p53-related pathways and the molecular pathogenesis of melanoma.

Cutaneous malignant melanoma (CMM) is a life-threatening cancer that can have a poor prognosis with high metastatic potential. Its incidence is rapidly increasing worldwide. Its molecular alterations involve multiple pathways, including those related to p53. Since 1981, more than 380 papers containing the terms 'p53 and melanoma' as key words in the Abstract have been published in the literature. However, in spite of these extensive investigations, a review of p53 and associated genes in CMM is still lacking. To remedy this issue, this review seeks to provide a brief overview of p53 and discuss the genes targeted along its related pathways.     

Guidelines for the collection, processing and storage of human bone marrow and peripheral stem cells for transplantation

SUMMARY. There are no current U.K. or international guidelines or regulations covering the production, processing and storage of haemopoietic cells such as to allow their engraftment following myeloablative therapy. This paper seeks to provide such guidelines. It enumerates how quality control and assurance can be applied to this area of transfusion medicine; procedural steps relating to bone marrow harvest on peripheral blood stem cell collection are outlined and recommended doses of nucleated cells suggested for both procedures. General specifications for identification, storage and transportation of bone marrow and peripheral blood stem cells are included and specific laboratory procedures related to the provision of haemopoietic cells for engraftment are outlined. Umbilical cord blood transplants and long-term bone marrow culture are alluded to but these are still in a research phase.     

Doppler in non-immune hydrops fetalis.

Fetal ultrasound studies were performed on 24 fetuses with non-immune hydrops to evaluate echocardiographic and cardiovascular Doppler parameters that may be useful in assessing hemodynamics and in predicting outcome. Of all cardiovascular parameters analyzed, only the presence of abnormal pulsations in the umbilical vein (p < 0.001) was found to be significantly different between the 11 survivors and 13 non-survivors. In a smaller subset of 12 fetuses, in whom inferior vena caval waveforms were recorded, survivors (n = 6) had a significantly lower percentage of retrograde flow in the inferior vena cava (p < 0.001) and higher inferior vena caval E/V velocity ratio (p < 0.001) than non-survivors (n = 6). Sixteen of the 24 cases examined had abnormal umbilical venous pulsations; 12 of the 16 (75%) died including all fetuses with hydrops due to twin-to-twin transfusion or congenital heart disease. When fetuses with pulsatile flow in the umbilical vein were compared with fetuses with normal umbilical venous flow, the following significant differences were found: lower right and left ventricular output velocities, larger inferior vena caval diameter, decreased shortening fractions of the right and left ventricles, and lower peak velocities at the aortic and pulmonary valves and in the ductus arteriosus.     

Long-term effects of thyroid stimulating hormone and insulin on intracellular pH in FRTL-5 cells.

We have studied the chronic effects of TSH (100 microU/ml) and insulin (10 micrograms/ml) on intracellular pH (pH(i)) in FRTL-5 cells using the pH sensitive probe 2'7-bis (2-carboxyethyl-5'-6') carboxyfluorescein. FRTL-5 cells were cultured on Petri dishes either in the presence of 4H, ie. Coons F-12 containing cortisol (10 nM), transferrin (0.5 microgram/ml), glycyl-histidyl lysine acetate (10 ng/ml) and somatostatin (10 micrograms/ml), or with 4H + insulin (5H), 4H + TSH, or 4H + TSH + insulin (6H). pH(i) was measured in small groups of cells by microspectrofluorimetry both in the presence and absence of bicarbonate ions after cells had been deprived of serum for at least a day. In the absence of TSH, insulin and bicarbonate ions, pH(i) was 7.26 +/- 0.18 (mean +/- SD, n = 49) rising to 7.89 +/- 0.09 (n = 59) and 7.43 +/- 0.1 (n = 55) in the presence of TSH (4H + TSH) and insulin (5H) respectively. Addition of both insulin and TSH (6H) resulted in a pH(i) of 7.75 +/- 0.09 (n = 40). In the absence of TSH and insulin, but the presence of bicarbonate ions, pH(i) was 7.29 +/- 0.12 (mean +/- SD n = 47) rising to 7.72 +/- 0.07 (n = 59) in 4H + TSH and 7.48 +/- 0.08 (n = 60) in 5H. pH(i) in the presence of both TSH and insulin was 7.81 +/- 0.03 (n = 60). In conclusion, both insulin and TSH caused an intracellular alkalinization, TSH markedly so, even in the presence of bicarbonate ions.     

Effect of acclimation on resting energy expenditure measurements.

BACKGROUND: Development of an acclimation protocol for use when measuring resting energy expenditure (REE) would simplify and standardize data collection. The purpose of this study was to determine if our 2 metabolic carts could be used interchangeably and to determine if excluding the first 3 or 5 minutes of data collected as an acclimation period would significantly improve the coefficients of variation (CVs) for oxygen consumed (VO(2)) and carbon dioxide produced (VCO(2)) when performing REE assessments with our metabolic cart systems. METHODS: Thirteen healthy, nonsmoking adults ranging in age from 32 to 45 years, with activity levels ranging from sedentary to highly active, participated. Indirect calorimetry was performed twice in the morning after 30 minutes of supine resting. Subjects had fasted for 12 hours, and did not exercise within the last 24 hours. The system order for testing was randomized for the first measurement. When the first measurement was completed, subjects were crossed over for measurement using a second metabolic cart. RESULTS: The CVs for VO(2) and VCO(2) were significantly lower when excluding the first 3 (VO(2), p = .0005), (VCO(2), p = .0024) or 5 minutes (VO(2), p = .0001, VCO(2), p = .0021) of data compared with no exclusions. No significant differences in CVs between the 3- and 5-minute exclusions were found for VO(2) (p = .3224) or VCO(2) (p = .2255). CONCLUSIONS: Clearly, our machines cannot be used interchangeably within a study. An acclimation period improves CVs of VO(2) and VCO(2.) The similarities in CVs led us to adopt a 3-minute acclimation period for measuring REE.     

Finger and hand replantation. Surgical technique.

An approach to the technique of either finger, thumb, or hand replantation is presented in this article. Acceptable alternative approaches exist, but I have found those techniques described as practical and useful. Variations of these techniques will be necessary depending on any number of circumstances, but these considerations should be individualized to the specific patient and injury pattern.     

Pelvic floor muscle training with biofeedback and bladder training in elderly women: a feasibility study.

OBJECTIVE: It is generally assumed that interventions used to treat urinary incontinence (UI) in young women could simply be applied to older competent and motivated women, but these assumptions have not been formally tested. The purpose of this study was to determine the feasibility of using physical therapies to treat UI in older women. DESIGN: Twelve-week time series. SETTINGS AND SUBJECTS: We recruited women older than 75 years with UI from an outpatient urology clinic and a waiting list for incontinence surgery. METHODS: After a baseline evaluation, the women collected data on their incontinence symptoms and bladder habits for 3 weeks using the 72-hour voiding diary and the 24-hour pad test. They then received 6 physical therapy treatments consisting of a combination of bladder training and pelvic floor muscle training assisted with biofeedback for 6 weeks. This was followed by another 3-week period of data collection and a final evaluation. RESULTS: Ten women participated in the study; 7 completed it. They were all comfortable with the treatment. They complied with the study demands in terms of attendance at treatment session (100%), data collection (96%), and completion of exercises at home (82%). The authors observed a decrease in the number of incontinent and urgency episodes. CONCLUSION: This preliminary study demonstrates that some women older than 75 years are good candidates to undertake physical therapies for UI and follow study demands. Random controlled studies that include this population will provide evidence regarding the effectiveness of these therapies.     

Renal cystic disease in infants and children.

Renal cystic disease is a common abnormality of the kidney in the pediatric age group. Cystic disease may occur as a sporadic dysplasia or, somewhat more commonly, represent a genetic disorder. Establishment of an accurate diagnosis, prognosis, and treatment requires a broad approach to the problem, including radiologic imaging, renal function testing, and occasionally surgical biopsy. Interpretation of the imaging studies requires understanding of the patterns of renal cystic disease in the pediatric age group.     

Isolation and characterization of a penicillinase from Pseudomonas cepacia 249.

Pseudomonas cepacia has an inducible beta-lactamase which is responsible for its novel ability to catabolize beta-lactam compounds. The gene encoding this enzyme, penA, was cloned from a genomic library of P. cepacia 249 on the broad-host-range cosmid pLAFR. This separated the penA gene from the gene encoding a second beta-lactamase in P. cepacia 249. Expression of penA was inducible in an Escherichia coli host strain by low levels of penicillin. The 33,500-molecular-weight enzyme had penicillinase activity not inhibited by clavulanic acid or sulbactam and was highly active against piperacillin and azlocillin. In comparison with other inducible beta-lactamases produced by gram-negative organisms, the penA enzyme had many properties which were similar to those of the penicillinase produced by Alcaligenes faecalis. It was unlike the ampC-type cephalosporinase produced by Pseudomonas aeruginosa.     

No linkage or association between multiple sclerosis and the myelin basic protein gene in affected sibling pairs.

Myelin basic protein was examined as a candidate gene for susceptibility to multiple sclerosis using two adjacent amplification fragment length polymorphisms (AmpFLPs), containing seven and six highly informative alleles respectively. No allelic association was found with multiple sclerosis, comparing 77 cases and 88 controls, and there was no evidence for linkage in 73 affected sibling pairs, using the methods of identity by descent and identity by state.