Effect of calcium replacement on the hemodynamic changes associated with high dose interleukin-2 therapy.

Administration of high-dose IL-2 results in hemodynamic changes that are similar to those seen in septic shock. These include a decrease in systemic vascular resistance (SVR) with a resultant drop in mean arterial pressure (MAP). Hypocalcemia is seen in septic shock and with IL-2 administration. Calcium replacement in septic shock has been reported to result in hemodynamic improvement; we therefore administered calcium to patients receiving high dose IL-2 to correct ionized hypocalcemia. Five consecutive patients underwent invasive hemodynamic monitoring before and during IL-2 administration. Calcium chloride was administered to correct ionized hypocalcemia, and hemodynamic parameters were monitored before and after calcium administration. Ionized hypocalcemia was associated with an elevation in parathyroid hormone levels. There was no toxicity related to the administration of calcium. An improvement in the MAP and SVR was seen early and late (after a dose of IL-2 was held) in the IL-2 treatment cycle; there were minimal effects at other points. Because of the potential hemodynamic benefit of calcium replacement, we recommend that ionized hypocalcemia be corrected in patients receiving high-dose IL-2.     

Early detection of colorectal cancer: a profile of current practice.

This study examines the prevalence of colorectal cancer screening among individuals in the general community. The survey was undertaken as part of a large scale general population survey of health practices and attitudes. A sample of 1090 people aged 40 years and over with no previous history of colorectal cancer or other predisposing condition was interviewed. Only 56% of this group reported that they regularly checked their bowel movements, the toilet bowl, or the toilet paper for signs of rectal bleeding. Only 13% could recall a doctor ever advising them to check for rectal bleeding; and 21% could recall a doctor asking them if they had ever noticed blood in their bowel movements. More involved practitioner-based procedures, such as digital rectal examination, fecal occult blood testing, endoscopy, and barium enema, were reported by only a minority of participants. Analysis of screening rates in the 9.3% of people who reported a family history of colorectal cancer revealed that this higher risk group was no more likely to be screened than those at average risk.     

Detection of alcohol-related problems in general practice.

While primary care has considerable potential as a site for detecting and intervening for alcohol-related problems, few doctors currently identify these problems. The judgments of eight primary care physicians about alcohol-related problems in 371 of their patients were compared with the patients' responses to the Short Michigan Alcoholism Screening Test (SMAST) and the CAGE. The CAGE classified 11.4% of the patients as alcoholics and the SMAST identified 23.9% as probable alcoholics. However, the doctors identified only a small proportion (7.0%) of their patients as having any level of alcohol-related problem. The doctors did not identify 65.0% of CAGE-defined alcoholics and 82.3% of those patients classified by the SMAST as probable alcoholics. The discrepancy between primary care physician's judgments and the SMAST and CAGE may be attributable to the doctor's failure to identify patients with alcohol-related problems. An alternative explanation is that the SMAST and CAGE are inappropriate screening tools for use in Australian primary care. The findings are discussed in terms of the implications for training doctors and for the development of better measures of alcohol-related problems for use within a primary care context.     

Teriparatide in the management of osteoporosis

Fracture of the hip is frequently a catastrophic event in the elderly, often resulting in death within a year and of the survivors, few regain pre-fracture quality of life. Although less appreciated, fractures of the spine result in significant morbidity and are also associated with increased mortality compared with individuals without a fracture. In recent years there has been an explosion in the development of new drugs for the treatment of osteoporosis. Recombinant human parathyroid hormone (1–34) (20 μg/day) is a recent addition to this armamentarium with a novel mechanism of action, which was approved by the US FDA for the treatment of post-menopausal osteoporosis and male osteoporosis secondary to hypogonadism in November 2002. It is the first osteoporosis treatment that leads to the formation of new bone with architecture similar to normal bone. Intense efforts have been made to understand the effect of teriparatide on antiresorptive therapy and vice versa. Although these relationships are not completely understood, the results of recent studies allow clinicians to begin to optimize therapeutic gains in bone mineral density and improve anti-fracture efficacy.     

Dose dependent effects of S-20098, a melatonin agonist,on direction of re-entrainment of rat circadian activity rhythms

The chronobiotic properties of melatonin are well documented. For example, following an 8-h phase advance of the light-dark cycle daily injections of melatonin administered at the pre-shift dark onset alter the direction of re-entrainment of rat activity rhythms. Using this 8-h phase advance paradigm, the effects of the melatonin agonist S-20098 (1 mg/kg and 3 mg/kg) on the rat circadian system were compared with those of melatonin. S-20098 altered the direction of reentrainment in the same manner as melatonin. A study using lower doses of S-20098 showed that the effect on direction of re-entrainment was dose-dependent, with 100% of rats responding at a dose of 100 µg/kg. S-20098 may, therefore, have therapeutic potential as a chronobiotic in the treatment of circadian disorders in humans.