Anaemia is an independent predictive marker for clinical prognosis in HIV-infected patients from across Europe. EuroSIDA study group.

OBJECTIVES: To describe changes in haemoglobin over time and to determine the joint prognostic value of the current haemoglobin, CD4 lymphocyte count and viral load among patients from across Europe. PATIENTS: The analysis included 6725 patients from EuroSIDA, an observational, prospective cohort of patients with HIV from across Europe. METHODS: Normal haemoglobin was defined as haemoglobin greater than 14 g/dl for men and 12 g/dl for women; mild anaemia was 8-14 g/dl for men and 8-12 g/dl for women; severe anaemia was defined as less than 8 g/dl for both males and females. Linear regression techniques were used to estimate the annual change in haemoglobin; standard survival techniques were used to describe disease progression and risk of death. RESULTS: At recruitment to the study, 40.4% had normal levels of haemoglobin, 58.2% had mild anaemia and 1.4% had severe anaemia. At 12 months after recruitment, the proportion of patients estimated to have died was 3.1% [95% confidence interval (CI) 2.3-3.9] for patients without anaemia, 15.9% for patients with mild anaemia (95% CI 14.5-17.2) and 40.8% for patients with severe anaemia (95% CI 27.9-53.6; P < 0.0001). In a multivariate, time-updated Cox proportional hazards model, adjusted for demographic factors, AIDS status and each antiretroviral treatment as time-dependent covariates, a 1 g/dl decrease in the latest haemoglobin level increased the hazard of death by 57% [relative hazard (RH) 1.57; 95% CI 1.41-1.75; P < 0.0001], a 50% drop in the most recent CD4 lymphocyte count increased the hazard by 51% (RH 1.51; 95% CI 1.35-1.70; P < 0.0001) and a log increase in the latest viral load increased the hazard by 37% (RH 1.37; 95% CI 1.15-1.63; P = 0.0005). CONCLUSIONS: Severe anaemia occurred infrequently among these patients but was associated with a much faster rate of disease progression. Among patients with similar CD4 lymphocyte counts and viral load, the latest value of haemoglobin was a strong independent prognostic marker for death.     

Myocardial dysfunction in donor hearts. A possible etiology.

BACKGROUND: Potential cardiac donors show various degrees of myocardial dysfunction, and the most severely affected hearts are unsuitable for transplantation. The cause of this acute heart failure is poorly understood. We investigated whether alterations in calcium-handling proteins, beta-adrenoceptor density, or the inhibitory G protein Gialpha could account for this phenomenon in unused donor hearts (n=4 to 8). We compared these with end-stage failing hearts (n=14 to 16) and nonfailing hearts (n=3 to 12). METHODS AND RESULTS: Myocardial samples were obtained from unused donor hearts displaying ejection fractions <30%. Both trabeculae and isolated myocytes responded as poorly as those from the group of failing hearts to increasing stimulation frequency with regard to inotropic function in vitro. Immunodetectable abundance of sarcoplasmic reticulum calcium-ATPase and sodium calcium exchanger were greater (177%; P<0.01) and smaller (29%; P<0.01), respectively, in the unused donor hearts relative to the failing group, which suggests that alterations of these proteins are not a common cause of contractile dysfunction in the 2 groups. Myocytes from the unused donor group were desensitized to isoprenaline to a similar degree as those from the failing heart group. However, beta-adrenoceptor density was reduced in the failing (P<0.001) but not in the unused donor heart group (P=0.37) relative to the nonfailing heart group (n=5). Gialpha activity was increased in samples from unused donor and failing hearts relative to nonfailing hearts (P<0.05). CONCLUSIONS: Increased activity of the inhibitory G protein Gialpha is a significant contributory factor for impaired contractility in these acutely failing donor hearts.     

Femtosecond dynamics of DNA-mediated electron transfer

Diverse biophysical and biochemical studies have sought to understand electron transfer (ET) in DNA in part because of its importance to DNA damage and its repair. However, the dynamics and mechanisms of the elementary processes of ET in this medium are not fully understood and have been heavily debated. Two fundamental issues are the distance over which charge is transported and the time-scale on which the transport through the pi-stack of the DNA base pairs may occur. With femtosecond resolution, we report direct observation in DNA of ultrafast ET, initiated by excitation of tethered ethidium (E), the intercalated electron acceptor (A); the electron donor (D) is 7-deazaguanine (Z), a modified base, placed at different, fixed distances from A. The ultrafast ET between these reactants in DNA has been observed with time constants of 5 ps and 75 ps and was found to be essentially independent of the D-A separation (10-17 A). However, the ET efficiency does depend on the D-A distance. The 5-ps decay corresponds to direct ET observed from 7-deazaguanine but not guanine to E. From measurements of orientation anisotropies, we conclude that the slower 75-ps process requires the reorientation of E before ET, similar to E/nucleotide complexes in water. These results reveal the nature of ultrafast ET and its mechanism: in DNA, ET cannot be described as in proteins simply by a phenomenological parameter, beta. Instead, the involvement of the base pairs controls the time scale and the degree of coherent transport.     

Innate Immunity: The Bridge between Adaptive Immunity and Inflammation,December 17, 1998, New York Academy of Sciences,New York,NY, USA

Inflammation Research -     

A survey of 2,851 patients with hemochromatosis: symptoms and response to treatment.

PURPOSE: Hemochromatosis is a genetic disorder of iron absorption that affects 5 per 1,000 persons and is associated with reduced health and quality of life. We sought to determine the type and frequency of symptoms that patients experienced before the diagnosis and the treatments that they received. METHODS: We mailed a questionnaire to 3,562 patients with hemochromatosis who were located using patient advocacy groups, physicians, blood centers, newsletters, and the Internet. RESULTS: Of the 2,851 respondents, 99% were white and 62% were men. Circumstances that led to diagnosis of hemochromatosis included symptoms (35%), an abnormal laboratory test (45%), and diagnosis of a family member with hemochromatosis (20%). The mean (+/- SD) age of symptom onset was 41 +/- 14 years. Symptoms had been present for an average of 10 +/- 10 years before the diagnosis was made. Among the 58% of patients with symptoms, 65% had physician-diagnosed arthritis and 52% had liver disease. The most common and troublesome symptoms were extreme fatigue (46%), arthralgia (44%), and loss of libido (26%). Physician instructions to patients included treatment with phlebotomy (90%), testing family members (75%), and avoiding iron supplements (65%). CONCLUSIONS: The diagnosis of hemochromatosis in most patients was delayed. Physician education is needed to increase the detection of patients with the disease and to improve its management.     

Microbiological and molecular diagnosis of deep localized cutaneous infection with Trichophyton mentagrophytes

We describe a healthy young woman with a localized deep dermal infection on the right side of the chest wall. It was caused by the dermatophyte Trichophyton mentagrophytes, and resolved after two pulses of oral itraconazole 200 mg twice daily for 1 week. As cultural and microscopic features did not enable a precise identification of the fungus, molecular investigation was undertaken. Patterns of HaeIII restriction digests of genomic DNA from the culture matched those from Arthroderma incurvata and A. benhamiae, which is the teleomorph of T. mentagrophytes var. mentagrophytes.     

Reversal of rapid visual loss in a patient with an imaging stable diffuse glioma following frontal lobectomy

A case of rapid painless visual deterioration without increase in tumor size in a patient with a corpus callosum glioma is presented. Visual acuity and fields improved following a frontal lobectomy.     

Evaluation of soy phytoestrogens for the treatment of hot flashes in breast cancer survivors: A North Central Cancer Treatment Group Trial.

PURPOSE: Hot flashes represent a significant clinical problem for some breast cancer survivors. Safe, effective treatment is needed for this prominent clinical problem. Although it has been shown that estrogen or progesterone replacement therapy can alleviate this problem, there are continued safety concerns regarding the use of hormonal therapies in these women. Based on anecdotal information, we hypothesized that soy-derived phytoestrogens, weak estrogen-like substances in the soybean that demonstrate estrogen agonist and/or antagonist effects when they bind to estrogen receptors, could alleviate hot flashes. This current trial was designed to investigate this hypothesis. PATIENTS AND METHODS: This double-blind clinical trial involved breast cancer survivors with substantial hot flashes. After randomization, patients underwent a 1-week baseline period with no therapy. This was followed by 4 weeks of either soy tablets or placebo. The patients then crossed over to the opposite arm in a double-blind manner for the last 4 weeks. Patients completed a daily questionnaire documenting hot flash frequency, intensity, and perceived side effects. RESULTS: Of the 177 women who were randomized and started the study substance, 155 (88%) provided useable data over the first 5 weeks; 149 provided usable data over the entire 9 weeks. There was no suggestion that the soy product was more effective in reducing hot flashes than the placebo. At study completion, patients preferred the soy product 33% of the time, the placebo 37% of the time, and neither substance 31% of the time. No toxicity was observed. CONCLUSION: The soy product did not alleviate hot flashes in breast cancer survivors.     

Selective serotonin re-uptake inhibitors in the treatment of self-injurious behaviour in adults with mental retardation

Self-injurious behaviour (SIB) amongst people with learning disabilities is very common and is often difficult to treat. This study supports the theory that serotonin is involved in the development of SIB in these individuals. Twelve patients suffering from mild to severe mental retardation were treated with either fluoxetine or fluvoxamine. Ten of them showed marked improvement of their SIB, clinically as well as objectively (according to scores on the adaptive behaviour scale). The treatment had to be discontinued in the other two patients because of the development of severe adverse effects to the medication. The results of this study are therefore in line with previous studies showing the effectivity of Selective Serotonin Re-uptake Inhibitors in the treatment of SIB in mentally retarded individuals. © 1998 John Wiley & Sons, Ltd.     

Estimating surgical volume—outcome relationships applying survival models: accounting for frailty and hospital fixed effects

This paper investigates the surgical volume–outcome relationship for patients undergoing hip fracture surgery in Quebec between 1991 and 1993. Using a duration model with multiple destinations which accounts for observed and unobserved (by the researcher) patient characteristics, our initial estimates show that higher surgical volume is associated with a higher conditional probability of live discharge from the hospital. However, these results reflect differences between hospitals rather than differences within hospitals over time: when we also control for differences between hospitals that are fixed over time, hospitals performing more surgeries in period t + 1 than in period t experience no significant change in outcomes, as would be predicted by the ‘practice makes perfect’ hypothesis. The volume–outcome relationship for hip fracture patients thus appears to reflect quality differences between high and low volume hospitals. © 1997 John Wiley & Sons, Ltd.