Periventricular nodular heterotopia: report of a pediatric series

Periventricular nodular heterotopia is a malformation that occurs in both males and females and is associated with a variety of clinical and neuroradiologic signs. A gene called filamin-1 (FLN-1) has recently been identified. We review the clinical and imaging findings from a series of pediatric patients with periventricular nodular heterotopia. Five patients (three males and two females; age range = 4-18 years) were investigated. In our series, periventricular nodular heterotopia can be the common denominator in different conditions. Periventricular nodular heterotopia can occur alone or be associated with cortical malformations. Epilepsy was present in three of the five patients and was resistant to drugs in one female. Mental retardation was present in three of the five patients. Two male patients had normal intelligence, with no cortical anomalies; patient 3 had unilateral periventricular nodular heterotopia. The associated malformations were more severe in the female patients and slight only in patient 1. The two females showed anomalies rarely reported in association with bilateral periventricular nodular heterotopia. We believe that other genes can be involved in children with atypical neuroradiologic periventricular nodular heterotopia. No mutations were detected in 6 of the 48 exons of the FLN-1 gene, although this does not allow any definitive conclusions to be reached. We conclude that our series of patients with periventricular nodular heterotopia clearly highlights the complexity of the clinical, neurologic, and neuroradiologic characteristics associated with this malformation.     

Finger systolic blood pressure indices for the diagnosis of vibration-induced white finger

OBJECTIVES: To compare the accuracy of several finger systolic blood pressure indices (FSBPIs) for the diagnosis of cold-induced Raynaud's phenomenon in vibration-exposed worker groups with different prevalences of vibration-induced white finger (VWF). METHODS: The finger systolic blood pressure (FSBP) in a test finger at 10 degrees C as a percentage of the pressure at 30 degrees C, corrected for the change in systolic blood pressure in a reference finger [FSBPI(A)] or the arm [FSBPI(B)], was measured in 455 healthy controls and 874 workers exposed to hand-transmitted vibration (HTV). The following FSBPIs were also calculated: FSBPI(C), as the ratio between FSBP in the test finger at 10 degrees C and FSBP in the same finger at 30 degrees C; and FSBPI(D), as the ratio of FSBP to arm systolic blood pressure during finger cooling to 10 degrees C. The finding of zero systolic blood pressure, FSBP(0), in the cooled finger was taken as an objective sign of Raynaud's attack with complete closure of the digital arteries. RESULTS: On a group basis, all FSBPIs could discriminate between the controls and the HTV workers. In the vibration-exposed worker population, the FSBPIs were significantly lower in the subjects affected with VWF than in those without vasospastic symptoms. The lower normal limits of FSBPIs were derived from the results of the cold test in the controls and were found to vary from 50% to 60%. The FSBPI(A) showed the best sensitivity for the detection of cold-induced digital arterial hyper-responsiveness in both the total sample of HTV workers (sensitivity 87%) and most of the vibration-exposed groups with different prevalence of VWF (sensitivity from 79% to 100%). The results of the receiver operating characteristic analysis suggested a higher diagnostic accuracy of FSBPI(A) when compared with the global performance of the other FSBPIs. In the whole sample of HTV workers, the predictive value of a positive cold test varied from 73% [FSBPI(D)] to 89% [FSBP(0)] and that of a negative test ranged between 89% [FSBP(0)] and 97% [FSBPI(A)]. CONCLUSIONS: The findings of this investigation and clinical experience suggest that a discriminating threshold of FSBPI(A) <60% during finger cooling to 10 degrees C is an appropriate diagnostic criterion for the detection of abnormal cold response in the digital arteries of most vibration-exposed workers with a true history of symptoms of finger whiteness at the medical interview.     

Seroprevalence of Helicobacter pylori in children with type 1 diabetes mellitus in Sardinia

A few studies have reported an increased prevalence of Helicobacterpylori (HP) infection in diabetic subjects, which may be one of the causes of gastrointestinal symptoms and chronic atrophic gastritis frequently seen in diabetes of long duration. We determined the prevalence of HP infection in children and adolescents with Type 1 diabetes mellitus (T1DM) in the area of Sassari (northern Sardinia, Italy), which is characterized by an ethnically homogenous population at high risk of T1DM. HP IgG and IgA titres were measured in 138 patients with T1DM and 138 age-matched healthy controls. The percentage of infected subjects did not differ between T1DM patients (29.7%) and controls (32.6%). Globally, infected subjects were more than 1 yr older (13.0 +/- 2.7 yr) than non-infected ones (11.8 +/- 2.9 yr), independently of the presence of T1DM; in most HP-positive subjects infection was asymptomatic, and only 2 subjects in each group reported clinically relevant symptoms. HP-positive and HP-negative diabetic patients had the same duration of the disease (5.6 +/- 3.5 vs 5.5 +/- 3.6 yr) and received very similar doses of insulin (0.94 +/- 0.27 vs 0.96 +/- 0.4 IU/kg/d), whereas mean HbA1c was significantly lower in HP-positive patients (7.8 +/- 1.6% vs 8.6 +/- 1.7%,p=0.02). We conclude that the prevalence of HP infection is not higher in Sardinian children with T1DM as compared to controls of similar age, and the overall clinical impact of HP infection in terms of gastrointestinal symptoms and diabetic control seems to be low.     

The GABA(B) receptor agonists baclofen and CGP 44532 prevent acquisition of alcohol drinking behaviour in alcohol-preferring rats

AIMS: The present study investigated the effect of the gamma-aminobutyric acid (GABA)(B) receptor agonists, baclofen and CGP 44532, on the acquisition of alcohol drinking behaviour in selectively bred Sardinian alcohol-preferring (sP) rats. METHODS: Baclofen [0, 1 and 3 mg/kg, intraperitoneally (i.p.)] and CGP 44532 (0, 0.1, 0.3 and 1 mg/kg, i.p.) were administered immediately before alcohol presentation to alcohol-naive sP rats. Alcohol was offered under the two-bottle free-choice regimen with unlimited access for 24 h/day. Drug treatment was repeated once daily for 10 consecutive days. RESULTS: Baclofen and CGP 44532, dose-dependently and with comparable efficacy, suppressed alcohol intake; compensatory increases in water intake left total fluid intakes virtually unchanged. CONCLUSIONS: These results demonstrate that baclofen and CGP 44532 prevent the acquisition of alcohol drinking behaviour in sP rats, and suggest the involvement of the GABA(B) receptor in the mechanisms underlying the disclosure and experience of the reinforcing properties of alcohol in this rat line.     

Phase I study of eniluracil and oral 5-fluorouracil in combination with docetaxel in the treatment of patients with metastatic breast carcinoma

PURPOSE: The authors conducted a single-institution Phase I clinical trial to determine the maximum tolerated doses and to define the toxic effects of oral eniluracil and oral 5-fluorouracil (5-FU) combined with docetaxel in patients with metastatic breast carcinoma. PATIENTS AND METHODS: Patients with metastatic breast carcinoma were eligible if they had disease progression after anthracycline-based therapy and had never been exposed to taxanes. The starting doses of oral eniluracil and oral 5-FU were 11.5 mg/m(2) and 1.15 mg/m(2), respectively, twice daily on Days 1-14. Docetaxel was given intravenously at a starting dose of 50 mg/m(2) on Day 1 only. The dose of docetaxel was escalated among cohorts until a maximum tolerated dose was reached. Courses were repeated every 21 days. RESULTS: The authors treated 19 patients with Stage IV breast carcinoma, of whom 5 had received prior chemotherapy for their metastatic disease. Fifty-three percent had a performance status of 1, and 53% had bone or soft tissue involvement as the dominant site of disease. All patients had received prior therapy with doxorubicin. The dose-limiting toxicity was neutropenic fever. No episodes of sepsis were observed. Significant antitumor activity was observed with a total of two complete and nine partial responses. The recommended doses for Phase II studies are 72 mg/m(2) docetaxel on Day 1 and 10.0/1.0 mg/m(2) oral eniluracil/5-FU twice daily for a total of 14 days, with courses being repeated every 21 days. CONCLUSIONS: The combination of oral eniluracil/5-FU and intravenous docetaxel is a safe and well tolerated regimen. Significant antitumor activity is associated with this combination.     

Hysteroscopic assessment of menopausal breast-cancer patients taking tamoxifen; there is a bias from the mode of endometrial sampling in estimating endometrial morbidity?

The aim of this study is to evaluate the accuracy of hysteroscopy in detecting tamoxifen-associated endometrial morbidity. Ninety-eight menopausal breast cancer patients taking tamoxifen underwent hysteroscopy because of an endometrial thickness above 4 mm measured by Transvaginal Ultrasonography. Thirty-one women recorded uterine bleeding while 67 were asymptomatic. Hysteroscopies with operative facilities were performed, mainly in out-patient setting. Hysteroscopic findings were matched with histopathology derived from various modalities of tissue collection as suction-curettage, oriented-streak curettage, hysteroscopically-targeted biopsies or polypectomies and hysterectomies. Accuracy of hysteroscopy to estimate a normal or abnormal endometrium was calculated. Abnormal endometrium was detected in 35 patients (64.5% in symptomatic and 22.3% in asymptomatic women, P < 0.001). We found six carcinomas, 18 polyps and 11 hyperplasias. Hysteroscopy showed sensitivity and specificity of 89.2 and 98.4%, respectively. By blind sampling, tissue collection was too scant to give a diagnosis in 29.1% of patients and in 80.5% of patients in whom hysteroscopy showed cystic atrophy the pathologist failed to confirm this condition. Moreover, eight endometrial polyps (36.3%) detected by hysteroscopy were missed. Conversely, by tissue sampling under vision no inadequate specimen was sent to the pathologist and all hysteroscopies showing cystic atrophy and polyps were pathologically confirmed. From literature data, the detection-rate of endometrial pathology in tamoxifen users varies from the lowest to the highest prevalences whether blind or hysteroscopically-targeted modalities of tissue sampling were used, respectively. Hysteroscopy with targeted sampling appears to be the most effective method to assess the endometrial lining. In our experience it is safe, well tolerated and it should be considered the reference test to assess a thickened endometrium in women under tamoxifen.     

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.     

The role of ultrasound-guided aspiration biopsy of peripheral pulmonary nodules: our experience

BACKGROUND: Peripheral lung lesions are difficult to diagnose with conventional methods: ultrasound-guided aspiration biopsy is an interesting prospect having been reported to have good sensitivity and specificity. PATIENTS AND METHODS: From January 1991 to August 2001 we investigated, in 268 patients, the role of ultrasound-guided transthoracic fine needle aspiration for cytological diagnosis of peripheral lung lesions. Nodule sizes ranged from 1 to 10 cm. RESULTS: From 268 patients, we obtained 174 positive specimens for malignancy, of which 155 were positive for primary lung tumors and 19 for metastasis; 76 negative; 9 inadequate; and 9 aspecific. One patient developed pneumothorax after needle aspiration and one patient emophtoe. The nodule size did not affect complication rate and diagnostic outcome. CONCLUSION: This diagnostic procedure appears to be effective, safe and feasible, even in bedridden patients. The cost is low (70Euro), the examination is fast (5-6 minutes) and well-tolerated and, if the specimen is inadequate or non-specific, it is possible to repeat the examination. Ultrasound-guided aspiration biopsy can replace the TC-guided biopsy in patients with peripheral lung nodules.     

Identification of a novel activity of human papillomavirus type 16 E6 protein in deregulating the G1/S transition

In this study we show that E6 of human papillomavirus has the ability to deregulate the cell cycle G1/S transition. In rodent immortalized fibroblasts (NIH3T3) serum deprivation or over-expression of the cyclin-dependent kinase inhibitors, p16(INK4a) or p27(KIP1), leads to G1 cell cycle arrest. HPV16 E6 overcomes the antiproliferative signals, gaining the ability to drive serum-deprived and p16(INK4a) or p27(KIP1) over-expressing cells into S phase. E6 protein from the benign HPV type 1 displays a similar activity to HPV16 E6 to deregulate the G1/S transition. Thus, this activity appears to be conserved between E6 proteins from non-oncogenic and oncogenic HPV types. Furthermore, we show that HPV16 E6 is not able to circumvent a G1 arrest imposed by pRb mutant in which all CDK phosphorylation sites have been mutated. These data indicate that the viral protein acts upstream of pRb and its mechanism in promoting cell cycle progression is dependent on pRb phosphorylation. In summary, this study describes a novel biological function of HPV E6 and shows that the S phase entry, required for viral DNA replication, is not exclusively controlled by E7, but that E6 also is involved in this event.     

Weak linkage at 4p16 to predisposition for human neuroblastoma

The most frequent genetic alterations described in neuroblastoma (NB) are amplification of MYCN oncogene and deletion of chromosome 1p, although somatic deletions have been demonstrated at other chromosomal intervals. Since loss of heterozygosity (LOH) at distal 4p has been observed in about 20-29% of neuroblastomas, we have evaluated deletions in 41 Italian NB samples by LOH analysis at loci mapping to 4p as follows: pter-D4S2936-D4S412-D4S2957-D4S432-D4S3023-D4S431-cen. Our analysis showed allele losses in eight out of 41 samples (19.5%) and allowed the identification of a smallest region of overlapping deletion (SRO) of 3.0 cM, delimited by D4S412 and D4S3023. Two of these tumors with 4p LOH are from patients belonging to a family with recurrent NB. Interestingly the genotyping of this family revealed an identical haplotype that includes the nonrecombinant loci D4S412, D4S2957 and D4S432 shared by all affected children and demonstrated that this haplotype is retained in the two tumors carrying somatic deletions from patients of this family. Furthermore linkage analysis was performed in two NB families and yielded an overall lod-score of 3.0 in the interval including the haplotype. This provides a confirmatory indication that the region delimited by D4S2936 and D4S3023, which also includes the new defined SRO, may harbor NB predisposing gene/s.