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Biomedical subjects

W Murray

Publications and source records attributed to W Murray.

At least 19 recordsLinked to original sources
PubMed1999

6-oxa isosteres of anacardic acids as potent inhibitors of bacterial histidine protein kinase (HPK)-mediated two-component regulatory systems.

A series of 6-oxa isosteres of anacardic acids (6-higher alkyl/alkenyl-2-hydroxybenzoic acids) was synthesised and several members were discovered to be among the most potent inhibitors (IC50 values < or = 5 microM) of the bacterial two-component regulatory systems, KinA/SpoOF and NRII/NRI, reported to date. The Gram-positive antibacterial activity in selected strains is also presented.

Anacardic Acids↗
PubMed1997

Computed tomography intravenous cholangiography.

Indications for direct visualization of the bile ducts include bile duct dilatation demonstrated by ultrasound or CT scanning, where the cause of the bile duct dilatation is uncertain or where the anatomy of bile duct obstruction needs further clarification. Another indication is right upper quadrant pain, particularly in a post-cholecystectomy patient, where choledocholithiasis is suspected. A possible new indication is pre-operative evaluation prior to laparoscopic cholecystectomy. The bile ducts are usually studied by endoscopic retrograde cholangiopancreatography (ERCP), or, less commonly, trans-hepatic cholangiography. The old technique of intravenous cholangiography has fallen into disrepute because of inconsistent bile-duct opacification. The advent of spiral CT scanning has renewed interest in intravenous cholangiography. The CT technique is very sensitive to the contrast agent in the bile ducts, and angiographic and three-dimensional reconstructions of the biliary tree can readily be obtained using the CT intravenous cholangiogram technique (CT IVC). Seven patients have been studied using this CT IVC technique, between February 1995 and June 1996, and are the subject of the present report. Eight further studies have since been performed. The results suggest that CT IVC could replace ERCP as the primary means of direct cholangiography, where pancreatic duct visualization is not required.

Aged↗
PubMed1996

The bundle-forming pili of enteropathogenic Escherichia coli: transcriptional regulation by environmental signals.

The bundle-forming pili (BFP) of enteropathogenic Escherichia coil (EPEC) are required for the development of circumscribed colonies of bacteria attached to the surfaces of cultured epithelial cells, a process termed the localized adherence (LA) phenotype. Similar lesions are evident in jejunal biopsies from EPEC-infected children. BFP production is not constitutive, but instead occurs upon transfer of bacteria from nutrient broth to tissue culture media, indicating that the expression of BFP may be environmentally regulated. To learn more about how BFP protein expression is induced during epithelial-cell adherence, bfpA-cat transcriptional fusions and northern blot analyses were employed to monitor bfpA expression as a function of environmental signals and growth kinetics. bfpA expression was found to be regulated at the transcriptional level, and to require a separate locus on the EPEC adherence factor (EAF) plasmid. Expression occurred selectively during exponential-growth phase and was greatest between 35 and 37 degrees C, and in the presence of calcium. Ammonium (20 mM) significantly reduced bfpA mRNA and protein expression and the development of the LA phenotype. Analysis of the bfpA upstream sequence and identification of the transcription initiation site revealed a conventional sigma (70)-dependent promoter and an AT-rich tract that might affect promoter activity. Taken together, these findings further support the pathogenic role of BFP by explaining how BFP production would commence in the small intestine and terminate in the colon and in external habitats.

Amino Acid Sequence↗
PubMed1994

Helium pneumoperitoneum for laparoscopic cholecystectomy: ventilatory and blood gas changes.

Laparoscopic cholecystectomy with carbon dioxide pneumoperitoneum may result in hypercarbia and acidosis in patients with cardiorespiratory disease. The aim of the present study was to assess helium as an alternative to carbon dioxide for creating the pneumoperitoneum. Ventilation requirements and carbon dioxide levels were assessed at the beginning and end of laparoscopic cholecystectomy using helium (n = 30) and carbon dioxide (n = 30) pneumoperitoneum. Insufflation with helium did not result in an increase in ventilation requirement although, like carbon dioxide pneumoperitoneum, it was associated with a mean rise in peak airway pressure (of 7 cmH2O; P < 0.001). There was also a 3.2-kPa increase in the alveolar-arterial oxygen gradient with helium (P = 0.006). Carbon dioxide pneumoperitoneum was associated with a significant rise in arterial carbon dioxide levels, despite increasing ventilation. Four patients with helium pneumoperitoneum had surgical emphysema for 5 days. Helium may be a suitable alternative to carbon dioxide for creating pneumoperitoneum in patients with severe cardiorespiratory disease. However, because of its low water solubility helium has a lower safety margin than carbon dioxide in the rare event of gas embolism.

Adult↗
PubMed1994

Hyperviscosity syndrome in disseminated breast adenocarcinoma.

Circulation within the bloodstream of mucin derived from mucin-producing adenocarcinomas has been documented infrequently but has been associated with vascular occlusion, organ infarction, and hyperviscosity. The nature of the mucin and the therapeutic role of plasmapheresis in this condition has not been reported. A 64-yr-old female, who had undergone a mastectomy 3 yrs previously for an infiltrating mucinous breast adenocarcinoma, presented with dementia. A blood film showed marked rouleaux and a bluish background. No abnormal bands were detected on plasma protein electrophoresis. Blood, serum and plasma viscosity were above the range of readability of the viscometer. A bone marrow biopsy showed replacement with tumor similar to the original. Repeated plasmaphereses substantially reduced viscosity and temporarily improved her mental state. Post mortem revealed numerous infarcts with eosinophilic mucoid material in the lumen of many small vessels. That the offending plasma constituent was a sialomucin was suggested by mucin stains of the tumor and peripheral blood, a plasma sialic acid level 10 x normal and a substantial fall in viscosity after in vitro treatment of plasma with neuraminidase.

Adenocarcinoma, Mucinous↗
PubMed1992

Pharmacokinetics of the digoxin-quinidine interaction via mixed-effect modelling.

It was the purpose of this study to evaluate the effect of quinidine administration on the population estimates of the volume of distribution (Vdpop) and clearance (CLpop) of digoxin. The data collected on 94 patients included 230 measured serum digoxin concentrations, height, age, sex, weight (wt), serum creatinine, history of digoxin and quinidine administration and the presence or absence of congestive heart failure (CHF). Using the NONMEM software program, estimates were obtained for CLpop and Vdpop. Variables tested for inclusion in the CLpop model were creatinine clearance (CLCR), CHF, wt, ideal bodyweight, quinidine (QUIN) [both as a discrete variable and in a dose-dependent manner], and body surface area. Variables tested for inclusion in the Vdpop model were CLCR, wt, ideal bodyweight, body surface area and quinidine. During model building a p-value of 0.05 was chosen for variable inclusion. The final model was as follows: CLpop (L/h) = (3.1 + 0.0516 x CLCR) x QUIN Vdpop (L) = (4.03 + 0.0832 x CLCR) x wt F = 0.82 where F is bioavailability. In the above, QUIN is 0.567 if quinidine is being concurrently administered and 1.0 if it is not. The coefficient of variation (CV) of CLpop was 44% while that of Vdpop was 48%. The residual intrasubject CV was 26%. These results compare favourably with previously derived methods of estimating digoxin CLpop and Vdpop but may improve on those methods due to the inclusion of quinidine in the model. These better estimates should result in improved initial dosage of digoxin.

Adult↗
PubMed1990

Audit of serum drug concentration analysis for patients in the surgical intensive care unit.

Serum drug concentration measurements can help the practitioner attain maximal therapeutic efficacy and minimal undesirable effects of certain medications. It is necessary, however, to obtain serum samples appropriately to assure that the result will provide useful information. In preparation for expansion of clinical pharmacy services to the surgical ICU, a study was performed to a) identify the drugs for which serum samples were requested and b) assess whether the results of the serum samples were being used appropriately to adjust doses. Currently, the pharmacy pharmacokinetics service routinely analyzes serum concentrations for antimicrobial agents, theophylline, and other drugs as requested. By the end of this year, we expect further expansion to include phenytoin, pentobarbital, phenobarbital, procainamide/NAPA, lidocaine, and digoxin.

Analgesics↗
PubMed1990

Nitrous oxide does not impair hepatic function in young or old surgical patients.

We investigated whether anesthesia including nitrous oxide (N2O) caused hepatic injury, and whether any adverse effect of N2O was affected by patient age. One hundred patients having total hip replacements were randomly assigned to a regimen that included or excluded N2O (50%-60%) during regional anesthesia supplemented with isoflurane and intravenous adjuvants. Using postoperative plasma levels of alanine aminotransferase, bilirubin, and alkaline phosphatase 1 and 3 days after surgery as indicators of hepatic impairment, we found no evidence that N2O causes hepatic injury in either young or old patients.

Aged↗
PubMed1989

Oesophageal cancer in South Africa. A review of 1926 cases.

From November 1985 to August 1988, the National Study Group for Oesophageal Cancer collected and centralized data on 1926 new cases of oesophageal cancer in South Africa. A standard data sheet was used to record the age, sex, and condition of the patients, the site, length, and circumferential extent of the tumor, the presence of extraoesophageal and distant spread, associated pulmonary disease, and the therapeutic technique selected for each case. A computerized audit of cases was reviewed to examine the performance status, stage of disease, and methods of treatment. There were 1438 men and 488 women (male to female ratio, 3 to 1) and their ages ranged from 20 to 100 years (mean age, 56 years). Twenty-four percent were admitted to the hospital with total dysphagia. The performance status was excellent or good in 49% of the patients and fair in 29%. Those in poor or desperate condition included 13% of the patients with oesophago-airway fistulae. The most common site of cancer was the mid-thoracic oesophagus (53% of the cases), but 8.3% had tumors longer than 10 cm involving two or more oesophageal segments. Using the American Joint Committee (AJC) system of staging, 2.8% of the patients were assessed as Stage I, 19.8% as Stage II, and 77.4% as Stage III. Thirty-seven percent of the patients were treated by oesophageal intubation, 35% by radiation therapy, and 22% by chemotherapy. Surgery was selected for 17% of the patients. Although the number of young patients appears to have increased, the typical South African patient with oesophageal cancer is a man 56 years of age, in excellent or good condition, with a mid-thoracic tumor 6 cm in length and Stage III disease. This patient is frequently treated by palliative intubation of the oesophagus but may be a candidate for more intensive anti-cancer therapy.

Black or African American↗
PubMed1988

Cross resistance pattern towards anticancer drugs of a human carcinoma multidrug-resistant cell line.

Puromycin-resistant (PurR) mutants/variants of a human carcinoma cell line (HeLa), which show greatly reduced cellular uptake of 3H-puromycin and 3H-daunomycin have been isolated after one- and two-step selections in presence of the drug. The cross-resistance pattern of these mutant cell lines towards numerous anticancer drugs and other inhibitors has been examined. Both the first- and the second-step mutants exhibited increased resistance to a number of antimitotic drugs (viz. vinblastine, vincristine, colchicine, taxol and maytansine), several protein synthesis inhibitors (viz. chalcomycin, bruceantin, harringtonine, homoharringtonine), a large number of DNA interactive compounds (viz. aclacinomycin A, actinomycin D, adriamycin, m-AMSA, chromomycin A3, coralyne sulphoacetate, daunomycin, ellipticine, mithramycin, mitoxantrone, 5-methoxysterigmatocystin, rubidazone, variamycin, VM26 and VP16-213) and a number of other drugs acting via other mechanisms (viz. Baker's antifol, nitidine chloride and rhodamine 123). Whereas the first-step mutants showed stable resistance to these drugs, the second-step lines partially reverted upon growth in non-selective medium. Further, treatment of these mutant lines with non-cytotoxic doses of the calcium channel blocker verapamil reverted or abolished their resistance to the above drugs in a dose-dependent manner. In contrast to the above compounds, the PurR mutants showed no significant cross-resistance to a large number of other drugs which included asaley, AT-125, 5-azacytidine, azaserine, cyclocytidine, cis-platin, cytosine arabinoside, chlorambucil, chlorpromazine, alpha-difluoromethyl ornithine, 5-fluorouracil, ftorafur, gallium nitrate, hydroxyurea, ICRF-159, ICRF-187, imipramine, methotraxate, 6-methylmercaptopurine riboside, mycophenolic acid, melphalan, mitomycin C, methyl GAG, nafoxidine, reumycin, 6-selenoguanosine, 6-thioguanine, tiazofurin, tamoxifen, thalicarpine, tiapamil and verapamil). These cross-resistance data should prove useful in developing suitable drug combinations to which cellular resistance would not develop readily.

Animals↗
PubMed1988

Malignant pancreatic somatostatinoma in a patient with dermatitis herpetiformis and coeliac disease.

A case of malignant somatostatinoma is reported in a patient with long-standing dermatitis herpetiformis and coeliac disease. The patient had non-specific abdominal pain of several years duration and came to attention because of weight loss despite strict adherence to a gluten-free diet. Plasma somatostatin levels were raised, and laparotomy showed a pancreatic tumour with metastases, which on histology, electron microscopy and immunohistochemistry proved to be a somatostatinoma. After a promising initial response to streptozotocin, she died 30 months later. This is the first reported occurrence of a somatostatinoma in a patient with coeliac disease, adding to the growing list of neoplastic complications in this condition.

Adenoma, Islet Cell↗
PubMed1987

MRI appearance of disseminated osseous tuberculosis.

Disseminated osseous tuberculosis is a rare disease. This is a report of two cases of disseminated osseous tuberculosis imaged with MRI at 1.5-T, CT, plain radiography and bone scintigraphy. CT and plain radiography demonstrated either highly destructive or cystic lesions with sclerotic margins. Bone scintigraphy and plain radiography were quite insensitive in detecting areas of involvement compared to MRI. On MRI the abnormal areas had short T-1 relaxation values, which is an atypical appearance for bony infections, and prolonged T-2 relaxation values. The reason for the T-1 relaxation behavior is uncertain. MRI also provided delineation of epidural extent.

Adult↗
PubMed1987

CT for determining the results of treatment of fractures of the wrist.

Eighteen CT examinations of the wrist were performed in 13 patients to evaluate the results of treatment for carpal fractures. In four cases with metal objects and in seven with cast materials, there was no difficulty achieving adequate CT studies. In 13 cases CT was found to be helpful in determining bony union in the presence of advanced osteoporosis. In six cases CT was excellent in evaluating bone-graft incorporation. CT affords improved detection of fractures perpendicular to the plane of the scan and also shows small areas of bone disruption, even with osteoporosis. Axial CT images can evaluate Lister's tubercle, a bony prominence on the dorsum of the distal radius, for hypertrophy, which can occur secondary to traumatic and degenerative changes. A hypertrophied tubercle can impinge on the extensor pollicis longus tendon and cause atrophy and disruption. The high cost of CT is offset by the possibility of reducing the patient's period of immobilization and, thereby, the length of time the patient is unable to participate in normal activities. In addition, since CT is often definitive, the number of supplemental or follow-up radiologic procedures or clinical appointments should be reduced. We conclude that CT is useful in evaluating the results of treatment of wrist injuries.

Carpal Bones↗
PubMed1986

A frameless stereotaxic integration of computerized tomographic imaging and the operating microscope.

A computer-based system has been developed for the integration and display of computerized tomography (CT) image data in the operating microscope in the correct perspective without requiring a stereotaxic frame. Spatial registration of the CT image data is accomplished by determination of the position of the operating microscope as its focal point is brought to each of three CT-imaged fiducial markers on the scalp. Monitoring of subsequent microscope positions allows appropriate reformatting of CT data into a common coordinate system. The position of the freely moveable microscope is determined by a non-imaging ultrasonic range-finder consisting of three spark gaps attached to the microscope and three microphones on a rigid support in the operating room. Measurement of the acoustic impulse transit times from the spark gaps to the microphones enables calculation of those distances and unique determination of the microscope position. The CT data are reformatted into a plane and orientation corresponding to the microscope's focal plane or to a deeper parallel plane if required. This reformatted information is then projected into the optics of the operating microscope using a miniature cathode ray tube and a beam splitter. The operating surgeon sees the CT information (such as a tumor boundary) superimposed upon the operating field in proper position, orientation, and scale.

Evaluation Studies as Topic↗
PubMed1984

A double-blind randomized trial of cimetidine in acute upper gastrointestinal bleeding.

Two hundred and thirteen patients were studied in a double-blind trial of cimetidine versus placebo in the treatment of acute upper gastrointestinal haemorrhage. One hundred and six patients were randomly allocated to receive cimetidine and 107 to receive placebo. There was no significant reduction in transfusion requirements, incidence of further haemorrhage, length of stay in hospital, or mortality in the treated group. There was no subgroup of patients with acute upper gastrointestinal bleeding which appeared to benefit from treatment with cimetidine.

Adolescent↗