Influence of menstrual cycle, parity and oral contraceptive use on steroid hormone receptors in normal breast.

Steroid receptor was assessed immunohistochemically in 158 samples of normal breast for variation through the menstrual cycle. Patterns and intensity of reaction were used in a semi-quantitative scoring system to examine the influence of cycle phase, cycle type, parity and age. The changes in oestrogen receptor for natural cycle and oral contraceptive (OC) cycles indicated down-regulation by progestins. Progesterone receptor did not vary significantly in natural cycles, but increased steadily through OC cycles. This study provides strong evidence that both oestrogen and progesterone influence breast epithelium, but dissimilarities from the endometrium are apparent. The interval since pregnancy had a significant negative effect on frequency and score of oestrogen receptor and score of progesterone receptor. Multivariate analysis established the phase of cycle and OC use as independent significant influences on oestrogen receptor. The interval since pregnancy was an independent significant factor for both oestrogen and progesterone receptor presence.     

The epidemiology of myasthenia gravis in central and western Virginia.

We conducted a study of the epidemiology of myasthenia gravis (MG) in four locations in central and western Virginia from 1970 through 1984. The population surveyed was 555,851 in 1984. A total of 73 new cases of MG occurred during the survey period, producing an overall average annual incidence rate of 9.1 per million. The point prevalence rate in 1980 was 13.4 per 100,000, and in 1984 it was 14.2. Approximately 15% of the population was black, and we found that incidence and prevalence rates for the black population were higher than the corresponding white population. When the population was subdivided into <50 and 50+ age groups, the incidence and prevalence were significantly higher in the older group. The rates we report here are higher than rates reported from any other locality. The reasons for the higher rates include optimal case identification, survey of a population with a higher incidence, and increasing aging of the population.     

The severity of airways obstruction as a determinant of treatment response in COPD

Guidelines recommend that patients with COPD are stratified arbitrarily by baseline severity (FEV₁) to decide when to initiate combination treatment with a long-acting β₂-agonist and an inhaled corticosteroid. Assessment of baseline FEV₁ as a continuous variable may provide a more reliable prediction of treatment effects. Patients from a 1-year, parallel-group, randomized controlled trial comparing 50 μg salmeterol (Sal), 500 μg fluticasone propionate (FP), the combination (Sal/FP) and placebo, (bid), were categorized post hoc into FEV₁ <50% and FEV₁ ≥50% predicted subgroups (n=949/513 respectively). Treatment effects on clinical outcomes – lung function, exacerbations, health status, diary card symptoms, and adverse events – were investigated. Treatment responses based on a pre-specified analysis explored treatment differences by severity as a continuous variable. Lung function improved with active treatment irrespective of FEV₁; Sal/FP had greatest effect. This improvement appeared additive in milder disease; synergistic in severe disease. Active therapy significantly reduced exacerbation rate in patients with FEV₁ <50% predicted, not in milder disease. Health status and breathlessness improved with Sal/FP irrespective of baseline FEV₁; adverse events were similar across subgroups. The spirometric response to Sal/FP varied with baseline FEV₁, and clinical benefits were not restricted to patients with severe disease. These data have implications for COPD management decisions, suggesting that arbitrary stratifications of baseline severity are not necessarily indicative of treatment efficacy and that the benefits of assessing baseline severity as a continuous variable should be assessed in future trials.     

Efficacy and tolerability of norfloxacin vs. ciprofloxacin in complicated urinary tract infection.

This prospective, open, randomized clinical study compared the efficacy and tolerability of norfloxacin and ciprofloxacin in adult patients with complicated urinary tract infection, defined as infection in the presence of an underlying anatomic or functional abnormality of the urinary tract. Seventy-two patients were randomized, 37 received norfloxacin (400 mg orally twice daily for 10-21 days) and 35 received ciprofloxacin (500 mg orally every 12 hours for 14-21 days). Patients were clinically assessed, and urine cultures were obtained following two to four days of therapy, and five to nine days and four to six weeks after discontinuation of therapy. Seventy-two percent of the norfloxacin group and 79 percent of the ciprofloxacin group were considered cured. This difference was not significant. One failure of norfloxacin therapy was associated with the emergence of resistant Pseudomonas aeruginosa. Following norfloxacin therapy, in 2 patients superinfections developed with resistant organisms (Staphylococcus epidermidis [1] and Pseudomonas maltophilia [1]). Twelve patients, 6 in each group, experienced adverse reactions, which were considered related to the study drug therapy in only four instances. Our results indicated comparable efficacy and tolerability of norfloxacin and ciprofloxacin in the treatment of complicated urinary tract infection in adults.     

Recovery from depression after electroconvulsive therapy is accompanied by evidence of increased tetrahydrobiopterin-dependent hydroxylation

Serum phenylalanine and tyrosine levels were measured in 26 patients with severe depression before and after receiving electroconvulsive therapy. The phenylalanine:tyrosine [P:T] ratio declined significantly for those responding to treatment but not for nonresponders. These findings are discussed in relation to tetrahydrobiopterin, the essential cofactor for the formation of noradrenaline, dopamine and serotonin and the hydroxylation of phenylalanine to tyrosine.     

Evaluation of a respiratory rate monitor in postsurgical patients.

STUDY OBJECTIVE: To evaluate the clinical use of a cardiorespiratory rate monitor in patients receiving epidural opioids following major surgery. DESIGN: For 6 hours during the night following surgery, patients were continuously monitored with a cardiorespiratory rate monitor and a pulse oximeter, as well as by an in-room observer. SETTING: Postoperative surgical ward at a university hospital. PATIENTS: Eight ASA physical status I and II patients ages 30 to 76 years. INTERVENTIONS: Any bradypneic, hypoxemic, bradycardic, or tachycardic event was confirmed by the observer and recorded. MEASUREMENTS AND MAIN RESULTS: The cardiorespiratory rate monitor accurately identified true bradypneic episodes in five of the eight patients. There were no false-positive alarms. The respiratory rate monitor and the pulse oximeter identified one episode of hypoxemia. There were no episodes of bradycardia or tachycardia. CONCLUSIONS: The cardiorespiratory rate monitor is useful in patients at risk for bradypnea following surgery.     

NLA-1: a 2-nitroimidazole radiosensitizer targeted to DNA by intercalation.

Targeting of electron affinic radiosensitizers to DNA via reversible non-covalent intercalative binding has potential for increasing sensitizer concentrations locally at the DNA target while decreasing accessibility to reductases responsible for bioactivation and cytotoxicity. We have prepared an DNA-targeted acridine-linked 2-nitroimidazole (NLA-1) as an example of such a compound. NLA-1 binds reversibly to DNA with an affinity similar to 9-aminoacridine, and is approximately 1000 times more potent than MISO as a cytotoxin, despite a similar reduction potential. It shows less enhancement of cytotoxicity under hypoxia (5- to 6-fold) than does MISO (approximately 11-fold), but is a potent hypoxia-selective radiosensitizer in AA8 cells with a concentration for an enhancement ratio of 1.6 (C1.6) of 9 microM. The mean intracellular concentration at the C1.6 is 400 microM, on which basis its potency is about twice that of MISO. The in vitro therapeutic index (aerobic cytotoxic potency/hypoxic C1.6) of NLA-1 is approximately 6-fold lower than that for MISO. NLA-1 lacks radiosensitizing activity against SCCVII or EMT6 tumors in vivo at the maximum tolerated dose (MTD) of 100 mumol.kg-1.