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Diabetes, peripheral neuropathy, and old age disability.

The purpose of this study was to determine whether peripheral neuropathy explains the apparent association between diabetes and disability in old age, and to evaluate the utility of lower extremity function tests in older diabetic adults with and without neuropathy. We evaluated 39 adults, aged 70-79 years, for pressure sensation (log(10)g), vibration perception threshold (VPT; microns), and electrophysiologic function of the peroneal nerve. The subjects included patients with established diabetic neuropathy (DN; n = 14), diabetic controls without neuropathy (DC; n = 13), and nondiabetic controls (NDC; n = 12). Nonparametric statistical methods were used to relate neuropathy measures to performance in tests of walking speed, static and dynamic balance, coordination, and ankle strength (kilograms). Significant age-adjusted correlations were observed between measures of sensory neuropathy and a variety of performance measures, and electrophysiologic measures were related to static balance. DN subjects had significantly higher pressure sensation than NDC (5.17 vs 3.38g, P < 0.05), higher VPT (62.5 vs 21.7 microm, P < 0.05), and lower peroneal motor response amplitudes at multiple sites. Pressure sensation and nerve conduction measures did not differ between DC and NDC. Compared with NDC, DN subjects performed significantly worse on tests of walking speed (0.99 vs 1.34 m/s; P < 0.05), static balance (4.9 vs 20.4 s; P < 0.05), dynamic balance (9.23 vs 25.52 s; P < 0.05), and coordination (6.73 vs 4.76 s; P < 0.05). No differences were observed in these measures between DC and NDC. Observed differences in physical abilities between older diabetic and nondiabetic adults may have been due to the subset of diabetic individuals with peripheral neuropathy. Quantitative measures of sensory and motor nerve function have distinct effects on physical performance. Interventions aimed at reducing the impact of diabetes-associated disability in old age may have the greatest impact among people with peripheral neuropathy.

Aged↗

Urgency of voiding and abdominal pressure transmission in women with mixed urinary incontinence.

AIMS: To ascertain whether abdominal pressure transmission (a.p.t.) to the urethra would be affected by urgency of voiding in women with mixed urinary incontinence. METHODS: We urodynamically assessed 80 consecutive women. Group 1 (n = 40), with stress incontinence, had stable bladders and no urgency. Group 2 (n = 40), with mixed (stress + urge) incontinence and overactive bladders, were split into Groups 2A (n = 20) and 2B (n = 20) according to the delay time of urgent void at cystometry (CMG) equating at least 2 min (taken as an index of moderate urgency) or, respectively, less than 2 min (taken as an index of severe urgency). Nonparametric statistics checked for significant differences in a.p.t. and in pelvic floor (peri-urethral) muscle strength level. We defined a.p.t. at stress (cough) urethral pressure profilometry (UPP) by the pressure transmission ratio (PTR). Pelvic floor muscle strength was defined at "holding" UPP by the maximum urethral pressure developed during attempts "to hold urine" (hMUP). RESULTS: PTR was reduced in all women, but PTR (and hMUP) proved relatively higher in Group 2, though nonsignificantly different values of PTR (and hMUP) were seen in Groups 2B and 1. CONCLUSIONS: Transmission of abdominal pressure to the urethra was reduced in all of the incontinent women. The mixed incontinence group, however, had a relatively less reduced (active component of) a.p.t., most likely dependent on a greater pelvic floor (peri-urethral) muscle strength level secondary to frequent contractions in response to urgency. Yet, of the same mixed incontinence patients, those with the most severe urgency degrees had relatively low pelvic floor (peri-urethral) muscle strength levels (eventually resulting from muscle fatigue? or primarily due to peri-urethral tissue atrophy?), which prevented (the active component of) a.p.t. from increasing.

Abdomen↗

Influences of dihydrotestosterone, testosterone, estradiol, progesterone, or prolactin on the cell kinetics of human hyperplastic prostatic tissue in organ culture.

In an effort to characterize the hormone sensitivity of human benign prostatic hyperplasia (BPH) maintained in organ cultures for 12-72 h, the influence of 5-alpha-dihydrotestosterone (DHT), testosterone (T), 17-beta-estradiol (E2), progesterone (Pg), or prolactin (PRL) was assessed on the cell proliferation rate of 25 BPH specimens by the use of tritiated thymidine incorporation followed by autoradiography. Significant increases in the thymidine-labeling index (TLI: percentage of labeled nuclei) were observed in glandular tissue after a 36-h incubation period in presence of DHT, E2, Pg, or PRL in 52%, 44%, 28%, and 60% of BPH cases, respectively. Nonparametric statistics (Spearman and Kendall rank correlation tests) have shown that 1) the steroid-induced TLI increases are dependent on the basal rate of cell proliferation, while the PRL-induced effect is independent of it, and 2) all the steroid-mediated effects on BPH TLI are correlated together, whereas they seem to be independent of the PRL-induced TLI increase. When T was compared with DHT on nine BPH specimens, three were found to be sensitive to both hormones, and two responded to DHT only. We propose that our study methods are suitable as a means to assess the hormone sensitivity of individual cases of BPH and possibly prostatic tumors.

Aged↗

Regression models for time to seroconversion following experimental bovine leukaemia virus infection.

This paper develops a parametric model for time to seroconversion after experimental bovine leukaemia virus (BLV) infection, and examines the effects of inoculation route, volume of inoculum, type of inoculation material, and antigen status of donor on seroconversion time. We used parametric and nonparametric statistical methodology to analyse interval data on 150 animals from 13 published reports. The log-logistic model fitted the observed times to seroconversion better than the log-normal or Weibull models, which were the considered alternatives.

Animals↗

Gelatin-sealed polyester resists Staphylococcus epidermidis biofilm infection.

BACKGROUND: The purpose of this study was to show that gelatin-impregnated polyester grafts inhibit Staphylococcus epidermidis biofilm infection in a canine model of aortic graft interposition. A clinically native species and two engineered strains, which differed in slime and adhesin antigen components, were compared to determine differential gelatin and slime interactions. METHODS: In vitro bacterial graft colonization was validated by immersion of graft segments in inoculating solutions (10(6) colony forming units/ml) of a clinically native species RP62A and two genetically engineered S. epidermidis species, M187sn3 (SN3: slime and adhesin negative) or M187sp11 (SP11: slime and adhesin positive), for 18 h at 23 degrees C. The grafts were washed, sonicated, and cultured to assess in vitro bacterial graft adherence. Grafts similarly inoculated were placed as aortic interposition grafts in dogs. Three sterile grafts were implanted as controls. Grafts were excised after 6 weeks and cultured for bacterial growth as in the in vitro study. Infection was defined by a positive culture in the excised grafts. Data were analyzed with nonparametric statistical methods. RESULTS: In vitro bacterial graft adherence in colony forming units per milliliter was similar at 18 h postsonication for RP62A (8 x 10(4) +/- 1 x 10(4)), SN3 (7 x 10(4) +/- 2 x 10(4)), and SP11 (6 x 10(4) +/- 2 x 10(4)) (P = NS). Only one of five grafts inoculated with RP62A was culture positive after 6 weeks. No grafts inoculated with the engineered strains SN3 or SP11 were culture positive after explanation. CONCLUSION: In vitro bacterial inoculation of gelatin-impregnated polyester was similar among the species and not dependent upon the presence of slime and adhesin components. Gelatin-impregnated polyester grafts demonstrated in vivo resistance to coagulase-negative staphylococcal biofilm infection.

Animals↗

Varicose veins possess greater quantities of MMP-1 than normal veins and demonstrate regional variation in MMP-1 and MMP-13.

BACKGROUND: Studies have reported that structural proteins such as elastin and collagen are decreased in varicose veins compared to normal controls. We hypothesized that the changes observed in varicose vein wall composition may be related to alterations in extracellular matrix remodeling proteins, such as the matrix metalloproteases and serine proteases. In addition we hypothesized that there may be regional variation in the expression of these enzymes within the leg. PATIENTS AND MATERIALS: One-centimeter segments of the proximal and distal greater saphenous vein (GSV) were obtained from patients undergoing ligation and stripping for venous insufficiency (vv) (n = 15) or GSV harvest in conjunction with coronary artery bypass grafting (CABG) (n = 7). All vv patients had incompetence of the GSV by color flow duplex. Vein specimens were examined for MMP-1, 3, and 13, tryptase, and GAPDH mRNA using semiquantitative RT-PCR analysis. Quantification of MMP-1 and 13 (active/latent forms) and tryptase was performed using Western blot analysis. Western blots were analyzed using scanning densitometry and standardized to normal controls and values expressed as the median densitometric index (D.I.). Nonparametric statistical methods (Wilcoxan signed rank test and Mann-Whitney U test) were used for analysis. RESULTS: We were able to amplify MMP-1, MMP-13, and tryptase mRNA from both proximal and distal segments of all greater saphenous veins studied. MMP-3 mRNA, however, was not found in either segment of any of the veins examined. A semiquantitative analysis of RT-PCR products comparing the ratio of MMP-1, MMP-13, or tryptase mRNA to GAPDH mRNA showed no difference between cases and controls nor proximal vs distal vein segments. Western blot analysis revealed larger quantities of MMP-1 in varicose veins than in nondiseased veins from CABG patients (48.0 +/- 36.7 D.I. vs 12.5 +/- 6.8 D.I., P = 0.036). Investigation into the regional variation of proteases revealed lower amounts of MMP-1 in distal than in proximal vein segments (37.9 +/- 35.0 D.I. vs 44.1 +/- 41.6 D.I., P = 0.01). Similarly, we found significantly less MMP-13 in distal segments of varicose veins than in proximal segments (152.8 +/- 130.0 D.I. vs 206.7 +/- 173.3 D.I., P = 0.006). CONCLUSIONS: This study found that MMP-1 protein is increased in varicose veins when compared to controls despite no differences in mRNA expression. In addition we found that there is regional variation of MMP-1 and MMP-13 in diseased varicose veins. Lower leg veins have significantly reduced amounts of these proteolytic enzymes when compared to veins of the upper thigh. These data suggest that posttranscriptional regulatory controls could be responsible for the observed differences.

Adult↗

Biogeographic origins of goannas (Varanidae): a molecular perspective.

This project aims to clarify the phylogenetic relationships among the extant species of Varanus in order to elucidate the origins of Varanidae, using DNA sequences. Results obtained for a minimum of 662 nucleotides of 12S rRNA sequence data from each of 21 extant species of Varanus indicate that the Australian varanids form a single monophyletic clade and also suggest that within the Australian varanids, members of the subgenus Odatria (pygmy monitors) may from a clade separate from those in the subgenus Varanus (large monitors). The Asian species appear to be sister taxa to the Australian species, while the two African species investigated were most divergent, suggesting that the Varanidae are not Gondwanic in origin. Hypothesis testing analyses were performed and involved constraining the 12S sequence data according to previously described topologies and testing the difference using parametric and nonparametric statistics. The phylogeny generated using 12S sequence data was statistically different from previously described morphological trees, while there was some support for topologies based on chomosomal and immunological datasets. Overall, our results suggest that the Australian species may be derived from an Asian source and are, therefore, in agreement with the hypothesis based on the fossil record suggesting that Varanidae may be Asian in origin.

Animals↗

Cementless Gustilo-Kyle and BIAS total hip arthroplasty: 2- to 5-year results.

We conducted extensive radiographic and clinical examination of 58 cementless total hip arthroplasties. Forty BIAS femoral stems had heads made of Co-base F 75 alloy and 18 Gustilo-Kyle femoral stems had Ti6A14V alloy heads. The cross-sectional geometry and location of the porous coating pads of the two stem types was identical, the BIAS component being slightly shorter. At the last follow-up, 27.8% of the Gustilo-Kyle femoral components and 2.5% of the BIAS femoral components were unstable. None of the acetabular components in the BIAS group as against 38.9% of the acetabular components in the Gustilo-Kyle group demonstrated wear of more than 1 mm. All unstable components which did not suffer intraoperative fracture had also acetabular wear of more than 1 mm. The only case with endosteal erosion was seen in a patient with an unstable implant displaying the most extensive wear. Nonparametric statistical analysis showed that the patients with Ti6A14V/polyethylene bearing surfaces had a statistically significantly higher extent of wear and a statistically significant higher incidence of femoral component loosening than patients with CrCoMo/polyethylene bearing surfaces.

Adult↗

Factors affecting human autopsy kidney-cortex and kidney-medulla platinum concentrations after cisplatin administration.

The objective of this study was to determine factors that affect cisplatin concentrations in human kidney cortex. We used flameless atomic absorption spectrophotometry to assay platinum in autopsy specimens of kidney cortex obtained from 83 cisplatin-treated patients. Concentrations were correlated with pretreatment factors and treatment conditions using univariate nonparametric statistics. Hierarchical stepwise multiple regression analyses of transformed (to normalize) data were then used to assess which factors were most important, controlling for other factors. Kidney-cortex platinum concentrations varied from 0 to 14.8 micrograms/g (median, 2.04 micrograms/g). The cumulative lifetime dose of cisplatin ranged from 10 to 1120 mg/m2 (median, 112 mg/m2). The time from the last cisplatin dose to death was < 1-609 days (median, 38 days). According to univariate statistics, factors that correlated (P < 0.05) with kidney-cortex platinum concentrations were the cisplatin dose per course, the pretreatment serum urea level, metoclopramide use (positive correlations), the time from the last cisplatin treatment to death, and the pretreatment serum albumin value (negative correlations). Factors that approached significance (0.05 < or = P < or = 0.10) were a history of hypertension, hyperbilirubinemia (positive), the serum calcium level, and phenytoin use (negative). In the multiple regression analysis, after controlling for the cisplatin dose per course and the time from the last treatment to death, only concurrent metoclopramide and phenytoin use entered the model. The hydration volume did not affect corrected kidney-cortex or kidney-medulla platinum concentrations. The following conclusions were reached: (1) it may be feasible to use lower hydration volumes than those used routinely, (2) any effect of hydration volume on cisplatin nephrotoxicity may not be mediated via a reduction in kidney-cortex platinum concentrations, (3) higher cisplatin doses might be tolerated with new 5-hydroxytryptamine-3 (5HT-3) antiemetics than were tolerated with metoclopramide, and (4) phenytoin should be tested for its ability to reduce cisplatin nephrotoxicity.

Autopsy↗

The effect of influential outliers on parameter estimation in regression analysis.

A comment is made on an article recently published in this journal by Borgeat, Elie, and Castonguay (1991). It is noted that the raw data contained an outlier which is shown to have had a large influence on their estimation of the regression coefficient. Analysis of the data using a nonparametric statistic that is optimal for long-tailed distributions showed that the true regression coefficient is probably smaller than that reported. Other approaches to the analysis of data containing influential outliers are discussed.

Biofeedback, Psychology↗

Preclinical radiobiology with pions: RBE--values for mouse skin damage as a function of single doses of pions.

The macroscopic reaction of the mouse skin was used to derive RBE values for negative pi-Mesons. Hind limbs of mice were irradiated with pions or X-rays. The pions were produced by the 590 MeV accelerator of the Schweizerisches Institut für Nuklearforschung (SIN). Early reaction was assessed over a period of 6--30 days after irradiation with single doses (20--45 Gy). The radiation damage was scored using an arbitrary scale of effect. The time pattern of development of the skin reaction and the subsequent healing after exposure both to pions and X-rays were similar, indicating that depletion and repopulation of the basal cells of the skin were comparable, both after pions and X-rays. RBE values as a function of pion doses at the peak (dose maximum), plateau and at the postpeak (12 mm downstream of the dose maximum) were computed with nonparametric statistical methods. The RBE at the peak and at the plateau relative to X-rays of the same dose rate was 1.15--1.25 and 0.85, respectively. The RBE of peak pions manifested a marked dependence on dose, when plateau pions were chosen as reference radiation. In this experiment there was no significant difference in RBE between peak and postpeak. The importance of some experimental condition (dose rate, irradiation volume) is discussed.

Animals↗

The Schilling test cannot be replaced by an absorption test with unlabeled vitamin B12.

It was the purpose of this study to evaluate the diagnostic usefulness of an oral absorption test using nonlabeled Vit B12 suggested by a commercial distributor as an alternative for the more expensive Schilling test (ST). Plasma levels of Vit B12 were measured with a commercial kit before and 4 h after oral administration of 1 mg Vit B12 in 32 normals, in 16 patients with normal ST, and in 14 patients with abnormal ST for determination of sensitivity and specificity with the ST as golden standard. In normals, a mean of 767 +/- 404 pg/ml before and 1096 +/- 776 pg/ml after oral Vit B12 with a mean increase of 331 +/- 453 pg/ml was measured. Because of the obvious large variation, no meaningful range for normal absorption could be established. In the two patient subsets, there was no Gaussian distribution of the results, with a meridian of Vit B12 increase after absorption of 142 pg/ml, range 27-2668 pg/ml, in the group with normal ST and a meridian of 244 pg/ml ranging from 40 to 2453 pg/ml in the group with abnormal ST. Statistical nonparametric analysis did not reveal any difference between the two groups. Assuming a minimum required increase of 100 pg/ml, as suggested by the kit distributor, a sensitivity of only 27% and a specificity of 75% was obtained.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Dose related effects of dexamethasone treatment on the ultrastructure of articular cartilage in rats.

Corticosteroid administration is known to cause degenerative changes in articular cartilage interfering with the cell metabolism of chondrocytes. The present study analyzes the ultrastructural changes in chondrocytes after systemic dexamethasone acetate treatment in relation to dosage, using a standardized morphometrical method. Five male Wistar rats of 300 g body weight in each experimental group were subjected to 3, 4 and 5 mg dexamethasone acetate by intramuscular injections of 1 mg per week. 1000 electron micrographs of single chondrocytes in the middle zone of hyaline cartilage from the knee joints were evaluated with standardized morphometry and nonparametric statistics. With increasing dexamethasone dosage the amount of rough endoplasmic reticulum and Golgi apparatus decreased. Considerably increased glycogen granula and clusters indicated a severe change in glycolytic pathways. Lysosomes duplicated in number. Degenerative changes were also manifested in lipid droplets and myeloid bodies, which, like the amount of microfilaments, exhibited a clear dosage-dependent increase under dexamethasone treatment. The ratio of dead versus living chondrocytes increased in relation to dosage up to 25% cell mortality.

Animals↗

Racial matching and service utilization among seriously mentally ill consumers in the rural South.

The authors examined racial matching between case manager and client for 677 seriously mentally ill consumers served through a rural community mental health center in the southeastern United States. Nonparametric statistics indicated that client-case manager dyads were more likely to be of the same race than of different races. Same-race dyads tended to have greater service utilization as indicated by a greater number of made appointments over the study period. An interaction was found for failed appointments where African Americans in same-race dyads were more likely to fail appointments, while caucasian consumers in same-race dyads were less likely to fail appointments.

Adult↗

Phasic production of urinary pyridinium crosslinks in mice: the effect of ovariectomy.

Considerable sample to sample variability in deoxypyridinoline crosslink/creatinine (Dpd/CREAT) ratio values was confirmed when twice-weekly sampling for 77 days was performed in C57 mice. Analysis of samples from individual mice indicated that, in the majority of mice in a given group (54-67%), phasic changes occurred with periodic peaks as much as 4-5 times basal values. Alignment of peaks in the individual time courses of mice revealed a clear cyclic crosslink production (periodicity 12-14 days) for the population, although not all mice gave a peak in every case. Ovariectomy (OVX) (compared to sham-operated mice) increased mean values of crosslink production by either C57 or C57 x 129 F1 mice from about 10 days after operation with highest values between 21 and 35 days, and then a decrease in the difference between sham and OVX, particularly in C57 mice. Analysis of both time courses for individual mice and distribution curves of the data from groups of mice indicated that OVX consistently increased basal crosslink values (6-9 ratio units) with phasic peak values superimposed. The peak alignment analysis reinforced this observation. The influence of the background variability was avoided by pooling data over one cycle time and the use of nonparametric statistics, and the effect of OVX was analyzed in several strains of mice. Crosslink levels and phasic production declined with age but were also influenced by manipulation of the mice, suggesting that experimental conditions should be rigorously controlled when this urinary crosslink measure is used as a parameter in mouse models of OVX-induced osteoporosis.

Amino Acids↗

Reliability of the timeline follow-back sexual behavior interview.

The reliability of self-reported sexual behavior is a question of utmost importance to human immunodeficiency virus (HIV) prevention research. The Timeline Follow-Back (TLFB) interview, which was developed to assess alcohol consumption on the event level, incorporates recall-enhancing techniques that result in reliable information. In this study, the TLFB interview was adapted to assess HIV-related sexual behaviors and their antecedents, and its reliability was assessed. The interview was administered to 110 participants (46% women, M age = 19.7; range = 18-41), and 58 participants who reported sexual behavior during the previous three months returned one week later for a second interview. Test-retest intraclass correlations (rho) from the TLFB protocol showed that all sexual behaviors were reported reliably (rho range = .86 to .97, median = .96). Bootstrapping, a nonparametric statistical technique, was used for significance testing in the reliability analyses. Reliability was equivalent across each of the three months assessed with the TLFB and was equivalent to conventional assessment methods (i.e. single-item questions). These findings show that the TLFB sexual behavior interview provides reliable reports of sexual behavior over three months and yields event-level data that are extremely valuable for sexual behavior and HIV-prevention research.

Adolescent↗

Influence of tumor grade on expression of CA 125 in serum and tissue in patients with serous ovarian carcinoma.

OBJECTIVE: The factors affecting CA 125 expression in tissue in serous carcinoma are not well known. The aim of our study was to establish how CA 125 expression in serum and tissue is affected by DNA-ploidy, proliferative activity of tumor cells, tumor grade and the stage of the disease. STUDY DESIGN: This retrospective study included 50 patients with ovarian carcinoma. The serum CA 125 level was determined preoperatively in all patients. Antigen expression in tissue was confirmed using CA 125-immunohistochemistry. Suspensions of nuclei were prepared from tissue sections and DNA-ploidy was determined using flow cytometry. Data were analyzed using nonparametric statistics and multivariant analysis. RESULTS: The average level of serum CA 125 was 674.5 U/ml and was significantly higher in advanced (p = 0.00044) and dedifferentiated (p = 0.00055) tumors and in tumors with a higher S-phase fraction (SPF) (p = 0.011). The mean percent of CA 125-positive cells in tissue was 38.3. CA 125 immunostaining was not related to tumor grade or DNA-ploidy. A positive CA 125 test in both tissue and serum was confirmed in 33 cases (66%). The correlation between expression of CA 125 in tissue and serum was weak (r = 0.28) and nonsignificant (p = 0.052). CONCLUSIONS: No reliable conclusions could be drawn on the influence of the studied parameters on expression of CA 125 in tissue and serum. The effect of tumor grade seems to be the strongest influence, particularly on CA 125 expression in serum, but it is not independent.

Adult↗

The effect of tyrosine kinase inhibitors on IgE-mediated histamine release from human lung mast cells and basophils.

OBJECTIVE AND DESIGN: To investigate the role of tyrosine kinases (TK) in IgE-mediated signal transduction in human lung mast cells (HLMC) and basophils. MATERIALS: Peripheral blood basophils (n > or = 4) and human lung mast cells (n > or = 6). TREATMENT: Cells were preincubated with TK inhibitor for 15 min at 37 degrees C, before the addition of anti-IgE. METHODS: Histamine release (HR) was assayed using a fluorimetric technique. Results were compared using nonparametric statistics. RESULTS: Piceatannol and ST638 significantly (p < or = 0.05) inhibited anti-IgE induced HR from HLMCs and basophils whilst lavendustin C had no effect in either cell type. Herbimycin A also significantly (p < or = 0.05) inhibited anti-IgE induced HR from both cell types, an effect which was dose dependent but did require a 16 h preincubation with drug. CONCLUSIONS: In summary, HLMCs and basophils exhibit distinct inhibitory profiles in the presence of various inhibitors of TK.

Basophils↗