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Biomedical subjects

R J Young

Publications and source records attributed to R J Young.

At least 19 recordsLinked to original sources
PubMed1998

Treatment strategies for small bowel bacterial overgrowth in short bowel syndrome.

BACKGROUND: Small bowel bacterial overgrowth is a common complication of short bowel syndrome, and although it is often controlled with antimicrobial therapy, alternative strategies may occasionally be needed. METHODS: Six patients with bacterial overgrowth are described, who did not respond to antimicrobial therapy and required additional medical or surgical measures to control the overgrowth. RESULTS: Recalcitrant bacterial overgrowth was successfully treated with periodic small bowel irrigation with a balanced hypertonic electrolyte solution, colonic flushes, encouraging frequent stooling, intestinal lengthening procedure, or probiotic therapy with Lactobacillus plantarum 299V and Lactobacillus GG. CONCLUSIONS: Small bowel bacterial overgrowth should be aggressively evaluated in patients with short bowel syndrome who are not progressing in a normal manner. Inadequate or incomplete response to antibiotic therapy is common, and several additional treatment possibilities are available.

Anti-Bacterial Agents↗
PubMed1997

Interaction of the low-affinity receptor CD23/Fc epsilonRII lectin domain with the Fc epsilon3-4 fragment of human immunoglobulin E.

CD23/Fc epsilonRII, the low-affinity receptor for IgE, is a multifunctional protein of importance in blood cell development and the immune system. We have studied the interaction of CD23 with IgE in solution using hydrodynamic methods applied to recombinant fragments of both ligands: sCD23, corresponding to the soluble lectin domain of CD23, and Fc epsilon3-4, a dimer of the C epsilon3-C epsilon4 sequence of IgE. The hydrodynamic, spectroscopic, and biological properties of these fragments suggest that they have a fully native structure. Sedimentation equilibrium studies on mixtures of sCD23 and Fc epsilon3-4 indicate that IgE has two binding sites for CD23, each characterized by affinities of approximately 10(5) M(-1). Analysis of the sedimentation as a function of temperature allows conclusions to be drawn about the thermodynamics of binding at the two sites. Binding at the first site is characterized by large changes in enthalpy (delta H(degree)To = -2.1 +/- 3.3 kcal mol(-1)) and heat capacity (delta Cp(degree) = -320 +/- 320 cal mol(-1) K(-1)), whereas binding at the second site is characterized by small changes in enthalpy (delta H(degree)To = 0.1 +/- 5.6 kcal mol(-1)) and heat capacity (delta Cp(degree) = -140 +/- 550 cal mol(-1) K(-1)). In native CD23, there are two or three lectin domains, associated through an alpha-helical coiled-coil stalk. The predicted structure of the CD23 oligomers and symmetry considerations rule out the possibility of two lectin domains from one oligomer binding to identical sites in IgE. The notion of two types of interaction in the 2:1 complex between CD23 and IgE is consistent with the thermodynamic data presented.

Binding Sites↗
PubMed1997

Influence of bacterial overgrowth and intestinal inflammation on duration of parenteral nutrition in children with short bowel syndrome.

OBJECTIVES: Massive intestinal resection results in short bowel syndrome and necessitates prolonged parenteral feeding. The purpose of this work was to assess the impact of late complications of short bowel syndrome, including intestinal bacterial overgrowth and enterocolitis, on the duration of parenteral nutrition (PN) in comparison with factors evident in the neonatal period. METHODS: Retrospective chart review. RESULTS: Of 49 children, 42 were weaned from parenteral nutrition after a treatment course of 17 +/- 14 months. In these 42, postresection small intestinal length equaled 81 +/- 65 cm; 45% had an ileocecal valve. Small intestinal length in the seven children who were PN dependent was 31 +/- 30 cm (p < 0.05); none had an ileocecal valve (p < 0.05). Bacterial overgrowth occurred in all seven PN-dependent children and in 23 of 42 children eventually weaned from PN (p < 0.05). When bacterial overgrowth was identified before weaning (n = 12), the duration pf PN was 28 +/- 17 months, but when bacterial overgrowth was first identified only after weaning (n = 11), the duration of PN was 16 +/- 13 months (p < 0.05). Small intestinal inflammation correlated with bacterial overgrowth (r = 0.69). Those children with severe enteritis identified before weaning remained on the PN regimen for 36 +/- 15 months, in comparison with 21 +/- 14 months in those with mild enteritis and 13 +/- 11 months in those without inflammation (p < 0.02). CONCLUSIONS: Although the length of small intestine remaining after resection is the best immediate predictor of final success in terminating PN in children with short bowel syndrome, PN is prolonged by bacterial overgrowth and associated enteritis in those who will ultimately be weaned.

Bacteria↗
PubMed1997

Intermittent bolus dosing of ceftazidime in critically ill patients.

Ceftazidime is frequently used in critically ill patients, particularly for the treatment of Pseudomonas aeruginosa infections. The recommended dosing regimen is based on pharmacokinetic data obtained in healthy volunteers and may not be appropriate in the critically ill. We administered ceftazidime in the maximum recommended dose (2 g i.v. every 8 h) to ten critically ill patients with normal plasma creatinine. Eighteen arterial blood samples were taken from each patient over the first 8 h for measurement of ceftazidime concentrations and subsequent compartmental pharmacokinetic analysis. An additional trough sample was taken from each patient on day 3. Although mean pharmacokinetic variables did not differ from previously reported data in normal volunteers there was wide variability in plasma drug concentrations. Three of our patients had plasma ceftazidime concentrations less than the MIC for P. aeruginosa (8 mg/L) and nine had concentrations less than 5 x MIC, which has been recommended to ensure efficacy. On day 3 trough ceftazidime concentrations were less than the MIC in four out of the seven patients in whom measurements were made and less than 5 x MIC in the remaining three. There was no clinical predictor of which patients would have low plasma concentrations. Our results show that plasma concentrations of ceftazidime are very variable when the recommended intermittent bolus dosing regimen is used and may result in inadequate plasma concentrations of drug in critical infections. This may result in treatment failure and the emergence of antibiotic resistance. A loading dose followed by continuous infusion should overcome these problems but this awaits in-vivo evaluation.

Adult↗
PubMed1997

Oxygen delivery, oxygen consumption, and gastric intramucosal pH are not improved by a computer-controlled, closed-loop, vecuronium infusion in severe sepsis and septic shock.

OBJECTIVE: To investigate the influence of the neuromuscular blocking agent vecuronium on oxygen delivery (DO2), oxygen consumption (VO2), oxygen extraction ratio, and gastric intramucosal pH in heavily sedated patients with severe sepsis or septic shock. DESIGN: Prospective, randomized, placebo-controlled, cross-over trial. SETTING: University hospital intensive care unit. PATIENTS: Eighteen mechanically ventilated patients with severe sepsis or septic shock. INTERVENTIONS: All patients were heavily sedated. After baseline measurement, a computer-controlled, closed-loop infusion of either vecuronium or saline was initiated and further measurements were made at 40 and 60 mins. The procedure was repeated with the alternative agent after return of neuromuscular function. MEASUREMENTS AND MAIN RESULTS: DO2, VO2, intramucosal pH were monitored using pulmonary artery catheters, a gas exchange monitor, and gastric tonometers. Changes from baseline were compared (paired t-test, p = .05). The vecuronium closed-loop infusion achieved T1 between 5% and 15% at 40 mins. There was a significant difference in the changes from baseline for static respiratory compliance in the vecuronium closed-loop infusion group compared with the saline closed-loop infusion group. There was no significant difference in the change from baseline for systemic or pulmonary vascular resistance, DO2, VO2, oxygen extraction ratio, or intramucosal pH. CONCLUSIONS: In these patients, vecuronium infusion achieved the targeted level of paralysis and improved respiratory compliance but did not alter intramucosal pH, VO2, DO2, or oxygen extraction ratios. With deep sedation, neuromuscular blockade in severe sepsis/septic shock does not significantly influence oxygen flux and should be abandoned as a routine method of improving tissue oxygenation in these patients.

Adult↗
PubMed1997

Gastric tonometry and prediction of outcome in the critically ill. Arterial to intramucosal pH gradient and carbon dioxide gradient.

Splanchnic ischaemia is thought to be of central importance in the development of multi-organ failure and hence death in critically ill patients. It has been suggested that the arterial to gastric intramucosal pH gradient and the difference in partial pressure of carbon dioxide between gastric mucosa and arterial blood are more sensitive markers of splanchnic ischaemia than gastric intramucosal pH itself and thus should be predictors of mortality in the critically ill. We studied 62 critically ill patients within 6 h of admission to the intensive care unit and found no significant difference at 0, 12 or 24 h after admission to the study in either the arterial to gastric intramucosal pH gradient or the difference in partial pressure of carbon dioxide between gastric mucosa and arterial blood between survivors and nonsurvivors. We conclude that in contrast to gastric intramucosal pH neither the arterial to gastric intramucosal pH gradient nor the difference in partial pressure of carbon dioxide between gastric mucosa and arterial blood distinguish survivors from nonsurvivors.

Adult↗
PubMed1997

Granulocyte-colony stimulating factor in the treatment of colchicine poisoning.

1. Colchicine is a highly active alkaloid used in the treatment of gouty arthritis and pseudogout. In overdose colchicine inhibits cell division effecting organs with a high rate of cell turn-over, such as the gastrointestinal tract and bone marrow. Early fatality results from cardiovascular collapse and respiratory failure, however pancytopenia and overwhelming septicaemia can occur later. 2. We describe a case of suicidal ingestion of 25-30 mg of colchicine in a previously healthy 43-year-old woman. Initial symptoms were mainly gastrointestinal. By day 5 she had developed severe pancytopenia and early sepsis, which were successfully treated using granulocyte colony stimulating factor (G-CSF) 600 micrograms s.c. 3. In vitro G-CSF is produced by the haematopoietic system. However, G-CSF can now be produced by recombinant DNA cloning technology and thus is available clinically. 4. There is no recognised antidote for colchicine poisoning and treatment is symptomatic. Fab fragments may have a promising future in eliminating colchicine from the body, but are currently not clinically available. In those patients that survive the initial phase of poisoning, G-CSF offers an effective method of treating the pancytopenia and preventing overwhelming septicaemia. Daily monitoring of the patient's haematological status is strongly recommended.

Adult↗
PubMed1997

Mitogenic actions of endothelin and other growth factors in ovine endometrium.

Endothelin-1 (ET-1) is present in ovine endometrium, primarily in epithelial cells, and increases around the time of implantation. We examined the cell type expressing ET-binding sites in vitro and whether ET-1 has mitogenic actions in the endometrium, alone or in synergy with other growth factors. Purified epithelial and stromal cells were prepared from luteal-phase endometrium. Specific receptors were demonstrated by binding of 125I-ET-1 and proliferative effects of ET-1 and/or other growth factors determined by uptake of [3H]thymidine by cells in serum-free culture. 125I-ET-1 bound to both epithelial (2516 +/- 820 c.p.m./well) and stromal (6368 +/- 1350 c.p.m./well) cells and was displaced by ET-1 (1 mumol l-1). There were no proliferative effects of ET on epithelial cells. ET-1 (10 nmol l-1) stimulated uptake of [3H]thymidine by stromal cells under serum-free conditions in 13/20 individual cell preparations, to 149 +/- 13% of control (untreated = 100%) with dose-dependence between the range of 1 to 100 nmol l-1. Stimulation by fetal calf serum was to 377 +/- 126% of control. The effects on proliferation by other growth factors (dose; % of control +/- S.E.M., number of positive/total number of cell preparations) were: IGF-I (13 nmol l-1; 182 +/- 14, 4/4), epidermal growth factor (EGF; 4.8 nmol l-1; 132 +/- 5%, 7/7), platelet-derived growth factor-BB (0.4 nmol l-1; 146 +/- 3, 2/2) and leukaemia inhibitory factor (0.4 nmol 1-1; 110 +/- 2, 3/3). All stimulations except that of EGF were significant and dose-responsive but only insulin was additive with ET (350 +/- 35, 5/5). ET-1 also stimulated expression of the the AP-1 cis element c-jun, this being maximal at 60 min of exposure to mitogen. ET-1, along with other growth factors has a likely paracrine role in cellular proliferation in the endometrium, possibly in association with blastocyst implantation.

Animals↗
PubMed1996

Comparison of intrathoracic and intra-abdominal measurements of central venous pressure.

BACKGROUND: Complications can arise from standard intrathoracic central venous pressure (CVP) measurements in critically ill, mechanically ventilated patients. We have assessed the feasibility of catheterisation by the femoral route to measure CVP in the abdomen (ACVP). We compared measurements by the standard jugular or subclavian route (TCVP) with simultaneous ACVP measurements by the femoral route. METHODS: Between June, 1994 and May, 1995, we recruited 20 critically ill adult patients with various disorders; all patients already had a TCVP line in situ. We placed a femoral catheter in the inferior vena cava close to the right atrium under electrocardiographic guidance. The catheter position was confirmed (and corrected if necessary) by chest radiography. CVP was measured from both sites hourly for 6 h. Positive end-expiratory pressure, mean airway pressure, and intra-abdominal pressure were recorded simultaneously. FINDINGS: One patient was excluded because radiography showed that the catheter position was incorrect. For 133 paired measurements of ACVP and TCVP in the remaining 19 patients, the mean difference was 0.45 mm Hg (SD 0.89: 95% Cl 0.30-0.60); the limits of agreement were -1.33 to 2.23 mm Hg (-1.63 to 2.53). We found a small tendency for the difference between ACVP and TCVP to increase as positive end-expiratory pressure and mean airway pressure increased; the difference was statistically, but not clinically, significant. INTERPRETATION: Our study showed that for clinical purposes CVP can be measured by a femoral catheter placed in the abdominal inferior vena cava near the right atrium. This approach can replace standard TCVP measurements in critically ill, mechanically ventilated patients.

Abdomen↗
PubMed1996

Paranodal structure in diabetic sensory polyneuropathy.

Observations have been made on the structure of the paranodal region at nodes of Ranvier in the sural nerve of patients with diabetic sensory polyneuropathy. The structure of the paranodes was examined with particular attention to the definition and assessment of axoglial dysjunction, which has been claimed to be a characteristic feature of both human and experimental diabetic neuropathy and which has been related to paranodal swelling. In the present series of cases it was not possible to confirm that axoglial dysjunction is a distinctive feature of diabetic polyneuropathy in fibres not undergoing active demyelination or wallerian-type degeneration, neither was excessive paranodal enlargement found.

Adult↗
PubMed1996

Upper airway obstruction caused by acquired inhibitor to factor VIII.

Bleeding caused by inhibitors to factor VIII is a rare medical emergency requiring immediate specialist investigation and management. Urgent initiation of therapy with high dose factor VIII concentrates may be life saving. Successful management of acute upper airway obstruction from uncontrolled haemorrhage into the oropharyngeal tissues should be achieved with fibreoptic guided nasotracheal intubation.

Adult↗
PubMed1996

Ranitidine therapy for esophagitis in children with developmental disabilities.

Esophagitis is common in children with cerebral palsy. Because histamine2-receptor antagonists such as ranitidine have not been uniformly effective, we treated disabled children with esophagitis with greater than usual doses. Endoscopy and pH monitoring were used to monitor dose and response to treatment. A dose of 9.3 +/- 0.9 mg/kg/day did not improve visual or microscopic esophagitis after 3 months. A dose of 14.8 +/- 3.9 mg/kg/day resulted in only slight microscopic improvement, but symptoms were improved. There was no correlation between esophageal reflux index at enrollment and either severity of esophagitis or response to treatment. Elevation of gastric pH by ranitidine was infrequent. These results affirm that pH monitoring does not reliably identify disabled children with reflux esophagitis nor does ranitidine reliably heal this disorder.

Adolescent↗
PubMed1996

Fatal acute hepatorenal failure following potassium permanganate ingestion.

Potassium permanganate (KMnO4), a powerful oxidizing agent, is readily available without prescription. Tissue contact produces coagulation necrosis and the lethal consequences of oral ingestion are well described, with most deaths because of airway oedema and obstruction or circulatory collapse. Whilst systemic toxicity is reported, its mechanism is unclear. We describe a case of suicidal ingestion of KMnO4 followed by acute hepatorenal toxicity resulting in the death of the patient. The clinical course bore close resemblance to that of severe paracetamol overdose. We discuss the pathogenesis of the systemic toxicity of KMnO4 and postulate that it is due to oxidative injury from free radicals generated by the absorbed permanganate ion. We recommend that N-acetyl cysteine be given within the first few hours to all patients with potassium permanganate poisoning.

Accidents, Home↗
PubMed1996

Reduced insulin-like growth factor binding protein-1 (IGFBP-1) levels correlate with increased cardiovascular risk in non-insulin dependent diabetes mellitus (NIDDM).

IGF-I and -II levels are altered in patients with atherogenic lipid profiles and may contribute to the development of macrovascular disease in NIDDM. We examined cardiovascular risk factors, IGF-I, IGF-II and IGFBP-1 in 74 NIDDM patients analysed as a whole group and according to treatment type. IGF-I was not significantly associated with cardiovascular risk factors but IGF-II levels correlated positively with total and LDL cholesterol most markedly in the diet treated group (0.72, p < 0.01 and 0.76, p < 0.01 respectively). In the whole group reduced IGFBP-1 levels were significantly associated with factors known to increase cardiovascular risk: i.e. low HDL cholesterol (0.31, p < 0.01) and elevated blood pressure (-0.35, p < 0.01), BMI (-0.37, p < 0.01), insulin (-0.29, p < 0.01) and proinsulin (-0.24, p < 0.01). In the treatment groups IGFBP-1 was lower in patients on diet alone (n = 11, 42.6 +/- 11.6 mu g/l) and sulphonylurea +/- insulin (n = 39, 53.2 +/- 7.6 mu g/l) relative to insulin treatment (n = 24, 103.0 +/- 19, 7 mu g/l, p < 0.05). The lower levels of IGFBP-1 were not due to a significant change in phosphorylation status from the highly phosphorylated circulating form since lesser and non-phosphorylated variants were undetectable in 53/74 patients. Multiple regression analysis revealed the best predictors of IGFBP-1 were BMI and MAP (R2 = 0.2. p < 0.001) and for blood pressure, IGFBP-1 and age (R2 = 0.47, p < 0.001). These findings indicate that in NIDDM patients low IGFBP-1 levels are associated with multiple factors predisposing to atherogenesis.

Blood Pressure↗