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Biomedical subjects

R S Williams

Publications and source records attributed to R S Williams.

At least 127 records · Page 7Linked to original sources
PubMed1994

How far to pass a nasogastric tube? Particular reference to the distance from the anterior nares to the upper oesophagus.

The length of the nasogastric tube inserted into a patient is frequently ill-considered. If an inappropriate length of tubing is passed this may result in feeding difficulties or inadequate aspiration of gastric contents. This study assessed the optimal length by assuming that the oesophagus is 25 cm long and that the tip of a nasogastric tube should lie 10 cm below the gastro-oesophageal junction. The portion of tubing from the anterior nasal spine to the cricopharyngeus was calculated by superimposing a Ryles tube over a soft tissue lateral neck radiograph. Two hundred and forty cases were reviewed by three independent observers. The median distance was found to be 21 cm. It is recommended that nasogastric tubes are marked at 56 cm and this point be secured level with the nasal vestibule.

Enteral Nutrition↗
PubMed1994

The passage of Florida's Statute on Assisted Reproductive Technology.

Until 1993, there were no statutes in the United States covering gestational surrogacy contracts, disposition of stored embryos and gametes, parentage of children born from donated gametes and embryos, and the inheritance rights of cryopreserved embryos of deceased donors. In March 1993, the Florida Assisted Reproductive Technology Act was passed to address some of these issues and to minimize the expense and emotional cost of related courtroom proceedings. Authors of the bill believed that motherhood of a newborn in the eyes of the law should be determined by two factors: genetic inheritance and the original intent of the woman to become the parent of record. The bill included the assumption that, in the cases of children born of gestational surrogacy, the commissioning genetic parents would be the "natural parents" of the child. Some of the reasons for legislative success of the statute include: 1) clear need for statutory guidance in cases involving reproductive technology, 2) relevance of the issue to cost containment (ie, judicial costs) in an era of health care reform, 3) careful use of scientific terminology and the support of the medical community, 4) involvement of a skilled legislative team, 5) participation of physician specialists in the development of the bill (ie, practicing gynecologists in assisted reproductive technology programs), 6) participation of the State of Florida legislative staff, and 7) consultation with appropriate lobbying groups (eg, Florida Catholic Conference). The successful legislative process that was followed to achieve passage of this bill can serve as an example for other states to emulate.

Female↗
PubMed1994

Localization of transforming growth factor beta isoforms TGF-beta 1, TGF-beta 2, and TGF-beta 3 in surgically induced pelvic adhesions in the rat.

OBJECTIVE: To investigate the presence and cellular distribution of transforming growth factor (TGF)-beta s in surgically induced pelvic fibrous adhesions in rat uterine horns subjected to burn, crush, and debridement injury. METHODS: Thirty injured and 20 uninjured rats were treated postoperatively with intraperitoneal administration of either 2 micrograms/mL of recombinant human TGF-beta, 10 micrograms/mL TGF-beta neutralizing antibody, or phosphate-buffered saline + 500 micrograms rat serum albumin for 5 consecutive days. The intact (uninjured) and fibrous tissues were analyzed immunohistochemically for the presence of TGF-beta s using polyclonal antibodies to TGF-beta s 1-3. RESULTS: The intact peritoneum immunostained with a lower intensity than fibrous adhesive tissues for TGF-beta 1, TGF-beta 2, and TGF-beta 3. The immunoreactive TGF-beta s were present in fibroblasts, inflammatory cells infiltrated into the fibrous adhesion, and endothelial and smooth-muscle cells of the arterioles. In the uterine tissue at the site of injury, the following immunostained for TGF-beta s: uterine serosal tissue, myometrial smooth-muscle cells, endometrial luminal and glandular epithelial cells, and inflammatory cells. However, endometrial stromal cells did not immunostain for TGF-beta s. There were no substantial differences in immunostaining intensities of fibrous adhesive tissues in the TGF-beta group, neutralizing TGF-beta antibody group, and the controls. CONCLUSION: The data suggest that TGF-beta s may play a role in the formation and maintenance of fibrous adhesions following intraperitoneal injury.

Animals↗
PubMed1994

Localization of transforming growth factor beta isoforms TGF-beta 1, TGF-beta 2, and TGF-beta 3 in surgically induced endometriosis in the rat.

OBJECTIVE: To elucidate the presence and cellular distribution of transforming growth factor beta (TGF-beta) in surgically induced endometriosis in the rat. METHODS: Endometriosis was induced by implanting pieces of uterine fragments in the mesenteric region adjacent to a blood vessel for a period of 4-6 weeks. The endometrial implants were removed and processed for immunohistochemical localization using isoform-specific polyclonal antibodies to TGF-beta 1, TGF-beta 2, and TGF-beta 3. RESULTS: All the cell types in the endometrial implants with the exception of stromal cells immunostained for TGF-beta 1 and TGF-beta 3, but not TGF-beta 2. The inflammatory cells that were infiltrated among endometriotic stromal cells and implant-associated cysts contained the highest immunostaining intensity for TGF-beta s 1-3, followed by luminal and glandular epithelial cells, fibroblasts of the fibrous adhesions, and endothelial and smooth-muscle cells of arterioles. The immunostaining intensity of TGF-beta 1 was substantially higher than that of TGF-beta 3 and TGF-beta 2, and intensity was similar to the endometrial tissue from cycling rats in diestrus II for TGF-beta 1 and estrus for TGF-beta 2 and TGF-beta 3. In the cycling rats, the order of immunostaining intensity in the endometrium was TGF-beta 1, TGF-beta 3, and TGF-beta 2, respectively, with a higher intensity in diestrus II and proestrus than in diestrus I and estrus. CONCLUSION: The results indicate that endometrial implants in surgically induced endometriosis contain immunoreactive TGF-beta s, which may imply a possible paracrine/autocrine role for the action of TGF-beta in the maintenance of viable endometriotic tissue and the development of fibrous adhesions associated with the implants.

Animals↗
PubMed1994

Successful implementation of a regional in vitro fertilization program.

In vitro fertilization and other assisted reproductive technologies are becoming widely accepted modalities of treatment for infertile couples. Like other modern technologies, in vitro fertilization requires specially trained physicians and scientists who need specially dedicated equipment and space. In addition, patients having the procedure must undergo timely laboratory tests and sonographic evaluations for monitoring follicular maturation. To make in vitro fertilization available to patients in north central Florida, the Division of Reproductive Endocrinology and Infertility of the Department of Obstetrics and Gynecology at the University of Florida College of Medicine in Gainesville established a system that utilizes local resources in three distant locations. Patients in an assisted reproductive technologies cycle are monitored at satellite locations but coordinated through the University of Florida in vitro fertilization team. Oocyte retrieval, laboratory handling of gametes and embryo transfer are performed at the Shands Teaching Hospital in Gainesville. Micromanipulation for severe male factor infertility and oocyte donation are available when needed. Preimplantation diagnosis for genetic conditions is under development. The ongoing pregnancy and delivery rate is 21% per cycle initiated from July 1, 1992, to July 3, 1993, 62% above the reported national pregnancy rate for 1991. This program may be a useful model for the development of collaborative efforts in delivering highly complex medical services to large populations.

Academic Medical Centers↗
PubMed1993

Sensitive liquid chromatographic method for the determination of a specific M1 agonist, LY246708, an investigational agent with potential for the treatment of Alzheimer's disease, in human plasma.

A reversed-phase HPLC method is reported for the determination of a new M1 agonist, LY246708, in human plasma. The compound and an internal standard were extracted from plasma with hexane at basic pH. The organic extract was evaporated to dryness and the residue was reconstituted with mobile phase [0.5% diethylamine (pH 3, adjusted with phosphoric acid)-acetonitrile (70:30, v/v)]. The analytes were separated from endogenous substances on a Zorbax CN column; the effluent was monitored by measuring its absorbance at 296 nm. The limit of quantification was determined at 1.5 ng/ml and the response was linear from 1.5 to 20 ng/ml. Validation studies showed the method to be both repeatable and reproducible. Its robustness was demonstrated by transfer between analytical laboratories and continued use in support of pharmacokinetic studies and therapeutic monitoring of the compound.

Alzheimer Disease↗
PubMed1993

Gradients of transgene expression directed by the human myoglobin promoter in the developing mouse heart.

Prior studies using transient transfection assays in cultured avian and murine skeletal myotubes indicate that the proximal 2-kb segment of the 5' flanking region of the human myoglobin gene contains transcriptional control elements sufficient to direct muscle-specific and developmentally regulated expression of reporter genes. To examine the function of the human myoglobin gene promoter during development of skeletal and cardiac myocytes in the intact animal, a 2.0-kb myoglobin gene upstream fragment was fused to an Escherichia coli lacZ reporter gene and injected into fertilized mouse oocytes. beta-Galactosidase (beta-gal) activity was detected selectively in cardiac and skeletal myocytes of fetal and adult transgenic mice. A distinctive spatial pattern of myoglobin promoter activity was observed in fetal hearts: beta-gal staining was more pronounced within the left ventricular subendocardium than within the subepicardium and was essentially undetectable in the ventricular trabeculae or atria. Expression of endogenous myoglobin mRNA and protein, assessed by in situ hybridization and immunohistochemistry, demonstrated a similar spatial pattern. In contrast, hearts from adult transgenic mice demonstrated essentially homogeneous expression of beta-gal and of endogenous myoglobin mRNA and protein throughout the myocardium, including the trabeculae and atria. These data indicate that the 2.0-kb upstream region of the human myoglobin gene includes cis-acting regulatory elements sufficient to direct transgene expression during murine cardiac development that is myocyte-specific and responsive to positional cues in a similar manner to the endogenous myoglobin gene.

Age Factors↗
PubMed1993

Mouse sperm-egg interaction in vitro in the presence of neem oil.

In vitro evidence is presented showing toxicity of neem oil on sperm-egg interaction in mouse. Cumulus oophorus-enclosed ova, inseminated with capacitated spermatozoa, were cultured in 1 ml of in vitro fertilization (IVF) medium and overlayered by 1 ml of different concentrations of neem oil (1, 5, 10, 25, 50 and 100%) for IVF duration of 4h. At the end of incubation, ova were allowed to grow in neem oil-free culture medium and assessed for fertilization, first cleavage (2-cell formation) and blastocyst formation in vitro at 4-14h, 24h and 108h post-insemination respectively. The study showed that the presence of neem oil at concentrations of 10, 25 and 50% caused inhibition of IVF in a dose-dependent manner. The toxic effect of exposure of 25 and 50% neem oil was further carried over to the first cleavage of the resulting fertilized ova and the toxic effect of 5, 10, 25 and 50% was carried over to the blastocyst formation from the resulting fertilized ova when grown in neem-oil free culture medium. A total of 94.1% inhibition of 2-cell formation and 100% inhibition of blastocyst formation from the inseminated ova was observed in 50 and 25% neem oil-treated groups respectively. Neem oil at 100% concentration caused 100% degeneration of ova at 1h of sperm-ova coculture. The study showed a direct toxic effect of neem oil on sperm-egg interaction in vitro and encourages research investigations of this herbal product as a pre-coital contraceptive.

Animals↗
PubMed1993

Induction of immediate-early genes by angiotensin II and endothelin-1 in adult rat cardiomyocytes.

OBJECTIVE: Few molecular signals for induction of myocardial hypertrophy have been identified. This study was carried out to investigate the action of angiotensin II and endothelin on the growth- and differentiation-related genes Egr-1 (early growth response gene 1) and c-fos in isolated adult rat cardiomyocytes. METHODS: Cardiac myocytes from male Wistar-Kyoto rats were isolated and incubated with angiotensin II and endothelin-1 in Dulbecco's modified Eagle's medium. RNA was isolated and blotted, and densitometric analysis was performed. All experiments were repeated at least three times. RESULTS: Endothelin-1 (10(-7) mmol/l) induced a 20-25-fold rise in Egr-1 messenger RNA within 15 min. This effect was dose-dependent. c-fos was induced 10-20-fold within 15 min with similar dose-response characteristics. Angiotensin II also induced Egr-1 and c-fos with kinetics similar to endothelin but a cofactor from fetal calf serum was needed for full c-fos expression. The protein kinase C activator phorbol 12-myristate 13-acetate also induced Egr-1. CONCLUSIONS: The results identify Egr-1 and c-fos as target genes for the action of endothelin and angiotensin II in the adult myocardium suggesting that induction of the genes may be part of the signal transduction pathway for angiotensin II and endothelin in the myocardium.

Angiotensin II↗
PubMed1993

RNA subunit of mitochondrial RNA-processing enzyme is induced by contractile activity in striated muscle.

A small RNA encoded within the nucleus of yeast and mammalian cells is an essential subunit of a mitochondrial RNA-processing endonuclease (RNase MRP) that generates primers for mitochondrial DNA (mtDNA) replication. We examined expression of MRP-RNA in specialized subtypes of mammalian striated muscles that differ markedly in respiratory activity and in muscles subjected to chronic stimulation via the motor nerve, a potent stimulus to mitochondrial biogenesis. MRP-RNA was more abundant in mitochondria-rich cardiac and slow-twitch skeletal muscles than in glycolytic fast-twitch skeletal muscles. Forced contractile activity resulting from nerve stimulation increased expression of MRP-RNA by 3.5-fold within the first day and by 14-fold within 14 days. Changes in abundance of MRP-RNA preceded but otherwise occurred in parallel to changes in specific activity of citrate synthase, a marker of mitochondrial proliferation shown previously to correlate with mtDNA copy number in this model. Another small RNA (U1) also was induced transiently (1-3 days) by nerve stimulation, but such changes were not sustained and were of less magnitude (< 4-fold) than changes in MRP-RNA. These findings are consistent with the hypothesis that MRP-RNA may have a regulatory function with respect to mtDNA replication and mitochondrial biogenesis.

Animals↗
PubMed1993

Sequence elements required for transcriptional activity of the human myoglobin promoter in intact myocardium.

To define sequence elements required for myoglobin gene transcription in the intact heart, we examined the expression of a reporter gene under the control of a 380-bp upstream segment (-373 to +7) from the human myoglobin gene in transgenic mouse embryos and after gene transfer into left ventricular myocardium of adult rats. This proximal upstream region was sufficient to direct expression of luciferase selectively in cardiac and skeletal muscle of mouse embryos and to recapitulate the pattern of expression of the endogenous mouse myoglobin gene. This same upstream region was transcriptionally active after injection of plasmid DNA into the left ventricular wall of adult rats. Point mutations within two evolutionarily conserved sequence elements--a cytosine-rich (CCAC-box) motif and an A+T-rich (A/T) motif--severely impaired transcription within the intact heart. Nuclear extracts from neonatal cardiomyocytes contain protein factors that bind to each of these elements in a sequence-specific manner. We conclude that combinatorial interactions between the cognate DNA binding factors that recognize these motifs are necessary for transcriptional activity of the myoglobin upstream region in cardiac muscle.

Animals↗
PubMed1993

Human heat shock protein 70 (hsp70) protects murine cells from injury during metabolic stress.

Expression of heat shock protein 70 (hsp70) is stimulated during ischemia, but its proposed cytoprotective function during metabolic stress has remained conjectural. We introduced a human hsp70 gene into mouse 10T1/2 cells and assessed the susceptibility of these cells to injury in response to conditions that mimic ischemia. Transiently transfected cells, in the absence of stress, expressed human hsp70 to levels equal to or greater than those induced by heat shock, as assessed by RNAse protection, immunoblot, and immunohistochemical analyses. By comparison to cells transfected with a control plasmid, cells expressing the human hsp70 transgene were resistant to injury induced by glucose deprivation and inhibition of mitochondrial respiration. These results provide direct evidence for a cytoprotective function of hsp70 during metabolic stress.

Animals↗
PubMed1993

Evidence for neuronal degeneration and dendritic plasticity in cortical pyramidal neurons of Huntington's disease: a quantitative Golgi study.

Aided by a computer microscope, the Eutectic Neuron Tracing System, we performed a quantitative analysis of 59 rapid Golgi-impregnated pyramidal neurons from the third and fifth prefrontal cortical layers (P III and P V neurons) in tissue sections obtained from seven autopsied Huntington's disease (HD) patients (grades 2 through 4) and 59 corresponding cells from eight age-matched control cases. Relative to controls, P III HD neurons had a significant increase in the number of primary dendritic segments arising from soma, total dendritic length, and total surface area. The HD cells also had significantly more dendritic branches at three intervals of measurement in a Sholl diagram (100 microns, 200 microns, and 400 microns from the soma) and a significant increase in the number of dendritic branching points. The dendritic spine density in P III HD neurons was comparable to that of control subjects and significantly lower than that in P V HD cells. The total number and the total density of dendritic swellings were significantly increased in both P III and P V neurons, being most numerous in grades 2 and 3 cases. Rare withered cells with shrunken dendritic trees, harboring few spines and numerous varicosities on their dendritic shafts, were present in HD but not in control cases. Thus, while a small fraction of prefrontal cortical pyramidals degenerates in HD, the plasticity of the remaining pyramidal neurons, evidenced as an orderly augmentation of the dendritic tree, may represent a compensatory response sufficient to maintain relatively normal metabolic function of the cortex in most adult-onset cases.

Adult↗
PubMed1993

Intrauterine insemination. Effect of wash media on pregnancy rates and sperm motility.

Testyolk Buffer has been shown to enhance sperm penetration in hamster penetration assays and increase fertilization of oocytes in in vitro fertilization. Based on these findings, we compared pregnancy rates and sperm motility in intrauterine inseminations done with sperm samples washed and resuspended in Ham's F10 as compared with Testyolk buffer. Charts were reviewed retrospectively from 1,098 husband and donor intrauterine inseminations performed at the University of Florida. Data were analyzed using life table analysis and the curves compared with the Mantel-Haenszel statistical test. In addition, sperm motility in fresh sperm was observed in samples incubated in Testyolk or Ham's F10, with motility counts performed at 0, 6 and 24 hours. Four hundred ninety-two Testyolk cycles and 579 Ham's F10 cycles were compared, with cumulative pregnancy rates at one year of 53% and 44%, respectively (P = .58). With donor sperm, 229 cycles with Testyolk and 314 cycles with Ham's F10 had cumulative pregnancy rates of 68% and 48%, respectively (P = .52). With husband insemination, 264 Testyolk and 253 Ham's F10 cycles had pregnancy rates of 37% and 35%, respectively (P = .23). Fresh sperm motility in 22 samples compared at 0, 6 and 24 hours in Ham's F10 (76%, 67.8%, 56.6%) versus Testyolk (76%, 67.7%, 58.8%) revealed no significant differences. There was also no difference in total motile sperm inseminated and postwash motility in 1,098 samples with Testyolk versus Ham's F10. This study demonstrates that there is no enhanced pregnancy rate or increased sperm motility when sperm are treated with Testyolk Buffer instead of Ham's F10.

Adult↗
PubMed1992

Benefits and risks of oral contraceptive use.

As a general rule, the lowest-dose oral contraceptive should be prescribed that minimizes side effects while maintaining contraceptive protection. A woman who experiences mild side effects should be encouraged to tolerate symptoms for three menstrual cycles before a decision is made to change the prescription. Compliance may also be improved by informing women of the noncontraceptive health benefits of oral contraceptives: less menstrual blood loss and a lower incidence of menorrhagia, irregular bleeding, benign breast disease, endometrial cancer, dysmenorrhea, ovarian cysts or tumors, and salpingitis. Adequate patient education and supportive counseling are key factors in patient satisfaction and hence compliance.

Age Factors↗
PubMed1992

Substance P in peritoneal fluid.

Substance P is a neuropeptide that has been identified in the ovary, fallopian tube, uterus, and vagina and in the hypothalamic-pituitary axis in both an animal model and human ovaries. We sought to determine if substance P is present in peritoneal fluid and, if so, whether it correlated with the cause of infertility. Its presence was determined by radioimmunoassay in the peritoneal fluid of 66 patients undergoing diagnostic laparoscopy for clinical indications related to infertility. Total volume of peritoneal fluid and cycle day were recorded; patients were evaluated in groups according to diagnosis: endometriosis (n = 24), pelvic adhesions (n = 18), and normal controls (n = 24). The level of substance P (mean +/- SEM) was 122 +/- 19 pg/ml for endometriosis and 130 +/- 19 pg/ml for pelvic adhesions. These values were not significantly different from the normal controls (130 +/- 25 pg/ml). There was no significant difference in levels between follicular and luteal phase of the menstrual cycle. We conclude that substance P is present normally in peritoneal fluid and that its levels are not affected by pelvic endometriosis or adhesions.

Ascitic Fluid↗