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Biomedical subjects

J Kelly

Publications and source records attributed to J Kelly.

At least 253 records · Page 14Linked to original sources
PubMed1996

Medroxyprogesterone and paraphiles: do testosterone levels matter?

We examine the associations between pretreatment testosterone (TTS) levels and sociodemographic, clinical, and sexual behavioral characteristics. Two groups, low and normal pretreatment TTS, were treated with medroxyprogesterone acetate (MPA) and compared on clinical response (deviant and nondeviant sexual behaviors; recidivism) and length of time to return to pretreatment TTS after discontinuing MPA. Thirteen paraphilic men who were treated with MPA and had TTS levels monitored at approximately three-month intervals during and after MPA were followed naturalistically. The principal outcome measures pertained to TTS levels and data from a self-report psychosexual inventory, which quantified deviant and nondeviant sexual activities. Time to return to baseline TTS levels were analyzed with Kaplan-Meier survival analysis. Nonparametric methods were used to compare the two groups on other variables. Multiple regression was used to examine the contribution of combinations of variables to TTS outcome. Subjects with low pretreatment TTS received MPA for longer periods of time, and older subjects took longer to return to pretreatment TTS levels despite being treated for shorter periods of time. Although subjects with lower pretreatment TTS levels may be more sensitive to MPA's TTS-suppressive effects, the multiple regression analysis showed that age may be an important determinant of the time it take for TTS levels to return to pretreatment baseline. Sociodemographic, clinical, and self-reported measures of sexual behavior did not distinguish between low and normal TTS level groups. Only one relapse was detected. Further studies with larger samples are required to better understand the role of TTS monitoring of sex offenders treated with MPA, in order to justify its continued use as a measurement of treatment adequacy and to study its potential role as a predictor of treatment outcome.

Age Factors↗
PubMed1995

SCH 51344 inhibits ras transformation by a novel mechanism.

A pyrazolo-quinoline compound, 6-methoxy-4-[2-[(2-hydroxyethoxyl)-ethyl]amino]-3-methyl-1M-pyrazo lo [3,4-b]quinoline (SCH 51344), was identified based on its ability to derepress human smooth muscle alpha-actin promoter activity in ras-transformed cells. In this study, we show that SCH 51344 reverts several key aspects of ras transformation, such as morphological changes, actin filament organization, and anchorage-independent growth, and also inhibits Val-12 Ras-induced maturation of Xenopus oocytes. SCH 51344 is also a potent inhibitor of the anchorage-independent growth of human tumor lines known to contain multiple genetic alterations in addition to activated ras genes. We have sought to determine whether SCH 51344 disrupts the signaling pathway that activates mitogen-activated protein (MAP) kinase or extracellular signal-regulated kinase (ERK) in normal and ras-transformed fibroblast cells. NIH 3T3 cells transformed by different oncogenes, which have products that participate at different steps of the Ras signaling pathway, were tested in a soft-agar colony formation assay to determine which step of the pathway is inhibited by SCH 51344. Our results indicate that SCH 51344 inhibits the ability of v-abl, v-mos, H-ras, v-raf, and mutant active MAP kinase kinase-transformed NIH 3T3 cells to grow in soft agar. Only v-fos-transformed cells were found to be resistant to the treatment of SCH 51344. SCH 51344 treatment had very little effect, if any, on the activation of MAP kinase kinase, MAP kinase, and p90RSK activity in response to growth factor stimulation. Treatment of ras-transformed cells with SCH 51344 led to stimulation of serum response factor DNA binding activity and activation of serum response element-dependent gene transcription, accounting for its ability to activate alpha-actin promoter activity in ras-transformed cells. Our results indicate that SCH 51344 inhibits ras transformation by a novel mechanism and acts at a point either downstream or parallel to extracellular signal-regulated kinase-dependent Ras signaling pathway.

3T3 Cells↗
PubMed1995

The sigma receptor ligand JO 1784 (igmesine hydrochloride) is neuroprotective in the gerbil model of global cerebral ischaemia.

To assess the effects of the novel sigma receptor ligand JO 1784 ((+)-N-cyclopropyl-methyl-N-methyl-1,4-diphenyl-1-yl-but-3-en-1-ylami ne, hydrochloride or igmesine hydrochloride) on behavioural and histological changes following cerebral ischaemia, the gerbil model of cerebral ischaemia was used. Two experiments were carried out. In the first animals were either sham operated, subjected to 5 min of bilateral carotid occlusion or administered JO 1784 (25, 50, 75 or 100 mg/kg p.o.) 1, 24 and 48 h after 5 min bilateral carotid occlusion and histological evaluation carried out 96 h after surgery. In the second experiment the effects of JO 1784 administered at a dose of 100 mg/kg i.p. 30 min, 6, 24 and 48 h post-surgery on home cage activity and nitric oxide (NO) synthase activity in the cortex, hippocampus, cerebellum and brain stem 4 days after surgery was examined. Extensive neuronal death was observed in the CA1 region of 5 min occluded animals. JO 1784 (50, 75 and 100 mg/kg) provided significant protection against this ischaemia-induced cell death (P < 0.03-0.005). In the second experiment a large increase in home cage activity was observed for 5 min occluded animals for 12 h after surgery (P = 0.0018-0.02). A large increase in NO synthase activity was observed in all brain regions for 5 min occluded animals. Post-administration of JO 1784 attenuated the ischaemia-induced hyperactivity and increased NO synthase activities.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Age-specific alterations in muscarinic stimulation of K(+)-evoked dopamine release from striatal slices by cholesterol and S-adenosyl-L-methionine.

The present experiments were carried out in order to test the hypothesis that age-related signal transduction (ST) deficits may occur as a result of structural changes in the membrane that are reflected partially as increased membrane microviscosity. Oxotremorine (oxo) enhancement of K(+)-evoked release of dopamine (K(+)-ERDA) was examined in superfused striatal slices from mature (6 months) and old (24 months) Wistar rats incubated (1 or 4 h, 37 degrees C) with graded concentrations of S-adenosyl-L-methionine (SAM) or cholesterol hemisuccinate (CHO) in a modified Krebs medium. Tissue was then assessed for one of the following: (a) the degree of oxo-enhanced K(+)-ERDA, (b) carbachol stimulated low Km GTPase activity, or (c) alterations in membrane microviscosity. In other experiments the tissue was incubated in CHO followed by SAM (or the reverse), and oxo-enhanced K(+)-ERDA examined. Results indicated that SAM treatment increased all the parameters in the striatal tissue from old animals, while CHO had selective, opposite effects in the striatal tissue obtained from young animals. CHO-SAM, or the reverse, produced the same pattern of results. These results suggest that ST deficits may involve age-related structural alterations in membranes that interfere with receptor-G protein coupling/uncoupling.

Aging↗
PubMed1995

Adriamycin-induced hepatic and myocardial lipid peroxidation and DNA damage, and enhanced excretion of urinary lipid metabolites in rats.

Adriamycin produces clinically useful responses in a variety of human cancers including lymphomas, leukemias, and solid tumors. However, the toxicity of adriamycin has limited its usefulness. Iron-catalyzed free radical reactions as the peroxidation of membrane lipids, inactivation of critical enzymes, and the inhibition of DNA, RNA and protein synthesis in heart, liver and kidney have been implicated in the toxicity of adriamycin. In order to further assess the role of oxidative stress in the toxicity of adriamycin, the effects of adriamycin were examined on the urinary excretion of lipid metabolites at 0, 6, 12, 24, 48 and 72 h post-treatment, and on myocardial and hepatic lipid peroxidation and nuclear DNA single strand breaks at 24 h post-treatment following single oral and intravenous (i.v.) doses of 10 mg/kg adriamycin. Urinary malondialdehyde (MDA), formaldehyde (FA), acetaldehyde (ACT) and acetone (ACON) excretion was significantly increased at all time points examined. Following the oral administration of adriamycin, maximum excretion of MDA, FA, ACT and ACON of 6.2-, 2.7-, 3.7- and 2.2-fold relative to control values, respectively, occurred 24 h after treatment. However, following the i.v. administration of adriamycin, greatest increases in excretion of MDA, FA and ACT reaching 6.9-, 3.3- and 6.3-fold relative to control values, respectively, were observed 6 h after treatment, while the greatest increase in ACON excretion of 4.2-fold relative to control values occurred 12 h post-treatment. Following oral and i.v. administration of adriamycin, significant increases were observed in myocardial and hepatic lipid peroxidation in mitochondrial and microsomal membranes, and myocardial and hepatic nuclei DNA single strand breaks 24 h after treatment. The results indicate that adriamycin administration induces myocardial and hepatic lipid peroxidation which may be responsible for enhanced excretion of urinary lipid metabolites as a result of membrane damage, and also induces enhanced DNA damage. These effects may be due to adriamycin-induced production of reactive oxygen species.

Acetaldehyde↗
PubMed1995

Expression of two T cell receptor alpha chains on the surface of normal murine T cells.

We have previously reported that a subset of T cells in T cell receptor (TCR)-transgenic mice may express two different alpha chains on their surface. The expression of two functional alpha chains has also been demonstrated for human peripheral blood T cells. In this report, we show that a proportion of normal murine lymph node T cells express two functional alpha chains on their surface. The extrapolated frequency of these cells present in the normal repertoire ranges from 7-21%, with an average of 15%. Our analysis of a small number of antigen-specific T cell clones suggests that the frequency of antigen-responsive cells expressing two surface alpha chains is relatively low. This raises the possibility that dual alpha chain T cells may have a selective disadvantage in responding to specific antigen.

Amino Acid Sequence↗
PubMed1995

Influence of toxicants on neural cell adhesion molecule-mediated neuroplasticity in the developing and adult animal: persistent effects of chronic perinatal low-level lead exposure.

The expression of neuroplastic neural cell adhesion molecule (NCAM) polysialylated neurons in the dentate of juvenile (postnatal day 40) and adult (postnatal day 80) rats exposed to low-level lead during the early postnatal period has been investigated. At both ages, the number of polysialylated neurons was decreased significantly in lead-exposed animals when expressed per unit area but not total dentate area. This could be attributed to an increase in the number and intercellular spacing of granule cells in the dentate of the lead-exposed animals. These effects are related to NCAM polysialylation dysfunction perturbing early hippocampal neurogenesis.

Age Factors↗
PubMed1995

Use of the abbreviated mental test to detect postoperative delirium in elderly people.

We investigated the validity of the abbreviated mental test (AMT) as a guide to the diagnosis of delirium in 100 patients aged more than 65 yr. Patients were assessed using the AMT on the day before and on the third day after operation. Fifteen patients were delirious on the third postoperative day; 10 of 43 patients undergoing orthopaedic surgery and five of 57 patients undergoing non-orthopaedic surgery. Delirium developed in four of 16 patients with a preoperative AMT score less than 8 and in 11 of 84 patients with a preoperative AMT score of 8 or more. Patients who developed delirium had a greater decline in AMT score (mean 2.7 (SD 0.9)) than patients who did not develop delirium (0.7 (1.0)) (P < 0.001). The sensitivity and specificity of a decline in AMT score of 2 or more points after surgery for diagnosis of postoperative delirium were 93% and 84%, respectively.

Aged↗
PubMed1995

Benzodiazepine use as a cause of cognitive impairment in elderly hospital inpatients.

BACKGROUND: Benzodiazepine drugs are used very frequently by the elderly and have been associated with a number of untoward events in them. In an earlier publication, we showed that there was an association between benzodiazepine use and episodes of confusion in hospital. The purpose of this study was to examine that association in more detail by studying only patients with intact cognitive function on admission and by taking into consideration a range of demographic, drug use, and clinical confounders. METHODS: A prospective cohort study was carried out of inpatients who had normal cognitive function on admission to hospital. The subjects were 418 hospital inpatients who had a normal result of a Mini-Mental State Examination (MMSE) performed within 24 hours of admission. They were aged 59-88 years. A clinical history and detailed drug use history were taken on admission and then the patients were followed prospectively for 10 days or until discharge, whichever was sooner. The MMSE was repeated every 2 days and all significant clinical events and episodes of delirium noted. RESULTS: 10.8% (95% Confidence Interval [CI]: 7.8-13.8%) of patients developed cognitive impairment (as indicated by a decrease in the MMSE). Factors that were statistically significantly related to the development of cognitive impairment included admission diagnoses of cancer or central nervous system (CNS) disease, alcohol consumption > 40 gms/day, hypoxia, and presence of benzodiazepines in the urine on admission. After adjusting for age, alcohol consumption, and admission diagnoses, those who reported taking benzodiazepines in daily doses equivalent to 5 mg or more of diazepam were at significantly higher risk of cognitive impairment than those who had not taken benzodiazepines (adjusted odds ratio = 3.5; 95% CI: 1.4-8.8). Twenty-one (5.0%, 95% CI: 2.9-7.1%) patients developed delirium as defined by the DSM-IIIR criteria. Age and hypoxia were statistically significantly related to the development of delirium. Due to the small number of cases of delirium, the power of the study to detect significant associations was low. CONCLUSIONS: Elderly hospital inpatients who have intact cognitive function on admission to hospital have a low risk of developing cognitive impairment and delirium during their hospital stay. In this population, however, benzodiazepine use accounted for 29% of cases of cognitive impairment which did occur. The data also suggest that dehydration, urinary retention, and an admission diagnosis of CNS disease may be important risk factors for delirium.

Aged↗
PubMed1995

A comparison of the effects of IGF-I and insulin on glucose metabolism, fat metabolism and the cardiovascular system in normal human volunteers.

The metabolic and cardiovascular effects of recombinant human IGF-I were compared to insulin in six normal subjects. Subjects were studied twice and intravenously received an infusion of [6,6-2H2]glucose (0-480 min) and in random order either IGF-I 20 micrograms kg-1 h-1 (43.7 pmol kg-1 min-1 or insulin 0.5 mU kg-1 min-1 (3.4 pmol kg-1 min-1) with an euglycaemic clamp. One subject was withdrawn following a serious adverse event. During the IGF-I infusion glucose appearance rate (Ra) decreased from 1.79 +/- 0.13 at baseline (150-180 min) to 0.35 +/- 0.26 mg kg-1 min-1 (P < 0.01) at 360 min, and glucose utilization rate (Rd) increased from 1.79 +/- 0.28 to 4.17 +/- 0.84 mg kg-1 min-1 (P < 0.01). There was no change in free fatty acids (FFA) and an increase (percentage change from pre-infusion mean) in cardiac output +l37.3% +/- 9% (P < 0.01), heart rate +13% +/- 2% (P < 0.01) and stroke volume +21% +/- 7% (P < 0.05). During the insulin infusion glucose Ra decreased from 1.89 +/- 0.13 to 0.34 +/- 0.33 mg kg-1 min-1 (P < 0.01) and FFA from 0.546 mmol l-1 to 0.198 mmol l-1 (P < 0.01), glucose Rd increased from 1.89 +/- 0.18 to 5.41 +/- 1.47 mg kg-1 min-1 (P < 0.01) and there were no significant changes in the cardiovascular variables.

Adult↗
PubMed1995

Renal transplantation in very young children.

Results of renal transplantation in very young children with end-stage chronic renal failure have been poor compared with those in older children and adults. Consequently small children either may not be treated or may be placed on chronic dialysis programmes. Between 1988 and 1992, six children under the age of 5 years received seven renal transplants at the Royal Children's Hospital, Parkville, Victoria, Australia; five from live donors and two from cadaver donors. All children were treated with peritoneal dialysis before transplantation, and immunosuppressed with a standardized regimen of cyclosporine, azathioprine and prednisolone. An extraperitoneal incision was used, and the donor renal vessels were anastomosed to the lower abdominal aorta and inferior vena cava or the common iliac vein. All children received intensive monitoring and fluid replacement during the peri-operative period. Patient survival was 100%. One cadaver graft failed 1 week after transplantation because of irreversible acute rejection. This child subsequently received a successful second transplant. Two children developed postoperative urinary fistulae which were treated successfully by further operation. Current renal function in all children is excellent. The success of this programme has led us to review our attitude towards renal transplantation in this age group and to advocate live donor renal transplantation as the treatment of choice in very young children with end-stage chronic renal failure whenever possible.

Cadaver↗
PubMed1995

Laparoscopic nephrectomy: initial experience and cost implications.

OBJECTIVE: To assess the results and cost implications of laparoscopic nephrectomy. PATIENTS AND METHODS: Ten patients underwent attempted laparoscopic nephrectomy and nephro-ureterectomy. The cost of the laparoscopic procedures was estimated to allow comparison with that of open surgery. RESULTS: Two patients required conversion to an open procedure, one for a colonic tear, the other for irretrievable loss of pneumoperitoneum. The median operating time for successful cases was 3 h (range 2.5-4). The mean morphine equivalent of analgesia delivered per patient was 18 mg (range 10-28). There was no mortality. Post-operative complications consisted of one case of prolonged ileus and another of chest infection. The median hospital stay of successful cases was 5 days (range 4-17), and the mean time to return to normal activity was 4 weeks (range 3-6). The cost of the procedure using re-usable instruments was approximately 2000 pounds, comprising 100 pounds for equipment. 900 pounds theatre costs and 1000 pounds for hospital stay. Using disposable equipment adds up to 900 pounds to the cost. In comparison an open nephrectomy typically costs around 2300 pounds. CONCLUSION: Laparoscopic nephrectomy is associated with lower analgesia requirements, shorter hospital stay and quicker return to work than equivalent open procedures. The cost, particularly when performed with re-usable instruments, is not prohibitive being comparable with that of open nephrectomy. With further experience it should become part of the armamentarium of urological surgeons.

Adolescent↗
PubMed1995

Use of heme and hemoglobin by Escherichia coli O157 and other Shiga-like-toxin-producing E. coli serogroups.

The virulence properties of Escherichia coli O157 isolates were compared with those of Shiga-like-toxin-producing E. coli of non-O157 serogroups. The growth of all E. coli O157 isolates was stimulated by both heme and hemoglobin, and all produced enterohemolysin. The incidence of these properties was significantly lower in the non-O157 isolates. This may contribute to the greater virulence and higher incidence of human infection caused by E. coli O157.

Bacterial Toxins↗
PubMed1995

The future of nursing in home health.

The home health industry has been expanding faster than any other segment of health care. This growth is expected to increase and many exciting opportunities will be available for nurses. A model utilizing advanced practice nurses in home health care utilizing is discussed.

Career Choice↗