Management of intermittent claudication with pentoxifylline: meta-analysis of randomized controlled trials

OBJECTIVE: To evaluate the efficacy of pentoxifylline therapy in improving the walking capacity of patients with moderate intermittent claudication. DATA SOURCES: A search of MEDLINE for trials published between 1976 and 1994 inclusive, and a bibliographic review of all articles retrieved. STUDY SELECTION: Randomized, placebo-controlled, double-blind clinical trials were selected that evaluated the pain-free walking distance (the distanced walked on a treadmill before the onset of calf pain) and the absolute claudication distance (the maximum distance walked on a treadmill) among patients with moderate intermittent claudication. Twelve study groups in 11 trials were included in the analysis. DATA EXTRACTION: In addition to information regarding the trial design, patient characteristics, dosages and treatment periods, the means and standard deviations were collected for both the pain-free walking and absolute claudication distances. Trial quality was also assessed. DATA SYNTHESIS: Overall, there was a statistically significant improvement in the pain-free walking distance after pentoxifylline therapy (weighted mean difference 29.4 m [95% confidence interval (CI) 13.0 to 45.9 m]); this finding was based on a total sample of 612 patients (308 in the treatment groups and 304 in the control groups). A significant improvement was also noted in the absolute claudication distance (weighted mean difference 48.4 m [95% CI 18.3 to 78.6 m]); this was based on a total sample of 511 patients (258 in the treatment group and 253 in the control group). In a sensitivity analysis of the pain-free walking distance, significant treatment effects and no statistically significant heterogeneity were found when only trials were included that were "medically eligible" (involved patients with stage II disease and a pain-free walking distance of 50 to 200 m). In a similar sensitivity analysis of the absolute claudication distance, the two conditions resulting in a significant treatment effect and no significant heterogeneity were the inclusion of "medically eligible" trials and those with a shorter treatment duration (13 weeks or less). CONCLUSION: Pentoxifylline therapy may be efficacious in improving the walking capacity of patients with moderate intermittent claudication. However, properly conducted clinical trials are required to provide a true estimate of the benefit.     

Measurement of blood volume and red cell mass: re-examination of 51Cr and 125I methods

Comparison of results of red cell mass (RCM) measurement by 51Cr and 125I methods in 119 patients showed virtual equivalence. Both methods have an acceptable coefficient of variation (CV) that is < 5%. The 125I method is simpler and much less expensive. Unrealistically narrow "normal ranges" for RCM are likely to lead to misdiagnosis of polycythemia vera. Upper normal limits of 39 mL/kg (males) and 32 mL/kg (females) are consistent with originally published data in normal persons; use of these limits as criteria would reduce the risk of misdiagnosis. No cases of "stress erythrocytosis" or Gaisbock Syndrome were encountered among the 119 cases reviewed.     

Skip lesions in temporal arteritis

Although isolated foci of arteritis ("skip lesions") are presumed to occur in temporal arteritis, there is little documentation of their existence or significance. We have identified skip lesions in 17 of 60 patients (28%) with temporal arteritis, based on a retrospective and prospective examination of temporal artery biopsy specimens. By examining more than 6,000 serial sections of arteries from patients with skip lesions, we have found foci or arteritis as short as 330 mu in length in an otherwise normal biopsy specimen. Our study emphasizes the need to biopsy long segments of artery, to examine multiple histologic sections, and to perform a contralateral temporal artery biopsy when frozen-section examination of the first side is normal.     

Interaction of A-nor, A, 19-dinor, and A-homo-5 alpha-androstane derivatives with the androgen receptor and the epididymal androgen-binding protein

The equilibrium affinity constant for rat prostate androgen receptor and epididymal androgen binding protein (ABP) has been determined for thirty-four potential progestogens. Three A-nor-, four A,19-dinor-, and one A-homo-5 alpha-androstane derivative bind to the androgen receptor (KD less than 0.5 muM). Five of these compounds also bind to ABP with an affinity of the same order of magnitude. "Anordrin" (compound 24) and "Dinordrins" (compounds 10, 14, 15, 16, 17), which are potential female contraceptives, do not bind with high affinity to the androgen receptor or to ABP. The following modifications in A-nor derivatives favour binding to the receptor as compared to ABP: 19-nor substitution (compound 1), C-18 methyl homologation (compound 5), 2 alpha-ethinylation (compound 22). One 2 alpha-allenyl A-nor derivative (compound 25) and one A-homo derivative (compound 34) bind almost exclusively to ABP. The interaction with either binding protein is decreased by oxidation or esterification of the hydroxyl group at C-17, and by addition of a 17 alpha-ethinyl group. The latter modifications are likely to increase the specificity of androstane derivatives for receptors other than androgen binding proteins, such as the progesterone receptor.     

RNA cleavage without hydrolysis. Splitting the catalytic activities of binase with Asn101 and Thr101 mutations

Members of the microbial guanyl-specific ribonuclease family catalyse the endonucleolytic cleavage of single-stranded RNA in a two-step reaction involving transesterification to form a 2',3'-cyclic phosphate and its subsequent hydrolysis to yield the respective 3'-phosphate. The extracellular ribonuclease from Bacillus intermedius (binase, RNase Bi) shares a common mechanism for RNA hydrolysis with mammalian RNases. Two catalytic residues in the active site of binase, Glu72 and His101, are thought to be involved in general acid-general base catalysis of RNA cleavage. Using site-directed mutagenesis, binase mutants were produced containing amino acid substitutions H101N and H101T and their catalytic properties towards RNA, poly(I), poly(A), GpC and guanosine 2',3'- cyclic phosphate (cGMP) substrates were studied. The engineered mutant proteins are active in the transesterification step which produces the 2',3'-cyclic phosphate species but they have lost the ability to catalyse hydrolysis of the cyclic phosphate to give the 3' monophosphate product.      

A single-headed dimer of Escherichia coli ribosomal protein L7/L12 supports protein synthesis

During protein synthesis, the two elongation factors Tu and G alternately bind to the 50S ribosomal subunit at a site of which the protein L7/L12 is an essential component. L7/L12 is present in each 50S subunit in four copies organized as two dimers. Each dimer consists of distinct domains: a single N-terminal ("tail") domain that is responsible for both dimerization and binding to the ribosome via interaction with the protein L10 and two independent globular C-terminal domains ("heads") that are required for binding of elongation factors to ribosomes. The two heads are connected by flexible hinge sequences to the N-terminal domain. Important questions concerning the mechanism by which L7/L12 interacts with elongation factors are posed by us in response to the presence of two dimers, two heads per dimer, and their dynamic, mobile properties. In an attempt to answer these questions, we constructed a single-headed dimer of L7/L12 by using recombinant DNA techniques and chemical cross-linking. This chimeric molecule was added to inactive core particles lacking wild-type L7/L12 and shown to restore activity to a level approaching that of wild-type two-headed L7/L12.     

The absence of a triphasic renovascular response by the multicalyceal kidney of the primate in reaction to acute, complete, unilateral, ureteric obstruction

The early renovascular response by the ipsilateral kidney to acute, total, unilateral, ureteric obstruction was investigated in the adult male chacma baboon (Papio ursinus). Complete occlusion was effected by ligating the ureter at the brim of the bony pelvis ("N"=10). Sham studies were enacted using the same method but the ureter was not obstructed ("N"=11). Haemodynamic reactions were monitored for 12 hours. Compared with the sham-occluded set, the renal pelvic pressures in the obstructed group were significantly increased (P<0.05) from the second hour of the inquiry. However, there were no significant differences in renal blood flow, either between or within the respective cohorts. In this study, the renovascular response to acute ureteric occlusion was similar to that displayed by the multicalyceal kidney of other species under identical conditions. This reaction was fundamentally different to that exhibited by the unicalyceal kidney under similar circumstances.     

An evaluation of current and alternative systems for quality grading carcasses of mature slaughter cows

Strip loins from 354 female bovine carcasses, selected to represent 30 skeletal maturity (A, B, C, D, and E) x marbling score (SA/MA/AB, MD, MT, SM, SL, and TR/PD) subclasses, were used to evaluate current and alternative systems for classifying cow carcasses into expected-palatability groups. Strip loins were vacuum-packaged, stored for 14 d postmortem at 2 degrees C, and frozen (-27 degrees C). Five steaks from each strip loin, each cooked to a different internal temperature (60, 66, 71, 77, or 82 degrees C), were used for shear force determinations. Two steaks from each strip loin, one cooked to 66 degrees C and the other to 77 degrees C, were used for sensory evaluation. Increased carcass maturity was associated with decreased tenderness and juiciness, increased flavor intensity, and a higher incidence of flavors described as "painty," "fishy," and "grassy." Position of a carcass within a maturity group had a negligible effect on palatability. Increased marbling was associated with greater tenderness and juiciness, a lower incidence of steaks with a "grassy" flavor, and a higher incidence of steaks with a flavor described as "fatty." Relationships between marbling and beef palatability traits were consistent across all maturity groups. Carcasses of maturities A through E were most effectively stratified according to differences in palatability when marbling scores were grouped as follows: 1) MD and higher; 2) SL, SM, MT; and 3) TR/PD. Among mature (C, D, and E maturity) carcasses, yellow-colored fat was associated with greater beef toughness and higher detection rates for "grassy" and "fishy" flavors. Higher end-point temperatures were associated with higher shear force values and lower ratings for muscle fiber tenderness, connective tissue amount, overall tenderness, and juiciness. Two alternative grading approaches (one involving current quality grading factors and the other involving the use of fat color as an additional grade factor) were developed for possible use in classification of cow carcasses into expected-palatability groups. Both alternative systems provided a more effective stratification of cow carcasses according to palatability differences than did the current USDA quality grading system.     

Thrombin regulates PDGF expression in bovine glomerular endothelial cells

BACKGROUND: Hispanic populations have been shown to be at high risk for smoking. The complex psychological process of adaptation to a different culture (acculturation) has been linked to smoking among Hispanic adults and adolescents. Although a positive association between acculturation and smoking appears to depend on gender among adults, research with Hispanic adolescents has ignored the moderating effect of gender. METHODS: Students in 22 New York City schools completed self-report questionnaires and provided carbon monoxide breath samples at two annual assessments. Sixth and seventh graders who identified themselves as Hispanics participated in the study (N = 1,295 at baseline; N = 1,034 at 1-year follow-up). The questionnaire included items related to smoking, acculturation, and demographic characteristics. RESULTS: Analyses were conducted to determine the effects of linguistic acculturation and gender on smoking. Girls smoked more frequently than boys at both time points. Being more acculturated was also associated with more smoking at the two survey assessments. As predicted, adolescent smoking depended on both gender and linguistic acculturation. For girls, but not boys, the highly acculturated adolescents smoked more frequently than either the bilingual or the less acculturated. CONCLUSIONS: Based on these findings, smoking prevention programs designed for Hispanic youth may benefit from an emphasis on Hispanic culture.     

Evaluating sources of traumatic spinal cord injury surveillance data in Colorado

The purpose of this study is to evaluate the sources reporting hospitalized spinal cord injury cases to the statewide, population-based surveillance system in Colorado for the year 1994. Three reporting sources were evaluated: clinical contact persons, medical records departments, and a centralized statewide hospital discharge database. Two evaluation strategies were utilized; these include both measures of accuracy and estimates of missed cases. For the latter, capture-recapture techniques were used to estimate the number of hospitalized spinal cord injury cases missed by all three reporting sources. The clinical contact persons reported 84 confirmed cases, missed 80 confirmed cases, and reported 10 cases that were later determined not to have spinal cord injuries, resulting in a sensitivity of 0.51. Medical records departments and the discharge database reported 143 and 147 cases, respectively, missed 21 and 17 confirmed cases, and reported 118 and 69 cases that were later determined not to be cases of hospitalized injuries of the spinal cord, resulting in sensitivities of 0.87 and 0.90. Capture-recapture results indicate all three sources combined missed an estimated 1-5 cases, yielding a total annual incidence rate for hospitalized spinal cord injury ranging from 45.1 to 46.3 per million population.