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Biomedical subjects

G White

Publications and source records attributed to G White.

At least 181 records · Page 10Linked to original sources
PubMed1985

Pharmacological, toxicological, and therapeutic evaluation in mice of doxorubicin entrapped in cardiolipin liposomes.

Doxorubicin possesses high affinity for binding to cardiolipin. We have utilized these properties in preparing stable liposomes of doxorubicin and cardiolipin with a net positive charge. Doxorubicin liposomes were formed by using 11.2 mumol of drug, 5.6 mumol of cardiolipin, 28.5 mumol of phosphatidylcholine, 19.5 mumol of cholesterol, and 11.1 mumol of stearylamine. These liposomes were sonicated for 90 min at 37 degrees followed by extensive dialysis against buffer. The pharmacological, toxicological, and therapeutic effects of doxorubicin entrapped in cardiolipin liposomes were compared with those of free doxorubicin in mice. At a dose of 4 mg/kg i.v., the peak cardiac concentration was achieved in 30 min following free doxorubicin administration, the value being 8.1 micrograms/g. The peak cardiac concentration with doxorubicin in cardiolipin liposomes was obtained at 5 min with a value of 2.8 micrograms/g of tissue. The cardiac concentration X time values for free doxorubicin for the 24-hr period of observation were 55.1 micrograms X hr/g, whereas it was only 7.8 micrograms X hr/g with the drug entrapped in cardiolipin liposomes. Compared to free drug, the liposomal entrapped doxorubicin significantly reduced the histopathological lesions in cardiac tissue of mice at a dose of 15 mg/kg as determined by electron microscopy. The nadir of peripheral white blood cell counts in mice with free drug, 6 mg/kg, was observed on Day 3 which was 50% of control, whereas with liposomal encapsulated drug it was reduced only 23% on Day 7. Doxorubicin in cardiolipin liposomes demonstrated enhanced chemotherapeutic potential against murine ascitic P388 leukemia with a 144% increased life span compared to 55% increased life span with free drug at a dose of 7.5 mg/kg on Days 1, 3, and 7. We conclude that doxorubicin liposomes developed in these studies possess improved therapeutic action as demonstrated by their ability to reduce the toxicity of the drug substantially.

Animals↗
PubMed1984

Evaluation of a mixture of trimethoprim and sulphaquinoxaline for the treatment of poultry: safety and palatability studies.

The safety of a 1:3 mixture of trimethoprim (TMP) and sulphaquinoxaline (SQX) for administration in food or water was assessed in broiler chickens, chicks of an egg laying strain and breeding fowl. The only effects recorded in six-week-old broilers medicated for seven days at levels ranging from 16 to 133 mg TMP plus SQX per kg bodyweight were decreases in water or food consumption, probably caused by unpalatability at overdosage levels, and associated decreases in weight gain and packed cell volume at an achieved overdose level of 4.4 times the recommended use concentration (RUC). Breeding fowl medicated at levels of 1 X or 3 X RUC for 14 days showed slightly reduced reproductive performance reflected by lowered egg production, egg weight and hatchability. These effects were temporary and performance equal to that of unmedicated birds was re-established by 14 days after medication ceased. Week-old chicks medicated for five days at levels from 0.7 to 4.7 X RUC showed normal growth rate over 12 days. Eleven-day-old chicks could not distinguish medicated from unmedicated water.

Animal Feed↗
PubMed1984

Effects of caloric restriction and weight loss on glycemic control, insulin release and resistance, and atherosclerotic risk in obese patients with type II diabetes mellitus.

This study was designed to determine: (1) the effectiveness and safety of protein-sparing fast and gastric bypass surgery for achieving weight reduction in obese patients with type II diabetes mellitus (non-insulin-dependent diabetes mellitus); (2) the effects of these interventions on glycemic control; (3) the effects of weight loss on insulin secretion and action; and (4) the effects of treatment on atherosclerotic risk factors. Six patients consumed only a protein supplement (1.4 g/kg ideal body weight) for up to six months until a final weight below 120 percent of ideal body weight was achieved or weight loss ceased. Six patients underwent gastric bypass surgery. Both groups of patients were studied before and after treatment while consuming a balanced weight-maintaining diet. Both protein-sparing fast and gastric bypass surgery were safe and successful in the short term in producing weight loss. Both treatments improved glycemic control. Mean fasting plasma glucose values fell from 287 to 168 mg/dl (p less than 0.01). Mean total glycosylated hemoglobin values declined from 11.9 to 8.2 percent (p less than 0.01) (normal reference interval 5.85 to 8.85 percent). Patients who achieved a final weight below 125 percent of ideal body weight had significantly better post-treatment fasting plasma glucose values (130 versus 196 mg/dl, p less than 0.05) and total glycosylated hemoglobin values (6.8 versus 9.0, p less than 0.02) than those whose weight remained above 125 percent of ideal. In diet-treated patients, improved glycemic control occurred with caloric restriction alone prior to significant weight loss. Improved glycemic control was accompanied by decreased insulin resistance. Mean steady-state plasma glucose values fell from 377 to 208 mg/dl (p less than 0.008), and mean fasting insulin values fell from 31.0 to 17.0 microU/ml (p less than 0.004). Acute-phase insulin release, which was markedly impaired before treatment, did not improve even in patients who had post-treatment fasting plasma glucose values below 130 mg/dl. Significant improvements in atherosclerotic risk factors occurred. Mean high-density lipoprotein cholesterol values increased from 33.8 to 40.5 mg/dl (0.006 less than p less than 0.008), and factor VIII coagulant activity decreased from 194 to 140 percent (p less than 0.005). Serum fibrinogen also decreased (393 to 347 mg/dl, p = 0.08), although the decrease did not reach clinical significance.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1984

Toronto multiagency child abuse research project: the abused and the abuser.

Information from 422 cases of child mistreatment in Toronto was gathered from the files of a child welfare agency and a children's hospital. These data were compared to patterns reported in previous studies and clinical writings on child mistreatment to investigate similarities and differences in families whose children have been abused in Canada, England, and the United States. Findings from the present study were similar to others in many respects. The differences were primarily in the area of lower incidences of such problems as perinatal difficulties in the children and intellectual limitations and social isolation in the parents; however, there was a higher incidence of single-parent families. The results suggest that clinicians should bear in mind that child mistreatment cannot be ruled out on the grounds that no serious problems have been noted for the child or the family.

Canada↗
PubMed1984

Trypanosoma cruzi from the Paraguayan Chaco: isoenzyme profiles of strains isolated at Makthlawaiya.

At Makthlawaiya, in the Paraguayan Chaco, the prevalence of Trypanosoma (Schizotrypanum) cruzi infection among both domestic Triatoma infestans and domestic dogs was 38%, and IgG anti-T. cruzi antibody was detected by the quantitative enzyme-linked immunosorbent assay (ELISA) in 80% (105/133) of human sera. Ninety percent (25/28) of T. cruzi strains isolated from both T. infestans and dogs showed heterozygous isoenzyme profiles for glucose phosphate isomerase, phosphoglucomutase and 6-phosphogluconate dehydrogenase. These strains appeared to be closely related to Bolivian zymodeme 2. Three Paraguayan T. cruzi strains showed homozygous isoenzyme profiles, similar to those of major Brazilian zymodemes. It was concluded that T. cruzi strains with heterozygous isoenzyme profiles predominate in domestic transmission cycles in this highly endemic area of the Paraguayan Chaco.

Animals↗
PubMed1983

Effect of various oral dose levels of a trimethoprim/sulphadiazine mixture on Bordetella bronchiseptica infection and on the proliferation of trimethoprim-resistant faecal coliforms in pigs.

When a 1:5 mixture of trimethoprim (TMP) and sulphadiazine was fed to pigs intra-nasally infected with bordetella bronchiseptica, 10 mg/kg/day was shown to be highly effective in suppressing the organism. This dose level had little effect on numbers of TMP-resistant coliforms in faeces, but oral doses of 30 mg/kg/day eventually selected a resistant population. It is suggested that the proliferation of resistant coliforms would be minimized by administration of the lowest oral dose rates of antibacterial drugs compatible with efficacy.

Administration, Oral↗
PubMed1983

Relative activities of acyclovir and BW759 against Aujeszky's disease and equine rhinopneumonitis viruses.

Compound BW759 (9-[2-hydroxy-1-(hydroxymethyl)ethoxymethyl]guanine) was shown to be about 230 times more active than acyclovir (9-[2-hydroxyethoxymethyl]guanine) (ACV) against Equid herpesvirus type 1 infection in Syrian hamsters and was more effective against Aujeszky's disease in mice. The therapeutic superiority of BW759 over ACV was greater than expected from quantitative inhibitory results in tissue culture with these viruses. When administered to hamsters at dose rates sufficient to prevent any Equid herpesvirus type 1-induced mortality (100 mg of ACV per kg per day; 3 mg of BW759 per kg per day), BW759 inhibited viral multiplication, as judged by histopathological observations, clinical chemistry, and liver virus concentrations, to a greater extent than ACV. Compound BW759 was particularly effective when administered via the oral route. The reasons for the superiority of BW759 over ACV remain to be elucidated.

Acyclovir↗
PubMed1983

Optimum fourier filtering of cardiac data: a minimum-error method: concise communication.

Random fluctuations limit the accuracy of quantities derived from cardiac time-activity curves (TACs). To overcome this problem, TACs are often fitted with a truncated Fourier series giving rise to two sources of error: (a) the truncated series may not adequately describe the TAC shape, causing errors in parameters calculated from the fit: and (b) successive TACs acquired from the same subject under identical circumstances will fluctuate due to limited counts, causing the Fourier fits (and parameters derived from them) to fluctuate. These two errors, respectively, decrease and increase as the number of harmonics increases, suggesting the existence of a minimum in total error. This number of harmonics for minimum error (NHME) was calculated for each of six common parameters used to describe LV TACs. The "true" value of each parameter was determined from TACs of very high statistical precision. Poisson noise was added to simulate lower count rates. For low-count TACs, use of either a smaller or a larger number of harmonics resulted in significantly greater error. NHME was found to occur at two harmonics for the systolic parameters studied, regardless of the noise level present in the TAC. For diastolic parameters, however, NHME was a strong function of the noise present in the TAC, varying from three harmonics for noise levels typical of regional TACs, to five or six harmonics for high-count global TACs.

Diastole↗
PubMed1983

Beneficial effects of verapamil on postischemic renal failure.

The effects of calcium blockade with verapamil on postischemic renal failure were tested in dogs. Two experiments were performed. In experiment 1 (n = 7), one kidney in each dog received an infusion of verapamil and the other received saline for 30 minutes prior to induction of 1 hour of ischemia. Inulin clearance (CIN), urine flow, and renal blood flow (RBF) were measured. Infusion of verapamil increased urine flow from 0.99 to 4.29 ml/min (P less than 0.001). CIN and RBF did not change significantly nor did urine flow in the saline-treated kidney. Three hours after ischemia there was no significant difference in CIN, although it was lower in verapamil-treated kidneys. RBF declined in both treatments. In experiment 2 (n = 6) kidneys were treated with verapamil and saline for 50 minutes beginning immediately after 1 hour of ischemia. Urine flow and CIN were significantly higher in verapamil-treated kidneys during the infusion (3.09 +/- 0.44 versus 0.26 +/- 0.12 ml/min, P less than 0.001; 28.6 +/- 7 .4 versus 6.2 +/- 3.1 ml/min, P less than 0.025, respectively). CIN remained elevated in verapamil-treated kidneys at 3 hours, however RBF was depressed in both verapamil- and saline-treated kidneys. These results suggest that verapamil is a potent diuretic and that verapamil can be given after renal ischemia with significant attenuation of postischemic renal failure.

Acute Kidney Injury↗
PubMed1983

Cytotoxicity of estramustine, a steroid-nitrogen mustard derivative, through non-DNA targets.

Estramustine is cytotoxic in HeLa and Walker 256 carcinoma cells (with or without acquired resistance to nitrogen mustards) at concentrations equivalent to other alkylating agents. Even at lethal estramustine levels, no damage to DNA occurs. Instead, a disproportionately high amount of intact estramustine binds hydrophobically to the structural proteins of the nucleus, the nuclear matrix. In HeLa cells, estradiol receptors are absent, and estradiol per se is not toxic. Thus, estramustine has a mechanism of action distinct from that of steroids and alkylating agents and may induce cytotoxicity through interactions with the proteins of the nuclear matrix.

Animals↗
PubMed1982

Comparative effects of oral administration of trimethoprim/sulphadiazine or oxytetracycline on the faecal flora of horses.

A study was carried out on the bacteriological faecal flora of horses before and after oral doses of oxytetracycline or trimethoprim plus sulphadiazine. Administration of oxytetracycline was rapidly followed by large increases in counts of coliforms. Bacteroides and Streptococcus species, the disappearance of Veillonella species, the appearance of Clostridium perfringens type A in large numbers and the accumulation of watery fluid in the rectal contents. These changes were not seen following administration of trimethoprim-sulphadiazine and it was concluded that oral treatment of horses with this combination was unlikely to be accompanied by the hazard of inducing colitis.

Administration, Oral↗
PubMed1981

Appraisal of the suitability of a disease model of acute salmonellosis in calves for chemotherapeutic studies.

When young calves were dosed orally with 10(10) organisms of a culture of Salmonella dublin, typical symptoms of acute salmonellosis followed with a death rate of 86 per cent. Peak mortality occurred six days after infection. As a result of a statistical appraisal of the consistency of mortality in groups of untreated calves a model is proposed for the therapeutic evaluation of antibacterial compounds, which compares the number of survivors in groups of seven or eight calves with a minimum of four needed for significant indication of efficacy. Bacteriological and pathological investigations showed that the experimental disease was initially an acute systemic infection followed by severe enteritis. Measurements of plasma concentrations of enzymes and other constituents did not achieve the desired objective of establishing a method of quantitative evaluation of the clinical status of individual animals, although some changes occurred which were consistent with the pathology of the disease and suggested possible mechanisms by which jaundice occurred.

Acute Disease↗