Calciphylaxis – a topical overview

'Calciphylaxis', a calcification syndrome associated with ischaemic cutaneous necrosis, is acquired naturally in humans in disease states. It is a life and limb-threatening complication, usually observed in patients with renal disease and secondary hyperparathyroidism, but known to occur in the absence of renal or parathyroid disease. The reported mortality rate, which ranges from 60-80%, relates to wound infection, sepsis and organ failure. It is a small-vessel vasculopathy, which is estimated to occur in about 4% of haemodialysis patients. Clinically, violaceous, reticulate areas of cutaneous necrosis and eschar may be evident, particularly in the extremities. In addition to the clinical picture, a raised calcium phosphorous product, an elevated parathyroid hormone level, radiographic evidence of vessel and soft-tissue calcification and the finding of mural calcification affecting small arteries and arterioles on histopathology help to confirm the diagnosis of this entity which generally has a poor prognosis. A high index of suspicion and an active multidisciplinary management approach, with rigorous attention to wound care and prevention of sepsis, are vital in the management of these patients. In this overview, we discuss the pathophysiology, clinical features and associations, risk factors, diagnosis and management issues relating to calciphylaxis.     

Psychotic symptoms and age of onset in affective disorders.

Prevalence of hallucinations and delusions was studied in 1,763 patients with unipolar major depression, bipolar affective disorder, and schizoaffective disorder. The authors found that the presence of psychotic features was negatively associated with age of onset for the group as a whole, and bipolar affective disorder (manic or mixed type) specifically. The clinical implications of the findings are discussed.     

Complicated mania. Comorbidity and immediate outcome in the treatment of mania

In a case-control study, 57 manics with antecedent or coexisting nonaffective psychiatric disorders (n = 38) or serious medical illnesses (n = 19) ("complicated mania") were compared with 114 age-, sex-, and year-of-admission-matched controls with no other disorder ("uncomplicated mania"). Significant differences emerged between the three groups in age, marital status, age at onset, number of prior hospitalizations and prior suicide attempts, organic features, and outcome measures (recovery and death rates). Patients were divided into four treatment groups based on primary mode of therapy during index admission; the groups included electroconvulsive therapy, adequate lithium carbonate, inadequate lithium carbonate, and neither treatment. Uncomplicated manics were significantly more likely to receive adequate lithium carbonate and less likely to receive inadequate lithium carbonate than were complicated manics. The latter patients had a significantly poorer immediate response to treatment overall, and to adequate lithium carbonate specifically. Seventy-eight (68.4%) uncomplicated manics had recovered ad discharge, compared with 26 (45.6%) complicated manics. Logistic regression suggested that the influence of comorbidity on outcome was more important for women than men. We conclude that complicated mania is a useful clinical construct.     

Mutations in the retinal guanylate cyclase (RETGC-1) gene in dominant cone-rod dystrophy

The dominant cone-rod dystrophy gene CORD6 has previously been mapped to within an 8 cM interval on chromosome 17p12-p13. The retinal- specific guanylate cyclase gene (RETGC-1), which maps to within this genetic interval and previously was implicated in Leber's congenital amaurosis, was screened for mutations within this family and in a panel of small families and individuals with various cone and cone- rod dystrophy phenotypes. A missense mutation (E837D) was identified in affected members of the CORD6 family, as well as a second missense mutation (R838C) in three other families with dominant cone-rod dystrophy. RETGC-1 is only the fourth gene to be implicated in cone-rod dystrophy and this is the first report of dominant mutations in this gene.      

Comparison between testosterone oenanthate-induced azoospermia and oligozoospermia in a male contraceptive study. IV. Suppression of endogenous testicular and adrenal androgens

Administration of supraphysiological doses of testosterone to normal men causes inhibition of spermatogenesis, but while most become azoospermic, 30-55% maintain a low rate of spermatogenesis. We have investigated whether there are differences in endogenous androgen production, of testicular and adrenal origin, which may be related to the degree of suppression of spermatogenesis. Thirty-three healthy Caucasian men were given weekly i.m. injections of 200 mg testosterone oenanthate (TE), 18 became azoospermic, while 15 remained oligozoospermic. Urinary excretion of epitestosterone, a specific testicular product, was reduced to <10% of pretreatment values, with no differences between the groups. Similar results were obtained for other markers of testicular steroidogenesis. Urinary and plasma adrenal androgens were also reduced during TE treatment: a statistically significant decrease in both (P < 0.001 and P < 0.05 respectively) was seen in the azoospermic but not oligozoospermic responders. These results suggest that testicular steroidogenesis is decreased to <10% by the administration of supraphysiological doses of exogenous testosterone. Differences in the degree of ongoing steroidogenesis in the testis do not appear to account for incomplete suppression of spermatogenesis, thus differences in androgen metabolism may underlie this heterogeneous response. A small but significant reduction in secretion of adrenal androgens was also detectable, the relevance of which is unclear.      

Primary esophageal motor disorders: clinical response to nifedipine

The effect of nifedipine on esophageal symptoms was evaluated in 20 patients with primary esophageal motor disorders. The patients were randomized to receive nifedipine (10 mg t.i.d.) or placebo for two weeks, and then crossed over to receive the other medication. Ten patients had hypertensive lower esophageal sphincter, four had diffuse esophageal spasm, three had vigorous achalasia, two had "nutcracker esophagus," and one patient had achalasia. The score of chest pain or dysphagia was recorded on a scale of 0 to 10 during each study. The patients who received nifedipine improved significantly compared to those who received placebo. This improvement was most marked in patients with hypertensive lower esophageal sphincter. No significant side effects or changes in blood pressure were encountered in any of the study groups. Our results indicate that patients with primary esophageal motor disorders have a good clinical response to nifedipine therapy.     

Differential expression of FMR1, FXR1 and FXR2 proteins in human brain and testis

Lack of expression of the fragile X mental retardation protein (FMRP) results in mental retardation and macroorchidism, seen as the major pathological symptoms in fragile X patients. FMRP is a cytoplasmic RNA- binding protein which cosediments with the 60S ribosomal subunit. Recently, two proteins homologous to FMRP were discovered: FXR1 and FXR2. These novel proteins interact with FMRP and with each other and they are also associated with the 60S ribosomal subunit. Here, we studied the expression pattern of the three proteins in brain and testis by immunohistochemistry. In adult brain, FMR1, FXR1 and FXR2 proteins are coexpressed in the cytoplasm of specific differentiated neurons only. However, we observed a different expression pattern in fetal brain as well as in adult and fetal testis, suggesting independent functions for the three proteins in those tissues during embryonic development and adult life.