Iowa record-linkage study: death rates in psychiatric patients

The Iowa record-linkage study was developed to investigate death rates in psychiatric patients, and involved computer matching of death certificates with a roster of patients. A list of all patients admitted to our hospital from 1972 through 1981 was obtained and after removing duplicate entries the list was pared to 5412 names. The record included multiple identifiers (e.g., name, gender, date-of-birth, hospital number). This information was then linked by computer with all Iowa death certificates for the same period; a total of 331 deaths were identified. Patients were assigned to a single psychiatric diagnostic category based on a computer program that reviewed each patient's clinical diagnoses and picked the one with the highest priority in a hierarchy we had created. Age and sex adjusted mortality tables were constructed, allowing us to compute expected numbers of deaths. Relative risk for premature death was greatest among women, and those under 20 years. Risk was associated with all psychiatric diagnoses and was significantly higher among patients of either gender with an organic mental disorder or schizophrenia; women with acute schizophrenia, depressive neuroses, alcoholism, drug abuse, and psychophysiological disorders; and men with neuroses. Death from natural causes, especially from heart disease, was significantly excessive among women, while death from accidents and suicides was excessive for both men and women. The overall SMR was 1.65 (P < 0.001). Most importantly, we found that the greatest excess of mortality occurred within the first 2 years following hospital discharge. Thus, we were able to demonstrate that risk of mortality in general, and of suicide specifically, differed according to age, gender, diagnosis, and portion of the follow-up. We have subsequently used this method to investigate specific risk factors associated with mortality in mood disorders, schizophrenia, and antisocial personality disorder. Findings from these studies are reported.     

Attenuation of neomycin ototoxicity by iron chelation

Increasing evidence suggests that aminoglycoside ototoxicity is mediated by the formation of an aminoglycoside-iron complex and that the creation of this complex is a preliminary step in generation of free radical species and subsequent hair cell death. In this study we have assessed the ability of the iron chelator deferoxamine to attenuate the hearing loss induced by an ototoxic dose of the aminoglycoside neomycin (100 mg/kg per day for 14 days). Experiments were carried out on pigmented guinea pigs weighing 250 to 300 g. Changes in auditory sensitivity were characterized by monitoring shifts in compound action potential (CAP) thresholds, recorded through indwelling electrodes implanted at the round window, vertex, and contralateral mastoid. Results show that animals receiving neomycin alone suffered a mean threshold shift exceeding 35 dB at all test frequencies (2.0, 4.0, and 8.0 kHz) 30 days after initiation of treatment. In comparison, all animals receiving cotherapy of neomycin and deferoxamine (150 mg/kg twice daily for 14 days) maintained their CAP threshold, suggesting significant protection from neomycin ototoxicity. A statistical comparison of treatment groups showed that in the animals receiving cotherapy with neomycin and deferoxamine, deferoxamine produced a significant protective effect against neomycin-induced ototoxicity (P < 0.001). These results provide further evidence of the intrinsic role of iron in aminoglycoside ototoxicity and suggest that deferoxamine may have a therapeutic role in attenuating the cytotoxic action of aminoglycoside antibiotics.     

Immunodiagnostic studies on Onchocerca volvulus and Mansonella perstans infections using a recombinant 33 kDa O. volvulus protein (Ov33)

A total detergent-soluble extract of adult female Onchocerca volvulus (OvAg) and a recombinant O. volvulus protein (Ov33) linked to glutathione-S-transferase (GST) were compared with regard to their serodiagnostic suitability for differentiating between O. volvulus and Mansonella perstans infections in a region endemic for both filarial worms in western Uganda. Using OvAg in an enzyme-linked immunosorbent assay (ELISA), 98.8% sensitivity was obtained examining 84 O. volvulus microfilariae (mf) carriers living in the hyperendemic area. However, 5 of 18 (28%) sera from M. perstans mf carriers without O. volvulus mf, from another area hypoendemic for O. volvulus, cross-reacted with OvAg. Using the recombinant antigen Ov33-GST in an ELISA and Western blot assay, sensitivity for O. volvulus remained high (97.2% and 98.8% respectively) while none of 90 sera from M. perstans mf carriers reacted positively. Both antigens were used to examine a batch of sera from 260 persons living in the onchocerciasis hyperendemic area who did not have mf in their skin snips (9.5% of 2728 persons examined); 116 of these sera (44.6%) were positive in the OvAg ELISA, compared to 85 (32.7%) and 69 (26.5%) which were positive in Ov33-GST ELISA and Ov33-GST Western blot, respectively. Reaction with GST alone was minimal. The recombinant antigen Ov33 efficiently differentiates between O. volvulus and M. perstans infections, and is sensitive when used to detect patent and prepatent or low-level O. volvulus infections.     

Characterization of multijoint finger stiffness: dependence on finger posture and force direction

The two-dimensional static stiffness of the index finger was measured with the interphalangeal joints in flexed and extended postures. The stiffness of the relaxed finger was compared with the stiffness when voluntary force was exerted in different directions. The finger stiffness was found to be anisotropic, with the direction of greatest stiffness being approximately parallel to the proximal phalange of the finger. This direction was relatively unaffected by finger posture or direction of finger force. Finger stiffness was more anisotropic when the interphalangeal joints were extended than flexed. The stiffness was most anisotropic when the interphalangeal joints were extended and force was being exerted in the direction of pointing, while it was least anisotropic when the interphalangeal joints were flexed and force was being exerted in directions normally associated with pinching and tapping actions. The stiffness of the individual finger joints was computed and the relation between stiffness and joint torque was examined. Previous studies, which examined single finger joints in isolation, had found that joint stiffness varied in a linear fashion with net joint torque. In contrast, we did not find a monotonic relation between joint stiffness and net joint torque, which we attributed to the need to vary the amount of cocontraction of antagonistic muscles when controlling the direction of finger force.