lntra- and Inter-Individual Variability in Growth Hormone Responses to Growth Hormone-Releasing Hormone*

Normal subjects show a wide range of growth hormone (GH) responses to growth hormone-releasing hormone (GHRH) stimulation, but it is uncertain whether this variability reflects differences among individuals or whether it would also be observed on repeated tests of the same subject. To clarify this, we tested nine normal men repeatedly with iv bolus doses of 1 μg/kg GHRH(1–44)NH₂. Most subjects showed wide variations in their GH responses on repeated testing, and the intra-individual variability was nearly as great as the inter-individual variability in responses, accounting for about two-thirds of the overall variance. A minority of subjects had lower and less variable responses. Ultradian fluctuations in hypothalamic somatostatin secretion may account for this marked intra-individual variability.     

Limited clinical usefulness of plasma corticotropin-releasing hormone, adrenocorticotropin and beta-endorphin measurements as markers of lung cancer.

We measured plasma corticotropin-releasing hormone (CRH), ACTH, beta-endorphin (beta-EP), and cortisol levels as possible tumor markers in a sequence of 103, randomly selected, patients with lung cancer but without the ectopic Cushing's syndrome and in 72 age- and sex-matched controls. Plasma CRH levels of cancer patients were similar to those of controls both in patients sampled in the morning or in the afternoon. On the other hand, plasma ACTH levels of cancer patients were significantly higher than control patients both in the morning and in the afternoon and showed a preserved circadian rhythm. However, about 35% of cancer patients sampled in the morning and about 60% of those sampled in the afternoon had ACTH levels within the 95% confidence interval (CI) of controls. Also plasma beta-EP levels were more elevated in cancer patients than controls in the morning but about 33% of them and about 80% of those sampled in the afternoon had beta-EP levels within the 95% CI of controls. Despite the higher plasma ACTH levels, cancer patients had cortisol plasma levels similar to controls with preserved circadian rhythm. In conclusion, although mean plasma ACTH and beta-EP were higher in patients affected by lung cancer, their measurements, as well as those of CRH, have practically no diagnostic value. Perhaps measurement of ACTH levels in the bronchial lavage may be more helpful.     

Variations in the severity of retinopathy seen in newborn rats supplemented with oxygen under different conditions of hyperbarism

The purposes of this experimental study were to evaluate the effects of oxygen supplementation delivered under hyperbaric conditions on the retinas of newborn rats and to determine the minimum and maximum levels of hyperbarism capable of protecting the retinal vessels from the toxic effects of oxygen without determining lethal effects in this experimental model. A control group of newborn rats were maintained with their mother for the first 12 days of life under room-air conditions. A second group of animals were exposed to a hyperbaric environment (+81 kPa) under normoxic conditions for the first 7 days of life and subsequently returned to normobaric conditions for the next 5 days. Examination of the retinal flat mounts from this latter group of animals revealed essentially normal vascular networks with only a modest degree of vasoconstriction. Two other litters of ratlings, with their mothers, were given supplemental oxygen at an FiO2 of 80% under a compression pressure of +101.25 kPa. In this group of animals, death of both of the mother rats from pulmonary edema occurred on the first day of treatment, and, in spite of immediate mother substitution, the newborn rats succumbed to the same complication. Five other groups, each containing two litters of newborn rats with their mothers, were exposed to FiO2s of 80% at hyperbaric levels ranging from +20.25- to +81.0 kPa for the first 7 days of life. On the eighth day, the FiO2s were reduced to 21%. After 5 days of room-air recovery, the animals were killed.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of peginterferon alfa-2a on liver histology in chronic hepatitis C: a meta-analysis of individual patient data

Multicenter randomized trials have shown that once-weekly pegylated interferon (peginterferon) alfa-2a is more efficacious than conventional interferon alfa-2a (IFN) in patients with chronic hepatitis C. We performed a meta-analysis of 1,013 previously untreated patients (from 3 randomized trials) with pretreatment and post-treatment liver biopsies to assess the differences between peginterferon alfa-2a and IFN in terms of their effects on liver histology. Reported values were standardized mean differences (SMD) between patients receiving peginterferon alfa-2a and those receiving IFN (post-treatment value minus baseline value for each group). We used a random-effects model to quantify the average effect of peginterferon alfa-2a on liver histology. Peginterferon alfa-2a significantly reduced fibrosis compared with IFN (SMD, -0.14; 95% CI: -0.27, -0.01; P =.04). A reduction in fibrosis was observed among sustained virologic responders (SMD, -0.59; 95% CI: -0.89, -0.30; P <.0001) and patients with recurrent disease (SMD, -0.34; 95% CI: -0.54, -0.14; P =.0007), whereas no significant reduction was observed among nonresponders (SMD, -0.13; 95% CI: -0.32, 0.05; P =.15). Logistic regression analysis indicated that patients with sustained virologic responses (SVRs) had an odds ratio (OR) of 1.61 (95% CI: 1.14, 2.29) for reduction in fibrosis compared with patients without SVRs, whereas obese patients (body mass index [BMI] > 30 kg/m(2)) had an OR of 0.56 (95% CI: 0.35, 0.90) compared with normal-weight (BMI < 25 kg/m(2)) and overweight patients (BMI, 25-30 kg/m(2)). In conclusion, in patients with chronic hepatitis C with or without cirrhosis, peginterferon alfa-2a (relative to IFN) significantly reduced fibrosis. The beneficial effects of peginterferon on liver histology are closely related to virologic response.     

Serological methods used for rabies post vaccination surveys: An analysis

The assessment of fox immunity following oral rabies vaccination (ORV) is commonly applied to assess the efficacy of an ORV campaign in the field. Several ELISA kits have been developed and validated for their use for rabies serology in wildlife as an alternative to neutralizing techniques (NT), such as the fluorescent antibody virus neutralization test (FAVN) and the rapid fluorescent foci inhibition test (RFFIT). At a European level, NT and ELISA tests are used interchangeably and on different types of samples collected for vaccination follow-up. This has resulted in a difficulty in comparing the results generated with different diagnostic tools. We have evaluated (a) the effect of two different matrices commonly used for serology in red foxes on the results of the FAVN and (b) the performance of two commercially available ELISAs in comparison with the FAVN, as a gold standard, using a panel of over 700 field fox samples. Moderate agreement was observed when comparing results from different matrices. We found a very low level of agreement and low values of relative sensitivity and specificity of the ELISAs tested in comparison with the FAVN. Our findings confirm, using a vast collection of field samples obtained during post-vaccination surveillance campaigns in Italy, the need for improved reliability of certain serological tests.     

Three cases of bartonellosis (cat scratch disease)

In the last years the number of Bartonella species has conspicuously increased, with better clinical and diagnostic definitions of the different related illnesses. We report, in the present article, 3 cases of cat-scratch disease, a particular bartonellosis mainly caused by Bartonella henselae which is transmitted by the cat. After an incubation period, cat-scratch disease clinically manifests as a regional lymphoadenitis, with the appearance of a small cutaneous lesion at the site of inoculation of the germ. The pathogenetic agent is susceptible to a number of antibacterial agents, such as penicillin, cephalosporins, aminoglycosides, tetracyclines, macrolides, quinolones, trimethoprim combined with sulphamethoxazole and rifampicin. The prognosis is usually favorable.