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Biomedical subjects

P Roberts

Publications and source records attributed to P Roberts.

At least 109 records · Page 6Linked to original sources
PubMed1994

Antagonism of presynaptically mediated depressant responses and cyclic AMP-coupled metabotropic glutamate receptors.

The depression of monosynaptic excitation of neonatal rat motoneurones by (1S,3S)- and (1S,3R)-1-aminocyclopentane-1,3-dicarboxylate (ACPD) and by L-2-amino-4-phosphonobutyrate (L-AP4), which is probably presynaptically mediated, is antagonized by (+/-)- and (+)-alpha-methyl-4-carboxyphenylglycine (MCPG). The same phenylglycine derivatives also antagonize the depression of forskolin-stimulated cyclic AMP synthesis effected by the two ACPD stereoisomers and by L-AP4. These results support previous suggestions that presynaptic depression is mediated by metabotropic glutamate receptors negatively coupled to adenylyl cyclase activity. MCPG is the first antagonist to be reported for these receptors.

Aminobutyrates↗
PubMed1994

The concentrations of clarithromycin and its 14-hydroxy metabolite in sputum of patients with bronchiectasis following single dose oral administration.

Clarithromycin and its metabolite, 14-hydroxy-clarithromycin are active against a wide range of respiratory pathogens. Antibiotics generally penetrate poorly into respiratory secretions which may therefore continue to harbour bacteria following bronchial infection. We have studied sputum and serum concentrations of clarithromycin and 14-hydroxy-clarithromycin in eight patients with idiopathic bronchiectasis without infective exacerbations (five male, three female; mean age 53.3 years). Oral single dose administration of 250 or 500 mg clarithromycin, separated by at least 6 days, was given to each patient. Serum and sputum samples were collected (the latter by physiotherapy at 0, 1, 2, 4, 8, 24 and 0, 4, 8 and 24 h respectively after administration of each dose. Serum sol phase was obtained by high speed centrifugation and concentrations of clarithromycin and 14-hydroxy-clarithromycin were determined by high performance liquid chromatography. Serum Cmax for clarithromycin and 14-hydroxy-clarithromycin were 1.20 mg/L (3 h) and 0.37 mg/L (3.1 h) for clarithromycin (250 mg)) and were 2.78 mg/L (2.5 h) and 0.68 mg/L (2.6 h) for clarithromycin (500 mg) respectively. Sputum Cmax for clarithromycin and 14-hydroxy-clarithromycin were 0.52 mg/L (5 h) and 0.30 mg/L (5.5 h) for clarithromycin (250 mg) and were 1.59 mg/L (5 h) and 0.47 mg/L (5.5 h) for clarithromycin (500 mg) respectively. The sputum/serum percentage ratios at Cmax (sputum) for clarithromycin and 14-hydroxy-clarithromycin were 74.3% and 113.9% (250 mg) and 94.7% and 99.9% (500 mg) respectively. We conclude that oral administration of clarithromycin to patients with bronchiectasis results in rapid penetration into respiratory mucus with persistent drug concentrations that exceed its MIC for many respiratory pathogens.

Administration, Oral↗
PubMed1994

Permissive underfeeding.

Dietary manipulation may influence outcome after infection and injury by altering production of inflammatory mediators and disease activity. Restricted nutrient intake may have beneficial effects on life-span, development of degenerative disease, autoimmune processes, renal injury, susceptibility to infection, and survival rate after infection. Nutritional therapies that serve to maximize nitrogen balance may adversely affect the host response to injury, especially when given in excess of energy and protein needs. The optimal calorie/protein intake during different phases of critical illness remains to be established. However, a short period of restricted intake may be beneficial.

Animals↗
PubMed1994

The enhancement of revascularisation of skeletal muscle transplants using the beta 2-agonist isoprenaline.

The effect of the beta 2-agonist isoprenaline on the revascularisation and regeneration of skeletal muscle transplants was studied using histological, morphometric and autoradiographic methods. Revascularisation of the transplants was accelerated in the isoprenaline-treated mice as evidenced by histological and autoradiographic results. The numbers of presumptive satellite cells were increased in the isoprenaline-treated mice. Significant increases in muscle cytoplasmic volume, endothelial cell volume, capillary and myofibre numbers, and the numbers of myofibres with peripheral nuclei were also found in transplants removed from the isoprenaline-treated mice (compared with controls). Reductions in myonuclear volume, 'other tissue' volume and numbers of myofibres with no nucleus sectioned were also found in transplants from isoprenaline-treated mice. Although there was an increased volume of regenerated muscle in the transplants, it cannot be concluded that this was because of the earlier transplant revascularisation, as beta 2-agonists have been shown to have a hypertrophic effect on skeletal muscle.

Animals↗
PubMed1994

[Pyomyositis].

Explore the source record for details and available documents.

Adult↗
PubMed1993

Cytogenetic abnormalities in mesoblastic nephroma: a link to Wilms' tumour?

Cytogenetic analysis of tumour material from a congenital mesoblastic nephroma is reported. Two cell lines were found, one with a normal 46,XY karyotype and the other with a hyperdiploid 51,XY karyotype, including a rearrangement of chromosome 11 at 11p15. This finding is of interest since loss of allelic heterozygosity at polymorphic 11p15 loci has been described in sporadic Wilms' tumour [1], and both cytogenetic [2] and molecular [3] changes of 11p15 are found in the Wiedemann-Beckwith syndrome, a condition with a predisposition to embryonal tumours, particularly Wilms' tumour. Our results lead us to speculate on the implications relating to the pathogenesis of this relatively benign tumour variant with respect to the current understanding of the genetics of Wilms' tumour.

Chromosome Deletion↗
PubMed1993

A halo jacket for stabilisation of the paediatric cervical spine.

Stabilisation of the paediatric cervical spine may be necessary in the management of trauma, infection and deformity. Surgery is technically difficult due to the immaturity of the bony elements and therefore external support is generally preferred. Our experience of halter traction and Minerva casts is that they either fail to achieve stability or are poorly tolerated. Halo pins are associated with significant pin tract complications in children. The technique for application of a plaster halo jacket is presented, together with the results of its use in eight children. Attention is drawn to the ease of application, tolerance by the patients and absence of significant complications.

Cervical Vertebrae↗
PubMed1993

Near-patient blood gas and electrolyte analyses are accurate when performed by non-laboratory-trained individuals.

OBJECTIVE: The objective of this study was to determine the accuracy of a near-patient blood gas and electrolyte analyzer when used by non-laboratory-trained clinicians in the critical care setting. METHODS: One hundred eighty-five blood samples (split samples) from 50 intensive care unit patients were analyzed by clinicians in the critical care environment using a near-patient blood gas and electrolyte analyzer (GEM Premier, Mallinckrodt Sensor Systems, Ann Arbor, MI). Near-patient measurements were compared with those obtained by laboratory technologists in an established intensive care unit laboratory. RESULTS: There was good agreement between the near-patient analyzer and the laboratory for pH, PCO2, sodium, potassium, ionized calcium, and hematocrit. Bias and precision were 0.006 and 0.03 for pH, 0.03 and 0.34 kPa for PCO2, 0.78 and 2.61 mmol/L for sodium, -0.11 and 0.12 mmol/L for potassium, -0.007 and 0.05 mmol/L for ionized calcium, and -0.99 and 1.33% for hematocrit. Bias between the laboratory instrument and the bedside analyzer was small for PO2 (-0.56 kPa). However, precision between instruments was significantly higher (2.39 kPa for all PO2 values and 1.61 kPa for PO2 < or = 13 kPa). CONCLUSIONS: The test instrument is accurate and reproducible when used in the clinical setting by non-laboratory-trained individuals. Non-laboratory-trained individuals can obtain laboratory results in the near-patient setting comparable to those obtained by trained laboratory technologists.

Blood Gas Analysis↗
PubMed1993

Failure of uncemented polyethylene acetabular components.

The authors describe the mode of failure of the Ring UPM (Downs Brothers, Surrey, United Kingdom) uncemented metal-on-plastic total hip arthroplasty. Erosion of the external surface of the uncemented acetabular cup led to early loosening in eight cases. The subsequent production of large quantities of polyethylene debris caused massive granulomata, resulting in osteolysis of the acetabulum and femur. Revision surgery was difficult because of the loss of bone stock. The serious consequences of failure of this design lead to the conclusion that uncemented, nonmetal-backed polyethylene acetabular components should not be used.

Acetabulum↗
PubMed1993

Alteration of growth, advancement of puberty, and season-appropriate circannual breeding during 28 months of photoperiod reversal in woodchucks (Marmota monax).

In woodchucks (Marmota monax), as in other marmotine rodents, endogenous circannual metabolic and reproductive cycles persist and free-run at intervals of 10-12 mo for up to 4 yr in a neutral photoperiod of 12L:12D. The annual metabolic cycle is not altered by exposure to constant long days or short days for several months. In the wild, changes in food intake cause body weight to peak in late summer and reach nadirs in early spring, and there is a single annual breeding season in late winter. To determine whether normal changes in photoperiod entrain the endogenous circannual cycle, aspects of reproduction, food intake, and body weight were studied for 28 mo in eight groups of woodchucks housed in light-controlled rooms. These included four groups of 7-10 males and four groups of 7-10 females exposed to automated and continuous daily changes in photoperiod. The imposed changes in photoperiod resembled native Northern Hemisphere (boreal) changes or Southern Hemisphere (austral) changes in photoperiod. The treatments started at the summer solstice shortly after capture as 2.5-mo-old juveniles or 14.5-mo-old yearling adults. In austral vs. boreal woodchucks, started as juveniles, annual increases in testosterone and testis descent at 5, 14, and 23 mo of study were advanced by 2, 5, and 6 mo, respectively. Annual increases in progesterone at 7, 16, and 25 mo of study were advanced by 4, 5, and 6 mo, respectively. The older woodchucks were significantly but less dramatically affected by austral photoperiod for the first 6 mo of study, and by 8-12 mo were advanced the same as the younger animals. At 16-17 and 26-27 mo of photoperiod reversal, 16 austral females had normal pregnancy rates (78%) and produced normal-sized litters (4.3 +/- 0.2) that were advanced by 5 and 6 mo, respectively, relative to those of boreal controls. Body weights in austral vs. boreal juveniles were reduced at 3-5 mo of study but not in older woodchucks. At 1 and then 2 yr of austral lighting, peaks in body weight were advanced by 4 and then 5 mo relative to boreal controls in young animals, and by 2 and then 5 mo in older animals. Between 1 and 2 yr of austral lighting in both age groups the nadirs in food intake (45 g per day) were about 16-25% of peak food intake 6-8 mo earlier, as in boreals, but advanced by 5-6 mo relative to boreals.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1993

Elucidation of the structural requirements for the bioactivation of mianserin in-vitro.

The aim of this study was to investigate structure-activity relationships among a series of compounds related to the antidepressant drug, mianserin, with respect to their ability to produce cytotoxic metabolites. Human peripheral lymphocytes were used as target cells and these were exposed to the individual compounds, in the presence or absence of a drug metabolizing system derived from human liver. The individual enantiomers of mianserin showed differences in their cytotoxicity profiles; the R-(-) isomer giving NADPH-dependent cytotoxicity while the S-(+) isomer showed direct cytotoxicity at high concentrations. Cytotoxicity was reduced by removal from mianserin of the nitrogen atom at the 5 position and by substitution of a methyl group for a hydrogen atom at position 14b. In contrast, insertion of an oxygen atom at position 10 of the drug molecule, precluding the formation of a carbonium ion, had little effect on cytotoxic metabolite formation. The data are consistent with the proposal that one or more iminium ions derived from mianserin are responsible for the cytotoxicity observed in this in-vitro system and that appropriate chemical modification may preclude bioactivation of mianserin by P450 enzymes.

Biotransformation↗
PubMed1993

A technique for removing an intrapelvic acetabular cup.

We describe a simple, retroperitoneal approach for the removal of acetabular components that have migrated into the pelvis. The dense fibrous tissue layer which surrounds the implant protects the iliac vessels during removal of the cup by this method.

Acetabulum↗
PubMed1993

Gut bacterial translocation/dissemination explains the increased mortality produced by parenteral nutrition following methotrexate.

Mortality is reported to be higher in methotrexate (MTX)-treated animals receiving total parenteral nutrition (TPN), compared to animals receiving enteral nutrition. The increased mortality is felt to be related to gut atrophy and bacterial translocation. In this study, we examined the effect of MTX (30 mg/kg) on survival, body weight loss, gut mass, and gut bacterial translocation in rats randomized to TPN or enteral nutrition. Twenty-four male Sprague-Dawley rats (n = 8 per group) were randomized to TPN, a peptide-based enteral diet (PEP), or CHOW. Animals were weighed daily and followed for survival (6 days). A separate group of rats (n = 6 per group) were similarly randomized and sacrificed at 3 days. Mesenteric lymph node complex, liver, spleen, lung, and blood were cultured for translocating bacteria. Body weight loss was similar in all groups (12.0-16.9 g/day). Mortality was significantly (P < 0.05) higher in the TPN animals (100%), compared to PEP (50%) and CHOW (25%) fed animals. All tissues in the TPN animals contained large quantities of bacteria, while most tissues in the CHOW group were free of bacteria. Bacterial counts in the PEP tissues were intermediate between TPN and CHOW. There were no significant differences between groups for gut weights or mucosal protein content. This study supports a direct relationship between bacterial translocation and mortality in rats following MTX.

Animals↗
PubMed1992

Elevation of free beta subunit of human choriogonadotropin and core beta fragment of human choriogonadotropin in the serum and urine of patients with malignant pancreatic and biliary disease.

Human choriogonadotropin (hCG), its free beta subunit (beta hCG), and the core beta hCG fragment (c beta hCG) were measured by highly sensitive time-resolved immunofluorometric assays in the serum and urine of 29 patients with pancreatic cancer, 7 patients with biliary cancer, and 45 patients with benign pancreatic or biliary diseases. The results were compared with those of an age- and sex-matched reference population of nonpregnant women and men. Of the various forms of hCG assayed in serum, beta hCG showed the best diagnostic accuracy, and c beta hCG was the best marker in urine. Elevated serum concentrations of beta hCG were observed in 72% of the patients with pancreatic cancer, in 6 of 7 patients with biliary cancer, and in 9% of those with benign disorders. The serum concentrations of c beta hCG were elevated in 45%, 57%, and 2%, respectively, and those in urine in 55%, 71%, and 11%, respectively. The molar concentrations of c beta hCG in serum were mostly lower than those of beta hCG. Thus beta hCG secreted into serum appears to be the main source of c beta hCG in urine. Provided that they are measured by sufficiently sensitive and specific assays, beta hCG in serum and c beta hCG in urine appear to be useful markers for pancreatic and biliary cancer.

Adult↗