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Biomedical subjects

P Rose

Publications and source records attributed to P Rose.

At least 91 records · Page 5Linked to original sources
PubMed1989

Factors contributing to the accelerated clearance of theophylline and antipyrine in adults with exocrine pancreatic disease.

1. Oxidative drug metabolizing capacity has been assessed by oral antipyrine and/or theophylline tests in consecutive patients with chronic pancreatitis (CP; alcoholic 24, idiopathic 47), acute pancreatitis (AP; 28) and pancreatic cancer (CA; 11). Most of the patients had drastically reduced their alcohol consumption and dietary fat intake for variable periods before the tests. Excellent bioavailability of theophylline was confirmed from paired oral and intravenous tests in seven subjects, including two with exocrine pancreatic failure. 2. The clearance of theophylline in the patients was faster than in 15 controls with a 'healthy lifestyle' [median 104 (range 18-320) ml h-1 kg-1 vs median 68 (range 50-97) ml h-1 kg-1, P less than 0.01]. The difference was especially apparent in the groups with alcoholic CP (P less than 0.001 and idiopathic CP (P less than 0.01), but not in the AP and CA group as a whole, although drug clearance in some 50% of those cases exceeded the reference range. 3. There was good correlation between theophylline and antipyrine clearance in a subset of 91 subjects who had both tests (15 controls, 76 patients), but antipyrine was much less sensitive as a marker of enzyme induction. This suggests that enzyme induction in pancreatic disease preferentially involves the polycyclic aromatic hydrocarbon-inducible subfamily of cytochrome P-450. 4. The lack of correlation between pancreatic secretory capacity in 56 cases, judged by a secretin-pancreozymin test, and theophylline clearance suggests that enzyme induction is not secondary to pancreatic dysfunction. 5. Multivariate regression analysis identified approximately 50% of variability in clearance of each probe.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Serum lymphocytotoxic activity in leprosy.

Sera from 167 patients across the spectrum of leprosy and 46 endemic controls were screened for lymphocytotoxic activity (LCA). The Terasaki microdroplet lymphocytotoxicity assay was performed at 37 degrees C and 15 degrees C to test sera for LCA against a panel of lymphocytes from 50 donors which represented most known HLA-ABC antigens. Raised complement-dependent LCA at 15 degrees C was seen in leprosy patients with histories of erythema nodosum leprosum (ENL) or reversal/Type I (I) reactions. Eighty-six per cent of lepromatous (LL) patients with a history of ENL (n = 21, P less than 0.001), 83% of borderline lepromatous (BL) and 88% of borderline tuberculoid patients (BT) with a history of Type I reactions (n = 12, P less than 0.01 and n = 24, P less than 0.001 respectively) had LCA compared to 39% of endemic controls (n = 46). LCA was attributed to IgM on the basis of reduced activity when serum was treated with both dithiothreitol or absorbed with antiserum for IgM. Removal of immune complexes and rheumatoid factor did not influence LCA. LCA-positive sera reacted similarly with allogeneic lymphocytes from either healthy donors or leprosy patients. Moreover LCA-positive sera reacted with autologous lymphocytes. Specificities for HLA-ABC antigens were not identified. The potential role of these autoantibodies, manifested in leprosy patients with hypersensitivity reactions remains speculative.

Adolescent↗
PubMed1988

Long term follow-up of bone mineral status in children with renal disease.

Bone mineral content (BMC) was measured by photon absorptiometry in the non-dominant forearm of children with chronic renal failure followed for a total of 2472 months. From 48 children, 302 measurements were made, and changes which occurred in BMC over time were correlated with several factors. Patients were divided into those who had received glucocorticoids (group 1) and those who had not (group 2). Group 1 patients had a lower mean serum creatinine (Cr) (p less than 0.05), a lower growth velocity (p greater than 0.02) and were more demineralized than group 2 patients. There was no correlation between BMC and height velocity or estimated creatinine clearance. BMC and height Z-score (SDS) were highly correlated. Over the period of study, group 1 patients remained shorter, had a lower height velocity, a lower BMC Z-score and a lower BMC for each serum creatinine level. Long-term therapeutic intervention with oral 1,25(OH)2D improved bone mineral status in three children in the nonsteroid group, but none of those in the steroid group. This study demonstrates that steroid administration is probably the most important factor causing bone demineralization, possibly even more important than renal failure.

Adolescent↗
PubMed1988

The treatment of chronic idiopathic thrombocytopenia with anti-D (Rho) immunoglobulin: its effectiveness, safety and mechanism of action.

Twenty-three courses of i.v. anti-D (Rho) immunoglobulin were administered to 13 Rh D-positive patients with chronic idiopathic thrombocytopenia (ITP). Clinically significant responses were seen in a proportion of patients treated with 500-2500 i.u. anti-D, but all those treated with 12,500 i.u. (180 i.u./kg) responded. Patients refractory to other forms of treatment responded well to anti-D, and previous splenectomy did not influence the clinical response. No adverse reactions were observed. The anti-D response was preceded by a lag period of 3-16 days and was maintained for 14-145 days. Platelet-associated IgG was increased after treatment, due to improved survival of immunosensitized platelets or platelet Fc receptor binding of high molecular weight IgG in the therapeutic material. There was no clinical or biochemical evidence of haemolysis. The erythrocyte direct Coombs' test remained positive for 3-45 days, and histological examination of splenic material showed no erythrophagocytosis. We conclude that anti-D (Rho) immunoglobulin is a safe and effective treatment for chronic ITP and that the therapeutic dose is now established in standardized units. The mechanism of action appears to be complex and is probably not due to macrophage Fc receptor blockade with immunosensitized red cells.

Adult↗
PubMed1987

Paracoccidioidin sensitization in Guyana--a preliminary skin test survey in hospitalized patients and laboratory workers.

Thirty-one percent of a group of 49 hospitalized patients or laboratory workers in Guyana showed positive intradermal paracoccidioidin tests in the presence of negative histoplasmin reactions. In 2 patients (4%), the intradermal reactions to paracoccidioidin were greater than 10 mm in diameter. The prevalence of positive reactors in a selected population suggests that paracoccidioidomycosis may be endemic in Guyana although no clinical case has been reported from the country. A further survey in a larger, unselected population would lead to a clearer understanding of the problem.

Adolescent↗
PubMed1987

Assessment of the immune deficit in leprosy patients and the effect of recombinant IL-2 in vitro.

Although the mechanism of immunologic unresponsiveness in lepromatous leprosy remains unknown, it has been shown that interleukin-2 (IL-2) production is defective in these patients. Peripheral blood mononuclear cells (PBMC) were isolated from treated (less than 16 months) and untreated leprosy patients as well as household contacts; age, sex, ethnically matched control subjects; and laboratory staff. PBMC were cultured for 6 days with sonicated Mycobacterium leprae (1-10 micrograms/ml), Dharmendra lepromin (1:10), or phenolic glycolipid-I (PGL-I) (0.05-5.0 micrograms/ml) in medium supplemented with various concentrations of recombinant IL-2 (rIL-2) or cultured for 3 days with one of the three mycobacterial antigens in the presence of concanavalin A (ConA). TT/BT patients and household control subjects had a robust response to M. leprae and lepromin, but were unresponsive to PGL-I delivered in liposomes. PBMC from LL patients did not respond to any of the three antigen preparations. rIL-2 induced proliferation of PBMC both in leprosy patients and control subjects regardless of the presence or absence of the three leprosy antigen preparations. This antigen nonspecific augmentation of proliferation by the wide range of doses of rIL-2 employed makes difficult the interpretation of the enhanced thymidine incorporation noted when rIL-2 is added in the presence of antigen to cultures of lymphocytes from LL patients. Our studies are at variance with reports that leprosy antigens, specifically PGL-I, induce immunological suppression, in that mycobacterial antigens did not cause significant suppression of the ConA-induced proliferations of PBMC from patients.

Adolescent↗
PubMed1986

Hypersecretion of biliary fatty acids in patients with exocrine pancreatic disease.

The fatty acid composition of bile secreted into the duodenum in the first 10 min after an intravenous (i.v.) injection of Boots secretin (2 CHRu kg-1) has been analysed by gas liquid chromatography in 11 healthy volunteers, 8 patients without pancreatic disease, 27 patients with exocrine pancreatic disease who had not altered their diet substantially (acute pancreatitis 8; chronic pancreatitis 16; cancer 3) and 11 patients with exocrine pancreatic disease on low fat intakes (40 g/day) for at least 6 months. The mean values for total fatty acid outputs (after back transformation of the logged data) were significantly higher in each subgroup of patients with pancreatic disease on their usual diets (acute 134, chronic 189, cancer 235 mg) than in the two subgroups of controls (30 and 55 mg), due to significant increases in the outputs of every fatty acid, C16:0 through to C22:5. This finding, which was usually not apparent in patients with pancreatic disease on low-fat diets, may reflect the combined influence of dietary fat intakes and hepatic enzyme induction. Comparison of the fatty acid outputs in endoscopically collected bile and duodenal juice after separate injections of secretin three hours apart indicate that: (a) analysis of duodenal juice within 10 min of stimulation by Boots secretin provides valuable information on the composition of hepatic bile; (b) the increased phospholipid output in the untreated patients is due to hypersecretion and does not merely represent a 'washout' phenomenon.

Acute Disease↗
PubMed1986

Dietary antioxidants and chronic pancreatitis.

Fifteen patients with idiopathic chronic pancreatitis (aged 17-78 years), who had not altered their diet since their first symptoms, completed 7-d weighed dietary records at home. The computed information was compared with that from 15 age- and sex-matched volunteers. Attention was focussed on the intakes of antioxidants and unsaturated fatty acids. The patients ingested less selenium, vitamin E, vitamin C and riboflavin than did controls (P less than 0.001, P less than 0.02, P less than 0.001 and P less than 0.05 respectively, using paired t-tests): selenium was by far the best discriminator on step-wise analysis. When the selenium intakes were examined alongside the results of theophylline tests--which reflect cytochromes P450 activities and, thereby, provide an index of antioxidant demand--a line of discrimination separated the majority of patients (with faster drug clearances and lower selenium intakes) and controls. There were no differences in the intakes of individual unsaturated fatty acids, C14:1 through to C24:6, between the two groups. However, amongst six subjects in the overlap zone, three with chronic pancreatitis habitually ate greater amounts of highly unsaturated fatty acids C20:4 to C24:6 inclusive (1970, 1049, 750 mg/d) than did three controls (329, 320, 82 mg/d). Animal experiments show that suboptimal intakes of dietary antioxidants and/or excessive intakes of highly unsaturated fatty acids and/or induction of cytochromes P450 facilitate peroxidation of cellular lipid membranes by free radicals. Our dietary data, taken in conjunction with pharmacokinetic data, thus suggest that a similar situation--favouring lipid peroxidation--may underlie human chronic pancreatitis.

Adolescent↗
PubMed1985

Induction of cytochromes P-450 in pancreatic disease: consequence, coincidence or cause?

We have examined the pharmacokinetics of antipyrine and of theophylline--validated probes for cytochromes P-450 activities--in a series of patients with pancreatic disease. The half-life of each drug was significantly lower, and its clearance faster, in patients than in controls and this pattern was detected in the subgroups with acute pancreatitis (6), chronic pancreatitis (22), or pancreatic cancer (4). These data suggest induction of cytochromes P-450 in all forms of exocrine pancreatic disease. Enzyme induction is unlikely to be secondary to pancreatic malfunction since there was no correlation between prevailing exocrine status, as assessed by secretin-pancreozymin tests, and the half-life or clearance of either drug. The corollary is that induction of the mono-oxygenases by environmental agents, both recognised and unidentified, is a primary event in pancreatic disease. The possible relevance of this finding is discussed.

Adolescent↗
PubMed1985

Prevention of coronary platelet aggregation with a phosphodiesterase inhibitor RX-RA 69.

The formation and prevention of coronary platelet thrombi (CPT) was studied in a modified Folts model in 23 anaesthetized dogs. The left circumflex coronary artery was acutely damaged and narrowed until resting flow started to fall. Spontaneous sharp decrease of flow indicated the acute formation of CPT. Intravenous infusion of 30 ng/kg/min of PGI2 prevented the formation of CTP. The effect lasted 3-7 min after termination of the infusion. RX-RA 69 a potent inhibitor of platelet phosphodiesterase (IC50 of 1 X 10(-9) mol/1) inhibited the formation of CPT for 9 and 18 min when 60 and 120 micrograms/kg were administered i.v. The results demonstrate that platelet aggregation induced by acute damage of the vascular wall can be inhibited by a potent PDE inhibitor.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1985

Quantitative assessment of tooth wear, alveolar-crest height and continuing eruption in a Romano-British population.

Although measurements from cement-enamel junction (CEJ) to alveolar crest (AC) have been used in assessing changes in alveolar-crest height as age or chronic inflammatory periodontal disease (CIPD) progresses, there is evidence from ancient populations that the position of AC remains almost constant throughout life and continuing eruption to compensate for attrition may explain why CEJ-AC measurements increase with age. Measurements of occlusal attrition and relationship of CEJ to AC were made on the cheek teeth of 500 Romano-British skulls by direct measurement or by reference to the fixed line of the inferior alveolar canal (IAC) on radiographs. Direct measurements indicated that there were usually no statistical differences between the vertical amounts of tooth substance lost by attrition and the change in the distance CEJ-AC as age progressed. Measurements on radiographs showed that posterior teeth continued to erupt to compensate for attrition and the AC remained static as age progressed. Bone deposition at the AC was seen in the majority of ground sections. Thus tooth wear appears to be compensated by continuing movement of teeth in an occlusal direction. The position of the AC remained almost constant throughout life; AC bone lost by CIPD seemed to be replaced during continuing tooth eruption.

Age Factors↗
PubMed1985

Strategies for increasing productivity.

In today's arena of competition, cost-containment, quality assurance, and high technology, the dietitian is challenged to develop and implement strategies that will assure an increase in productivity. Within a government system, such strategies must address the political climate as well as administrative and management issues. Prior to modifying any system or part of a system, it is critical to develop evaluation criteria. Each of the eight strategies discussed in this article is effective in promoting an increase in productivity.

Cost Control↗