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Biomedical subjects

C Marshall

Publications and source records attributed to C Marshall.

At least 37 records · Page 2Linked to original sources
PubMed1999

How do small GTPase signal transduction pathways regulate cell cycle entry?

A variety of studies have shown that activation of the cell cycle machinery requires the participation of multiple signalling pathways. These pathways include Ras-dependent effectors such as the extracellular-signal related kinases, otherwise known as mitogen-activated protein kinases (ERKs, MAPKs), phosphatidylinositol 3 (PI3)-kinase and p21Ral pathways, as well as other signalling pathways regulated by the small GTPases p21Rho, p21Rac and p21Cdc42.

Cell Cycle↗
PubMed1999

Evaluation of a protocol for the non-operative management of perforated peptic ulcer.

BACKGROUND: The non-operative management of perforated peptic ulcer has previously been shown to be both safe and effective although it remains controversial. A protocol for non-operative management was set up in this hospital in 1989. Adherence to the guidelines in the protocol has been audited over a 6-year period with a review of outcome. METHODS: The case-notes of patients with a diagnosis of perforated peptic ulcer were reviewed. Twelve guidelines from the protocol were selected for evaluation of compliance to the protocol. RESULTS: Forty-nine patients underwent non-operative treatment initially. Eight patients failed to respond and underwent operation. Complications included abscess formation (seven patients), renal failure (one), gastric ileus (one), chest infection (two), and cardiac failure and stroke (one). Four deaths occurred in this group. Adherence to certain protocol guidelines was poor, notably those concerning prevention of thromboembolism, use of antibiotics, use of contrast examination to confirm the diagnosis and referral for follow-up endoscopy. Two gastric cancers were detected on subsequent endoscopy. CONCLUSION: This experience demonstrates that non-operative treatment can be used successfully in a general hospital. Adherence to protocol guidelines was found to be variable and the protocol has therefore been simplified. This study highlights the need for an accurate diagnosis and the importance of follow-up endoscopy.

Adolescent↗
PubMed1999

Endothelin-1 is elevated in monocrotaline pulmonary hypertension.

These studies document striking pulmonary vasoconstrictor response to nitric oxide synthase (NOS) inhibition in monocrotaline (MCT) pulmonary hypertension in rats. This constriction is caused by elevated endothelin (ET)-1 production acting on ETA receptors. Isolated, red blood cell plus buffer-perfused lungs from rats were studied 3 wk after MCT (60 mg/kg) or saline injection. MCT-injected rats developed pulmonary hypertension, right ventricular hypertrophy, and heightened pulmonary vasoconstriction to ANG II and the NOS inhibitor NG-monomethyl-L-arginine (L-NMMA). In MCT-injected lungs, the magnitude of the pulmonary pressor response to NOS inhibition correlated strongly with the extent of pulmonary hypertension. Pretreatment of isolated MCT-injected lungs with combined ETA (BQ-123) plus ETB (BQ-788) antagonists or ETA antagonist alone prevented the L-NMMA-induced constriction. Addition of ETA antagonist reversed established L-NMMA-induced constriction; ETB antagonist did not. ET-1 concentrations were elevated in MCT-injected lung perfusate compared with sham-injected lung perfusate, but ET-1 levels did not differ before and after NOS inhibition. NOS inhibition enhanced hypoxic pulmonary vasoconstriction in both sham- and MCT-injected lungs, but the enhancement was greater in MCT-injected lungs. Results suggest that in MCT pulmonary hypertension, elevated endogenous ET-1 production acting through ETA receptors causes pulmonary vasoconstriction that is normally masked by endogenous NO production.

Angiotensin II↗
PubMed1999

Collaborative prototyping approaches for ICU decision aid design.

When computer-based aids do not support the human users' decision-making strategies or anticipate the organizational impacts of technological change, advances in information technology may degrade rather than enhance decision-making performance. Such failures suggest the design of human-computer cooperation for problem solving and decision-making must be driven by human cognitive and organizational process requirements rather than computer technology. Decision- and user-centered development techniques involve domain experts and end-users in the earliest phases of design to evolve an understanding of requirements through iterative prototyping. This paper presents a collaborative approach to cognitive systems engineering applied to developing a clinical aid to assist respiratory care in the surgical ICU.

Computer Systems↗
PubMed1998

Bowel dysfunction after bladder reconstruction.

PURPOSE: Bowel function may be disturbed after intestinal segments are used in urinary reconstruction. The etiology of this condition and its incidence in different patient groups is unclear. We studied the incidence of bowel disturbance in patients who underwent bladder replacement, continent diversion, enterocystoplasty for idiopathic detrusor instability and ileal conduit diversion. MATERIALS AND METHODS: We evaluated 71 patients after ileal conduit diversion and 82 after bladder reconstruction, including clam enterocystoplasty for detrusor instability in 28, neurogenic bladder dysfunction in 26 and nonneuropathic conditions in 28. We noted the severity of symptoms, such as frequency of defecation, nocturnal diarrhea, flatus leakage, fecal urgency, fecal incontinence and explosive diarrhea, as well as quality of life. RESULTS: Of the patients who underwent bladder reconstruction 24% had symptoms of bowel dysfunction preoperatively and 42% of those who were asymptomatic preoperatively described new bowel symptoms postoperatively. These symptoms were most common and severe in 54% of patients after clam enterocystoplasty for detrusor instability compared to 26% with neuropathy, 14% with a nonneuropathic condition and 15% with an ileal conduit. Compared to those in other groups patients who underwent enterocystoplasty for detrusor instability had a significantly higher incidence of nocturnal bowel movements (18 versus less than 4%, p <0.01), flatus leakage (29 versus less than 8%, p <0.01), fecal urgency (39 versus less than 12%, p <0.001) and fecal incontinence (32 versus less than 16%, p <0.001). The length of ileum used for clam enterocystoplasty was only slightly greater than that used for ileal conduit operations (25 versus 18 cm.). Of the patients who underwent enterocystoplasty for detrusor instability 29% regretted undergoing the procedure due to subsequent bowel symptoms. CONCLUSIONS: After enterocystoplasty for detrusor instability patients are at risk of significant bowel symptoms. The development of new bowel symptoms was associated with poor patient satisfaction.

Adult↗
PubMed1998

Single- versus multiple-dose antimicrobial prophylaxis for major surgery: a systematic review.

BACKGROUND: Single-dose antimicrobial prophylaxis for major surgery is a widely accepted principle; recommendations have been based on laboratory studies and numerous clinical trials published in the last 25 years. In practice, single-dose prophylaxis has not been universally accepted and multiple-dose regimens are still used in some centres. Moreover, the principle has recently been challenged by the results of an Australian study of vascular surgery. The aim of this current systematic review is to determine the overall efficacy of single versus multiple-dose antimicrobial prophylaxis for major surgery and across surgical disciplines. METHODS: Relevant studies were identified in the medical literature using the MEDLINE database and other search strategies. Trials included in the review were prospective and randomized, had the same antimicrobial in each treatment arm and were published in English. Rates of postoperative surgical site infections (SSI) were extracted, 2 x 2 tables prepared and odds ratios (OR) [with 95% confidence intervals (95% CI)] calculated. Data were then combined using fixed and random effects models to provide an overall figure. In this context, a high value for the combined OR, with 95% CI > 1.0, indicates superiority of multiple-dose regimens and a low OR, with 95% CI < 1.0, suggests the opposite. A combined OR close to 1.0, with narrow 95% CI straddling 1.0, indicates no clear advantage of one regimen over another. Further subgroup analyses were also performed. RESULTS: Combined OR by both fixed (1.06, 95% CI, 0.89-1.25) and random effects (1.04, 95% CI, 0.86-1.25) models indicated no clear advantage of either single or multiple-dose regimens in preventing SSI. Likewise, subgroup analysis showed no statistically significant differences associated with type of antimicrobial used (beta-lactam vs other), blinded wound assessment, length of the multiple-dose arm (> 24 h vs 24 h or less) or type of surgery (obstetric and gynaecological vs other). CONCLUSIONS: Continued use of single-dose antimicrobial prophylaxis for major surgery is recommended. Further studies are required, especially in previously neglected surgical disciplines.

Anti-Bacterial Agents↗
PubMed1998

Role of wall tension in hypoxic responses of isolated rat pulmonary arteries.

The changes in force developed during 40-min exposures to hypoxia (37 +/- 1 mmHg) were recorded in large (0.84 +/- 0.02-mm-diameter) and small (0.39 +/- 0.01-mm-diameter) intrapulmonary arteries during combinations of mechanical wall stretch tensions (passive + active myogenic components), equivalent to transmural vascular pressures of 5, 15, 30, 50, and 100 mmHg, and active (vasoconstriction) tensions, stimulated by PGF2alpha in doses of 0, 25, 50, and 75% effective concentrations. Constriction was observed in all arteries during the first minute; however, at any active tension, the pattern of the subsequent response was a function of the stretch tension. At 5, 15, and 30 mmHg, the constriction decreased slightly at 5 min and then increased again to remain constrictor throughout. At 50 and 100 mmHg, the initial constriction was followed by persistent dilation. Hypoxic constrictor responses, most resembling those observed in lungs in vivo and in vitro, were observed when the mechanical stretch wall tension was equivalent to 15 or 30 mmHg and the dose of PGF2alpha was 25 or 50% effective concentration. These observations reconcile many apparently contradictory results reported previously.

Animals↗
PubMed1998

Improved oxygenation with prostaglandin F2alpha with and without inhaled nitric oxide in dogs.

Dogs of mixed breed (n = 7) were anesthetized, right lung atelectasis was established, and the cyclooxygenase pathway was blocked with ibuprofen. Measurements of pulmonary gas exchange were performed (fractional concentration of inspired O2 = 0.95) after infusions of prostaglandin F2alpha (PGF2alpha; 2 microg . kg-1 . min-1), ventilation with nitric oxide (NO; 40 ppm), or both (PGF2alpha + NO) in random order. The arterial PO2 (PaO2) under control conditions was 117 +/- 16 Torr (shunt = 33 +/- 2.5%), was unchanged with NO alone (PaO2 = 114 +/- 17 Torr; shunt = 35.7 +/- 3. 1%), but was significantly improved with PGF2alpha alone (PaO2 = 180 +/- 28 Torr; shunt = 23.2 +/- 2.8%) and with the combination of PGF2alpha + NO (PaO2 = 202 +/- 30 Torr; shunt = 20.9 +/- 2.5%). The addition of NO did not significantly enhance the effectiveness of the PGF2alpha on PaO2. Simulation of these data in a computer model, combining pulmonary gas exchange and pulmonary blood flow, reproduced the results on the basis that vasoconstriction with PGF2alpha was maximal under hypoxia in the atelectatic lung and reduced by hyperoxia in the ventilated lung, consistent with the hypothesis of O2 dependence of PGF2alpha vasoconstriction.

Administration, Inhalation↗
PubMed1997

Improvement in oxygenation by phenylephrine and nitric oxide in patients with adult respiratory distress syndrome.

BACKGROUND: Inhaled nitric oxide (NO), a selective vasodilator, improves oxygenation in many patients with adult respiratory distress syndrome (ARDS). Vasoconstrictors may also improve oxygenation, possibly by enhancing hypoxic pulmonary vasoconstriction. This study compared the effects of phenylephrine, NO, and their combination in patients with ARDS. METHODS: Twelve patients with ARDS (PaO2/FIO2 180; Murray score 2) were studied. Each patient received three treatments in random order: intravenous phenylephrine, 50-200 micrograms/min, titrated to a 20% increase in mean arterial blood pressure; inhaled NO, 40 ppm; and the combination (phenylephrine+NO). Hemodynamics and blood gas measurements were made during each treatment and at pre- and posttreatment baselines. RESULTS: All three treatments improved PaO2 overall. Six patients were "phenylephrine-responders" (delta PaO2 > 10 mmHg), and six were "phenylephrine-nonresponders." In phenylephrine-responders, the effect of phenylephrine was comparable with that of NO (PaO2 from 105 +/- 14 to 132 +/- 14 mmHg with phenylephrine, and from 110 +/- 14 to 143 +/- 19 mmHg with NO), and the effect of phenylephrine+NO was greater than that of either treatment alone (PaO2 from 123 +/- 13 to 178 +/- 23 mmHg). In phenylephrine-nonresponders, phenylephrine did not affect PaO2, and the effect of phenylephrine+NO was not statistically different from that of NO alone (PaO2 from 82 +/- 12 to 138 +/- 28 mmHg with NO; from 84 +/- 12 to 127 +/- 23 mmHg with phenylephrine+NO). Data are mean +/- SEM. CONCLUSIONS: Phenylephrine alone can improve PaO2 in patients with ARDS. In phenylephrine-responsive patients, phenylephrine augments the improvement in PaO2 seen with inhaled NO. These results may reflect selective enhancement of hypoxic pulmonary vasoconstriction by phenylephrine, which complements selective vasodilation by NO.

Adult↗
PubMed1996

Injuries related to car crime: the joy-riding epidemic.

'Joy-riding' is the term used, somewhat inappropriately, for the offence of taking a vehicle without the owner's consent. In certain areas, mainly deprived inner-city estates, there has been an increase in this crime. The aim of this study was to investigate its impact on the workload of an inner-city teaching hospital's busy accident and orthopaedic departments. In this prospective study, all patients admitted to hospital as a result of road-traffic accidents (RTAs) were identified during a 9 month period. A total of 1576 patients were admitted to the trauma unit. One hundred and fifty-two admissions were as a result of RTA and 20 (13 per cent) of these patients had injuries as a result of car crime. Of this group, eight were severely injured (ISS > 16) and six of these were innocent bystanders. Three patients (one joy-rider and two innocent bystanders) died as a result of car crime. The average length of hospital stay was 12 days (1-62 days) and the hospital in-patient costs were estimated to be at least 5200 pounds per patient. Injuries related to car crime results in a significant amount of work and financial cost to the National Health Service.

Accidents, Traffic↗