Aetiology of congenital absence of vas deferens: genetic study of three generations

Bilateral congenital absence of the vas deferens (CAVD) is aform of male sterility (found in otherwise normal men) of unknownaetiology. Because males with cystic fibrosis (CF) almost invariablyhave CAVD as well, we investigated the hypothesis that men withisolated CAVD might share a common genetic background with maleswith CF. Genetic testing for CF was carried out in three generationsof subjects: 44 patients with CAVD and their wives, 24 of theirparents, and 13 of their offspring generated by microsurgicalepididymal sperm aspiration (MESA) and in-vitro fertilization(IVF). DNA extracted from peripheral lymphocytes was amplifiedby the polymerase chain reaction (PCR) and then analysed for12 mutations in the cystic fibrosis transmembrane conductanceregulatory (CFTR) gene. Among 44 patients tested with CAVD,26 (59%) were positive for at least one CF mutation, while thecarrier frequency for CF mutations in the general populationis only 4%. Four patients were found to be compound heterozygotes,three with genotypes Delta F-508/R117H, one with R553X/R117H.Among 24 parents tested, 15 (seven fathers, eight mothers) hadsons with CAVD who were positive for CF mutations. Of these,nine (four fathers and five mothers) were found to be carriersfor CF mutations. These four fathers, although carriers of CFmutations, were obviously fertile. Of the 13 offspring tested,six (three boys and three girls) had CF positive fathers. Ofthese, three (two girls and one boy) were found to be carriersfor CF mutations. These MESA/IVF children are the first offpsringto whom men with CAVD have been able to transmit CF mutations.All of the MESA/IVF male offspring (like their grandfathers)had a normal vas deferens bilaterally, including one carrierfor Delta F-508. This study revealed, by genetic testing ofotherwise normal men with sterility caused by CAVD, a new populationof patients with a variant form of CF and highlighted the possibilitythat carrier frequency for CF is higher than previously thought.Compound heterozygosity for CF mutations and not carrier conditionis associated with isolated CAVD. It is concluded that geneticcounselling and screening for CF should be offered to couplesundergoing sperm aspiration and IVF procedures when CAVD isa factor in their infertility.     

Suppression of lymphokine-activated killer cell generation by tumor-infiltrating lymphocytes

A functional analysis of tumor-infiltrating lymphocytes (TILs) from renal cell carcinoma (RCC) and malignant melanoma was performed. TILs were expanded in recombinant interleukin-2 (50 U/ml) in Iscoves medium. Phenotypic and functional (cytolytic vs regulatory) analyses were carried out with the fresh and expanded TIL populations after 4 weeks in culture. Only one TIL population from an RCC case (out of six cases studied) was CD8+ and demonstrated MHC class I-restricted tumor-specific cytotoxicity against the autologous RCC target. TIL populations from the other five cases became predominantly CD4+ and they neither killed the respective autologous tumor cells nor killed the NK-sensitive target K-562 cells. When studied for other functions, two CD4+ TIL populations were found to suppress the lymphokine-activated killer cell response by peripheral blood lymphocytes (PBL) in coculture. Of these two, a TIL population from an RCC case (MJ TIL) was used to study the cellular and molecular mechanisms of suppression. The MJ TIL synthesized a supernatant factor that blocked activation of resting PBL as measured by the induction of high-affinity IL-2 receptor (IL-2R) when stimulated by phytohemagglutinin but did not down-regulate the fully expressed IL-2R on activated T cells. The suppression of high-affinity IL-2R induction on T cells did not result from tumor necrosis factor-alpha and beta or from transforming growth factor-beta as these cytokines were not detected in the cell-free supernatant from the MJ TIL culture. The supernatant factor also suppressed IL-2-mediated enhancement of cytotoxicity by natural killer (NK) cells without demonstrating direct toxic effect on the NK cells. Thus, when TIL are used for adoptive immunocytotherapy, it may be useful to fully characterize them functionally, in vitro.     

Exhaled breath condensate cysteinyl leukotrienes are increased in children with exercise-induced bronchoconstriction

BACKGROUND: It is recognized that airway inflammation has a central role in the pathogenesis of asthma, but how it relates to exercise-induced bronchoconstriction (EIB) is not completely understood. OBJECTIVE: The aim of our study was to investigate the relationship between EIB and baseline concentrations of cysteinyl leukotrienes (Cys-LTs) and other inflammatory markers in exhaled breath condensate (EBC). METHODS: EBC was collected, and the fraction of exhaled nitric oxide (FE NO ) was measured in a group of 19 asthmatic children, after which they performed a treadmill exercise test. Fourteen healthy children were enrolled as control subjects. RESULTS: The asthmatic children were divided into the EIB group (decrease in FEV 1 , > or =12%) and the non-EIB group. The EBC was analyzed for the presence of Cys-LTs, leukotriene B 4 , and ammonia. Asthmatic patients with EIB (mean FEV 1 decrease, 23% +/- 3%) had higher Cys-LT concentrations than either asthmatic patients without EIB or control subjects (42.2 pg/mL [median] vs 11.7 pg/mL and 5.8 pg/mL; P < .05 and P < .001, respectively). Ammonia concentrations were lower in both the EIB and non-EIB groups than in control subjects (253.2 microM and 334.6 microM vs 798.4 microM; P < .01 and P < .05, respectively). No difference in EBC leukotriene B 4 levels was found among the 3 groups. Both asthmatic groups had higher FE NO levels than control subjects ( P < .001). EBC Cys-LT ( P < .01; r = 0.7) and FE NO ( P < .05; r = 0.5) values both correlated significantly with the postexercise FEV 1 decrease. CONCLUSION: this study shows that EBC Cys-LT values are higher in asthmatic children with EIB and correlate with the decrease in FEV 1 after exercise. These findings suggest that the pathways of both Cys-LT and nitric oxide are involved in the pathogenesis of EIB.     

Early detachment of titanium particles from various different surfaces of endosseous dental implants

Titanium (Ti) endosseous dental screws with different surfaces (smooth titanium--STi, titanium plasma-sprayed-TPS, alumina oxide sandblasted and acid-etched--Al-SLA, zirconium oxide sandblasted and acid etched--Zr-SLA) were implanted in femura and tibiae of sheep to investigate the biological evolution of the peri-implant tissues and detachment of Ti debris from the implant surfaces in early healing. Implants were not loaded. Sections of the screws and the peri-implant tissues obtained by sawing and grinding were analysed by light microscopy immediately after implantation (time 0) and after 14 days. All samples showed new bone trabeculae and vascularised medullary spaces in those areas where gaps between the implants and host bone were visible. In contrast, no osteogenesis was induced in the areas where the implants were initially positioned in close contact with the host bone. Chips of the pre-existing bone inducing new peri-implant neo-osteogenesis were surrounded by new bone trabeculae. The threads of some screws appeared to be deformed where the host bone showed fractures. Ti granules of 3-60 microm were detectable only in the peri-implant tissues of TPS implants both immediately after surgery and after 14 days, thus suggesting that this phenomenon may be related to the friction of the TPS coating during surgical insertion.     

The role of external ventricular drainage for the management of posterior cranial fossa tumours: a systematic review

Neurosurgical Review - Posterior cranial fossa tumours frequently develop hydrocephalus as first presentation in up to 80% of paediatric patients and 21.4% of adults, although it resolves after...     

Nocturnal Paroxysmal Dystonia with Short-Lasting Attacks: Three Cases with Evidence for an Epileptic Frontal Lobe Origin of Seizures

The epileptic or nonepileptic origin of nocturnal paroxysmal dystonia (NPD) has been debated. We studied three patients with frequent attacks during non-REM sleep. During prolonged video-EEG monitoring, two patients had a convulsive seizure after a typical NPD episode and on these occasions EEG showed epileptiform discharge. In the three patients, attacks occurred repeatedly with different intensity, representing "fragments" of the same seizure. These fragments of the attack could occur periodically every 20-40 s. We postulate that short NPD attacks are actually epileptic seizures originating from the frontal lobes. The rhythmicity of the episodes may be due to rhythmic oscillation of cortical function during non-REM sleep.     

Cyclical use of tamoxifen and high-dose medroxyprogesterone acetate in advanced estrogen receptor positive breast cancer

Summary One-hundred and seventy patients with estrogen receptor positive (10 pmol/g protein) advanced breast cancer have been treated in a prospective randomized study either with continuous tamoxifen 30 mg × 1 daily (TAM), or with TAM 30 mg × 1 daily for 8 weeks alternating with medroxyprogesterone acetate 500 mg × 2 daily for 8 weeks (TAM/HD-MPA). The response rate was 62% in the group treated with cyclic TAM/HD-MPA versus 41% in the TAM alone group (p = 0.02). There was no significant difference in duration of remissions or survival.     

Choice of neurosurgical approach in the treatment of cranial base lesions

The authors describe a series of surgical approaches that they found particularly useful for the exposure and removal of lesions involving the skull base. These are: 1) fronto-naso-orbital approach; 2) frontotemporo-orbito-zygomatic approach; 3) subtemporal transpetrosal approach; 4) temporo-suboccipital transpetrosal approach (retrolabyrinthine presigmoid; transsigmoid; translabyrintine amend transcochlear presigmoid); 5) dorsolateral approach to the foramen magnum and lower clivus.As the approaches are complex and carry potential risks of morbidity, not only it is important to have a good knowledge of basic anatomy but also to closely follow the indications for each one. In this type of surgery where it is often difficult to achieve complete removal of the lesion by a single route of attack, more than one approach may be employed in different surgical steps. Finally, all these approaches demand extremely scrupulos surgical reconstruction to avoid dangerous postoperative complications that may jeopardize the previous work of the surgeon.