Tabaco y peso corporal / Smoking and body weight

Resumen En esta revisión, se analiza la literatura existente en relación al tabaco y el peso corporal, su rol en el cambio de peso corporal según el consumo de tabaco o cesación de este y las diferentes alternativas farmacológicas validadas para el manejo de este problema, cada vez más prevalente.

This review analyses the existing literature regarding tobacco and body weight, its role in the change of body weight according to smoking consumption or cessation and the different pharmacological alternatives validated used to address this issue, which is everyday more prevalent

[Metabolic Syndrome: clinical and pathophysiological basis for a rational therapeutical approach]. / Síndrome metabólico: Bases clínicas y fisiopatológicas para un enfoque terapéutico racional.

Regardless of the diagnostic criteria, the metabolic syndrome is found at least in 20% of the population. The adipose tissue plays an important role in the insulin resistance found in this syndrome. Free fatty acids released by intra-abdominal adipocytes produce an inflammatory and pro-thrombotic response and the persistence of the insulin resistance state, phenomenon termed lipotoxicity. This altered phenotype explains the development of the different components of the metabolic syndrome, such as hypertension, dyslipidemia and altered glucose metabolism. The treatment is based on weight loss and healthy lifestyle. A balanced diet, physical activity and avoidance of smoking are key management features. The use of drugs with pleiotropic effects, which inhibit the renin angiotensin aldosterone axis or acts on the peroxisome proliferators-activated receptors (PPAR) seems promising.

Síndrome metabólico: bases clínicas y fisiopatológicas para un enfoque terapéutico racional / Metabolic Syndrome: clinical and pathophysiological basis for a rational therapeutical approach

Regardless of the diagnostic criteria, the metabolic syndrome is found at least in 20 percent of the population. The adipose tissue plays an important role in the insulin resistance found in this syndrome. Free fatty acids released by intra-abdominal adipocytes produce an inflammatory and pro-thrombotic response and the persistence of the insulin resistance state, phenomenon termed lipotoxicity. This altered phenotype explains the development of the different components of the metabolic syndrome, such as hypertension, dyslipidemia and altered glucose metabolism. The treatment is based on weight loss and healthy lifestyle. A balanced diet, physical activity and avoidance of smoking are key management features. The use of drugs with pleiotropic effects, which inhibit the renin angiotensin aldosterone axis or acts on the peroxisome proliferators-activated receptors (PPAR) seems promising.

[Molecular diagnosis and combined lipid lowering therapy of heterozygous familial hypercholesterolemia. Report of one case]. / Hipercolesterolemia familiar heterocigota: diagnóstico molecular y terapia combinada. Caso clínico.

Heterozygous familial hypercholesterolemia affects one every 400 individuals, is caused by mutations in the LDL receptor gene and is associated with premature coronary artery disease. Nowadays, LDL cholesterol can be efficiently reduced with the new therapies to reduce blood lipids. We report a female patient who consulted in 1975, when she was 46 years old, for severe hypercholesterolemia. In 2003, a sample of leukocyte DNA was obtained and the uncommon 1705+1G>A mutation of the LDL receptor gene was detected. No mutations in the apolipoprotein B gene were found. The patient was treated successfully with simvastatin 80 mg/day and ezetimibe 10 mg/day and LDL cholesterol levels were reduced below 200 mg/dl.

Hipercolesterolemia familiar heterocigota: diagnóstico molecular y terapia combinada. Caso clínico / Molecular diagnosis and combined lipid lowering therapy of heterozygous familial hypercholesterolemia: Report of one case

Heterozygous familial hypercholesterolemia affects one every 400 individuals, is caused by mutations in the LDL receptor gene and is associated with premature coronary artery disease. Nowadays, LDL cholesterol can be efficiently reduced with the new therapies to reduce blood lipids. We report a female patient who consulted in 1975, when she was 46 years old, for severe hypercholesterolemia. In 2003, a sample of leukocyte DNA was obtained and the uncommon 1705 + 1G >A mutation of the LDL receptor gene was detected. No mutations in the apolipoprotein B gene were found. The patient was treated successfully with simvastatin 80 mg/day and ezetimibe 10 mg/day and LDL cholesterol levels were reduced below 200 mg/dl.

[Atrioventricular node catheter ablation with condenser discharge and radiofrequency]. / Ablación del nódulo atrioventricular con descarga de condensadores y radiofrecuencia.

The AV junction ablation was useful to treat patients with drug-refractory supraventricular arrhythmias. The purpose of this study was to determine short and long-term success and complications of the atrioventricular nodal catheter ablation and to compare direct current and radiofrequency energy. Forty patients underwent AV nodal ablation with direct current energy (Group I) and forty patients with radiofrequency (Group II). They were followed up for a mean of 76 +/- 49 and 28 +/- 20 months, respectively. Persistent complete AV block was successfully induced during the first ablation session in 45% of 40 patients who underwent DC energy, while in 50% it was modulated. All patients in the radiofrequency group had complete AV block. The rate of recurrence of AV conduction was 7.5% and 2.5% respectively. Immediate complications did not occur after either procedure. One patient died suddenly in each group during follow-up. AV nodal ablation with radiofrequency energy appears to be as efficacious and safe as direct current energy.

Effects of in ovo exposure to 2,3,7,8-TCDD on F1 generation adult chickens (Gallus gallus).

White Leghorn chickens (Gallus gallus) were used as surrogate species for the resident wild turkeys found on the Times Beach, Missouri, Superfund site. Parental chickens were injected with concentrations of 2,3,7,8-TCDD which modeled soil concentrations before (200 ppb) and after remediation (1ppb)[1]. Offspring were followed through development to assess alterations in reproductive maturity through the use of a four-way breeding study. F1 adult females exposed to a maternal dose of 8.6 ng/day began egg production approximately two weeks later than did F1 control adult females. By week eight, however, egg production between groups was equivalent. No differences were observed in eggshell gland estrogen or progesterone receptor levels.

Effects of environmentally relevant concentrations of 2,3,7,8-TCDD on domestic chicken immune function and CYP450 activity: F1 generation and egg injection studies.

Domestic chickens (Gallus gallus) were used as a surrogate species for wild turkey to assess risk from environmental 2,3,7,8-TCDD exposure. Lymphocyte proliferation and CYP450 induction were assessed in adults exposed via i.m. injection, in F1 14-day old hatchlings, in F1 adults (30-weeks old), and in 14-day old hatchlings exposed via yolk sac injections. Hatchlings from injected eggs exhibited a dose-response in lymphocyte proliferation, IgM titers, EROD, and PROD endpoints. Exposed adults showed a significant dose-dependent increase in CYP450 induction. F1 14-day old chicks exhibited a significant dose-dependent suppression of B-cell proliferation and induction of CYP450 enzymes. F1 adult proliferative responses exhibited B-cell suppression, that was not statistically significant. Significant sex-dependent EROD and MROD induction was also observed in F1 adults, indicating mixed-function oxidase imprinting from maternal exposure.

Cytokine patterns in adults with AIDS.

BACKGROUND: It has been reported that in HIV infected patients enhanced production of IL-4 and IL-10 in response to stimulation of peripheral blood lymphocytes with phytohemagglutinin is associated with disease progression. Some have proposed that a switch from a cytokine profile associated with CD4+ Th1 predominance (IL-2, IFN-G, TNF-B) to Th2 predominance (IL-4, IL-5) plays a major role in the progression of HIV infection. Others find no clear evidence for the dichotomy of Th1 and Th2 predominance in HIV infected patients Discrepant results have been reported in studied populations in which only a few cytokines have been examined. METHODS: Thirty-one adult patients with AIDS but without other active infections provided serum and peripheral blood lymphocytes for determination of cytokine levels. Their responses were compared to those of five normal healthy volunteers without active infection. ELISA techniques were employed to quantitate cytokine levels. Both circulating lymphocyte and enriched lymphocyte populations were studied with and without stimulation employing phytohemagglutinin and/or rhIL-2. RESULTS: Patterns of cytokine expression were analyzed in 31 adult patients with AIDS but without other active infections. All had CD4+ cell counts below 50 and large viral loads (Roche PCR). The unstimulated cytokine profile in these patients generally showed marked elevations in IL-1, IL-3, IL-4, IFN-G, TNF-A, TNF-B, OSM, and TGF-B. Minimal elevations compared to normal healthy volunteers were noted for IL-2, IL-6, IL-8, IL-12, IFN-A, and IL-6SR. The levels of RANTES were lower than in normal healthy volunteers. Responses of peripheral blood lymphocytes to stimulation with phytohemagglutinin showed enhancement of all cytokines in all subjects studied though the response was much less marked in AIDS patients than in normal volunteers with the exception of IL-3, IL-4, IL-8, TNF-B, and TGF-B which are increased. Little difference in IL-2 and IL-12 expression was noted between stimulated peripheral blood lymphocytes of AIDS patients and normal healthy volunteers. No relation was noted with patient age or with any use of antiretroviral agents. Recombinant human IL-2 was a less potent stimulant than was phytohemagglutinin. CONCLUSION: The character of cytokine response in AIDS patients may be directly related to the stimulus employed in test systems. There is no evidence for Th1/Th2 dysregulation. Cytokine elevations in AIDS patients generally are reflective of chronic infection (the virus). Lymphocytes from AIDS patients do not respond as well to stimulation as do those from normal healthy volunteers. The stimulated lymphocyte response in AIDS patients suggests there is underlying low-grade host versus virus reaction in these patients (exaggerated responses of IL-3, IL-4, IL-8, TGF-B).

Immunomodulation in the treatment of multiple sclerosis and amyotrophic lateral sclerosis: a model for autoimmune disorders.

Seventeen multiple sclerosis (MS) patients progressing under conventional therapy (average treatment duration: 3 years) with performance status 3-4 (mean Disability Status Scale [DSS]: 82) who demonstrated circulating lymphokine inhibitor factors were selected for a monthly immunomodulatory protocol using plasmapheresis, followed by 3 days of human intravenous immunoglobulin, and low-dose methylprednisolone, cyclophosphamide, interferon-a, and interferon-g, as well as octreide. Twelve of the 17 patients presented with visual problems, 12 had lower extremity weakness or paraperesis/paralysis, and 6 had bladder/bowel dysfunction. Following 4 months of therapy, 4 recovered completely, 7 showed loss of paralysis/paraparesis, and 5 had improvement in lower extremity weakness. One patient progressed (mean DSS: 51). Lymphokine inhibitor factors declined in 14 patients with concomitant normalization of circulating immune complexes. Eight patients experienced rises in CD4 levels with stabilization of CD8 levels. Hypotension and hypocalcemia were observed during plasmapheresis. Twelve patients with amyotrophic lateral sclerosis with poor performance status also were studied. Four of the 12 improved with the regimen, whereas six stabilized disease. Similar alterations in laboratory parameters were described. The rationale for this approach is discussed.

Fetal weights and measurements as determined by postmortem examination and their correlation with ultrasound examination.

Two hundred fifty fetuses from healthy singleton pregnancies terminated other than on health grounds at 21 to 26 weeks gestation were examined by ultrasound in utero and by autopsy. No significant maturational difference between male and female fetuses was noted, although larger biparietal distances (0.2 cm) and smaller femur lengths (0.2 cm) were seen in female fetuses at 23 weeks gestation, and heavier body weights were also noted (80 g). No maturational difference was noted between white and nonwhite populations. Maternal age was not a significant variable. Organ weights and fetal anthropometric measurements are provided. Biparietal diameter as determined by ultrasound examination of the fetus in utero is an excellent predictor of gestational age and correlated well with actual caliper measurements on the fetus (coefficient of variation [CV] < 5%). Femur length determined by ultrasound examination of the fetus in utero is significantly low compared with actual length (CV = 23%) and is not a reliable indicator of fetal development. A large CV (17%) was also seen for calculated fetal weight.

Is metastatic breast cancer, refractory to usual therapy, curable?

Breast cancer with metastatic disease is presently incurable. Significantly shorter survival rates are seen in premenopausal women despite usual therapies when compared to survival rates in older women. Median survival rates of 24-30 months are documented in large-scale prospective clinical trials of previously untreated women with metastatic breast cancer regardless of the protocol employed (chemotherapy, hormone therapy). High dose chemotherapy followed by autologous stem cell rescue (bone marrow or peripheral blood) is associated with significant response and possibly improved survival in chemosensitive patients with metastatic disease without visceral metastases though with significant toxicities and cost (median survival rate of 20 months). Patients with refractory disease have dismal results regardless of therapy (median survival rates of 8-9 months in a number of prospective trials with or without stem cell rescue). The use of alpha-interferon in such patients has not improved response. Whole body hyperthermia is of benefit in the presence of liver metastases although median survival rate is in the range of 12 months. New treatment approaches with curative intent are clearly required. We report fifty-nine patients with metastatic breast cancer refractory to common therapies who were treated with whole body hyperthermia (40 degrees C) with low dose chemotherapy and immunomodulation: five presented with brain metastases; 13 with multiple bone metastases; 8 with liver metastases; 10 with lung metastases; and 23 with multiple soft tissue metastases. Fifteen were premenopausal; 44 postmenopausal. Twenty-three achieved complete remission. Fourteen have been sustained with patients remaining alive from 17-80 months (median, 40 months). Nine failed after 20-40 months of being disease-free (mean, 32 months).(ABSTRACT TRUNCATED AT 250 WORDS)

Whole body hyperthermia associated with beta-carotene supplementation in patients with AIDS.

The objective of this work was to check possible additive beneficial effects of whole body hyperthermia (WBH) associated with beta-carotene (BC) supplementation in patients with AIDS. In a pilot study, 10 HIV positive patients, (8 with AIDS and 2 with AIDS related complex, ARC), after AZT or DDI discontinuation, were first treated with one single session of WBH applied with a non-invasive procedure at 42 degrees C core temperature for one hour, and subsequently supplemented with BC 120 mg daily continuously. All patients well tolerated the non-invasive WBH as well as the high dose BC supplementation. Apart from one patient who died after 4 months, all the others underwent an HIV burden diminution, clinical improvement and amelioration of laboratory data, along with an subjective improvement of their life quality. With reference to control groups, namely (a) only WBH applied with extracorporeal procedure to 31 AIDS patients, and (b) only BC supplementation at high dosage applied to 64 ARC patients, the combined physical and BC supplemental treatments clearly showed a better and longer lasting response.

Systemic hyperthermia in the treatment of HIV-related disseminated Kaposi's sarcoma. Long-term follow-up of patients treated with low-flow extracorporeal perfusion hyperthermia.

Treatment of HIV and related malignancies with pharmacologic and biologic agents has not appreciably modified the course of disease. Immunologic impairment remains the critical factor in response. We report the long-term results of a single session of low-flow (0.3 L/min) extracorporeal perfusion hyperthermia on 29 men and 2 women with disseminated Kaposi's sarcoma and profound immunologic impairment. Any antiretroviral drug employed by the patient was stopped 72 hours prior to treatment and withheld during the period of follow-up. Core temperature was raised to 42 degrees C and held for 1 hour with extracorporeal perfusion and ex vivo blood heating to 49 degrees C as the means of temperature control. Of 31 patients, 2 died of complications secondary to treatment (cardiac arrhythmia; CNS bleed). There were two cases of intravascular coagulopathy. Pressure point skin damage may occur despite adequate cushioning. At 30 days posttreatment complete or partial regressions were seen in 20/29 of those treated, with regressions persisting in 14/29 of those treated by 120 days posttreatment. At 360 days, 4/29 maintain tumor regressions with 1 in complete remission (at 26 months). The patient in complete remission remains culture-negative and PCR-negative for HIV. CD4+ counts rose from around 250 to, and remain around, 800 in this man. Selected healed lesions were biopsied to demonstrate tumor absence. Patients were selected for treatment if pretreatment testing of the tumor showed regression in vitro with heat exposure. Analysis of the early and midterm failures showed little sustained rise of the CD4+ cells if presenting total CD4+ counts were below 50 and had been at such low levels for extended periods, although other surrogate markers of HIV activity declined (semiquantitative PCR) during this period and is felt to support the hypothesis of apoptosis proposed in this illness. Analysis of the tumors of the few men not responding demonstrated elevated levels of IL-6 as compared to responders (12 vs < 1 pg/ml). At 120 days 29/31 patients remained alive (expected, 20). At 360 days, 21/31 remained alive (expected, 11). In no patient was HIV activity stimulated with heat exposure. CMV retinitis did clear in some patients treated (both techniques), but treatment alone did not prevent later development of retinopathy. EBV parameters were markedly altered in the short term with heat exposure in some patients. Few patients showed herpes simplex activation. Varicella-zoster virus remitted in some patients. There is utility in the use of systemic hyperthermia to control HIV and related malignancy.(ABSTRACT TRUNCATED AT 400 WORDS)

Immunomodulation in the treatment of malignant disorders.

In this study, 91 patients with metastatic solid tumor were treated with an immunomodulatory regimen of interferons -a and -g as well as octreide in pulse administration, followed in selected patients by low dose perilymphatic administration of interleukin-2. Pharmacosensitivity studies of patient tumor directed concomitant chemotherapy. High levels of circulating interferon-a (> 50 IU/ml) and the presence of lymphokine inhibitor factor were identified prior to treatment. None of the patients was able to produce autologous interferon. All patients had been previously treated with surgery and/or radiation therapy and/or chemotherapy. Patients had also received second line chemotherapy and/or radiotherapy per current protocols. At 30 days following immunomodulatory therapy, 6/91 patients were in complete remission; 12/91 were in partial remission; six patients progressed. At 180 days, with concomitant stem cell assay directed chemotherapy, 24/91 patients were in complete remission; 36/91 demonstrated a partial remission. Six patients progressed. Responders demonstrated a fall in circulating interferon levels as well as lymphokine inhibitor factor concomitantly with reduction in tumor burden. NK cell activity increased. Marrow studies demonstrated rises in granulocyte and thrombocyte stem cell activity. Macrophage activity also increased. The rationale for the approach is discussed.

Plasmapheresis combined with interferon: an effective therapy for multiple sclerosis.

The rationale for the use of interferon (IFN) in the treatment of multiple sclerosis (MS) is based on its recognized antiviral and immunomodulating actions. The pathogenesis of MS is believed to be due to an immunologic response in a genetically predisposed individual, localized within the central nervous system white matter, and triggered by exposure to an environmental agent such as a virus. Based on our personal experience we find that the efficacy of IFN therapy is hampered in MS patients by the presence of an interferon inhibitor factor (IIF) in the patients' sera which we have isolated and characterized. When plasmapheresis (PP) was done on 24 MS patients with intermittent 3-day administration of IFN-alpha and human leukocyte IFN, marked increase of IFN in 18 patients and modest increase in three patients correlated with clinical improvement. Three clinical nonresponders showed no increase in IFN levels following therapy. The ability to remove IIF and lymphokine inhibitor factor (LIF) by PP may explain the successful treatment of our patients. We describe the evaluation of helper T cells, suppressor T cells, HLADR antigen, natural killer cells, and monocyte/macrophage cell populations by flow cytometry before and after PP. A significant increase in these immune-competent cells correlated with marked improvement in Kurtzke disability status scale in 13 patients, while eight stabilized. Patients showing progression of the disease either showed decrease or no change in these parameters after therapy. Encouraging results from this pilot study suggest that PP combined with immunomodulatory regimens of IFN may be an effective therapy for MS.