Patients with Fabry disease on dialysis in the United States.

BACKGROUND.: Fabry disease results from an X-linked deficiency of lysosomal alpha-galactosidase A and is a rare cause of end-stage renal disease. Little is known about the characteristics of patients with Fabry disease that initiate dialysis in the United States, although data from Europe suggests these individuals have a poor survival. METHODS.: Using the United States Renal Disease System database, we first studied in detail 42 Fabry patients who initiated dialysis between April 1995 (following the introduction of the new detailed HCFA 2728 form) and July 1998. To examine crude survival in a larger cohort, 95 Fabry patients were studied who initiated dialysis between 1985 and 1993, similar to the European Registry. Diabetic and non-diabetic controls matched by age, gender, race, year of dialysis initiation, and initial dialysis modality were examined for comparison. RESULTS.: During the years 1995 to 1998, the mean age of Fabry patients that initiated dialysis was 42 years, 83% were Caucasian, and 10% were African American. Despite the X-linked inheritance of Fabry disease, 12% of Fabry patients on dialysis were female. At initiation of dialysis mean serum albumin and creatinine were significantly higher and mean body mass index was significantly lower among Fabry patients, but mean glomerular filtration rate was similar to controls. Fabry patients tended to have a lower three-year survival compared to non-diabetic controls, but the results were not significantly different. In a larger cohort of Fabry patients who initiated dialysis between 1985 and 1993, the three-year survival of Fabry patients was significantly lower than non-diabetic controls: 63% (95% CI, 50 to 75%) versus 74% (95% CI, 67 to 80%; P=0.03). CONCLUSION.: End-stage renal disease is associated with significant morbidity and mortality among patients with Fabry disease. Recent evidence that progression of Fabry disease may be attenuated by enzyme replacement therapy necessitates increased awareness of Fabry disease and its comorbidities.     

Reduced graft-versus-host disease-inducing capacity of T cells after activation, culturing, and magnetic cell sorting selection in an allogeneic bone marrow transplantation model in rats.

Graft-versus-host disease (GvHD), a major complication of allogeneic bone marrow transplantation, has been ascribed to mature T cells in the graft. Because T cells play an important role in engraftment of the bone marrow and decrease the probability of relapse of leukemia, a treatment strategy was developed to preserve the benefits of T cells in the graft and to control the severe complications of GvHD. This can be accomplished by the genetic modification of donor T cells with a suicide gene that allows their selective in vivo elimination and subsequently the abrogation of GvHD. For clinical benefit the alloreactivity of herpes simplex virus thymidine kinase (HSV-TK) gene-transduced T cells should be retained. Therefore, we investigated the influence of gene transduction and the selection procedure on T cells. We demonstrated that activation and culturing of T cells reduce their capacity to induce lethal GvHD in an allogeneic rat bone marrow transplantation model. Furthermore, positive immunomagnetic selection of gene-transduced T cells resulted in loss of the GvHD-inducing capacity of HSV-TK(+) T cells directly after MACS (magnetic cell sorting) selection; this loss could be recovered by a 1-day expansion of the selected T cells. No effect on alloreactivity was observed to be caused by the gene transduction procedure. Our study resulted in the development of an optimized culture and gene transduction protocol with preservation of T cell alloreactivity. Treatment of transplanted rats with ganciclovir resulted in a rapid reduction in the number of HSV-TK(+) T cells in the peripheral blood and in increased survival of the animals.     

Acoustic variations in reading produced by speakers with spasmodic dysphonia pre-botox injection and within early stages of post-botox injection.

Acoustic analysis of a reading passage was used to identify the abnormal phonatory events associated with adductor spasmodic dysphonia (ADSD) pre- and postinjection of Botulinum Toxin A (Botox). Thirty-one patients (age 22 to 74 years) diagnosed with ADSD were included for study. All patients were new recipients of Botox, and the examination of their voice occurred before and after their initial injection of Botox. Acoustic events were identified from reading samples of the Rainbow Passage produced by each of the patients. These events were examined from sentences containing primarily voiced sound segments. Dependent variables included the number of phonatory breaks, frequency shifts, and aperiodic segments--all variables previously defined by the investigators. Additionally, calculated variables were made of the percentage of time these events occurred relative to the duration of the cumulative voiced segments. A sex- and age-matched control group (+/-2 years) was included for statistical comparison. Results indicated that those with ADSD produced more aberrant acoustic events than the controls. Aperiodicity was the predominant acoustic event produced during the reading, followed by frequency shifts and phonatory breaks. Within the ADSD group, the number of atypical acoustic events decreased following Botox injection. It is important that the occurrence of specific abnormal acoustic events was sufficient to differentiate the disordered speakers from the controls following as well as preceding initial Botox injection, as indicated by discriminant function analysis. This paper complements our previous work using this acoustic analysis method for defining the abnormal events present in the voice of those with ADSD and further suggests that these measures can be used in conjunction with perceptual impressions to differentiate speakers on the basis of initial severity.     

Comparison of ThinPrep versus conventional smear cytopreparatory techniques for fine-needle aspiration specimens of head and neck masses.

OBJECTIVES: Diagnostic accuracy of the ThinPrep process (Cytyc, Boxborough, MA) was compared with that of conventional (smear) cytopreparation for fine-needle aspiration (FNA) of head and neck masses. METHODS: In a prospective, randomized, single-blinded study, 209 patients served as their own controls and underwent 236 FNAs using ThinPrep and conventional (smear) cytopreparatory techniques. RESULTS: ThinPrep produced less air-drying artifact and less mechanical distortion than the conventional method. The conventional technique was diagnostic in 63% of samples; the ThinPrep technique was diagnostic in 55% of samples. When all results were combined, pathologists subjectively preferred the conventional technique but accepted use of ThinPrep as the only cytopreparatory technique for most head and neck masses. CONCLUSIONS: For adequately experienced cytopathologists, ThinPrep is acceptable for FNA of salivary masses, neck cysts, metastatic lymph nodes, and thyroid lesions. Conventional smear technique should be used for FNA of nonmetastatic lymphoid lesions. Use of ThinPrep can complement use of the conventional (smear) cytopreparatory technique when aspirate is nondiagnostic or bloody, when the patient has a blood-borne infectious disease, when the clinician is inexperienced, or when aspirate has entered the syringe.     

No impact of repeated endoscopic screens on gastric cancer mortality in a prospectively followed Chinese population at high risk.

BACKGROUND: Gastric cancer (GC) is the leading cause of cancer deaths in China. Our study prospectively evaluated the impact of repeated endoscopic screens on GC mortality in a high-risk population in China. METHODS: Between 1989 and 1999, a population-based gastroscopic screening was conducted in 4,394 residents of Linqu County, China, a region with the highest rates of GC worldwide. Residents ages 35 to 64 years received initial gastroscopies with biopsies in 1989. Repeated endoscopies were performed in 1994 and 1999. Cancer occurrences and deaths were actively monitored throughout the entire period until July 2000. Mortality from GC was compared with expected values based on mortality rates obtained for Linqu in the 1990-1992 Chinese Cancer Mortality Survey. RESULTS: Between March 1989 and July 2000, 39,303 person-years were accumulated; 85 new GCs occurred, 29 (34.5%) were in early stage. Fifty-eight cases (68%) were identified at one of the screens. The number of observed deaths from GC (37) was close to the expected (36.8). The standardized mortality ratio was 1.01 (95% CI 0.72-1.37) for the entire cohort, 1.13 (95% CI 0.77-1.57) for males, and 0.65 (95% CI 0.26-1.32) for females. CONCLUSIONS: Despite high population coverage with repeated screens, no reduction in GC mortality was observed in this high-risk population in China.