No major effect of orciprenaline and propranolol upon ACTH-induced cortisol secretion.

Preclinical research suggests adrenal beta-adrenergic receptors to be involved in the regulation of steroid synthesis. In a group of healthy male volunteers, we compared ACTH-induced cortisol and dehydroepiandrosterone (DHEA) secretion after pre-treatment with orciprenaline, propranolol or placebo. Neither baseline nor ACTH-induced steroid secretion differed between these conditions. Our data do not support the hypothesis that the adrenal beta-receptor plays a major role in steroid secretion in humans.     

Thirty-year follow-up of superior vena cava-pulmonary artery (Glenn) shunts.

The first superior vena cava-pulmonary artery shunt (Glenn shunt) in our series was performed in February 1958. From then through September 1988, 91 patients have undergone this procedure for a wide variety of congenital defects. We here report follow-up data available on all patients. Ages ranged from 2 days to 46 years (mean 6.8). Diagnoses were as follows: tricuspid atresia, 27; single ventricle, 22; tetralogy of Fallot, 14; D-transposition of the great arteries, ventricular septal defect, and pulmonary stenosis, 9; D-transposition, 5; Ebstein's anomaly, 4; pulmonary atresia + intact septum, 4; and others, 6. The hospital mortality rate was 7.7% (one death in the last 53 patients, 1.9%). Five deaths occurred in patients less than 6 months old. There were 20 late deaths (22%) with actuarial survival rates of 84% and 66% at 10 and 20 years, respectively. Pulmonary arteriovenous fistula formation was seen in 18 patients (19.7%), six of whom have undergone therapeutic embolization with improvement in saturation. The prevalence of pulmonary arteriovenous fistula increases with time after shunt. No long-term shunt thrombosis or stricture formation was seen. Fifty percent of shunts were still functioning at 20 years. Palliation was limited because of decrease in blood flow to the contralateral pulmonary artery, collaterals between the inferior and superior venae cavae, and pulmonary arteriovenous fistula formation. Improvement in saturation was obtained in eight otherwise inoperable patients by creation of a right axillary arteriovenous fistula up to 19 years after the Glenn shunt. Three patients had conversion of a Blalock-Taussig shunt to a Glenn shunt with improvement in congestive heart failure. Twenty-six patients have undergone a Fontan procedure with two deaths. Compared with the group having a Fontan procedure without a prior Glenn operation, there was no difference in early or late mortality. Thirty years after a Glenn shunt, the first patient in this series is working full time after having undergone a modified Fontan procedure in 1981. We conclude that the Glenn connection, usually with supplemental procedures to enhance oxygenation, has provided excellent physiologic palliation with low mortality up to 30 years with no late thrombosis or stricture formation. The incidence of pulmonary arteriovenous fistula increases with time and can be effectively treated with embolization. Physiologic repair after the Glenn shunt carries a low mortality. Although currently used infrequently, superior vena cava-pulmonary artery shunting remains a useful method of palliation in selected patients.(ABSTRACT TRUNCATED AT 400 WORDS)     

The importance of self-examination in the earliest diagnosis of multiple primary cutaneous melanomas: a report of 47 cases

BACKGROUND: Development of more than one primary melanoma in a patient is a relatively uncommon but well-recognized phenomenon. Its frequency has ranged from 1.2% to 8.2% in several series. This subgroup of patients with multiple primary lesions has not been characterized sufficiently. We report the experience of the Melanoma Unit of University Hospital Spedali Civili of Brescia, Italy. METHOD: Study subjects were drawn from 1240 patients with histologically confirmed melanoma, including melanoma in situ. From this group, multiple melanomas developed in 47 patients (3.79%). Every one of our patients has been taught to perform self-examination of the skin to detect suspicious pigmented lesions. RESULTS: Of the 47 patients described in this study, 38 had two primary melanomas, 7 had three melanomas and 2 had 5 and 10 melanomas, respectively. Mean age at first diagnosis was 46.2 years. The majority of subsequent melanomas (74.5%) were removed within 5 years of the initial operation. Synchronous lesions were found in 10 patients. In male patients, the lesion appeared most frequently on the trunk; in female patients, melanoma appeared mostly on the lower extremities. The second primary melanomas developed in the same anatomic region from the first in 53.2% of our patients. The proportion of in situ to invasive melanomas was greater for the second melanomas compared with the first melanomas. Regarding invasive melanomas, the mean thickness of the first melanomas was 1.31 mm compared with 0.66 mm for the second ones. Dividing patients into two groups, of more and less than 50, it is highlighted that in older patients synchronous lesions appear more frequently (36.4% vs. 8.0%); the median time interval between sequential melanomas is longer (84 vs. 63.7 months); and the ratio between the primary and secondary melanoma mean thickness is lower (1.21 : 1.08 vs. 1.43 : 0.63 mm). CONCLUSIONS: The study confirms that second primary melanoma is usually thinner than the first lesion, and it is more common in the same region of the body as the initial melanoma. The highest risk for a second melanoma is during the first 5 years, but a much longer time interval of 28 years is possible. Continued medical follow-up with complete skin examinations seems prudent, but it is very important to promote self-skin evaluation in patients to detect not only metastases but also subsequent primary melanomas in their earliest phases.     

Interleukin 6 Influences Germinal Center Development and Antibody Production via a Contribution of C3 Complement Component

Mice rendered deficient for interleukin (IL) 6 by gene targeting were evaluated for their response to T cell–dependent antigens. Antigen-specific immunoglobulin (Ig)M levels were unaffected whereas all IgG isotypes showed varying degrees of alteration. Germinal center reactions occurred but remained physically smaller in comparison to those in the wild-type mice. This concurred with the observations that molecules involved in initial signaling events leading to germinal center formation were not altered (e.g., B7.2, CD40 and tumor necrosis factor R1). T cell priming was not impaired nor was a gross imbalance of T helper cell (Th) 1 versus Th2 cytokines observed. However, B7.1 molecules, absent from wild-type counterparts, were detected on germinal center B cells isolated from the deficient mice suggesting a modification of costimulatory signaling. A second alteration involved impaired de novo synthesis of C3 both in serum and germinal center cells from IL-6–deficient mice. Indeed, C3 provided an essential stimulatory signal for wild-type germinal center cells as both monoclonal antibodies that interrupted C3-CD21 interactions and sheep anti–mouse C3 antibodies caused a significant decrease in antigen-specific antibody production. In addition, germinal center cells isolated from C3–deficient mice produced a similar defect in isotype production. Low density cells with dendritic morphology were the local source of IL-6 and not the germinal center lymphocytes. Adding IL-6 in vitro to IL-6–deficient germinal center cells stimulated cell cycle progression and increased levels of antibody production. These findings reveal that the germinal center produces and uses molecules of the innate immune system, evolutionarily pirating them in order to optimally generate high affinity antibody responses.     

Critical ovarian hyperstimulation syndrome in a coasted in-vitro fertilization patient

We report an instance of critical ovarian hyperstimulation syndrome in a highly responsive in-vitro fertilization patient despite the preventive measure of a 4 day 'coast' interval during which no gonadotrophins were administered while gonadotrophin-releasing hormone agonist therapy continued until serum oestradiol concentrations fell below 3000 pg/ml.      

Hapten-induced colitis associated with maintained Th1 and inflammatory responses in IFN-gamma receptor-deficient mice

IFN-gamma is a potent pro-inflammatory cytokine thought to be involved in the pathogenesis of Crohn's disease. To further define the role of IFN-gamma in intestinal inflammation, we studied the effects of intra-colonic 2,4,6-trinitrobenzene sulfonic acid (TNBS) instillation in mice with a functionally inactivated IFN-gamma receptor 1 (IFN-gammaR1(- / -)). Our results indicate that IFN-gamma is not necessary for the induction of hapten-induced colitis: after TNBS administration both wild-type and IFN-gammaR1(- / -) mice lost body weight, and the histological features of TNBS-induced colitis were comparable. Colons of IFN-gammaR1(- / -) mice contained a greater number of cells, represented by macrophages and CD4(+) T cells; caudal lymph node cells produced more IFN-gamma and TNF-alpha upon stimulation in vitro. Moreover, IL-18 and IL-12 p40 RNA levels were comparably up-regulated after TNBS treatment in IFN-gammaR1(- / -) wild-type mice. These findings demonstrate that IFN-gamma is dispensable for the development of TNBS-induced colitis. Importantly, the production of Th1 cytokines (e. g. IFN-gamma and TNF-alpha) by caudal lymph node T lymphocytes was enhanced rather than decreased in IFNgammaR1(- / -) mice with no evidence for default Th2 development.