The in vitro and in vivo effects of extracorporeal shock waves on malignant cells

Summary The in vitro cytotoxic effect of extracorporeal shock waves (ESW) on renal cell carcinoma (RCC) cells was compared to the effect on normal human embryonic kidney (NHEK) cells. In the in vitro studies cell samples were brought into the second focal point and exposed to different numbers of shock wave impulses. The four parameters of RCC tumor cell injury which were measured, i.e., cell viability, cell growth, cell attachment and electron microscopic evidence of damage, were augmented with increasing SW levels. At 2,000 shock waves (SW) a significant decrease in RCC viability, cell growth and cell attachment was seen compared to the NHEK cells. In the in vivo experiment a FANFT induced bladder tumor was transplanted into the right hind legs of C3H/He mice and the tumors were exposed to 1,400 SW. Preliminary data showed that 1,400 SW at day 12 post transplant significantly inhibited tumor growth. Combining 1,400 SW with cis-diamminedichloroplatinum (4 mg/kg) did not enhance the tumor inhibitory effect of each individually. Doxorubicin (5 mg/kg) and 1,400 SW produced a significant synergistic tumor inhibitory effect.Supported by The University Urological Research Foundation     

Lymphocyte subpopulations in anaphylactoid purpura.

The immunoglobulins, complement components C3 and C4, lymphocyte subpopulations, and K-cell activity were studied in 13 children with anaphylactoid purpura and in 12 children of the same ages who acted as controls. The children with anaphylactoid purpura had significantly lower T-cell counts, greater K-cell activity and IgM values, and lower C3 levels than the controls.     

Primary Hepatitis A vaccination failure is a rare although possible event: results of a retrospective study

A case of Hepatitis A occurred in a traveller in spite of a complete course of immunization with a combined HAV and HBV vaccine [Taliani G, Sbaragli S, Bartoloni A, Santini MG, Tozzi A, Paradisi F. Hepatitis A vaccine failure: how to treat the threat. Vaccine 2003;21(31):4505-6]. A retrospective study was performed to evaluate whether the failure was primary or could be attributed to a specific lot of vaccine or to its inadequate handling and/or storage. Two distinct populations of vaccinees were selected in a 1:2 proportion. The case group (N=31) included subjects who were vaccinated in the same period and with the same lot and batch of vaccine as the case. The control group (N=62) included subjects who received different lot and batch of the same vaccine as the case group. A persisting antibody response to HAV vaccine was found among all subjects (anti-HAV >20mIU/ml). The overall anti-HBs seropositivity rate (anti-HBs >10mIU/ml) was 74%, without significant difference between the case (77%) and the control group (73%; P>0.05). The reported Hepatitis A case can be attributed to a rare primary vaccine failure rather than to inefficacy of a specific lot of vaccine or to inappropriate vaccine handling or storage. Our study supports the indications for use of combined Hepatitis A+B immunization in travellers at risk for both infections, but stresses the need for information on correct hygienic behaviours while abroad.     

Randomized controlled trial: effect of nutritional counselling in general practice

OBJECTIVES: To investigate the effectiveness of a non-structured 15-min educational intervention by general practitioners (GPs) on modifications of daily diet among healthy adults. DESIGN: Two arms randomized trial lasting 12 months. SETTING: Italian general practitioner wards. Subjects A total of 3,186 men and women aged 18-65 years recruited in the medical ward by their GPs. INTERVENTIONS: An educational intervention and a brochure on the basics of a healthy diet based on the Italian Guidelines for a Correct Nutrition, 1998. The main study goal was to attain an intake of fruits and vegetables >5 servings per day. Follow-up visit every 6 months. Main outcome measures Weight, blood pressure, and a 40-items Food Frequency Questionnaire. RESULTS: The intervention group showed a slightly reduced net intake of meat and a slightly increased net intake of fruits and vegetables, fish products, and olive oil. Body mass index (BMI) changed only in the treatment arm [-0.41 95% confidence interval (95% CI) -0.11 to -0.53]. The net change at 1 year in the intervention arm was +1.31 (CI 0.90-4.39) for fruits and vegetables, and -0.22 (-0.11 to -0.69) for meat (portions per week). We also computed a 'healthy diet score' reflecting compliance with recommended dietary habits. In the intervention group, the mean score at recruitment was significantly lower than the mean score at the end of follow-up (Crude score change = 0.29; CI 0.19-0.48). No differences were observed in the control group (Crude score change = -0.04; CI -0.22-0.02). The difference in score from baseline to the final visit, comparing the intervention vs the control group, was statistically significant (P < 0.001) (MANOVA adjusted by sex, BMI, education, and time). CONCLUSIONS: A brief educational intervention by GPs can induce multiple diet changes that may lower BMI and potentially reduce chronic disease risk in generally healthy adults.     

Administration of recombinant human erythropoietin alpha before autologous stem cell transplantation reduces transfusion requirement in multiple myeloma patients

Recombinant human erythropoietin administered after peripheral blood stem cell transplantation (PBSCT) has been ineffective for the treatment of anemia. We administered recombinant human erythropoietin alpha (rHuEPO) prior to high-dose therapy after peripheral blood stem cell (PBSC) collection to evaluate its efficacy on transfusion requirements and hematological parameters during the post-transplant aplastic phase. Twenty-two multiple myeloma patients (EPO-MM) were included in the trial to receive rHuEPO 10,000 IU subcutaneous daily starting 30 days before PBSCT. Forty hemoglobin (Hb)-matched patients who had not received rHuEPO before transplant were retrospectively selected (Ctr-MM) for comparative data. None of the patients received transfusions at study entry. All but one patient responded to rHuEPO. However, no significant differences in Hb levels were obtained between the two groups at the time of transplantation. At nadir, the EPO-MM cases had a significantly higher Hb level (median 10 g/dl versus 7.6 g/d; p=0.001). Consequently, less than 20% of EPO-MM patients required packed red blood cell (PRBC) transfusions compared to more than half the Ctr-MM patients (p=0.007). Furthermore, the number of PRBC transfusions performed in the EPO-MM group was significantly lower (median 0 versus 1; p=0.008). Independently of Hb levels at PBSCT, rHuEPO therapy was significantly associated with a lower risk of transfusion requirement. In conclusion, rHuEPO is shown to be effective when administered prior to high-dose therapy in MM.     

Comparison of effectiveness of carvedilol versus bisoprolol for prevention of postdischarge atrial fibrillation after coronary artery bypass grafting in patients with heart failure

Atrial fibrillation (AF) occurs frequently soon after coronary artery bypass grafting (CABG) and often results in increased mortality and morbidity, particularly in patients with heart failure. New-onset AF is also a common event in the early period after discharge from a cardiac surgery clinic. Current guidelines recommend β blockers as first-line medication for the prevention of AF after CABG. In this prospective study, we investigated the effectiveness of the highly selective β1 receptor antagonist bisoprolol compared to the less selective β blocker carvedilol in preventing postdischarge AF after CABG in patients with decreased left ventricular function. Three hundred twenty patients (231 men, 89 women, mean age 66 ± 10 years) with ejection fraction <40% who underwent CABG and were then referred to an in-hospital cardiac rehabilitation program were randomized to receive bisoprolol (n = 160) or carvedilol (n = 160) starting 4 to 5 days after surgery. Bisoprolol was started at 1.25 mg 1 time/day and carvedilol was started 3.125 mg 2 times/day. All patients underwent continuous telemetric electrocardiographic monitoring for 5 days after entry in the study and thereafter 2 times/day routinely up to hospital discharge. During follow-up, 23 patients (14.6%) in the bisoprolol group and 37 patients (23%) in the carvedilol group developed AF (relative risk 0.6, confidence interval 0.4 to 0.9, p = 0.032). Twenty-six percent of all AF episodes were asymptomatic. At the 4-week outpatient visit, those in the bisoprolol group showed a significantly greater decrease in heart rate, being in sinus rhythm or AF (-15.6 ± 3 vs -9.4 ± 3 beats/min, p = 0.021), whereas changes in systolic and diastolic blood pressures did not differ significantly. In conclusion, bisoprolol is more effective than carvedilol in decreasing the incidence of postdischarge AF after CABG in patients with decreased left ventricular function.     

Facial self-induced paraffinoma in an elderly woman

A 72-year-old Caucasian woman without remarkable medical history presented with an asymptomatic bilateral periocular swelling, which had been present for 2 months. Physical examination showed symmetric indurated periocular erythematous plaques (Figure 1). Biopsy of a skin lesion revealed aggregates of vacuoles of different sizes (Figure 2) surrounded by a prominent inflammatory infiltrate constituted by macrophages, lymphocytes, neutrophils, and granulomatous foreign body reaction throughout the reticular dermis and hypodermis. These histological findings were consistent with the injection of an oily foreign substance. The patient denied the self-induced nature of the lesions, so she was referred for psychiatric evaluation and admitted having self-injected mineral oil as an impulsive attempt to get attention from her family. She was diagnosed with borderline personality disorder (BPD) and started treatment with oral fluoxetine, showing a rapid decrease of impulsive behavior and anxiety from the second week with a mean dose of 80 mg/d.     

Gene expression in nanotoxicology research: analysis by differential display in BALB3T3 fibroblasts exposed to cobalt particles and ions

Broadly defined, nanoscale materials are substances in which at least one critical dimension is less than 100 nm. Nanoscale materials are employed in several industrial applications as well as in biology and medicine. Despite their wide use, very little research has been carried out on the potential toxicity of nanoparticles. For this reason, we report on a molecular approach in nanotoxicology research. Using the differential display technique, we focused our attention on mRNA expression in a BALB3T3 A31-1-1 cell line that was not exposed and exposed for 72 h to 1 μM of cobalt microparticles (Co-μ), nanoparticles (Co-nano), and ions. In the experiments, we obtained 10 differentially expressed sequences. These genes represent candidate biomarkers capable of indicating specific cellular effects after Co-nano exposure. In addition, our results show that treatment with Co-nano somehow activates cellular pathways of defense and repair mechanisms. It is also evident that molecular techniques are valuable tools in nanotoxicology research, where they will certainly find wide use.