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Biomedical subjects

M Hill

Publications and source records attributed to M Hill.

At least 361 records · Page 20Linked to original sources
PubMed1985

A comparison of the endocrine effects of low dose aminoglutethimide with and without hydrocortisone in postmenopausal breast cancer patients.

The endocrine effects of 125 mg (low dose) aminoglutethimide (AG) twice daily (b.d.) were compared with those of 125 mg AG + 20 mg hydrocortisone (HC) b.d. in 23 and 45 postmenopausal patients with advanced breast cancer, respectively. The patients in each group were drawn from two separate populations, but the mean age and weight of the groups were similar and there were no significant differences between the pretreatment serum levels of the hormones investigated. Serum oestrone and oestradiol levels were suppressed by both treatments, but there was a significantly greater suppression by AG + HC. This greater suppression is probably due to the observed increase in serum androstenedione (i.e. precursor) levels with AG alone, whilst with AG + HC these levels were found to be reduced. In terms of suppression of serum oestrogen levels it is of benefit to combine low dose AG with HC.

Adult↗
PubMed1985

Orthostatic effect of imipramine and doxepin in depressed geriatric outpatients.

Blood pressure measurements were collected from 36 depressed geriatric outpatients (ages 55 to 81 years) enrolled in a double-blind, placebo-controlled study of the efficacy of doxepin and imipramine. Mean systolic postural changes were 25.9 mm Hg for imipramine, significantly higher than the 10.5 mm Hg for doxepin, and 12.4 mm Hg for placebo. The orthostatic drop in the imipramine group was only weakly related to dose and did not correlate with amount of pretreatment orthostatic hypotension or with duration of treatment. The increased orthostatic hypotension occurred early in treatment and at low doses of imipramine. Accordingly, caution is advised in the use of imipramine for the elderly.

Age Factors↗
PubMed1985

RSV provirus with same flanking sequences is found on different size classes of Chinese hamster chromosomes.

Rous sarcoma virus(RSV)-transformed Chinese hamster fibroblasts, containing approximately ten copies of the DNA domain comprising a single provirus and its flanking cellular sequences, were arrested in metaphase, and the chromosomes were fractionated by size in a sucrose gradient. The resolution of polymorphic ribosomal genes, the dihydrofolate reductase gene, and the c-src gene demonstrated that the gradient can distinguish between small, medium, and large chromosomes. The same DNA domain carrying the RSV provirus was found to be associated with chromosomes of all three size classes. Polymorphic copies of the domain in small and large chromosomes could be distinguished from those in medium-sized chromosomes because of the polymorphism in the XhoI and EcoRI sites on 5' and 3' adjacent cellular sequences, respectively. The presence of the same provirus domain on different chromosomes, together with the karyological data showing trisomies in the same chromosome size classes, suggest that the provirus domain, possibly the entire replicon, was duplicated and transferred to different nonhomologous chromosomes, and the transfer was followed by duplication of the target chromosomes. The possibility that proviral long terminal repeats might be involved in replicon transfer is discussed.

Animals↗
PubMed1985

Measurement of tobramycin concentrations in saliva.

Paired serum and saliva specimens were obtained from 16 patients and three volunteers who had received tobramycin. In addition, saliva was collected from ten controls who had not taken any drugs in the previous week. Tobramycin concentrations were measured in duplicate by the Emit assay modified to obtain precise results at concentrations greater than 0.25 microgram/ml. The drug was undetectable in 32 of 34 saliva specimens and only trace amounts were present in the other two, even though corresponding steady-state serum concentrations were greater than or equal to 4.0 micrograms/ml for 29 of 34 specimens. Tobramycin values were zero for all ten saliva specimens from controls. These results probably can be extrapolated to other aminoglycoside antibiotics since most are hydrophilic and ionized at physiologic pH, which disfavors penetration into saliva. We conclude that saliva cannot be used as a noninvasive indirect method of measuring aminoglycoside serum concentrations to guide dosage adjustments.

Adolescent↗
PubMed1985

Food-induced "dose-dumping" from a once-a-day theophylline product as a cause of theophylline toxicity.

Three slow-release preparations of theophylline have received approval from the U.S. Food and Drug Administration (FDA) for "once-daily" dosing indications, amid controversy regarding the appropriateness of this decision. Because of specific concerns regarding data submitted to the FDA in support of the first of these products to be approved, Theo-24, we examined the absorption characteristics of this newly marketed formulation. Eight healthy volunteers received, in a crossover manner, single doses of a theophylline reference solution and Theo-24, taken both fasting and after a breakfast of bacon and eggs. The concentrations of theophylline were measured up to 60 hours after the dose. Absorption of Theo-24 after an overnight fast was very slow, with only 71 +/- 6 percent (mean +/- SE) of the dose ultimately absorbed. In contrast, food caused precipitous "dose-dumping," resulting in dose-normalized peak levels in the serum that averaged 2.3 times higher than after a fasting dose. About half of the dose was absorbed in a four-hour period, generally beginning six to eight hours after the postprandial dose, and complete absorption was then attained within 24 hours (p less than 0.001). Toxic effects of theophylline occurred in four subjects when they took the dose with food whereas no toxic effects occurred during the fasting regimen. Consequently, doses of Theo-24 that would have attained a predicted peak concentration of 15 micrograms/ml after multiple dosing taken without food would, if taken with food, have resulted in larger fluctuations and in peak concentrations in the potentially toxic range for six of the eight subjects.

Adult↗
PubMed1985

Normal and pathological microbial flora of the upper gastrointestinal tract.

The resting gastric juice of normal adults in north-western Europe usually contains less than 10(3) micro-organisms/ml. Gastric sterility in such individuals is based on acidity. During meals or after an H2-receptor antagonist, gastric pH levels favour microbial growth but gastric emptying and recurrence of acid conditions resterilizes the stomach. If gastric pH remains above 4, colonization takes place. Studies suggest that gastric pH is normally high, with resultant bacterial colonization, in most of Asia, Africa, south and central America and, possibly, southern and eastern Europe. The biochemical activity of the gastric flora is also pH-dependent. Mucosal colonization occurs only if gastric pH is high. The small intestine is normally sterile because bacteria are killed by bile or pancreatic enzymes. Overgrowth can occur if there are areas inaccessible to these and may have severe metabolic consequences.

Adult↗
PubMed1984

Local opsonization by secreted macrophage complement components. Role of receptors for complement in uptake of zymosan.

We have examined the role of macrophage (M phi plasma membrane receptors for the cleaved third complement component (iC3b; CR3) and mannosyl, fucosyl terminated glycoproteins (MFR) in uptake of unopsonized zymosan. Monoclonal antibodies against CR3, M1/70 (Mac-1) and MO1, each inhibited approximately 50% of uptake of 125I-zymosan by murine and human M phi, respectively. Yeast mannan inhibited 0-50% of zymosan uptake in various M phi, in parallel with their expression of MFR. We demonstrated that M phi were the source of C3 in our assay and that the activity of other components of the complement system, namely a C3 convertase, factor I, and a factor I cofactor were also present in serum-free cultures of human monocytes. Macrophage C3 was deposited rapidly, within 10 min, on the zymosan particles and mediated binding, ingestion, and stimulation of superoxide release in BCG-activated and thioglycollate-elicited peritoneal M phi via CR3. Local secretion of complement proteins by M phi themselves can therefore opsonize pathogens and cells able to activate the alternative pathway and effect their destruction.

Animals↗
PubMed1984

Effects of excess dietary cholesterol on adrenal cholesterol accumulation and steroidogenesis.

Rats maintained on diets containing 3% cholesterol for 10 weeks show marked increase in adrenal cholesterol content. The greatest part of the increase is in the cholesterol ester fraction (329%), although free cholesterol is also elevated (140%). Morphologically, a marked increase in the lipid droplet content of the cells is observed. The microsomal fraction was enriched in cholesterol with parallel increases in microsomal ACAT activity in both normal and supplemented groups. Neutral cytosolic cholesterol esterase is unaffected by the diet. No significant increase in cholesterol occurred in the mitochondrial fraction. However, cholesterol binding to cytochrome P450 was affected by the diet under certain conditions. Cholesterol supplementation elevates adrenal corticosteroid levels (43%). Mild stress results in greater increases in adrenal corticosteroids after dietary supplementation. Aminoglutethimide produces inhibition of the stress induced increase in adrenal corticosteroids. This inhibition is less pronounced in cholesterol supplemented animals than in normal animals. The lack of similar effects on plasma corticosteroid levels suggests that enhanced metabolism and clearance of the plasma corticosteroids may be taking place.

Adrenal Glands↗
PubMed1984

A survey of dietary nitrate in well-water users.

The hypothesis that high nitrate ingestion may increase the risk of stomach cancer has led to concern over rising levels of nitrate in drinking water, but with little consideration as to whether nitrate from water makes a major contribution to total nitrate intake. In order to investigate the relative importance of water and food as sources of nitrate, 404 adult well-water users completed a diet diary over a 48-hour period and provided a 24-hour urine specimen and a sample of their drinking water. Where the waterborne nitrate level is less than 50 mg/I, as recommended by the World Health Organization (WHO), 30% of ingested nitrate is from water. As the well-water nitrate concentration rises the contribution of water to daily intake increases; at levels between 50 and 100 mg/I, on average, nearly 70% of daily intake is from water, and above 100 mg/I over 80% of daily intake is waterborne. Thus it is only at levels above those currently recommended by the WHO that waterborne nitrate appears to be the major contributor to total nitrate intake.

Adult↗
PubMed1984

Comparison between the bacterial and oligosaccharide content of ileostomy effluent in subjects taking diets rich in refined or unrefined carbohydrate.

Dietary surveys have shown that patients with Crohn's disease tend to eat more sucrose than control subjects and this investigation was undertaken to determine whether a diet rich in refined carbohydrate affects the bacterial flora of the terminal ileum. Ileostomy effluent in five patients with Crohn's disease and five with ulcerative colitis after two weeks on a diet rich in sucrose and refined cereal has been compared with the same period on a diet low in sucrose and rich in unrefined cereal. Observations were made hourly for nine hours after equicaloric breakfasts representing the two diets. The amount of ileostomy effluent was greater on the unrefined carbohydrate diet both in terms of wet weight (238 +/- 89 g vs 162 +/- 79 g, p less than 0.02) and dry weight (23 X 6 +/- 6.8 g vs 14.9 +/- 6.6 g, p less than 0.01); surprisingly, the amount of glucose and oligosaccharide was also greater (169 +/- 41 mg vs 82 +/- 26 mg, p less than 0.001) in all 10 volunteers. The bacteriological flora per gram was also higher on the unrefined carbohydrate diet after the test meal (p less than 0.02 between three and six hours) as a result of a general increase in all organisms. The relative proportions of the organisms did not vary between the two diets. No differences were detected between patients with ulcerative colitis and those with Crohn's disease.

Adult↗
PubMed1983

Amplification of the provirus region in Rous sarcoma virus-transformed Chinese hamster cells and segregation of the amplified copies in somatic cell hybrids.

Four independent clones of RSV-transformed Chinese hamster fibroblasts were isolated. Southern blots and dot hybridization studies showed that in three out of four clones there were four to eight times as many integrated proviruses as in the fourth clone which contained at least one complete provirus. Restriction mapping studies showed that although the integration site varied from clone to clone, all the proviral copies in the same clone shared the same flanking cellular sequences. In one clone there are at least two polymorphic proviral variants A and B, one with and one without a BglI site. Further experiments were performed to see if the variants could be physically separated. RSV-Transformed Chinese hamster cells resistant to thioguanine were fused with mouse cells to give somatic hybrids which preferentially segregate Chinese hamster chromosomes. Ten out of eleven hybrids positive for virus rescue have lost up to 90% of the parental provirus copies. Four of these hybrids were found to contain the provirus variant A alone, one the variant B alone, and the rest contained both variants. All the proviruses retained in somatic hybrids shared the flanking cellular sequences of the parental provirus. Provirus segregation in somatic hybrids confirms that multiple (about ten) copies of the provirus region are present in the karyotype of parental RSV-transformed cells and, furthermore, suggests that the amplified copies of this region are translocated to different chromosomes.

Animals↗
PubMed1983

Topical protection against long-wave ultraviolet A.

A PABA ester-oxybenzone preparation is superior to PABA or sulisobenzone alone in protecting the skin from methoxsalen-induced ultraviolet A (UVA) phototoxicity after water substantivity challenge. Such a mixture would be useful as a UVA screen for uninvolved or actinically damaged skin in patients receiving psoralens and ultraviolet A (PUVA) therapy. An effective topical UVA screen also may protect against UVA-induced diseases like solar urticaria, polymorphic light eruptions, drug-induced phototoxicity or photoallergy, and possibly against the deep degenerative changes of solar elastosis.

4-Aminobenzoic Acid↗
PubMed1983

Post-traumatic stress disorder in Hispanic Vietnam veterans. Clinical phenomenology and sociocultural characteristics.

The complex symptomatology of Hispanic Vietnam veterans receiving treatment for post-traumatic stress disorders (PTSD) was explored with the National Institute of Mental Health Diagnostic Interview Schedule, a structured diagnostic interview that yields current and lifetime operational diagnoses (e.g., DSM-III). Social networks and level of acculturation of these veterans were also examined and compared to those of a "control" group and a sample of veterans with DSM-III schizophrenic disorder (both samples included only Hispanic veterans from the Vietnam and post-Vietnam eras). All subjects reported heavy combat stress and met DSM-III criteria for PTSD. Most were very symptomatic and had significant social impairment. PTSD was rarely seen as a discrete entity but appeared instead mixed with symptom clusters cutting across various DSM-III diagnoses. Social networks of PTSD veterans were intermediate in size, frequency of contact with network members, and network density to those of the comparison groups. A distinctive feature of the PTSD group was the high proportion of negative relationships with close family members, especially spouses. "Highly" symptomatic PTSD veterans reported significantly smaller networks, fewer contacts outside the close family circle, and more negative emotionality directed toward family members than "minimally" symptomatic veterans. While all Hispanic groups studied were not significantly different in level of acculturation, PTSD veterans appeared more alienated from their cultural heritage than the other groups. The severe and polymorphous psychopathology found among these veterans suggests that "rap" groups alone may not constitute an adequate therapeutic approach and that more formal psychiatric therapies should be additionally considered in the management of Vietnam-linked PTSD.

Acculturation↗