Response from lieberman and colleagues

Respond on comments on Lieberman's article: Cyclosiloxanes Produce Fatal Liver and Lung Damage in Mice. Environ Health Perspect 107:161-165     

Decreased facilitation by angiotensin II of noradrenergic neurotransmission in isolated mesenteric artery of rabbits with chronic heart failure

Both in human and in experimental heart failure (HF), the renin-angiotensin system and the sympathetic nervous system are activated. In a previous study a facilitatory action of angiotensin II (Ang II) was shown in the rabbit mesenteric artery, which was mediated via prejunctionally located Ang II type 1 (AT ) receptors. Very little is known about the effects of Ang II on sympathetic neurotransmission at the peripheral level in congestive heart failure (CFH). Accordingly, in the isolated mesenteric arteries obtained from rabbits with experimentally induced CHF, as well as in age-matched control rabbits, the effect of Ang II on contractions provoked by electrical field stimulation was investigated in the presence and absence of the AT receptor antagonist eprosartan. Additionally, to investigate a possible postjunctional facilitation, the effects of Ang II on alpha-adrenoceptor-mediated responses were studied using noradrenaline (NA). Lastly, the vasoconstrictor effects of Ang II were compared between HF rabbits and controls, by constructing concentration-response curves to Ang II. In control rabbits, Ang II 0.5 n caused an enhancement of stimulation-induced responses by a factor 3.2 +/- 0.5, 2.4 +/- 0.3, and 1.5 +/- 0.08, at 1, 2, and 4 Hz, respectively ( < 0.05 at all frequencies compared with vehicle). In rabbits with HF, the enhancement by Ang II (0.5 n ) amounted to a factor 2.1 +/- 0.2, 1.7 +/- 0.1, and 1.2 +/- 0.04, at 1, 2, and 4 Hz, respectively ( < 0.05 compared with vehicle at all frequencies). Accordingly, the enhancing effect of Ang II was more pronounced in the control group compared with rabbits with HF ( < 0.05 at each frequency). Eprosartan (1 nM -0.1 microM) could inhibit the facilitatory effects of Ang II in arteries from HF as well as from control rabbits. Contractile responses to exogenous NA (3 n -0.1 m ) were the same in HF rabbits and controls, and they were unaltered in the presence of Ang II 0.5 n Ang II (0.1 nM -1 microM) caused a concentration-dependent increase in contractile force, which was the same in HF rabbits and controls. From these findings it can be concluded that in rabbits with CHF as well as in control animals, Ang II facilitates the stimulation-induced vasoconstrictor responses via prejunctionally located AT receptors. The facilitating effect was decreased in vessels obtained from rabbits with CHF, whereas responses to exogenous Ang II were unchanged. These findings may be explained by downregulation or uncoupling of the prejunctional AT receptor.     

Trichinella infection and clinical disease

Trichinellosis is caused by ingestion of insufficiently cooked meat contaminated with infective larvae of <it>Trichinella</it> species. The clinical course is highly variable, ranging from no apparent infection to severe and even fatal disease. We report two illustrative cases of trichinellosis. Returning to Denmark a few days after having eaten roasted pork in the Republic of Serbia, a female patient suffered from severe vomiting, epigastric pain, diarrhoea, and later myalgia, generalized oedema, and prostration. A biopsy showed heavy infestation with <it>Trichinella spiralis</it>, 2000 larvae/g of muscle. Life-threatening cardiopulmonary, renal and central nervous system complications developed. The patient recovered after several months. Her husband, who also ate the pork, did not have clinical symptoms, but an increased eosinophil count and a single larva in a muscle biopsy confirmed infection. The epidemiology, clinical manifestations, diagnosis, treatment and prevention of trichinellosis are reviewed.      

Hepatitis B Immunisation in Health Care Workers

Background

Hepatitis B virus (HBV) infection is an important occupational risk in health care workers (HCW). In spite of HBV vaccine availability in Armed Forces, the high prevalence of HBV infection in HCW continues to be a problem. The study was undertaken to study the HBV vaccine-compliance among HCW.

Methods

A cross-sectional study was conducted at a tertiary care hospital. HCW were requested to fill up the pre set questionnaire to assess the HBV vaccination coverage.

Result

Amongst 254 HCW, only 57.7% were vaccinated against HBV. The vaccine compliance was lowest among housekeeping professionals. The mean age at vaccination was high (30.5 years). Amongst the vaccine non-compliant subjects, 34.3% were above 30 years of age. 32.2% HCW completed primary vaccination after spending more than 10 years in the profession. Accessibility of HBV vaccine, knowledge and perception of HBV risk were important factors in vaccine non-compliance.

Conclusion

Due to low and delayed HBV vaccine-compliance, HCW continue to be at the risk of occupational HBV. Health education highlighting occupational risk of HBV, accessibility of vaccine and mandatory vaccination of HCW is recommended to increase HBV vaccine compliance among HCW.Key Words: Health care workers, Hepatitis B virus, Occupational risk, Hepatitis B vaccine     

Dietary n-3 fatty acids promote arrhythmias during acute regional myocardial ischemia in isolated pig hearts

OBJECTIVE: Dietary supplementation with fish oil-derived n-3 fatty acids reduces mortality in patients with myocardial infarction, but may have adverse effects in angina patients. The underlying electrophysiologic mechanisms are poorly understood. We studied the arrhythmias and the electrophysiologic changes during regional ischemia in hearts from pigs fed a diet rich in fish oil. METHODS: Pigs received diets rich in fish oil, in sunflower oil, or a control diet for 8 weeks. Hearts were isolated and perfused. Ischemia was created by occluding the left anterior descending artery. Diastolic stimulation threshold, refractory period, conduction velocity, activation recovery intervals and the maximum downstroke velocity of 176 electrograms were measured in the ischemic zone. Spontaneous arrhythmias during 75 min of regional ischemia were counted. RESULTS: More episodes of spontaneous ischemia-induced sustained ventricular tachycardia and ventricular fibrillation occurred in the fish oil and sunflower oil group than in the control group. More inexcitable myocardium was present in the ischemic zone in the group fed fish oil or sunflower oil than in the control group after 20 min of ischemia. After 40 min of ischemia, more block occurred in the control group than in the other groups. The downstroke velocity of the electrograms in the ischemic border zone was lower in the fish oil group and sunflower oil group than in the control after 20 min. CONCLUSIONS: A diet rich in fish oil results in proarrhythmia compared to a control diet during regional ischemia in pigs. Myocardial excitability is reduced in the fish oil and sunflower oil group during the early phase of arrhythmogenesis. In the late phase of arrhythmogenesis, excitability is more reduced in the control group than in the fish oil and sunflower oil group.     

Chronic inhibition of Na+/H+-exchanger attenuates cardiac hypertrophy and prevents cellular remodeling in heart failure

OBJECTIVE: In patients with heart disease, the transition from compensatory hypertrophy to heart failure (HF) is associated with altered calcium handling. Up-regulated Na(+)/H(+)-exchanger (NHE-1) activity underlies increased [Na(+)](i) and disturbance of cellular calcium handling in HF. We hypothesize that chronic inhibition of NHE-1 activity prevents the hypertrophic response, cellular remodeling, and development of HF. METHODS: Rabbits received a control or cariporide (inhibitor of NHE-1) diet for 3 months, starting after induction of combined volume and pressure overload. Age-matched animals served as control. Development of HF was examined echocardiographically and electrocardiographically after 3 months. [Na(+)](i), [Ca(2+)](i), pH(i), and action potentials were measured in left ventricular midmural myocytes with SBFI, indo-1, SNARF, and di-4-anepps. Sarcoplasmic reticulum calcium content was calculated from the response of [Ca(2+)](i) to rapid cooling. Calcium after-transients were elicited by cessation of rapid stimulation (3 Hz) in the presence of 100 nmol/l noradrenalin. RESULTS: Chronic treatment of rabbits with the specific Na(+)/H(+)-exchanger activity inhibitor cariporide greatly attenuated development of hypertrophy and entirely abolished development of HF; the heart/body weight ratio increased only little, no change in lung weight occurred, left ventricular dimensions and fractional shortening changed mildly, ascites was not present, QT duration did not increase, and sudden death did not occur. Chronic cariporide treatment also prevented cellular electrical and ionic remodeling. Myocyte dimensions were unaltered, action potentials were not prolonged, cytoplasmic sodium and NHE-1 activity did not increase, cytoplasmic and SR calcium handling remained undisturbed, and no increase of the incidence of calcium after-transient dependent delayed after depolarizations (DADs) occurred. CONCLUSION: We conclude that enhanced activity of NHE-1 underlies cardiac cellular electrical and ionic remodeling in experimental heart failure, and that chronic dietary treatment with cariporide attenuates hypertrophy, development of HF, and cellular remodeling.     

Parental psychopathology and migraine headaches among adolescent girls

Migraine headaches and depression often co-occur within individuals, and both syndromes run in families. However, knowledge about how these disorders relate across generations, as well as how migraine relates to other forms of psychopathology, is sparse. This study examined risk for migraine among female adolescent offspring of parents with different types of psychopathology. The sample was drawn from the Minnesota Twin Family Study, a community-based study of adolescents and their families ( n  = 674, 17-year-old female adolescents and their biological parents). Diagnoses of maternal, paternal and offspring major depression, antisocial behaviour, alcohol dependence and drug dependence were based on structured interviews. Migraine headaches in each family member were assessed via interviews with the mother. Parental depression, antisocial behaviour and drug dependence were associated with offspring migraine. These associations mostly remained significant even when parental migraine and the corresponding type of psychopathology in offspring were adjusted for. In contrast, there were no significant associations between parental psychopathology and offspring stomach problems, indicating that these associations did not extend to all offspring somatic symptoms. These results emphasize the need to look at antisocial behaviour and substance-related problems when examining associations between migraine and psychopathology, and indicate that more research on inter-generational links between migraine and psychopathology is needed.     

The metabolite 1 alpha,25-dihydroxyvitamin D3 enhances lymphokine- mediated activation of the oxidative metabolism of the U937 cell line and phosphorylation of a 48-kD respiratory burst-associated protein

U937 cells respond to a variety of stimuli with increased differentiation as manifested by reduced growth, increased adherence, increased expression of several surface receptors, and increased capacity for phagocytosis and formation of reactive oxygen intermediates. In the present study the effects of lymphocyte conditioned media, recombinant interferon-gamma (IFN-gamma), and 1 alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3) on the ability to form reactive oxygen intermediates by U937 cells were measured by using the luminol-dependent luminescence (LDL) assay. Neither 1,25(OH)2D3 alone nor IFN-gamma alone enhanced competence for phorbol myristate acetate- stimulated LDL. Cells were capable of moderate LDL after exposure to lymphocyte conditioned media, and this was enhanced by 1,25(OH)2D3 (10(- 8) mol/L) and other vitamin D metabolites at higher concentrations. This effect was not secondary to accelerated production of myeloperoxidase, which is important in the LDL assay. Enhanced phorbol myristate acetate-stimulated phosphorylation of a 48-kd substrate was observed in 32P-labeled intact cells treated with 1,25(OH)2D3 alone or in combination with IFN-gamma. Treatment of cells with IFN-gamma or lymphocyte conditioned media did not alter phosphorylation. These results support the concept that 1,25(OH)2D3 plays a role in phagocyte differentiation and activation beyond the effects of lymphokines. Protein kinase C-mediated phosphorylation reactions may be necessary for the ability of U937 cells to reduce O2 and required for maximal activity under some conditions of incubation.     

The management of stage I--II Hodgkin's disease with irradiation alone or combined modality therapy: the Stanford experience

At Stanford University, between 1968 and 1978, 230 patients with pathologic stage I--II Hodgkin's disease were treated on prospective clinical trials with either irradiation alone or irradiation followed by 6 cycles of adjuvant combination chemotherapy. The actuarial survival at 10 yr was 84% for patients in either treatment group. Freedom from relapse at 10 yr was 77% among patients treated with irradiation alone and 84% after treatment with combined modality therapy [p(Gehan) = 0.09]. Freedom from second relapse at 10 yr was 89% and 94%, respectively [p(Gehan) = 0.56]. Several prognostic factors were evaluated in order to identify patients at high risk for relapse or with poor ultimate survival after initial treatment with irradiation alone. Systemic symptoms, histologic subtype, age, and limited extranodal involvement (E-lesions) did not affect the prognosis of patients and failed to identify patients whose survival could be improved by the routine use of combined modality therapy. Patients with large mediastinal masses (mediastinal mass ratio greater than or equal to 1/3) had a significantly poorer freedom from relapse when treated with irradiation alone than when treated initially with combined modality therapy [45% versus 81% at 10 yr, p(Gehan) = 0.03). The 10-yr survival of these patients, however, was not significantly different (84% versus 74%). The implications of these observations on the management of patient with early stage Hodgkin's disease are discussed.