A large family with pure autosomal dominant hereditary spastic paraplegia from southern Italy mapping to chromosome 14q11.2-q24.3

A large Italian pedigree from southern Italy with autosomal dominant uncomplicated spastic paraplegia is reported. The clinical picture was uniform and characterized by insidiously progressive lower extremity weakness and spasticity. The mean age at onset of symptoms was 8.3 years. Significant linkage to the SPG3 locus on chromosome 14 was detected. The authors also report their search for mutations in a gene located in the region and its exclusion as a candidate for SPG3. Received: 14 November 2001, Received in revised form: 8 April 2002, Accepted: 23 April 2002 Correspondence to A. Quattrone, MD     

Assessment of efficacy of bothropic antivenom therapy on microcirculatory effects induced by Bothrops jararaca snake venom.

Intravenous administration of antibothropic antivenom (BAv) neutralises the systemic effects, but does not efficiently reverse the local symptoms elicited by the Bothrops jararaca venom (BjV). The mechanisms involved in this poor protection have not been clarified. In this work, intravital microscopy studies were carried out to determine the efficacy of different schedules of BAv treatment on local effects evoked by topical application of BjV in the microcirculatory network of the internal spermatic fascia of Wistar rats. Results demonstrated that BAv administration 15 min before, simultaneously with, or 15 min after BjV application did not totally reverse the local symptoms, represented by disturbances of coagulation, development of haemorrhage lesions, vascular permeability increase and increment on leukocyte-endothelium interactions. This lack of effectiveness neither reflects an inadequate amount of specific antibodies in the antivenom against toxins responsible for local effects nor an insufficient dose of circulating BAv during the assays. Administration of fluorescein isothiocyanate (FITC) labelled-BAv showed the dynamics of distribution of the antivenom in the microcirculatory network. Images obtained from prior and simultaneously treated animals showed that the antivenom remains at luminal side of vessels before venom application, and the latency time to antivenom leakage is coincidental to that for local effects evoked by the venom. In addition, images from posterior treatment demonstrated that the intense alterations in the microcirculatory network impair antivenom distribution at the site of injection. Together, our data show that the lack of effectiveness of antivenom therapy is due to impaired and delayed venom and antivenom interaction at the site of injury.     

Involvement of adenosine A1 and A2A receptors in the motor effects of caffeine after its acute and chronic administration.

The involvement of adenosine A(1) and A(2A) receptors in the motor effects of caffeine is still a matter of debate. In the present study, counteraction of the motor-depressant effects of the selective A(1) receptor agonist CPA and the A(2A) receptor agonist CGS 21680 by caffeine, the selective A(1) receptor antagonist CPT, and the A(2A) receptor antagonist MSX-3 was compared. CPT and MSX-3 produced motor activation at the same doses that selectively counteracted motor depression induced by CPA and CGS 21680, respectively. Caffeine also counteracted motor depression induced by CPA and CGS 21680 at doses that produced motor activation. However, caffeine was less effective than CPT at counteracting CPA and even less effective than MSX-3 at counteracting CGS 21680. On the other hand, when administered alone in habituated animals, caffeine produced stronger motor activation than CPT or MSX-3. An additive effect on motor activation was obtained when CPT and MSX-3 were coadministered. Altogether, these results suggest that the motor-activating effects of acutely administered caffeine in rats involve the central blockade of both A(1) and A(2A) receptors. Chronic exposure to caffeine in the drinking water (1.0 mg/ml) resulted in tolerance to the motor effects of an acute administration of caffeine, lack of tolerance to amphetamine, apparent tolerance to MSX-3 (shift to the left of its 'bell-shaped' dose-response curve), and true cross-tolerance to CPT. The present results suggest that development of tolerance to the effects of A(1) receptor blockade might be mostly responsible for the tolerance to the motor-activating effects of caffeine and that the residual motor-activating effects of caffeine in tolerant individuals might be mostly because of A(2A) receptor blockade.     

Concurrent boost radiotherapy as preoperative treatment for locally advanced rectal carcinoma: a new beam arrangement

PURPOSE: To describe a new beam arrangement for preoperative concurrent boost radiotherapy in locally advanced rectal carcinoma. MATERIAL AND METHODS: Three different volumes, ie posterior pelvis, total mesorectal space, and gross tumor volume plus 2 cm, are selected to receive radiation doses of 47 Gy, 51 Gy, and 54 Gy, respectively, in 24 fractions. There are two prerequisites for the use of such a radiotherapy schedule: complete displacement of the small bowel outside the boost volume, and horizontal positioning of the rectal long axis. Both conditions can be attained by patient positioning on a new device, the "Up-Down Table" (UDT). The dose gradient between the three volumes is realized with two daily arc rotation fields with an isocenter that is different from the three additional multileaf collimator pelvic fields (postero-anterior + 2 laterolateral). RESULTS: The treatment data are reported according to the ICRU 62 criteria. A comparison was made between concurrent arc rotation and concomitant static boost techniques. CONCLUSION: The new beam arrangement, with the use of the UDT, allows to administer different radiation doses to three volumes with different tumor cell density in order to obtain the same probability of local response in all target volumes without increasing the toxicity.     

Carboplatin plus vinorelbine plus G-CSF in elderly patients with extensive-stage small-cell lung cancer: a poorly tolerated regimen. Results of a multicentre phase II study

PURPOSE AND METHODS: A multicentre phase II trial (single-stage design) was undertaken to test the activity and toxicity of carboplatin (AUC 5 according to Calvert, day 1) plus vinorelbine (25 mg/m(2) days 1 and 8) with lenograstim support, every 3 weeks in the first line treatment of elderly patients, aged 65 or more, affected by extensive small-cell lung cancer (SCLC). The primary end-point of the trial was the objective response rate. Twenty-three responses among 37 patients were considered necessary to proceed to a phase III trial. RESULTS: Twenty-eight patients were enrolled (median age 70 years). Treatment was remarkably toxic. Three patients died while on treatment. Eleven patients (39.3%, 95% exact confidence interval (CI): 21.5-59.4) had an objective response, that was complete in 2 cases. Median time to progression was 5.1 months (95% CI: 3.3-6.7). Median survival was 7.9 months (95% CI: 4.8-14.4). CONCLUSION: Carboplatin plus vinorelbine is poorly tolerated and not sufficiently active to warrant phase III comparison with standard chemotherapy regimens in elderly patients with extensive SCLC.     

Posterior wall laceration of the thoracic trachea: the transcervical–transtracheal approach

A large membranous wall laceration of the thoracic trachea was surgically treated. The surgical approach consists on a low collar incision followed by a longitudinal tracheotomy. The membranous tear was repaired with a running suture and tracheotomy sutured with interrupted crossed stitches. The procedure was effective and endoscopic follow-up showed a perfect healing process with no signs of tracheal stenosis. This new technique proved to be a reliable, quick and safe procedure, which allows to repair membranous lacerations as far as the carina, avoiding thoracotomy.     

Internal jugular vein patency after lateral neck dissection: a prospective study

In spite of anatomical preservation of the internal jugular vein (IJV), an occlusion rate of the vessel of up to 30% has been documented after selective or modified radical neck dissections. The aim of the present prospective study was to evaluate the patency of the IJV following selective lateral neck dissection (LND) in 34 patients affected by squamous cell carcinoma of the upper aerodigestive tract who underwent surgery concomitantly on the primary site and the neck. Eighteen patients received unilateral and 16 bilateral LND, for a total of 50 IJVs. Postoperative radiotherapy on the neck was delivered in four patients with histologic evidence of micro-extracapsular spread; the impact of this variable on IJV patency was assessed by the Fisher test. A preoperative baseline study of vein patency and flow by ultrasonography (US) was obtained. Postoperative controls were scheduled at 1 week, 1 month and 3 months following surgery. No patient developed either wound infection or a pharyngocutaneous fistula, and no signs or symptoms of IJV occlusion were observed during the postoperative course. At the first US control, 25 IJVs (50%) did not present any alteration in patency, and 23 (46%) and 2 (4%) had a reduced or absent flow, respectively. At the second and third controls, 33 (66%) and 45 (90%) of the IJVs presented with normal flow, respectively. At the end of the study, none of the patients showed evidence of occlusion. Postoperative radiotherapy did not have a statistically significant impact on IJV patency ( P=0.09). In conclusion, long-term IJV occlusion after LND has to be considered an exceedingly rare event with negligible morbidity. However, alterations of IJV flow frequently occur in the immediate postoperative course.