Severe neurological disorders and refractory aspergillosis in an adolescent treated by vincristine and voriconazole.

WHAT IS KNOWN AND OBJECTIVE: Voriconazole and vincristine are major therapeutics in paediatric haematology. However, the risk-benefit ratio of the treatment of invasive aspergillosis with voriconazole in patients receiving vincristine-based chemotherapy remains unclear. CASE DESCRIPTION: We report severe peripheral and central neurological disorders in a 14-year-old girl with T-cell acute lymphoblastic leukaemia and pulmonary aspergillosis. The case describes a strong exacerbation by voriconazole of the vincristine-induced neuropathic pains. It shows the high variability of the trough serum concentration of voriconazole leading to antifungal treatment failure and suggests that its own central neurotoxicity could also be potentiated by vincristine. WHAT IS NEW AND CONCLUSION: Given the risk of either insufficient antifungal efficacy or excessive neurological disorders, this case warns on a probable unfavourable risk-benefit profile of voriconazole during vincristine-based chemotherapy in adolescents.

Pilot study of the efficacy and safety of a modified-release magnesium 250 mg tablet (Sincromag) for the treatment of premenstrual syndrome.

BACKGROUND: Magnesium deficiency has been implicated as a possible contributing factor to some symptoms of premenstrual syndrome (PMS) and several studies have reported a lower intracellular magnesium concentration in women with PMS. Thus, it has been suggested that magnesium supplementation may improve certain symptoms in women with PMS. OBJECTIVE: This open-label study assessed the efficacy and safety of a patented modified-release magnesium 250 mg tablet for improving symptoms in women affected by PMS. METHODS: After a 3-month observational period, women aged 18-45 years with a regular menstrual cycle (from 25-35 days) who were affected by PMS (determined by a score of > or =25 points on a PMS questionnaire) [n = 41] were given the modified-release magnesium tablet over three menstrual cycles, beginning 20 days after the start of their last menstrual period and continuing until the start of their next menstrual period. RESULTS: PMS symptoms improved during magnesium treatment. After 3 months, the mean total PMS score (primary endpoint), as assessed by the investigator using Moos' Modified Menstrual Distress Questionnaire, was significantly lower than before therapy (p < 0.0001). During the same period, the mean PMS scores, as recorded in patients' diaries (secondary efficacy variables), also showed significant improvements (p < 0.0001 for all subscales). The relative decreases in total PMS scores, as assessed by investigator and patient, were 35.1% and 33.5%, respectively. The magnesium tablet was well tolerated, with vertigo the only treatment-related adverse event reported (one patient). CONCLUSIONS: We concluded that modified-release magnesium was effective in reducing premenstrual symptoms in women with PMS in this preliminary study.

Factors associated with climacteric symptoms in women around menopause attending menopause clinics in Italy.

OBJECTIVE: To obtain data on correlates of climacteric symptoms in women around menopause attending menopause clinics in Italy. METHODS: Since 1997 a large cross sectional study has been conducted on the characteristics of women around menopause attending a network of first level menopause outpatient's clinics in Italy. A total of 66,501 (mean age 54.4 years) women are considered in the present paper. RESULTS: The odds ratios of moderate and severe hot flashes/night sweats were lower in more educated women and (for severe symptoms only) in women reporting regular physical activity. Depression, difficulty to sleep, forgetfulness and irritability tended to be less frequent in more educated women and (depression only) in women reporting regular physical activity. Parous women reported more frequently these symptoms. CONCLUSIONS: This large study confirms in Southern European population that low education, body mass index and low physical activity are associated with climacteric symptoms. Parous women are at greater risk of psychological symptoms.

Simple clinical score and laboratory-based method to predict bacterial etiology of acute diarrhea in childhood.

We describe a two-step predictive method to assess the probability of bacterial etiology in cases of diarrhea. The patients are divided into three probability groups (high, intermediate, low) according to a clinical score. Thereafter the patients in the intermediate group are further assigned to the high or low probability group according to the presence or absence of fecal leukocytes. We developed the method in an initial series of 157 children with acute diarrhea; the reproducibility of the method was tested in a second series of 180 cases. Eighty-six percent of patients in the first series and 81% in the second were correctly classified by our method. We suggest its use, especially in pediatric practice, to identify children with the highest probability of bacterial diarrhea, thus reserving stool culture to a few selected cases because only a minority of children with diarrhea have a recognized bacterial etiology.

Identification of the human beta-casein C-terminal fragments that specifically bind to purified antibodies to bovine beta-lactoglobulin.

The presence of foreign proteins in human milk after the ingestion of bovine dairy products is thought to be one of the possible causes of allergic sensitization in exclusively breast-fed predisposed infants. The immunologic determination of bovine beta-lactoglobulin (LG) concentration in human milk has been reported by several researchers, but the results are conflicting. Moreover, a strong cross-reactivity between antibodies to bovine beta-LG and human milk proteins and peptides was reported, throwing doubt on the reliability of radioimmunoassay and enzyme-linked immunosorbent assay detection and quantification assays for bovine beta-LG in human milk. Thus, the goal of this study was to isolate human milk peptides with a molecular mass >or= 1,000 Da cross-reactive with antibodies to bovine beta-LG in order to identify possible common epitopes between human and bovine milk proteins. The proteins were first isolated by affinity chromatography with purified polyclonal antibodies to bovine beta-LG, followed by gel filtration fast phase liquid chromatography and reverse phase-high performance liquid chromatography purification of the components specifically bound in the affinity separation step. Affinity-bound peptides were identified by determining their amino acid sequence. All the sequenced peptides belonged to the C-terminal part of human beta-casein, which confirms the cross-reactivity of human milk proteins and peptides with antibodies to bovine beta-LG and allows the identification of possible common epitopes between the two proteins. No bovine beta-LG peptides with a molecular mass >or= 1,000 Da were found in our milk samples from healthy mothers on a diet rich in bovine milk and dairy products.

The immunopathogenesis of primary biliary cirrhosis.

There have been several recent advances in our understanding of primary biliary cirrhosis. Foremost amongst these has been the cloning and identification of the mitochondrial autoantigens as members of the 2-oxo-dehydrogenase complex. These include the E2 components of PBC, BCKD and OGDC. The immunodominant autoepitopes of the autoantigens have been mapped and, in all cases, correspond to the inner lipoyl domain. Limited progress has also been made on T cells, particularly the CD4 response. However, the fundamental mechanisms and the role, if any, of CD8 cells are unknown. Finally, at least 2 groups have identified a molecule that cross-reacts with PDC-E2, i.e., a mimic, on the luminal surface of biliary epithelium in PBC but not controls. The identification of this molecule will be critical in further understanding the immune response of this disease.

[Renal insufficiency due to cholesterol embolism. 4 cases]. / Insufficienza renale da embolia colesterinica. Quattro casi.

Atheroembolic disease is a complication of atheromatous disease and is quite often misunderstood. A precise diagnosis can be made difficult, by the lack of specific tests. The first case, in which we identified this disease, resulted from a bladder biopsy, in the instance of a patient with a suspected carcinoma. The experience, with this initial patient, led us to identification of a further 3 cases, within our previous 2 years case histories. One must consider the possibility of atheroembolic disease during the differential diagnosis of acute renal failure in geriatric patients, given the serious prognosis.

Clinico-statistico-epidemiologic survey on benign and malignant breast diseases among patients hospitalized at a gynecologic department.

An empirical approach to the detection of groups of women at high risk of developing breast carcinoma by a score-system is presented. A comparison between the diffusion of breast self-examination and Pap-test, and a comparison between medical breast checks and gynecologic ones are also presented.

[Indications and limitations of subcutaneous mastectomy in the treatment of breast carcinoma]. / Indicazioni e limiti della mastectomia sottocutanea nel trattamento del carcinoma mammario.

The reasons that led to subcutaneous mastectomy in some initial stage breast cancer patients are reported. After removal of the mammary gland, this surgical technique provides for prosthetic reconstruction and should therefore be confined to women with initial stage cancer who for psychological or aesthetic reasons refuse more destructive operations. The technique is described and results obtained discussed, recalling that this type of non-destructive operation will be increasingly in demand in the future but needs preclinical diagnosis of the local disease and its systemic diffusion.

[Epidemiologic and diagnostic observations on hemorrhage of the upper gastroenteric tract]. / Osservazioni epidemiologiche e diagnostiche sulle emorragie del tratto gastroenterico superiore.

Acute upper gastrointestinal (GI) bleeding causes, according to the authors' experience, 1.65% of all annual hospitalizations. Mortality rate among high risk patients is about 20% and cirrhotic patients have a particularly poor outcome (70% of deaths caused by gastrointestinal hemorrhage). Endoscopy has been performed in 329 cases to identify the active site of bleeding (7.22% of 4791 "EGDS" performed from 1984 to 1988). In this retrospective study gastric and duodenal peptic diseases, have been observed more frequently than esophageal varices ruptures (11.8%) and in 25% of patients Gl bleeding was associated with the use of potentially dangerous drugs (NSAID and/or Steroids). A prompt endoscopy is fundamental to recognize the etiology and for a better management of the patient; unfortunately, even if improvements have been obtained in the diagnosis and therapy, the mortality caused by gastrointestinal hemorrhage is not significantly reduced.

Benign recurrent intrahepatic cholestasis. Some reflections on a case followed for 20 years.

Benign recurrent intrahepatic cholestasis (BRIC) is a form of cholestasis of obscure aetiology characterized by recurrent episodes of jaundice and itching associated with a morphological picture of pure intrahepatic cholestasis. No effective treatment has yet been found among the many that have been proposed and the invariably benign nature of the condition has been questioned. A case of BRIC followed for a period of 20 years is described. This case is of great interest from these two points of view: 1) the histologic and electron microscopic findings 23 and 41 years after the first episode of cholestasis, respectively, failed to reveal evidence of the possible future development of cirrhosis; 2) treatment with ursodeoxycholic acid proved ineffective both therapeutically and in the prevention of episodes of bile stasis: on the contrary, calculosis of the common bile duct appeared after 8 months from the onset of the treatment.

Ethnic differences in the distribution of CYP3A5 gene polymorphisms.

The genetic polymorphism affecting the CYP3A5 enzyme is responsible for interindividual and interethnic variability in the metabolism of CYP3A5 substrates. The full extent of the CYP3A5 genetic polymorphism was analysed in French Caucasian, Gabonese and Tunisian populations using a polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) strategy. In the three populations, eight, 17 and ten single nucleotide polymorphisms (SNPs), respectively, were identified, among which nine correspond to rare new mutations. Also identified were 16 alleles including eight new allelic variants. Significant differences were observed in the distribution of these alleles. Particularly, the frequency of the CYP3A5*3C null allele in French Caucasians (81.3%) and in Tunisians (80.0%) is higher than in the Gabonese population (12.5%) (p < 0.001). Considering the CYP3A5 genotypes of the tested individuals, only 10.4% of French Caucasians and 30.0% of Tunisians were identified as CYP3A5 expressors. In contrast, 90.0% of Gabonese subjects appear to express the CYP3A5 protein.

Risk factors for type 2 diabetes in women attending menopause clinics in Italy: a cross-sectional study.

OBJECTIVE: To analyze risk factors for type 2 diabetes among women attending menopause clinics in Italy for counselling about the menopause. SUBJECTS: Women attending a network of first-level outpatient menopause clinics in Italy for general counselling about menopause or treatment of menopausal symptoms. METHODS: Cross-sectional study with no exclusion criteria. Type 2 diabetes was defined according to National Diabetes Data Groups Indications and the fasting blood glucose at an oral glucose tolerance test within the previous year. RESULTS: Out of the 44 694 considered in this analysis, 808 had a diagnosis of diabetes type 2 (1.8%). In comparison with women aged < 50 years, the multivariate odds ratios (OR) of type 2 diabetes were 1.31 (95% confidence interval (CI), 0.99-1.74) for women aged 50-52 years, 1.66 (95% CI, 1.27-2.17) at 53-56 years and 2.84 (95% CI, 2.20-3.67) in women aged > or = 57 years. Type 2 diabetes was less frequently reported in more educated women (OR high school/university vs. primary school = 0.44 (95% CI, 0.36-0.55)). Being overweight was associated with an increased risk of type 2 diabetes. In comparison with women reporting a low level of physical activity, the multivariate OR of type 2 diabetes was 0.67 (95% CI, 0.54-0.84) for women reporting regular physical activity. In comparison with premenopausal women, the multivariate OR of type 2 diabetes was 1.38 (95% CI, 1.03-1.84) in women with natural menopause. This finding was present also after allowing for the potential confounding effect of age. The multivariate OR of diabetes for users of hormonal replacement therapy was 0.58 (95% CI, 0.46-0.73). CONCLUSIONS: This large cross-sectional study suggests that postmenopausal women are at higher risk of type 2 diabetes after allowance for the effect of age. Other main determinants of risk of type 2 diabetes in women around menopause were low socioeconomic status and being overweight. Diabetes was found less frequently in those taking hormone replacement therapy.