A high frequency of the A30, B18, DR3, DRw52, DQw2 extended haplotype in Sardinian celiac disease patients: Further evidence that disease susceptibility is conferred by DQ A1*0501, B1*0201

This study characterizes by serological and molecular methods the HLA class I and class II alleles in a group of celiac disease children, their parents and a control group of Sardinian descent. We found the DR3-DQw2 haplotype in all patients which was, in almost all cases (84%), associated with the HLA-A30, B18, DR3, DRw52, DQw2 extended haplotype named "Sardinian haplotype" because of its frequency (12-15%) in this Caucasian population. This is the first time that this DQw2-linked haplotype has been reported with such a high frequency in CD. However, no different distribution of "Sardinian haplotype" was found comparing CD patients with 91 haplotyped DQw2-positive controls. This finding indicates that the DQw2 antigen in Sardinians is almost always associated with the A30, B18, DR3, DRw52, DQw2 extended haplotype. The DQA1 and DQB1 second exon sequence analysis of the B18,DR3 and B8,DR3 haplotypes showed the DQA1*0501 and DQB1*0201 alleles which shared the already published sequences. DPB1 subtyping showed the DPB1*0301 allele more frequently (p less than 0.005) in CD patients but this difference was no longer significant when patients and controls, both heterozygous for the DR3-DQw2 haplotype, were compared. We suggest that the divergent HLA extended haplotypes and DP allele associated with CD, described in different Caucasian populations, can be explained by the particular DQw2 linkage disequilibrium in each population.     

Neuroendocrine carcinoma of the thymus: Aspiration biopsy,immunocytochemistry, and clinicopathologic correlates

We report three cases of well-differentiated neuroendocrine carcinoma originating primarily in the anterior mediastinum which had been initially investigated by fine-needle aspiration cytology in conjunction with immunocytochemistry and subsequently recognized as thymic in origin. Aspirates consisted of loosely cohesive or aggregated medium sized elements with round to oval nuclei and scanty cytoplasm. in all cases the Romanowsky stain provided an excellent delineation of definite paranuclear inclusion-like structures having a semicircular or discoid appearance which appeared to contain cytokeratin by immunocytochemical studies and were very similar to the intermediate filament paranuclear “buttons” found in neuroendocrine Merkel cell carcinoma of the skin. This appears to be a novel cytologic observation for thymic neuroendocrine carcinoma. We discuss the significance of the above cytologic and immunocytochemical findings and their possible role in the diagnosis of thymic neuroendocrine carcinoma by fine-needle aspiration biopsy. © 1995 Wiley- Liss, Inc.     

Metabolic fate of zetidoline,a new neuroleptic agent,in man

Summary Healthy volunteers administered orally a single dose (20 mg) of [2-¹⁴C]zetidoline, a new dopamine antagonist, exhibited rapid absorption of radioactivity with peak plasma levels of 250–300 ng/ml achieved in 1 h. The compound underwent intensive metabolic first-pass so that plasma radioactivity was represented mostly by two products, metabolite B endowed with neuroleptic activity, and metabolite D inactive, while unchanged zetidoline was not detected. Disappearance of radioactivity from plasma was rapid with a half-life of 1.78±0.20 h.The simultaneous assay of plasma prolactin showed increased levels of the hormone (+464% at the peak time) up to the 6th h after dosing, with plasma concentration profile which mimic those of metabolite B.The radioactive test-dose was eliminated mainly via the kidneys with an average urinary recovery of 84.7±1.7% in 4 days (73.4±1.1% within 8 h). The main urinary metabolite (metabolite G) and two minor ones (metabolites B and D) were purified and their structures assigned by IR, MS and NMR spectroscopy, they are: 1-(3-chloro-4-hydroxyphenyl)-3[2-(3,3-dimethyl-1-azetidinyl)ethyl]imidazolidin-2-one, metabolite B; 1-[2-(3,3-dimethyl-1-azetidinyl)ethyl]imidazolidin-2-one, metabolite D and the 4-O-sulphate ester of metabolite B, metabolite G.The metabolic fate of zetidoline in man follows the same phase I reactions demonstrated in rats and dogs, while the phase II reaction is sulphoconjugation instead of the glucuronidation observed in animals.     

In vitro Metabolism of Bumetanide

A new metabolite of the diuretic drug bumetanide, the 4-[(4-hydroxy)-phenoxy] analog (7), was identified in incubation mixtures of rat liver microsomes. Phenobarbital and clofibrate pretreatment to induce microsomal enzymes changed the relative amounts of the six metabolites formed. Compound 7was the most prevalent metabolite after clofibrate pretreatment.     

Sarcopenia and Appendicular Muscle Mass as Predictors of Impaired Fasting Glucose/Type 2 Diabetes in Elderly Women

Elderly women exhibit a high risk of type 2 diabetes (T2D), but no definitive data exist about the possible role of postmenopausal increases in visceral adiposity, the loss of lean body mass, or decreases in the sum of the lean mass of arms and legs (appendicular skeletal muscle mass (ASMM)). This retrospective, longitudinal study investigated whether body composition (bioelectrical impedance analysis) predicted the development of impaired fasting glucose (IFG) or T2D in a cohort of 159 elderly women (age: 71 ± 5 years, follow-up: 94 months) from southern Italy (Clinical Nutrition and Geriatric Units of the “Mater Domini” University Hospital in Catanzaro, Calabria region, and the “P. Giaccone ”University Hospital in Palermo, Sicily region). Sarcopenia was defined in a subgroup of 128 women according to the EWGSOP criteria as the presence of low muscle strength (handgrip strength <16 kg) plus low muscle mass (reported as appendicular skeletal muscle mass <15 kg). Participants with a low ASMM had a higher IFG/T2D incidence than those with a normal ASMM (17% vs. 6%, p-adjusted = 0.044); this finding was independent of BMI, fat mass, waist circumference, and habitual fat intake (OR = 3.81, p = 0.034). A higher incidence of IFG/T2D was observed in the subgroup with sarcopenia than those without sarcopenia (33% vs. 7%, p-adjusted = 0.005) independent of BMI and fat mass (OR = 6.75, p = 0.007). In conclusion, this study demonstrates that elderly women with low ASMM had a higher probability of developing IFG/T2D. Further studies are needed to confirm these results in men and in other age groups.     

Intracranial capillary hemangiomas: literature review in pediatric and adult population

Neurosurgical Review - Capillary hemangiomas (CHs) of the central nervous system represent a rare diagnosed pathology. CHs are benign vascular tumors whose most common manifestations are dermal and...     

Conversion of Fused Hip to Total Hip Arthroplasty: Long-Term Clinical and Radiological Outcomes

BackgroundDespite promising results at the mid-term followup, several aspects of conversion of the fused hip to total hip arthroplasty (THA) remain controversial. The aim of this study was to evaluate clinical and radiological outcomes with a minimum 5-year followup in patients who underwent conversion of the fused hip to THA.MethodsFifty-seven patients (59 hips) were evaluated. The Harris Hip Score (HHS), range of motion (ROM), and the Visual Analogue Scale (VAS) were used to assess hip function and low back pain. Subjective satisfaction with surgery and the presence of the Trendelenburg sign was also evaluated. Radiological assessment was performed pre- and postoperatively to evaluate loosening and heterotopic ossification (HO).ResultsAfter a mean followup of 13.0 ± 6.2 years, HHS and VAS significantly improved from 46.0 ± 16.7 to 80.8 ± 18.8 and from 4.4 ± 1.5 to 2.1 ± 1.4 (both P < .001), respectively. Twenty-three patients (40.4%) had a positive Trendelenburg sign, and HOs were found in 29 cases (49.1%). An overall 29.8% complication rate was noted. Smoking habits and rheumatoid arthritis were predictive of Trendelenburg sign (P = .046 and P = .038, respectively). Implant survival rate as the end point was 98.7 ± 1.3% at 5 years, 92.4 ± 3.3% at 10 years, 82.1 ± 5.7% at 15 years, and 73.4 ± 8.0% at 20 and 25 years. A worse cumulative implant survival rate was noted in patients who underwent previous hip surgery, defined as any hip operation before fusion (P = .005).ConclusionConversion of the fused hip to hip arthroplasty provides high levels of hip functionality and satisfaction with surgery at long-term followup. An implant survival rate higher than 70% can be expected 25 years postoperatively.