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Biomedical subjects

S Hill

Publications and source records attributed to S Hill.

At least 235 records · Page 13Linked to original sources
PubMed1986

Techniques for assessing the activity of topically applied retinoids.

The retinoid drugs have profound effects on many aspects of skin biology. The exact activity profile depends on the particular analog and its route of administration. The topical retinoids used at present have marked therapeutic effects on epidermal cell production and desquamation. All-trans-retinoic acid (tretinoin) also acts on dermal connective tissue and microvasculature in a way that is less well established but may also be of therapeutic benefit. We investigated both tretinoin and motretinide in normal subjects and in patients with ichthyosis. The quantitative dansyl chloride test has been particularly useful in monitoring the desquamatory action of these topically applied retinoids. Both compounds resulted in enhanced rates of epidermopoiesis and desquamation. Marked changes in the cytochemical profile of the epidermis were also detected, changes that differed somewhat from the alterations induced by the systemic administration of etretinate. Changes in dermal structure and vascularization were monitored by A-scan ultrasound and laser Doppler flowmetry. However, only minor changes were recorded, probably because of the comparatively short application time. These newer techniques for investigating skin structure and function offer considerable opportunities for delineating the action of retinoids.

Administration, Topical↗
PubMed1986

Approaches to prevention of asbestos-induced lung disease using polyethylene glycol (PEG)-conjugated catalase.

Asbestos-associated damage to cells of the respiratory tract in vitro can be prevented by the simultaneous addition of scavengers of active oxygen species to cultures. To determine if administration of scavenger enzymes to animals and humans is a plausible approach to the prevention of asbestos-induced lung disease, osmotic pumps were filled with various concentrations of PEG-coupled catalase and implanted subcutaneously into Fischer 344 rats over a 28-day period. At 3, 14, and 28 days after implantation of the pumps, the animals were evaluated for levels of catalase in serum and lung. In addition, lung tissue and lavage fluids were examined at 28 days for biochemical and morphologic indications of cell injury, inflammation, and fibrotic lung disease. At all time points examined, the administration of PEG-catalase caused a dosage-dependent increase in serum levels of catalase. The levels of lung catalase were evaluated at 28 days but not at earlier time periods. In comparison to control rats, the amounts of enzymes (lactic dehydrogenase, alkaline phosphatase), protein, and cells in lavage fluids from treated animals were unaltered. Moreover, the lungs showed no evidence of inflammation or fibrotic disease as determined by differential cell counts in lavage and measurement of hydroxyproline. These studies suggest that administration of PEG-catalase does not cause injury or other alterations in lung tissue and can be pursued as a feasible approach to prevention of asbestosis.

Animals↗
PubMed1986

Therapeutic progress--review XXIII. Are we making progress in the treatment of acute stroke?

The principal purpose of the treatment of acute stroke is to ensure that the quality of life of those affected is returned to as near normal as possible. Early nursing and physiotherapy are important components of effective management of acute stroke. It is not the intention of this review to examine these aspects which are so well described elsewhere (1). Instead, the theoretical and clinical bases for the various specific treatments advocated in recent years to reduce brain damage after ischaemic insult will be considered to serve as a guide for clinicians. Areas in this field where further research may prove rewarding are highlighted.

Acute Disease↗
PubMed1986

Serous carcinoma of the ovary: CT identification of metastatic calcified implants.

The metastasis along peritoneal surfaces of serous cystadenocarcinoma, the most common ovarian malignancy, occurs early and is present in most patients at the time of clinical diagnosis. In many patients, however, computed tomography (CT) is unable to demonstrate peritoneal metastases because of their small size and similarly has been unable to demonstrate metastases in normal sized lymph nodes. Serous cystadenocarcinoma contains histologic calcification in approximately 30% of cases; thus, CT scans were retrospectively reviewed in 15 patients with pathologically proved stage III or IV disease to detect calcified peritoneal metastases. Six patients had calcified peritoneal implants, five of which had perihepatic calcifications. One of the five also had calcified lymphatic metastases, some of which were in normal sized nodes. In three of these five, the examination was otherwise normal. Search for these calcifications should improve the sensitivity of CT in diagnosing metastases from ovarian carcinoma.

Calcinosis↗
PubMed1986

The role of high-energy phosphate in norepinephrine-induced acute renal failure in the dog.

Previous studies have demonstrated that pretreatment with mannitol, furosemide, or bradykinin can attenuate the severity of norepinephrine-induced renal functional impairment. The present studies were designed to evaluate the possibility that these agents are protective, in part, by preserving cellular metabolic integrity. The renal cortex was repetitively biopsied during the course of this study, and high-pressure liquid chromatography was used to analyze the tissue content of adenine nucleotides (expressed in nanomoles per gram of wet tissue). The adenine nucleotide charge ratio (CR) and total adenine nucleotide (TAN) content were calculated as indices of cellular metabolic integrity. In addition to the above-established protective agents, phenoxybenzamine was used to evaluate a direct toxic effect of norepinephrine on renal tissue. Inulin clearance at 3 hours post infusion (expressed as a percent of control) was 7% with norepinephrine alone and, in the protected groups, 36% with bradykinin, 61% with furosemide, 51% with mannitol, and 100% with phenoxybenzamine. There was no change in CR or TAN with phenoxybenzamine. In contrast, during norepinephrine administration CR fell significantly in all other groups. Three hours after stopping norepinephrine, CR had returned toward control values and the level of CR was significantly better in all protected groups when compared with norepinephrine alone. Similarly, the levels of TAN were significantly diminished in the norepinephrine-alone group when compared to all protected groups, and there was significantly more tubular necrosis as well. The maintenance of higher levels of TAN and the preserved ability to regenerate adenosine triphosphate in the protected groups, when compared to the norepinephrine-alone group, support the contention that these agents offer protection, at least in part, by preserving cellular metabolic integrity.

Acute Kidney Injury↗
PubMed1986

Perceptual field dependency: predisposing trait or consequence of alcoholism?

Perceptual field dependency often has been reported in alcoholics and frequently implicated as a predisposing trait in alcoholism. Comparing sons of alcoholics who are at high risk for alcoholism to sons of depressed fathers and control fathers (nonalcoholics without history of depression) revealed, however, no differences on the rod and frame test. These results do not support the hypothesis that field dependency is a risk factor in alcoholism.

Adolescent↗
PubMed1985

Electron transfer to nitrogenase in Klebsiella pneumoniae. nifF gene cloned and the gene product, a flavodoxin, purified.

The nifF gene of Klebsiella pneumoniae was cloned into a multicopy plasmid in order to construct a strain that synthesizes and retains an elevated concentration of the gene product relative to the wild-type strain. Characterization of the isolated flavodoxin, which serves as an electron donor to nitrogenase, shows unambiguously that it is the product of the nifF gene.

Amino Acids↗
PubMed1985

Prediction of growth and development in intensive care nursery graduates at 12 months of age.

Although many perinatal events have been linked with the outcome status of neonatal intensive care unit (NICU) graduates, few studies have evaluated the cumulative longitudinal prediction of outcome. This study followed up 65 term and 139 premature NICU graduates to 12 months' chronologic age. Variables that were utilized in predicting 12-month growth and the neurologic and developmental outcome were maternal and neonatal medical factors, prior growth measurements, and neonatal behavior, which was measured with the Brazelton Scale for term infants and with a modified version for premature infants. The neurologic status was normal in 141 (71.9%) of 204 infants. The average Bayley Scale Mental Developmental Index was 112.7, and the average Psychomotor Developmental Index was 97.5, which was corrected for early gestation. Predictions of 12-month neurologic and developmental status were weak and had been derived only by variables from the neonatal behavioral examination; endurance predicted neurologic status and the motor cluster predicted cognitive and motor development. The prediction of growth at 12 months was high and was derived from prior growth parameters. Thus, although predictions of neurodevelopmental status at 12 months' chronologic age were low, the variables that aided in predicting were from the neonatal behavioral evaluation. This finding provides support for recommending that the functional status of the NICU graduate as well as the more traditional list of perinatal problems be considered when contemplating the infants' short-term outcome.

Child Development↗
PubMed1985

A molecular genetic study of nif expression in Klebsiella pneumoniae at the level of transcription, translation and nitrogenase activity.

A comprehensive study of nif expression in Klebsiella pneumoniae at the level of transcription, translation and nitrogenase activity during derepression and repression by NH+4 and O2 revealed that (1) transcription and translation rates remained coupled under all conditions; (2) these rates reached a peak during derepression and then decreased to a low level; (3) the transcription profile of nifLA had two peaks; the first was at 1 h before and the second coincided with that of the other operons; and (4) the peaks of nif transcription coincided with a trough in the profile of stringent regulation of RNA synthesis. Our results provide strong evidence that nif-specific repression by NH+4 and O2 occurs exclusively by transcription inhibition and that repression by O2 is independent of transcriptional regulation of the nifLA operon. We have also found evidence which together with the results of previous work shows that O2 repression of nifA mediated transcription involves the nifL gene product.

Ammonia↗
PubMed1984

The effect of a keto acid-amino acid supplement to a restricted diet on the progression of chronic renal failure.

We treated 24 patients who had chronic renal failure with a low-phosphorus diet containing 20 to 30 g of mixed-quality protein, supplemented by amino acids and their keto analogues. Seventeen patients had well-defined rates of progression before treatment, as assessed by serial determinations of serum creatinine levels. By extrapolating these rates of progression, we found that 10 of the 17 (59 per cent) had a clinically important slower rise in creatinine levels during long-term treatment (average, 20 months) than predicted; none had a faster rise than predicted. Seven of the 17 patients began treatment before creatinine reached the level of 8 mg per deciliter; in six of the seven, followed for an average of 22 months, creatinine has remained at or below the level at the start of treatment. Nutrition, as assessed by body weight, nitrogen balance, serum albumin, and serum transferrin, has been well maintained. This regimen slowed or arrested the rise in creatinine levels and thus must have slowed or halted the progression of renal insufficiency in a majority of cases, especially when treatment was initiated before creatinine had reached the level of 8 mg per deciliter. The mechanism underlying this effect remains to be determined.

Adult↗
PubMed1984

Calcified parathyroid glands detected by computed tomography.

Computed tomographic demonstration of single calcified parathyroid glands in two patients corresponded to operative findings of a calcified carcinoma and a calcified adenoma. The CT demonstration of a calcified parathyroid gland should suggest carcinoma, and the operative approach should be planned to permit an en bloc resection.

Adenoma↗
PubMed1984

Synthesis and activity of nitrogenase in Klebsiella pneumoniae exposed to low concentrations of oxygen.

Effects of very low concentrations of dissolved O2 on nitrogenase activity in Klebsiella pneumoniae were studied in a stirred chamber system which enabled simultaneous measurements of steady-state O2 concentrations, O2 consumption and C2H2 reduction. A strain carrying a chromosomal nifH::lac fusion as well as the Nif+ plasmid pRD1, expressed nitrogenase activity with 80 nM-O2, a concentration known to inhibit nifH::lac expression by about 50% Thus nitrogenase activity in vivo was no more sensitive to O2 than expression of nifH::lac. When compared with anaerobic treatments, dissolved O2 near 30 nM apparently stimulated nitrogenase derepression and enhanced the activity of nitrogenase synthesized anaerobically. Thus, in this organism, N2 fixation occurs in microaerobic as well as anaerobic conditions.

Enzyme Repression↗
PubMed1983

Immune responses in patients with brain tumors. Factors such as anti-convulsants that may contribute to impaired cell-mediated immunity.

The responsiveness of lymphocytes obtained from patients with brain tumors to in vitro stimulation with mitogenic lectins was examined. The previously reported finding of decreased responsiveness was confirmed. To investigate the factors responsible for the hyporesponsiveness, mitogen (phytohemagglutinin and pokeweed mitogen) induced lymphocyte activation was evaluated using lymphocytes from 22 patients with brain tumors and 22 normal individuals. Lymphocytes from 13 patients with brain tumors, showed depressed responsiveness when cultured in autologous serum; in eight this was marked and in five moderate. Normal, rather than autologous, serum corrected lymphocyte function from only one of the markedly hyporesponsive patients, suggesting the existence of an intrinsic lymphocyte abnormality in some patients with brain tumors. However, serum from the hyporesponsive patients depressed mitogen-induced activation of lymphocytes from both tumor patients and normals. The presence of suppressive serum factors could not be related to the nature of the tumor (benign versus malignant, site, cell type or degree of anaplasia). The present studies showed that significant depression of in vitro lymphocyte responsiveness occurred with exposure to two anti-convulsant agents (phenytoin and phenobarbital) and dexamethasone. Thus, impaired lymphocyte function in patients with brain tumors may have a complex explanation with drug (corticosteroids, anticonvulsants) induced suppression playing a significant role.

Adenoma↗
PubMed1983

Sclerosteosis: neurogenetic and pathophysiologic analysis of an American kinship.

We studied an American kinship with sclerosteosis, an autosomal-recessive disorder of bone remodeling and bone overgrowth of the calvaria, skull base, and tubular bones. Unlike osteopetrosis, which is attributed to abnormal immune and osteoclast function as well as bone resorption, sclerosteosis appears to be primarily a disorder of osteoblast (bone formation) hyperactivity. Related to cranial vascular and neural foraminal narrowing and reduced intracranial volume, affected patients with sclerosteosis demonstrate frequent seventh nerve palsy, progressive optic and cranial neuropathies, mixed hearing loss, brainstem compression, intracranial hypertension with increased elastance, and sudden, premature death. Management should involve early childhood identification of homozygotes, monitoring and aggressive treatment of intracranial hypertension, and extensive bone removal from skull, posterior fossa, and cervical spine.

Adult↗
PubMed1983

Successful treatment of primary central nervous system lymphomas with chemotherapy after osmotic blood-brain barrier opening.

Three patients with primary central nervous system (CNS) lymphoma have had major tumor regression with multiagent chemotherapy given in association with reversible blood-brain barrier opening used to enhance drug delivery to the tumor. In addition, in one patient barrier modification was carried out in the posterior fossa by mannitol infusion into the vertebral artery without untoward effects, an approach not heretofore accomplished. Computed tomographic (CT) studies documented that discontinuation of steroids rapidly effected an increase in the delivery of contrast agent to the tumor. CT monitoring of the degree of barrier modification showed tumor nodules and tumor size not apparent on the control scans, thereby providing additional evidence of the existence of a blood-brain barrier in CNS tumors. These studies further show that drug (contrast) delivery to the tumor, as well as to the surrounding barrier, is enhanced after reversible blood-brain barrier modification. Finally, chemotherapy administered by this approach resulted in defined, objective tumor responses in these three patients.

Adult↗
PubMed1983

Special training under simulated stat lab conditions.

A course has been devised to simulate a hospital stat lab environment for students in a 2-year MLT Associate Degree program. This course ensures that each student will individually perform a wide variety of laboratory procedures and report results under hospital-like circumstances. This course, which has received favorable comment from NAACLS, circumvents problems of insufficient placement situations, inadequate supervision, and limited variety of student experience in hospital sites. Course procedures, objectives, and student evaluation methods are described.

Clinical Laboratory Techniques↗
PubMed1982

Influence of low oxygen concentration on derepression of nitrogenase in Klebsiella pneumoniae.

Effects of oxygen derepression of nitrogenase were studied in Klebsiella pneumoniae, using oxyleghaemoglobin to supply and monitor very low dissolved O2 concentrations in a steady-state system. Expression of the nifH gene was studied by using a nifH::lac fusion strain, which aslo carried the Nif+ plasmid pRD1 so that the production of active nitrogenase could also be monitored. When compared with anaerobic treatments, very low concentrations of dissolved O2 inhibited derepression of both nifH::lac and pRD1 nif. Fifty percent inhibition of derepression occurred at 0.1 microM-O2. The apparent Ks of the dominant terminal oxidase was 0.08 microM-O2. These results suggest that there is a close relationship between the terminal respiratory system of these bacteria and the repression of nitrogenase by O2.

Enzyme Repression↗