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Biomedical subjects

J Simpson

Publications and source records attributed to J Simpson.

At least 181 records · Page 10Linked to original sources
PubMed1995

Interpretation of measured red cell mass and plasma volume in adults: Expert Panel on Radionuclides of the International Council for Standardization in Haematology.

Four European centres provided height and weight data on 202 males and 204 females undergoing red cell mass (RCM) and plasma volume (PV) measurements. For these populations, the RCM and PV predictions by the various published methods were compared. It was shown clearly that predictions based solely on body weight were inappropriate, particularly because approximately half of the male and female populations could be regarded as overweight or obese. Although there was reasonable agreement in the prediction values given by the formulae based on both height and weight, it was not possible to establish which formulae could be recommended. For that reason, the published literature containing normal RCM and PV measurements were re-examined. RCM data for 283 males and 171 females and PV data for 100 males and 67 females were included. Measurements were standardized for variables such as trapped plasma in the PCV, exclusion of buffy coat in the PCV and calculation of PV at zero time. As a result of this analysis, prediction formulae based on surface area for RCM and PV with 98/99% reference ranges have been established.

Adult↗
PubMed1995

Corticotrophin-releasing hormone and corticotrophin-releasing hormone binding protein in normal and pre-eclamptic human pregnancies.

OBJECTIVE: To measure the plasma levels of corticotrophin-releasing hormone and corticotrophin-releasing hormone binding protein in normal pregnancy and in pregnancies complicated by pre-eclampsia. SETTING: John Radcliffe Hospital, Oxford and St Thomas's Hospital, London. SUBJECTS: One hundred and twenty pregnant women sampled prospectively throughout gestation, of whom 91 experienced a normal pregnancy and eight developed pre-eclampsia; in a second study, 10 women with severe pre-eclampsia, presenting at a range of gestational ages, were sampled once and compared with appropriately matched normal pregnant women. MAIN OUTCOME MEASURE: Plasma levels of corticotrophin-releasing hormone determined by immunoradiometric assay. Plasma levels of corticotrophin-releasing hormone binding protein measured by direct radioimmunoassay. RESULTS: In the prospective study, plasma samples from women with pre-eclampsia exhibited higher (390.2 versus 292.7 pmol/l at 36 weeks) levels of corticotrophin-releasing hormone and significantly lower (5.24 versus 8.14 nmol/l at 36 weeks, P < 0.002) levels of corticotrophin-releasing hormone binding protein than normal controls. In the second, single time point study a significant elevation in CRH (P < 0.002) and reduction in CRH-BP (P < 0.001) was found in pre-eclamptic pregnancies compared with controls. CONCLUSIONS: In human pregnancies complicated by pre-eclampsia there is an elevated level of corticotrophin releasing hormone whilst there is less corticotrophin-releasing hormone binding protein; therefore there is a net increase in free potentially bioactive hormone which may play a role in the pathology of the disease.

Adolescent↗
PubMed1995

Reduction of interferon-gamma as a critical mechanism by which ultraviolet radiation prevents tumor rejection.

Mice irradiated with UVB, unlike nonirradiated mice, are highly susceptible to syngeneic, immunogenic tumors induced by UVB irradiation or by chemicals. We postulated that UV induced susceptibility to immunogenic tumors results from a reduction in host capacity to generate an interferon (IFN)-gamma immune response to tumor antigens. Shaved BALB/c mice were exposed to 6 x 10(5) J m-2 of UVB radiation delivered intermittently over 12 weeks. The UVB-irradiated and nonirradiated mice received intradermal injections of UVM12 or BP2 tumor cells. After 0, 1.5, 3, 7 or 21 days, draining lymph nodes were excised. Lymph node cells were incubated with UVM12 or BP2 cells that had received 2.5 Gy of gamma-radiation. After 48 h in culture, supernatants were analyzed for IFN-gamma content by enzyme-linked immunosorbent assay and cellular RNA was extracted for mRNA detection by reverse transcriptase-polymerase chain reaction analysis. At 7 days after tumor injection, draining lymph node cells from nonirradiated control mice secreted significant levels of IFN-gamma and contained at least 0.0729 amol of IFN-gamma mRNA/microgram cDNA upon in vitro exposure to gamma-irradiated tumor cells. Draining lymph node cells removed from UV-irradiated mice contained only 18% as much IFN-gamma mRNA and secreted little or no IFN-gamma when exposed to gamma-irradiated tumor cells. A single injection of antibody directed against murine IFN-gamma rendered normal mice as susceptible as UV-irradiated mice to BP2 tumor cells. Thus, chronic UV irradiation leads to an inability of host tumor draining lymph node cells to mount an IFN-gamma response to tumor antigens.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Randomised, double blind trial of two loading dose regimens of diamorphine in ventilated newborn infants.

AIMS: To compare the safety and efficacy of two loading doses of diamorphine in 27 ventilated newborn infants in a randomised double blind trial. METHODS: Fifty or 200 mcg/kg were infused intravenously over 30 minutes, followed by a 15 mcg/kg/hour continuous infusion. Serial measurements were made of physiology, behaviour, and stress hormones. RESULTS: Both loading doses produced small but significant falls in blood pressure. The 200 mcg/kg dose produced greater respiratory depression, and two infants deteriorated clinically, requiring resuscitation. Loading reduced respiratory effort in most of the infants, but had little effect on behavioural activity. Stress hormone concentrations were reduced at six hours in both dosage groups; differences between loading doses were not significant. Morphine, morphine-3-glucuronide, and morphine-6-glucuronide were detected in the plasma of all patients. No significant differences in concentrations between loading doses were found. CONCLUSIONS: Diamorphine reduces the stress response in ventilated newborn infants. A high loading dose confers no benefit, and may produce undesirable physiological effects. A 50 mcg/kg loading dose seems to be safe and effective.

Analgesics, Opioid↗
PubMed1995

Isolation and characterisation of human proximal tubular cells derived from kidney cortical segments.

1. Human renal proximal tubular cells (HPTC) were isolated by collagenase digestion and purified following filtration and isopycnic Percoll density centrifugation. This method used cortical tissue obtained from surgical nephrectomies and was both rapid and simple, providing a preparation of cells with high viability (> 93 +/- 3%) and recovery (16 +/- 7 x 10(6) cells g-1 of cortical tissue). 2. Characterisation of the isolated cells showed that, in terms of morphology, enzyme profile, transport systems and hormonal responsiveness, they were > 95% proximal tubular. The transport systems obeyed Michaelis-Menten kinetics, with the kinetic parameters of the glucose transport system (Km = 2.5mM, Vmax = 7.7 nmol min-1 mg-1 protein) suggesting a higher proportion of PT cells originating from the S1-S2 segment of the nephron. Isolated HPTC also maintained levels of reduced glutathione (GSH) (11.9 +/- 3.2 nmol mg-1 protein) and exhibited cytochrome P450-dependent activity, levels of spectrally determined P450 being 0.22 +/- 0.07 nmol mg-1 protein. 3. These results demonstrate the isolation of a viable and functioning homogeneous preparation of HPTC from cortical tissue, with potential for use in short term pharmacological, physiological and toxicological studies.

Alanine Transaminase↗
PubMed1995

Squamous cell carcinoma of the pyriform sinus: a nonrandomized comparison of therapeutic modalities and long-term results.

From January 1964 through December 1991, 408 patients with squamous cell carcinomas involving the pyriform sinus were treated at Washington University Medical Center. Their ages ranged from 29 to 83 years (mean, 62.3; median 59) and the male to female ratio was 5:1. The mean duration of symptoms prior to diagnosis was 3.9 months (range 1 to 32 months) and 89% had a smoking or ethanol history. Sixty-seven percent had T3 or T4 lesions and 87% were stage III or IV at presentation. Sixty-nine percent had neck metastases. The treatment strategy varied with respect to radiation and reconstruction. Prior to 1978, preoperative radiation (3.5 to 5000 cGy) was used. Postoperative radiation was given thereafter (600+ Gy). Since 1982, flap reconstruction (usually pectoralis major myocutaneous) has been used to close the partial laryngopharyngectomy (PLP) defect. Almost all N0 necks were treated by radiation or surgery and all N1-N3 lesions were treated by combined therapy. Pyriform tumors were subdivided into three groups: 1. one-wall lesions (n = 48), 2. medial-wall lesions which involved the aryepiglottic fold or supraglottis (N = 267), and 3. two- or three-wall lesions which extended to the pyriform apex or post-cricoid region (N = 93). Ninety-five patients had single-modality therapy and 302 had combined treatment. Two hundred seven patients had conservation surgery (PLP) and 157 had total laryngopharyngectomy alone or in combination with radiation. Thirty-three patients were treated by radiation alone. Eleven patients were excluded from the study because of distant metastases (TxNxM1) at presentation. The cumulative survival (NED) at 5, 10, 15, and 20 years was 56%, 35%, 31%, and 20%, respectively. The cumulative locoregional control rate was 71%. At 5 years (NED), the cure rates for one-wall lesions (73%) were better than for medial-wall lesions (63%) or 2- and 3-wall lesions (49%). One-wall lesions were smaller, medial-wall lesions behaved similar to supraglottic tumors, and two- or three-wall tumors behaved as hypopharyngeal tumors. The cure rates were related to T stage with T1 + T2 > T3 + T4 (28%). Neck metastases reduced the cure rate by 26% and N1 > N2-N3 by an additional 12%. Other factors contributing to therapeutic failure were distant metastases (17.7%), second primary tumors (6.2%; oropharynx and lung were most common), and intercurrent disease fatalities (9.5%). The secondary therapeutic salvage rate was 44% for surgery and 32% for radiation therapy. The therapeutic complication rate was 19% with 3.6% leading to fatality.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1995

Squamous cell carcinomas of the aryepiglottic fold: therapeutic results and long-term follow-up.

Three hundred fifteen patients with squamous cell carcinomas involving the aryepiglottic (A-E) folds were treated between January 1964 and December 1991. The age ranged from 39 to 87 years (mean, 62.4 years; median, 61.3 years) and the male-to-female ratio was 5:1 (54 women and 261 men). Symptom duration prior to diagnosis was 4.8 months. Eighty percent of patients had T3 and T4 lesions and 56.3% had neck metastases at presentation. Six patients (1.8%) had distant metastases and were excluded from this study. Clinically the tumors presented as either exophytic infiltrating lesions which were confined to the A-E fold (n = 57) or mucosally spreading tumors which extended to the lateral supraglottis or pyriform sinus (n = 258). Prior to 1978 preoperative radiation (3000 to 5000 cGy) was used. Higher doses of postoperative radiation (5000 to 6000+ cGy) were used thereafter. After 1982 the use of myocutaneous flaps for closure of partial laryngopharyngectomy defects was routine. Almost all N0 neck disease was treated by radiation or surgery. Combined therapy was used in N1-N3 disease. One quarter of the patients had single-modality therapy (25.7%; 81 patients) with a cumulative 5-year disease-free survival of 53%. The remainder of the patients (n = 234) had combined therapy with a cumulative 5-year survival of 67.2%. The latter group had 163 conservation surgeries and 121 total laryngectomy resections. The 5-year disease-free survival for preoperative radiation with surgery (68%) and postoperative radiation with surgery (64%) was similar. Those treated by radiation alone had a 34% 5-year disease-free survival and those treated with surgery alone had a 61% 5-year disease-free survival. The cumulative locoregional control rate was 77%. The cumulative disease-free survival at 5, 10, 15, and 20 years is 66%, 57%, 55%, and 55%, respectively. Infiltrating tumors had a better disease-free survival (by more than 10%) than spreading tumors. The 5-year survival rates were separated well by clinical stages of tumors. In patients with T1 tumors the 5-year survival was 87%; in those with T2 tumors, 80%; in those with T3 tumors, 78%; and in those with T4 tumors, 41%. The survival rate was greater in those with N0 tumors than in those with N+ tumors by 25% and greater in those with N1 tumors than in those with N2 + N3 tumors by an additional 18%. The overall complication rate was 26% and in 7.7% these were fatal.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1995

A mammogram coupon program: a collaborative effort to provide mammograms to uninsured women in Connecticut.

A collaborative effort to provide free screening mammograms to uninsured women throughout Connecticut using monies raised by the Connecticut RACE FOR THE CURE was launched during National Breast Cancer Awareness Month, October 1994. The program involved 55 American College of Radiology (ACR) accredited mammography facilities and 48 social service agencies. Eligibility criteria stipulated that participants be age 40 or older, be asymptomatic, have no health insurance, and have not had a mammogram within the last year. A total of 531 women received screening mammograms with four breast cancers diagnosed. The typical woman who was screened was white, between age 40 and 59, had a low income, a high school education or less, and no health insurance. Most had had a mammogram at some point in her life, but had not had one in the last two years. It was found that recruiting eligible women was more difficult than initially estimated. Many of the participating social service agencies served clients already on assistance, and, therefore, had mammogram coverage. Mass media, in particular television, proved to be a powerful recruiting tool which reached primarily "working poor" women. Future efforts should allow for a lengthier planning time to recruit hard-to-reach women and anticipate the need for case management to ensure follow-up of abnormal findings.

Adult↗
PubMed1995

Aortic regurgitation at diagnosis of HLA-B27 associated spondyloarthropathy.

A 14-year-old boy with a 9 month history of rheumatic symptoms was found to have hemodynamically significant aortic regurgitation in association with an HLA-B27 associated spondyloarthropathy (SpA). Valvular incompetence due to aortitis can occur early in the clinical course of pediatric patients with SpA, and careful cardiac monitoring is warranted.

Adolescent↗
PubMed1994

n of 1 trials comparing a non-steroidal anti-inflammatory drug with paracetamol in osteoarthritis.

OBJECTIVE: To evaluate the efficacy of paracetamol and a non-steroidal anti-inflammatory drug for symptom relief in osteoarthritis. DESIGN: Double blind, randomised, controlled trials in individual patients (n of 1 trials). Three treatment cycles with two weeks' each of paracetamol (1 g twice daily) and diclofenac (50 mg twice daily) prepared in identical gelatin capsules. SETTING: General practices in metropolitan Sydney, Australia. SUBJECTS: 25 patients (median age 64 years) with pain of osteoarthritis (median duration of disease eight years) considered by their general practitioners to require regular treatment. 20 were already taking non-steroidal anti-inflammatory drugs. MAIN OUTCOME MEASURES: Diary of pain and stiffness, function, and side effects. RESULTS: 15 patients completed the study, five withdrew early but had made a therapeutic decision, and five dropped out very early. Results from 20 patients were analysed. Several patterns of response evolved. Eight of the 20 patients found no clear difference, symptoms being adequately controlled by paracetamol; five indicated a clear preference for the non-steroidal anti-inflammatory drug; two showed control of symptoms after their initial two weeks of the non-steroidal anti-inflammatory drug which continued throughout subsequent treatment changes; in five the non-steroidal anti-inflammatory drug may have been better but neither agent gave satisfactory control. After three months nine of the 20 patients had adequate symptom control with paracetamol alone. CONCLUSIONS: Of 1 studies--that is, randomised trials in individual patients--are clinically useful in deciding treatment in heterogeneous conditions which require long term symptomatic relief. In osteoarthritis many patients currently receiving or being considered for non-steroidal anti-inflammatory drugs may achieve adequate control with paracetamol.

Acetaminophen↗
PubMed1994

Reduction of dapsone hydroxylamine to dapsone during methaemoglobin formation in human erythrocytes in vitro. III: Effect of diabetes.

The fate of dapsone hydroxylamine has been investigated in diabetic and normal human erythrocytes. In erythrocytes from four type 1 (insulin dependent) diabetic subjects, there was a significant decrease in dapsone hydroxylamine-mediated methaemoglobin formation compared with cells drawn from normal individuals (P < 0.01). However, the ability of the diabetic cells to detoxify the hydroxylamine to dapsone was not correspondingly reduced and was not different to normal cells. The initial rate of the accelerating effect of diethyl dithiocarbamate (DDC) on hydroxylamine-mediated methaemoglobin and dapsone formation was significantly reduced in diabetic compared with normal cells. There was no significant difference in hydroxylamine-dependent methaemoglobin formation between diabetic erythrocytes pretreated with either statil or sorbinil and untreated diabetic cells. Dapsone recovery in diabetic erythrocytes incubated with statil was not significantly different from statil-free incubations. However, in the presence of sorbinil, there was a marked reduction in dapsone formation at all four time points, (P < 0.001 at 15 min). Mean measured levels of glutathione did not differ significantly between the normal (380 +/- 30.9 mg/L; N = 8) and diabetic (349 +/- 58.7 mg/L; N = 8) volunteers. In summary, although diabetic erythrocytes were less sensitive to the effect of dapsone hydroxylamine-mediated methaemoglobin formation in comparison with normal cells, glutathione-dependent hydroxylamine reduction to dapsone was unaffected.

Dapsone↗
PubMed1994

Reduction of dapsone hydroxylamine to dapsone during methaemoglobin formation in human erythrocytes in vitro. IV: Implications for the development of agranulocytosis.

We have studied the efflux of dapsone hydroxylamine from normal and diabetic erythrocytes by the use of a two-compartment (1 and 2) in vitro dialysis system, in order to model the in vivo blood supply to the bone marrow. When both types of erythrocytes were dialysed against mononuclear leucocytes, the hydroxylamine crossed the membrane and caused significantly greater white cell death compared with dialysis of leucocytes against untreated erythrocytes. However, in the case of both normal and diabetic cells, the presence of the glutathione depletor diethyl maleate (DEM) caused a marked reduction in movement of hydroxylamine from compartment 1 to 2. Diethyl dithiocarbamate (DDC), a methaemoglobin accelerant, caused a marked reduction in movement of hydroxylamine from erythrocytes (diabetic and normal) in compartment 1 to 2 which led to a significant reduction in white cell death compared with the absence of DDC (18.3 +/- 5.5 vs 34.8 +/- 8.1%, P < 0.05). Dapsone recovery from compartment 1 rose significantly in the presence of DDC compared with control in both erythrocyte types. In contrast, recovery of dapsone from normal erythrocytes incubated in compartment 1 was significantly reduced by the presence of DEM compared with control, although there was no difference between control and DEM-treated diabetic cells. Dapsone analysis in compartment 2 revealed a significant increase in dapsone recovery in both diabetic (11.3 +/- 1.1%) and normal (11.9 +/- 1.1%) erythrocytes in the presence of DDC compared with diabetic (3.3 +/- 0.4%) and normal control (4.8 +/- 2.0%, P < 0.001). The presence of DEM in compartment 1 caused a significant fall in dapsone recovery in compartment 2 (3.7 +/- 0.26) compared with control (4.7 +/- 0.36%, P < 0.05). Hence, dapsone hydroxylamine is capable of leeching out of normal and diabetic erythrocytes, traversing a semipermeable membrane and causing toxicity to human mononucleocyte cells in vitro. This process may be one of the first stages in immune-mediated agranulocytosis.

Agranulocytosis↗