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.     

The spectral signature method for the analysis of PET brain images

We introduce the concept of the metabolic centroid spectrum as the feature space to characterize the distribution of metabolic activity in three-dimensional brains. The method computes the metabolic centroid of a brain subvolume for each increment of metabolic activity occurring in the whole brain. The result is the metabolic spectral signature, a continuous three-dimensional curve whose shape reflects the distribution of metabolic rates in the brain. The method's sensitivity to metabolic distribution asymmetries is greatly increased over that of the metabolic centroid method, while retaining its advantages; it is almost invariant to head size, head positioning, photon scatter, and the positron emission tomography (PET) camera's full width at half-maximum. It does not require magnetic resonance, computed tomography, or x-ray images. To test the method we analyzed the metabolic PET images of 40 normal subjects and 20 schizophrenics. The results show a unification of several metabolic characteristics of schizophrenic brains, such as laterality, hypofrontality, cortical/subcortical abnormalities, and overall brain hypometabolism, which were identified by different laboratories in separate studies using differing methodologies. Here they are presented by a single automatic objective method.     

HLA-DPB1 gene polymorphism and multiple sclerosis: a large case-control study in the southwest of France

The polymorphism at the HLA-DPB1 locus has been characterized in a large number of patients with multiple sclerosis (n = 112) and in healthy controls (n = 115). Both patients and controls lived in the southwest of France (in the Pyrénées Atlantiques) and had similar ethnic background. The typing procedure involved the selective amplification of the second exon of the DPB1 locus by polymerase chain reaction, followed by hybridization of the amplified DNA with 14 sequence-specific oligonucleotide probes. Individual alleles were identified by the pattern of hybridization of the different probes. The distribution of the DPB1 alleles was not significantly different in multiple sclerosis patients and controls (p = 0.11). This does not corroborate the reported association of multiple sclerosis with the primed lymphocyte typing (PLT)-defined DPw4 specificity and is not in favour of a role played by polymorphic residues of the DP molecule in susceptibility to multiple sclerosis.     

CT evaluation of Crohn's disease: effect on patient management

CT scans from 80 consecutive patients with clinically symptomatic Crohn's disease were reviewed retrospectively to determine the effect of CT diagnosis on patient management. The initial clinical impression and any subsequent change in patient management because of the CT findings were noted. In 22 (28%) of the 80 patients, significant previously unsuspected findings led to a change in medical or surgical management. These included 12 patients with fistulae, four with abscess, two with avascular necrosis of the femoral head, two with sacral osteomyelitis, and single cases of pelvic inflammatory disease and femoral vein thrombosis.     

Human glomeruli release fatty acids which stimulate thromboxane synthesis in platelets

The cell-free medium of isolated human glomeruli exhibited a procoagulant activity and stimulated thromboxane (TXB2) synthesis in human platelets in a dose-dependent manner. The amount of TXB2 measured was 16-fold higher than what could have been predicted (TXB2 synthesized by the platelets under control conditions plus TXB2 present in the glomerular supernatant). The lipid extract of the glomerular supernatant and its purified fraction including the fatty acids was still able to stimulate--although at a lesser degree--TXB2 synthesis in platelets. Stimulation was abolished after treatment of this fraction by charcoal or albumin. Gas chromatography/mass spectrometry analysis demonstrated the presence in the purified glomerular fraction of several long-chain saturated or monoenoic fatty acids at a total concentration of 80 microM with the following order of abundance: stearic, palmitic, myristic and oleic acids. Addition to human platelets of these same exogenous synthetic acids resulted in a dose-dependent stimulation of TX synthesis. It was maximum with three or four fatty acids tested in combination, but still present with myristic acid used separately. Arachidonic acid was absent in the glomerular supernatant. Thus the stimulation observed could not be related to a greater availability of substrate. Fatty acids did not act on platelets through a non-specific detergent effect since addition of high doses of detergents inhibited TXB2 formation in platelets. The combination of fatty acids from glomerular origin identified in the present study represents a novel factor involved in the control of intracapillary hemostasis, but different from the procoagulant activity common to many tissues.(ABSTRACT TRUNCATED AT 250 WORDS)     

Decreasing incidence of peptic ulcer complications after the introduction of the proton pump inhibitors, a study of the Swedish population from 1974–2002

Background  

Despite a decreasing incidence of peptic ulcer disease, most previous studies report a stabile incidence of ulcer complications. We wanted to investigate the incidence of peptic ulcer complications in Sweden before and after the introduction of the proton pump inhibitors (PPI) in 1988 and compare these data to the sales of non-steroid anti-inflammatory drugs (NSAID) and acetylsalicylic acid (ASA).     

West Nile virus quantification in feces of experimentally infected American and fish crows.

To better understand the potential environmental health risk presented by West Nile virus (WNV)-contaminated feces, we quantified the amount of WNV present in the feces of experimentally infected American crows (Corvus brachyrhynchos) and fish crows (Corvus ossifragus). Peak fecal titers ranged from 10(3.5) to 10(8.8) plaque-forming units (PFU)/g for 10 American crows and from 10(2.3) to 10(6.4) PFU/g for 10 fish crows. The presence of infectious WNV in bird feces indicates a potential for direct transmission of WNV. Thus, handlers of sick or dead birds should take appropriate precautions to avoid exposure to fecal material.