Biomedical subjects

D A White

Publications and source records attributed to D A White.

At least 19 recordsLinked to original sources

PubMed1995

Modulation of hepatic apolipoprotein B, 3-hydroxy-3-methylglutaryl-CoA reductase and low-density lipoprotein receptor mRNA and plasma lipoprotein concentrations by defined dietary fats. Comparison of trimyristin, tripalmitin, tristearin and triolein.

Different dietary fatty acids exert specific effects on plasma lipids but the mechanism by which this occurs is unknown. Hamsters were fed on low-cholesterol diets containing triacylglycerols enriched in specific saturated fatty acids, and effects on plasma lipids and the expression of genes involved in hepatic lipoprotein metabolism were measured. Trimyristin and tripalmitin caused significant rises in low-density lipoprotein (LDL) cholesterol which were accompanied by significant reductions in hepatic LDL receptor mRNA levels. Tripalmitin also increased hepatic expression of the apolipoprotein B gene, implying an increased production of LDL via very-low-density lipoprotein (VLDL) and decreased removal of LDL in animals fed this fat. Hepatic levels of 3-hydroxy-3-methylglutaryl-CoA reductase mRNA did not vary significantly between the groups. Compared with triolein, tristearin had little effect on hepatic gene expression or total plasma cholesterol. However, it caused a marked decrease in VLDL cholesterol and a rise in LDL cholesterol such that overall it appeared to be neutral. Lipid analysis suggested a rapid desaturation of much of the dietary stearate. The differential changes in plasma lipids and hepatic mRNA levels induced by specific dietary fats suggests a role for fatty acids or a metabolite thereof in the regulation of the expression of genes involved in lipoprotein metabolism.

Adipose Tissue↗

PubMed1995

Regulation of hamster hepatic microsomal triglyceride transfer protein mRNA levels by dietary fats.

The effect of dietary fat on hepatic microsomal triglyceride transfer protein(MTP) large subunit mRNA levels in the hamster was examined. Increasing the dietary fat concentration from 11.7 energy % to 46.8 energy % caused a 60% increase in hepatic MTP mRNA; this increase was shown to be dose-dependent (r = 0.688 p = 0.0023). MTP mRNA levels correlated significantly with several plasma lipoprotein cholesterol parameters. No significant relationship was observed between MTP mRNA and either plasma or VLDL triglyceride. The nature of the dietary fatty acids also influenced MTP mRNA levels, with trimyristin and tripalmitin enriched diets significantly elevating MTP mRNA relative to diets enriched in triolein and trilinolein.

Animals↗

PubMed1995

Folstein vs modified Mini-Mental State Examination in geriatric stroke. Stability, validity, and screening utility.

OBJECTIVE: Two studies were conducted with the Folstein Mini-Mental State Examination (MMS) and the Modified Mini-Mental State Examination (3MS) to examine whether the expanded version is a more useful screening tool in stroke populations. DESIGN: Clinical utility of screening tests (MMS and 3MS) was evaluated in reference to neuropsychological performance and functional outcome in rehabilitation. SETTING: Medical rehabilitation unit of university-affiliated hospital. PATIENTS: Two groups (n = 77, and n = 70) of patients who were admitted consecutively. MAIN OUTCOME MEASURES: Neuropsychological performance and functional outcome (functional independence measure). RESULTS: The reliability, stability, and validity of the 3MS were established in the stroke population. Classification accuracy did not differ between the MMS and 3MS, although the 3MS had higher sensitivity. In detecting cognitive impairment when compared with the extended neuropsychological battery, both instruments were adequate in patients with left-sided cerebrovascular accidents and were ineffective in patients with right-sided cerebrovascular accidents. The 3MS correlated with some cognitive domains missed by the MMS, thus adding useful clinical information. Finally, the 3MS was a significantly better predictor of functional outcome than the MMS. CONCLUSIONS: The 3MS was found to be a reliable, valid, and stable cognitive screening instrument in the stroke population. Classification accuracy indicates that both screening instruments are not strong in their ability to detect cognitive impairment in patients with stroke, especially in right-sided cerebrovascular accidents. The 3MS does have some advantages over the MMS; the expanded version of the screen not only provides additional cognitive information but also allows for better predicting of functional outcome.

Aged↗

PubMed1995

Is a telephone helpline of value to the workplace smoker?

This paper reports the findings of the evaluation of a national smokers' helpline which was set up by British Telecom (BT) for its employees. The helpline formed part of a new comprehensive smoking policy for all BT staff. Over 1000 employees, more than 3.0% of all smokers, phoned the helpline during the first three months of its operation. Two-thirds of callers tried to quit smoking after calling the helpline, and a quarter were still successful three months later. One in six callers reduced the number of cigarettes that they smoked on working days. While the helpline and other cessation support services were evaluated positively by callers, it appears that helplines only appeal to a small minority of smokers. However, they do seem to be an effective mechanism for a nationwide company to identify those smokers who want support, and a useful means of centralizing the administration of support services. They are potentially a cost-effective option for larger employers.

Adolescent↗

PubMed1995

Syndrome of acute dyspnea related to combined mitomycin plus vinca alkaloid chemotherapy.

We report the incidence, clinical features, and course of acute dyspnea following combination chemotherapy using mitomycin and vindesine or vinblastine. The courses of 387 patients with advanced non-small cell lung cancer receiving combined mitomycin and vinca alkaloid chemotherapy were analyzed. Of these patients, 25 experienced acute respiratory distress. Factors contributing to the dyspnea are reported. The syndrome is characterized by the sudden onset of dyspnea without other respiratory symptoms. Acute shortness of breath always occurred on a day when a vinca alkaloid was administered. The median number of previous doses of vinca alkaloid at the time of the event was 10 and the median number of prior mitomycin doses was 3. Rechallenge with the drug in two cases led to recurrence. The incidence was 4% in a group of 378 patients on four protocols for non-small cell lung cancer. Radiographs of 87% of patients showed new focal or diffuse interstitial infiltrates. Arterial blood gases demonstrated low PO2 and increase in A-a gradient. Pulmonary function tests revealed severely impaired diffusing capacity. Substantial improvement occurred over 24 hours. Approximately 60% of the patients experienced chronic respiratory impairment that only partially responded to corticosteroid therapy. No other causes for this syndrome were identified. A syndrome of acute dyspnea occurred in 4% of patients treated with mitomycin and vinca alkaloid therapy. The syndrome has a distinctive presentation, which can lead to chronic pulmonary insufficiency. Clinicians caring for patients receiving combined therapy with mitomycin and a vinca alkaloid should be aware of this type of acute pulmonary toxicity. Further studies are necessary to clarify its etiology.

Acute Disease↗

PubMed1995

Diffuse idiopathic pulmonary neuroendocrine cell proliferation presenting as interstitial lung disease.

Pulmonary neuroendocrine cell (PNEC) hyperplasia typically occurs as an adaptive response in persons living at high altitudes and as a reactive response in the setting of lung injury. However, previous studies suggest that PNEC hyperplasia can occur in the absence of preexisting lung disease and may even give rise to airway disease through the development of pulmonary tumorlets and airway fibrosis and perhaps the release of paracrine secretions. We describe a patient with diffuse PNEC proliferation of a probable hyperplastic nature developing in the absence of a chronic pulmonary disorder who presented clinically with an interstitial lung process. Open lung biopsy displayed a florid intraepithelial population of PNEC diffusely involving the distal airways and alveoli with desquamation and filling of alveolar spaces by nests of PNEC. The presence of alveolar thickening was attributable to the intraepithelial proliferation of PNEC associated with interstitial fibrosis and accounted for mild reductions in the pulmonary diffusing capacity. The neuroendocrine differentiation of this proliferation was evident by light microscopic and ultrastructural examination. The absence of airway fibrosis and pulmonary tumorlets was in agreement with the lack of clinical airway disease in this case. The intraepithelial growth and absence of parenchymal invasion in this lesion favor a diffuse, florid PNEC hyperplasia with mild dysplastic features over a pulmonary neuroendocrine neoplasm.

Aged↗

PubMed1995

The changing pharmacodynamics of metocurine identify the onset and offset of canine gastrocnemius disuse atrophy.

BACKGROUND: Immobilization of skeletal muscle results in disuse atrophy and resistance to nondepolarizing muscle relaxants. We studied the pharmacodynamics of metocurine (MTC) to identify the development and recovery of disuse-related resistance to MTC. METHODS: Nineteen dogs underwent cast immobilization of a hind limb for as long as 3 weeks. Before, during, and after casting, dogs were intermittently anesthetized with thiamylal-N2O-fentanyl. The blood concentration of MTC and the corresponding degree of paralysis after a brief infusion were recorded and were used to characterize the pharmacokinetics and pharmacodynamics of MTC. RESULTS: Pharmacodynamic study of the response to MTC demonstrated resistance by the 4th day of casting. The effect-site concentration associated with 50% paralysis of twitch increased after 3 weeks from approximately 250 to 750 ng/ml. After cast removal, resistance persisted for 2 more weeks. Six weeks after cast removal, the effect-site concentration associated with 50% paralysis of twitch was normal in every dog. CONCLUSIONS: Within the context of this study of immobilization disuse atrophy, pharmacokinetic and pharmacodynamic characterization of antagonist responses can be used to infer muscle disuse-related changes in acetylcholine receptors.

Acetylcholine↗

PubMed1995

Pulmonary infection in the immunocompromised patient.

Pneumonia in the immunocompromised patient remains a significant cause of morbidity and mortality. These patients are susceptible to a wide variety of organisms, but specific infections tend to occur in well defined settings. The type of infection can be predicted based on the nature and severity of the immune defect, past patient exposures, chemotherapy given, radiographic presentation, and acuteness of illness. New treatments, including growth factors, the oral antifungal agents, and antiviral drugs, such as ganciclovir and acyclovir, have improved management and prognosis in some cases. However, some problems have increased with a significant risk of spontaneous pneumothorax now seen with Pneumocystis carinii infection. Bronchoscopy with bronchoalveolar lavage plays a major role in diagnosis, particularly for P carinii and cytomegalovirus infection. However, open lung biopsy remains essential for diagnosis in some settings. Surgical resection for control of hemoptysis and for removal of residual foci of disease also are an integral part of management of pulmonary fungal infections in the immunosuppressed patient.

AIDS-Related Opportunistic Infections↗

PubMed1993

Ultrastructural morphology, cytochemistry, and morphometry of eosinophil granules in Chédiak-Higashi syndrome.

Lysosomal enlargement in Chédiak-Higashi Syndrome (CHS) occurs to varying degrees in different cell types and has provided insight into the pathophysiology of lysosomal granules. This study was undertaken to determine the extent of involvement of eosinophil crystalloid granules (CGs) and smaller non-crystalloid granules (NCGs) in giant granule formation. Eosinophils from two CHS patients were evaluated after glutaraldehyde fixation and staining for morphologic examination, peroxidase, and complex carbohydrate using uranyl acetate-lead citrate, diaminobenzidine-lead citrate, and periodate-thiocarbohydrazide-silver proteinate (PA-TCH-SP) methods, respectively. Although many CGs appeared normal in shape and size, several CGs appeared enlarged and a few measured over 5 microns in diameter, consistent with giant granule formation in CHS. These giant granules either occasionally contained a single large crystalloid or, more frequently, contained numerous normal-size crystalloids. Enlargement of granules was also observed in some precursor CGs of bone marrow early eosinophils, indicating that giant granule formation was initiated during granule genesis. Almost all NCGs in late eosinophils were small granules and stained strongly with PA-TCH-SP in contrast to CGs. Most, but not all small granules were peroxidase-positive in eosinophil precursors, whereas the percentage of peroxidase-negative small granules increased in late eosinophils. This indicated the presence of at least two small granule populations. Morphometric studies indicated CHS selectively involved CGs and demonstrated that neither the average size nor numbers of NCGs were significantly different from normal eosinophils. Thus, these studies indicate that CHS selectively involves CGs, and demonstrate preservation of normal granule size and heterogeneity for NCGs in late eosinophils. These observations suggest that the underlying CHS pathophysiology does not involve all lysosomal subpopulations.

Carbohydrate Metabolism↗

PubMed1993

Regulation of insulin-like growth factor binding proteins in young growing animals by alteration of energy status.

The regulation of plasma insulin-like growth factor binding proteins (IGFBPs) by energy status has been assessed in 2-month-old pigs. Energy balance was modified by altering thermoregulatory demand and energy intake, with litter-mates being kept for several weeks at either 35 or 10 degrees C on a high (H) or low (L) level of food intake (where H = 2L); plasma samples were taken 20-24 h after the last meal. The two major forms of circulating IGFBP, as estimated by Western blot analysis, were identified putatively as IGFBP-2 and IGFBP-3 (relative molecular weights of 34 and 40-45 kDa respectively). There were significant differences in IGFBP profiles between the four treatment groups of 35H, 35L, 10H and 10L: the 40-45 kDa IGFBP (putative IGFBP-3) was elevated both in the warm and on a high food intake (P < 0.001), and there was a marked reciprocal relation between the 40-45 and 34 kDa IGFBPs. The relative concentration of the 34 kDa IGFBP (putative IGFBP-2) was greatest in the 10L and least in the 35H group. It is concluded that long-term alterations in energy balance, induced by changes in either intake or thermoregulatory demand, can significantly affect the plasma profile of IGFBPs during the first two months of life.

Aging↗

PubMed1992

The inhibition of the oxidation of low density lipoprotein by (+)-catechin, a naturally occurring flavonoid.

(+)-Catechin inhibited the copper-catalysed oxidation of human low density lipoprotein (LDL) in a dose-dependent manner with complete inhibition at 20 micrograms/mL. The flavonoid at a concentration of 50 micrograms/mL also inhibited oxidation of LDL induced by the mouse transformed macrophage J774, human monocyte-derived macrophages and vascular endothelial cells isolated from human umbilical cords. LDL modified by copper-catalysed or cell-induced oxidation was endocytosed and degraded by human macrophages at a much greater rate than native LDL. LDL reisolated from copper or cell incubations in the presence of (+)-catechin was endocytosed and degraded at rates similar to native LDL. (+)-Catechin appeared to inhibit the uptake and degradation by macrophages of cell-modified LDL. The actions of (+)-catechin on cell-induced oxidation of LDL are consistent with the ability of flavonoids of similar structure to inhibit lipoxygenases and with a role for lipoxygenases in cell-induced modification of LDL in vivo.

Animals↗

PubMed1992

Inhibition of protein N-glycosylation has no effect on the binding of acetyl LDL to J774 cells.

Acetyl-LDL (Ac-LDL) bound to transformed mouse macrophage J774 cells in a high affinity, saturable and specific manner. When cells were cultured for 24h in the presence of tunicamycin such that incorporation of N-linked sugars into protein but not protein synthesis itself was inhibited significantly, the binding characteristics of Ac-LDL to the cells were unaltered. In this respect the Ac-LDL receptor of J774 cells is similar to the asialoglycoprotein receptor of HepG2 cells.

Animals↗

PubMed1992

A neuromuscular monitoring system based on a personal computer.

We have developed a computerized neuromuscular monitoring system (NMMS) using commercially available subsystems, i.e., computer equipment, clinical nerve stimulator, force transducer, and strip-chart recorder. This NMMS was developed for acquisition and analysis of data for research and teaching purposes. Computer analysis of the muscle response to stimulation allows graphic and numeric presentation of the twitch response and calculated ratios. Since the system can store and recall data, research data can be accessed for analysis and graphic presentation. An IBM PC/AT computer is used as the central controller and data processor. The computer controls timing of the nerve stimulator output, initiates data acquisition, and adjusts the paper speed of the strip chart recorder. The data processing functions include establishing control response values (when no neuromuscular blockade is present), displaying force versus time and calculated data graphically and numerically, and storing these data for further analysis. The general purpose nature of the computer and strip chart recording equipment allow modification of the system primarily by changes in software. For example, new patterns of nerve stimulation, such as the posttetanic count, can be programmed into the computer system along with appropriate data display and analysis routines. The NMMS has functioned well in the operating room environment. We have had no episodes of electrocautery interference with the computer functions. The automated features have enhanced the utility of the NMMS.(ABSTRACT TRUNCATED AT 250 WORDS)

Computer Systems↗

PubMed1992

Mechanism of hypotension following rapid infusion of protamine sulfate in anesthetized dogs.

Protamine sulfate (PS), used to neutralize the anticoagulant effect of heparin, is often associated with systemic hypotension. Whether this hypotension is secondary to a depression of myocardial function is not clear. The present study tested the hypothesis that systemic hypotension was accompanied by a depression in myocardial function and examined the possible role of histamine in mediating the cardiovascular response to PS. Seven conditioned dogs were chronically instrumented with pressure and ultrasonic dimension transducers. Studies were conducted under halothane anesthesia 7 to 10 days after instrumentation. Cardiac contractility was assessed using the slope, Ees, of the linear regression of the left ventricular end-systolic pressure-diameter relationship. Intravenous infusion of PS, 5 mg/kg, when given in periods of less than 30 seconds, decreased systemic arterial pressure by 45% (from 101 +/- to 54 +/- 5 mm Hg) without change in heart rate. Cardiac output decreased by 22% from control and the slope Ees decreased by 37% (from 14.5 +/- 1.2 to 8.7 +/- 1.4 mm Hg/mm). Systemic vascular resistance decreased by 34% (from 2581 +/- 121 to 1712 +/- 200 dyne.s.cm-5). The cardiovascular depression caused by PS was transient and could not be reproduced by a repeated dose given within a 60-minute period. Antagonists of histamine (diphenhydramine and cimetidine) could not attenuate the PS-induced cardiovascular depression. This depression was independent of preheparinization and did not occur when PS was infused slowly over a 2-minute period. The data clearly demonstrate negative inotropic and vasodilator effects of PS following rapid administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Inhalation↗

PubMed1992

Comparison of low-dose intramuscular and intravenous salcatonin in the treatment of primary hyperparathyroidism.

The treatment of hypercalcaemia with low-dose salcatonin (100 U/d), administered either as a single intramuscular bolus or as a continuous intravenous infusion for five days, was examined in two groups of 10 patients with primary hyperparathyroidism, in a randomized open parallel study. Both the peak (0.31 +/- 0.035 mmol/L v 0.13 +/- 0.034 mmol/L) and overall (0.073 +/- 0.016 mmol/L v 0.018 +/- 0.016 mmol/L) hypocalcaemic responses were greater in the infusion group. The peak reduction in serum calcium occurred on day 2 of treatment after which there was a progressive attenuation of response. All the differences between the two methods of administration wer due to renal rather than bony effects of salcatonin. Possible causes of progressive resistance to treatment included reductions in sodium excretion and serum phosphate. It is concluded that low-dose salcatonin administered as a continuous infusion was more effective than the same dose given as a bolus. The kidney played a pivotal role both in the cause of the hypercalcaemia and in the response to treatment, including the rapid development of resistance which limits the use of salmon calcitonin in primary hyperparathyroidism to short-term reduction of serum calcium.

Alkaline Phosphatase↗

PubMed1992

Up-and-down regulation of skeletal muscle acetylcholine receptors. Effects on neuromuscular blockers.

Multiple factors alter the interaction of muscle relaxants with the NMJ. This review has focused on the aberrant responses caused principally by alterations in AChRs (table 1). Many pathologic states increase (up-regulate) AChR number. These include upper and lower motor neuron lesions, muscle trauma, burns, and immobilization. Pre- or postjunctional inhibition of neurotransmission by drugs or toxins also up-regulate AChRs. These include alpha- and beta-BT, NDMR, anticonvulsants, and clostridial toxins. We speculate that other bacterial toxins also up-regulate AChR. With proliferation of AChRs, agonist drug dose-response curves are shifted to the left. The exaggerated release of potassium when depolarization occurs with the use of agonists such as SCh and decamethonium can be attributed to the increased number of AChR. Thus, SCh should be avoided in patients who are in the susceptible phase (see section V). In the presence of increased AChR, the requirement for NDMR is markedly increased. Thus, the response to NDMR may be used as an indirect estimator of increased sensitivity to SCh (table 1). The most extensively studied pathologic state in which there is a decrease in AChRs is myasthenia gravis; there is immunologically mediated destruction and/or functional blockade of AChRs. The pathophysiologic and pharmacologic changes in LEMS are quite distinct from those of myasthenia gravis. Decreased AChRs in myasthenia gravis result in resistance to agonists and increased sensitivity to competitive antagonists. In conditioning exercise, the perturbed muscles show sensitivity to NDMR that may be due to decreased AChRs. Chronic elevations of ACh observed with organophosphorus poisoning or chronic use of reversible cholinesterase inhibitors results in down-regulation of AChRs. In this condition, SCh should be avoided because its metabolic breakdown would be impaired; the requirement for NDMR may be decreased. All of the varied responses to SCh and NDMR, which are associated with concomitant changes in AChRs, are analogous to drug-receptor interactions observed in other biologic systems.

Animals↗

PubMed1992

Pulmonary complications in lymphoma patients treated with high-dose therapy autologous bone marrow transplantation.

To define the incidence and spectrum of pulmonary complications following autologous bone marrow transplantation (BMT), we retrospectively reviewed the course of 77 consecutive patients with Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) who failed conventional therapy and underwent autologous BMT. Forty-five percent of the 77 patients developed respiratory complications with a mortality from pulmonary causes of 26%. A total of 38 episodes of respiratory compromise occurred in 35 patients. Infections accounted for 15 episodes (39%) and included bacterial (16%), Aspergillus (8%) cytomegalovirus (8%), Herpes simplex (3%), and other (5%) pneumonias. The spectrum of infections was similar to that reported following allogeneic BMT, but cytomegalovirus pneumonia was not as frequent a problem in those with autologous transplant. Mortality from pulmonary infections was 33%. Noninfectious disorders accounted for 23 episodes (61%) and included recurrent HD (18%), radiation/drug toxicity (16%), and acute respiratory failure thought secondary to pulmonary alveolar hemorrhage (26%). This latter entity developed acutely within 2 wk following BMT and was associated with use of thoracic radiation for treatment of malignant disease in the chest just prior to BMT (p < 0.05). It was not associated with the age of the patient or presence of thrombocytopenia, coagulopathy, renal insufficiency or neutropenia (p NS). Mortality from noninfectious causes was 65%, but in those with pulmonary hemorrhage it was 100%. In conclusion, pulmonary complications are a major source of morbidity and mortality in patients with HD and NHL undergoing autologous BMT.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1992

Catatonia and the neuroleptic malignant syndrome--a single entity?

Separate episodes of both catatonia and the so-called 'neuroleptic malignant syndrome' (NMS) occurred within the same patient. The only evidence for NMS in this case was prior administration of a neuroleptic and the presence of generalised muscular rigidity. It is suggested that it is misleading to view these conditions as separate diagnostic entities and that NMS is probably more correctly incorporated into the catatonic disorders.

Adult↗