Search PubMed⌕ Search

Biomedical subjects

J McLeod

Publications and source records attributed to J McLeod.

At least 19 recordsLinked to original sources
PubMed2007

Evidence for non-genomic transmission of ecological information via maternal behavior in female rats.

Maternal behavior is flexible and programs offspring development. Using a novel manipulation, we demonstrate that rat maternal behavior is sensitive to ecologically relevant stimuli. Long-Evans hooded rat dams (F0) and pups were exposed to a predator condition (cat odor) or a control condition (no odor) for 1 h on the day of parturition. Predator-exposed F0 dams displayed significantly more maternal behavior (licking/grooming, arched-back nursing) relative to control-exposed dams across five subsequent observation days. Female offspring (F1) were raised to adulthood, bred and maternal behavior was observed. F1 dams reared by a predator-exposed F0 dam displayed significantly higher maternal behavior relative to F1 dams reared by a control-exposed F0 dam across 5 days of observation. Increased levels of maternal behavior in predator-reared (PR) F1 dams were evident even in F1 females that had been cross-fostered (CF) from a control-exposed F0 dam, suggesting a non-genomic transmission of increased levels of maternal behavior. Lactating PR F1 dams had significantly elevated estrogen receptor alpha and beta mRNA in the medial preoptic area relative to control-reared (CR) F1 dams. Furthermore, among CR F1 dams, there was no significant difference between those dams that had been CF from predator-exposed F0 dams and those that had been sham CF. These results support the hypothesis that flexible rat maternal behavior can shape offspring development according to current environmental conditions. The results also suggest that estrogen signaling may be part of an epigenetic mechanism by which changes in maternal behavior are passed from F0 to F1 dams.

Animals↗
PubMed2001

Multiple-dose pharmacokinetics confirm no accumulation and dose proportionality of the novel promotile drug tegaserod (HTF 919).

OBJECTIVE: To evaluate the steady-state pharmacokinetics (PK) and dose proportionality of the selective 5-HT4 receptor partial agonist tegaserod (HTF 919) in healthy subjects. METHODS: Eighteen subjects were given 2, 6, or 12-mg doses of tegaserod twice daily (b.i.d.) for 5 days, with PK and safety assessments made during the 12 h or 24 h following first administration, and 12 h after the final dose. RESULTS: Tegaserod was rapidly absorbed [time to reach measured maximum plasma concentration after multiple administrations (tmax,ss) 1 h]. Steady-state PK were consistent with single-dose PK characteristics supporting that there was no accumulation of tegaserod in plasma based on systemic exposure. Mean measured maximum plasma concentration after multiple administrations (Cmax,ss) and area under the plasma concentration-time curve over one dosing interval (tau, 0-12 h after drug administration, AUC tau) were between 0.7 +/- 0.3 ng/ml and 5.6 +/- 2.9 ng/ml and 2.4 +/- 1.3 h.ng/ml and 20.4 +/- 14.0 h.ng/ml, respectively, indicating dose-proportional PK of tegaserod in the range 2-12 mg b.i.d. Tegaserod was safe and well tolerated. No serious adverse events were reported. CONCLUSION: Tegaserod exhibits no accumulation and dose-proportional PK after multiple doses.

Adult↗
PubMed2001

The pharmacokinetics of the novel promotile drug, tegaserod, are similar in healthy subjects-male and female, elderly and young.

BACKGROUND: Tegaserod (HTF 919) is a selective 5-HT4 receptor partial agonist in development for the treatment of irritable bowel syndrome. AIM: This study aimed to assess the effect of age and gender on the single-dose pharmacokinetics of tegaserod. METHODS: In a parallel-group, open-label study, a single dose of tegaserod (12 mg) was administered to four groups of healthy young male, young female, elderly male and elderly female subjects (n=10 per group). Blood samples were collected from 0 to 24 h postdose. Non-compartmental pharmacokinetics evaluation and statistical analysis (ANOVA and Wilcoxon signed ranks test for tmax) were performed. RESULTS: Tegaserod was well tolerated in all groups. There was no effect of age or gender on tmax and Cmax. Gender did not affect AUC0-infinity and AUC0-tz; there was a statistically significant effect of age on these parameters. AUC0-infinity and AUC0-tz in the elderly were greater than in the young (AUC0-infinity ratio 1.37, P < 0.001; AUC0-tz ratio 1.23, P=0.029). This increase in exposure is judged not to be clinically relevant because it is within the variability in the pharmacokinetics parameters of tegaserod and because the dose-response relationship of tegaserod is relatively shallow. CONCLUSIONS: No dose adjustment for age or gender is recommended in tegaserod therapy.

Adolescent↗
PubMed2001

A qualitative study of patients' views on anxiety and depression.

BACKGROUND: In the management of patients with anxiety and depression in general practice, the emphasis has been on improving detection and appropriate use of drug therapies by health professionals. Patients' own perceptions of their problems and what services they would prefer have not often been sought. AIM: To explore patient perspectives in relation to their healthcare needs in anxiety and depression. DESIGN OF STUDY: Semi-structured individual and focus group interviews. SETTING: A total of 27 patients from an urban four-partner group general practice who were identified as having anxiety and depression by a practice population questionnaire survey. METHOD: All interviews were transcribed and the major themes were summarised using grounded theory analysis. RESULTS: Patients seek many different ways of coping with their problems but view their general practice as a focal point for help. Their experiences are dominated by the struggle to control unwelcome and intrusive thoughts and to live in a hostile and threatening world. They also have distinct preferences regarding their health needs and there is universal scepticism about drug therapies. CONCLUSION: Patients describe personal and professional barriers to seeking help and have particular views on the treatment options. This perspective contrasts with the current professional emphasis on detection and drug use. This view is therefore central to informing the debate on management of neurotic disorders in primary care and on improving the care of these patients.

Adolescent↗
PubMed1997

Nosocomial pneumonia on general medical and surgical wards in a tertiary-care hospital.

OBJECTIVE: To describe the demographic, clinical, and microbiologic characteristics of patients who develop nosocomial pneumonia on general medical and surgical wards of a tertiary-care hospital. DESIGN: A 1-year, prospective, descriptive study. SETTING: A 1,100-bed, tertiary-care, urban hospital. POPULATION: Patients experiencing nosocomial pneumonia were identified through surveillance on general medical and surgical wards, using a standard case definition. RESULTS: 92 pneumonias in 85 patients on general wards were identified. The mean age of patients was 63 +/- 17 years, 55 patients (65%) were male, and 75 cases of pneumonia (81%) were acquired on surgical wards. Bacteremia was identified in 8 (13%) of 62 episodes, and 48 (52%) grew potential pathogens from respiratory specimens. Twenty-six patients (28%) required transfer to the intensive-care unit (ICU), and 20 (22%) received mechanical ventilation. By multivariate analysis, patients with a thoracic surgical procedure or with Staphylococcus aureus isolated from respiratory secretions were more likely to require ICU admission. The overall mortality rate was 20% (17/85), with a directly associated mortality of 14% (12/85). Patients who died were older, more frequently resided on a medical ward, and had a greater mean number of comorbidities. These patients often were treated nonaggressively and were not considered candidates for ICU admission due to advanced age and poor underlying clinical status. CONCLUSIONS: Although the morbidity of nosocomial pneumonia in this population was high, as evidenced by high rates of transfer to ICU, the directly associated mortality was relatively low. Those requiring ICU admission require further study to identify preventive measures that could decrease the morbidity in this group. Interventions to prevent pneumonia or to improve prognosis may not be feasible for the majority of these patients who die from nosocomial pneumonia.

Adult↗
PubMed1996

Effects of antigen presentation on superantigen-induced apoptosis mediated by Fas/Fas ligand interactions in human T cells.

Stimulation of T cells with bacterial superantigens has several distinct functional outcomes including proliferation, anergy and apoptosis. At present however, the mechanisms that dictate whether activation, anergy, or apoptosis predominate are unclear. In this study we have investigated the effects of superantigen presentation to mature superantigen-reactive human T-cell lines. Despite expressing major histocompatibility complex (MHC) class II molecules, these lines failed to proliferate in response to superantigen in the absence of antigen-presenting cells (APC) but proliferated when minimal APC were added. In the absence of APC a significant proportion of the T cells underwent apoptosis. This response was rapid, antigen dependent and largely abolished by the addition of cyclosporin A. Interestingly the response was not blocked by the addition of a number of antibodies to cell surface molecules including MHC class II and intracellular adhesion molecule-1. Using both a bioassay and messenger RNA analysis we were able to demonstrate that stimulation of these T cells with superantigen resulted in the induction of Fas-ligand expression on the T cells and furthermore, the ability of these cells to induce apoptosis was inhibited by the addition of blocking Fas antibodies as well as a Fas-Fc fusion protein. These data demonstrate that stimulation of T cells with staphylococcal enterotoxin B induces expression of Fas-ligand resulting in T-cell apoptosis; however, the final outcome of proliferation or apoptosis is determined by the presence of APC.

Antigen Presentation↗
PubMed1995

Nerves containing nitric oxide synthase and their possible function in the control of catecholamine secretion in the bovine adrenal medulla.

NADPH-diaphorase reactivity and neuronal nitric oxide synthase (nNOS) immunostaining have been localised in sections of bovine adrenal glands. Both were present in nerve fibres and terminals in the subcapsular region and running between zona glomerulosa cells, amongst the medullary chromaffin cells, between large ganglion cells in rare encapsulated medullary ganglia and in large nerve bundles running through the cortex. Occasional isolated fibres were stained in deeper cortical layers. Both NADPH-diaphorase reactivity and nNOS immunoreactivity were present in a population of ganglion cells located individually or in small groups at the medullary-cortical boundary. NADPH-diaphorase reactivity was also found in all cortical cells (zona glomerulosa cells being more densely stained than other cortical cells) and in large fibrous structures in large nerve bundles (tentatively identified as glial cells): these structures were not stained with antisera to nNOS. Chromaffin cells were not stained with either technique. The possible role of neurally-released nitric oxide in the regulation of nerve-induced catecholamine secretion from chromaffin cells was investigated in isolated, perfused, bovine adrenal glands. The secretion of both adrenaline and noradrenaline in response to field stimulation of adrenal nerves at either 2 Hz or 10 Hz was unaffected by the presence of N omega-nitro-L-arginine (30 microM), sodium nitroprusside (10 microM) or L-arginine (100 microM) in the perfusing solution. It is concluded that, although nitric oxide may be generated and released from adrenal medullary nerves innervating chromaffin cells, it does not play a direct role in the acute regulation of adrenal catecholamine secretion.

Adrenal Glands↗
PubMed1993

Clostridium difficile enteritis in a Canadian tertiary care hospital.

Nosocomial Clostridium difficile enteritis causes epidemic and endemic infection. The authors report the incidence of C difficile enteritis in a tertiary care hospital. The overall incidence rate over two years in the authors' institution was 22.2 cases per 100,000 in-patient-days; this rate appeared to decline over the study period (from 30.0 cases per 100,000 in 1990 to 11.2 at study end in 1992). Continued surveillance will determine whether this is a durable trend. An average of 5.25 cases per month occurs in the authors' hospital. A 50% increase overall was selected as the threshold for outbreak investigation. Surveillance of ward and specialty specific rates will allow clustering detection.

Cluster Analysis↗
PubMed1990

Effect of 12-O-tetradecanoylphorbol-13-acetate (TPA) on substance P-induced histamine release from rat peritoneal mast cells.

12-O-tetradecanoylphorbol-13-acetate (TPA, 1 to 30 ng/ml) produced a dose-related inhibition of substance P (SP)-induced histamine release from rat peritoneal mast cells. TPA itself induced some histamine release over this concentration range (maximum release about 20% of total). Maximum inhibition of SP-induced release by TPA required preincubation with TPA for at least 10 min. The inhibitory action of TPA was observed in the absence as well as in the presence of extracellular calcium (0.4 mM). Inhibition of diacylglycerol kinase by R 59022 or of diacylglycerol lipase by RHC 80267 reduced SP-induced histamine release. Oleolylacetylglycerol (OAG, 50 microM) inhibited histamine release induced by SP but was less potent than TPA. It is concluded that protein kinase C activation in rat peritoneal mast cells is associated with inhibition of SP-induced histamine release.

Animals↗
PubMed1990

Randomized, double-blind comparison of the efficacies, costs, and vaginal flora alterations with single-dose ceftriaxone and multidose cefazolin prophylaxis in vaginal hysterectomy.

A comparison of efficacies, costs, and effects on vaginal microflora of one preoperative and three postoperative 1-g doses of cefazolin versus those of one preoperative 1-g dose of ceftriaxone was done with 65 and 73 women, respectively, undergoing elective vaginal hysterectomy. Patient infection rates were not statistically different between the cefazolin group (six events in 6 of 73 patients [8.2%]) and the ceftriaxone group (11 events in 9 of 65 patients [13.8%]). Side effects, including diarrhea, were minimal and similar between the two groups. Significant shifts in the cervicovaginal microflora of the patients occurred postoperatively, with a marked increase in enterococci and a drop in nonenterococcal streptococci. No shifts among aerobic, facultative gram-negative rods and staphylococci were observed. Among the anaerobes, a significant decrease in the number of patients harboring nonsporulating, gram-positive rods and a less striking concomitant increase in Bacteriodes species and members of the family Peptococcaceae were noted. No qualitative differences were noted between the two groups that received prophylactic therapy. Aside from enterococci, cefazolin or ceftriaxone resistance among vaginal isolates (greater than or equal to 10(3)/ml) was minimal. Selection of resistant isolates was not different between the treatment groups. We could not detect a difference between a single 1-g dose of ceftriaxone and multidose cefazolin for infection prophylaxis in patients undergoing a vaginal hysterectomy. However, the total acquisition, preparation, and administration costs were greater for the ceftriaxone regimen than they were for the cefazolin regimen. Cefazolin should therefore remain the drug of choice for infection prophylaxis in uncomplicated vaginal hysterectomies.

Bacteria↗
PubMed1990

Evaluation of a Fife 'Novopen' clinic held within a diabetes patient education centre.

In common with other hospitals throughout the United Kingdom, a diabetic patient education centre has been established at the Victoria Hospital, Kirkcaldy. Many activities now take place within the centre including a 'Novopen' Clinic at which insulin requiring diabetic patients are converted to a multiple injection method of delivering soluble human insulin. An evaluation of the Novopen Clinic, including the first 60 patients attending, has demonstrated a statistically significant fall in random blood sugar estimations (mean fall 2.0 m.moles 1(-1), 95 per cent confidence intervals 1.5 m.moles 1(-1) to 2.5 m.moles) since conversion at the Novopen Clinic. Changes in mean daily insulin intake (mean increase of 1.6 units per day) and glycosylated haemoglobin (mean fall of 0.88 per cent) were not significant. One hundred per cent of patients surveyed described the Novopen Clinic as 'helpful' or very 'helpful'. Staff see the clinic offering significant opportunities for patient education. The estimated cost of the clinic per new patient was 147 pounds.

Diabetes Mellitus↗
PubMed1989

Epidemic of nosocomial Legionnaires' disease in renal transplant recipients: a case-control and environmental study.

An outbreak of Legionella pneumophila pneumonia occurred in 6 of 49 new renal transplant recipients over the course of 13 months. We compared infected patients (cases) and uninfected patients (controls) with respect to potential risk factors. Corticosteroid use, need for hemodialysis and number of days of hemodialysis were significantly greater among the cases. Logistic regression analysis identified corticosteroid dosage and number of days of hemodialysis as independent risk factors. Lymphopenia and monocytopenia were correlated with the amount of corticosteroid administered and occurred to a greater degree in the cases. All clinical isolates were of L. pneumophila serogroup 1, subtype Philadelphia 1, which was also cultured from a recovery room sink outside the operating room where the transplants were done. Other areas of the hospital were colonized with other, heterogeneous strains of L. pneumophila. The organism was not eliminated from the hospital water supply despite shock chlorination and superheating of water tanks. The epidemic ended when new transplant recipients routinely received prophylactic trimethoprim-sulfamethoxazole (160-800 mg given orally once daily) while in hospital after transplantation. Corticosteroid-induced monocytopenia and lymphopenia and the complement activation and monocyte depletion effects of hemodialysis may combine to increase susceptibility to Legionnaires' disease.

Adult↗
PubMed1986

A study of the prostaglandin and thromboxane content of the central nervous tissues with the development of chronic relapsing allergic encephalomyelitis.

Levels of PGE, PGF2 alpha, 6-oxo-PGF1 alpha and thromboxane (TXB2) in spinal cords and cerebellums of guinea pigs at different stages of chronic relapsing allergic encephalomyelitis (CREAE) were compared with those in Freund's adjuvant-treated, age-matched controls. PGE and TXB2 levels were found to be increased in spinal cords during acute and relapse phases of the disease. The number of lesions in the spinal cord was similarly increased in acute and relapse stages. There was, however, no similar correlation between number of lesions and eicosanoid levels in the cerebellum with the clinical stages of the disease based on hind limb paralysis. In the acute phase and remission lesion numbers were low, and high levels, similar to those found in the spinal cord, were only found in the relapse phase. Eicosanoid levels were high in the acute phase and remission, and generally low in relapse. The spinal cord levels of eicosanoids in remission and relapse correlated well with previous data obtained from the CSF of patients with multiple sclerosis.

6-Ketoprostaglandin F1 alpha↗