Safety and efficacy of therapy with botulinum toxin in obesity: a pilot study

Background Botulin toxin (BTX) has been proposed as a potential obesity treatment.Methods In a pilot study, the short-term efficacy and safety of BTX was assessed in eight subjects (four men, four women; median age, 46 years; range, 35–57 years) with severe obesity (median body mass index [BMI], 47.1 kg/m²; range 38.2–56.7 kg/m²) and multiple dietary treatment failures. In a single endoscopic session, 500 UI of BTX-A was injected in the gastric antral region.Results No clinically significant side effects were observed. In all patients, despite their not being on a specific diet, a reduction of body weight was observed at 1 month (median baseline weight, 124.4 kg vs 121.8 kg at 1 month; P < 0.05). Two treatment-unrelated dropouts were observed. At 4 months, three of the six patients had a further weight loss. The treatment effect was apparently independent of changes in hunger or satiety, or of changes in fasting and postprandial plasma ghrelin and serum leptin, thus suggesting a different pharmacological mechanism.Conclusions BTX-A treatment appears to be safe and well tolerated by obese patients, while its short-term efficacy varied widely.     

Impact of the earthquake of September 26, 1997 in Umbria, Italy on the socioenvironmental and psychophysical conditions of an elderly population

The consequences of natural disasters on the social and health status of older people have not been deeply considered. The aim of this study was to evaluate the socioenvironmental and psychophysical conditions of an elderly population after a devastating earthquake. A randomly selected group of 332 older people (> or =64 years) was selected among 1548 eligible subjects living in the city of Nocera Umbra four months after an earthquake of 5.6 magnitude on the Richter scale. Three geriatricians evaluated the study subjects by means of a structured interview, and standardized scales, which considered physical and mental status, mood and anxiety, and self-perception of well-being, as well as the characteristics of family composition and social interactions. Of the study subjects, 11.1% lived alone, and 33.4% with the spouse only. Most were self-sufficient in the basic activities of daily life. Musculoskeletal diseases and hypertension were the most frequently observed pathologies in this geriatric population. In addition, 47.9% of the subjects lived in temporary houses; this group more frequently suffered from hypertension, and had a higher score of comorbidity as measured by Cumulative Illness Rating Scale (CIRS) compared to people who remained at home. People living in the pre-fabricated huts also showed a higher score on the Geriatric Depression Scale and the Hamilton scale for anxiety, and complained more often of their health status, evaluated as self-perception of well-being, when compared to the home dwellers. Although all the studied subjects suffered from the discomforts caused by the earthquake, the precariousness of living in temporary houses, whose structural characteristics do not take the needs of elderly subjects into account, could justify the higher distress experienced by persons housed in the huts. These observations suggest that, after natural disasters, emergency programs should be more adapted to elderly people, whose needs and expectations are often different from those of young adults.     

Nonarteritic anterior ischemic optic neuropathy treated with intravenous prostaglandin E1 and steroids

BACKGROUND:

Acute nonarteritic anterior ischemic optic neuropathy (NAION) is considered to be acute ischemia of the posterior ciliary arteries. Prostaglandin E1 (PGE1), a powerful microcirculation vasodilator, has been shown to improve ocular blood flow.

DESIGN:

A nonrandomized, comparative trial.

METHODS:

Eight consecutive cases of NAION were treated with intravenous steroids and PGE1. Seven control cases of NAION were treated with acetylsalicylic acid and oral steroids. Fisher’s exact test was used for statistical analysis.

RESULTS:

The visual acuity improved in seven cases of NAION treated with PGE1 and was unchanged in one. Of the seven control cases, four had no change in vision and three lost further visual acuity on follow-up visits.

CONCLUSIONS:

Intravenous PGE1 and steroids should be considered in cases of NAION to immediately restore blood flow to the optic nerve and improve visual acuity.     

Rearrangements of the RAR-α gene in acute promyelocytic leukaemia:

We have used genomic probes which specifically recognize DNA rearrangements of the RAR-alpha locus on chromosome 17q21 in patients with acute promyelocytic leukaemia (APL) and acute myeloid leukaemia (AML) subtypes. Molecular data were examined in comparison with morphological and immunophenotypic characterization at diagnosis in 20 hypergranular FAB M3 cases, five microgranular APL (M3v), 51 non-M3 AML and 12 myeloid CML blast crises. Rearrangements of the RAR-alpha locus were only detected in 23/25 APL cases and in none of the other FAB subtypes analysed. Surface marker characterization showed a consistent immunophenotypic profile--HLADR negative, CD9 and CD13/33 positive--in all M3 and M3v cases. Neither HLADR negativity nor CD9 positivity were associated with RAR-alpha rearrangements in non M3 AML. Our data indicate that RAR-alpha gene rearrangements are relevant diagnostic features of both M3 and M3v, and may prove useful molecular marker for follow-up analysis in APL patients.     

Comparative study of time-course of hemodynamic effect of isosorbide dinitrate spray and sublingual tablets in patients with pulmonary congestion

Summary We compared the time-course of the hemodynamic effect of isosorbide dinitrate (ISDN), 5 mg, in the form of sublingual tablet and oral spray, in 15 patients with isolated chronic pulmonary congestion (pulmonary arterial end-diastolic pressure of 15 mmHg or more in the presence of normal or only slightly reduced cardiac index). Both formulations produced significant reductions in the pulmonary arterial end-diastolic pressure. The effect of ISDN tablet (sublingually) became evident at 10 minutes after administration and was maximal at 30 minutes. The effect of ISDN oral spray became evident at 3 minutes and reached a peak at 10 minutes. The magnitude of hemodynamic response was similar. These findings indicate that ISDN oral spray is superior to ISDN sublingual tablets for rapid relief of pulmonary congestion     

Survival after aortic valve replacement for aortic stenosis: does left ventricular mass regression have a clinical correlate?

AIM: The effects of post-operative left ventricular mass regression (LVMR) on clinical outcome after aortic valve surgery remains to be established. This study was intended to establish the impact of patient characteristics on post-operative survival in patients referred for aortic valve replacement (AVR), with particular regard to LVMR. METHODS AND RESULTS: Two hundred and sixty consecutive cases submitted to aortic valve replacement for valvular stenosis were prospectively followed for a mean of 28+/-9 months. Baseline, characteristics and extent of LVMR were tested for association with survival by uni- and multivariable analysis. Ten deaths occurred during hospital stay and 52 during out-of-hospital follow-up. Mean left ventricular mass decreased from 190+/-43 to 158+/-70 g/m2 (P<0.001). Older age, advanced functional class, hypertension, reduced left ventricle ejection fraction, and high pre-operative left ventricular mass index were associated with reduced survival. Overall the extent of LVMR did not influence the clinical results, while only early (<6 months) LVMR was weakly associated with mid-term outcome. CONCLUSION: Survival after aortic valve surgery is mainly determined by the pre-operative functional cardiac and systemic status. The extent of LVMR does not correlate with clinical outcome, whereas aggressive treatment of hypertension may improve post-operative survival.     

Prostate cancer cell proliferation is strongly reduced by the epidermal growth factor receptor tyrosine kinase inhibitor ZD1839 in vitro on human cell lines and primary cultures

PURPOSE: To investigate the effects of the epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) ZD1839 ('Iressa') on the cellular proliferation of androgen-sensitive and androgen-independent human prostatic cancer cell lines and primary cultures in vitro. EXPERIMENTAL DESIGN: In this study, we investigated the effects of the quinazoline ZD1839, a potent, selective EGFR-TKI, on the EGFR autophosphorylation and cellular proliferation of androgen-sensitive (ND1, LNCaP, and ALVA-31) and androgen-independent (PC3, DU145, and TSU-Pr1) human prostatic cancer cell lines and 20 primary cultures derived from human prostatic cancer tissue. RESULTS: EGFR was present and phosphorylated in all cell lines tested. ZD1839 reduced EGFR autophosphorylation in intact cell lines with IC(50)s of 0.46-0.97 microM, and inhibited cellular proliferation with IC(50)s of 0.37-1.03 microM. Constitutive EGFR autophosphorylation was low in primary cell cultures, but addition of EGF (50 ng/ml) caused marked EGFR autophosphorylation; cellular proliferation in the presence of EGF was inhibited by ZD1839 with a mean IC(50) of 0.45 microM. At doses >1 microM, ZD1839 induced apoptosis in both androgen-dependent and androgen-independent PCa cell lines. CONCLUSION. Our experiments suggest that EGFR-TKIs such as ZD1839 may have potential in blocking the growth and progression of human prostatic cancers even in early phases of the disease.     

Predictors and Clinical Impact of Prosthesis-Patient Mismatch After Self-Expandable TAVR in Small Annuli

ObjectivesThe aim of this study was to define predictors of prosthesis-patient mismatch (PPM) and its impact on mortality after transcatheter aortic valve replacement (TAVR) with self-expandable valves (SEVs) in patients with small annuli.BackgroundTAVR seems to reduce the risk for PPM compared with surgical aortic valve replacement, especially in patients with small aortic annuli. Nevertheless, predictors and impact of PPM in this population have not been clarified yet.MethodsPredictors of PPM and all-cause mortality were investigated using multivariable logistic regression analysis from the cohort of the TAVI-SMALL (International Multicenter Registry to Evaluate the Performance of Self-Expandable Valves in Small Aortic Annuli) registry, which included patients with severe aortic stenosis and small annuli (annular perimeter <72 mm or area <400 mm² on computed tomography) treated with transcatheter SEVs: 445 patients with (n = 129) and without (n = 316) PPM were enrolled.ResultsIntra-annular valves conferred increased risk for PPM (odds ratio [OR]: 2.36; 95% confidence interval [CI]: 1.16 to 4.81), while post-dilation (OR: 0.46; 95% CI: 0.25–0.84) and valve oversizing (OR: 0.53; 95% CI: 0.28–1.00) seemed to protect against PPM occurrence. At a median follow-up of 354 days, patients with severe PPM, but not those with moderate PPM, had a higher all-cause mortality rate compared with those without PPM (log-rank p = 0.008). Multivariable Cox regression confirmed severe PPM as an independent predictor of all-cause mortality (hazard ratio: 4.27; 95% CI: 1.34 to 13.6).ConclusionsAmong patients with aortic stenosis and small aortic annuli undergoing transcatheter SEV implantation, use of intra-annular valves yielded higher risk for PPM; conversely, post-dilation and valve oversizing protected against PPM occurrence. Severe PPM was independently associated with all-cause mortality.