Virological and pharmacological parameters predicting the response to lopinavir-ritonavir in heavily protease inhibitor-experienced patients

The genotypic inhibitory quotient (GIQ) has been proposed as a way to integrate drug exposure and genotypic resistance to protease inhibitors and can be useful to enhance the predictivity of virologic response for boosted protease inhibitors. The aim of this study was to evaluate the predictivity of the GIQ in 116 protease inhibitor-experienced patients treated with lopinavir-ritonavir. The overall decrease in human immunodeficiency virus type 1 (HIV-1) RNA from baseline to month 6 was a median of -1.50 log(10) copies/ml and 40% of patients had plasma HIV-1 RNA below 400 copies/ml at month 6. The overall median lopinavir study-state C(min) concentration was 5,856 ng/ml. Using univariate linear regression analyses, both lopinavir GIQ and the number of baseline lopinavir mutations were highly associated with virologic response through 6 months. In the multivariate analysis, only lopinavir GIQ, baseline HIV RNA, and the number of prior protease inhibitors were significantly associated with response. When the analysis was limited to patients with more highly mutant viruses (three or more lopinavir mutations), only lopinavir GIQ remained significantly associated with virologic response. This study suggests that GIQ could be a better predictor of the virologic response than virological (genotype) or pharmacological (minimal plasma concentration) approaches used separately, especially among patients with at least three protease inhibitor resistance mutations. Therapeutic drug monitoring for patients treated by lopinavir-ritonavir would likely be most useful in patients with substantially resistant viruses.     

Clinical aspects of dysosmia and presentation of European Olfactory Test of "sniffin sticks": a review

The medical community has neglected olfactory dysfunction for a long time. However, over the last two decades, remarkable progress has been made in terms of understanding the sense of smell and both the assessment and diagnosis of olfactory dysfunction. Currently, there are only a few validated olfactory tests. The most commonly used one is the University of Pennsylvania Smell Identification Test. Owing to its cultural biases, this test is mostly used in the United States. "Sniffin' Sticks" are one of the first European tests to be widely used. Since their development in 1996, they have been applied in numerous studies and have found increasing use in otolaryngology clinics. The goal of this article is to present Sniffin' Sticks and to provide a review of clinical olfactory research during recent years.     

Analysis of cardiac parameters in animals with epilepsy: possible cause of sudden death?

Among the causes for sudden death in epilepsy, cardiac dysfunction has been an area of interest. Based on this, the aim of our study was to evaluate the heart rate (in vivo and in vitro) and ventricular pressure in vitro of rats with epilepsy induced by pilocarpine. Adult male Wistar rats (n=6) were given pilocarpine hydrochloride to induce status epilepticus. Control rats (n=6) received saline solution instead pilocarpine. Our results showed significant differences in the mean of heart rate in vivo between the groups. In contrast, we did not find differences during in vitro experiments. Our results suggest a central nervous system modulation on the heart, which could explain the sudden unexpected death in epilepsy.     

Medial temporal lobe atrophy and white matter hyperintensities are associated with mild cognitive deficits in non-disabled elderly people: the LADIS study

OBJECTIVE: To assess the associations of medial temporal lobe atrophy (MTA) and white matter hyperintensities (WMH) with cognitive function in a large group of independently functioning elderly people. METHODS: Data were drawn from the multicentre, multinational leukoaraiosis and disability (LADIS) project which is studying prospectively the role of WMH as an independent predictor of the transition to disability in non-disabled elderly people. In all, 639 participants were enrolled in the LADIS study. For the present analysis, data on 581 subjects were available. Cognitive function was assessed by the mini-mental state examination (MMSE). Visual ratings of WMH and MTA were undertaken on magnetic resonance images (MRI). RESULTS: The presence of either severe WMH or MTA was associated with a modest but non-significant increase in frequency of mild cognitive deficits (severe WMH: odds ratio (OR) = 1.9 (95% confidence interval (CI), 1.0 to 3.7); MTA present: OR = 1.5 (95% CI, 0.8 to 2.8)). However, subjects with the combination of MTA and severe WMH had a more than fourfold increase in frequency of mild cognitive deficits (OR = 4.1 (95% CI, 2.3 to 7.4)). Analysis of variance with post hoc Bonferroni t tests showed that subjects with both MTA and severe WMH performed worse on MMSE than those with either no MRI abnormality or a single MRI abnormality (p<0.05). CONCLUSIONS: These results provide further evidence for the combined involvement of both Alzheimer type pathology and vascular pathology in the earliest stages of cognitive decline and suggest an additive effect of WMH and MTA.     

Percutaneous uterine artery embolization for the treatment of symptomatic fibroids: current status

Uterine artery embolization (UAE) is increasingly being used as an alternative treatment to hysterectomy for symptomatic fibroids. Symptoms of pelvic pressure, urinary frequency and menorrhagia are controlled in 73-98% of patients who undergo UAE. At the 1-year follow-up, the uterus may shrink by up to 55% but re-growth of fibroid may however occur. The rate of major complications and amenorrhoea following this procedure is low, ranging in most series from 1 to 3.5% and 1 to 7%, respectively. Nevertheless, the rate of amenorrhoea in women over 45 seems to be higher. In order to completely block the arterial supply to the fibroid, UAE is typically performed in both uterine arteries. Different embolic agents are used such as polyvinyl alcohol, gelfoam and more recently gelatine tris-acryl microspheres. After UAE, perfusion of the uterus is maintained. Uterine function is therefore conserved and although women who become pregnant after UAE seem to be at risk for malpresentation, pre-term birth, cesarean delivery and postpartum hemorrhage, successful pregnancies after UAE have been reported in some series. A major technical problem with UAE remains the possible presence of fibroid blood supply from other sources, such as the ovarian arteries or other pelvic branches, which can lead to failure of the procedure. In conclusion, although randomized trials are still underway, UAE appears a good option for those patients who whish to conserve their fertility or when surgery is contra-indicated. However, to evaluate the long-term effects of UAE longer follow up is required.     

A screening instrument for a Sicilian neuroepidemiological survey in the elderly

We evaluated the sensitivity and specificity of a screening instrument developed for use in a two-phase neuroepidemiological survey in Sicily. The Sicilian Epidemiological Dementia Study (SEDES) project will evaluate the prevalence and incidence of dementia, parkinsonisms and essential tremor in four Sicilian municipalities. It is a two-phase door-to-door survey. To identify subjects with possible neurological disorders, in this study, we developed a screening instrument including a symptoms questionnaire and simple physical tasks for parkinsonisms and essential tremor. The Mini-Mental State Examination (MMSE) was chosen for screening dementia. The symptoms questionnaire and simple tasks developed to identify possible patients with parkinsonism and essential tremor, was tested in a hospital setting. To evaluate sensitivity, we selected 20 patients with essential tremor and 40 with Parkinson's disease (20 with Stages I-II and 20 with Stages III-V) [Neurology 17 (1967) 427]. To evaluate specificity we also selected 20 healthy subjects. The screening instrument was administered in a hospital setting by trained interviewers. Sensitivity of the screening instrument (questionnaire plus simple tasks) was 100% for essential tremor and parkinsonisms regardless of the stage. Specificity of the instrument was 90% (95% CI 66.9-98.2); the predictive positive value was 90.9%, while the negative predictive value was 100%. Even if validity was assessed in a hospital setting, the high sensitivity and specificity obtained suggest that the instrument could be an appropriate screening tool for parkinsonisms and essential tremor in a two-phase neuroepidemiological survey.     

Determinants of erectile dysfunction risk in a large series of Italian men attending andrology clinics

OBJECTIVE: To assess determinants of ED in men who asked for a free of charge andrologic consultation during a week focused on andrologic prevention in Italy. METHODS: Men were invited to attend 178 participating andrology centers for a free of charge visit for counselling about urologic or andrologic conditions. Data were recorded with a simple questionnaire used by all centers. RESULTS: 2499 (19.9%) were diagnosed having ED. The frequency of ED increased with age, ranging from 4.6% in men under 25 years, to 37.6% in men over 74. In comparison with men with primary education the OR of ED was 0.8 (95% CI 0.7-0.9) in men with secondary education and 0.7 (95% CI 0.6-0.9) in those with university degree. After adjusting for age, the risk of ED was significantly higher in men consuming more than 3 glasses/day of alcoholic drinking (OR 1.4, 95% CI 1.1-2.0), in subjects smoking more than 10 cigarettes/day (OR 1.2, CI 95% 1.1-1.4) and in former smokers (OR 1.2, CI 95% 1.1-1.4). Men performing at least two hours per week of physical activity had a decreased risk of ED (OR 0.8, CI 95% 0.7-0.9). We found an increased risk of ED in men with diabetes (OR 1.2, 95% CI 1.1-1.4), hypertension (OR 1.3, 95% CI 1.1-1.4), cardiopathy (OR 1.5, 95% CI 1.3-1.8) and hypercholesterolemia (OR 1.4, 95% CI 1.2-1.6). CONCLUSIONS: This study provides further data on determinants of ED risk in a large data set and underlines the relationship between ED and cardiovascular diseases.     

Trisacryl Gelatin Microspheres Versus Polyvinyl Alcohol Particles in the Preoperative Embolization of Bone Neoplasms

The aim of this study was to compare the efficacy of trisacryl gelatin microspheres versus polyvinyl alcohol particles (PVA) in the preoperative embolization of bone neoplasms, on the basis of intraoperative blood loss quantified by the differences in preoperative and postoperative hematic levels of hemoglobin, hematocrit and erythrocytes count. From January 1997 to December 2002, preoperative embolization of bone tumors (either primary or secondary) was carried out in 49 patients (age range 12/78), 20 of whom were treated with trysacril gelatin microspheres (group A) and 29 with PVA particles (group B). The delay between embolization and surgery ranged from 1 to 13 days in group A and 1 to 4 days in group B. As used in international protocols, we considered hematic levels of hemoglobin, hematocrit and erythrocytes count for the measurement of intraoperative blood loss then the differences in pre- and postoperative levels were used as statistical comparative parameters. We compared the values of patients treated with embospheres (n = 10) and PVA (n = 18) alone, and patients treated with (group A = 10; group B = 11) versus patients treated without other additional embolic materials in each group (group A = 10; group B = 18). According to the Students t-test (p < 0.05), the difference of hematic parameters between patients treated by embospheres and PVA alone were significant; otherwise there was no significant difference between patients treated with only one embolic material (embospheres and PVA) versus those treated with other additional embolic agents in each group. The patients treated with microspheres had a minor quantification of intraoperative blood loss compared to those who received PVA particles. Furthermore, they had a minor increase of bleeding related to the delay time between embolization and surgery. The use of additional embolic material did not improve the efficacy of the procedure in either group of patients.     

Simultaneous liver-kidney transplantation for glycogen storage disease type IA (von Gierke's disease)

INTRODUCTION: Glycogen storage disease type Ia (GSDIa) is due to the deficiency of glucose-6-phosphatase activity in the liver, kidney, and intestine. Although significant progress has been achieved in the management of patients with GSDIa, complications still emerge. The potential for development of liver adenomatosis and kidney failure makes these patients candidates for simultaneous liver-kidney transplantation (SLKT). Herein, we describe such a transplantation in a patient affected by this rare storage disease. METHODS: A 25-year-old female patient with GSDIa developed hepatic adenoma and kidney failure despite dietary therapy. The patient underwent an SLKT from a cadaveric donor. RESULTS: The operative time was 8 hours without hemotransfusion. Only a transitory lactic acidosis was observed. Laboratory results normalized on postoperative day 7. The patient was discharged on postoperative day 9. After 4 months, the patient is in good condition with well-functioning kidney and liver allografts. CONCLUSION: Patients with end-stage renal disease secondary to GSDIa should be considered for SLKT, especially when the disease is in an early stage.