Range of motion and complications after postburn heterotopic bone excision about the elbow

OBJECTIVE: To review the results of surgical management of heterotopic ossification about the elbow in burned patients. DESIGN: Retrospective analysis with long-term patient follow-up. MATERIALS AND METHODS: Eleven patients with 16 elbows requiring surgery were admitted between January 1, 1982 and December 31, 1993. A posterior approach to the elbow with release of the encased ulnar nerve +/- anterior transposition and transolecranon osteotomy to access extensive bone formation in the olecranon fossa was employed. Eight patients (11 elbows) were available for long-term follow-up conducted at mean 50 +/- 13 months after surgery. Long-term follow-up consisted of measurement of range of elbow motion, as well as clinical assessment of ulnar nerve function. MAIN RESULTS: For the 11 elbows examined postoperatively, the mean range of motion preoperatively in flexion-extension was 11 degrees +/- 5 degrees compared to 89 degrees +/- 12 degrees postoperatively (p < 0.001). Three patients with poor long-term results had ankylosis of the joint preoperatively. Of four patients with ulnar nerve paresis preoperatively, none had ulnar nerve dysfunction at follow-up. Of 16 elbows operated on, four (25%) had postoperative complications. Two suffered soft-tissue breakdown with hardware exposure requiring abdominal flap closure, one early failure of olecranon fixation, and one late infected hardware. CONCLUSIONS: Surgery for both limited range of motion as well as ulnar nerve compression is effective in cases of heterotopic ossification about the elbows of burned patients. Early operative intervention is indicated in progressive disease, particularly ulnar nerve palsy, if soft-tissue quality is adequate. Complications with 25% of elbows suggest that use of olecranon osteotomy for joint access may warrant review.     

A twin and family study of the association between immune system dysfunction and dyslexia using blood serum immunoassay and survey data

We conducted a study of the association between developmental reading disability (DRD) and immune disorders (ID) using both survey and immunoassay data in two separate samples of families. One sample was made up of twins and their parents and was ascertained through a population-based sampling scheme. The other sample was a set of extended pedigrees selected for apparent autosomal dominant transmission of DRD. We failed to find an association between DRD and ID in either sample, regardless of the method used to assess immune system function. Even though our twin sample provided evidence that both DRD and immune conditions were significantly heritable, there was no evidence for a genetic correlation between ID and DRD nor was there any clear indication that a special subgroup of individuals may be comorbid for these conditions because of genetic reasons. How these negative findings can be reconciled with the developmental hypothesis of Geschwind, Behan, Galaburda, and colleagues, and how they may relate to the gene locus influencing DRD that has been recently located in the HLA region of the short arm of chromosome 6 is discussed.     

rHuEpo for the treatment of anemia in myelofibrosis with myeloid metaplasia. Experience in 6 patients and meta-analytical approach

BACKGROUND AND OBJECTIVE: Experience with recombinant human erythropoietin (rHuEPO) in the treatment of the anemia secondary to myelofibrosis with myeloid metaplasia (MMM) is slight up to now. We present our results of the treatment of 6 patients and a review of the literature in search of possible parameters predicting response to this treatment. DESIGN AND METHODS: From January 1994 to June 1996 all transfusion-dependent patients with MMM diagnosed in our hospital were included in this study. We established a minimum period of 4 weeks of treatment and a maximum of 12 if no response was observed. Initial dosages used were 100 U/kg s.c. 3 times weekly, increasing by 50 U/kg every 4 weeks where no response was observed. Response was defined as a reduction > or = 30% of the previous transfusional needs. The review of the literature was made using a MEDLINE search (January 1990-December 1996) on the keywords erythropoietin, myelofibrosis, and agnogenic myeloid metaplasia. A statistical study was made in search of possible parameters to predict response. The parameters studied include age, sex, hemoglobin, serum erythropoietin (sEPO) levels, transfusional dependency, transfusional requirements per month prior to treatment, maximum dosages used and dosage at which response was obtained. RESULTS: Only 2 of our 6 patients responded, both at a dosage of 600 U/kg/week (200 U/kg 3 times weekly s.c.). In addition to our 6 patients we have found only 28 other patients in the literature. For statistical calculation 2 of our patients were not considered as they did not complete the period of study. The overall rate of response was 17/32 (53.1%). In the univariate analysis comparing responders and non-responders we found a tendency to significance with respect to sex (p = 0.07), sEPO (p = 0.07) and transfusional needs in units of packed red blood cells per month (PRBC/m) (p = 0.13). In this way patients with low sEPO, females and those with low transfusional needs (< 3 PRBC/m) respond better. This better response in females could be explained by the fact that their disease situation was more stable (with both lower sEPO levels and transfusional dependency). The best cut-off point in the sEPO to predict response was 123 mU/mL. No important side-effects have been observed except three cases of aggravation of splenomegaly. In two cases this condition improved when the rHuEPO was discontinued. The association of rHuEPO with hydroxyurea or interferon does not seem to affect the response. INTERPRETATION AND CONCLUSIONS: Though the number of patients is low, our data suggest that some MMM patients, in particular females and individuals with low sEPO levels and with low transfusional needs, might benefit from rHuEPO in terms of elevation of hemoglobin levels. Unfortunately, transfusion dependent-patients, i.e. those in whom a beneficial effect of rHuEPO would be most welcome, are unlikely to respond, and more generally, treatment is not cost effective in medically responsive patients.     

Forensic psychiatry in Britain

This report provides an overview of the criminal forensic mental health system in Great Britain, that is England and Wales. The report is based on the author's participant observation as a visiting consultant psychiatrist at a regional forensic facility in Manchester, England during early 1994. British law casts a net over a wider population of forensic patients than does U.S. law. There is a forensic care system in the British National Health Service that is parallel to and independent of the general psychiatric care system. The forensic system provides continuity of care from prison through maximum security hospitals to regional medium secure facilities, and finally, into the community. Community care is provided by psychiatrists and social workers and, if necessary, by psychiatric nurses. This system appears to provide effective treatment for persons with major mental disorders and histories of violence. Differences between Britain and the United States in philosophy of government, in law, and in forensic training and practice are discussed. The fundamental difference is a greater British belief in the capacity of government to act in the best interests of the individual. Current problems in the British health care system and plans to privatize some services are also discussed.     

IAP-family protein survivin inhibits caspase activity and apoptosis induced by Fas (CD95), Bax, caspases, and anticancer drugs

Survivin is a member of the inhibitor of apoptosis protein (IAP) family. We investigated the antiapoptotic mechanism of Survivin, as well as its expression in 60 human tumor cell lines used for the National Cancer Institute's anticancer drug screening program. In cotransfection experiments, cell death induced by Bax or Fas (CD 95) was partially inhibited (mean +/- SD, 65% +/- 8%) by Survivin, whereas XIAP, another IAP family member, almost completely blocked cell death (93% +/- 4%) under the same conditions. Survivin and XIAP also protected 293 cells from apoptosis induced by overexpression of procaspase-3 and -7 and inhibited the processing of these zymogens into active caspases. In vitro binding experiments indicated that, like other IAP-family proteins, Survivin binds specifically to the terminal effector cell death proteases, caspase-3 and -7, but not to the proximal initiator protease caspase-8. Using a cell-free system in which cytosolic extracts were derived from control- or Survivin-transfected cells and where caspases were activated either by addition of cytochrome c and dATP or by adding recombinant active caspase-8, Survivin was able to substantially reduce caspase activity, as measured by cleavage of a tetrapeptide substrate, AspGluValAsp-aminofluorocoumarin. Similar results were obtained in intact cells when Survivin was overexpressed by gene transfection and caspase activation was induced by the anticancer drug etoposide. Survivin was expressed in all 60 cancer cell lines analyzed, with highest levels in breast and lung cancers and lowest levels in renal cancers. These findings indicate that Survivin, which is commonly expressed in human tumor cell lines, can bind the effector cell death proteases caspase-3 and -7 in vitro and inhibits caspase activity and cell death in cells exposed to diverse apoptotic stimuli. Although quantitative differences may exist, these observations suggest commonality in the mechanisms used by IAP-family proteins to suppress apoptosis.