ON RHODOPSIN IN SOLUTION

1. The properties of rhodopsin in solution have been examined in preparations from marine fishes, frogs, and mammals. 2. The bleaching of neutral rhodopsin in solution includes a photic and at least three thermal ("dark") processes. Thermal reactions account for approximately half the total fall in extinction at 500 mµ. 3. Bleaching has been investigated at various pH''s from 3.9 to about 11. With increase in pH the velocity of the thermal components increases rapidly. Though the spectrum of rhodopsin itself is scarcely affected by change in pH, the spectra of all product-mixtures following irradiation are highly pH-labile. 4. The spectrum of pure rhodopsin—or of the rhodopsin chromophore—is fixed within narrow limits. The extinction at 400 mµ lies between 0.20 to 0.32 of that at the maximum. 5. Within the limitations of available data, the spectrum of pure rhodopsin corresponds in form and position with the spectral sensitivity of human rod vision, computed at the retinal surface. 6. The nature of bleaching of rhodopsin in solution, its kinetics, and its significance in the retinal cycle are discussed.     

Randomised trial of two-drug and four-drug maintenance chemotherapy in advanced or recurrent Hodgkin's disease. Medical Research Council's working party on lymphomas.

Between 1970 and 1975, 108 patients who presented with advanced or recurrent Hodgkin''s disease and were free of disease after six courses of chemotherapy with mustine, vinblastine, procarbazine, and prednisone (MVPP) were allocated at random to one of two regiments of maintenance treatment: either intermittent treatment with vinblastine and procarbazine or intermittent treatment with MVPP. After a median follow-up period of nearly five years there was no significant difference between the two groups in either the rate of relapse or death rate. Six of the 55 patients given the two-drug regimen died compared with 10 of the 53 given the four-drug regimen. The four-drug required hospital attendance and was less agreeable than the two-drug regimen. The efficacy of maintenance chemotherapy with the two-drug regimen was no less than that with the four-drug regimen, but the two-drug regimen had several practical advantages.     

Cervical antibodies in patients with oral herpes simplex virus type 1 (HSV-1) infection: local anamnestic responses after genital HSV-2 infection.

Herpes simplex virus (HSV)-specific immunoglobulin A, immunoglobulin G, and secretory-component-containing immunoglobulins were identified in cervical and salivary secretions from six subjects with oral HSV type 1 (HSV-1) infections. Anamnestic cervical and salivary antibody responses were detected in two HSV-1-seropositive women with newly acquired genital HSV-2 infections. These data implicate the common mucosal immune system in antibody responses to HSV.     

How effective is nicotine replacement therapy in helping people to stop smoking?

OBJECTIVE--To assess the efficacy of nicotine replacement therapy in helping people to stop smoking. DESIGN--Analysis of the results of 28 randomised trials of nicotine 2 mg chewing gum, six trials of nicotine 4 mg chewing gum, and six trials of nicotine transdermal patch. SUBJECTS AND SETTING--Subjects were self referred (responding to advertisements or attending anti-smoking clinics) in 20 trials and invited (general practice or hospital patients) in 20. Therapists in self referred trials were generally experienced in helping people stop smoking but not in invited trials. MAIN OUTCOME MEASURE--Efficacy was defined as difference in percentages of treated and control subjects who had stopped smoking at one year. RESULTS--Efficacy was highly significant (P < 0.001) for both gum and patch. Nicotine 2 mg chewing gum had an overall efficacy of 6% (95% confidence interval 4% to 8%), greater in self referred subjects than in invited subjects (11% v 3%). Efficacy depended on the extent of dependence on nicotine as assessed by a simple questionnaire; it was 16% (7% to 25%) in "high dependence" smokers, but in "low dependence" smokers there was no significant effect. The 4 mg gum was effective in about one third of "high dependence" smokers. The efficacy of the nicotine patch (9% (6% to 13%) overall) was less strongly related to nicotine dependence, perhaps because the patch cannot deliver a bolus of nicotine to satisfy craving. CONCLUSIONS--Both gum and patch are effective aids to help nicotine dependent smokers who seek help in stopping. Among the most highly nicotine dependent smokers (those craving a cigarette on waking) the 4 mg gum is the most effective form of replacement therapy; it could enable one third to stop. In less highly dependent smokers the different preparations are comparable in their efficacy but the patch offers greater convenience and minimal need for instruction in its use. Overall, nicotine replacement therapy could enable about 15% of smokers who seek help in stopping smoking to give up the habit.     

Use of personal medical records for research purposes.

The established practice of doctors using medical records for research purposes is threatened by the recent proposed guidelines from the Department of Health, the BMA, and the European Commission. The European Commission has proposed that explicit consent should be obtained from each patient before his or her medical records can be used; the proposals from the Department of Health and the BMA would require all research that needs access to personal medical records to be submitted to an ethics committee. We believe that these proposals would seriously impair an entire category of research and suggest therefore that another set of guidelines, proposed by a Royal College of Physicians'' working group, should be used to modify the proposals. The guidelines of the working group encourage the use of medical records for research and ensure that such use can be made in a confidential manner without causing harm.     

Prospective study of effect of switching from cigarettes to pipes or cigars on mortality from three smoking related diseases.

OBJECTIVE: To estimate the extent to which cigarette smokers who switch to cigars or pipes alter their risk of dying of three-smoking related diseases-lung cancer, ischaemic heart disease, and chronic obstructive lung disease. DESIGN: A prospective study of 21520 men aged 35-64 years when recruited in 1975-82 with detailed history of smoking and measurement of carboxyhaemoglobin. MAIN OUTCOME MEASURES: Notification of deaths (to 1993) classified by cause. RESULTS: Pipe and cigar smokers who had switched from cigarettes over 20 years before entry to the study smoked less tobacco than cigarette smokers (8.1 g/day v 20 g/day), but they had the same consumption as pipe and cigar smokers who had never smoked cigarettes (8.1 g) and had higher carboxyhaemoglobin saturations (1.2% v 1.0%, P < 0.001), indicating that they inhaled tobacco smoke to a greater extent. They had a 51% higher risk of dying of the three smoking related diseases than pipe or cigar smokers who had never smoked cigarettes (relative risk 1.51; 95% confidence interval 0.96 to 2.38), a 68% higher risk than lifelong non-smokers (1.68; 1.16 to 2.45), a 57% higher risk than former cigarette smokers who gave up smoking over 20 years before entry (1.57; 1.04 to 2.38), and a 46% lower risk than continuing cigarette smokers (0.54; 0.38 to 0.77). CONCLUSION: Cigarette smokers who have difficulty in giving up smoking altogether are better off changing to cigars or pipes than continuing to smoke cigarettes. Much of the effect is due to the reduction in the quantity of tobacco smoked, and some is due to inhaling less. Men who switch do not, however, achieve the lower risk of pipe and cigar smokers who have never smoked cigarettes. All pipe and cigar smokers have a greater risk of lung cancer than lifelong non-smokers or former smokers.     

Placebo controlled trial of nicotine chewing gum in general practice.

Of 2110 adult cigarette smokers originally recruited to a study of the effect of antismoking advice in general practice, 429 who reported at follow up after one year that they had tried unsuccessfully to stop smoking were offered "a special antismoking chewing gum," either nicotine gum or a placebo gum, in a double blind study. Of 200 who were willing to try the gum, 101 were randomly allocated to the nicotine gum and 99 to the placebo gum. They were followed up at six months by an unannounced home visit, at which they were interviewed and asked to provide a breath sample for analysis of carbon monoxide. Twenty five claimed that they had stopped smoking, but, of them, seven exhaled levels of carbon monoxide indicative of continued smoking. Of the 18 in whom giving up smoking was validated, 10 had received active gum and eight placebo gum, a difference which was not significant (odds in favour of nicotine gum = 1.25, 95% confidence limits 0.47-3.31). The value of nicotine chewing gum, if any, can be quite small when it is used in general practice.     

Inhaling and lung cancer: an anomaly explained.

An objective index of inhaling cigarette smoke based on carboxyhaemoglobin concentrations and the carbon monoxide yields of cigarettes was used to investigate possible systematic differences in the extent of inhaling among light and heavy smokers when classified according to their self described inhaling habits. A total of 2108 men who smoked cigarettes were studied. Heavy smokers (20 or more cigarettes a day) had a higher average inhaling index than light smokers (fewer than 20 cigarettes a day) both among those who said that they inhaled and among those who said that they did not. This observation, together with indirect evidence that heavy smokers who inhale deeply may to some extent avoid depositing smoke condensate on their main bronchial epithelium, explains a hitherto unresolved anomaly--namely, that the risk of lung cancer is less among heavy cigarette smokers who say that they inhale than it is among those who say that they do not inhale.     

Mycobacterium tuberculosis Bacteremia in a Cohort of HIV-Infected Patients Hospitalized with Severe Sepsis in Uganda–High Frequency,Low Clinical Sand Derivation of a Clinical Prediction Score

Background

When manifested as Mycobacterium tuberculosis (MTB) bacteremia, disseminated MTB infection clinically mimics other serious blood stream infections often hindering early diagnosis and initiation of potentially life-saving anti-tuberculosis therapy. In a cohort of hospitalized HIV-infected Ugandan patients with severe sepsis, we report the frequency, management and outcomes of patients with MTB bacteremia and propose a risk score based on clinical predictors of MTB bacteremia.

Methods

We prospectively enrolled adult patients with severe sepsis at two Ugandan hospitals and obtained blood cultures for MTB identification. Multivariable logistic regression modeling was used to determine predictors of MTB bacteremia and to inform the stratification of patients into MTB bacteremia risk categories based on relevant patient characteristics.

Results

Among 368 HIV-infected patients with a syndrome of severe sepsis, eighty-six (23%) had MTB bacteremia. Patients with MTB bacteremia had a significantly lower median CD4 count (17 vs 64 lymphocytes/mm³, p<0.001) and a higher 30-day mortality (53% vs 32%, p = 0.001) than patients without MTB bacteremia. A minority of patients with MTB bacteremia underwent standard MTB diagnostic testing (24%) or received empiric anti-tuberculosis therapy (15%). Independent factors associated with MTB bacteremia included male sex, increased heart rate, low CD4 count, absence of highly active anti-retroviral therapy, chief complaint of fever, low serum sodium and low hemoglobin. A risk score derived from a model containing these independent predictors had good predictive accuracy [area under the curve = 0.85, 95% CI 0.80–0.89].

Conclusions

Nearly 1 in 4 adult HIV-infected patients hospitalized with severe sepsis in 2 Ugandan hospitals had MTB bacteremia. Among patients in whom MTB was suspected, standard tests for diagnosing pulmonary MTB were inaccurate for correctly classifying patients with or without bloodstream MTB infection. A MTB bacteremia risk score can improve early diagnosis of MTB bacteremia particularly in settings with increased HIV and MTB co-infection.