Presymptomatic geographical distribution of ALS patients suggests the involvement of environmental factors in the disease pathogenesis.

BACKGROUND: Given that the pathogenetic process of ALS begins many years prior to its clinical onset, examining patients' residential histories may offer insights on the disease risk factors. Here, we analyzed the spatial distribution of a large ALS cohort in the 50 years preceding the disease onset. METHODS: Data from the PARALS register were used. A spatial cluster analysis was performed at the time of disease onset and at 1-year intervals up to 50 years prior to that. RESULTS: A total of 1124 patients were included. The analysis revealed a higher-incidence cluster in a large area (435,000 inhabitants) west of Turin. From 9 to 2 years before their onset, 105 cases were expected and 150 were observed, resulting in a relative risk of 1.49 (P = 0.04). We also found a surprising high number of patients pairs (51) and trios (3) who lived in the same dwelling while not being related. Noticeably, these occurrences were not observed in large dwellings as we would have expected. The probability of this occurring in smaller buildings only by chance was very low (P = 0.01 and P = 0.04 for pairs and trios, respectively). CONCLUSIONS: We identified a higher-incidence ALS cluster in the years preceding the disease onset. The cluster area being densely populated, many exposures could have contributed to the high incidence ALS cluster, while we could not find a shared exposure among the dwellings where multiple patients had lived. However, these findings support that exogenous factors are likely involved in the ALS pathogenesis.

NADPH oxidase 2 (NOX2) enzyme activation in patients with chronic inflammatory demyelinating polyneuropathy.

BACKGROUND AND PURPOSE: Chronic inflammatory demyelinating polyneuropathy (CIDP) is an acquired immunomediated condition affecting the peripheral nervous system where probably macrophages are the primary effector cells for demyelination. Reactive oxygen species (ROS), catalyzed by the NOX family of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase enzymes, can induce peroxidation and are potentially injurious to myelin. Our aim was to assess the activity of NOX2, an isoform of NOX, in a series of CIDP patients and to analyze the effect of intravenous immunoglobulin (IVIg) on NOX2. METHODS: Thirty CIDP patients treated with IVIg and 30 control subjects were enrolled. To evaluate NOX2 activity, neutrophil and monocyte oxidative burst was measured directly in fresh whole blood using the Phagoburst™ assay, a fluorescence-activated cell sorting method. The mean fluorescence intensity, emitted in response to different stimuli, leads to the production of ROS and corresponds to the percentage of oxidizing cells and their enzymatic activity. RESULTS: Mean fluorescence intensity values for granulocyte and monocyte burst in patients (mean 633.3, SD 191; mean 111.8, SD 28.5) were different from those measured in healthy controls (granulocytes, mean 436.6, SD 137.0, P = 0.0003; monocytes, mean 78.2, SD 17.3, P = 0.000001). Moreover, IVIg administration increased both granulocyte (P = 0.005) and monocyte (P = 0.0009) burst. CONCLUSION: Our findings demonstrate that oxidative burst is significantly increased in CIDP patients and that treatment with IVIg enhances oxidative values, thus representing a possible IVIg therapeutic effect linked to a regulatory effect of ROS. Based on this, the development of treatments targeting the specific activation of NOX may be beneficial in autoimmune disorders.

ALS clinical trials: do enrolled patients accurately represent the ALS population?

OBJECTIVE: To assess the effect of eligibility criteria in amyotrophic lateral sclerosis (ALS) clinical trials on the representativeness of the enrolled population. METHODS: Patients enrolled in 8 placebo-controlled clinical trials in our ALS center from 2003 to 2008 were compared 1) to the patients included a prospective epidemiologic register (Piemonte and Valle d'Aosta register for ALS, PARALS) in the same period and 2) the subset of PARALS patients who met the usual criteria for inclusion in clinical trials (PARALS-ct) (definite, probable, probable laboratory-supported ALS; age between 18 and 75 years; disease duration <36 months; vital capacity at diagnosis ≥70%; score ≥3 at the items swallowing and respiratory insufficiency at the Amyotrophic Lateral Sclerosis Functional Rating Scale-revised scale; riluzole therapy). RESULTS: A total of 164 patients were enrolled in 8 different clinical trials. The PARALS cohort included 813 patients, of whom 539 (66.3%) met the entry criteria for clinical trials. Patients enrolled in clinical trials were different from both epidemiologic cohorts, since they were younger, had a longer diagnostic delay, and were more likely to have a spinal onset, and to be men. Tracheostomy-free survival was significantly longer in the group of patients enrolled in clinical trials (median survival time, trial patients, 3.9 years [95% confidence interval (CI) 3.4-4.4]; PARALS, 2.6 [2.4-2.8]; PARALS-ct, 2.9 [2.7-3.1]). CONCLUSIONS: Patients enrolled in clinical trials do not satisfactorily represent the ALS population; consequently, the findings of ALS trials lack of external validity (generalizability). Efforts should be made to improve patients' recruitment in trials, particularly enrolling incident rather than prevalent cases.

Significance of lymph node sampling in epithelial carcinoma of the ovary.

From 1979 to 1984, 127 patients operated on for ovarian cancer underwent pelvic, para-aortic, or pelvic and para-aortic lymph node sampling. Forty-seven patients proved to be stage I(14 IA and 33 IC), 14 were stage II(3 IIA, 8 IIB, and 3 IIC), 58 were stage III (7 IIIA, 13 IIIB, and 38 IIIC), and 8 were stage IV. Positive lymph nodes were found in 4.2% of patients at stage I, 35.7% at stage II, 41.3% at stage III, and 87.5% at stage IV. With regard to grading, positive lymph nodes were found in 4.4% of G1, in 21.6% of G2, and in 49.1% of G3. A significant increase in survival (P = 0.04) was found for patients classified as stage IIIC only according to lymph node involvement compared to patients in peritoneal stage IIIC with positive lymph nodes (3-year survival: 46% vs 12%). A small increase in survival was observed for N- patients compared to N+ patients, at both stage III and IV, even with same residual tumor size, but the difference is not statistically significant. All other things being equal, because the prevalence of lymph node positivity depends closely on the number of lymph nodes removed and examined (OR = 3.9 for >10 lymph nodes removed compared to 1-5 lymph nodes removed), lymph node sampling does not seem to be a reliable method for evaluating the retroperitoneal status. With regard to the therapeutic role of systematic lymphadenectomy, few data in literature are available and, most important, are not derived from experimental studies. Probably, only randomized studies with a large number of patients will provide useful answers.

[The role of Papanicolaou test in gynecologic practice]. / Il ruolo del test di Papanicolaou nella practica ginecologica.

The paper analyses the importance of Papanicolaou's test in gynecological diagnostics and reports an interesting checklist drawn up by the "Istituto Superiore di Sanità" with which all women should be familiar in order to diagnose cervical cancer at an early stage.

[Uterine rupture in modern obstetrics]. / La rottura d'utero nella moderna ostetricia.

The paper reports 18 cases of womb rupture observed in the Institute of Gynecology and Obstetrics at the University of Turin from April 1978 to June 1988. Following an analysis of the data relating to the above cases, the paper concludes that in order to reduce the incidence of womb rupture it is important to hospitalize high-risk patients preferably before the start of labour so as to intervent using caesarian section.

[Uterine fibromyoma in pregnancy]. / Fibromiomi uterini in gravidanza.

Data are reported relating to the study of 100 pregnant women, aged between 30 and 49 years old, effected by one or more fibroma nodules on the body of the womb. From an analysis of results, it appears that appropriate obstetric care can significantly reduce the risk of both maternal and fetal complications.

[Thromboembolic disease in obstetrics. Current concepts]. / Malattia tromboembolica in ostetricia. Concezioni attuali.

Thromboembolic disease during pregnancy and confinement is an important cause of mortality and obstetric morbidity. The onset of thromboembolic disease is caused by vascular damage, stasis and hypercoagulability, factors which are all present during gestation. All A. agree that it is of fundamental importance to intervene immediately in cases of active thromboembolic disease, but also to take suitable prophylactic measures to prevent the onset of disease.

[Urinary tract infection during pregnancy]. / Le infezioni delle vie urinarie in gravidanza.

Infections of the urinary tract are particularly frequent in pregnancy (3-10%). Immediate treatment of all symptomatic forms and screening for asymptomatic forms are vital to prevent damage to mother and fetus.

[Inflammation of the uterine corpus: endometritis]. / Le flogosi del corpo dell'utero: endometriti.

In industrialised countries endometritis is a problem which represents an increasing risk to personal health and to society. In almost all cases the inflammatory process which affects the uterine mucosa forms part of a more generalised infection which involves the entire internal genital system (PID). The most important problem associated with pelvic phlogosis is increased sterility, a greater number of ectopic pregnancies and chronic pelvic pain. In order to treat the symptoms of genito-pelvic infection, an early diagnosis and adequate medical therapy are indispensable. In this event it may be possible to prevent invalidating effects on fertility and chronic pelvic pain.

[Hormonal contraception using estroprogestins]. / La contraccezione ormonale mediante estroprogestinici.

Today the estroprogestagen pill is the most valid method of contraception given that its benefits far outweigh its risks. The paper stresses the importance of a thorough anamnestic, clinical and laboratory examination so as to obtain correct and safe steroid contraception. The efficacy and excellent tolerance of the combined method currently make it the most widespread form of oral contraception.

PIP: Oral contraceptive (OCs) of high efficacy containing estroprogestins (EP) were introduced in the 1960's and since then more than 250 million used them. Their benefits include regular menstrual cycles and protection against genital tumors. Dosage seems to be directly related to risks and benefits, therefore new types of low-dose progestins have been developed. Their mechanism of action is based on hypothalamic- hypophysic control, EP suppress the production of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Their effects are as follows: the cervical mucus becomes more viscous providing a barrier against spermatozoa, regressive (atrophy) modifications and proliferative alterations of the endometrium, and metrorrhagia induced by estrogens and amenorrhea provoked by progestins. The sequential pill requires administration of estrogens in the 1st phase and estroprogestins in the 2nd phase. They minimize physiological and hormonal effects, but the failure rate is 2-3% per woman year. Combined methods of monophasic, biphasic, and triphasic design are used from the 1st to 5th day of menstruation. They block ovulation with a high degree of efficacy, but the stimulating action of EP on the endometrium produces spotting, premature or late metrorrhagia, and amenorrhea. OCs protect against malignant epithelial tumors of the ovaries. It is estimated that 1700 ovarian carcinomas and 2000 endometrial carcinomas are averted each year by the use of the pill in the US. Endometrial cancer risk is halved by EP. 7 epidemiological studies have found no association between the pill and breast cancer, and the risk of benign mammary lesions is also reduced. Accurate anamnesis is mandatory for prescribing safe OCs including screening for coagulation, hepatic function and glycemia tests, and colposcopic examination. Smoking and the pill as well as age under 16 and over 36 increase risks. Nonetheless, the benefits of EP contraceptives outweigh the risks.