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Biomedical subjects

W K Vaughn

Publications and source records attributed to W K Vaughn.

At least 55 records · Page 3Linked to original sources

Effects of streptozotocin- and alloxan-induced diabetes mellitus on mouse follicular and early embryo development.

Mice were made diabetic by intraperitoneal injection of streptozotocin or alloxan. Germinal vesicle breakdown in the ovarian follicles at 8 h after hCG in control animals (57%) was significantly greater than in streptozotocin-(24%) and alloxan-(42%) diabetic animals (P less than 0.001). This delay in oocyte maturation was reversible by in-vivo insulin administration to diabetic mice. A developmental delay was also found for embryos recovered from diabetic mice. This developmental delay extended into the 72 h in-vitro cultures. Compared to control embryos, those from alloxan- and streptozotocin-treated mice demonstrated marked impairment in development as assessed by (1) distribution of developmental cell stages at each observation period and (2) rates of development which increasingly diverged at each observation period. In diabetic mice treated with insulin in vivo, the percentage of 2-cell embryos recovered increased. Furthermore, in streptozotocin- and alloxan-animals treated with insulin, the rate of in-vitro development of embryos, as well as their developmental stage distribution improved. We therefore suggest that uncontrolled diabetes mellitus, as well as contributing to the development of congenital malformations, may deleteriously affect reproductive performance both before fertilization and at the very earliest gestational stages.

Alloxan↗

Pitt-UNOS Liver Transplant Registry.

The Pitt-UNOS Liver Transplant Registry maintains a computerized database of all orthotopic liver transplantations (OLTX) performed in the United States since October 1, 1987. Recipient data, which are collected at the time of transplantation and at specified follow-up time periods, are reported to the Registry directly, while donor data are transmitted through UNOS Central. During the first year of registration (October 1, 1987 through September 30, 1988), 1,561 liver transplantations were performed on 1,377 patients; 146 patients received 2 livers and another 19 patients received 3 livers. There were 29 multiorgan transplants, including 18 liver/kidney, 7 liver/pancreas, 1 liver/small bowel, 2 liver/kidney/heart, and 1 liver/kidney/pancreas. Among the 52 centers reporting at least 1 liver transplant during this time period, 34 (65%) performed less than 20 procedures and only 7 (13%) performed at least 50 transplantations. Sixty-three percent of the donors were male; 63% were less than 25 years of age and in 72% the cause of death was motor vehicle accidents, gunshot wounds, or cerebrovascular accidents. Recipients were older than donors, 37% above age 45. About 25% of the recipients required intensive care or life support. The majority suffered from cirrhosis of cholestatic, autoimmune, viral, alcoholic, or unspecified etiology. The 6-month cumulative survival following OLTX was 76%, and the 6-month retransplant-free survival rate was 69%. Survival rates at 1 year were 72% and 64%, respectively. Factors associated with patient survival were diagnosis of liver disease and work (UNOS) status. Patients with fulminant liver failure or malignancies had the poorest survival, and patients with cholestatic cirrhosis or other cirrhosis had the best.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The impact of purposeful sharing by HLA matching in the South Eastern Organ Procurement Foundation (SEOPF).

A voluntary system was created to foster early sharing of well-matched organs between like-minded renal transplantation programs. In the two historic periods 1982-85 and 1985-86, sharing programs (Category I & II) and nonsharing programs (Category III) had similar graft survival. In the study period 1986-88, graft survival improved in Category I and II programs and was unchanged in Category III programs. Highly sensitized recipients in sharing programs had an incremental gain of 15.0%, patients receiving multiple grafts 12.6%. Grafts derived from local donors and transplants in less sensitized patients also were improved but for less obvious reasons. The implementation of this study was followed by a slight decrement in delayed graft function. It is our conclusion that early graft sharing can result in improved overall early graft survival.

Graft Survival↗

The effect of the incubation temperature on the cleavage rate of mouse embryos in vitro.

We have studied the effect of an elevated incubation temperature on the in vitro cleavage rate of one- and two-cell mouse embryos. Two-cell embryos demonstrated a significantly higher rate of cleavage when incubated at 39 degrees C as compared to 37 or 41 degrees C. When recovered at the one-cell stage, the difference in cleavage rate between the groups incubated at 37 and 39 degrees C did not reach significance. While the morphology of the embryos incubated at 37 degrees C did not differ from that of the embryos incubated at 39 degrees C in either group, a significantly higher rate of degeneration was noted in the group of two-cell embryos incubated at 41 degrees C. These findings may apply to the human in vitro fertilization and embryo transfer system (IVF-ET), where the existing "lag" between embryo and endometrium could be narrowed if embryo cleavage rates could be accelerated. Further documentation of the normality of these "advanced" embryos is required.

Animals↗

Impact of recurrent otitis media on middle ear function, hearing, and language.

Whether recurrent otitis media in infants and young children is followed by delayed language development was addressed by following 210 normal subjects longitudinally through the first 2 years of life with pneumatic otoscopy and tympanometry performed at every physician encounter. Otitis accounted for 26% of the medical visits. One hundred fifty-six of these children had speech and hearing evaluation at 2 years of age. Thirty percent of the children with recurrent otitis media had a mild or moderate hearing loss. However, after multiple speech and language tests, we could not identify a delay in language acquisition in the otitis-prone children. At 3 to 4 years old, 36 children, including nine with a hearing loss at 2 years of age, were retested; all nine had normal hearing. Recurrent otitis media induced a temporary decrease in hearing sensitivity demonstrable at 2 years of age, which appeared to resolve as the children matured and which was not associated with delay in language acquisition.

Child, Preschool↗

Antagonists for acute oral cadmium chloride intoxication.

An examination has been carried out on the relative efficacy of a number of chelating agents when acting as antagonists for oral cadmium chloride intoxication in mice. The compounds were administered orally after the oral administration of cadmium chloride at 1 mmol/kg. Of the compounds examined, several were useful in terms of enhancing survival, but by far the most effective in both enhancing survival and leaving minimal residual levels of cadmium in the liver and the kidney, was meso-2,3-dimercaptosuccinic acid (DMSA). Several polyaminocarboxylic acids also enhanced survival. The most effective of these in reducing liver and kidney levels of cadmium were diethylenetriaminepentaacetic acid (DTPA), trans-1,2-diaminocyclohexane-N,N,N'N'-tetraacetic acid (CDTA), and triethylenetetraminehexaacetic acid (TTHA). D-Penicillamine (DPA) was found to promote survival but also led to kidney cadmium levels higher than those found in the controls. Sodium 2,3-dimercaptopropane-1-sulfonate (DMPS) was as effective in promoting survival as DMSA but left levels of cadmium in the kidney and liver that were approximately four times greater than those found with DMSA.

Administration, Oral↗

The effect of zinc on the dithiocarbamate-induced mobilization of cadmium deposits in mice.

In comparison with similar experiments in which no zinc acetate was used, the addition of small amounts of zinc acetate to sodium N-methyl-N-dithiocarboxyglucamine produces a significant increase in the amount of cadmium mobilized from the liver and kidneys of mice loaded ip with 10 mg CdCl2.2.5H2O/kg 2 wk prior to the initiation of treatment. Neither treatment results in the transport of significant amounts of cadmium to the brain. The injection of zinc acetate alone did not produce this effect. Experiments in which zinc acetate in drinking water was administered to cadmium-loaded animals showed that the liver and kidney cadmium levels were significantly increased, presumably via zinc-mediated processes in which cadmium from other organs was mobilized to the liver and kidneys.

Acetates↗

Organ sharing for good HLA-A,B, and DR matching improves cadaver renal graft survival in SEOPF: retrospective and prospective studies considering delayed graft function, race, center effects, cyclosporine, and other factors.

1. HLA matching is associated significantly with factors including CsA use, ALS use, recipient race, prior graft loss, presensitization, preservation time and most strongly, with organ sharing. However, HLA match is not directly associated with delayed graft function. 2. By univariate and multivariate analyses, good HLA matching provides significant benefits in graft survival regardless of CsA use, organ source or other potentially confounding factors. 3. HLA-A,B, and DR matching have independent and essentially equivalent benefits on graft survival in CsA-treated patients, whereas HLA-A,B matching has a greater benefit in non-CsA-treated patients. 4. Organ sharing, per se, provides no direct detrimental effect on graft survival by univariate or multivariate analysis. 5. By multivariate and univariate analyses, shared/well-matched kidneys provide significantly better graft survival than local/poorly matched kidneys. 6. Delayed graft function is associated in a complex relationship with organ sharing, prior graft failure, presensitization, and CsA use. 7. The increased rate of delayed graft function associated with organ sharing is overcome by the benefit of good HLA matching. 8. Since April 1986, purposeful organ sharing at SEOPF centers for good HLA matching has been associated with improved graft survival, especially in patients at high risk due to presensitization or prior graft failure.

Actuarial Analysis↗

The effect of random measurement errors on kinetic transport parameter estimation.

Saturation kinetics experiments, in which uptake U of a substance across a transport barrier is measured as a function of initial concentration difference C, are used to describe transport of nutrients. Many such processes are characterized by low- and high-affinity systems in which kinetic parameters Vmax and Km differ by orders of magnitude. Transformations of equations to straight-line relationships between U and C are popular methods of parameter estimation. The aims of this study are (1) to show effects of random errors in U measurement on Vmax and Km estimation in a two-affinity process under several transformations: Lineweaver-Burk (1/U vs. 1/C), Hanes (C/U vs. C), Eadie-Hofstee (U/C vs. U), and Wolff (U vs. U/C), and (2) to indicate strategies for minimizing effects of errors. Two transport properties will illustrate: an ideal process of low- (Vmax = 100, Km = 10) and high-affinity (Vmax = 1, Km = .1) systems to which random error is added, and experimental uptake of 5-methyltetrahydrofolic acid by isolated hepatocytes.

Age Factors↗

An analysis of ambulance accidents in Tennessee.

In an effort to improve our program for ambulance crash and related injury prevention, we analyzed 102 consecutive ambulance accidents. Incidents reported included those that resulted in human injury or in which property damage exceeded $200. Multiple logistic regression was used to determine the association between circumstances reported at the time of the accidents and the risk of injury. Twenty-nine accidents contributed to a total of 65 injured victims, with one death. The variable most strongly associated with the probability of an injury-accident was use of a passenger restraint device. Darkness and occurrence at an intersection were variables showing increased risk, but were not statistically significant. The interaction of variables did not have a combined influence on the incidence of injury. The mean delay to hospital care after an accident was 9.4 minutes. Based on our data, we conclude that passenger restraints for both ambulance attendants and passengers should be mandatory, and we suggest that traffic signals be strictly heeded at intersections and speed limits in urban settings be obeyed.

Accidents, Traffic↗

Ethanol inhibits human and hamster sperm penetration of eggs.

The effect of alcohol on the fertilizing ability of both human and hamster spermatozoa was examined by an in vitro fertilization assay using hamster ova. Spermatozoa were incubated in capacitating media for 3 hr (hamster sperm) and 4 hr (human sperm). Hamster ova were inseminated with preincubated sperm and were examined after 2 to 3 hr. Ethanol was added to the capacitating media at concentrations of 25, 50, 100, 200, and 400 mg%. Fertilization of zona-free hamster eggs by human spermatozoa was reduced from 49.6% in no alcohol to 16.7% in 400 mg% ethanol. Fertilization of hamster eggs by hamster sperm revealed a reduction from 63.6% to 33.7% in cumulus-intact eggs and from 65.8% to 10.8% in cumulus-free eggs in the presence of ethanol at 400 mg%. Hamster sperm acrosome reaction was reduced from 47% to 12%. When these hamster sperm with reduced acrosome reaction were placed with zona-free hamster eggs, the 100% fertilization rate was not reduced; however, the fertilization index, which reflects the number of swelling sperm heads per egg, was reduced from 8.5 to 1.8. This suggests that as little as 12% of the sperm with an acrosome reaction is sufficient to fertilize 100% of the zona-free eggs. If ethanol was added to the insemination media only, there was no inhibition of fertilization by human sperm or hamster sperm that had been previously capacitated in an ethanol-free media. Removal of the ethanol from the preincubated sperm produced fertilization at control levels; thus the inhibitory effect is reversible. These results indicate that ethanol may affect fertilization by an inhibition of the capacitation and/or acrosome reaction process.

Acrosome↗

Combination clomiphene citrate/human menopausal gonadotropin stimulation protocols for in vitro fertilization-embryo transfer.

Various protocols have been utilized for stimulation of multiple ovarian follicles in patients undergoing in vitro fertilization-embryo transfer (IVF-ET). Previous studies have suggested that the combination of clomiphene citrate (CC) and human menopausal gonadotropins (hMG) is superior to either CC or hMG alone in terms of follicular development, oocyte recovery, and embryo transfer. However, no significant increase in viable pregnancy rates has been reported with any of the protocols. This report examines five different CC/hMG protocols. While differences were seen in terms of serum estradiol response and fertilization rates of mature oocytes among the various protocols, no significant differences were found in terms of follicular development, oocyte recovery, embryo transfer, or pregnancy. The pregnancy rate in IVF-ET appears unaffected by variations in the dose and timing of CC and hMG in a combination protocol.

Adult↗

Follicular fluid transferrin levels in preovulatory human follicles.

There is transferrin-like protein present in the follicular fluid of stimulated ovarian cycles. The transferrin concentration correlates with the follicular morphologic maturity and steroidogenesis, varies among follicles, and often exceeds serum concentrations. An intermediate range of transferrin concentration is associated with the highest likelihood of oocyte fertilization in vitro. The biological significance of these observations may relate to an optimum degree of follicle maturation.

Body Fluids↗