Femoral bone mineral density at the time of hip fracture is higher in women with versus without type 2 diabetes mellitus: a cross-sectional study.

PURPOSE: To compare femoral bone mineral density (BMD) levels in hip-fracture women with versus without type 2 diabetes mellitus (T2DM). We hypothesized that BMD levels could be higher in the women with T2DM than in controls and we aimed to quantify the BMD discrepancy associated with the presence of T2DM. METHODS: At a median of 20 days after the occurrence of an original hip fracture due to fragility we measured BMD by dual-energy x-ray absorptiometry at the non-fractured femur. RESULTS: We studied 751 women with subacute hip fracture. Femoral BMD was significantly higher in the 111 women with T2DM than in the 640 without diabetes: mean T-score between-group difference was 0.50, (95% CI from 0.30 to 0.69, P < 0.001). The association between the presence of T2DM and femoral BMD persisted after adjustment for age, body mass index, hip-fracture type, neurologic diseases, parathyroid hormone, 25-hydroxyvitamin D and estimated glomerular filtration rate (P < 0.001). For a woman without versus with T2DM, the adjusted odds ratio to have a femoral BMD T-score below the threshold of - 2.5 was 2.13 (95% CI from 1.33 to 3.42, P = 0.002). CONCLUSIONS: Fragility fractures of the hip occurred in women with T2DM at a femoral BMD level higher than in control women. In the clinical assessment of fracture risk, we support the adjustment based on the 0.5 BMD T-score difference between women with and without T2DM, although further data from robust longitudinal studies is needed to validate the BMD-based adjustment of fracture risk estimation.

Enterolith causing acute afferent loop syndrome after Billroth II gastrectomy: a case report.

Enterolith is a rare cause of afferent loop obstruction following Billroth II gastrectomy. We report a case of acute afferent loop syndrome (ALS) due to a huge enterolith, necessitating prompt surgery. The clinical pattern may mimic acute cholangitis and/or pancreatitis. Delayed diagnosis may result in severe complications such as bowel ischemia or perforation. Only 14 reported cases of enterolith causing afferent loop obstruction were found in the English literature.

Are all left bundle branch blocks the same? Myocardial mechanical implications by cardiovascular magnetic resonance.

AIMS: Left bundle branch block (LBBB) is usually associated with structural myocardial diseases progressively leading to left ventricular (LV) dysfunction. We sought to determine the mechanical implications of LBBB (as defined based on Strauss' criteria) by Cardiovascular Magnetic Resonance (CMR). METHOD AND RESULTS: We included consecutive patients referred to CMR to assess the structural cause of LBBB. CMR scans consisted of cine, stress perfusion, and late gadolinium enhancement (LGE) sequences. Myocardial deformation was assessed by tissue tracking analysis; LGE was quantified using the full width at half maximum method. We included 86 patients [63% male, 70 years (60-72)] with mean QRS duration 150 ± 13 msec. A structural disease was identified on CMR in 53% of patients (ischemic heart disease, IHD, 31%; non-ischemic heart disease, NIHD, 22%), while LBBB-related septal dyssynchrony (SD) was the only abnormality in 47%. LGE was found in 42% of patients. LVEF and myocardial deformation were impaired. Despite similar ECG characteristics, myocardial strain differed significantly between IHD, NIHD and SD patients, and patients with SD showed less impaired myocardial deformation. Indexed LV end-systolic volume and LGE extent were independently associated with impaired strain. CONCLUSIONS: Patients with LBBB show different structural and mechanical properties, and LGE extent has an unfavourable effect on myocardial mechanics.

Quantitative evaluation of functional limitation of upper limb movements in subjects affected by ataxia.

BACKGROUND AND PURPOSE: The design of useful and effective treatment strategies for movement disorders largely depends on the ability to objectively quantify changes in performances, providing reliable outcome measures. Evaluation of ataxia remains mainly assigned to different clinical scales, providing a semi-quantitative assessment. The aim of this study was to quantitatively characterize functional changes in upper limb movements in ataxic patients, using an optoelectronic system for objective measurements. METHODS: Fourteen patients with cerebellar ataxia and 27 healthy subjects were analyzed using an optoelectronic system with passive markers during pointing task and hand-to-mouth movement. Quantitative parameters capable of characterizing ataxic movements were defined using recorded kinematics. RESULTS: In both the considered functional movements, ataxic patients showed increased adjustment during the last phase of movement. The movement was less smooth than that in controls, with a fragmented trajectory presenting more direction changes than controls. CONCLUSIONS: The proposed protocol allows the quantitative characterization of the motion pattern of ataxic subjects in a non-invasive way. We believe that this analysis could represent a good tool for ataxia evaluation in a clinical context such as neurorehabilitation.

CAR-dependent and CAR-independent pathways of adenovirus vector-mediated gene transfer and expression in human fibroblasts.

Primary fibroblasts are not efficiently transduced by subgroup C adenovirus (Ad) vectors because they express low levels of the high-affinity Coxsackie virus and adenovirus receptor (CAR). In the present study, we have used primary human dermal fibroblasts as a model to explore strategies by which Ad vectors can be designed to enter cells deficient in CAR. Using an Ad vector expressing the human CAR cDNA (AdCAR) at high multiplicity of infection, primary fibroblasts were converted from being CAR deficient to CAR sufficient. Efficiency of subsequent gene transfer by standard Ad5-based vectors and Ad5-based vectors with alterations in penton and fiber was evaluated. Marked enhancement of binding and transgene expression by standard Ad5 vectors was achieved in CAR-sufficient fibroblasts. Expression by AdDeltaRGDbetagal, an Ad5-based vector lacking the arginine-glycine-aspartate (RGD) alphaV integrin recognition site from its penton base, was achieved in CAR-sufficient, but not CAR-deficient, cells. Fiber-altered Ad5-based vectors, including (a) AdF(pK7)betagal (bearing seven lysines on the end of fiber) (b) AdF(RGD)betagal (bearing a high-affinity RGD sequence on the end of fiber), and (c) AdF9sK betagal (bearing a short fiber and Ad9 knob), demonstrated enhanced gene transfer in CAR-deficient fibroblasts, with no further enhancement in CAR-sufficient fibroblasts. Together, these observations demonstrate that CAR deficiency on Ad targets can be circumvented either by supplying CAR or by modifying the Ad fiber to bind to other cell-surface receptors.

Managing ulcerative colitis in remission phase: usefulness of Casperome®, an innovative lecithin-based delivery system of Boswellia serrata extract.

OBJECTIVE: Boswellia serrata extracts (BSE) have been traditionally used for the treatment of several inflammatory diseases. The aim of this study was to evaluate the efficacy of a novel delivery form of BSE (Casperome®) in Ulcerative Colitis (UC) during minimally symptomatic remission phase. PATIENTS AND METHODS: In this open-label, observational, registry study, informed participants with UC in remission phase (n = 43) freely decided to receive the oral daily Casperome® supplementation (n = 22) or no supplementation (n = 21) for 4 weeks. Several parameters associated with minimally symptomatic UC in remission were evaluated at the inclusion and the end of the study. RESULTS: A significant beneficial effect of Casperome® was observed for all the parameters evaluated, namely: diffuse intestinal pain, evident and occult blood in stools, bowel movements and cramps, watery stools, malaise, anemia, rectal involvement, number of white blood cells as well as need for concomitant drugs and medical attention. Faecal concentration of calprotectin, a marker of bowel inflammation, resulted ameliorated in Casperome® supplemented patients. CONCLUSIONS: Our study showed that Casperome® supplementation attenuates symptoms associated with mild UC in remission, reducing the use of drugs and medical consultations. Therefore, our study suggests that Casperome® supplementation could represent a promising alternative approach to manage minimally symptomatic UC and maintain the remission phase.

Quantitative PCR reveals increased levels of tumor necrosis factor-alpha mRNA in peripheral blood mononuclear cells of multiple sclerosis patients during relapses.

Quantification of tumor necrosis factor-alpha (TNF-alpha) mRNA in peripheral blood mononuclear cells (PBMC) could provide information about disease activity in multiple sclerosis (MS); however, specific competitive methods must be utilized. A competitor cDNA, having the same sequence of the target TNF-alpha cDNA, a part from an internal 49-bp deletion, was generated and used to set-up a quantitative polymerase chain reaction (PCR) to quantify mRNA of TNF-alpha. Competitor and target were co-amplified using the same primers. The rates of generation of competitor and target TNF-alpha conformed closely to the prediction of the mathematical model, and a high level of accuracy and reproducibility was achieved. The method was applied to quantify TNF-alpha mRNA in PBMC of normal subjects and multiple sclerosis (MS) patients both during clinical relapses and remissions. A statistically significant higher level of TNF-alpha mRNA was detected during relapses than during remissions. High levels of TNF-alpha mRNA were found in 44% of relapses and 12% of samples during remissions, suggesting that TNF-alpha mRNA synthesis is abnormal in MS.

Expression analysis and mutational screening of the epithelium-specific ets gene-1 (ESE-1) in patients with squamous anal cancer.

To investigate whether ESE-1 gene abnormalities are involved in alterations of epithelial cell differentiation in squamous anal cancer ESE-1 expression and structure were screened in six patients by reverse transcriptase-polymerase chain reaction (RT-PCR) and automated sequence analysis. The complete cDNA of isoform ESE-1b was always expressed and correctly spliced, with single nucleotide polymorphism being observed in two cases. Presence of ESE-1b point mutations was excluded. Expression of SPRR2A and ENDOA/CK8, two epithelium-specific ESE-1 target genes, were revealed by RT-PCR in all cases. This first report of expression of ESE-1, and of SPRR2A and ENDOA/CK8 (both related to terminal differentiation in different types of epithelia lining) in anal cancer excludes the hypothesis that these genes influenced carcinogenesis in our patients. Despite selecting of patients without clinical evidence of HPV infection, PCR consistently revealed HPV-16 DNA, highlighting the importance of HPV infection in anal cancer.

Expression profile of epidermal differentiation complex genes in normal and anal cancer cells.

Anal cancer originates from a peculiar histological region and provides a useful model for investigating alterations in proliferation and/or differentiation of neoplastic keratinocytes. Epidermal differentiation complex (EDC) genes, which form one of the major gene clusters in the human genome, are involved in the terminal differentiation of epithelial cells and in many instances have been implicated in epithelial tumours. We constructed a DNA macroarray capable of characterising the expression profiles of the entire EDC gene complex in normal mucosa and anal cancer biopsies of seven unrelated patients. Brain tissue and cultured keratinocytes were used as controls. All anal cancer samples showed expression profiles in which none of the EDC genes was silent, as evaluated by phosphor-imager analysis. Variance analysis showed significantly lower expression of SPRR2 with respect to SPRR1 or SPRR3, and significantly higher expression of S100A8 than of other S100A subfamily members. At hierarchical clustering analysis, the four basaloid anal cancer cases conglomerated in the top five positions. The macroarray method used by us provides the first demonstration of the expression profile of the EDC gene family in anal cancer, and is capable of producing significant information on the subgrouping of epithelial tumours such as anal cancer.

Detection of brain metastases: comparison of contrast-enhanced MR with unenhanced MR and enhanced CT.

Contrast-enhanced MR studies were compared with noncontrast MR and contrast-enhanced CT scans in the evaluation of intraparenchymal brain metastases. Fifty consecutive inpatients were studied with short and long repetition time (TR) sequences before and after the administration of gadopentetate dimeglumine. In addition, a delayed short TR sequence was performed. The contrast CT, noncontrast MR, immediate postcontrast short TR sequence, postcontrast long TR sequence, and delayed postcontrast short TR sequence were each read blindly and independently by two neuroradiologists. These results were then compared with a final interpretation, reached by all the neuroradiologists in the study, using all the clinical information and imaging findings. Postcontrast short TR scans proved to be superior to other sequences. They were particularly useful in the detection of metastases in the posterior fossa and cortex. The delayed postcontrast short TR scan held no definite advantage over the immediate postcontrast short TR scan, although metastases were sometimes seen slightly better after the delay. While long TR sequences were not always sensitive or specific, they often did provide ancillary information and were particularly useful in cases of hemorrhagic metastases. Because of these findings, we recommend that the evaluation of intraparenchymal metastases consist of a single postcontrast long TR scan followed by a single postcontrast short TR scan. While these sequences should be very accurate in the detection of metastases, we also generally perform a single precontrast short TR scan as well, since the question of hemorrhage or bone lesion may be clinically relevant.

Stability-indicating high-performance liquid chromatographic analysis of lidocaine hydrochloride and lidocaine hydrochloride with epinephrine injectable solutions.

A reversed-phase, high-performance liquid chromatographic (HPLC) procedure, which is specific and quantitative for lidocaine hydrochloride, epinephrine, and methylparaben, was developed for the analysis of lidocaine hydrochloride and lidocaine hydrochloride with epinephrine solutions for injection. Epinephrine sulfonic acid and adrenochrome are separated in this system. Also separated are lidocaine and methylparaben and their respective degradation products, 2-6-xylidine and p-hydroxybenzoic acid. The analysis requires that three detectors (two UV and one electrochemical) be connected in series. By using this arrangement, lidocaine hydrochloride and methylparaben are quantitated by UV at 254 and 280 nm, respectively, while epinephrine is quantitated electrochemically. The method is simple, accurate, precise, and rapid. No sample preparation or internal standard is necessary, and only a 2-microliter sample volume is required for analysis. Chromatographic conditions include a mu Bondapak CN column and a mobile phase of 0.01 M 1-octanesulfonic acid sodium salt, 0.1 mM edetate disodium, 2% acetic acid, 2% acetonitrile, and 1% methanol in water.

Assay of tocainide in blood by high-pressure liquid chromatography.

A sensitive, specific, high-pressure liquid chromatographic assay for the determination of tocainide in whole blood is described. The residue from a methylene chloride extract of alkalinized blood was resolvated in a mobile phase of methanol--water (47:53) containing 1% acetic acid and 6.16 mM 1-octanesulfonic acid, adjusted to pH 4.0. Chromatography was performed on a reversed-phase column with detection at 254 or 225 nm. The limits of accurate measurement were 2 microgram/ml for a 1-ml blood sample monitored at 254 nm and 0.2 microgram/ml for a 2-ml sample monitored at 225 nm. The assay was tested on samples from emergency protocol patients and was also found suitable for single-dose pharmacokinetic studies.

Advances in management of meconium aspiration syndrome.

Meconium Aspiration Syndrome (MAS) is a leading cause of respiratory distress in the newborn. Antenatal diagnosis of meconium stained amniotic fluid and fetal distress is important to reduce morbidity and mortality in the neonates. Amnioinfusion of saline and tracheal suctioning of meconium are preventive interventions. Babies with MAS who continue to have respiratory distress need to be put on conventional ventilators. Increasing hypoxia, hypercarbia and barotrauma warrants changing to high frequency oscillatory ventilation. Pulmonary hypertension is an important complication which should be promptly recognized. Nitric oxide therapy used with high frequency ventilation has improved the outcome of babies with severe MAS and pulmonary hypertension. Some of these babies who continue to worsen clinically need to be put on ECMO circuit. Surfactant infusion in babies with MAS has been shown to improve gas exchange, resolve pulmonary hypertension and decrease oxygenation index. Total and partial liquid ventilation with perflurocarbon improves oxygenation, increases lung expansion and increases pulmonary blood flow in model studies of animals with MAS. Surfactant infusion and liquid ventilation are newer promising modes of therapeutic interventions in babies with severe MAS.

Olanzapine therapy in hallucinatory visions related to Bonnet syndrome.

Charles Bonnet syndrome (CBS) is characterised by the triad of complex visual hallucinations, ocular pathology causing visual deterioration and preserved cognitive status. We report a case of a 62-year-old man with a brief history of visual hallucinations. The patient complained of amaurosis with optic nerve atrophy in his left eye and a severe impairment of visual acuity in the right and suddenly experienced complex, vivid, elaborate and coloured visual hallucinations persisting long after eye closure and stopping during sleep. The patient maintained his insight, criticising these visions as unreal and felt distressed by them. Hallucination onset was 3 days before hospital admission. No cognitive impairment and no diseases apart from prostatic adenoma treated with alpha-lythic therapy were reported. Neurological examination and neuroimaging data were normal. Therapy with olanzapine (OLZ) 5 mg/day led to a progressive clearance of visual hallucinations in seven days and was gradually reduced and withdrawn. Three months later the visions reappeared and OLZ 5 mg/day yielded a persisting remission so that at the follow-up examination after 1 year on therapy the patient is still asymptomatic. To date, no established treatment for CBS is stated and in some patients the hallucinations fade spontaneously; in our case an antipsychotic therapy with OLZ was effective while generally anticonvulsant drugs with different mechanism of action such as carbamazepine, valproate and gabapentin are proposed.