Poly(ADP–ribose) polymerase is found in both the nucleus and cytoplasm of human CNS neurons

There is evidence that inhibitors of poly(ADP–ribose) polymerase (PARP) may be therapeutically useful in neurodegenerative diseases. Using immunocytochemistry, we have investigated the distribution of PARP in the human CNS. Some neuronal groups showed cytoplasmic staining in addition to the expected staining of nuclei. Considerable variation between different neuronal groups was noted: motor neurons in the spinal cord showed greatest cytoplasmic staining, whereas staining was virtually absent in other neurons, notably in the hippocampus. These results indicate that PARP can be associated with sub-cellular components other than the nucleus, and may indicate additional roles for this enzyme.     

Isolated post-challenge hyperglycaemia confirmed as a risk factor for mortality

Abstract Aims/hypothesis. The aim of this study was to examine the possible link between isolated post-challenge hyperglycaemia (2-h post-challenge plasma glucose ≥ 11.1 mmol/l, and fasting plasma glucose < 7.0 mmol/l) and mortality. Methods. The data from three population based longitudinal studies (in Mauritius, Fiji and Nauru) were pooled and mortality rates were determined in 9179 people who were followed for between 5 and 12 years. Results. There were 595 people with previously diagnosed diabetes, and 799 with newly diagnosed diabetes, of whom 243 (31) had isolated post-challenge hyperglycaemia. In comparison with people without diabetes, people with isolated post-challenge hyperglycaemia had an increased risk of all-cause mortality [Cox proportional hazards ratio (95 % CI): 2.7 (1.8–3.9) – men; 2.0 (1.3–3.3) – women], and of cardiovascular mortality [2.3 (1.2–4.2) – men; 2.6 (1.3–5.1) – women]. In addition, men with isolated post-challenge hyperglycaemia had a high risk of cancer death [8.0 (3.6–17.9)]. Conclusion/interpretation. These data show that isolated post-challenge hyperglycaemia, which can only be identified by the 2-h glucose, is common, and at least doubles the mortality risk. This should be considered in the design of screening programmes that use only fasting glucose [Diabetologia (1999) 42: 1050–1054] Received: 18 March 1999 and in revised form: 27 May 1999     

Reuse of catheters for percutaneous transluminal coronary angioplasty: effects on procedure time and clinical outcomes.

In July 1996, because of concern regarding the possible transmission of Creutzfeldt-Jakob disease, the province of Quebec stopped the reuse of percutaneous transluminal coronary angioplasty (PTCA) catheters. Prior to this time, PTCA balloon catheters were used a maximum of four times and guide catheters a maximum of two times in the cardiac catheterization laboratory at our institution. After this time, only new catheters were used. In order to examine the effects of catheter reuse on duration of PTCA procedures and clinical outcomes, we compared 53 consecutive patients undergoing PTCA prior to 21 July 1996 with 54 consecutive patients undergoing PTCA after that time. A total of 81 men and 26 women underwent PTCA (average age, 64 +/- 12 years). There were no significant differences between the single-use and reuse groups with respect to baseline characteristics. There were also no significant differences in the numbers of PTCA catheters used (97 vs. 103, P = NS) or angiographic success rates (88% vs. 83%, P = NS). There was a trend for total procedure time and fluoroscopy time to be slightly longer for single-use compared with reuse cases (49.2 vs. 45.7 min and 19.7 vs. 16.8 min, respectively; P = NS for both comparisons). However, after controlling for case severity and the use of stents, there were no significant differences in total procedure time or fluoroscopy time between the two groups. We found little evidence to suggest that the reuse of PTCA catheters is associated with longer total procedure time or fluoroscopy time. We conclude that if catheter reuse is not found to be associated with infectious disease transmission, its widespread use should be considered. Cathet. Cardiovasc. Intervent. 48:54-60, 1999.     

The effect of orthodontic treatment on plaque and gingivitis

The aim of the present investigation was to evaluate the relationship between the receipt of orthodontic treatment and subsequent periodontal health. Data from 417 children who were classified at baseline as having significant occlusal variations and who were present at the follow-up examination 3 years later were selected from an original cohort of 1015. One hundred fourteen of these children received orthodontic treatment over this time period and provided two groups of children for comparison in this study. Plaque indices, bleeding indices, and degree of dental irregularity were recorded for each incisor and canine tooth. There were significant reductions in the plaque and gingivitis scores on all tooth surfaces between the baseline and 3-year examination in the two groups of children. The children who had received orthodontic treatment had the greater reduction, but this appeared to be more related to behavioral factors than to improved tooth alignment.     

Triple antibiotics for the treatment of infected joint replacements. Case report and commentary

Combination antibiotics are frequently used in the treatment of infected joint arthroplasties to achieve synergistic activity against the infecting organisms. A case is presented in which triple antibiotic therapy was used in the treatment of an infected hip arthroplasty. The antibiotic combination proved to have an antagonistic effect despite documented sensitivities to the individual drugs. Serum antimicrobial assays are recommended in the treatment of all prosthetic joint infections.     

In vivo kinetics of a covalent growth hormone-binding protein complex

The biologic function of the newly recognized binding proteins (BP) for human growth hormone (hGH) in human plasma is largely unknown; hGH circulates in part in complexed form in association with the BP. In a previous study we showed that the in vivo kinetics of hGH were altered in the presence of the BP. However, that study gave only qualitative information because the BP was present in excess and the complex was subject to dissociation in vivo. To gain more quantitative information about the in vivo behavior of complexed hGH, metabolic clearance (MCR), distribution volume (Vd), and degradation rate of a covalently crosslinked, stoichiometrically correct, chemically stable hGH-BP complex were measured. The MCR and the degradation rate of complexed hGH were tenfold lower than those of free hGH (P less than .001), and its Vd was significantly smaller than that for free hGH (P less than .001). The covalent complex was fully immunoreactive with polyclonal anti-hGH antibodies. We conclude that complexed hGH is protected from clearance and degradation by being restricted from access to degradation sites, including the proximal renal tubule and receptor-mediated delivery to intracellular proteolygic organelles. The data developed also yield preliminary information about the in vivo distribution of the BP itself. These data provide important guidelines for future studies regarding the in vivo effects of the BP. In addition, the results indicate that the principal epitope(s) of hGH remain(s) exposed on the outer surface of the complex.     

Antiandrogens do not reverse androgen-induced inhibition of sex hormone-binding globulin levels in adult female rhesus monkeys

Studies were done to determine if changes in plasma sex hormone-binding globulin (SHBG) levels could serve as a specific marker of androgenic and antiandrogenic activities in rhesus monkeys. Treatment of adult female monkeys for 11 days with 17 alpha-methyltestosterone (MeT) produced dose and time-dependent reductions in SHBG levels. However, the non-steroidal antiandrogen flutamide (80 mg/monkey.day) did not inhibit the reduction in SHBG levels when coadministered with MeT, nor did it have an effect on SHBG levels when given alone. In contrast, the steroidal antiandrogens Win 49596 (100 mg/monkey.day) and cyproterone acetate (80 mg/monkey.day) significantly (P less than 0.01) reduced SHBG plasma concentration to about 50% of pretreatment control values whether given alone or in combination with MeT. Furthermore, Win 49596 reduced SHBG levels at doses as low as 4 mg/monkey, whereas cortico-steroid-binding globulin levels were not affected. In ovariectomized monkeys, MeT treatment (4 mg/monkey.day for 15 days) reduced plasma SHBG levels to 42% of pretreatment values and delayed the onset of withdrawal menstrual bleeding compared to that in controls. When administered concurrently with MeT, flutamide (100 mg/monkey.day) antagonized the effect on withdrawal bleeding, but was without effect on SHBG levels. Therefore, plasma SHBG levels cannot be used as a specific indicator of androgenic or antiandrogenic activity and may not be regulated through the classical androgen receptor.     

Peptic ulcer and gastric carcinoma: diagnosis with biphasic radiography compared with fiberoptic endoscopy

The diagnostic value of biphasic radiographic examination of the stomach and duodenum was compared with that of fiberoptic endoscopy in a prospective, blinded study of 385 patients with dyspepsia. This investigation was directed at gastric malignancies and peptic ulcers. Methodologically there is no absolute standard for a study of this kind because histologic examination is useful for detection of cancer but inadequate for ulcers. As an alternative, kappa indexes and the sensitivity and specificity, as derived by Hui and Walter, were calculated and compared. For the detection of gastric carcinoma, radiographic and endoscopic findings had almost perfect agreement beyond chance. For gastric ulcers, radiography and endoscopy had substantial agreement, which became perfect if small ulcers (less than 5 mm) were excluded. For duodenal ulcers, radiography had a lower sensitivity than endoscopy; this disagreement disappeared if small ulcers were excluded. Both methods have equal merit; choice of the initial diagnostic procedure will therefore depend on cost, discomfort to the patient, and risk of complications.     

Cytoreductive surgery impedes metastasis and enhances the immune response: a preliminary report

In an effort to determine the effect of cytoreductive surgery on the metastatic process, MAT-LyLu flank tumors were excised from Copenhagen x Fischer rats and the effects of this surgery on metastatic lung lesions were observed. Cytoreduction resulted in a decrease in lung lesions (P less than 0.05). Adjuvant cyclophosphamide (CTX) further enhanced this beneficial effect. A concurrent increase in the helper/suppressor ratios suggested that this beneficial response might be mediated by the host's immune response.