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Biomedical subjects

D Page

Publications and source records attributed to D Page.

At least 37 records · Page 2Linked to original sources

A probabilistic learning approach to whole-genome operon prediction.

We present a computational approach to predicting operons in the genomes of prokaryotic organisms. Our approach uses machine learning methods to induce predictive models for this task from a rich variety of data types including sequence data, gene expression data, and functional annotations associated with genes. We use multiple learned models that individually predict promoters, terminators and operons themselves. A key part of our approach is a dynamic programming method that uses our predictions to map every known and putative gene in a given genome into its most probable operon. We evaluate our approach using data from the E. coli K-12 genome.

Gene Expression Profiling↗

Treatment failure and methadone dose in a public methadone maintenance treatment programme in Geneva.

The aim of this study was to identify predictors of treatment failure in a methadone maintenance treatment programme in Geneva. All patients (n = 149) starting treatment between May 1993 and May 1995 were followed until end of treatment or 31st July 1996. The proportion of depressed patients decreased significantly over time, as did the proportion of those injecting illegal drugs. The overall treatment failure was 21%. The probability of treatment failure was higher for women than for men (RR 2.2, P = 0.03) and decreased in successive cohorts. There was no correlation between the methadone dose at 2 months and treatment outcome, probably because doses were individualised and the associated level of psycho-social services high.

Adult↗

Insulin and related factors in premenopausal breast cancer risk.

BACKGROUND: Insulin and insulin-like growth factor I (IGF-I) are important mitogens in vitro and in vivo. It has been hypothesized that these factors may play an important role in the development of breast cancer. METHODS: A case-control study comparing plasma insulin levels in 99 premenopausal women with newly diagnosed node-negative invasive carcinoma of the breast and 99 age-matched controls with incident biopsied non-proliferative breast disease (NP) was conducted. Women with known diabetes were excluded. RESULTS: For the entire study group, mean age was 42.6 +/- 5.1 years and mean weight was 62.9 +/- 10.3 kg. After adjustment for age and weight, elevated insulin levels were significantly associated with breast cancer, Odds Ratio (OR) for women in the highest insulin quintile versus the lowest quintile = 2.83 (95% Confidence Interval [CI] 1.22-6.58). There were no statistically significant differences between cases and controls for IGF-I and IGFBP-1 levels. However, after adjustment for age, the association between plasma levels of insulin-like growth factor binding protein 3 (IGFBP-3) and breast cancer approached statistical significance; OR for highest quintile versus lowest quintile of IGFBP-3 being 2.05 (95% CI, 0.93-4.53). All results were independent of diet and other known risk factors for breast cancer. CONCLUSION: Circulating insulin levels and possibly IGFBP-3 levels are elevated in women with premenopausal breast cancer. This association may reflect an underlying syndrome of insulin resistance that is independent of obesity.

Adult↗

Azoospermic men with deletion of the DAZ gene cluster are capable of completing spermatogenesis: fertilization, normal embryonic development and pregnancy occur when retrieved testicular spermatozoa are used for intracytoplasmic sperm injection.

Some men with non-obstructive azoospermia harbour fully formed spermatozoa within their testicular tissue that can be used to achieve pregnancy via intracytoplasmic sperm injection (ICSI). Recently, Reijo et al. (1995) provided compelling evidence that the DAZ gene cluster is a strong candidate for one of the elusive azoospermia factors (AZF) located on the long arm of the Y chromosome. The DAZ gene cluster is deleted in 13% of azoospermic men and a small percentage of severely oligozoospermic men. Vertical transmission from father to son of AZF region deletions has also been described. Presumably these fathers were oligozoospermic. This led us to ask whether the azoospermic male with deletions of the AZF/DAZ region can also complete minimal spermatogenesis and whether any spermatozoa found could participate in fertilization, embryo development and pregnancy. Three out of six (50%) of the azoospermic men with AZF/DAZ deletions had spermatozoa identified within their harvested testicular tissue. When these spermatozoa were used for ICSI, fertilization occurred in 36% of injected oocytes. This compared favourably with testicular spermatozoa retrieved from non-obstructive azoospermic men without AZF/DAZ gene deletions. In one case, a twin conception resulted, which represents the first term pregnancy reported using spermatozoa from an AZF/DAZ deleted azoospermic male. Therefore it is necessary to take the possibility of transmission of infertility or sterility to our patients' offspring seriously when utilizing today's reproductive technologies, as spermatogenesis in men with AZF/DAZ deletions is by no means an exceptional occurrence.

Chromosome Mapping↗

Is ultrasonography a reliable way to confirm the diagnosis of Morton's neuroma?

The diagnosis of Morton's neuroma is based on patient history and clinical findings. Occasionally, however, the diagnosis still remains in doubt despite careful examination. While magnetic resonance imaging (MRI) has been used to evaluate such cases, its specificity remains unproven and its availability is not universal. Ultrasonography may offer a reasonable alternative to MRI. Eight patients clinically diagnosed with neuromas who had not responded to conservative care underwent ultrasonography. Sonography in each demonstrated a round or oval echogenic mass where a neuroma was believed to be present. Sonography on a control group of 10 asymptomatic patients (20 feet) revealed no such mass. Pathologic inspections of surgically resected specimens confirmed the diagnosis of Morton's neuroma. With no false positive results, this preliminary study indicates ultrasonography may be a specific diagnostic test for Morton's neuroma.

Adult↗

Effects of pentoxifylline on circulating cytokine concentrations and hemodynamics in patients with septic shock: results from a double-blind, randomized, placebo-controlled study.

OBJECTIVE: To determine whether a continuous intravenous infusion of pentoxifylline, a methylxanthine derivative, alters the serum cytokine concentrations and/or hemodynamic measurements in patients with septic shock. DESIGN: A prospective, randomized, double-blind, placebo-controlled study. SETTING: Medical intensive care unit in a university hospital. PATIENTS: Sixteen patients with septic shock. INTERVENTIONS: Patients were randomly assigned to receive either pentoxifylline (1 mg/kg) followed by an infusion of 1.5 mg/kg/hr for 24 hrs (n = 8), or placebo (n = 8). MEASUREMENTS AND MAIN RESULTS: Tumor necrosis factor (TNF) and interleukin (IL)-6 concentrations were measured by radioimmunoassays; IL-8 concentrations by an enzyme-linked immunosorbent assay (ELISA) and pentoxifylline concentrations by high-performance liquid chromatography at 0, 3, 6, 12, 18, 24 and 48 hrs after study entry. Pulmonary artery catheter-derived hemodynamics were measured at 0, 0.75, 3, 6, 12, 18, and 24 hrs. In pentoxifylline-treated patients, at 24 hrs, serum concentrations of TNF were significantly lower compared with controls (12 +/- 2 vs. 42 +/- 12 pg/mL, respectively, p = .04). Serum concentrations of IL-6 and IL-8 did not differ between the two treatment groups. There were also no significant differences in any hemodynamic and oxygenation measurements comparing the two treatment groups. Pentoxifylline concentrations were 1,544 +/- 241 ng/mL after the initial dose, and 5,776 +/- 1,781 ng/mL at the end of the 24-hr infusion. Five patients in the pentoxifylline group and four patients in the placebo group died. CONCLUSIONS: Pentoxifylline is able to decrease serum TNF but not IL-6 or IL-8 serum concentrations during septic shock. Pentoxifylline was well tolerated by all eight patients with no adverse effect. Further studies are needed to determine if pentoxifylline's ability to lower circulating TNF concentration without altering hemodynamics will improve outcome in septic shock.

Adult↗

Laparoscopic knot security.

The security of several types of laparoscopic and open knots and varying suture materials was tested in an attempt to improve suture and knot selection for advanced laparoscopic procedures. Six different types of knots and five suture materials were tested. All sutures were of 2-0 size, and laparoscopic knots were tied using a pelvic trainer. A typical number of square throws was used for each suture. Stress was gradually applied by withdrawing the ends of a manual digital tensiometer until either the knot slipped or the suture parted. The maximum stress withstood by the knot-suture complex was recorded, as was whether the knot was secure (i.e., whether the knot held until the suture broke). The data were analyzed using analysis of variance to compare the knot security of the various knot types and the different sutures using a given knot. No significant difference was found in security or stress resistance between laparoscopic square and open square knots or in the Dacron, polypropylene, and expand polytetrafluoroethylene (ePTFE) extracorporeal and intracorporeal knots, with the exception of ePTFE intracorporeal knots, which were significantly less secure (p = 0.028). Silk suture was significantly less secure than all the other sutures tested for all knots tested (p < 0.0001). The Roeder's and Fisherman's knots were the least secure of all laparoscopic knots in all sutures tested (p < 0.0001), with the exception of polyglactin tied with a fisherman's knot, which was as secure as the extracorporeal and intracorporeal polyglactin knots. These experiments showed laparoscopic square knots to be as secure as open square knots; removing the operating finger from the knot does not seem to affect the security of a well-tied square knot. Furthermore, of the permanent sutures tested, there was no substantive difference in the security of laparoscopic intracorporeally and extracorporeally tied knots, except that ePTFE was more secure when tied with extracorporeal throws. Our data also suggest that silk is not as secure as other permanent suture materials.

Humans↗