Commentary on wheeley and heath: The human development liaison specialist

Four main issues are examined which cut across the Wheeley and Heath articles: clarifying the liaison role, the liaison process, the organizational place for liaison, and barriers to establishing liaison. The argument that liaison work is a political act is presented. Heath's rejection of advocacy as an adversarial stance is supported. Bartering as the effective strategy of collaboration is discussed. The likelihood of rational planning as a sufficient approach to collaboration is judged to be low. The division of liaison in a community into school-based and mental health system-based agencies is recommended. Finally, political will and leadership are offered as the elements most needed to establish the liaison role.     

Hydrogen sulfide is a novel prosecretory neuromodulator in the Guinea-pig and human colon

BACKGROUND & AIMS: Hydrogen sulfide (H(2)S) has been suggested as a novel gasomediator. We explored its unknown neuromodulatory role in human and guinea-pig colon. METHODS: We used immunohistochemistry to detect H(2)S-producing enzymes cystathionine gamma-lyase (CSE) and cystathionine beta-synthase (CBS) in enteric neurons, Ussing chambers to measure mucosal ion secretion, and neuroimaging with voltage- and Ca(++)-sensitive dyes to record H(2)S effects on guinea-pig and human enteric neurons. RESULTS: More than 90% of guinea-pig and human submucous and myenteric neurons were colabeled for CSE and CBS. Myenteric interstitial cells of Cajal were CSE-immunoreactive. The exogenous H(2)S donor NaHS (0.2-2.5 mmol/L) concentration-dependently increased chloride secretion in human and guinea-pig submucosa/mucosa preparations, but not in the colonic epithelial cell line T84. The secretory response was reduced significantly by tetrodotoxin (0.5 micromol/L), capsaicin desensitization (10 micromol/L), and the transient receptor potentials vanilloid receptor 1 antagonist capsazepine (10 micromol/L). The endogenous H(2)S donor L-cysteine also induced secretion that was diminished significantly by capsaicin desensitization, the CBS inhibitor amino-oxyacetic acid, and the CSE inhibitor propargylglycine. NaHS increased spike discharge in 23% of guinea-pig and 36% of human submucous neurons, but had no effect on Ca(++) mobilization in cultured guinea-pig enteric neurons. This excitatory response was reduced significantly by capsaicin desensitization and capsazepine, but not by glibenclamide (10 micromol/L). CONCLUSIONS: The presence of H(2)S-producing enzymes in human and guinea-pig enteric neurons, the excitatory action on enteric neurons, and the prosecretory effects of NaHS suggest H(2)S as a novel gut-signaling molecule. Its action mainly involves transient receptor potentials vanilloid receptor 1 receptors on extrinsic afferent terminals, which in turn activate enteric neurons.     

Differential effects of dopamine on glucoregulatory hormones in rats

The effect of dopamine at different doses on serum concentrations of insulin, glucose and corticosterone and on plasma glucagon concentration was investigated in rats. Dopamine was given intravenously over 6 h with infusion rates of 2.5, 7.5, 15, and 60 micrograms/kg.min and in combination with phentolamine. Serum insulin concentration was unchanged at low doses of dopamine. It was significantly increased from 6.0 +/- 0.7 ng/ml to 13.7 +/- 2.3 ng/ml (P less than 0.01) when 7.5 micrograms/kg.min of dopamine were used, whereas it was significantly depressed to 3.96 +/- 0.89 and to 4.0 +/- 0.34 ng/ml (P less than 0.01), respectively, at the high doses of dopamine. This latter effect could be reversed to 6.7 +/- 1.19 ng/ml and inverted to 9.2 +/- 1.7 ng/ml (P less than 0.01) by simultaneously applied phentolamine at appropriate dosages. Serum glucose levels were markedly elevated from 154 +/- 7 to 234 +/- 42 mg/dl (P less than 0.01) by the higher doses of dopamine. A significant alteration of glucagon plasma concentrations from 18.9 +/- 2.8 to 42.3 +/- 14 pg/ml (P less than 0.01) was elicited only by 7.5 micrograms/kg.min of dopamine. The data clearly demonstrate that exogenous dopamine acts differently on glucose homeostasis according to the dosage. The study provides strong evidence that dopamine decreases insulin levels via alpha-adrenergic receptor stimulation. This effect may contribute to the deterioration of glucose homeostasis with high doses of dopamine.     

Prognostic value of quantitative troponin T measurements in unstable angina/non-ST-segment elevation acute myocardial infarction treated early and predominantly with percutaneous coronary intervention

PURPOSE: To evaluate the effect of baseline cardiac troponin T measurements on in-hospital and long-term outcomes in patients with unstable angina/non-ST-segment elevation myocardial infarction who are treated with an early invasive strategy. METHODS: We conducted a prospective cohort study involving 1024 consecutive patients with unstable angina/non-ST-segment elevation myocardial infarction. Patients were stratified according to quantitative troponin T measurements on admission, and underwent coronary angiography and subsequent coronary stenting of the culprit lesion as the primary revascularization strategy within 24 hours. The primary endpoint was all-cause mortality. RESULTS: The risk of in-hospital and long-term mortality increased with absolute levels of troponin T. In-hospital mortality was 0.7% (3/449) in patients with levels <0.010 microg/L, 2.0% (4/197) in those with levels from 0.010 to 0.035 microg/L, 3.2% (6/186) in those with levels from 0.035 to 0.229 microg/L, and 4.7% (9/192) in patients with levels >0.229 microg/L. Cumulative 2-year mortality rates were 2.8%, 8.0%, 10.5%, and 14.8% from the lowest to highest troponin T groups (P <0.001). In contrast, the risk of nonfatal myocardial infarction assumed an inverted U-shaped curve and was lower in the lowest and highest troponin T groups. CONCLUSION: Troponin T remains a strong predictor of mortality, even at low levels, in patients with unstable angina/non-ST-segment elevation myocardial infarction who are treated with early revascularization. The risk associated with elevated levels is linear for death but not for myocardial infarction.     

Infections by viruses of the families Bunyaviridae and Filoviridae

Rift Valley fever is the most important bunyaviral disease of animals in Africa. The virus, transmitted by mosquitoes, causes abortions and mortality in young animals in addition to haemorrhagic fevers in humans. Although vaccines against this virus are available, the uses of these vaccines are limited because of deleterious effects or incomplete protection, justifying further studies to improve the existing vaccines or to develop others. Nairobi sheep disease is transmitted by ticks. The disease is endemic in East Africa and sporadic cases are reported in India and Sri Lanka. Other viruses transmitted by mosquitoes or midges are teratogenic in cattle or sheep, these include Akabane and related viruses in Asia, Australia and the Middle East, and Cache Valley in North America. The Marburg and Ebola viruses of the genus Filovirus are associated with epidemics in Central Africa with high fatality rates in humans; some outbreaks were related to contact with monkeys. Another subtype of Ebola virus was first described in a quarantine facility in the United States of America among cynomolgus monkeys (Macaca fascicularis) from the Philippines. The reservoir of these viruses remains unknown.     

Effects of dexamethasone on the hypothalamic-pituitary-adrenal axis in preterm infants

The effects of dexamethasone therapy on the hypothalamic-pituitary-adrenal axis were tested in 10 premature infants with bronchopulmonary dysplasia by means of the corticotropin-releasing hormone stimulation test before therapy and on the seventh day of therapy. Adrenocorticotropic hormone and cortisol levels were determined by radioimmunoassay. There was significant suppression of the hypothalamic-pituitary-adrenal axis after 7 days of a currently used dexamethasone treatment regimen. A site of suppression was located at the level of the pituitary gland.     

Isolated congenital tuberculosis otitis in a preterm infant

We report an unusual case of localized congenital tuberculosis otitis in a preterm infant. Unlike disseminated congenital cases, the manifestations of localized otitis are associated with a triad of signs: (i) regional lymphadenopathy in the absence of typical systemic features of tuberculosis; (ii) delayed onset of presentation; and (iii) refractory otitis unresponsive to conventional antimicrobial agents. The need for greater diligence in looking for neonatal tuberculosis is emphasized, especially in an ethnic or socioeconomic environment where the disease is prevalent. Congenital tuberculosis, otitis, preterm
PC Ng, Department of Paediatrics, Level 6, Clinical Sciences Building, Prince of Wales Hospital, Shatin, NT, Hong Kong     

Inhibition of O6-alkylguanine-DNA alkyltransferase in animal and human ovarian tumor cell lines by O6-benzylguanine and sensitization to BCNU

O⁶-Alkylguanine-DNA alkyltransferase (O⁶-AGT) activity in rat ovarian tumor lines O-342 and O-342/DDP was 103.4±18.4 and 240.9±40.2 fmol/mg protein, respectively; thus, cisplatin (DDP) resistance was paralleled by an increase in O⁶-AGT activity by a factor of approximately 2.3. The DDP-resistant line expressed a collateral resistance to BCNU. Both lines could be sensitized to BCNU by O⁶-BG, with sensitization factors of 6.0 and 2.1, respectively. In neither line did depletion of O⁶-AGT have any sensitizing effect towards DDP. In the human ovarian cancer lines SK-OV-3 and OAW 42, O⁶-AGT activity was 337.6±18.2 and 180.0±39.9 fmol/mg protein, respectively; in these lines depletion of O⁶-AGT activity by O⁶-BG treatment resulted in sensitization factors of 3.0 and 4.1, respectively. The increase in sensitivity of ovarian tumor cell lines against a chloroethylating agent by O⁶-AGT depletion and possible pharmacological advantages of regional (i.p.) administration of this combination might be beneficial in advanced ovarian cancer.Abbreviations BCNU (1,3-bis(2-chloroethyl)-1-nitrosourea) - CENU 2-chloroethylnitrosourea - DDP cisplatin ED₅₀, the effective dose required to inhibit colony formation or cell proliferation by 50% - O⁶-AGT O⁶-alkylguanine-DNA alkyltransferase - O⁶-BG O⁶-benzylguanine SF sensitization factor