral injection of 6-hydroxydopamine into the locus ceruleus. Cerebral noradrenaline remained depleted throughout the 8-week duration of the study. Ligand-binding assays showed increased beta-adrenergic receptors 2 weeks after locus ceruleus lesion with recovery occurring by 4 weeks. There were no changes in alpha 1-adrenergic receptors. Isoproterenol-induced cyclic AMP generation increased at 2 weeks after lesion but recovered at 8 weeks. Dual wavelength reflection spectrophotometric measurements of cytochrome oxidase reduction/oxidation and local blood volume shifts, provoked in situ by direct cortical stimulation, also demonstrated abnormalities at 2 weeks with recovery by 4 weeks after lesion. Thus, in vivo and in vitro changes after locus ceruleus lesion are reversible and the time course of these changes is related temporally. These data suggest that cerebral cortex has adaptive capabilities which are activated to compensate for prolonged noradrenaline depletion. We also speculate that there may be a causal relationship between the in vitro and in vivo parameters studied.
Reiter's syndrome following salmonella enteritidis (Gärtner) infection in an HLA-B27 carrier is described. Some weeks after an episode of fever and diarrhea, a 33-year-old male presented with sacroiliitis, Achilles tendinitis and aphthous stomatitis. During the next few months he developed chronic arthritis, mild conjunctivitis, severe iritis, oligospermia and nonspecific asymptomatic urethritis.
The extraordinary ability of the turtle to withstand prolonged anoxia was examined in cerebral cortex in situ by recording changes in the reduction/oxidation ratio of cytochrome a,a3 by reflection spectrophotometry. Inspiration of 100% oxygen increased the oxidation of cytochrome a,a3 beyond that of the air breathing control, suggesting that cytochrome a,a3 is not fully oxidized under normoxic conditions in turtle brain. A similar response was seen also in cerebral cortex of the rat. The significance of the cytochrome a,a3 reduction in these intact tissues is discussed. Both severe hypoxia (100% N2) and asphyxia produced increasing levels of reduced cytochrome a,a3 in turtle and rat brains. The rat of change produced by N2 inspiration was greater than that produced by asphyxia in both species. This is interpreted as demonstrating an open pulmonary blood circulation during anoxia. In turtles, levels of reduced cytochrome a,a3 were maintained for over 3 h of continual N2 inspiration. Subsequent inspiration of room air resulted in a full restoration of turtle brain cytochrome a,a3 redox state within 30 sex. In the rat, continued N2 inspiration resulted in a rapid reduction of cytochrome a,a3 to a plateau (3 min) which became irreversible within a short period. An extended tolerance of N2 inspiration found in rats cooled to temperatures approximating that of the turtle was inadequate to account for the wide species of difference. We suggest that special adaptations, not related to the redox state of cytochrome oxidase under normoxic conditions, are responsible for maintaining the functional integrity and the capacity for cytochrome oxidase re-oxidation of turtle brain mitochondria under prolonged anoxia.
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Temperature coefficients of both cat and toad brain have been calculated for the active metabolic state induced by electrical stimulation. Values are higher than most of the values previously reported for "rest" metabolism, whether calculated from Arrhenius plots or from linear graphs. Relative rates of oxidative metabolism were obtained by measuring the time course of the transient changes in NADH fluorescence and cytochrome aa3 absorption by reflectance techniques directly from the surface of the exposed cat cerebral cortex in vivo and from the isolated intact toad brain mounted in a cuvet. These findings demonstrate that such optical methods accurately record metabolic processes.
In a study of 12 critically ill patients, values for mixed venous oxygen saturation (SVO2) were measured from samples of pulmonary arterial blood drawn at five rates of withdrawal (1, 3, 10, 20, and 30 ml/min). Samples were drawn from properly placed pulmonary arterial catheters with the balloon deflated. Physiologic stability was documented at the beginning and end of the sampling period in all but one patient. Results in each patient demonstrated a close grouping of values for SVO2 obtained at the five rates of withdrawal (largest standard deviation, 1.9 percent). Evaluations by paired t-test comparing all rates of withdrawal with the slowest rate (1 ml/min) showed no significant differences. The rate of withdrawal of the sample is not associated with significant errors in SVO2 when samples are drawn from a properly positioned pulmonary arterial catheter.
Four patients with active seronegative psoriatic arthropathy were treated with retinoid (Ro 10-9359) in a daily dose of 30 mg for at least four months. Within the first 4--6 weeks of treatment all patients showed marked improvement of arthritis as measured by the number of swollen joints, the Ritchie joint index, morning stiffness and the pain experienced. One patient stopped taking her concomitant medication of nonsteroidal anti-inflammatory agent, while the others were able to reduce the intake of such drugs substantially. None of the patients were taking steroids. The elevated erythrocyte sedimentation rate observed in all patients studied also fell gradually in the course of treatment. With the exception of dry lips observed in two patients, other adverse effect such as extensive mucosa dryness and cheilitis, as commonly seen in patients receiving this agent, were not recorded. In view of these encouraging preliminary results we are now conducting a multicenter control study to substantiate these findings.
Unilateral lesion of the locus coeruleus and the resultant norepinephrine depletion in the ipsilateral cerebrum alters the relationship between cerebral metabolic demands and local delivery of oxygen and substrates. This effect of norepinephrine depletion is demonstrated by slower recovery of the redox ratio of cytochrome a,a3 during increased metabolic demands induced by local cortical stimulation.
Eighteen patients with a variety of illnesses but no history of thyroid disease were shown to have elevated serum total and free thyroxine (T4) concentrations but low serum total triiodothyronine (T3) levels. Thyroid function tests were requested initially to excluded the possibility of hyperthyroidism in a setting of hypermetabolism. Clinical and laboratory follow-up investigations demonstrated that 15 patients were euthyroid and that hormonal alterations were transient features of the intercurrent illnesses. Three patients did, in fact, have hyperthyroidism. Retrospective analysis of diagnostic data demonstrated that of the initial thyroid function screening tests, serum total T3 concentration, the T3/TF4 ratio, and the indirectly measured free T3 (FT3) index were the most useful parameters in excluding hyperthyroidism. The FT3 index was the most helpful, being normal or low in all the euthyroid and high in each of the hyperthyroid patients.
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Non-invasive optical techniques were used to monitor the effects of increasing cerebral energy demand on metabolic capabilities and vascular reactivity in young and aged brain. Low level of electrical stimulation of the cortex, in both young (4--7 months) and aged (24--28 months) rat brain, were accompanied by transient oxidations of NADH and cytochrome oxidase (a,a3) as measured by microfluorometry and reflection spectrophotometry respectively. Stimulation sufficient to produce spreading cortical depression was accompanied by an oxidation of both NADH and cytochrome a,a3 in young brain together with an increase in local blood volume. There was either no change or a slight disoxygenation of hemoglobin. In aged brain, however, spreading depression was associated with an oxidation of NADH and a reduction of cytochrome a,a3 together with an increase in local blood volume and an oxygenation of hemoglobin. The present results indicate that the relationship between microcirculation and the terminal oxidase step of the respiratory chain is altered in aged brain when energy demand is high.
Changes in the ratio of reduced/oxidized cytochrome a,a3 were measured by reflection spectrophotometry in decerebrate cat spinal cord during microelectrode monitoring of extracellular K+ and extracellular potential. In 'resting' cord, cytochrome a,a3 was approximately 60% reduced, compared to 30% in cerebral cortex and 1% in isolated mitochondria. Stimulation of a dorsal root or afferent nerve caused linearly correlated responses, consisting of oxidation of cytochrome a,a3, elevation of K+0 and a negative shift of potential. In spinal cord, unlike cerebral cortex, the local volume of blood increased upon stimulation. The rate of recovery of the oxidation response of cytochrome a,a3 was consistently faster in cord than in cortex. Pentobarbital (i.v.) in anesthetic dosage reduced the amplitude and slowed the rate of recovery of all 4 parameters, indicating that the optical signals originate from gray matter. It is speculated that the spinal cord, even more than cortex, may depend for its viability on the maintenance of PO2 above a certain level, and that much of the metabolic activity following stimulation is associated with the restoration of ionic gradients.
13 patients in complete and prolonged remission after treatment with cytostatic chemotherapy for disseminated Hodgkin's disease have been investigated for immune competence by a total of 27 immunological parameters. 11 patients had abnormal values for lymphocyte populations, lymphocyte function and skin tests. The immune profile described is suitable for long-term evaluation of patients under immunosuppressive therapy.
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There is today both a need and an opportunity to develop and test a variety of models--organizational and financial--for improving the delivery of health care services. This article describes the structure and functioning of one such model and highlights the organizational problems expected to arise during its implementation. The proposed health plan is intended to facilitate the access of Medicaid-eligible, inner-city families to already available health services. The central hypothesis is that in low-income urban areas the elementary schools offer an organizational focus for the development of a health plan. As a prepaid, community-based model, this plan is designed to address the issues of accessibility, equity, accountability, continuity of care, and consumer participation, primarily through the development of a coordinating agency, the health plan office (HPO), which assures the linking of consumers and providers of health care. Adapted from the Kaiser-Permanente model, the HPO also assumes responsibility for marketing, enrollment, coordination of services, consumer advocacy, and quality surveillance.
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