Confounders contributing to the reported associations of coffee or caffeine with disease

The role of caffeine or coffee in causing or promoting the incidence of serious disease is equivocal. Two design factors may account for the discrepancies in reported findings on the effects of coffee drinking: (a) imprecision of measurement and (b) confounding variables. A study of 2,714 white U.S. adults disclosed that, of 32 risk factors analyzed by linear and logistic regression, only sex and cigarette smoking were found to be important potential confounders of caffeine and coffee intake. Partial R2 values of the other 30 risk factors were relatively small and were inconsistent for each sex. It is unlikely that any of these factors could explain any of the reported associations between caffeine or coffee consumption and certain diseases. However, certain weak associations with caffeine or coffee intake should be included in the study design when they are known to be risk factors of a disease under investigation. These factors for men are dietary fat intake, vitamin C intake, and body mass index; and for women are vitamin use, alcohol intake, stress, and perceived health status.     

Physical Therapy and Complementary and Alternative Medicine: An Educational Tool for Enhancing Integration

In an outpatient rehabilitation setting, both patients’ use and therapists’ knowledge of complementary and alternative medicine (CAM) varies widely. Based on this observation and a recognition of CAM as an emerging practice area for rehabilitation professionals, it was felt that a thorough and consistent approach to the education and orientation of physical therapists to the world of CAM and integrative care was needed. This special interest paper will describe one center’s approach, development, and use of a unique and comprehensive training manual designed to provide both a structured and standardized approach for educating physical therapists about CAM and related therapeutic modalities. This innovative teaching tool allows for multiple methods of content delivery within a multidisciplinary format and can be used for those who practice currently or desire to practice in an integrative care environment.     

Radiotherapy of periocular basal cell carcinomas: recurrence rates and treatment with special attention to the medical canthus.

Basal cell carcinomas of the eyelids, especially those in the medial canthal area, may cause extensive local destruction. Recurrent tumours are more aggressive and become progressively more difficult to treat; this is especially true for postirradiated recurrent, medial canthal, basal cell carcinomas. Tumours in this area should thus be treated by a technique which allows tissue sampling in order to gauge the adequacy of the treatment, with the goal being complete extirpation of the tumour. Excision monitored by frozen section control or Mohs' surgery is our recommendation based on a retrospective analyses of 631 eyelid basal cell carcinomas, half of which were primary tumours and half recurrent.     

Inhibition of phosphoribosylpyrophosphate synthetase by 4-methoxy-(MRPP) and 4-amino-8-(D-ribofuranosylamino) pyrimido[5,4-d]pyrimidine (ARPP)

The basis for the antitumor activities of the exocyclic amino nucleosides 4-amino-(ARPP) and 4-methoxy-8-(D-ribofuranosylamino)pyrimido[5,4-d]pyrimidine (MRPP) was investigated. The primary target of these nucleosides appeared to be 5-phospho-alpha-D-ribofuranose-1-pyrophosphate (PRPP) synthetase. MRPP-5'-monophosphate was a competitive inhibitor (Ki = 40 microM) of the activation of this enzyme by the cofactor inorganic phosphate (K alpha = 2.2 mM). Consequently, ARPP and MRPP treatment of WI-L2 cultures rapidly inhibited both de novo pyrimidine and purine synthesis as well as the nucleotide salvage reactions dependent on PRPP, ARPP or MRPP treatment completely prevented [14C]bicarbonate incorporation into acid-soluble pyrimidine and purine nucleotides. The rate of salvage of [8-14C]hypoxanthine to form IMP was decreased by 85%. Treatment of cells with these agents caused a 50% reduction in the steady-state level of PRPP. When the capacity of the treated cells for sustained synthesis of PRPP was examined by adenine incorporation, the rate of adenine uptake was inhibited by greater than 50%. In vivo treatment of BDF1 mice with a single dose of ARPP (173 mg/kg) or MRPP (62 mg/kg) extended the mean life span of the mice, which had been inoculated intraperitoneally 1 day earlier with 1 x 10(6) L1210 murine leukemia cells, by 62 and 82% respectively. These studies indicate that MRPP and ARPP inhibit PRPP synthetase, and that PRPP synthetase may be a viable target in the development of certain antitumor agents.     

Urinary hydroxypyridinium cross-links of collagen in primary hyperparathyroidism.

Urinary concentrations of the collagen cross-links, pyridinoline (PYD) and deoxypyridinoline (DPD), were determined in 87 patients with untreated or surgically treated primary hyperparathyroidism (PHPT). Eighty-four healthy individuals, matched for age and sex, constituted the control group for the excretion of pyridinium cross-links. In addition, a subgroup of 25 patients with PHPT was followed longitudinally for up to 2 yr after successful parathyroidectomy. Mean urinary excretion of PYD (46.8 +/- 2.7 nmol/mmol creatinine) and DPD (17.6 +/- 1.3 nmol/mmol creatinine) was significantly higher in patients with untreated PHPT than in normal subjects (P less than 0.001). In the group undergoing successful parathyroidectomy, mean urinary concentrations of PYD (34 +/- 2.5) and DPD (9.4 +/- 0.8) were similar to those in normal controls and significantly lower than those in the untreated patient population (P less than 0.001). The urinary concentration of both cross-links was significantly correlated with serum levels of both alkaline phosphatase and PTH. Mean urinary concentrations of both cross-link compounds decreased significantly within 6 months in patients followed longitudinally and as early as 2 weeks after surgery in individual patients compared to presurgical baseline values. These changes preceded the reduction in serum alkaline phosphatase and hydroxyproline by approximately 6 months. The results demonstrate that urinary hydroxypyridinium cross-links of collagen are useful indices in the clinical assessment of bone involvement in PHPT.     

Moderate drinking in ex-alcoholics: recent studies

The literature on the occurrence of moderate drinking in ex-alcoholics that has been published since the Rand report in 1976 is reviewed. Although differences in diagnosis, definitions of moderate drinking and length of follow-up make strict comparisons of the studies difficult, the majority of studies seem to indicate that the earlier reports of the frequency of such moderate drinking may be overly optimistic. Depending on the definition of moderate drinking that is used, the longer the interval required for alcoholics to sustain moderate, problem-free drinking, the less likely is such an outcome. Among treated alcoholics, the percentage probably ranges from about 2 to 12%; the percentage may be higher among alcoholics identified in community population samples. Thus far, the only factor common to alcoholics who are able to achieve moderate drinking is their being mild cases (i.e., having fewer lifetime alcohol-related problems than other alcoholics). Factors pertinent in assessing discrepancies between the various studies are discussed.