Predictors of cognitive level and depression severity are different in patients with left and right hemispheric stroke within the first year of illness

Causes of cognitive impairment after stroke are not yet clear because a large number of sociodemographic and clinical variables complicate the understanding of the phenomenon. We aim to evaluate sociodemographic and clinical predictors of cognitive level and depression in subjects with different lesion laterality. We assessed 153 right (n = 87) and left (n = 66) unilateral first-ever stroke patients within the first year of illness with the Structured Clinical Interview for DSM-IV-Patient Edition, the Hamilton Depression Rating Scale, the Hamilton Anxiety Rating Scale, the State Trait Anger Expression Inventory, the Barthel Index, and the Mini Mental State Examination (MMSE). Sociodemographic variables were also measured. Sixty-two (41 %) patients suffered from Major Depression (MDD), and 26 (17 %) suffered from Minor Depression (MIND). An univariate analysis of variance showed that MMSE scores were different throughout the groups of left and right stroke patients with MDD, MIND and without depression. Left stroke patients with MDD were more cognitively impaired than all the other groups. This result was valid after controlling for the effect of lesion location on cognitive level difference between the groups. A series of stepwise multiple regression analyses indicated that depression severity was a predictor of cognitive level and vice-versa in left hemispheric stroke patients only. Moreover, educational level in right hemispheric stroke patients and state-anger and number of regions affected in left hemispheric stroke patients were other predictors of cognitive level. The study confirms the hypothesis that predictors of cognitive level and depression severity are different in subjects with different laterality of lesion and that MDD is associated with cognitive impairment in left stroke patients. Received: 4 February 2002, Received in revised form: 14 May 2002, Accepted: 22 May 2002 Correspondence to Gianfranco Spaletta, MD     

Missense and splice site mutations in SPG4 suggest loss-of-function in dominant spastic paraplegia

We studied nine Italian families with a pure form of autosomal dominant spastic paraplegia (ADHSP) to assess the frequency of mutations in the SPG4 gene. We observed marked intrafamilial variability in both age-at-onset and clinical severity, ranging from severe congenital presentation to mild involvement after age 55 years to healthy carriers of the mutation after age 70. Four of nine probands harboured SPG4 mutations, We identified three new SPG4 mutations, all predicting a loss-of-function with apparently important consequences for spastin function. RT-PCR studies predict loss-of-function as a possible mechanism leading to spastin-related HSP. The current study expands the spectrum of allelic variants in SPG4, confirming their pathological significance in pure AD-HSP and suggesting implications for the presumed function of spastin. Received: 15 December 2000, Received in revised form: 29 May 2001, Accepted: 18 June 2001     

A novel mutation in the SURF1 gene in a child with Leigh disease,peripheral neuropathy,and cytochrome-c oxidase deficiency

We report a 16-month-old boy with psychomotor regression, muscle hypotonia, peripheral neuropathy, and lactic acidosis. Brain magnetic resonance imaging showed a bilateral abnormal signal in the substantia nigra and in the subthalamic nucleus, suggestive of Leigh disease. Histochemical analysis of skeletal muscle showed decreased cytochrome-c oxidase activity. Biochemical analysis of respiratory chain enzymes in muscle homogenate and in cultured fibroblasts showed isolated cytochrome-c oxidase deficiency. Western blot analysis in fibroblasts showed the absence of Surf1 protein. Genetic analysis of the SURF1 gene revealed that the patient was compound heterozygous for a previously reported mutation at the splice-junction site of intron 3 (240 + 1G > T), and for a novel 4-bp deletion in exon 6 (531_534delAAAT). Our data further enlarge the spectrum of mutations in SURF1 gene in patients with Leigh disease and cytochrome-c oxidase deficiency, contributing to better characterization of the clinical and neuroradiologic features of this group of patients for genotype-phenotype correlations.     

The ketogenic diet in children, adolescents and young adults with refractory epilepsy: an Italian multicentric experience

PURPOSE: This collaborative study by three Italian groups of child neuropsychiatrists was carried on to evaluate the efficacy and safety of the classic 4:1 ketogenic diet as add-on treatment in refractory partial or generalized epilepsy in children, adolescents and young adults. METHODS: We performed a prospective add-on study in 56 refractory epilepsy young patients (age 1-23 years, mean 10.4 years), all with both symptomatic and cryptogenic, generalized or partial epilepsies. Child neuropsychiatrists worked with nutritional team for sample selection and patients management. The ketogenic diet was added to the baseline antiepileptic drugs and the efficacy was rated according to seizure type and frequency. During treatment, seizure frequency, side effects, urine and blood ketone levels and other parameters were systematically evaluated. RESULTS: Patients have been treated for 1-18 months (mean 5 months). A >50% reduction in seizure frequency was gained in 37.5 and 26.8% of patients after 3 and 6 months, respectively, at 12 months, this number fell by 8.9%. No significant relationship between diet efficacy and seizure or epilepsy type, age at diet onset, sex and etiology of epilepsy was noted. Nevertheless, it seems noteworthy that 64% of our patients with neuronal migration disorders improved on this diet. Adverse effects occurred, mainly in the first weeks of treatment, in 32 patients (57.1%), but were generally mild and transient. In seven patients (12.5%) it was possible to withdraw one to two AED after 3-4 months on ketogenic diet. CONCLUSION: This initial experience with the ketogenic diet was effective in difficult-to-treat patients with partial and generalized epilepsies, though its efficacy dropped significantly by 9-12 months.     

External and internal dose in subjects occupationally exposed to ochratoxin A

OBJECTIVES: Ochratoxin A (OA) is a ubiquitous mycotoxin that can contaminate foods, drinks, and animal feeds worldwide. Humans and animals can therefore absorb this toxin via the gastrointestinal tract after ingestion of contaminated products. OA is known to exert toxic effects, particularly on the renal system, and the International Agency for Research on Cancer (IARC) classified it as a "possible human carcinogen" (Group 2B). The measurement of OA serum levels is an effective method of evaluating internal doses. Inhalation of airborne OA can represent a source of additional exposure. We determined the levels of serum OA in workers exposed to airborne dust originating from the handling or processing of contaminated foods. METHODS: We carried out area and personal sampling for airborne OA determination in three industries where coffee, cocoa beans, and spices, foods highly susceptible to contamination, were being processed. OA levels in the serum of six healthy workers employed in these factories were measured in samples collected at the end of the work shift. RESULTS: Airborne OA measured in the three industries, both by personal and area sampling, ranged from < 0.003 to 8.15 ng/m(3), while the levels measured in the breathing zone of the six workers who agreed to biological monitoring varied from 0.006 to 0.087 ng/m(3). OA serum levels ranged from 0.94 to 3.28 ng/ml, the latter values rather largely exceeding those of the control group (0.03 to 0.95 ng/ml). CONCLUSIONS: Our findings suggest that occupational exposure to this mycotoxin may represent a health risk for workers, especially if preventive and protection measures are not adopted in the workplaces. Airborne exposure levels can result in an increase of OA levels in serum, and this finding suggest that environmental and biological monitoring should be undertaken in workplaces where OA-contaminated products are handled or processed.     

Nutritional characteristics of a rural Southern Italy population: the Ventimiglia di Sicilia Project

OBJECTIVE: Knowledge of alimentary habits among populations permits a better definition of appropriate public health interventions. We designed the epidemiological project "Ventimiglia di Sicilia" to characterize the risk profile in a rural village with low total cholesterol levels and low early cardiovascular mortality but with a large prevalence of overweight and obesity, which previously have been significantly associated with total mortality. METHODS: 488 individuals of age 20 to 69 years were included in the dietary survey conducted by a seven-day food record. RESULTS: Alimentary habits were characterized by high consumption of total and complex carbohydrates (respectively 52.5 +/- 7.6% and 46.6 +/- 8.2% of daily energy) and by a low cholesterol intake (92.5 +/- 35.0 mg/1000 kcal/day). Fat intake was 34.7 +/- 7.7% of daily energy due to a higher consumption of monounsaturated fats in respect to saturated fats (respectively 20.5 +/- 5.1% and 10.2 +/- 2.9% of daily energy). In particular, in this population there was a large consumption of bread, pasta, fresh vegetables, olive oil and fruits. We also observed an excess of total calories (about 2900 kcal/day in men and 2100 kcal/day in women) not balanced by a high degree of physical activity levels. Furthermore we found a significant higher total and saturated fat consumption in the youngest individuals and in people with higher educational levels. CONCLUSIONS: Dietary habits of Ventimiglia di Sicilia still follow the nutritional characteristics typical of the Mediterranean diet. The high total calorie intake indicates a quantitative more than qualitative problem, which may account the large prevalence of overweight and obesity and may represent a public health issue that needs to be corrected in such a rural population.     

Expression of 90K (Mac-2 BP) correlates with distant metastasis and predicts survival in stage I non-small cell lung cancer patients

90K, also known as Mac-2 binding protein, is a secreted glycoprotein that binds galectins, beta1-integrins, collagens, and fibronectin, and has some relevance in cell-cell and cell-extracellular matrix adhesion. Previous studies have shown that serum levels of 90K have prognostic value in several neoplasms. In the present study, the role of the expression of 90K as an adverse prognostic indicator in 72 pathological stage I non-small cell lung cancer patients was investigated immunohistochemically. All of the patients underwent complete surgical removal of the tumor. The median length of follow-up care was 54 months. High level of 90K expression (90K staining of > or =50% of the neoplastic cells) was observed in 20 of the 72 (28%) tumors. Expression of 90K was confirmed by ELISA. The results showed that a high expression of 90K correlates with adverse prognosis. Among patients with high 90K expression, the disease-free and overall survival rates were significantly lower than the same rates of those with low expression (P = 0. 0001 and P = 0. 0003, respectively). The incidence of distant metastases in the patients with high 90K expression (60%; 12 of 20 patients) was significantly higher than that of in the patients with low expression (21%; 11 of 53 patients; P = 0.0038). The results of multivariate analysis confirmed that a high 90K expression was a significant factor to predict poor prognosis. We suggest that 90K expression could be a useful prognostic factor in patients with stage I non-small cell lung cancer, likely as an indicator of the metastatic propensity of the tumor.     

Post-menopausal hormonal therapy and gallbladder cancer risk

The relation between post-menopausal hormone replacement therapy (HRT) and gallbladder cancer was analyzed in women above age 45 years, using data of a case-control study conducted in Italy between 1985 and 1997, on 31 incident, histologically confirmed cases and 3,702 controls in hospital for acute, non-neoplastic conditions. The multivariate odds ratio (OR) was 3.2 (95% confidence interval: 1.1-9.3) for those who had ever used HRT and the OR tended to rise with longer duration. Although based on small numbers, due to the rarity of the disease, these findings provide the first direct epidemiological evidence of an association between HRT and gallbladder cancer.