Hormone therapy and risk for dementia: where do we go from here?

Prospective observational studies suggest that hormone therapy (HT) might confer protection against the development of Alzheimer's disease. In contrast, recent findings from the Women's Health Initiative Memory Study (WHIMS) indicated a doubling of the risk of all-cause dementia in women randomized to receive HT after age 64. The discrepancy between findings from observational studies and the WHIMS is commonly attributed to the lack of treatment bias in the randomized trial. However, there are other potentially important dfferences between the WHIMS and the observational studies. These include timing of initiation of HT and type of HT regimen used. The present review focuses on the clinical and basic science studies bearing on these clinically important issues. Additional clinical studies are needed to understand the external generalizability of the WHIMS results to populations of women for whom HT remains an indication.     

Genetic polymorphisms of the UDP-glucuronosyltransferase 1A7 gene and irinotecan toxicity in Japanese cancer patients.

Irinotecan often causes unpredictably severe, occasionally fatal, toxicity involving leukopenia or diarrhea. It is converted by carboxyesterase to an active metabolite, SN-38, which is further conjugated and detoxified to SN-38-glucuronide by UDP-glucuronosyltransferase (UGT). We genotyped the UGT1A7 gene by direct sequencing analysis and polymerase chain reaction-restriction fragment length polymorphism in 118 cancer patients and 108 healthy subjects. All the patients had received irinotecan-containing chemotherapy and were evaluated to see whether the variant UGT1A7 genotype would increase the likelihood of severe toxicity of irinotecan consisting of grade 4 leukopenia and/or grade 3 or more diarrhea. Among the 26 patients with severe toxicity, the allele frequencies were 61.5% for UGT1A7 (*)1, 15.4% for UGT1A7 (*)2, and 23.1% for UGT1A7 (*)3. On the other hand, the frequencies were 63.6% for UGT1A7 (*)1, 15.8% for UGT1A7 (*)2, and 20.7% for UGT1A7 (*)3 among the 92 patients without severe toxicity. None of the 118 patients had UGT1A7 (*)4. Neither univariate analysis (odds ratio, 1.13; 95% confidential interval, 0.46 - 2.75) nor multivariate logistic regression analysis (odds ratio, 0.74; 95% confidential interval, 0.26 - 2.07) found any significant association between carrying at least one of the variant alleles and the occurrence of severe toxicity. The distribution of UGT1A7 genotypes in 108 healthy subjects was not significantly different from that in the patients (P = 0.99 and 0.86 for those with and without severe toxicity, respectively), but significantly less than that in Caucasians reported previously (P < 0.001). The results suggested that determination of UGT1A7 genotypes would not be useful for predicting severe toxicity of irinotecan.     

The direct costs of nosocomial catheter-associated urinary tract infection in the era of managed care.

OBJECTIVE: To determine the additional direct costs of hospitalization attributable to catheter-associated urinary tract infection (CAUTI) in 1,497 newly catheterized patients. DESIGN: Prospective observational and laboratory study. SETTING: University hospital. METHODS: Data were collected on risk factors for CAUTI (defined as > 10(3) colony-forming units [CFU]/mL), severity of illness, and diagnostic and therapeutic interventions in consenting newly catheterized patients. Daily urine cultures were obtained from each newly catheterized patient, but the results of these cultures were not revealed to his or her physician. During the study, one of the investigators (DGM) reviewed each patient's record and made a judgment as to which of the diagnostic tests and treatments ordered and what incremental length of stay could reasonably be ascribed to his or her CAUTI. The total hospital costs for each patient were also obtained. RESULTS: Overall, 235 patients acquired CAUTIs during the study; most of the CAUTIs were completely asymptomatic, and only 52% were diagnosed by the patients' physicians using the hospital laboratory. Only 1 patient with a CAUTI had a secondary bloodstream infection. Thirty-three (13%) of the CAUTIs were caused by Escherichia coli; 63 (25%) by Klebsiella, Enterobacter, Citrobacter, Pseudomonas aeruginosa, or other antibiotic-resistant, gram-negative bacilli; 87 (35%) by enterococci or staphylococci; and 67 (27%) by Candida species. The 123 CAUTIs diagnosed by the hospital laboratory were judged to have been responsible for an additional $20,662 in extra costs of diagnostic tests and $35,872 in extra medication costs, a mean of $589 (median, $356) per CAUTI. CAUTIs caused by E. coli cost considerably less than infections caused by other gram-negative bacilli ($363.3 +/- $228.2 vs $690.4 +/- $783.7; P = .02) or yeasts ($821.2 +/- $2,169.9). There were less striking differences in the costs per CAUTI caused by staphylococci or enterococci ($387.1 +/- $434.8). CONCLUSIONS: The extra direct costs associated with nosocomial CAUTI found in this prospective study, which was done in the era of managed care during the late 1990s, are substantially lower than those reported in the largest comparable studies done more than 15 years ago, most of which were retrospective, reflecting the powerful impact of cost-containment measures that are now implemented in managed care.     

A case of multiple sclerosis with pure alexia

We report here a case of multiple sclerosis (MS) showing pure alexia. The patient was a 28 year-old, right-handed male student of medicine. He had been healthy prior to college, but when he tried to read the newspaper one morning in January of 1983, he suddenly became aware that he could not. He could speak fluently and had no disturbances of auditory comprehension. No signs of abnormality were noted in his writing ability. Thereafter, the patient occasionally experienced difficulty in reading, together with right homonymous hemianopsia. These symptoms, however, usually vanished following sleep. In April, 1984, the patient experienced headache and ataxia when walking, followed by repeated remission and exacerbation of the symptoms. Corticosteroid therapy produced complete disappearance of the headache and ataxia. In September of 1985, he was hospitalized at our department due to the clouding of consciousness accompanied by convulsions. Neurologically, no abnormalities of the ocular fundus were noted and Babinski's sign was negative, but left hemiplegia was observed. Neuropsychologically, his intelligence was normal and he had no difficulty in writing, but paralexia was noted. There were no disorders of spontaneous speech or auditory comprehension. Examination by CT scan and magnetic resonance imaging revealed a number of lesions in the white substance of the cerebrum, including the left occipital lobe. The abnormal signs seen radiographically vanished when cortical hormones were administered. It has been thought that the symptoms of multiple sclerosis are due mainly to disorders of the white substance, and that MS seldom produces symptoms of aphasia, due to the fact that the lesions in this disease are generally small.(ABSTRACT TRUNCATED AT 250 WORDS)     

Prevalence of antibodies to human T-lymphotropic virus types I and II in volunteer blood donors and high-risk groups in northwestern Greece

BACKGROUND: In addition to human immunodeficiency virus, human T- lymphotropic virus types I and II (HTLV-I/II) is prevalent among blood donors in the United States. In Greece, there are no epidemiologic data regarding the prevalence of HTLV-I/II among volunteer blood donors and high-risk groups. STUDY DESIGN AND METHODS: To determine the prevalence of HTLV-I/II infections in northwestern Greece, a seroepidemiologic study was conducted among volunteer blood donors, multiply transfused patients, heroin addicts, and chronic hemodialysis patients. The subjects were tested for serologic evidence of HTLV-I/II infection by enzyme immunoassays and specific protein immunoblot confirmatory test. RESULTS: None of the volunteer blood donors and heroin addicts had detectable antibodies to HTLV-I/II. Only 1 (1.45%) of the 69 multiply transfused patients had indeterminate results, while 2 (1.2%) of 163 hemodialysis patients were positive. CONCLUSION: In northwestern Greece, routine screening for HTLV-I and HTLV-II infections does not appear to be required. However, the finding of seropositivity among hemodialysis patients requires further evaluation of the origin of the infection, as its zero prevalence in this population seems to exclude transfusion transmission.