Relationship of abdominal obesity with cardiovascular disease,diabetes and hyperlipidaemia in Spain

Objectives To evaluate the relevance of obesity and abdominal obesity in the prevalence of cardiovascular disease (CVD), diabetes mellitus, hyperlipidaemia and hypertension in primary care patients and to ascertain whether waist circumference (WC) measurement should be included in routine clinical practice in addition to body mass index (BMI). Methods As part of the IDEA study, primary care physicians from Spain recruited patients aged 18–80 years. WC and BMI and the presence of CVD, diabetes mellitus, hyperlipidaemia and hypertension were recorded. Finally, 17 980 were analysed. An age‐related increase in adiposity was observed. Overall 33% were obese by BMI, and 51% of subjects presented abdominal obesity by the National Cholesterol Education Program Adult Treatment Panel III (NCEP‐ATPIII) (WC > 102 cm for men and > 88 cm for women). Although there was a correlation between BMI and WC, they presented different distribution patterns. Women, but not men, with a high level of education, professional activity and smoking were associated with a lower WC. Abdominal obesity was significantly associated with CVD. Some subjects with abdominal obesity but lean by BMI, showed an increased prevalence of CVD and diabetes. Furthermore, abdominal obesity was strongly associated with dyslipidaemia and hypertension. Conclusions Half of the primary care patients studied showed abdominal obesity as measured by WC, whereas one‐third was obese by BMI. Abdominal obesity was strongly associated with CVD and diabetes, even in patients lean by BMI. WC should be included in the routine clinical practice in addition to BMI.     

Successful treatment of disseminated Fusarium infection in an immunocompromised child

We report the first know case of disseminated fungal infection due to Fusarium proliferatum in a bone marrow transplant recipient to our knowledge. Fusarium was cultured from the blood, a paranasal sinus, and necrotic skin lesions. The isolate was sensitive to amphotericin B and on further sensitivity testing, synergy was demonstrated using rifampin in combination with amphotericin B. The patient had this infection while she was receiving alternate-day amphotericin, rifampin, and 5-flucytosine (5-FC) therapy. The infection was documented within 48 h of discontinuing daily granulocyte transfusions, which she had received for 3 weeks. The 5-FC was discontinued when sensitivities showed the organism resistant. After 6 weeks of treatment she showed complete remission of the infection, although neutrophil counts remained below 0.25 X 10(9)/L. From this case and from a review of the literature, it appears that synergic antifungal agents combined with leukocyte transfusions may be beneficial in the successful treatment of fusariosis in the compromised host.     

Influence of an antagonist of slow-reacting substance of anaphylaxis on the cardiovascular manifestations of hypoxia in piglets

Leukotrienes have been implicated in the pathogenesis of hypoxic pulmonary hypertension in adult animals and in persistent pulmonary hypertension with accompanying hypoxemia in the neonate. In order to elucidate the role of leukotrienes in hypoxic pulmonary hypertension in a young animal model, the effects of a leukotriene antagonist, FPL 57231, were evaluated in anesthetized piglets. Cardiac output and vascular pressures were measured and pulmonary and systemic vascular resistances calculated prior to and during hypoxia. These measurements were compared during continued hypoxia between a control and treatment group which received FPL 57231. FPL 57231 infusion resulted in significant decreases in mean pulmonary artery pressure (p less than 0.04), pulmonary vascular resistance (p less than 0.01) and the ratio of pulmonary/systemic vascular resistance (p less than 0.01). Systemic vascular resistance fell approximately 25% from hypoxic baseline (p less than 0.01) while PVR decreased 54%. There were no differences between groups in mean systemic arterial pressure, cardiac output, pH, or PaCO2. In addition, pretreatment with FPL 57231 attenuated the hemodynamic response to hypoxia. These data suggest that leukotrienes may, in part, mediate hypoxic pulmonary vasoconstriction in piglets.     

Severe cutaneous vasculitis following intravenous infusion of gammaglobulin in a patient with type II mixed cryoglobulinemia

Intravenous infusion of gammaglobulins (IVIG) is one of the treatments of choice in patients with type II mixed cryoglobulinemia (MC). We describe the case of a patient with MC who suffered an adverse generalised reaction with severe cutaneous vasculitis accompanied by a sudden increase in cryocrit levels shortly after being treated with IVIG. When the same gammaglobulin preparation was added in vitro to a sample of the patient's serum, a strong increment in cryoglobulin precipitation and depletion of the monoclonal IgM peak resulted. We suggest that this simple method of studying the displacement of the precipitation reaction could help to predict the outcome of treatment and must be performed before starting IVIG in patients with MC.     

N-acetylcysteine potentiates the antihypertensive effect of ACE inhibitors in hypertensive patients

Sulfhydryl group donors, such as N-acetylcysteine (NAC), may enhance the antihypertensive effect of some drugs through a nitric oxide (NO) mechanism. It has been observed that the hypotensive effect of angiotensin-converting enzyme inhibitors (ACEIs) is, at least partially, mediated by NO. We performed a within patient crossover study with the aim to investigate the potential effect of NAC on the ACEI antihypertensive action, via an NO-dependent mechanism. We studied 18 smoker (> 10 years of habit and > 10 cigarettes daily) hypertensive patients (15 males and three females, aged 69 +/- 5 years) on ACEI therapy (11 captopril and seven enalapril). Patients were randomly allocated to two treatment arms. In one arm, the patients (n = 10) initially received the addition of NAC (600 mg t.i.d.) to the ACEI regimen. In the other group (n = 8), the patients remained only on ACEI. After 21 days, the therapeutic patterns were crossed. The first group received only ACEI, and the second group received ACEI and NAC and completed other 21-day treatment period. We evaluate the effect of NAC on each patient by ambulatory blood pressure monitoring (ABPM), performed at the end of each therapeutic regimen. A significant decrease in systolic and diastolic 24-h blood pressure (24 hBP) and daytime BP (dtBP) was achieved with the combination of ACEI and NAC (ACEI + NAC) when compared to the period with only ACEI: 24 hBP = 146.1 +/- 4.2 vs 137 +/- 3.1 (p < 0.05) and 89.2 +/- 2.8 vs 83.5 +/- 3.7mmHg (p = 0.01). DtBP: 149.7 +/- 5.6 vs 141 +/- 3.7 and 92.1 +/- 4 vs 86 +/- 3.2 (both, p < 0.05). No significant difference was observed in night-time BP (ntBP). The NAC effect was not statistically different for the two ACEIs. In conclusion, the addition of NAC to an ACEI potentiates its antihypertensive effect during 24hBP and dtBP in smoker hypertensives. This effect may be mediated by an NO-dependent mechanism, probably through the protective effect of NAC on NO oxidation.     

Reversible skeletal abnormalities in gamma-glutamyl transpeptidase-deficient mice

Gamma-glutamyl transpeptidase (GGT) is a widely distributed ectopeptidase responsible for the degradation of glutathione in the gamma-glutamyl cycle. This cycle is implicated in the metabolism of cysteine, and absence of GGT causes a severe intracellular decrease in this amino acid. GGT-deficient (GGT-/-) mice have multiple metabolic abnormalities and are dwarf. We show here that this latter phenotype is due to a decreased of the growth plate cartilage total height resulting from a proliferative defect of chondrocytes. In addition, analysis of vertebrae and tibiae of GGT-/- mice revealed a severe osteopenia. Histomorphometric studies showed that this low bone mass phenotype results from an increased osteoclast number and activity as well as from a marked decrease in osteoblast activity. Interestingly, neither osteoblasts, osteoclasts, nor chondrocytes express GGT, suggesting that the observed defects are secondary to other abnormalities. N-acetylcysteine supplementation has been shown to reverse the metabolic abnormalities of the GGT-/- mice and in particular to restore the level of IGF-1 and sex steroids in these mice. Consistent with these previous observations, N-acetylcysteine treatment of GGT-/- mice ameliorates their skeletal abnormalities by normalizing chondrocytes proliferation and osteoblastic function. In contrast, resorbtion parameters are only partially normalized in GGT-/- N-acetylcysteine-treated mice, suggesting that GGT regulates osteoclast biology at least partly independently of these hormones. These results establish the importance of cysteine metabolism for the regulation of bone remodeling and longitudinal growth.     

Management of peritoneal surface malignancy with cytoreductive surgery and perioperative intraperitoneal chemotherapy.

AIMS: A new treatment strategy combining maximal cytoreductive surgery for treatment of macroscopic disease and maximal perioperative intraperitoneal chemotherapy for residual microscopic disease, suggests that in a selected group of patients benefit is possible. The purpose of this study was to report our experience with this combined treatment and to identify the principal prognostic factors. METHODS: The study included 266 patients from 9 institutions operated on between July 1990 and July 2004. The median age was 55 years. RESULTS: The mortality rate was 7.8% and the morbidity rate 37.5%. The overall median survival was 13.7 months. Positive independent prognostic factors by multivariate analysis were gender, perioperative intraperitoneal chemotherapy and treatment by the second-look procedure. CONCLUSIONS: The therapeutic approach combining cytoreductive surgery with perioperative intraperitoneal chemotherapy achieved long-term survival in a selected group of patients with an acceptable morbidity and mortality.     

Tumour inmunology: How close to the target?

Strategies based on immunotherapy as a treatment of cancer have been applied clinically for over more than 100 years. However, only the advances produced in the past two decades which changed the understanding of how T lymphocytes recognise and destroy antigenic targets permitted to establish tumour immunology on solid grounds. It is now generally accepted that established tumours represent selected variants that have escaped the surveillance of the individual immune system. Implicit in that idea is the production by tumour cells of certain tumour-specific molecules that can be targeted by the immune system. A great number of altered or even normal proteins have been discovered in the last years that can evoke a tumour-directed immune attack. The induction of anti-tumour immune responses by vaccination with those tumour specific molecules or by treatment with antigen-specific antibodies is now currently under investigation in many clinical trials. Of particular interest is the idiotypic region of the immunoglobulin molecule, which acts as a clonal marker of B-lymphocyte neoplasias: The immunisation of lymphoma patients with their own tumour immunoglobulin has been proved effective in the treatment of that incurable condition.