Biomedical subjects

T Creagh

Publications and source records attributed to T Creagh.

17 recordsLinked to original sources

PubMed2003

Neutrophil bactericidal function is defective in patients with recurrent urinary tract infections.

Urinary tract infection (UTI), most frequently caused by Escherichia coli, is one of the most common bacterial infections in humans. It is a host inflammatory response to bacterial invasion in which large numbers of neutrophils are recruited into the bladder in response to cytokines secreted by the infected bladder epithelium. We hypothesise that an impaired host neutrophil response leads to susceptibility to recurrent UTI (rUTI). Therefore, the neutrophil inflammatory response of patients with a history of rUTI was compared to healthy controls. No difference in neutrophil adhesion receptor expression or complement receptor expression following bacterial stimulus was detected between the two groups. However, the expression of the IgG receptor CD16, bacterial phagocytosis and reactive oxygen intermediate (ROI) production were significantly reduced in UTI patient neutrophils compared to controls. Neutrophils from rUTI patients have a significantly reduced bactericidal function when compared to healthy controls, with the former showing a reduced capacity for activation. This reduced neutrophil function may result in defective bacterial clearance and lead to susceptibility to recurrent infection.

Adult↗

PubMed2001

Safety and pharmacokinetics of single doses of (+)-calanolide a, a novel, naturally occurring nonnucleoside reverse transcriptase inhibitor, in healthy, human immunodeficiency virus-negative human subjects.

(+)-Calanolide A is a novel, naturally occurring, nonnucleoside inhibitor of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase first isolated from a tropical tree (Calophyllum lanigerum) in the Malaysian rain forest. Previous studies have demonstrated that (+)-calanolide A has specific activity against the reverse transcriptase of HIV-1 and a favorable safety profile in animals. In addition, (+)-calanolide A exhibits a unique HIV-1 resistance profile in vitro. The safety and pharmacokinetics of (+)-calanolide A was examined in four successive single-dose cohorts (200, 400, 600, and 800 mg) in healthy, HIV-negative volunteers. In this initial phase I study, the toxicity of (+)-calanolide A was minimal in the 47 subjects treated. Dizziness, taste perversion, headache, eructation, and nausea were the most frequently reported adverse events. These events were not all judged to be related to study medication nor were they dose related. While 51% of subjects reported mild and transient dizziness, in many cases this appeared to be temporally related to phlebotomy. Calculation of the terminal-phase half-life (t(1/2)) was precluded by intrasubject variability in the 200-, 400-, and 600-mg dose cohorts but was approximately 20 h for the 800-mg dose group. (+)-Calanolide A was rapidly absorbed following administration, with time to maximum concentration of drug in plasma (T(max)) values occurring between 2.4 and 5.2 h postdosing depending on the dose. Plasma levels of (+)-calanolide A at all dosing levels were quite variable; however, both the mean concentration in plasma (C(max)), and the area under the plasma concentration-time curve increased proportionately in relation to the dose. Although raw plasma drug levels were higher in women than in men, when doses were normalized for body mass, the pharmacokinetic profiles were virtually identical with those observed for males. In general, levels of (+)-calanolide A in human plasma were higher than would have been predicted from animal studies, yet the safety profile remained benign. In conclusion, this study demonstrated the safety and favorable pharmacokinetic profile of single doses of (+)-calanolide A in healthy, HIV-negative individuals.

Adolescent↗

PubMed1995

Pathologist variation in reporting cervical borderline epithelial abnormalities and cervical intraepithelial neoplasia.

AIMS: To evaluate the interobserver variation in the diagnosis of cervical intraepithelial lesions, including the new category "borderline abnormalities of uncertain significance" (BAUS) which has not been tested before. METHODS: Biopsy specimens of 122 patients were reviewed by five histopathologists and the diagnoses subjected to kappa statistical analysis. RESULTS: There was poor interobserver agreement in all categories, particularly between BAUS and normal tissue. CONCLUSIONS: The current guidelines for the histological diagnosis of cervical intraepithelial neoplasia and BAUS are poorly reproducible.

Biopsy↗

PubMed1994

Transurethral microwave thermotherapy versus transurethral catheter therapy for benign prostatic hyperplasia.

Transurethral microwave thermotherapy (TUMT) is a single outpatient treatment for benign prostatic hyperplasia. It produces good symptomatic relief but minimal objective improvement in mean flow rates. We wished to evaluate the placebo effect of the transurethral catheter. We evaluated 40 patients with outflow obstruction, 20 had TUMT for 1 h and 20 had a catheter placed in the urethra without treatment for 1 h. Urinary flow rates improved in both groups (12.8-14.6 with TUMT, 10.0-12.4 with catheter). Significant reduction from pretreatment values occurred in symptom scores and postvoid residual urine volume in both groups following treatment. The subjective results of TUMT and the placebo effect seen in the catheter group cast doubt on our understanding of the mechanism of action of TUMT.

Humans↗

PubMed1993

Haemospermia: how to proceed?

Haemospermia is an alarming symptom but does it signify serious disease and how should it be investigated? A retrospective review of 44 men showed no evidence of malignancy and infection as the commonest cause. Standard investigation with midstream specimen of urine, intravenous pyelogram and cystoscopy is unhelpful. Microscopy and culture of a first stream specimen of urine or expressed prostatic secretions is the investigation of choice. Cystoscopy should be reserved for patients with recurrent haemospermia.

Adult↗

PubMed1993

Pharmacological manipulation of acute cyclosporin ischemic renal injury with trimetazidine.

Cyclosporin has had a major impact on organ transplantation, but associated nephrotoxicity is a significant problem. Renal hypothermia, a known anti-ischemic maneuver, limits cyclosporin-ischemic renal failure. Pharmacological manipulation with an anti-ischemic agent, such as trimetazidine, may prevent cyclosporin nephrotoxicity. We tested this hypothesis in a canine single kidney model of cyclosporin-enhanced ischemic renal failure. Trimetazidine treatment was associated with significantly better biochemical and histological markers of renal function and structure. Trimetazidine may have a role to play in protecting against cyclosporin nephrotoxicity in clinical renal transplantation.

Animals↗

PubMed1992

Treatment strategy for piezoelectric shock wave lithotripsy of upper ureteral calculi.

In situ piezoelectric lithotripsy monotherapy for upper ureteral stones is an attractive option because it can be conducted on an outpatient basis. Difficulty in calculus localization with ultrasound is the limiting factor. We reviewed our experience with 99 patients treated for upper ureteral calculi with the EDAP LT.01 lithotriptor. For stones above the lower renal border we achieved a 53% stone-free rate compared to 25% for calculi below the lower renal border. In situ piezoelectric lithotripsy of upper ureteral calculi may be considered for stones above the lower renal border.

Adolescent↗

PubMed1992

Regional hypothermia protects against tourniquet neuropathy.

Ischaemic nerve injury has been suggested as the mechanism for post-tourniquet limb paralysis. As hypothermia has been shown to prolong ischaemia time in many tissues, we tested the hypothesis that cold protection would reduce tourniquet induced neural injury. In 16 male Wistar rats a tourniquet was applied to the right hind limb for 3 h. In eight rats both hind limbs were maintained at room temperature (27 degrees C) while the limb temperature was decreased to 4 degrees C by application of cold polyglycol gel packs in the remaining eight animals. Motor nerve conduction velocity (MNCV) and the amplitude of muscle motor units (AMMU) in response to nerve stimulation were measured at 0 h, 1 h and 1 week post-tourniquet release. Application of the tourniquet for 3 h abolished nerve conduction in all animals. Hypothermia resulted in a significant improvement in AMMU (5.8 +/- vs. 0.6 +/- 0.4 mv, p less than 0.05) at 1 h and in MNCV (26.6 +/- 1.6 vs. 8.1 +/- 4.4 ms-1, p less than 0.05) and AMMU (18.5 +/- 2.0 vs. 9.7 +/- 4.5 mv, p less than 0.05) at 1 week. Hypothermia without ischaemia also reduced MNCV (44.2 +/- 9.4 vs. 74.3 +/- 8.9 ms-1, p less than 0.05) and AMMU (28.1 +/- 2.8 vs. 36.3 +/- 8.4 mv, N.S.). These data indicate that hypothermia reduces normal MNCV and protects nerve function during tourniquet ischaemia. These results support the ischaemic hypothesis for post-tourniquet nerve injury. Cold protection may have clinical applications for surgical procedures performed with tourniquet ischaemia.

Animals↗

PubMed1992

Peritoneum-preserving radical nephrectomy in a patient on continuous ambulatory peritoneal dialysis.

We describe a pararectus retroperitoneal approach for radical nephrectomy in a patient on chronic ambulatory peritoneal dialysis. This approach allows early ligation of the renal pedicle pre-operatively and immediate resumption of peritoneal dialysis post-operatively.

Aged↗

PubMed1992

Incidence and natural history of Mycobacterium avium-complex infections in patients with advanced human immunodeficiency virus disease treated with zidovudine. The Zidovudine Epidemiology Study Group.

To determine the incidence and natural history of Mycobacterium avium-complex infections in persons with advanced human immunodeficiency virus (HIV) infection, we studied a multicenter cohort of 1,020 persons with acquired immunodeficiency syndrome (AIDS) or the AIDS-related complex (ARC) and CD4 cell count < 0.250 x 10(9)/L initially treated with zidovudine between April 1987 and April 1988. M. avium-complex infections developed in 123 (12%) patients during follow-up, with a 2-yr actuarial risk of 19%. Patients with an initial diagnosis of Pneumocystis carinii pneumonia were more likely to develop M. avium-complex infections than patients with an initial diagnosis of another opportunistic disease or of ARC (p = 0.002). Individuals developing M. avium-complex infections had lower baseline CD4 cell counts, hematocrits, lymphocyte counts, and total white blood cell counts than those who did not develop M. avium-complex infection. During follow-up, individuals who developed M. avium-complex infections were more likely to have severe anemia, to experience zidovudine dose reductions, and to die than were patients without M. avium-complex (p < 0.001). By proportional hazards analysis, a baseline CD4 cell count < 0.100 x 10(9)/L, development of severe anemia, P. carinii pneumonia during follow-up, and zidovudine dose interruption were significantly associated with subsequently developing M. avium-complex infection. A proportional hazards analysis of survival showed that M. avium-complex infection, severe anemia, zidovudine dose interruption, occurrence of an opportunistic infection, CD4 cell count < 0.100 x 10(9)/L, baseline AIDS diagnosis, and transfusion independently predicted an increased risk of death.(ABSTRACT TRUNCATED AT 250 WORDS)

AIDS-Related Complex↗

PubMed1988