Genome-wide scan in a large complex pedigree with predominantly male schizophrenics from the island of Kosrae: evidence for linkage to chromosome 2q.

It is widely accepted that founder populations hold promise for mapping loci for complex traits. However, the outcome of these mapping efforts will most likely depend on the individual demographic characteristics and historical circumstances surrounding the founding of a given genetic isolate. The 'ideal' features of a founder population are currently unknown. The Micronesian islandic population of Kosrae, one of the four islands comprising the Federated States of Micronesia (FSM), was founded by a small number of settlers and went through a secondary genetic 'bottleneck' in the mid-19th century. The potential for reduced etiological (genetic and environmental) heterogeneity, as well as the opportunity to ascertain extended and statistically powerful pedigrees makes the Kosraen population attractive for mapping schizophrenia susceptibility genes. Our exhaustive case ascertainment from this islandic population identified 32 patients who met DSM-IV criteria for schizophrenia or schizoaffective disorder. Three of these were siblings in one nuclear family, and 27 were from a single large and complex schizophrenia kindred that includes a total of 251 individuals. One of the most startling findings in our ascertained sample was the great difference in male and female disease rates. A genome-wide scan provided initial suggestive evidence for linkage to markers on chromosomes 1, 2, 3, 7, 13, 15, 19, and X. Follow-up multipoint analyses gave additional support for a region on 2q37 that includes a schizophrenia locus previously identified in another small genetic isolate, with a well-established recent genealogical history and a small number of founders, located on the eastern border of Finland. In addition to providing further support for a schizophrenia susceptibility locus at 2q37, our results highlight the analytic challenges associated with extremely large and complex pedigrees, as well as the limitations associated with genetic studies of complex traits in small islandic populations.

An iron-binding exochelin prevents restenosis due to coronary artery balloon injury in a porcine model.

Background- Vascular smooth muscle cell (VSMC) proliferation is a critical factor in the neointima formation that causes restenosis after coronary angioplasty (PTCA). Desferri-exochelin 772SM (D-EXO), a highly diffusible, lipophilic iron chelator secreted by Mycobacterium tuberculosis, inhibits proliferation of VSMCs in culture. We hypothesized that treatment with D-EXO would inhibit neointima formation in balloon-injured vessels in vivo. Methods and Results- We subjected 24 pigs to overstretch coronary artery injury with standard PTCA balloons and then administered intramural injections of either D-EXO (n=14) or vehicle (n=10) through an Infiltrator catheter. Treatments were randomized, and the investigators were blinded with regard to treatment group until data analysis was completed. One month later, we euthanized the pigs, excised the injured coronary segments, made multiple sections of each segment, and identified the site of maximal neointima formation. An injury score based on the degree of disruption of the internal or external elastic lamina or media was assigned. D-EXO reduced stenosis index (neointima area divided by the area within the internal elastic lamina), adjusted for injury score, by 47%. Neointima thickness was also reduced. Conclusions- D-EXO, injected intramurally, substantially inhibited formation of neointima in a porcine vascular injury model.

Surgery on the affected upper extremity of patients with a history of complex regional pain syndrome: a retrospective study of 100 patients.

Surgery on the extremity affected with complex regional pain syndrome (CRPS) is generally avoided because of the risk that the symptoms will recur or worsen. Perioperative sympathectomy or stellate ganglion block has previously been recommended for CRPS patients requiring surgery of the affected upper extremity. We evaluated 100 patients with a history of upper extremity CRPS undergoing surgery on the affected extremity. All signs and symptoms of CRPS had resolved before surgery. After completion of the surgical procedure half of the patients (n = 50) underwent a stellate ganglion block; the other half received no intervention. The recurrence rate of CRPS was significantly lower in those patients receiving a postoperative stellate ganglion block (n = 5; 10%) compared with those receiving no intervention (n = 36; 72%). We conclude that performing a perioperative stellate ganglion block in patients with a history of CRPS can significantly reduce the recurrence rate of this disease process.

An exochelin of Mycobacterium tuberculosis reversibly arrests growth of human vascular smooth muscle cells in vitro.

Proliferation of vascular smooth muscle cells (VSMC) is characteristic of restenosis following balloon angioplasty. We show here that a low concentration of a novel iron chelator, desferri-exochelin 772SM, reversibly arrests the growth of human VSMC in vitro, specifically in G(0)/G(1) and S phases. The lipophilic desferri-exochelin is effective more rapidly and at a 10-fold lower concentration than the nonlipophilic iron chelator deferoxamine. Treatment of growth-synchronized VSMC with the desferri-exochelin results in down-regulation of cyclin E/ Cdk2 and cyclin A/Cdk2 activity but does not affect the cyclin D/Cdk4/retinoblastoma phosphorylation pathway. Both DNA replication and RNA transcription are inhibited in exochelin-treated cells, but protein synthesis is not. The ability of desferri-exochelin 772SM to reversibly block the growth of VSMC in vitro with no apparent cytotoxicity suggests that the exochelin may be useful as a therapeutic agent to limit restenosis in injured vessels.

Iron-mediated cardiovascular injury.

Iron is an essential element for normal cellular function and general health. However, iron may play a pathologic role in certain cardiac conditions including reperfusion injury, hemochromatosis, beta-thalassemia and coronary atherosclerosis. It also may play a role in injury due to anthracycline cardiotoxicity. Removal of iron via phlebotomy for hemochromatosis and chelation therapy for beta-thalassemia are proven treatments. Cell culture, and isolated organ and animal studies suggest that depleting iron stores may prevent reperfusion injury, restenosis and even atherogenesis. This article will review mechanisms by which iron overload states and normal iron stores contribute to cardiovascular pathophysiology and the accumulating evidence that iron chelation may prevent restenosis and atherogenesis.

Good planning alleviates bad effects of stoppages.

Work stoppages can stifle, if not halt, the activity of a hospital, especially when they involve nurses. What lessons can be learned from a strike? How do administrators "reintegrate" striking professionals after a settlement? In the following article Elizabeth Rosenthal cites a study involving nurses to address those issues.

Tenosynovitis: tendon and nerve entrapment.

The pathophysiology associated with tendon and nerve entrapment due to idiopathic tenosynovitis of the hand and wrist is discussed. The basis of clinical symptoms, nonoperative and operative treatment, complications, and prognosis relating to stenosing tenosynovitis and carpal tunnel syndrome are reviewed. A systematic approach to developing a philosophy for operative treatment is based upon severity of symptoms and findings at surgery. Deformities of the median nerve are classified into grades that correlate with symptoms and influence selection of the surgical procedure.

Treatment of fingertip and nail bed injuries.

The techniques for treating lacerations, amputations and loss of tissue, and injury of the perionychium are described in detail. The various local and distal flaps used for reconstruction and their appropriate application are also discussed. Rehabilitation of the digital tips is based on adaptation of the sensitive part to gradually increasing frequency and duration of stimulation.