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↗