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.     

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.     

Maxillary sinus puncture and culture in the diagnosis of acute rhinosinusitis: the case for pursuing alternative culture methods.

OBJECTIVE: Traditional assessments of the microbial flora associated with acute bacterial rhinosinusitis have relied on maxillary sinus punctures (taps) and culture. These taps are now considered the gold standard for obtaining cultures and are used as the method of identifying bacterial pathogens in antimicrobial trials. Maxillary sinus taps are limited by discomfort to the patients and technical concerns. Because of these factors, the standard of performing taps has limited antibiotic trials and microbial surveillance. Alternatives to maxillary sinus taps have been explored. STUDY DESIGN: We conducted a retrospective, systematic review of the literature from 1950 to 2000 of articles comparing culture techniques in the nose and paranasal sinuses for acute bacterial rhinosinusitis. RESULTS: Nasal cultures have poor correlation to maxillary sinus cultures, whereas there is 60% to 85% concordance between endoscopically guided middle meatal cultures and maxillary sinus cultures. These studies, however, are all limited by small sample sizes and therefore are inadequate to make any concrete recommendations regarding the relative role of endoscopically guided middle meatal cultures as a formal method of pathogen identification in acute bacterial rhinosinusitis. CONCLUSION: A formal prospective study with sufficient sample size to assess the concordance between the microbial flora of the maxillary sinus punctures and middle meatal cultures in acute rhinosinusitis is recommended.     

Ischemic rat brain extracts induce human marrow stromal cell growth factor production

Intravenous administration of human bone marrow stromal cells (hMSCs) after middle cerebral artery occlusion (MCAo) in rats provides functional benefit. We tested the hypothesis that these functional benefits are derived in part from hMSC production of growth and trophic factors. Quantitative sandwich enzyme‐linked immunosorbent assay (ELISA) of hMSCs cultured with normal and MCAo brain extracts were performed. hMSCs cultured in supernatant derived from ischemic brain extracts increased production of brain‐derived neurotrophic factor (BDNF), nerve growth factor (NGF), vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF). These neurotrophins and angiogenic growth factors increased in a post‐ischemia time‐dependent manner. The hMSC capacity to increase expression of growth and trophic factors may be the key to the benefit provided by transplanted hMSCs in the ischemic brain.     

An experimental collagen-impregnated dacron graft: Potential for endothelial seeding

This study evaluates the potential for endothelial seeding of a collagen-impregnated Dacron graft with or without surface modifiers (fibronectin, heparin) to attach and retain these cells during flow. Human umbilical endothelial cells were harvested, cultured, labeled with Indium111-oxine and seeded onto 30 mm X 4 mm diameter grafts. Six graft surfaces were studied: 1) a collagen-impregnated Dacron graft, HemashieldR (C); 2) C + fibronectin (C + F); 3) C + heparin (C + H); 4) C + F + H; 5) HytrelR + F (Hyt + F); and 6) Hyt + F + H. Radioactive loss determined the percentage attachment and then percentage retention of labeled inoculum after a one-hour in vitro perfusion. Scanning electron and light microscopy demonstrated the endothelium on the graft surface following perfusion. Fibronectin-coated grafts had a significantly higher percentage attachment than those without fibronectin (ANOVA, P less than 0.05). However, the percentage retention following perfusion was similar for all Dacron grafts and statistically inferior to the HytrelR grafts studied (ANOVA, P less than 0.05). SEM evaluation of the C + F + H graft surface was qualitatively the most impressive Dacron surface for seeding, yet was inferior to the HytrelR graft. We conclude that fibronectin benefits the initial attachment of endothelium to collagen-coated Dacron rivaling the HytrelR surface. Fibronectin does not improve percentage retention of the HemashieldR surface during perfusion, therefore, some of its initial benefit is lost.     

Infantile Digital Fibroma Treated With Mohs Micrographic Surgery

BACKGROUND: Infantile digital fibroma (IDF) is a rare benign fibrous tumor of childhood that frequently recurs despite local excision. Conservative, nonsurgical management may result in regression and/or joint deformity. OBJECTIVE: To describe the histologic features of IDF and discuss a case excised using Mohs micrographic surgery (MMS). METHODS: Case report and review of the clinical, histologic, and ultrastructural features. RESULTS: Characteristic inclusion bodies of actin were identified with hematoxylin and eosin, Masson's trichrome, and rapid actin immunostain. The tumor was debulked and the majority was removed after one stage of MMS, except where the deep margin approached the joint space. The defect healed by secondary intention. At 2 years the patient had no recurrence or functional joint deformity. CONCLUSION: MMS is a surgical treatment option for IDF.     

Increased ratio of saturated to unsaturated C18 fatty acids in colonic adenocarcinoma: Implications for cryotherapy and lipid raft function

Mammalian fatty acid synthase (FASE) overexpression has been shown in a number of human malignancies including colonic adenocarcinoma. Since FASE synthesizes only saturated fatty acids, we hypothesized that cancer cells have a greater proportion of long-chain saturated fatty acids. We studied and found an unequivocal increase in saturated C18 fatty acid (stearic acid) in colonic adenocarcinoma compared to adjacent normal colonic mucosa. The increase is even more striking when measured as a ratio of stearic acid to the unsaturated C18 fatty acids (oleic acid and linoleic acid). This change in fatty acid composition of the cancer cells should significantly alter their physical and biological properties. The increase in relative proportion of saturated fatty acids should make the cancer cells more susceptible to cryodamage and measurement of fatty acid composition of cancer cells may help individualize the temperature for cryotherapy. Also, the lipid alterations may affect the structure and functions of lipid rafts, which may enable the cancer cells to affect signaling mechanisms such as those involved in cell growth and apoptosis. Dietary or therapeutic interventions targeting lipid rafts may thus be an option for cancer treatment.     

A new transthyretin variant (Glu61Gly) associated with cardiomyopathy.

We report the identification of a new transthyretin (TTR) gene mutation and variant protein, Glu61Gly, in a 55-year-old man with progressive cardiomyopathy, mild peripheral neuropathy and bilateral carpal tunnel syndrome. A diagnosis of TTR-associated familial amyloidosis (ATTR) was considered after an endomyocardial biopsy revealed amyloid deposits in the heart of a patient who had no family history of amyloidosis and no evidence of a plasma cell dyscrasia. Serum screening for a TTR variant by isoelectric focusing (IEF) was positive and prompted further studies to identify the genetic abnormality and to characterize the amyloidogenic protein. Direct DNA sequence analysis of all four coding regions in the TTR gene demonstrated heterozygosity in exon 3. Near equal amounts of guanine (G) and adenine (A) were observed at the second base position of codon 61. The wild-type (GAG) and mutated (GGG) sequences found in codon 61 correspond to glutamic acid (Glu) and glycine (Gly) residues, amino acids which differ in mass by -72 Da. Mass spectrometric analyses of TTR immunoprecipitated from serum showed the presence of both wild-type and variant proteins. The observed mass results for the wild-type and variant proteins were consistent with the predicted values calculated from the genetic analysis data.     

Trends in physical activity behaviours and attitudes among South Australian youth between 1985 and 2004

Rising youth obesity is a serious public health concern. There is a widespread view that declining physical activity is contributing to this trend. A total of 929 young South Australians (age = 9–15 years) were surveyed in 1985 and 2004 on usual physical activity in several contexts, including attitudes to physical activity. Eight of 10 South Australian schools participating in the 1985 Schools Health and Fitness Survey were revisited in 2004. Comparisons were made on: organised sport, active transport, physical education (PE), playground activity, vigorous physical activity (VPA), total leisure-time physical activity (LTPA), and attitudes to PE and school sport. The questionnaire and method of administration were identical in both surveys. There were no differences between surveys in club and school sport participation, walking to school, and reported enjoyment of PE and school sport. In 2004 fewer children rode to school, but PE classes were more frequent. The percentage of children who ‘sit and talk’ during school breaks had increased, with a decreased percentage of older girls who ‘run around’ during school breaks. There was a significantly higher LTPA in MET.min in 2004 for boys, which was particularly evident at higher percentiles. There were no changes in mean or distribution of LTPA for the whole sample or girls. The percentage of respondents reporting ≥3 bouts of VPA in the previous week rose from 51% (1985) to 76% (2004). There is no consistent evidence of declining physical activity among South Australian youth. It is apparent that physical activity in some contexts has declined, while in other contexts levels are the same or higher than in 1985. This underscores the complex nature of physical activity and the influences on this behaviour.