Glossopharyngeal neuralgia associated with cardiac syncope: long term treatment with permanent pacing and carbamazepine

Glossopharyngeal neuralgia associated with cardiac syncope developed in a 53 year old man. Symptoms were controlled with temporary and permanent transvenous pacing and carbamazepine.     

Canthaxanthin induces apoptosis in human cancer cell lines

To investigate the possibility that canthaxanthin inhibits cancer cell growth by inducing apoptosis, human WiDr colon adenocarcinoma and SK- MEL-2 melanoma cells were treated with two different doses of the carotenoid for 48 h. Canthaxanthin was incorporated and/or associated to cells. The treatment with the carotenoid caused growth inhibition in both cell types. Concomitantly, apoptosis was induced. Increasing time of exposure and carotenoid concentration, this effect was more pronounced. At 48 h, the percentages of apoptotic cells were 13 and 15, using 1 microM canthaxanthin, and 18 and 20, using 10 microM canthaxanthin in WiDr and SK-MEL-2 cells, respectively. This study represents the first demonstration that canthaxanthin is able to induce apoptosis in tumour cells.      

Use of growth-stimulatory hormones to improve the in vitro therapeutic index of doxorubicin for human breast tumors

Tumor-specific growth factors that increase the proliferative rate of tumor cells should, in theory, enhance the efficacy of cytotoxic drugs that have cell-cycle-dependent activity. To test this hypothesis, we measured the cytotoxicity of doxorubicin for clonogenic breast tumor cells in the presence and the absence of hormones that stimulate their in vitro growth (17 beta-estradiol, epidermal growth factor, hydrocortisone, and insulin). These growth factors increased the sensitivity to doxorubicin of the clonogenic cell populations from 20 of 25 breast tumors. Their effect was greatest on tumors from hormone-responsive patients. In contrast, these hormones increased the clonogenicity and sensitivity to doxorubicin of bone marrow progenitor cells to a much lesser degree. Hence, under the effect of these growth factors, the in vitro therapeutic index of doxorubicin improved for most of the tumors tested, while tamoxifen citrate, a tumor growth-inhibitory hormone, had the opposite effect. We conclude that tumor tissue-specific growth-stimulatory hormones can improve the in vitro efficacy of cell cycle-active anticancer drugs.     

Hypertension control in two Canadian communities: evidence for better treatment and overlabelling

We evaluated the prevalence and control of hypertension in two Canadian cities without university medical centre facilities. A stratified multistage probability sample was selected, and we interviewed 6258 adults between the ages of 30 and 69 inclusive. Blood pressure measurements were obtained during home interviews. Up to two further visits were made to people with untreated blood pressure elevation. By a diagnostic criterion of 90 mmHg, the hypertension prevalence was 114/1000. Six per cent of the hypertensives were undetected, 6% detected but untreated, 17% treated but uncontrolled and 70% were being treated and controlled. Control was better in females and older subjects. These findings show no disadvantages to hypertensives living away from university medical centres. We found a hypertension prevalence of 143/1000 among people who reported being diagnosed as hypertensive but who had normal blood pressure while not on medication. These results suggest a problem with over-labelling of hypertensives.     

Blood cyclosporin concentrations and renal allograft dysfunction

Forty nine renal allograft recipients taking oral cyclosporin suffered 76 episodes of renal dysfunction within six months of transplantation. These episodes were diagnosed as graft rejection or cyclosporin induced nephrotoxicity on the basis of histological findings in allograft biopsy specimens and the response to treatment. Mean predose blood cyclosporin concentrations measured by radioimmunoassay during the week before the onset of renal dysfunction were significantly higher when the cause was cyclosporin toxicity rather than graft rejection (392 v 741 nmol/l (471 v 891 ng/ml). During this period there was a significant association between both the frequency of measurements above 666 nmol/l (800 ng/ml) and the diagnosis of toxicity and the frequency of measurements below 333 nmol/l (400 ng/ml) and the diagnosis of allograft rejection. Cyclosporin measurements made at the time of biopsy and reference to the highest or lowest concentrations measured during the week preceding biopsy were of less value in distinguishing between the two groups. Despite lacking specificity for the parent compound, the radioimmunoassay used produced results which were of clinical value in optimising cyclosporin treatment.     

Kinetics of digoxin and anti-digoxin antibody fragments during treatment of digoxin toxicity.

Anti-digoxin antibody fragments (ADAF, 80 mg) were infused intravenously to successfully treat severe digoxin toxicity in an 82 year old woman. During treatment, total and free digoxin were determined using an Abbot TDX analyser and an ultrafiltration technique. ADAF were measured by an enzyme-linked immunosorbent assay. By 1 h after ADAF, total serum digoxin concentrations had risen 12-fold from a pretreatment level of 15.4 nmol l-1 but free digoxin fell from 10 to 0.1 nmol l-1, indicating greater than 99.9% digoxin binding to ADAF. However, the low free levels had rebounded to 7.7 nmol l-1 by 12 h, but despite this rise the patient's condition had improved. A serum ADAF/digoxin molar ratio of around five was associated with the low concentration of free digoxin at 1 h, while at later times with ratios roughly between 3 and 4, the free digoxin concentrations ranged between 2.0 and 7.7 nmol l-1. ADAF were mainly confined to the plasma during the first hour, but subsequently distributed into an apparent volume of 193 ml kg-1. The elimination half-lives of ADAF and total digoxin were 96 and 55 h, respectively. More than 50% of the estimated digoxin load had been excreted in the urine by 5 days; for ADAF the equivalent figure was only about 3%. Renal and/or bacterial degradation may have contributed to the low detection of urinary ADAF.