Management of patients with carotid stenosis

Carotid atherosclerosis is one of the main risk factors for ischemic stroke. The annual risk of ipsilateral stroke for asymptomatic, albeit severe stenoses is as low as 1 to 2%, but increases to 13% in patients with recent ischemic symptoms. However the risk decreases after the first 2-3 years from the symptomatic episode, dropping to 3%. Echo-color Doppler ultrasonography is the screening method of choice, being highly accurate, noninvasive and low-cost. Carotid angiography still represents the gold standard, however, less invasive techniques as RM angiography and Angio-CT are becoming increasingly common. Based on NASCET, ECST and ACAS results, carotid endarterectomy (CE) is strongly recommended for severe symptomatic stenoses, while for the moderate symptomatic and the severe asymptomatic ones the benefit in terms of stroke risk reduction is modest and surgery should be restricted to selected cases in surgical centers of high experience. For severe asymptomatic stenoses NNT is too high to recommend indiscriminate surgery; we are waiting for the results of ACSRS trial, designed to identify a subset of patients at risk of ipsilateral stroke greater than 4%/y, that may be considered for CE, while patients at low risk will be spared from unnecessary operation. Apart from surgery, in all patients with carotid atherosclerosis correction of cardiovascular risk factors is mandatory. Antiplatelet therapy (ASA alone or with dypiridamole, ticlopidine) is effective in secondary prophylaxis of athero-thrombotic stroke; its use in asymptomatic carotid stenoses can be recommended, even if more because of a plausible rationale than of clinical trial-based evidences.     

Histopathology of carotid body in heroin addiction. Possible chemosensitive impairment

AIMS: To perform a morphometric analysis of carotid bodies in opiate addicts. METHODS AND RESULTS: Carotid bodies were sampled at autopsy from 35 subjects who died of heroin intoxication (mean age 26 years), and from eight young (22 years) and eight older subjects (66.5 years) who died of trauma. Sections were stained with haematoxylin-eosin, azan-Mallory, and double-labelling immunohistochemistry with antineuronal specific enolase and anti-S100, to count type I and type II cells. Interlobular and intralobular connective tissue was increased both in the opiate cases (43.45 +/- 6.79%, P < 0.001, and 13.34 +/- 5.72%, P < 0.001, respectively) and older cases (46.67 +/- 1.65%, P < 0.001, and 9.62 +/- 2.11%, P < 0.05, respectively) compared with young cases (33.17 +/- 6.41% and 4.33 +/- 1.84%, respectively). The percentage of type II cells in the opiate cases (51.6 +/- 7.3%, P < 0.001) and in the older controls (49.0 +/- 7.2%, P < 0.01) was higher than in the young cases (37.9 +/- 3.0%). Among type I cells, the light cell percentage in the opiate cases (65.85 +/- 11%, P < 0.001) was reduced with respect to the two control groups (82.8 +/- 5.34%, young; 81.62 +/- 8.58%, older). CONCLUSIONS: The increases in connective tissue and type II cells are similar to findings in ageing and chronic pulmonary disease, and may be ascribed to glomic hypoxia. A direct action of opiates should be taken into account for the decrease in light cells in heroin addiction. The histopathological changes in the carotid body, by impairing chemosensivity, may play a role in the fatal cardiorespiratory derangement of heroin addicts.     

Increased aneuploidy in spermatozoa from testicular tumour patients after chemotherapy with cisplatin, etoposide and bleomycin

Testicular cancer is the most common neoplasia occurring in the young male population. The PEB (cisplatin, etoposide and bleomycin) adjuvant chemotherapy usually proposed after orchidectomy in non seminomatous tumours, and in metastatic seminomas, has improved the long-term survival of these patients. Following an azoospermic period, sperm cell recovery is generally observed after treatment delivery, but little is known about the genetic consequences on these new spermatozoa. To estimate the chromosomal consequences of this chemotherapy on sperm cells during the period of recovery of spermatogenesis, sperm cell aneuploidy was studied in testicular cancer patients, at 6-18 months after PEB adjuvant chemotherapy delivery, using fluorescence in-situ hybridization (FISH) of chromosomes 7, 16, 18, X and Y with specific DNA probes. A significant increase in the frequency of diploidy and disomy for chromosomes 16, 18 and XY was observed in treated patients compared with a healthy control group. Spermatozoa aneuploidy occurring during the spermatogenesis recovery period might be a possible side effect of the PEB regimen. Thus, practitioners should be advised to provide counselling about the need for an appropriate duration of contraception. Moreover, genetic counselling should be offered in cases of pregnancy occurring soon after the end of chemotherapy.     

Regional hyperthermia applicator design using FDTD modelling

Recently published results confirm the positive effect of regional hyperthermia combined with external radiotherapy on pelvic tumours. Several studies have been published on the improvement of RF annular array applicator systems with dipoles and a closed water bolus. This study investigates the performance of a next-generation applicator system for regional hyperthermia with a multi-ring annular array of antennas and an open water bolus. A cavity slot antenna is introduced to enhance the directivity and reduce mutual coupling between the antennas. Several design parameters, i.e. dimensions, number of antennas and operating frequency, have been evaluated using several patient models. Performance indices have been defined to evaluate the effect of parameter variation on the specific absorption rate (SAR) distribution. The performance of the new applicator type is compared with the Coaxial TEM. Operating frequency appears to be the main parameter with a positive influence on the performance. A SAR increase in tumour of 1.7 relative to the Coaxial TEM system can be obtained with a three-ring, six-antenna per ring cavity slot applicator operating at 150 MHz.     

Role of immune-derived diffusible mediators in AIDS-associated neurological disorders

Neurologic abnormalities are common in HIV-1 infected patients and often represent the dominant clinical manifestation of pediatric AIDS. Although the neurological dysfunction has been directly related to CNS invasion by HIV-1, the pathogenesis of neurologic disorders remains unclear. This review will first discuss the spectrum of potential interactions between HIV-1 and neural (neuronal and glial) cells, in the face of experimental data. Next, we will focus on the role of immune-derived cytokines and other soluble compounds which have been proposed to act as neurotoxic mediators and appear to play a role in the pathogenesis of AIDS-associated neurodegeneration.     

Molecular Evidence for the Existence of Two Distinct Subgroups in Cucumber Mosaic Cucumovirus

Infectious full-length cDNA clones from the genomic RNAs of a subgroup II cucumber mosaic cucumovirus strain (Trk7) were obtained. Sequence analysis of the whole genome revealed strong homology (99%) to the genome of Q-CMV, the only subgroup II strain whose entire genomic nucleotide sequence had been available in the database, and an overall 75% homology to those of subgroup I strains. We provide sequence comparisons of different parts of 1a, 2a and 2b proteins of Cucumovirus species, and propose phylogenetic trees based on these protein sequences.     

Familial adenomatous polyposis coli: five novel mutations in exon 15 of the adenomatous polyposis coli (APC) gene in Italian patients. Mutations in brief no. 225. Online

Germline mutations within the adenomatous polyposis coli (APC) gene, a tumor suppressor gene, are responsible for most cases of familial adenomatous polyposis (FAP), an autosomal dominantly inherited predisposition to colorectal cancer. To date, more than 300 germ-line causative mutations within this gene have been described (Beroud and Soussi, 1996). Of these, about 95% are chain-terminating mutations, and more than 60% have been localized within exon 15 (Nagase and Nakamura, 1993, Beroud and Soussi, 1996). Using polymerase chain reaction-single strand conformation polymorphism, protein truncation test (PTT) and DNA sequencing we have identified five new frameshift mutations (2523insCTTA, 2638delA, 2803insA, 3185delAA, 4145delTCATGT), all occurring within exon 15 and giving rise to truncated protein products. Two of these new mutations are of particular interest because of the unusual phenotypic features shown by probands. The phenotype of the proband bearing the 2523insCTTA mutation at codon 842 was very aggressive with onset of the symptoms at 12 years, while the patient bearing the 3185delAA mutation at codon 1062 exhibited features of an attenuated form of FAP (AAPC). Our data reiterate the great heterogeneity of the mutational spectrum in FAP that gives rise to an extreme variability of the clinical expression.     

Peroxisomal localization of the immunoreactiveβ-oxidation enzymes in a neonate with aβ-oxidation defect

Summary A boy born to healthy, unrelated parents, presented at birth with hypotonia and seizures. Very long chain fatty acids in the plasma were strongly elevated; bile acid intermediates and plasmalogen biosynthesis were normal. Acyl-CoA oxidase activity was normal. The patient died at the age of 3 months. The cerebellum and medulla oblongata showed neuronal migration defects. The specific biochemical basis for the impaired peroxisomal-oxidation has not been found. The three immunoreactive peroxisomal- oxidation enzymes and catalase were localized in the hepatocellular peroxisomes. Aberrant features of the peroxisomes included: a subpopulation of organelles larger than 1 m, an amorphous nucleoid in many organelles, and invaginations of the peroxisomal membrane into the matrix. Peroxisomes in the proximal renal tubules also contained the three immunoreactive-oxidation enzymes. Regularly spaced trilamellar inclusions were seen in hepatic macrophages; they were much more abundant in adrenocortical macrophages. The inclusions were birefringent and resistant to acetone extraction. Distinct hepatic fibrosis had developed over a period of 2.5 months. We speculate that the impaired-oxidation is due to a defect at the level of the peroxisomal carnitine octanoyl or -acetyl transferase, responsible for the export of-oxidation products.     

Ultrasonography in the early diagnosis of psoriasis-associated enthesopathy

The aim of the present study was to detect entheseal abnormalities by means of ultrasonography (US) in patients with psoriasis. We evaluated 24 patients with psoriasis who underwent clinical and ultrasonographic examination of both lower limbs at the calcaneal insertions of the Achilles tendons and at the flexor and extensor tendons of all fingers of the hand. Fourteen patients with psoriatic arthritis were used as controls. US was performed using a real-time scanner (ATL SDI 3000) with a 5-12 MHz linear array transducer. Longitudinal and transverse scans of the talocrural joints, Achilles tendons and both the flexor and extensor tendons of the fingers of both hands were obtained at rest and during active and passive movements. On clinical examination no entheseal site was abnormal, but on US examination 33% of patients showed abnormalities. In particular, six psoriasis patients (25%) who were asymptomatic showed effusion around the extensor tendon of the first digit of the left hand and around the extensor tendon of the third and fourth digits of both hands; two patients (8.3%) showed a hypoechoic nodular formation of the flexor tendon sheath of the left hand. We conclude that entheseal abnormalities not detected at clinical examination were present in 33% of patients with psoriasis who underwent US examination. Therefore, we suggest the routine use of ultrasonography in the early diagnosis and in treatment and follow-up of patients with tendon enthesopathy, since these factors may have implications for therapy.