Genetics and biochemistry of primary congenital glaucoma

Several observations noted by early investigators supported the supposition that in most cases, congenital glaucoma is determined by genetic factors. The genetic heterogeneity of PCG was confirmed by genetic linkage studies conducted in the 1990s when the authors determined that CYP1B1 is the congenital glaucoma gene at the GLC3A locus. The coding sequence of CYP1B1 has been subjected to extensive screening in familial and sporadic cases of glaucoma from numerous countries and from a large number of ethnic groups. These studies have provided evidence for extensive allelic heterogeneity at the GLC3A locus. This article also discusses the molecular evidence for reduced penetrance in congenital glaucoma and the phenotypic heterogeneity of CYP1B1 mutations, mouse models of CYP1B1, and the biochemistry of CYP1B1.     

Telemedicine for the operating room of the future

Telemedicine is becoming a subset of information science and should benefit tremendously from the geometric growth of information architecture in hospitals. The use of telemedicine to break the isolation of the operating room is a highly achievable goal. An open operating room has information on demand for the personnel, fluid communication among operating room personnel, and broad interaction with the learner community and consultants. In an operating room with significant data capture, the patient is brought into the process not only as a real person, but also as a huge data set that acquires all the events of the surgery. The data include the visual, electrical, and mechanical events that define the surgical procedure. As part of a dynamic electronic medical record, they are available to those who are present and those who are asked to help from even a great distance away with real-time advice. The data are also available to those who seek to understand what happened to the patient afterwards for the purpose of root cause analysis, near miss analysis, instruction, or more accurate medical records.     

Delayed life-threatening hemorrhage after transrectal prostate needle biopsy

Minor hematochezia after transrectal ultrasound and prostate needle biopsy is well reported. We present a case report of a 64-yr-old man on aspirin and with poorly controlled hypertension who developed severe hematochezia requiring blood transfusion. The bleeding was stopped with digital compression. The literature on hemorrhagic complications after prostate needle biopsy is reviewed.     

Spinal flexibility and balance control among community-dwelling adults with and without Parkinson's disease

BACKGROUND: One area of research that requires further elaboration is the relationship between impairments and functional limitations. By identifying specific contributors to functional limitations, it may be possible to establish intervention strategies, including exercise approaches, that can delay or ameliorate decline in function. The association between impaired spinal flexibility and functional limitations has not been studied in depth. The purposes of this study were to determine (a) the associations between spinal flexibility and functional limitations; (b) the relative contribution of spinal flexibility to specific functional limitations; and (c) how disease state (Parkinson's disease [PD] vs no PD) modified these relationships. METHODS: Participants included 251 community-dwelling adults, 56 of whom were with diagnosed PD and 195 were without PD or other specific disorders. Measures included spinal flexibility (i.e., functional axial rotation [FAR]) and configuration (i.e., thoracic kyphosis and lumbar lordosis), functional limitations (i.e., functional reach, supine-to-stand time, 10-m walk, and 360 degrees turn). RESULTS: Canonical correlation (Can R) demonstrated significant associations between spinal measures and functional limitations (Can R = .488, p = .0001). After controlling for age, gender, race, body mass index, comorbidity, confidence, and depression, a multivariate regression model demonstrated that spinal flexibility contributed significantly to functional reach (R2 = .334 for the overall model, p = .0001). Based on the parameter estimate of 0.026, the results prediet that FAR accounts for a 4.6-inch difference in reach distance between the least and most flexible of the participants. In addition, there were significant differences between almost all measurements for the PD compared with the non-PD participants. CONCLUSION: Results clearly implicate spinal flexibility as a contributor to functional reach, a measure of functional limitation and an established measure of balance control. Further work is needed to determine the extent to which spinal flexibility can be improved and the effect of that improvement on balance.     

Quality of life and Parkinson's disease

BACKGROUND: People with Parkinson's disease (PD) have a progressive loss of function eventually leading to severe disability. Although PD would be expected to have a profound impact on an individual's psychosocial health, there is relatively limited research on its psychosocial effect. The purposes of this study were (a) to examine the relationships between physical disability, depression, and control beliefs and quality of life in people with PD and (b) to characterize how these psychosocial variables differ by stage of disease. METHODS: Eighty-six individuals from five stages based on clinical disability, ages 51-87, were interviewed. Established instruments were used to measure physical disability, depression, and control beliefs. Quality of life (QOL) was rated on a 5-point Likert scale. RESULTS: A multivariable regression model including physical disability, stage of disease, depression, mastery, and health locus of control predicted QOL (R2 = 0.48), with mastery as the only significant predictor (p = .0001). There were significant differences by PD stage for all variables (p < .05). CONCLUSIONS: Mastery predicted quality of life in individuals with PD even when depression and physical disability were included in the model. Differences in psychosocial variables by stage of PD suggest that the psychosocial profile of PD patients may change as the disease progresses.     

Innervation of supporting cells in the apical turns of the guinea pig cochlea is from type II afferent fibers

The outer supporting cells in the apical turns of the guinea pig cochlea receive a dense innervation. Our previous study (Fechner et al. [1998] J. Comp. Neurol. 400:299-300) suggested that this innervation of the Deiters' and Hensen's supporting cells was not derived from efferent fibers of the olivocochlear bundle, but its origin has not been further specified. To test the hypothesis that the innervation was afferent in origin, we traced apical afferent fibers that were retrogradely labeled by extracellular injections of horseradish peroxidase. Labeled afferent fibers were of two types: type I fibers contacted inner hair cells, whereas type II fibers crossed the tunnel and contacted outer hair cells. Significantly, most of the type II fibers also formed branches to the outer supporting cells. Although a few olivocochlear efferent fibers formed such branches, counts indicated that the overwhelming majority of the branches were produced by type II afferent fibers. These branches were not produced by basal type II fibers. Apical type II fibers also differed from basal fibers by having shorter lengths, spiraling both apically and basally, and contacting all three rows of outer hair cells. These innervation differences suggest differences in the ways that information from outer hair cells is processed in the apex versus the base of the cochlea.     

Intravenous gammaglobulin treatment of chronic idiopathic thrombocytopenic purpura

High-dose intravenous gammaglobulin (IVIgG) was given to 12 children and adults with chronic idiopathic thrombocytopenic purpura (ITP) to avoid splenectomy or because they either failed to respond to or required maintenance with high doses of steroids and/or immunosuppressives. The average platelet count increase to initial therapy was 239,500/microliters (range 23,000-790,000). A concomitant IgG Fc receptor blockade, measured by IgG-sensitized 51Cr-labeled autologous erythrocytes, was seen in 11 of 11 patients tested, both splenectomized and not splenectomized, lasting 3-4 wk. Six or more months after treatment, 2 children are in remission, 2 children and 2 adults are stable requiring no therapy with platelet counts of approximately 50,000 and 30,000, respectively, 3 children require maintenance IVIgG therapy at 2-10-wk intervals, and 1 child and 2 adults have become refractory to further IVIgG. Splenectomy was not performed in 4 children. Two adults were able to discontinue daily prednisone. The 3 patients who became unresponsive to Swiss Red Cross gamma-globulin (IgSRK) therapy did so in conjunction with a markedly elevated platelet-associated IgG and IgM. Serum IgM increased an average of 103 mg/dl after the IVIgG infusions. No significant side effects were seen.     

Linkage of the MHC to familial multiple sclerosis suggests genetic heterogeneity. The Multiple Sclerosis Genetics Group

Multiple sclerosis (MS) is a demyelinating autoimmune disease of the central nervous system. While its etiology is not well understood, genetic factors are clearly involved. Until recently, most genetic studies in MS have been association studies using the case-control design testing specific candidate genes and studying only sporadic cases. The only consistently replicated finding has been an association with the HLA-DR2 allele within the major histocompatibility complex (MHC) on chromosome 6. Using the genetic linkage design, however, evidence for and against linkage of the MHC to MS has been found, fostering suggestions that sporadic and familial MS have different etiologies. Most recently, two of four genomic screens demonstrated linkage to the MHC, although specific allelic associations were not tested. Here, a dataset of 98 multiplex families was studied to test for an association to the HLA-DR2 allele in familial MS and to determine if genetic linkage to the MHC was due solely to such an association. Three highly polymorphic markers (HLA-DR, D6S273 and TNFbeta) in the MHC demonstrated strong genetic linkage (parametric lod scores of 4.60, 2.20 and 1.24, respectively) and a specific association with the HLA-DR2 allele was confirmed (TDT; P < 0.001). Stratifying the results by HLA-DR2 status showed that the linkage results were limited to families segregating HLA-DR2 alleles. These results demonstrate that genetic linkage to the MHC can be explained by the HLA-DR2 allelic association. They also indicate that sporadic and familial MS share a common genetic susceptibility. In addition, preliminary calculations suggest that the MHC explains between 17 and 62% of the genetic etiology of MS. This heterogeneity is also supported by the minority of families showing no linkage or association with loci within the MHC.      

Differences in the mechanism of functional interaction between NADPH-cytochrome P-450 reductase and its redox partners

Selective methylamidation of NADPH-cytochrome P-450 reductase (EC 1.6.2.4) carboxyl groups was used to assess the relative importance of these groups in the enzyme-catalyzed reduction of cytochromes c, b5, and P-450. Methylamidation of as few as 7 mol of carboxyl groups per mol of reductase caused 80% inhibition of cytochrome c reduction, 50% inhibition of rat liver microsomal RLM3 reduction, and up to 90% inhibition in the capacity of the reductase to support reconstituted monooxygenase activities of RLM3, RLM5, and LM2. In marked contrast, cytochrome b5 reduction measured under comparable conditions was stimulated by 50%. The impaired interactions between the reductase and cytochromes P-450 LM2 and RLM5 were shown not to arise from an impaired capacity for the proteins to bind each other but more likely to be due to an inhibition of a step(s) subsequent to complex formation between the oxidized proteins. These results show that the reductase interacts functionally with cytochrome c and cytochromes P-450 on the one hand and cytochrome b5 on the other through different mechanisms.