Blur adaptation: clinical and refractive considerations

The human visual system is amenable to a number of adaptive processes; one such process, or collection of processes, is the adaptation to blur. Blur adaptation can be observed as an improvement in vision under degraded conditions, and these changes occur relatively rapidly following exposure to blur. The potential important future directions of this research area and the clinical implications of blur adaptation are discussed.     

Serum ionic fluoride levels in haemodialysis and continuous ambulatory peritoneal dialysis patients

High serum fluoride (F-) in patients with chronic renal failure (CRF) and end-stage renal disease (ESRD) is associated with risk of renal osteodystrophy and other bone changes. This study was done to determine F- in normal healthy controls and patients with ESRD on haemodialysis (HD) or peritoneal dialysis (PD). Seventeen healthy controls (12 males, 5 females) and 39 ESRD patients on dialysis (17 males, 22 females) were recruited in the study in a community with 47.4 +/- 3.28 microM/l (range 44-51 microM/l) of F- content in drinking water. Control subjects showed a mean serum F- concentration of 1.08 +/- 0.350 microM/l. Males in control group showed slightly higher F- levels (1.15 +/- 0.334, range 0.55-1.9 microM/l) than females (0.92 +/- 0.370, range 0.6-1.5 microM/l). Mean serum F- concentration did not correlate significantly with age and sex among control subjects, whereas such correlation was observed in patients with ESRD on dialysis. Mean serum F- concentration was significantly higher in patients on dialysis (2.67 +/- 1.09, range 0.8-5.2 microM/l) than normal controls. When grouped according to sex, the mean serum F- concentration in males (3.05 +/- 1.04, range 1.8-5.2 microM/l) was significantly higher than females (2.38 +/- 1.08, range 0.8-5.2 microM/l). When patients were grouped according to age, it was observed that F- concentration was significantly higher in patients with age groups 21-70 (2.86 +/- 1.05) than those with age group 13-20 years (1.42 +/- 0.531). Thus F- concentration correlated with age and sex, being higher in males and above 20 years. Despite appreciable clearance of F- (39-90%) across the peritoneum, patients on CAPD showed higher serum F- concentration than those on HD (3.1 +/- 1.97 vs 2.5 +/- 1.137 microM/l). Of the total 39 patients on dialysis 39% had their serum F- concentration above 3.0 microM/l, posing the risk of renal osteodystrophy.      

Variability in consultation rates and practitioner level of diagnostic certainty.

BACKGROUND. This study was designed to determine the variability in the consultation practices of family physicians and family nurse practitioners in an urban group practice, and to examine the relation between the referring practitioner's diagnostic certainty at the time of the consultation request, the specificity of the request to the consultant, and the frequency with which the practitioner ordered consultations in that specialty. METHODS. This study examined consultations requested by six family physicians and two family nurse practitioners that were directed to nine medical and surgical specialties in connection with 35,218 family practice visits made over a 19-month period in an urban family practice. Requests for consultation were scored based on the level of certainty of the referring practitioner's diagnosis at the time of consultation and the specificity of the consultation request. RESULTS. There was nearly a fivefold variation in the overall specialty consultation rates among providers, with even greater variation in each individual specialty area studied. Referral rate correlated positively with certainty of diagnosis (r = .40). There was no consistent relation between request specificity and referral rate. CONCLUSIONS. Consultation rates vary widely, even among family physicians and nurse practitioners within the same practice. The rate at which a practitioner orders consultations in a specialty area increases in relation to the practitioner's certainty of the diagnosis at the time the consultation was requested. Diagnostic certainty is discussed as a possible indicator of a referring practitioner's knowledge in a specialty area, implying that the greater a practitioner's knowledge in a specialty area, the more he or she consults with specialists in the field. Financial incentives that attempt to decrease specialty consultation should be reexamined in light of these findings.     

In vivo measurement of the shear modulus of the human vocal fold: interim results from eight patients

The shear modulus of the vocal fold is an essential parameter required to enhance our understanding of how the vocal fold operates, to develop mathematical models of phonatation, and to provide benchmarks to quantify the effectiveness of surgical procedures. The authors announced the successful deployment of an instrument to measure vocal fold elasticity in vivo last year, and now present the data taken from eight patients in vivo. The shear modulus was measured at the mid-membranous point, in a transverse direction with respect to the axis drawn between the anterior commissure and vocal process. The range of mean shear modulus results is 701–2,225 Pa, with a mean value of 1,371 Pa.     

Is the risk of bipolar disorder in twins equal to the risk in singletons? A nationwide register-based study

BACKGROUND: A previous study demonstrated a higher rate of schizophrenia in dizygotic twins than in the general population, and a higher rate of schizophrenia in siblings of dizygotic twins than in siblings of monozygotic twins and singletons, pointing to a common genetic predisposition for dizygotic twinning and schizophrenia. The aim of the present study was to investigate whether these findings also apply to bipolar disorder. METHODS: Through record linkage between The Danish Twin Register, The Danish Psychiatric Central Register and The Danish Civil Registration System, the rate of bipolar disorder (diagnosed for the first time during admission to hospital) in dizygotic and monozygotic twins was compared with the rate in singletons, and the rate in siblings and parents of twins was compared with the rate in siblings and parents of singletons. RESULTS: The rate of bipolar disorder was the same in dizygotic twins, monozygotic twins and singletons as well as for parents and siblings of dizygotic twins, monozygotic twins and singletons. LIMITATIONS: The study is a register-based study, only including hospitalized patients. CONCLUSION: This study shows that there is an equal rate of bipolar disorder in twins and in singletons. Assuming that DZ twinning is under some genetic influence, a differential relationship between schizophrenia and DZ twinning on one hand and bipolar disorder and DZ twinning on the other hand may suggest differences in the genetic basis of the two diseases. The finding that the rate of bipolar disorder in monozygotic twins is the same as the rate of bipolar disorder in singletons supports studies finding no association between bipolar disorder and obstetric complications.     

Gene therapy for sarcoma

Soft tissue sarcomas are mesenchymal tumors which respond poorly to systemic therapy. Recent studies suggest a higher response rate with an increased doxorubicin dosage. However, this was parallel with a profound hematotoxicity in 75% of patients. Transfer of the human multidrug resistance 1 (MDR1) gene to normal hematopoietic stem cells and transplantation may significantly reduce the hematotoxicity of anthracyclin-based chemotherapy. To test this concept of supportive gene therapy in advance of a clinical study, we transduced mobilized peripheral blood progenitor cells (PBPC) with the retroviral vector SF91m3 containing the human MDR1 gene, transplanted these cells to immune-deficient mice, allowed 6 weeks for engraftment to occur and treated the animals with MDR1-based chemotherapy. In the MDR1-transduced group the human leukocytes were significantly protected from the toxicity of chemotherapy (p < 0.05). While the gene transfer rate was in the range of 10% and thus comparable to recent clinical trials, the gene expression was 59% of transduced cells and thus significantly higher than previously reported for less-advanced vectors. On the other hand, ifosfamide, a drug which has been used successfully for stem cell mobilization, is active in soft tissue sarcoma. Due to these favorable characteristics sarcoma is an attractive target to test the efficacy of MDR1 gene therapy in a clinical setting. Gene therapeutic strategies may also be used to directly target sarcoma cells, e.g. by transfer of suicide genes. We found that adenoassociated virus 2 (AAV-2) vectors efficiently transduce human HS-1 and HT1080 sarcoma cells (>90%) while other tumor cell lines and primary human PBPC were less susceptible. The thymidine kinase (TK) suicide gene was cloned into an AAV-2 vector and a complete kill of TK-transduced HS-1 and HT1080 cells was observed following exposure to aciclovir or ganciclovir (GCV), while >90% of mock-transduced HS-1 cells survived at these dosages. Transplantation of those sarcoma cells to nonobese diabetic (NOD)/LtSz-severe-combined immunodeficient (scid)/scid (NOD/SCID) mice resulted in a survival of >5 months in the AAV-TK-transduced/GCV-treated group, while the mice in the mock-transduced/GCV-treated group had died after 3 weeks. These data show that soft tissue sarcomas are a particularly suitable model system for the development and clinical testing of new gene therapeutic concepts.