Subtyping depression by clinical features: the Australasian database

OBJECTIVE: To distinguish psychotic, melancholic and a residual non-melancholic class on the basis of clinical features alone. Previous studies at our Mood Disorders Unit (MDU) favour a hierarchical model, with the classes able to be distinguished by two specific clinical features, but any such intramural study risks rater bias and requires external replication. METHOD: This replication study involved 27 Australasian psychiatrist raters, thus extending the sample and raters beyond the MDU facility. They collected clinical feature data using a standardized assessment with precoded rating options. A psychotic depression (PD) class was derived by respecting DSM-IV decision rules while a cluster analysis distinguished melancholic (MEL) and non-melancholic classes. RESULTS: The MELs were distinguished virtually entirely by the presence of significant psychomotor disturbance (PMD), as rated by the observationally based CORE measure, with over-representation on only three of an extensive set of 'endogeneity symptoms'. CONCLUSION: In comparison to PMD, endogeneity symptoms appear to be poor indicators of 'melancholic' type, confounding typology with severity. Results again support the hierarchical model.     

Interferon induction of natural killer cytotoxicity in human neonates

Low natural killer cytotoxicity has been associated with serious herpes simplex virus infections. Neonates' mononuclear cells had significantly lower NKC to HSV infected (P less than 0.001) and uninfected (P less than 0.005) target cells than did adults' MC. Under appropriate conditions, both neonates' MC to NKC was increased by exogenous human leukocyte interferon. Although neonates' and adults' MC had a similar sensitivity to interferon, there was a significant (P = 0.05) lack of consistency in neonates' MC response. Twenty-three percent (4/17) of neonates' MC samples did not respond with increased NKC in the presence of interferon, unlike adults' MC, all of which demonstrated increased NKC. Neonates' MC did not suppress adults' MC-NKC. These data demonstrate the efficacy of interferon as an NKC stimulator in the neonate, but indicate a heterogeneous response of neonatal cells. We are encouraged with the prospect of clinical trials of interferon to treat severe viral infections in neonates. We urge the inclusion of immune surveillance in these trials.     

Blockage of drug resistance in vitro by disulfiram, a drug used to treat alcoholism

BACKGROUND: P-glycoprotein (P-gp) pumps a wide range of cytotoxic drugs out of cells. Inhibiting maturation of P-gp would be a novel method for circumventing P-gp-mediated multidrug resistance, which complicates cancer chemotherapy and treatment of patients infected with human immunodeficiency virus. We examined the effect of disulfiram (Antabuse(TM)) on the maturation and activity of P-gp. METHODS: Embryonic kidney cells were transfected with a complementary DNA for the P-pg gene, and the effects of disulfiram on the sensitivity of the transfected cells to cytotoxic agents were determined. Enzyme assays were used to determine the effects of disulfiram on the verapamil-stimulated adenosine triphosphatase (ATPase) activity of P-gp. Disulfiram modifies cysteine residues, and mutant forms of P-gp that lack individual cysteines were used to determine whether particular cysteine residues mediate disulfiram's effects on P-gp activity. Maturation of recombinant P-gp was followed on immunoblots. RESULTS: Disulfiram increased the sensitivity of P-gp-transfected cells to vinblastine and colchicine and inhibited P-gp's verapamil-stimulated ATPase activity. Half-maximal inhibition of ATPase activity occurred at 13.5 microM disulfiram. Disulfiram (at 100 microM) inhibited a P-gp mutant by 43% (95% confidence interval [CI] = 37%-48%) when cysteine was present at position 431 only and by 72% (95% CI = 66%-77%) when cysteine was present at position 1074 only. Treatment of P-gp-transfected cells with 50 nM disulfiram blocked maturation of recombinant P-gp. CONCLUSIONS: Disulfiram can potentially reduce P-gp-mediated drug resistance by inhibiting P-gp activity (possibly via cysteine modification) and/or by blocking its maturation. These results suggest that disulfiram has the potential to increase the efficacy of drug therapies for cancer and acquired immunodeficiency syndrome.     

Outcome assessment of the Ministry of Health Malaysia dialysis programme

We describe the outcomes on haemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD) provided by the Ministry of Health (MOH). The assessment was based on data from the Malaysian Dialysis Registry on 2480 HD and 732 CAPD patients who commenced dialysis between 1980 and 1996. Young patients (age < 40) have remarkable long term survival (life expectancies of 16 years on HD, 18 years on CAPD). Adjusting for background mortality, relative survival of older patients was as good as younger ones. Diabetics did poorly. 52% of HD and 26% of CAPD patients were employed in 1996. 71% of HD patients scored 10(normal) on QL index (a measure of quality of life) while 60% of CAPD patients have similar score. Differences in rehabilitation and QL index scores by age, gender and diabetes were also observed. Outcomes of dialysis in the MOH programme are reassuring.     

Comparison of acetorphan with clonidine for opiate withdrawal symptoms

OBJECTIVE AND METHOD: The authors compared the effects of acetorphan, an enkephalinase inhibitor, with those of clonidine for the treatment of the opioid withdrawal syndrome. Nineteen patients addicted to heroin or synthetic opiates who were undergoing drug withdrawal and displayed a withdrawal syndrome according to DSM-III criteria were studied for 5 days in a hospital setting. In a double-blind trial, 10 subjects were given acetorphan intravenously and nine were given clonidine; objective signs and subjective symptoms of withdrawal were recorded. RESULTS: On several objective signs, the effect of acetorphan was more marked than that of clonidine, whereas the two drugs exhibited similar efficacy with respect to the subjective components of withdrawal. No side effect was noted in the subjects who received acetorphan. CONCLUSIONS: Enkephalinase inhibition may constitute a novel and safe therapeutic approach to the opioid withdrawal syndrome.     

Psychiatric comorbidity and causal disease models

In psychiatry, comorbidity is the rule rather than the exception. Up to 45% of all patients are classified as having more than one psychiatric disorder. These high rates of comorbidity have led to a debate concerning the interpretation of this phenomenon. Some authors emphasize the problematic character of the high rates of comorbidity because they indicate absent zones of rarities. Others consider comorbid conditions to be a validator for a particular reclassification of diseases. In this paper we will show that those at first sight contrasting interpretations of comorbidity are based on similar assumptions about disease models. The underlying ideas are that firstly high rates of comorbidity are the result of the absence of causally defined diseases in psychiatry, and second that causal disease models are preferable to non-causal disease models. We will argue that there are good reasons to seek after causal understanding of psychiatric disorders, but that causal disease models will not rule out high rates of comorbidity — neither in psychiatry, nor in medicine in general. By bringing to the fore these underlying assumptions, we hope to clear the ground for a different understanding of comorbidity, and of models for psychiatric diseases.     

中风后抗轴突生长抑制因子DNA免疫促进局部脑缺血后神经再生

目的评价中风后给予轴突生长抑制因子DNA疫苗对局部脑缺血后神经再生的促进作用。方法采用阻断大脑中动脉血流成功诱导左侧局部脑缺血后，经腓肠肌注射轴突生长抑制因子DNA疫苗。立体定向注射生物素葡聚糖胺追踪皮质红核投射的新生轴突。结果中风后给予轴突生长抑制因子DNA疫苗可增加跨过中线终止于对侧红核相应区域的生物素葡聚糖胺标记阳性交叉纤维（P〈0．05）。结论中风后给予轴突生长抑制因子DNA疫苗可促进局部脑缺血后的轴突再生。