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Biomedical subjects

B McGrath

Publications and source records attributed to B McGrath.

At least 19 recordsLinked to original sources
PubMed2002

The role of conjugative transposons in the Enterobacteriaceae.

Although widely studied in gram-positive Streptococci and in the gram-negative Bacteroides, there is a scarcity of information on the occurrence and nature of conjugative transposon-like elements in the well-studied Enterobacteriaceae. In fact, some of the major reviews on conjugative transposons prior to 1996 failed to mention their occurrence in this group. Recently, their presence has been reported in Salmonella, Vibrio and Proteus species, and in some cases such as the SXT element in Vibrio and the IncJ group element CTnR391, there has been some molecular characterization. The elements thus far examined appear to be larger than the common gram-positive conjugative transposons and to be mosaic in structure, with genes derived from several sources. Recent evidence suggests that in the Enterobacteriaceae the elements may be related to enteric pathogenicity islands. The evolution, distribution and role of these elements in the Enterobacteriaceae is discussed.

Amino Acid Sequence↗
PubMed2001

The efficacy of direct current stimulation for lumbar intertransverse process fusions in an animal model.

STUDY DESIGN: Posterolateral lumbar intertransverse process fusion using a rabbit model with autologous bone graft and direct current stimulation was compared with fusion achieved by using autologous bone graft alone. OBJECTIVES: To determine the efficacy of direct current electrical stimulation for the posterolateral lumbar intertransverse process fusion technique by using a 20-microA current and the more recently developed 60-microA current delivered by an implantable direct current stimulator. SUMMARY OF BACKGROUND DATA: Previous studies have demonstrated a positive effect of direct current electrical stimulation on posterior spinal fusion techniques. However, until recently, the environment of an intertransverse fusion was not well simulated. The current research examined the posterolateral lumbar intertransverse process fusion technique with direct current electrical stimulation using a rabbit model. This appears to parallel human fusion techniques more closely and allows for lower cost and technical ease. METHODS: In this study, 44 adult New Zealand white rabbits underwent an L5-L6 intertransverse process fusion. All the fusions used an autologous bone graft obtained from bilateral posterior iliac crests. A device was implanted in all the rabbits subcutaneously, and they were divided randomly into three groups: a sham or nonfunctioning group, a 20-microA low-current stimulator group, and a 60-microA higher-current stimulator group. Spinal fusion was evaluated radiographically, histologically, and manually as well as by biomechanical testing 5 weeks after surgery. RESULTS: Radiographic grades, manual palpation, biomechanical strength, and stiffness showed an increasing trend from sham or inactive stimulator groups to low-current and then to high-current stimulator groups. Histologic analysis revealed that the higher-current stimulator showed that, statistically, the healing response of the host tissue to the autograft had increased significantly, as compared with the sham. CONCLUSIONS: Direct current electrical stimulation is efficacious in improving both the healing rate and strength in this posterolateral lumbar fusion model. In addition, it appears that this effect is enhanced by increasing the stimulation current from 20 microA to 60 microA.

Animals↗
PubMed2001

Clear cell sarcoma: the Roswell Park experience.

BACKGROUND AND OBJECTIVES: Clear cell sarcoma of the tendons and aponeuroses (CCSTA) is an aggressive, rare soft-tissue tumor with approximately 300 reported cases. Although it appears to be histogenetically related to melanoma, its clinical behavior resembles soft tissue sarcoma with a propensity for lymph node metastases. We report our experience at a tertiary cancer center. METHODS: Eight cases of CCSTA evaluated at Roswell Park Cancer Institute between 1970 and 1998 were reviewed retrospectively. Patient data analyzed included patient age, gender, anatomic location, size of tumor, development of local, regional and distant recurrence, and patient status at last follow up. RESULTS: Six of eight patients were alive at 2 years, while three of seven patients were alive at 5 years. Of the patients alive with no evidence of recurrence, two had tumors of less than 2 cm, and the remaining patient had incomplete information regarding tumor size. Five patients recurred within 2 years of definitive surgical management. Four had tumors > 5 cm. All five patients progressed to metastatic disease at a median follow up of 20 months (range 1-108 months) following definitive surgical management and all eventually died of their disease at a median of 3 months (range 0-24 months) from presentation with metastatic disease. Four of five patients with lesions > 5 cm received adjuvant chemotherapy with intent to cure, but all eventually died of disease at 4, 22, 34, and 41 months from initial presentation. CONCLUSIONS: CCSTA is an aggressive tumor of the soft tissues. Early recognition and management are associated with an excellent long-term prognosis. Tumors greater than 5 cm warrant aggressive surgical management and treatment, and are at high risk of the development of distant disease. Aggressive multiagent chemotherapy appeared to have no impact on outcome. Other adjuvant therapeutic options including immunotherapy should be investigated.

Adolescent↗
PubMed2001

Effects of ACE inhibitor therapy on derived central arterial waveforms in hypertension.

Large artery properties constitute an important component of left ventricular afterload in hypertension. The present study examined whether such properties were particularly responsive to angiotensin converting enzyme inhibitor therapy. A prospective, randomized, 12-week study in 138 previously treated hypertensive subjects, in 67 of whom usual treatment (UC) was replaced with perindopril (P) therapy. Large artery properties were assessed as central arterial pressure augmentation determined by applanation tonometry of the radial artery and a transfer function. At baseline both augmentation index (AI, %) and pressure (AP, mm Hg) were related to body size, heart rate, and gender. In addition AP was related to age and systolic blood pressure (BP). After 12 weeks of treatment AP decreased significantly in both perindopril and UC groups, whereas AI only decreased significantly (151.7%+/-2.3% to 144.9%+/-2.6%) in those treated with perindopril. Decreases in AP (-4.2+/-0.9 mm Hg v -1.9+/-0.7 mm Hg) and AI (-6.8%+/-2.2% v -2.2%+/-2.5%) from week 0 to week 12 were greater in the perindopril-treated group, but differences between groups failed to reach statistical significance (P = .05 and .09, respectively). The change in AI during the 12-week treatment period was dependent on the initial heart rate (P < .001), systolic BP (P < .05), weight (P < .001), and sex (P < .001), but not on treatment group (P > .5). Al at 12 weeks was negatively correlated with heart rate but regression slopes for the association were virtually identical for perindopril and UC groups. Perindopril treatment produces a greater decrease in AI than continuation with previous therapy, but this can be largely explained by hemodynamic changes rather than direct arterial effects.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2001

Malignant fibrous histiocytoma: an institutional review.

BACKGROUND: A thorough understanding of malignant fibrous histiocytoma (MFH), the most common subtype of soft tissue sarcoma, will lead to improved histologic-specific protocols. METHODS: 126 patients with histologically confirmed MFH were analyzed. The median follow-up was 42 months (range 1-233 months). RESULTS: Overall survival was 58% at 5 years and 38% at 10 years. Grade significantly influenced prognosis, with 10-year survival of 90%, 60%, and 20% for low, intermediate, and high grade tumors, respectively (p = 0.0007). Distant metastases at initial presentation (p = 0.0002) and size of the primary tumor (p = 0.0007) influenced outcome. Neither anatomic site nor depth of the primary tumor were significant prognostic factors. Positive microscopic margins were associated with a decreased disease-free survival (p = 0.006). CONCLUSIONS: Tumor grade, size, and distant metastases at initial presentation remain the most important prognostic factors for MFH. Resection with negative microscopic margins decreased the incidence of local recurrence.

Disease-Free Survival↗
PubMed2001

Evidence that parenteral testosterone therapy may improve endothelium-dependent and -independent vasodilation in postmenopausal women already receiving estrogen.

The gender difference in cardiovascular disease has been partly attributed to higher androgenic hormone levels. Although testosterone in women may not affect lipids, it remains unknown whether it negates favorable estrogenic effects on endothelial function. We have investigated the effects of testosterone implant therapy on arterial reactivity encompassing endothelial-dependent and -independent vasodilation in women using hormone replacement therapy (HRT). B-mode ultrasound measurements of resting brachial artery diameter, following reactive hyperemia [endothelium-dependent flow- mediated dilation (FMD)] and following glyceryl trinitrate (GTN) (endothelium-independent dilation), were recorded in 33 postmenopausal women stabilized on HRT (>6 months), at baseline, and 6 weeks after a testosterone implant (50 mg), with 15 postmenopausal nonusers of HRT serving as controls. In the brachial artery, baseline resting diameter was similar (0.40 +/- 0.01 vs. 0.41 +/- 0.01 cm, P = 0.5). In the treated group, testosterone levels increased (0.99 +/- 0.08 to 4.99 +/- 0.3 nmol/L, P < 0.001), associated with a mean 42% increase in FMD (6.4% +/- 0.7 to 9.1% +/- 1.1, P = 0.03). The control group did not change (8.1% +/- 1.4 to 5.6% +/- 1.0, P = 0.4). ANOVA of repeated measures (P = 0.04) and mean change (P = 0.02) in FMD both demonstrated significantly greater improvement with testosterone compared with controls. GTN induced vasodilation increased with testosterone treatment (14.9% +/- 0.9 to 17.8% +/- 1.2, P = 0.03). Our preliminary data indicate that parenteral testosterone therapy improves both endothelial-dependent (flow-mediated) and endothelium-independent (GTN-mediated) brachial artery vasodilation in postmenopausal women using long-term estrogen therapy. The mechanisms underlying these potentially beneficial cardiovascular effects require further investigation.

Brachial Artery↗
PubMed2000

Reelin binds alpha3beta1 integrin and inhibits neuronal migration.

Mice that are mutant for Reelin or Dab1, or doubly mutant for the VLDL receptor (VLDLR) and ApoE receptor 2 (ApoER2), show disorders of cerebral cortical lamination. How Reelin and its receptors regulate laminar organization of cerebral cortex is unknown. We show that Reelin inhibits migration of cortical neurons and enables detachment of neurons from radial glia. Recombinant and native Reelin associate with alpha3beta1 integrin, which regulates neuron-glia interactions and is required to achieve proper laminar organization. The effect of Reelin on cortical neuronal migration in vitro and in vivo depends on interactions between Reelin and alpha3beta1 integrin. Absence of alpha3beta1 leads to a reduction of Dab1, a signaling protein acting downstream of Reelin. Thus, Reelin may arrest neuronal migration and promote normal cortical lamination by binding alpha3beta1 integrin and modulating integrin-mediated cellular adhesion.

Adaptor Proteins, Signal Transducing↗
PubMed2000

General practitioners' beliefs, attitudes and reported actions towards chronic fatigue syndrome.

OBJECTIVE: To undertake a survey of Australian general practitioners (GPs) to explore their beliefs, attitudes and reported actions with respect to chronic fatigue syndrome (CFS). METHOD: A random sample of 2090 Australian GPs, stratified by state, was surveyed in May-August 1995. RESULTS: A 77% response rate was obtained. For the majority of practitioners who pursue a diagnosis of CFS, six symptoms were considered to be of significance: chronic unremitting fatigue for over 6 months; failure to recover energy after rest; reduced exercise tolerance; prostration for several days after exercise; generalised myalgia and poor concentration. Individual counselling was the most frequently used treatment. Thirty-one percent of practitioners reported that they did not believe that CFS is a distinct syndrome. Of these, 70% reported that the most likely cause of chronic fatigue was depression. CONCLUSION: There is considerable diversity of opinion between practitioners about CFS. The diversity extends from questioning whether the syndrome even exists to different strategies for diagnosis and management.

Adult↗
PubMed2000

General practitioners' views on patient care research.

BACKGROUND: Little research has been undertaken into the factors affecting recruitment by Australian general practitioners of patients for clinical trials. Understanding the differences between recruiters and non-recruiters will assist researchers in better supporting general practitioners involved in such research. METHOD: A survey of general practitioners involved in recruiting patients for clinical trials for the RACGP Research Program was undertaken. RESULTS: Recruiters were more likely to be interested in learning more about research, to perceive involvement as worthwhile, to desire a good relationship with Research Program staff and to feel the doctor-patient relationship assists recruitment. DISCUSSION: Recruiters in general are average general practitioners, male, middle-aged and work in group practices. Most felt some discomfort in recruiting patients, but believed the strong doctor-patient relationship assisted in the process. CONCLUSION: The Research Program needs to recruit general practitioners interested in research, choose topics of interest, keep recruitment protocols simple and stay in contact.

Australia↗
PubMed1999

Transient peroneal nerve palsies from injuries placed in traction splints.

Two patients thought to have distal femur fractures presented to the emergency department (ED) of a level 1 trauma center with traction splints applied to their lower extremities. Both patients had varying degrees of peroneal nerve palsies. Neither patient sustained a fracture, but both had a lateral collateral ligament injury and one an associated anterior cruciate ligament tear. One patient had a sensory and motor block, while the other had loss of sensation on the dorsum of his foot. After removal of the traction splint both regained peroneal nerve function within 6 hours. Although assessment of ligamentous knee injuries are not a priority in the trauma setting, clinicians should be aware of this possible complication in a patient with a lateral soft tissue injury to the knee who is placed in a traction splint that is not indicated for immobilization of this type of injury.

Adult↗
PubMed1999

Volume expansion does not activate neuronal projections from the NTS or depressor VLM to the RVLM.

We investigated whether a monosynaptic connection from the nucleus tractus solitarius (NTS) or the depressor ventrolateral medulla (VLM) to the pressor region of the rostral VLM (RVLM) constituted part of the reflex pathway activated by cardiopulmonary baroreceptors. Volume expansion in the conscious rabbit, which elicits renal nerve inhibition predominantly via cardiac mechanoreceptors, was used as the stimulus. The protein Fos was used as a marker of neuronal activation. The retrogradely transported tracer rhodamine-tagged microspheres, previously injected into the pressor region of the RVLM, identified medullary neurons that projected to that region. Volume expansion significantly increased the number of Fos-positive cell nuclei in the NTS and in the depressor VLM. Neurons that projected to the RVLM were found throughout the depressor region of the VLM and in the NTS but were not activated by volume expansion. Thus, although the central reflex pathways activated by volume expansion include the NTS and the depressor region of the VLM, we could not find evidence for a monosynaptic connection between those regions and the RVLM.

Animals↗
PubMed1998

An outbreak of an unusual strain of Serratia marcescens in two Dublin hospitals.

We describe a serious outbreak of infection caused by a strain of Serratia marcescens in two Dublin hospitals which occurred over an 11 week period and affected a total of 15 patients. A contaminated bed-pan macerator in the Intensive Care Unit of one hospital was identified as the possible source of infection and spread of the organism probably occurred via hand transmission by hospital personnel and via patient transfer to a second hospital. All isolates of S. marcescens involved in the outbreak had the same antimicrobial susceptibility pattern, with reduced susceptibility to gentamicin, cefotaxime and ciprofloxacin. Epidemiological typing revealed that the strains of S. marcescens isolated in the outbreak were of an uncommon serotype, O21:K14, and using pulsed-field gel electrophoresis, XbaI DNA macrorestriction profiles clustered at 90% similarity. The DNA patterns of the outbreak strain were also highly similar to S. marcescens isolates of the same serotype recovered from a separate Dublin hospital during the same time period as the outbreak described here. In addition, the isolates clustered at 82% similarity with strains of the same serotype from a retrospective collection of S. marcescens isolates from various hospitals in the Dublin area, indicating that these may be genetic variants of the same strain. Although the outbreak was brought under control following implementation of infection control measures, a significant number of similar O:21 isolates of S. marcescens have since been identified in four Dublin hospitals. These results suggest the unique spread of a single strain of S. marcescens in Dublin hospitals.

Cross Infection↗
PubMed1997

Hormonal therapy increases arterial compliance in postmenopausal women.

OBJECTIVES: This study investigated the effects of hormonal therapy on large arterial properties. BACKGROUND: Arterial stiffness is an emerging risk marker for coronary heart disease and is potentially modifiable. Postmenopausal use of hormonal therapy is associated with a lower risk of coronary heart disease. METHODS: Total systemic arterial compliance (SAC) and pulse wave velocity (PWV) were determined in 26 premenopausal and 52 postmenopausal women, 26 of whom were taking hormonal therapy. RESULTS: Arterial compliance was greater in the premenopausal group (mean +/- SEM 0.57 +/- 0.04 arbitrary compliance units [ACU]) than in the postmenopausal group not taking hormonal therapy (0.26 +/- 0.02 ACU, p = 0.001). Postmenopausal women taking hormonal therapy had a significantly increased total SAC compared with women not taking hormonal therapy (0.43 +/- 0.02 vs. 0.26 +/- 0.02 ACU, p = 0.001). PWV in the aortofemoral region in the premenopausal women was 6.0 +/- 0.2 vs. 8.9 +/- 0.3 m/s (p < 0.001) in untreated postmenopausal women. However, postmenopausal women taking hormonal therapy had a significantly lower PWV than those not taking hormonal therapy (7.9 +/- 0.2 vs. 8.9 +/- 0.3 m/s, p = 0.01). Eleven postmenopausal women had their hormone replacement therapy withdrawn for 4 weeks, resulting in a significant decrease in SAC and a significant increase in aortofemoral PWV. CONCLUSIONS: The increased SAC and decreased PWV in women receiving hormonal therapy suggest that such therapy may decrease stiffness of the aorta and large arteries in postmenopausal women, with potential benefit for age-related cardiovascular disorders. The reduction of arterial compliance with age appears to be altered with hormonal therapy.

Adolescent↗
PubMed1994

Effect of continuous venovenous hemofiltration with dialysis on hormone and catecholamine clearance in critically ill patients with acute renal failure.

OBJECTIVES: To measure the effect of continuous venovenous hemofiltration with dialysis on cardiovascular stability in the critically ill patients and to assess the extraction of a number of hormones and catecholamines by continuous venovenous hemofiltration with dialysis. DESIGN: Prospective, clinical study. SETTING: Intensive care unit of a tertiary medical center. PATIENTS: Twenty critically ill patients with acute renal failure. INTERVENTIONS: Timed collections of serum and ultradiafiltrate in patients receiving continuous venovenous hemofiltration with dialysis, with measurements of their catecholamine and hormonal content and calculation of continuous venovenous hemofiltration with dialysis clearances and daily extractions. Correlation of changes in catecholamines with prospectively collected hemodynamic data during the first 24 hrs of continuous venovenous hemofiltration with dialysis therapy. MEASUREMENTS AND MAIN RESULTS: No significant changes in dopamine, epinephrine, and norepinephrine requirements or plasma concentrations were seen during the first 24 hrs of continuous venovenous hemofiltration with dialysis. Overall daily losses of catecholamines in the ultradiafiltrate were small (dopamine 404 micrograms; epinephrine 32 micrograms; norepinephrine 29 micrograms). Hemodynamic variables remained stable during this period of continuous venovenous hemofiltration with dialysis therapy. All studied hormones were detected in the ultradiafiltrate, but their mean daily extractions were very small (aldosterone 0.37 micrograms; parathyroid hormone 53.4 pmol; cortisol 4.8 mg; T4 and T3 [trace amounts]; thyroid-stimulating hormone 2.6 mU; testosterone [trace amounts]). CONCLUSIONS: In critically ill patients with acute renal failure, continuous venovenous hemofiltration with dialysis results in minimal losses of catecholamines and is associated with cardiovascular stability. It causes only minor losses of several hormones. These losses are unlikely to be clinically important. Thus, blood purification achieved by continuous venovenous hemofiltration with dialysis does not produce significant catecholamine or hormonal losses and is associated with hemodynamic stability.

Acute Kidney Injury↗