Mortality studies of machining fluid exposure in the automobile industry. V: A case-control study of pancreatic cancer

MANOVA and repeated measures ANOVA approaches have provided evidence of a number of limitations in several event-related potential (ERP) studies due to violations of their statistical assumptions and the typically moderate size of the available sample. Alternative, computer-intensive methods based on permutation principles have recently been developed. Up to now this methodology has focused mostly on magnitude differences between scalp distributions as measured by t statistics. In this paper the scope of permutation techniques in ERP analysis was widened. A new statistic (D statistic) is introduced to compare the shapes of scalp distributions of ERPs. Additionally a general non-parametric combinatory technique is introduced to evaluate, by means of multivariate permutation tests, several time points and/or recording sites in ERP data. The methodology described here was used to test if two ERP components elicited during word-pair matching tasks to semantic or phonological incongruences had different scalp distributions.     

A review of methodologies for assessing drug effectiveness and a new proposal: randomized database studies

The need to evaluate the effects of health technologies in clinical practice is increasingly important. In this article, we review the advantages and limitations of naturalistic randomized clinical trials (RCTs) and database analyses, the two primary methods for evaluating treatment effectiveness. Also, we comment on a newer research strategy, cross-design synthesis, which proposes the complementary use of both experimental RCTs and observational database methodologies to avoid the main weaknesses of each: respectively, the lack of external and internal validity. Finally, we propose a new strategy--randomized database studies--capable of generating results with an acceptable balance between internal and external validity. This strategy consists of the simultaneous use of both experimental and observational tools in the assessment of drugs' effectiveness. Randomization is essential to minimize comparison bias, and one possibility for such studies is that randomization modules could be included in computer-based patient records. Although we identify some of the difficulties in implementing the process, the progressive standardization of clinical practice and the development and widespread adoption of improved computer-based patient records could facilitate the use of randomized database studies as a new method of research.     

Genomic organization of a human cystine transporter gene (SLC3A1) and identification of novel mutations causing cystinuria

Cystinuria is a common inherited aminoaciduria that leads to recurrent cystine nephrolithiasis. Mutations in a gene encoding a renal amino acid transporter (SLC3A1) have been identified in patients with cystinuria establishing one molecular cause for the disease. To facilitate systematic screening of this gene for mutations, we have delineated the complete genomic organization of the SLC3A1 coding region using polymerase chain reaction strategies. The complete coding region of the gene is contained within a single yeast artificial chromosome clone and consists of 10 exons and 9 introns. Oligonucleotide primers capable of amplifying selected exons have been made and used in mutational analysis of DNA from 24 cystinuria probands. We illustrate the usefulness of this approach by identifying two novel SLC3A1 mutations. One novel mutation causes replacement of a highly conserved arginine residue (arginine-452) with tryptophan in the cytoplasmic loop between the putative third and fourth membrane spanning segments. A second previously unreported mutation results in replacement of a highly conserved tyrosine (tyrosine-461) residue with histidine in the same region of the protein. In addition, we detected three previously reported SLC3A1 mutations, R270X, 1500 +1/G to T, and M467T, the latter being present in approximately 20% of cystinuria chromosomes examined. Our findings provide a foundation for the development of more accessible diagnostic screening assays for detecting SLC3A1 mutations using patient genomic DNA, and also contribute to the emerging spectrum of cystinuria genotypes.     

Listing's plane dependence on alternating fixation in a strabismus patient

Listing's law of the eye is one of the best studied findings in motor control, but its functional meaning is still incompletely understood and its status in neurological disorders and in strabismus is almost entirely unknown. We investigated the mechanisms underlying Listing's law and its possible clinical relevance. The dual magnetic search coil technique was used to record three-dimensional binocular eye movements in a stereoblind strabismic patient with good visual acuity in both eyes and capable of voluntarily alternating fixation. This technique yielded an accurate, objective and simultaneous measure of ocular misalignment in three dimensions and showed that the squint angle depended on which eye was fixating. Saccadic eye movement data throughout the oculomotor range were used to fit Listing's plane. Listing's primary position and the thickness of the plane for each eye were calculated for three different fixation conditions. For comparison, control measurements were taken from four normals. In the patient, no large deviations from normal values for the thickness of Listing's plane and the confidence limits of the Listing primary position were found. The most remarkable abnormality was that the orientation of Listing's plane depended on which eye was fixating. Both the change in ocular misalignment and the shift of Listing's primary positions observed when changing fixation are probably linked to accommodation-related vergence. Despite repeated surgery at early age, the patient had well-defined Listing planes for both eyes, but their alignment during left-eye fixation was abnormal. The obedience to Listing's law may reflect a strategy which minimizes muscular effort in each eye separately. The abnormal fixation-condition dependence is probably due to an aberrant coupling with vergence.     

HIV-1 disease progression and AIDS-defining disorders in rural Uganda

BACKGROUND: The majority of people infected with HIV-1 live in Africa, yet little is known about the natural history of the disease in that continent. We studied survival times, disease progression, and AIDS-defining disorders, according to the proposed WHO staging system, in a population-based, rural cohort in Uganda. METHODS: In 1990 we recruited a random sample of people already infected with HIV-1 (as prevalent cases) detected during the initial survey round of a general-population study to form a natural-history cohort. Individuals from the general-population cohort who seroconverted between 1990 and 1995 (incident cases) were also invited to enroll. Participants were seen routinely every 3 months and when they were III. FINDINGS: By the end of 1995, 93 prevalent cases and 86 incident cases had been enrolled. Four patients in the prevalent group were in stage 4 (AIDS) at the initial visit. During the next 5 years, 37 prevalent cases progressed to AIDS. Seven incident cases progressed to AIDS and the cumulative progression to AIDS at 1, 3, and 5 years after seroconversion was 2%, 6%, and 22%, respectively. The cumulative probability of AIDS at 4 years from entering stages 1, 2, and 3 was 11%, 33%, and 58%, respectively. There were 47 deaths among prevalent cases and seven among incident cases during follow-up. The cumulative mortality 4 years after patients entered stages 1, 2, 3, and 4 was 9%, 33%, 56%, and 86%, respectively. The median survival after the onset of AIDS was 9.3 months. INTERPRETATION: Our results are important for the setting of priorities and rationalisation of treatment availability in countries with poor resources. We found that progression rates to AIDS are similar to those in developed countries for homosexual cohorts and greater than for cohorts infected by other modes of transmission. However, we have found that the rates of all-cause mortality are much higher and the progression times to death are shorter than in developed countries.     

Murine splenic proliferative response to human recombinant erythropoietin along hypoxia

Hypoxia is the best physiological stress to disturb the erythropoietic steady state. The present study has been undertaken in the aim to analize the splenic erythropoietic proliferative response with different doses of recombinant human erythropoietin under hypoxic conditions along 18 days using the DNA synthesis assay. Normoxic splenic progenitors failed to show significative erythroid replication at 0 days. A clearly rh Epo response was noticed from 2 to 8 days of hypoxia. Splenic proliferation returned to basal pattern from 10 days to the end of the experience. The highest proliferative activity, 25 fold increase over control (p < 0.001), was found at 6 days from 62.5 to 250 mU/ml rh Epo. These results support suggestions that hypoxia induces a transiently erythroid splenic proliferative response changing its quantitative parameters in the Epo dose-response relationship during the physiological adaptation.     

KCNE1 mutations cause jervell and Lange-Nielsen syndrome

The third reported case of pelvic gliomatosis found within foci of endometriosis is documented 16 years after the removal of a benign cystic teratoma. Grossly at laparoscopy the lesions appear as typical deep fibrotic endometriotic implants.