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Biomedical subjects

J Jones

Publications and source records attributed to J Jones.

At least 487 records · Page 27Linked to original sources
PubMed1992

Administration of human recombinant insulin-like growth factor-I to patients following major gastrointestinal surgery.

OBJECTIVE: The aim was to study the pharmacokinetic parameters and biological activity of a single dose of human recombinant IGF-I (rhIGF-I) administered to patients following major gastrointestinal surgery. DESIGN: A double blind placebo controlled externally randomized study of 30 patients; the study commencing 24 hours after major colonic or gastric surgery. MEASUREMENTS: After a baseline blood sampling day, IGF-I (40 micrograms/kg by single subcutaneous dose, n = 20) or placebo (n = 10) was administered and serum and urine samples collected over the ensuing 72 hours. Serum IGF-I, IGF-II, IGF binding proteins (IGFBP-1, IGFBP-3), GH and insulin were measured by radioimmunoassay. Serum IGF bioactivity was assessed using a validated porcine cartilage bioassay. Serum and urinary electrolytes were measured by standard methodology. RESULTS: Serum immunoreactive IGF-I levels peaked at 4 hours following injection of IGF-I (1.09 +/- 0.12 U/ml mean +/- SEM), remained elevated for 15 hours and returned to basal levels by 24 hours after injection. IGF bioactivity was increased by 57% 6 hours after IGF-I injection. Mean levels of IGFBP-1 and IGFBP-3, IGF-II and GH were unaffected by IGF-I administration. Insulin levels were suppressed at 30 minutes following injection of IGF-I compared with the placebo group (16.9 +/- 3.0 mU/I vs 32.3 +/- 7.1, P = 0.02); thereafter, there were no differences in insulin levels. The mean change in serum creatinine following IGF-I (-6.3 +/- 3.0 mmol/l) was significantly different from that in the control group (+7.2 +/- 6.2, P = 0.03). Creatinine clearance rose from a mean of 71.6 +/- 7.5 ml/min to 83.2 +/- 7.6 ml/min after IGF-I treatment (P = 0.02). In the IGF treated patients, cholesterol levels consistently fell (-0.20 +/- 0.05 mmol/l); this was not observed in the placebo group (+0.20 +/- 0.14, P = 0.006). Basal serum potassium levels in the IGF treatment group (4.1 +/- 0.1 mmol/l) fell to 3.8 +/- 0.1 at 4 hours (P = 0.002) and 3.6 +/- 0.1 at 10 hours (P = 0.001) returning to a level of 4.0 +/- 0.1 (P = 0.293) at 24 hours after injection. There were no other observed differences in serum or urinary electrolytes or serum free fatty acids and triglycerides. Pharmacokinetic parameters derived from baseline adjusted IGF-I measurements revealed a slow absorption of the administered dose with a Tmax of 5.0 +/- 0.43 hours and an elimination half-life of 10.8 +/- 1.2 hours. The computed volume of distribution was 0.33 +/- 0.05 I/kg and the clearance on average 25 ml/min. CONCLUSION: A single subcutaneous dose of IGF-I normalized circulating IGF-I levels in post-operative patients, was well tolerated and without side-effects. IGF bioactivity was increased and associated with a fall in serum cholesterol, potassium and creatinine levels and a rise in creatinine clearance. Further long-term studies are now required to assess the anabolic effects of rhIGF-I in this type of patient group.

Aged↗
PubMed1992

Guidelines for the use of fresh frozen plasma. British Committee for Standards in Haematology, Working Party of the Blood Transfusion Task Force.

Fresh frozen plasma should only be used to treat bleeding episodes or prepare patients for surgery in certain defined situations. Definite indications for the use of FFP: 1. Replacement of single coagulation factor deficiencies, where a specific or combined factor concentrate is unavailable. 2. Immediate reversal or warfarin effect. 3. Acute disseminated intravascular coagulation (DIC). 4. Thrombotic thrombocytopenic purpura (TTP). Conditional uses: FFP only indicated in the presence of bleeding and disturbed coagulation: 1. Massive transfusion. 2. Liver disease. 3. cardiopulmonary bypass surgery. 4. Special paediatric indications. No justification for the use of FFP: 1. Hypovolaemia. 2. Plasma exchange procedures. 3. 'Formula' replacement. 4. Nutritional support. 5. Treatment of immunodeficiency states.

Adult↗
PubMed1992

Estimation of erythropoietin secretion rate in normal and uremic subjects.

We have developed a method for directly estimating the secretion rate of endogenous erythropoietin (EPO) in human subjects. Carrier-free recombinant human EPO was labeled with 125I by the chloramine T method. Human serum albumin was then added prior to removal of free iodide. Seven normal subjects and nine patients with chronic uremia and anemia were studied. Each subject received a bolus of 125I-EPO according to body size and then a constant infusion for 5 h. Secretion rate was calculated as the rate of infusion divided by serum EPO specific activity given by the protein-bound counts divided by the EPO concentration. Serum EPO concentration was significantly higher in the patients than the controls (mean 30.9 pg/ml vs. 11.1 pg/ml, P < 0.05), although all values were within the normal range. Mean EPO secretion rate was 255 in the patients (range 68-1,101) and 190 pg.kg-1 x h-1 in the normal group (range 52-382). This difference was not significant. As the subjects were in a steady state, EPO disappearance/degradation was the same in patients compared with controls despite a relatively hypoplastic marrow.

Adult↗
PubMed1992

Detection of HIV-1 protein and nucleic acid in enterochromaffin cells of HIV-1-seropositive patients.

Diarrhea contributes significantly to the morbidity and mortality of patients with the acquired immunodeficiency syndrome (AIDS). Up to 50% of AIDS patients have diarrhea, and an etiologic agent for this cannot be identified in all of them. Recent evidence suggests that enterochromaffin cells may be infected by the human immunodeficiency virus type 1 (HIV-1) and may contribute to the unexplained diarrhea. To test this hypothesis further, endoscopic biopsies of duodena from 22 HIV-1 seropositive patients [17 with diarrhea (> 500 g/day and > 3 bowel movements/day), five without diarrhea] and from 15 normal controls (no HIV risk factors) without diarrhea were studied. Formalin-fixed and paraffin-embedded 5-microns sections were examined by immunocytochemistry, using a monoclonal antibody to the HIV-1 gp41 protein, and by in situ hybridization with a full-length biotinylated HIV-1 DNA probe. Positive staining for gp41 was detected in crypt cells, consistent with the location, size, and morphology of enterochromaffin cells, in 11 of 17 HIV-1-seropositive patients with diarrhea, and in none of five without diarrhea. Nucleic acid hybridization staining was performed in five of the 11 patients who had positive gp41 staining; all showed HIV nucleic acid sequences in similar cells. All three of the five patients with positive staining for HIV nucleic acid sequences had diarrhea for which no etiologic agent for diarrhea could be found, and one each had cryptosporidia or microsporidia. No staining was observed in any of the samples from normal control tissues. These results suggest that HIV-1 may infect enterochromaffin cells and possibly alter their function. This, in turn, may contribute to the diarrhea associated with AIDS.

Adult↗
PubMed1992

Risk factors for coronary heart disease in a black population.

A matched case control study using population-based controls was done over a 2-year period in an urban, public hospital setting. The object of the study was to determine if the established risk factors for coronary heart disease--hypertension, diabetes mellitus, hypercholesterolemia, cigarette smoking, low socioeconomic status (as reflected by occupational class and educational level), marital status, and obesity were associated with coronary heart disease in a black population. The established risk factors were found to be significant in this patient population, as was obesity. Being divorced or separated was a risk factor for women but not for men.

Black or African American↗
PubMed1992

Performance of proficiency survey samples in two immunoradiometric assays of human growth hormone and comparison with patients' samples.

The immunoradiometric assay (IRMA) used in our laboratory for the measurement of growth hormone (hGH; somatotropin) performed badly in the national proficiency survey program, the U.K. External Quality Assessment Scheme (EQAS). We compared our assay with another IRMA, which gave similar results for patients' samples and performed adequately in EQAS. The samples from EQAS are collected from patients with polycythemia and fall into two categories: those containing endogenous hGH and those supplemented with pituitary-derived hGH. Analysis of the two groups separately showed that the differences between the two IRMAS were in the measurement of the endogenous hormone. The reason for this appears to be a matrix effect related to the fact that the EQAS serum samples are collected from polycythemic patients.

Growth Hormone↗
PubMed1992

What will happen to the quality of care with fewer junior doctors? A Delphi study of consultant physicians' views.

Hospital medical staffing: achieving a balance proposed a reduction in the number of junior doctors and an expansion in the number of consultant posts. This change was to be subject to the 'safety net'--that the number of staff should not fall below a minimum safe level for 24-hour emergency cover. However, no operational definition of 'safe' was offered. Consultant physicians in one NHS region were interviewed to find out how they thought safety would be affected by a reduction in junior doctor numbers. It emerged that consultants' concerns over reductions in staff covered a wider range of issues than just the clinical effectiveness of care. The interpretation of safety extended to cover general adverse effects on care. A survey, using the Delphi method, revealed that consultant physicians were most concerned over reductions in the humanity of care if numbers of junior staff were reduced. This included such factors as the time spent by patients waiting in outpatient and A&E departments, and the time doctors spend talking to patients. Consultants were less concerned over the effect of reduced staff numbers on the technical efficiency of provision, and least of all on the effectiveness of care. This last point was seen to be a reflection of consultant physicians' confidence in the basic medical knowledge and skill of their junior staff.

Attitude of Health Personnel↗
PubMed1992

School health education: challenge for national and international agencies.

There are, in today's world, more than a billion young people of school age. Hundreds of millions of them are enrolled in the schools. They constitute the greatest single readily-reachable population group and present one of our greatest opportunities toward achieving a brighter health future. Are we availing ourselves of this opportunity? It is sad but true that too often school health education is considered as "something extra", a matter of peripheral interest, and is given low priority in school curriculum. Yet these young people--in the schools and outside them--are the parents, the citizens, the leaders of tomorrow. Theirs is the health of the future. We cannot afford to leave the health citizenship of the future to a generation only causally educated about life.

Adolescent↗
PubMed1991

Killing of cells by perforin. Resistance to killing is not due to diminished binding of perforin to the cell membrane.

Different cell types vary widely in their susceptibility to killing by the pore-forming cytolytic molecule perforin. In particular, the cells responsible for synthesis of perforin, i.e. cytotoxic T lymphocytes (CTL) and natural killer (NK) cells, are very resistant to cytolysis by this molecule. It has previously been suggested that resistance is due, at least in part, to diminished binding of perforin to these cells. The purpose of the present study was to compare binding of perforin to sensitive and resistant cell types. To this end, perforin was biosynthetically labelled prior to purification. The purified labelled protein was then utilized to obtain a direct measure of the amount of perforin bound to cells during attack. Resistant cells (CTL, neutrophils) bound at least as much perforin as did sensitive cells (K562, HL60 etc.), indicating that resistance to perforin involves mechanisms operating after binding of the lytic molecule.

Animals↗
PubMed1991

Twenty five years of case finding and audit in a socially deprived community.

OBJECTIVE: To evaluate audit and case finding (whole population care) in a community over 25 years. DESIGN: Contemporary screening for and audits of care of chronic disease and risk factors; retrospective review of computerised practice records; and comparisons of mortality and social indices with neighbouring communities. SETTING: One general practice in Glyncorrwg, West Glamorgan. SUBJECTS: 1800 people registered with the practice in 1987 and 558 people who died from 1964 to 1987, whose records had been retained. MAIN OUTCOME MEASURES: Detection of high blood pressure, smoking, airways obstruction, obesity, diabetes, and alcohol problems in adults aged 20-79; prevalence of smoking in this population and in hypertensive and diabetic groups; age standardised mortality ratios in relation to indices of social deprivation. RESULTS: In the population aged 20-79 (1207 patients) 249 (21%) had peak expiratory flow rate less than 50% of expected value or which improved by 15% or more with an inhaled beta agonist, 207 (17%) had body mass index at or over 30 kg/m2, 118 (10%) had untreated mean arterial pressures greater than 159/104 mm Hg (three readings), 80 (7%) (65 (16%) men, 15 (4%) women) had recognised alcohol problems, and 35 (3%) had diabetes. The proportion of men aged 20-64 who said they smoked fell from 61% (290/476) in 1968-70 to 36% (162/456) in 1985 whereas that of women who smoked was unchanged (43%, 187/436 v 42%, 190/448 respectively). In 116 screened hypertensive patients group mean blood pressure fell from 186/110 mm Hg before treatment to 146/84 mm Hg at 1987 audit, as did the proportion of smokers (56% v 20%), but body mass index and total cholesterol concentration showed no significant change. In 34 diabetic patients mean blood pressure and the proportion of smokers fell (171/93 mm Hg v 155/81 mm Hg; 44% v 12%). The age standardised mortality ratio in 1981-6 was lower than in a neighbouring village without a developed case finding programme (actual to expected deaths less than 65 = 21 to 22 in Glyncorrwg, 48 to 30 in control village). CONCLUSIONS: Whole population care through organised case finding and audit is feasible but only with a labour intensive approach combining accessibility, flexibility, and continuity, as well as a planned and structured approach, which requires substantial expansion of staff numbers and assiduous recording. It may reduce risks for at least some high risk groups. Despite their shortcomings the available data are consistent with the hypothesis that whole population care helps reduce mortality. Incentives in the new contract, which encourage the uncritical development of structured process, may diminish health outputs.

Adult↗
PubMed1991

Selective secretion of annexin 1, a protein without a signal sequence, by the human prostate gland.

Annexins are primarily intracellular proteins as would be predicted from their lack of hydrophobic signal sequences. However, we now report that the human prostate gland selectively secretes high concentrations of annexin 1 (also called lipocortin 1 and p35) and a proteolytic cleavage product, des1-29-annexin 1, into seminal plasma. Secreted annexin 1 had a blocked amino terminus and was structurally indistinguishable from intracellular annexin 1. Although annexin 1 and the structurally related protein, annexin 4, co-localized to many of the same cells of the ductal epithelium of the prostate, annexin 4 was not secreted. Thus, the secretion of annexin 1 appears to involve a highly selective mechanism that does not involve targeting to the endoplasmic reticulum by a hydrophobic signal sequence.

Amino Acid Sequence↗
PubMed1991

Adenosine deaminase, Ada, is in mouse chromosome 2H3, and is not allelic with wasted, wst.

The adenosine deaminase locus (Ada) in the mouse has been localized by in situ hybridization to band 2H3. Linkage analysis of backcross data has shown that Ada is 13.8 +/- 2.7 cM from the coat texture mutant, ragged, Ra. From the results of earlier work (Abbott, C. M., et al., Proc. Natl. Acad. Sci. USA 83:693, 1986), it had been suggested that wst was a low-activity allele of Ada, but this cannot be so because Ada and wst have been found to be nonallelic.

Adenosine Deaminase↗
PubMed1991

The molecular characterization of an A:T to G:C transition in the Hbb-b1 gene of the murine homologue of hemoglobin Rainier.

An N-ethyl-N-nitrosourea (ENU)-induced mutation in the Hbb-b1 gene of the mouse hemoglobin-beta complex (Hbb) has been shown to result in a high-oxygen affinity hemoglobin, homologous with hemoglobin Rainier in man (Peters, J., et al., Genetics 110:709, 1985). Substitution of beta 145 tyrosine by cysteine had occurred in both human and mouse forms, probably as the result of a point mutation. Provided that sufficient sequence information is available, point mutations can be directly and rapidly analyzed by allele-specific amplification (ASA), as this technique is sensitive enough to detect single nucleotide differences. We report the use of ASA to detect and characterize the mutation in the murine beta-globin gene, Hbb-b1d-m1, and find that the codon for beta 145 tyrosine (TAC) has been replaced by the codon for cysteine (TGC). Therefore, ENU induced an A:T----G:C transition.

Alleles↗
PubMed1991

A rapid visual test for predicting fetal lung maturity.

A rapid bedside test has been devised that enables an untrained observer to predict (p less than 0.001) when amniotic fluid will be greater than or equal to 0.15 at an optical density of 650 nm, lecithin/sphingomyelin ratio will be greater than or equal to 2.0, or when phosphatidylglycerol will be present. By a visual comparison of the turbidity of unspun amniotic fluid against positive (mature) or negative (immature) controls, technicians and resident physicians who had had no special training were able to classify correctly 87.2% (82/94) of unknown amniotic fluid samples. The sensitivity of the new test is 90.8% (58/65); the specificity is 70.3% (23/29). Thus, when more sophisticated methods are not readily available, we believe that this easily performed and accurate test can provide supplemental or preliminary data for patient management. In remote geographic areas our method could serve as the primary source of information about fetal lung maturity.

Amniotic Fluid↗
PubMed1991

Changes in temporal and spatial patterns of Gi protein expression in postimplantation mouse embryos.

We previously demonstrated the presence of GTP-binding proteins, G proteins, in the preimplantation mouse embryo (Jones and Schultz, 1990. Dev. Biol. 139, 250-262). These studies have been extended to the Day 6.5, 7.5, and 8.5 gestation embryo by employing PT-catalyzed ADP-ribosylation and immunoblotting techniques. We report here that the amount of embryonic alpha i increases from Day 6.5 to Day 7.5 of gestation, and remains at about the same level at Day 8.5. In contrast, the extent of PT-catalyzed ADP-ribosylation of Gi alpha protein(s) decreases between Days 6.5 and 7.5--this decrease is global and not restricted to a particular germ layer of the Day 7.5 embryo--and then dramatically increases by Day 8.5 of gestation. In the Day 8.5 gestation embryo, the extent of PT-catalyzed ADP-ribosylation of Gi alpha proteins increases along the anterior-posterior axis, whereas the amount of immunoreactive alpha i subunit decreases along this axis. By using a combination of PT-catalyzed ADP-ribosylation and immunoprecipitation with antisera specific for alpha i1, alpha i2, or alpha i3, we report that all three alpha i subtypes are present in the Day 8.5 gestation mouse embryo. Results of these experiments suggest that an activation of Gi proteins occurs between Days 6.5 and 7.5 of gestation in the postimplantation embryo, a time during which the embryo is gastrulating, and that a decreasing gradient of activation exists along the anterior to posterior axis in the Day 8.5 gestation embryo. Last, we report that oocytes, eggs, and preimplantation embryos possess all three subtypes of alpha i.

Amino Acid Sequence↗