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Biomedical subjects

P Wilson

Publications and source records attributed to P Wilson.

At least 19 recordsLinked to original sources
PubMed1992

Phase I and pharmacokinetic study of rhizoxin.

Rhizoxin is a tubulin-binding cytotoxic compound, isolated from the fungus Rhizopus chinensis, with significant antineoplastic activity in several murine and human tumor models. In this Phase I study, the drug was administered by i.v. bolus injection at 3-wk intervals. Twenty-four patients with refractory solid tumors were treated; 60 courses of rhizoxin were given, at doses ranging from 0.8 to 2.6 mg/m2. Grade 3 mucositis, Grade 4 leukopenia, and Grade 3 diarrhea were dose limiting but reversible at 2.6 mg/m2, the maximum tolerated dose for both previously untreated and heavily pretreated patients. Alopecia and moderate discomfort at the injection site occurred at all doses. Other sequelae, including peripheral neuropathy, phlebitis, and nausea and vomiting, were sporadic and mild. Two heavily pretreated patients with recurrent breast cancer had minor responses to rhizoxin, one at 1.6 mg/m2 and the other at 2.6 mg/m2. Plasma concentrations of rhizoxin were measured by high-performance liquid chromatography. The drug was not detectable (less than 5 ng/ml) at doses of 0.8 mg/m2 and 1.6 mg/m2 and was not measurable 10 min after injection at 2.0 mg/m2. At 2.6 mg/m2, there was considerable intersubject variation in the plasma concentration-time profiles; the area under the curve ranged from 0.29 to 0.96 microgram/ml.min. Rhizoxin has shown some clinical activity in this Phase I study, and a dose of 2.0 mg/m2 is recommended for Phase II studies using this schedule.

Adult↗
PubMed1992

Indomethacin and postprandial gallbladder emptying.

Patients with gallstone disease commonly have impaired gallbladder emptying. To see whether non-steroidal anti-inflammatory drugs (NSAIDs) prevent gallstone formation by improving gallbladder emptying, we assessed the effect of indomethacin on postprandial emptying in healthy subjects and in patients with gallstone disease. Subjects received indomethacin 25 mg three times a day for a week and matching placebo for another week. Compared with placebo, indomethacin improved postprandial gallbladder emptying in all 7 patients with gallstone disease. This finding was not recorded in healthy subjects with normal gallbladders. The prevention of gallstone formation associated with ingestion of NSAIDs may be due mainly to a prokinetic effect on the gallbladder since there is no evidence to suggest that these drugs affect cholesterol crystal nucleation at ordinary therapeutic doses in man or animals.

Adult↗
PubMed1992

Inhibition of cholesterol synthesis by cyclopropylamine derivatives of squalene in human hepatoblastoma cells in culture.

Two squalene derivatives, trisnorsqualene cyclopropylamine and trisnorsqualene N-methylcyclopropylamine, were synthesized and tested for inhibition of lanosterol and squalene epoxide formation from squalene in rat hepatic microsomes, and for the inhibition of cholesterol synthesis in human cultured hepatoblastoma (HepG2) cells. Trisnorsqualene cyclopropylamine inhibited [3H]-squalene conversion to [3H]squalene epoxide in microsomes (IC50 = 5.0 microM), indicating that this derivative inhibited squalene mono-oxygenase. Trisnorsqualene N-methylcyclopropylamine inhibited [3H]squalene conversion to [3H]lanosterol (IC50 = 12.0 microM) and caused [3H]-squalene epoxide to accumulate in microsomes, indicating that this derivative inhibited 2,3-oxidosqualene cyclase. Cholesterol biosynthesis from [14C]acetate in HepG2 cells was inhibited by both derivatives (IC50 = 1.0 microM for trisnorsqualene cyclopropylamine; IC50 = 0.5 microM for trisnorsqualene N-methylcyclopropylamine). Cells incubated with trisnorsqualene cyclopropylamine accumulated [14C]squalene, while cells incubated with trisnorsqualene N-methylcyclopropylamine accumulated [14C]squalene epoxide and [14C]squalene diepoxide. The concentration range of inhibitor which caused these intermediates to accumulate coincided with that which inhibited cholesterol synthesis. The results indicate that cyclopropylamine derivatives of squalene are effective inhibitors of cholesterol synthesis, and that substitutions at the nitrogen affect enzyme selectivity and thus the mechanism of action of the compounds.

Acetates↗
PubMed1992

Parathyroid stimulation after bleeding in man.

A role for the PTH-calcium axis in the normal bone-marrow response to bleeding or erythropoietin administration has been demonstrated in rats. We studied 20 autologous blood donors, each donating two units of blood, who served as a human bleeding model. Fifteen patients completed the study. Blood donations were followed by a significant increase in serum intact PTH (2.15 +/- 0.67 to 2.81 +/- 0.84 pmol/l; p = 0.0003) and protein-corrected total calcium (2.43 +/- 0.09 to 2.49 +/- 0.08 mmol/l; p = 0.2). All the individual values remained within the normal range. PTH weakly correlated with the reticulocyte count, but not with the corrected serum calcium. We conclude that moderate bleeding in humans is followed by a physiological increase in serum PTH and calcium.

Adolescent↗
PubMed1991

Elective laparoscopic cholecystectomy for "all-comers".

Laparoscopic cholecystectomy is a safe and effective procedure in specialist centres, but its wider application will depend on the ability of general surgeons to become skilled in this technique. 180 patients underwent elective laparoscopic cholecystectomy during a nine-month period at a single district general hospital. All patients who would have been eligible for elective open cholecystectomy were offered the laparoscopic alternative. Laparoscopic cholecystectomy was abandoned in favour of an open procedure in 10 (6%) patients. Median operating time was 55 min. 2 patients had serious morbidity (right hepatic duct injury and a duodenal fistula) and there were no deaths. 3 patients required subsequent treatment for retained common duct stones. 90% of patients were discharged within 48 h of the operation and the median time to resume full activity after discharge was 12 days. Laparoscopic cholecystectomy is a safe and cost-effective technique in a district general hospital.

Adult↗
PubMed1991

Immunocytochemical determination of estrogen receptor, progesterone receptor, and 1,25-dihydroxyvitamin D3 receptor in breast cancer and relationship to prognosis.

We have determined the estrogen receptor, progesterone receptor (PR), and 1,25-dihydroxyvitamin D3 receptor content of 136 breast carcinomas by an immunocytochemical method. The presence of the three receptors was not related to clinical features of presentation such as T-stage or to age or menopausal status. However, each of the three receptors has a different relationship to the course of the disease in these patients. The presence of PR was significantly associated with an improved overall survival (chi 2 = 4.61, P = 0.032). Patients whose tumors contained immunocytochemically detectable 1,25-dihydroxyvitamin D3 receptor had a longer disease-free interval than those patients with negative tumors (chi 2 = 4.01, P = 0.045). The presence of estrogen receptor and PR were found to correlate with an increased survival between relapse and death (P = 0.027 and P = 0.09, respectively). The relationships between estrogen receptor and PR and prognosis are more apparent when the degree of cell staining is considered. Combined receptor analysis improves our ability to predict the course of the disease and may therefore facilitate better management of the patients.

Adult↗
PubMed1991

Fatal pulmonary arterial occlusive vascular disease following chemotherapy in a 9-month-old infant.

Fatal pulmonary hypertension developed in an infant during the 7-month period in which he received, via a central venous catheter, combination chemotherapy for stage IV neuroblastoma as well as intermittent parenteral feeding. In a lung biopsy and at autopsy, small pulmonary arteries showed diffuse medial hypertrophy and peripheral muscularization, very extensive concentric intimal fibrosis, and focal eccentric fibrosis evolving from organizing thrombi. Pulmonary veins were normal. Hypothetically, chemotherapeutic drug therapy (possibly potentiated either by the parenteral nutrition or simply by the vehicular fluids causing volume loading of the pulmonary circulation) could cause occlusive pulmonary arterial disease by several mechanisms, but the association has not been described previously, although use of such drugs has been reported with pulmonary veno-occlusive disease.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Influences of acculturation and musical sophistication on perception of musical interval patterns.

Influences of acculturation and musical sophistication on music perception were examined. Judgments for mistuning were obtained for Ss differing in musical sophistication who listened to a melody that was based on interval patterns from Western and Javanese musical scales. Less musically sophisticated Ss' judgments were better for Western than Javanese patterns. Musicians' thresholds did not differ across Western and Javanese patterns. Differences in judgments across scales are accountable to acculturation through listening exposure and musical sophistication gained through formal experience.

Acculturation↗
PubMed1991

Clinical signs of early osteoarthritis: reproducibility and relation to x ray changes in 541 women in the general population.

The definition and classification of early clinically apparent osteoarthritis both in clinical situations and in epidemiological surveys remains a problem. Few data exist on the between-observer reproducibility of simple clinical methods of detecting hand and knee osteoarthritis in the population and their sensitivity and specificity as compared with radiography. Two observers first studied the reproducibility of a number of clinical signs in 41 middle aged women. Good rates of agreement were found for most of the clinical signs tested (kappa = 0.54-1.0). The more reproducible signs were then tested on a population of 541 women, aged 45-65, drawn from general practice, screening centres, and patients previously attending hospital for non-rheumatic problems. The major clinical signs used had a high specificity (87-99%) and lower sensitivity (20-49%) when compared with radiographs graded on the Kellgren and Lawrence scale (2+ = positive). When analysis was restricted to symptomatic radiographic osteoarthritis, levels of sensitivity were increased and specificity was lowered. These data show that certain physical signs of osteoarthritis are reproducible and may be used to identify clinical disease. They are not a substitute for radiographs, however, if radiographic change is regarded as the 'gold standard' of diagnosis. As the clinical signs tested seemed specific for osteoarthritis they may be of value in screening populations for clinical disease.

Female↗
PubMed1991

Effect of neonatal denervation of hindlimb digits on the somatotopic organization of lumbar spinocervical tract neurons in the cat.

1. The effect of transection and ligation of the digital nerves of either one (toe 3) or two (toe 3 and toe 4) hindpaw digits, in the first postnatal week, on the tactile receptive fields (RFs) of spinocervical tract (SCT) neurons was studied in adult, alpha-chloralose-anesthetized cats. Immediately before recording, the digital nerves of the corresponding digit(s) of the opposite, intact hindpaw were transected, and the neonatally lesioned digital nerves were recut proximal to the transection neuroma. 2. In the medial part of the dorsal horn at the L6-L7 level, the digits of the hindlimb are represented in the RFs of SCT cells in a precise axial sequence from the most medial digit (toe 2) rostrally to the most lateral digit (toe 5) caudally. Acute denervation of one or two digits in the adult produced an area in the ipsilateral dorsal horn in which SCT cells lacked any RFs. When acute denervation was restricted to a single digit, the unresponsive region of dorsal horn was approximately 3 mm in length, and when two digits were denervated the unresponsive zone was approximately 6 mm long. Because the representation of the toes of the left hindpaw is a mirror image of that of the right, the rostrocaudal extent and position of the region of unresponsive SCT cells was used to assess the location of the borders of the chronically deprived region on the opposite side of the cord. 3. In all cats examined after neonatal denervation of toe 3, most (89%) of the SCT cells sampled within the chronically deprived toe 3 representation had RFs. These RFs were either on toe 2 (44%) or toe 4 (18%), and a large proportion of cells (38%) had multiple RFs with components on both toe 2 and toe 4. In most cases the cells fired briskly to displacement of hairs or light touch of the skin within these RFs. SCT cells with a RF on toe 2 and/or toe 4 were found throughout the whole 3-mm length of the chronically deprived toe 3 region, but cells with a RF on toe 2 were more commonly found than cells with a RF on toe 4 at axial distances greater than or equal to 1.5 mm from the boundary of the normal representations of the respective digit. 4. After chronic, neonatal denervation of both toe 3 and toe 4, 59% of SCT cells sampled overall had RFs, but there was a large degree of interanimal variation in the proportion of unresponsive neurons.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1991

Evidence for reduced fibrinolytic activity in unstable angina at rest. Clinical, biochemical, and angiographic correlates.

BACKGROUND: The goal of this study was to evaluate the role of the fibrinolytic system in patients with unstable angina at rest associated with transient electrocardiographic changes. METHODS AND RESULTS: Tissue plasminogen activator activity in plasma was comparable among patients with unstable angina (n = 17), patients with stable exertional angina (n = 10), and control patients with normal coronary arteriograms (n = 8). In contrast, plasminogen activator inhibitor-1 (PAI-1) activity in plasma was elevated in the unstable angina group (21.67 +/- 9.52 AU/ml) as compared with either the stable angina group (12.01 +/- 7.06 AU/ml, p less than 0.02) or the controls (12.49 +/- 8.54 AU/ml, p less than 0.02). Coronary angiography performed within 24 hours after the last anginal episode showed a similar extent of coronary artery disease in the unstable and stable angina groups. However, intracoronary thrombi were observed in eight patients in the unstable angina group while no thrombus was noted in the stable angina group (chi 2 = 7.22, p less than 0.01). CONCLUSIONS: We conclude that patients with unstable angina at rest have a reduced fibrinolytic activity and an increased incidence of intracoronary thrombi. It is postulated that elevated PAI-1 activity in the presence of coronary arterial wall injury may be an important factor leading to the development of acute coronary syndromes.

Angina Pectoris↗
PubMed1991

Cell rearrangement during gastrulation of Xenopus: direct observation of cultured explants.

We have analyzed cell behavior in the organizer region of the Xenopus laevis gastrula by making high resolution time-lapse recordings of cultured explants. The dorsal marginal zone, comprising among other tissues prospective notochord and somitic mesoderm, was cut from early gastrulae and cultured in a way that permits high resolution microscopy of the deep mesodermal cells, whose organized intercalation produces the dramatic movements of convergent extension. At first, the explants extend without much convergence. This initial expansion results from rapid radial intercalation, or exchange of cells between layers. During the second half of gastrulation, the explants begin to converge strongly toward the midline while continuing to extend vigorously. This second phase of extension is driven by mediolateral cell intercalation, the rearrangement of cells within each layer to lengthen and narrow the array. Toward the end of gastrulation, fissures separate the central notochord from the somitic mesoderm on each side, and cells in both tissues elongate mediolaterally as they intercalate. A detailed analysis of the spatial and temporal pattern of these behaviors shows that both radial and mediolateral intercalation begin first in anterior tissue, demonstrating that the anterior-posterior timing gradient so evident in the mesoderm of the neurula is already forming in the gastrula. Finally, time-lapse recordings of intact embryos reveal that radial intercalation takes places primarily before involution, while mediolateral intercalation begins as the mesoderm goes around the lip. We discuss the significance of these findings to our understanding of both the mechanics of gastrulation and the patterning of the dorsal axis.

Animals↗
PubMed1979

Immunosurveillance in pre-malignant occupational bladder disease.

A population of workers exposed to bladder carcinogens has been studied by comparing their immunoreactivity against bladder cancer cells and against a control cancer cell with that found in normal individuals and in patients with bladder cancer. Data are presented which indicate equivalent increases in specific reactivity against bladder cancer cells in clinically normal carcinogen-exposed workers and in patients with bladder cancer. Increases in reactivity are related to degree of exposure and also to early malignant changes in the urothelium. This indicates that immune recognition of tumour antigens does occur before development of overt malignancy.

1-Naphthylamine↗
PubMed1979

Multiple axis image reconstruction from axial transverse data.

The technique for alternate axis reconstruction from axial transverse computed tomography data is presented. The utility of the method as an adjunct to diagnosis, radiotherapy treatment planning, and tumor biopsy is discussed. The relative radiation dose and resolution characteristics between this and other methods are compared.

Data Display↗