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Biomedical subjects

K Waite

Publications and source records attributed to K Waite.

18 recordsLinked to original sources
PubMed2001

Daily access to pasture turnout prevents loss of mineral in the third metacarpus of Arabian weanlings.

Seventeen Arabian weanlings were used to determine the influence of housing on third metacarpal bone mass. Animals were separated into three treatment groups: Pasture (n = 6), Stall (n = 5), and Partial-Pasture (n = 6). Radiographs of the left third metacarpus were taken every 28 d to determine radiographic bone aluminum equivalence (RBAE). Serum was collected every 14 d and analyzed for osteocalcin, carboxyterminal telopeptide of type I collagen (ICTP), and keratan sulfate. Hip and wither height, BW, and cannon circumference were measured every 28 d. Lateral RBAE in the pastured group increased linearly from d 0 to d 56 (P = 0.001). In the Pasture group, total RBAE increased from d 0 to 56 (P = 0.05) and medial RBAE tended to increase from d 0 to d 28 (P = 0.06). The Partial Pasture group increased from d 0 to 56 in medial (P = 0.02) and tended to increase in total RBAE (P = 0.08). Although the Stall group demonstrated an increase in total RBAE from d 0 to 56 (P = 0.04), the Partial Pasture group tended to have greater total RBAE than the Stall group at d 28 (P = 0.08), and the Pasture group had greater lateral RBAE at d 28 (P = 0.005) and 56 (P = 0.007) than did the Stall group. At d 28, medial RBAE was greater in the Pasture (P = 0.003) and Partial Pasture (P = 0.05) groups than in the Stall group. Pasture and Stall groups tended to decrease in osteocalcin (P = 0.06), whereas Partial Pasture weanlings decreased (P = 0.01) from d 0 to 56. All treatment groups decreased from d 0 to 56 in ICTP (P < 0.01). Pastured weanlings decreased from d 0 to 42 in serum keratin sulfate (P < 0.05), whereas the Stall group decreased from d 0 to 56 (P = 0.05). All treatment groups increased in wither height (P < or = 0.01), hip height (P < or = 0.001), and BW (P < or = 0.01). Both the Pasture and Partial Pasture weanlings demonstrated greater cannon circumference than Stall weanlings on d 28 (P < or = 0.05) and 56 (P < or = 0.005). These data demonstrate that pasture rearing or 12-h daily turnout is beneficial to maintaining and increasing bone mineral content in weanling Arabian horses.

Animal Nutritional Physiological Phenomena↗
PubMed1999

Transcriptional activation of the murine CTP:phosphocholine cytidylyltransferase gene (Ctpct): combined action of upstream stimulatory and inhibitory cis-acting elements.

CTP:phosphocholine cytidylyltransferase plays a key role in regulating the rate of phosphatidylcholine biosynthesis. However, the proximal regulatory elements for the gene (Ctpct) that encode this enzyme and the cognate transcription factors involved have not been characterized. Ctpct promoter activities were deduced from promoter deletion constructs linked to a luciferase reporter and transiently transfected into C3H10T1/2 and McArdle RH7777 cells. Positive regulatory elements were located between -130 and -52 bp from the transcription start site. Basal expression resided downstream between -52 and +38 bp. DNase I protection and electromobility-shift assays indicated that Sp1-related nuclear factors bind to a stimulatory, a possible inhibitory and minimal promoter element. Gel-shift assays confirmed that all three regulatory regions bound Sp1. Sp1 was further implicated when Sp1-deficient Drosophila cells were co-transfected with promoter-reporter constructs and an Sp1 construct. DNase I assays also indicated that the Ap1 binding elements could be occupied in the proximal activator and minimal promoter regions. Gel-shift assays demonstrated that the distal activator region could bind Ap1 and an unknown transcription factor. We conclude that Sp1, Ap1 and an unknown transcription factor have important roles in regulating expression of the Ctpct gene.

Animals↗
PubMed1999

A pilot study of daily subcutaneous interleukin-10 in patients with chronic hepatitis C infection.

The Th1/Th2 cytokine balance is important in persistence of infection and liver injury in chronic hepatitis C. The aim of this study was to administer the anti-inflammatory cytokine, recombinant human interleukin-10 (rHuIL-10), for 28 days in patients with chronic hepatitis C and to assess the safety and measure the effect on alanine aminotransferase (ALT, a marker of hepatic inflammation) levels and serum hepatitis C virus (HCV) RNA values. Three treatment-naive and 13 interferon (IFN) nonresponder patients (total 16 patients) with compensated chronic HCV infection were enrolled in this study. Patients were randomized to receive rHuIL-10 at a dose of 4 or 8 microg/kg/day as a single daily subcutaneous injection for 28 days. ALT values and serum HCV RNA were measured at days 0, 1, 3, 8, 15, 22, and 28 during therapy and at follow-up 2 and 4 weeks after cessation of the 4-week treatment period. ALT values normalized in 9 of 16 patients during therapy and remained normal until the end of treatment in 8 patients. The decreases in ALT values occurred in both the 4 microg and 8 microg dosage groups and were seen in both IFN naive and nonresponder patients. Mean ALT values fell significantly during the study period but usually returned to pretreatment levels by the end of the 4-week follow-up period (p < 0.05). HCV RNA concentrations did not vary significantly during or after therapy. (No patient had either an increase or a decrease in HCV RNA levels of > or =1.5 log during the study.) The drug was well tolerated, with no adverse symptoms noted. Platelet counts fell transiently to 73,000 and 63,000 in 2 patients. No other toxicity was observed, and no patients discontinued therapy. In chronic hepatitis C, short-term therapy with IL-10 was well tolerated and caused transient normalization of ALT values in 50% of patients, which returned to pretreatment levels on cessation of treatment. There were no significant changes observed in serum HCV RNA concentrations during the study. These immunomodulatory effects are similar to those observed with ribavirin monotherapy in chronic hepatitis C. Further study of rHuIL-10 alone or in combination with antiviral agents in chronic hepatitis C is warranted.

Alanine Transaminase↗
PubMed1997

Intracerebroventricular neuropeptide Y acutely influences glucose metabolism and insulin sensitivity in the rat.

Acute administration of neuropeptide Y(NPY) into the hypothalamus and third cerebral ventricle (ICV) increases respiratory quotient, reduces energy expenditure and increases circulating, insulin, glucagon and corticosterone. Therefore, it is likely that hypothalamic NPY has acute effects on the metabolism of fuels, such as glucose. To test this hypothesis, we determined if ICV infusion of NPY influences glucose metabolism and its sensitivity to insulin in conscious, unrestrained rats, not given access to food. Glucose turnover was 4.7+/-0.3 mg/min, 45-55 min after ICV NPY was administered at 3 microg/h vs 3.7+/-0.2 (P<0.05) for ICV saline. In a time course study, glucose turnover was significantly increased 30 min, and remained elevated at 50 min after starting a similar ICV NPY infusion. In neither study was plasma glucose, insulin, glucagon or corticosterone significantly affected by ICV NPY. During an hyperinsulinaemic euglycaemic clamp, the glucose infusion rate corrected for body weight and insulin concentration, M/I was 0.22+/-0.03 for NPY vs 0.36+/-0.05 mg min(-1) kg(-1) microU(-1) ml (P<0.05) for saline. NPY treatment prevented the decline in glucose production rate but did not influence the rise in glucose disposal rate resulting from hyperinsulinaemia. It was concluded that ICV NPY rapidly stimulates glucose turnover by a mechanism that does not depend on changes in insulin, glucagon or corticosterone secretion. Furthermore, ICV NPY decreased insulin sensitivity by reducing the effect of insulin on glucose production but not on whole body glucose disposal.

Animals↗
PubMed1996

Intracerebroventricular neuropeptide Y produces hyperinsulinemia in the presence and absence of food.

Acute administration of neuropeptide Y into the hypothalamus or cerebral ventricles produces hyperphagia and hyperinsulinemia. However, it is not known to what extent the hyperinsulinemia depends on the food intake. Consequently, serum insulin and glucose, as well as food and water consumption, were measured over 3 h, following injection of 1-20 micrograms neuropeptide Y into the third ventricle of adult female rats. In the presence of food, 1-10 micrograms neuropeptide Y produced a dose-dependent increase in food and water intake and serum insulin. Insulin levels were closely correlated with the quantity of food ingested. In the absence of food, 1-20 micrograms neuropeptide Y produced a dose-dependent increase in water intake, whereas 1-5 micrograms produced a does-dependent increase in serum insulin. We concluded that ICV neuropeptide Y can stimulate insulin secretion even at low doses and this response does not completely depend on food intake.

Animals↗
PubMed1996

Some acute effects of intracerebroventricular neuropeptide Y on insulin secretion and glucose metabolism in the rat.

Acute administration of neuropeptide Y(NPY) into the hypothalamus and cerebral ventricles can stimulate insulin secretion in the absence of available food. However, the relationship of this effect to blood glucose and other hormones which regulate glucose metabolism remains unclear. The purpose of this study was to compare the effects of NPY injected into the third ventricle (ICV) on serum insulin, glucose, glucagon, corticosterone and non-esterified fatty acids. Studies were performed on conscious, unrestrained female rats, not given access to food. ICV NPY, 2 and 5 micrograms produced an increase in serum insulin and glucagon, while the 5 micrograms dose only increased plasma glucose transiently and increased non-esterified fatty acids for a longer period. Corticosterone was not affected by ICV NPY. The insulinaemic response to i.v. glucose, 0.5 g/kg was doubled by ICV NPY, 4 micrograms. The maximal insulin levels were 113 +/- 18 for ICV NPY versus 67 +/- 8 microU/ml for ICV saline-treated animals. The glycaemic response was not altered. The hypoglycaemic response to i.v. insulin, 0.15 U/kg was significantly attenuated by ICV NPY, 5 micrograms. We concluded that ICV NPY promotes insulin secretion in the absence of available food and may potentiate the insulinaemic response to hyperglycaemia. Furthermore, possibly through its effects on glucagon and non-esterified fatty acids, ICV NPY may decrease the ability of insulin to control glucose metabolism.

Animals↗
PubMed1996

Effects of gold thioglucose on neuropeptide Y messenger RNA levels in the mouse hypothalamus.

Elevated hypothalamic neuropeptide Y (NPY) expression is found in several rodent genetic models of obesity, but any association in nongenetic models of obesity is unclear. Consequently, we have measured NPY mRNA levels in the ventromedial hypothalamus of a well-characterized model of obesity, the gold thioglucose (GTG)-injected mouse. Fourteen days after injection (early stage), animals were hyperphagic but not obese, hyperglycemic, or overtly hyperinsulinemic. Ten weeks after treatment (late stage), animals were obese, markedly hyperinsulinemic, and hyperglycemic. In both the early and late stages, NPY mRNA levels were reduced in the arcuate nucleus of GTG-injected animals. Although overnight fasting doubled NPY mRNA levels in control animals, there was no change at either stage in GTG-injected animals. NPY mRNA levels in the deep layers of the cerebral cortex and in the dentate gyrus were not affected by GTG treatment or overnight fasting. We conclude that GTG treatment reduces the expression of NPY mRNA in the arcuate nucleus and that, therefore, increased hypothalamic NPY expression is unlikely to be an important factor causing the obesity and other metabolic changes found in this model.

Animals↗
PubMed1994

Lack of association between patients' measured burden of disease and risk for hospital readmission.

Identifying patients at increased risk for hospital readmission is important for clinicians, health policy-makers, hospital administrators, and researchers. We used a retrospective case-control design to compare the clinimetric properties of five validated indices that measure a patient's disease burden. The study was conducted on a random sample of patients discharged from the general medicine service at the Durham Department of Veterans Affairs Medical Center. Trained observers (two research assistants, one nurse, and two physicians) blinded to readmission status abstracted the required data elements from the medical record for three indices (Charlson, Kaplan-Feinstein, Index of Coexistent Disease). The hospital's computer provided data elements for two indices (Smith, adapted Charlson). Indices varied in the time required to complete, the ability to capture individual heterogeneity, and inter-observer variability. However, none of the indices discriminated among patients who did and those who did not have 6-month hospital readmissions. Factors other than summary scores derived from these indices should be used to identify patients at high risk for readmission.

Aged↗
PubMed1993

Effects of streptozotocin-induced diabetes mellitus and insulin treatment on neuropeptide Y mRNA in the rat hypothalamus.

Levels of neuropeptide Y and neuropeptide Y mRNA are increased in the arcuate nucleus of severely diabetic rats which may be the result of the associated marked hypoinsulinaemia. We hypothesised that if neuropeptide Y mRNA is regulated by physiological changes in circulating insulin, then the relatively minor changes in circulating insulin found in mild diabetes would also affect neuropeptide Y expression and its response to changing insulin levels should be rapid. Neuropeptide Y mRNA was quantified by in situ hybridisation through the rostral, mid and caudal levels of the arcuate nucleus of adult female rats. Neuropeptide Y mRNA was significantly increased at all three levels of the arcuate nucleus, 7 days after i.v. administration of 40 mg/kg streptozotocin. Neuropeptide Y mRNA was not further increased in the arcuate nucleus of animals given 50 mg/kg streptozotocin. In the former group, serum glucose was increased but insulin levels and body weights were the same as in control rats. In the 50 mg/kg streptozotocin group, serum glucose was further increased while serum insulin and body weight were reduced. In addition, neuropeptide Y mRNA was not altered in the hypothalamic dorsomedial nucleus or the thalamic reticular nucleus. When diabetic rats were treated for 20 h with s.c. insulin, there was decreased neuropeptide Y mRNA in the arcuate nucleus. We conclude that neuropeptide Y mRNA in the arcuate nucleus is responsive to small changes in circulating insulin levels and the response occurs within 20 h. These data support that circulating insulin may contribute to control of neuropeptide Y expression under physiological conditions.

Animals↗
PubMed1989

Topical iodine-containing antiseptics and neonatal hypothyroidism in very-low-birthweight infants.

The thyroid function of very-low-birthweight (VLBW; below 1500 g) infants admitted to neonatal intensive-care units was studied at two hospitals; one routinely used topical iodinated antiseptic agents and the other used chlorhexidine-containing antiseptics. Serial monitoring of urinary iodine excretion and serum thyrotropin and thyroxine levels was undertaken from birth for the first 4 weeks of life. Urinary iodine excretion rose dramatically in the 54 iodine-exposed infants and was up to fifty times greater than in the 29 non-exposed infants. Within 14 days, 25% (9 of 36) of the infants exposed to iodine had serum thyrotropin levels above 20 mIU/l, compared with none of the control group. The mean serum thyroxine level in these 9 infants (44.1 nmol/l) was significantly lower than that in exposed infants with normal thyrotropin levels (83.1 nmol/l) and in the non-exposed control group (83.0 nmol/l); thyroxine levels fell before serum thyrotropin rose. These disturbances in thyroid function correlated positively with urinary iodine excretion and hence iodine absorption. Thyroid function had returned to normal by the time of discharge from hospital. It is concluded that iodine absorption, from topical iodine-containing antiseptics, may cause hypothyroidism during a critical period of neurological development in the newborn infant. The routine use of iodine antisepsis in VLBW infants should be avoided because of this effect.

Administration, Topical↗
PubMed1986

Binding characteristics of thyroxin binding globulin in serum of normal, pregnant, and severely ill euthyroid patients.

Serum from normal, pregnant, and severely ill patients was stripped of endogenous thyroid hormones and diluted 1100-fold in barbital buffer. We then used it to study the binding characteristics of thyroxin binding globulin (TBG), noting significant differences in binding capacities among the groups. The mean (+/- SD) triiodothyronine/thyroxin ratio for binding capacity was 18 +/- 4 for normal subjects. The ratio was significantly increased in pregnant patients, 21 +/- 4 (p less than 0.05), and significantly lower in severely ill patients, 12 +/- 4 (p less than 0.05). When serum was diluted before assay, to give a uniform TBG concentration among groups, these apparent differences in binding characteristics were eliminated. It therefore is unlikely that different molecular species of TBG account for the variations in binding characteristics in these clinical states. Apparently, the distribution of thyroxin and triiodothyronine among the binding sites on TBG changes with variations in TBG concentration. This may explain the discrepancies observed in the concentrations of free thyroid hormones as estimated by various methodologies.

Binding, Competitive↗
PubMed1983

Plasma contamination accounts for thyroid hormone binding in nuclear protein extracts from human mononuclear cells.

Plasma protein contamination accounted for high affinity thyroid hormone binding to a nuclear protein extract from human blood mononuclear cells. The degree of contamination was directly related to the number of times the cells were washed before the nuclear protein was extracted. After three washes, no specific binding was detected. Plasma contamination was estimated to be 0.3-0.5 microliter/assay tube. The TBG concentration in this volume of plasma was consistent with the concentration of 0.2 micrograms/ml measured by RIA in the nuclear extract. Total specific binding of [125I] T4 and [125I] T3 can be attributed to plasma contamination, as 0.3 microliter of plasma gave identical binding. Furthermore, a TBG antiserum abolished specific T4 and T3 binding to the nuclear protein extract. These data are consistent with TBG being the major plasma contaminant. In fourteen normal, euthyroid subjects, the higher mean maximum binding capacity (MBC) for T4 (1.63 +/- 0.27 SD) compared to T3 (0.25 +/- 0.21 pmol/mg protein; P less than 0.001) and the same binding affinity (Ka, 2.0 +/- 0.7 x 10(9)/mol) for both T4 and T3 are the same as found in plasma. The higher MBC for T4 (5.8 +/- 1.0) and T3 (0.69 +/- 0.2 pmol/mg protein) in two hypothyroid subjects are consistent with the higher mean TBG concentration of 28 +/- 5 micrograms/ml compared to the level in ten normal subjects (19.2 +/- 1.8 micrograms/ml; P less than 0.001). In two subjects with low normal TBG concentrations of 15 micrograms/ml, the T4 maximum specific binding of 9% was lower than found in normal subjects 16.6 +/- 7.6%. We conclude that the methodology described previously and used in this study is invalid for measuring thyroid hormone nuclear receptor status in humans.

Blood Proteins↗
PubMed1982

Thyroid hormone binding to putative nuclear receptors in human mononuclear blood cells.

Nuclear protein extracts from mononuclear cells in normal subjects, subjects with the clinical syndrome of thyroid hormone resistance and cultured B lymphocytes bound thyroxine (T4) Ka; 1 . 3-3 . 5 X 10(9) m-1) and triiodothyronine (T3) (Ka; 1 . 2-3 . 9 X 10(9) m-1) with similar affinities. When an extra wash step was introduced, the maximum specific binding of T4 and T3 was reduced by 75% and binding was abolished by three washes. These data suggest binding is to a serum protein contaminant present in the mononuclear cell preparation.

Adolescent↗
PubMedDate not supplied

Preconceptual caffeine exposure increases glucose utilization and accelerates development in the preimplantation rat embryo.

The present study was designed to investigate whether caffeine administered daily throughout the estrous cycle prior to fertilization affected the development of the subsequent preimplantation day 5 rat embryo. The viability parameters chosen for assessment were glucose utilization, cell number, and stage of embryonic development (morula to hatched blastocyst). Two independently replicated experiments were conducted. Together these experiments demonstrated that after fertilization, a proportion of affected oocytes maturing in a caffeine-perfused ovarian environment used and oxidised glucose at a significantly higher rate and were significantly more advanced developmentally compared with their litter mates or with the control counterparts. Cell number per embryo and the number of embryos recovered (litter size) remained constant, suggesting that caffeine, at the doses used, is unlikely to affect the ovulation rate or prevent fertilization. This study is significant because it demonstrates for the first time that a drug such as caffeine, when administered prior to ovulation and genomic activation, causes a quantitative difference in growth promoting energy utilization in a proportion of susceptible embryos after genome activation. A link between genomic imprinting and changed developmental program in the preimplantation embryos was suggested.

Animals↗
PubMedDate not supplied

The provision of a semen cryopreservation service for male cancer sufferers in the Republic of Ireland.

BACKGROUND: Chemotherapy, radiotherapy and surgery for cancer all carry risks of sterility. Semen cryopreservation would allow procreational ability to be preserved. METHODS: A human-assisted reproduction unit was set up in the Rotunda Hospital where semen was cryopreserved and stored for use. RESULTS: Semen was frozen for procreational potential during 1998 from 58 males about to have oncology therapy likely to render them sterile. The planning for this service and the modus operandi now in place are described. While cryopreservation was not unsuccessful in any case, substandard samples were obtained from 14 men. Pre-freeze viral tests tested positive for CMV in six patients. One pregnancy is already on-going utilising IVF with thawed semen. One patient's death has been notified and the frozen semen disposed of. CONCLUSION: The service is, at present, outside public purse provision. It is hoped that in the near future this will change, as the deficit between charges and costs cannot be sustained in-house forever.

Cryopreservation↗
PubMedDate not supplied

Initial experiences of a testicular sperm extraction programme for assisted reproduction in Ireland.

BACKGROUND: The technique aspirating spermatozoa from the testis is a new development in male infertility treatment. It is appropriate for infertile couples where the male has azoospermia but is still producing live motile spermatozoa in the testes. AIM: To describe the initial experiences of a testicular sperm extraction programme (TESE) coupled with intracytoplasmic sperm injection (ICSI) in 18 men during 1998. METHODS: Spermatozoa were obtained by direct aspiration from the testes using a 16 gauge needle with cannula and negative suction under local anaesthetic. All samples obtained were to be cryopreserved for use in a subsequent ICSI cycle. RESULTS: All five men with congenital bilateral absence of the vas deferens to be carriers of cystic fibrosis gene mutations. No gene deletions were found in their wives. No other cyto or molecular genetic abnormalities were otherwise found. Twenty one procedures were carried out. The mean number of aspirations was 1.72. Eleven samples from 10 men had sperm suitable for ICSI post-freeze. Post-procedure pain was the universal side-effect. Eight couples had a single attempt at ICSI, two couples two each. Fertilisation rate was 71.4%. Two pregnancies were achieved. CONCLUSION: TESE may give hope in selected cases of azoospermia of fathering a child without the involvement of a third party.

Adult↗