gamma-Aminobutyric acid stimulates pituitary growth hormone secretion in the neonatal rat. A superfusion study

The putative inhibitory neurotransmitter gamma-aminobutyric acid (GABA) elicited a dose-dependent increase in GH secretion from the pituitary of newborn rats. GH secretion increased within 3 min after GABA administration with a peak response at 5-6 min. The lowest effective dose of the GABA agonist muscimol was about 10 times smaller than that of GABA. The GABA effect was antagonized by picrotoxin and bicuculline, suggesting that GABA acts at GABA-A type receptors. The pituitary responsiveness to GABA gradually decreased during the second and third postnatal weeks. If the neonatal pituitaries were continuously exposed to GABA for 3 h GH secretion rapidly increased to a maximum within the first 10 min and then gradually decreased to a less elevated level by 1 h and remained at this level for the next 2 h. After 3 h of GABA exposure muscimol had no effect on GH secretion but human pancreatic GH-releasing factor stimulated it, indicating receptor desensitization during prolonged GABA administration. The significance of GABAergic regulation of GH secretion in the neonate is emphasized by the finding that simultaneous administration of picrotoxin diminished the GH releasing activity of the hypothalamic extract of 2-day-old rats by more than 60%. These results indicate that in the postnatal period the regulation of GH secretion differs from that of the adult animal and GABA might play an important role in the maintenance of the high GH secretion during the first days of life.     

Dissections of regional lymph nodes for treatment of skin cancer: predicting annual caseloads that will optimise outcomes

IntroductionDissection of regional lymph nodes (RLNs) can lead to significant morbidity and a high prevalence of complications. Published guidance states that these procedures should be carried out by surgeons who are members of a specialist skin multidisciplinary team who carry out a combined minimum of 15 axillary/groin dissections per year. However, there is little evidence to guide this minimum figure of procedures. We report on the burden of service provision and prevalence of complications across the South West of England and Wales.MethodsA 12-month review of dissections of RLNs for skin cancer was undertaken covering five Plastic Surgery Units with a collective catchment of 8.4 million people. Detailed data were collected on patient demographics, pathology, timing of surgery, and prevalence of complications.ResultsA total of 163 dissections were carried out. Forty-three per cent of patients experienced one or more complication. In that 12-month period, an average of 8 axillary/groin dissections was carried out per surgeon. A funnel plot demonstrated that the prevalence of complications for individual surgeons was within the limit of the plot but, in many cases, this was based only on a relatively small number of procedures per consultant. If surgeons carried out 10 procedures per year, the upper and lower limits on the plot were 73% and 11%, respectively.ConclusionsFunnel plots can provide a useful guide as to whether the prevalence of complications for procedures for individual surgeons lies within acceptable limits. Based on these results, 10 procedures per consultant per year should be sufficient to enable meaningful assessment of the prevalence of complications.     

Tripeptide aldehyde protease inhibitors may depress in vitro prolactin and growth hormone release

The effects of novel nontoxic tripeptide aldehyde inhibitors of proteolytic enzymes were examined in order to investigate the possibility that serine-thiol protease(s) may be involved in PRL and GH secretion. Rat anterior pituitary cells maintained in culture for 7-8 days or freshly taken pituitary quarters were treated with BOC-DPhe-Pro-Arg-H (BOC-dPPA), DPhe-Pro-Arg-H (dPPA), BOC-DPhe-Leu-Lys-H (BOC-dPLL), or BOC-DPhe-Phe-Lys (BOC-dPPL). Newly synthetized [3H]PRL and [3H]GH as well as immunoreactive (i) hormones (iPRL, iGH) were measured in the incubation media and cell homogenates. Four hours of incubation in the presence of 0.1 mM dPPA resulted in a 30% decrease of [3H]PRL and iPRL release by cell cultures; the inhibition by BOC-dPPA was 60% and 48%, respectively. [3H]PRL biosynthesis was unchanged or slightly decreased. The effect of these tripeptide aldehydes on [3H]GH and iGH release was less pronounced but statistically significant. Pituitary quarters treated with 1.0 or 3.0 mM BOC-dPPA release 20% and 57% less [3H]PRL than the controls. In the same system BOC-dPPA in a 1.0 mM concentration did not effect GH secretion, and 3.0 mM BOC-dPPA inhibited [3H]GH output by 27%. Forty micromolars of BOC-dPPL decreased by 47%, 0.2 mM by 79%, and 1.0 mM by 94% [3H]PRL release from pituitary quarters. GH secretion was not influenced. A similar selectivity was observed when BOC-dPLL was used. It is clear that by serine-thiol protease inhibitors whose effects are sequence and dose dependent, PRL and GH release are decreased. The relative inhibiting potency on PRL release was BOC-dPPL greater than BOC-dPLL greater than BOC-dPPA greater than dPPA. The biosynthesis of [3H]PRL was reduced only in the presence of the highest tripeptide aldehyde concentrations or long (8 h) exposure, and only 1.0 mM Boc-dPPL reduced [3H]GH biosynthesis by 30%. The data suggest that proteolysis may be involved in the process of PRL and GH release and the enzyme(s) in question may be serine-thiol protease(s).     

Nodding syndrome in Mundri county,South Sudan: environmental,nutritional and infectious factors

Background

Nodding Syndrome is a seizure disorder of children in Mundri County, Western Equatoria, South Sudan. The disorder is reported to be spreading in South Sudan and northern Uganda.

Objective

To describe environmental, nutritional, infectious, and other factors that existed before and during the de novo 1991 appearance and subsequent increase in cases through 2001.

Methods

Household surveys, informant interviews, and case-control studies conducted in Lui town and Amadi village in 2001–2002 were supplemented in 2012 by informant interviews in Lui and Juba, South Sudan.

Results

Nodding Syndrome was associated with Onchocerca volvulus and Mansonella perstans infections, with food use of a variety of sorghum (serena) introduced as part of an emergency relief program, and was inversely associated with a history of measles infection. There was no evidence to suggest exposure to a manmade neurotoxic pollutant or chemical agent, other than chemically dressed seed intended for planting but used for food. Food use of cyanogenic plants was documented, and exposure to fungal contaminants could not be excluded.

Conclusion

Nodding Syndrome in South Sudan has an unknown etiology. Further research is recommended on the association of Nodding Syndrome with onchocerciasis/mansonelliasis and neurotoxins in plant materials used for food.     

Hepatitis C and blood transfusion among children attending the Sickle Cell Clinic at Mulago Hospital,Uganda

Background

Hepatitis C virus (HCV) accounts for 90% of post-transfusion hepatitis. In Uganda, there has been limited research of prevalence of HCV among sickle cell anaemia (SS) patients, a group at risk for multiple transfusions.

Objectives

To establish prevalence of HCV infection and determine whether blood transfusion increases risk among SS patients.

Methods

244 SS patients aged 1–18 years were recruited by consecutive sampling. Socio-demographic, clinical and transfusion history was collected. Clinical examination done and blood tested for HCV by MEIA.

Results

244 children were recruited. Of these, 159 (65%) had a history of blood transfusion. Among the transfused, five patients were HCV positive. Four of these were over 12 years of age. Among patients with no history of transfusion, one patient aged 14 years was HCV positive. Risk of HCV was higher among the transfused OR 2.7(CI 0.31–24). Patients who received more than two units were more likely to be HCV positive (p=0.03).

Conclusions

HCV prevalence of 2.5% was low but higher than that reported by other investigators in Uganda. Blood transfusion was a major contributing factor in occurrence of HCV. Children who get repeated transfusions should be screened for Hepatitis C and screening of blood for HCV prior to transfusion would help reduce occurrence of the disease.     

The rise of plasma ACTH induced by ether is mediated through neural pathways entering the medial basal hypothalamus

The effect of ether stress on the release of immunoreactive ACTH was studied in rats with an antero-lateral cut around the medial basal hypothalamus. Ether failed to raise the plasma ACTH level of rats in which an antero-lateral hypothalamic cut and adrenalectomy had been performed 7 to 8 days previously. Plasma ACTH was also unchanged in rats exposed to ether 2 h after an antero-lateral cut. These data suggest that intact neural pathways entering the medial basal hypothalamus from the antero-lateral direction are necessary for the ACTH releasing action of ether stress.     

Multiple primary malignancies in patients with Merkel cell carcinoma1

Background Merkel cell carcinoma (MCC) is a rare malignant cutaneous tumour, the incidence of which is increasing. Second malignancies have been reported to occur with high incidence in these patients. Objectives We report the rate and nature of multiple malignancies in patients with MCC treated over a 10 year period in Addenbrooke’s Hospital in Cambridge, United Kingdom, as well as the temporal relationship of these additional malignancies to the diagnosis of MCC. Results The 27 patients had an approximately equal sex incidence with a median age at diagnosis of 79 years. Seventy percent (n=19) of patients had a second primary malignant tumour; and 7 of these patients had two or more tumours in addition to the MCC. Eighteen patients had additional cutaneous malignancies: melanoma, squamous cell carcinoma and basal cell carcinoma, and 8 patients presented non‐cutaneous malignancy including colorectal, haematological and breast tumours. Of the 28 additional tumours in our patients, half were diagnosed prior to presentation of MCC, 32% within 6 months of diagnosis, and 18% between 6 months and 3 years after diagnosis. Possible reasons for the high rate of additional tumours in this population are discussed. Conclusions Our figures reflect a higher incidence of multiple malignancies in those with Merkel cell tumour than has previously been reported. This has important implications for the care and surveillance of these patients.