The evolving role of the senior healthcare executive.
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Biomedical subjects
Publications and source records attributed to K Spiegel.
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In order to determine whether sleep disturbances would affect the hormonal patterns and the normal relationships between hormone pulses and sleep stages, the 24-hour profiles of cortisol, prolactin and plasma renin activity (PRA) were analysed in 6 sleeping sickness patients studied at Brazzaville and in 5 healthy African controls studied in Abidjan. Polysomnographic recordings were done continuously and blood was taken every 10 minutes throughout the 24-hour period. Plasma was analyzed for cortisol, prolactin and PRA. The circadian rhythm of cortisol, considered as an example of an endogenous rhythm was attenuated in all the patients but one, but as in normal subjects, slow wave sleep (SWS) remained associated with the declining phases of the secretory episodes. Prolactin and PRA profiles, which are strongly influenced by the sleep-wake cycle did not show the increase normally associated with long sleep periods and reflected the spreading of sleep and wakefulness throughout the 24-hour period. However, rapid-eye movement (REM) sleep began in sleeping sickness patients, as in normal subjects, during the descending phases of prolactin pulses. In both groups, PRA reflected the sleep stage distribution with non rapid-eye movement (NREM) sleep occurring during the ascending phases and REM sleep during the descending phases of the oscillations. However, in sleeping sickness patients, the marked sleep fragmentation often did not allow sufficient time for PRA to increase significantly, as observed with regular NREM-REM sleep cycles. These results demonstrate that, together with the disruption of the sleep-wake cycle, there are profound differences in the temporal organization of the 24 hour hormone profiles in human African trypanosomiasis.(ABSTRACT TRUNCATED AT 250 WORDS)
OBJECTIVE: To evaluate the relative contribution of sleep and the endogenous circadian rhythmicity in producing the 24-h variations in the plasma renin activity. METHODS: Ten normal young men were studied, under basal conditions with normal nocturnal sleep from 2300-0700 h and once after a night of total sleep deprivation followed by 8 h daytime sleep from 0700 to 1500 h. Plasma renin activity was measured every 10 min for 24 h and the profiles were analysed using the pulse detection program ULTRA. RESULTS: During the 8 h night-time sleep a significant increase in the mean plasma renin activity levels occurred compared with the subsequent 8-h waking periods. After the shift in the sleep period, a sleep-associated increase was clearly apparent during the daytime hours. The number of the amplitude of the oscillations, linked to the non-rapid eye movement-rapid eye movement sleep cycles, increased during sleep (at whatever time it occurred), and were dependent on the regularity and the length of the sleep cycles. In awake subjects the plasma renin activity generally fluctuated in a more damped and irregular manner, but occasionally the plasma renin activity oscillated at a regular periodicity with two dominant peaks centred around 100 and 50 min. CONCLUSION: These results demonstrate that the 24-h plasma renin activity variations are not circadian in nature but are related to sleep processes, which create the nycthemeral rhythm by increasing both the frequency and the amplitude of the oscillations.
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The search for novel therapeutics for human cognitive disorders has intensified. Neurotransmitter replacement therapies represent a short-term hope for treating cognitive dysfunction associated with Alzheimer's disease (AD). AD, however, is clearly a neurodegenerative disease and is characterized by a loss of synaptic elements. Ultimately, synaptic loss must be halted to alter the disease course. Agents mimicking or modulating the actions of neurotrophic factors may be useful. They may restore lost function and exert anabolic effects on existing neurons, making treated cells less susceptible to neurotoxic insult (i.e., excitotoxicity, oxidative stress, etc.). Intervening in the biogenesis of amyloid plaques and blunting local inflammatory responses may provide the ultimate treatment for AD. The success of any treatment, however, rests on early diagnosis. Early intervention in the neurodegenerative disease process will be required. Without early intervention, the risk of maintaining patients in a premorbid state is high. Therefore, it is likely that no single approach will provide optimal therapy for the AD patient and multifactorial treatment strategies may be required.
An intravenous line insertion and blood drawing team was introduced as a pilot project in a large municipal hospital in the New York City. The program successfully accomplished the goals of reducing house staff workload, improving house staff morale and patient care, and increasing available time for house staff education.
It was demonstrated by the experiments performed in vivo in mice (peripheral blood leukocyte number determination), and in vitro on mouse thymocytes (autologous rosette forming cell number determination) that tuftsin (Thr-Lys-Pro-Arg), a natural phagocytosis-stimulating factor, inhibits the action of interleukin 1 alpha. This effect is interpreted by us in the terms of structural correspondence between tuftsin and "retro-tuftsin"-like sequence 210-213 of the IL-1 alpha peptide chain. The analysis of tertiary structure shows that this sequence is localized in the exposed fragment of the IL-1 alpha molecule, probably responsible for the interaction with the receptor.
The C-terminal SP7-11 pentapeptide (Phe-Phe-Gly-Leu-Met-NH2) was found to suppress in vitro the immune response in a dose of 1-5 micrograms/ml. It produced also a distinct immunosuppression in vivo, by both per os and intraperitoneal, applications. In contrast, the N-terminal SP1-4 fragment (Arg-Pro-Lys-Pro) suppressed the response at a dose of 0.1 microgram/ml, but stimulated it slightly at higher doses (1-5 micrograms/ml). A structural analog of SP1-4 (Gly-Pro-Arg-Pro tetrapeptide) was found to be a strong immunosuppressor at a dose of 5 micrograms/ml, indicating the importance of N-terminal basic residue for the immunoregulatory activity of intact SP.
Coculture of sympathetic neurons with ganglion nonneuronal cells elevated levels of preprosomatostatin mRNA but did not alter neuronal synthesis, content, or release of somatostatin. Treatment of sympathetic neurons with culture medium conditioned by exposure to ganglion nonneuronal cells similarly elevated preprosomatostatin mRNA. Treatment with conditioned medium elevated somatostatin levels in pure neuronal cultures, but not in neurons cocultured with nonneuronal cells. Conditioned medium also failed to increase peptide levels in neurons cultured on a substratum of killed nonneuronal cells, despite a large increase in preprosomatostatin mRNA. These observations suggest that contact of sympathetic neurons with nonneuronal cell membranes inhibits the increase in peptide synthesis, but not the increase in preprosomatostatin mRNA after treatment with conditioned medium. Thus neuronal interactions with nonneuronal cells regulate somatostatin metabolism at both the mRNA and peptide levels. Regulatory effects on the mRNA and the peptide are separable and do not necessarily occur in parallel, and translational controls may be the rate-limiting factors.
In June 1988, the New York State Hospital Review and Planning Council approved major revisions in the state hospital code (Part 405). Among the most controversial of these changes were the recommendations of the Bell Commission concerning limitations on resident work hours, new emergency service requirements, and enhancements in ancillary staffing. The ancillary staffing mandated by the new code regulations for teaching hospitals include the provision at all times of intravenous services, phlebotomy services, messenger services, transport services, nurses aides, housekeeping services, and other ancillary support in a manner sufficient to meet patient care needs and to prevent adverse impact on the delivery of medical and nursing care. The intent of the new health code requirements is to reduce or eliminate many of the nonphysician tasks performed by residents so as to effectively reduce their workload. We conducted a survey of Medicine residents at Queens Hospital Center to assess the amount of time they presently devote to nonphysician tasks, their perceptions of the need for ancillary staff to relieve them of the burden of these nonphysician tasks, and their evaluation of the effectiveness of a recently instituted intravenous therapy team.
Regulation of preprosomatostatin mRNA and tyrosine hydroxylase mRNA were examined in sympathetic neurons of the rat superior cervical ganglion (SCG). Surgical denervation of the adult SCG increased ganglion levels of preprosomatostatin (SS) mRNA more than 11-fold, and levels of the mRNA remained elevated 14 days after surgery. By contrast, denervation decreased levels of tyrosine hydroxylase (TH) mRNA. Potassium- or veratridine-induced membrane depolarization of cultured neonatal sympathetic neurons decreased levels of SS mRNA but elevated levels of TH mRNA. Sodium channel blockade with tetrodotoxin prevented the effects of veratridine on SS and TH mRNAs. In toto these observations suggest that transsynaptic nerve impulse activity and sympathetic neuron membrane depolarization decrease SS synthesis but increase TH synthesis at the mRNA level. Thus nerve impulse activity may alter the relative levels of different transmitters co-expressed in the same neuronal population by inhibiting levels of some species of mRNA while simultaneously stimulating levels of others.
We demonstrated, with the aid of PRP, that precursors of helper T cells in the humoral immune response to SRBC belong to a minor thymocyte subset bearing the: Thy-1 +/-, H-2+, L3T4-, lyt 2-, CD3- phenotype. We showed, in addition, that PRP induced among the double negative (L3T4-, lyt 2-) thymocytes an appearance of differentiation antigens such as: L3T4, lyt 2, CD3 and T-cell receptor (alpha/beta). The data presented in this paper are in accordance with the present view on the process of T-cell maturation.
Children suffering from JCA showed an elevated percentage of OKT4+ T lymphocytes and an increased ratio of OKT4+ to OKT8+ lymphocytes. Several children showing a significant aggravation of the disease, were selected for a 3-week treatment with TFX. In 7 out of 10 patients a pronounced clinical and laboratory improvement was registered, accompanied by a normalization of the OKT4+ to OKT8+ lymphocyte ratio.
PRP-hexapeptide possessing the azo-bridge between Tyr1 and Phe5 residues, called azo-PRP-hexapeptide: (formula; see text), was synthesized and tested for immunoregulatory activity. High biological activity of the synthesized azo-PRP-hexapeptide suggests that the biologically active conformation of PRP-hexapeptide must be such that both aromatic rings (Tyr and Phe) are apparently close to each other.
The characterization of surface and intracellular markers of hematopoietic cells by immunocytochemical methods is widely used. While examination of cells of the peripheral blood can easily be performed, investigations of bone marrow cells can be hampered by technical difficulties in labeling routine marrow smears or by limited size of specimens required for cytocentrifugation. A simple and highly efficient method for isolation of bone marrow cells by a microseparation technique is described. Only two to three drops of a routine bone marrow aspirate are necessary for preparation of up to 100 cytocentrifuge slides thereby exceeding separation efficiency of conventional gradient centrifugation by three- to more than four-fold. The application of the method for marker studies on normal marrow and marrow from patients with hematologic malignancies is exemplified.
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It has been previously found that a proline-rich polypeptide (PRP) isolated from ovine colostrum has a regulatory effect on the immune response. A nonapeptide fragment Val-Glu-Ser-Tyr-Val-Pro-Leu-Phe-Pro was isolated from the chymotryptic digest of PRP. The nonapeptide showed biological activity similar to PRP. The determined amino acid sequence was now confirmed by synthesis. Synthetic nonapeptide as well as its C-terminal hexapeptide, Tyr-Val-Pro-Leu-Phe-Pro, showed biological activity similar to PRP and the nonapeptide obtained from PRP.
Hydrazide of cysteine, introduced intraperitoneally or per os in three doses for three consecutive days after immunization of mice with SRBC, caused a stimulation or an inhibition of the humoral immune response, determined on day 4 as a number of cells in the spleen producing antibodies of 19S and 7S class. The stimulation of the humoral immune response was induced by the dose of 100 micrograms per mouse and was more significant in the case of the 7S response. High doses of HD, on the other hand (1 mg per mouse i.p. and 1-5 mg per mouse per os) caused an inhibition of the humoral immune response which was more pronounced in the case of the secondary immune response. The mechanism of action of HD in the course of the immune response and its possible application in therapy is discussed.