Intratubular germ cell neoplasia: associated infertility and review of the diagnostic modalities.

The incidence of testicular neoplasia has increased, and its early detection has become a pressing clinical issue. The strong association between male subfertility and risk of testicular neoplasia is consistent with the existence of common pathogenetic factors. Most forms of testicular germ tumors are believed to stem from a common precursor, intratubular germ cell neoplasia (ITGCN), also known as testicular carcinoma in situ. Identification of ITGCN cells in testicular biopsies, however, is a diagnostic challenge and markers are sorely needed to assist in the accurate identification of the lesion.

Absence of RBM expression as a marker of intratubular (in situ) germ cell neoplasia of the testis.

RBM (RNA-binding motif) protein is a marker of male germ cells. This protein is encoded by the Azoospermia factor region-b (AZF-b) of the human Y chromosome and is expressed exclusively in the male germ cell line, that is, spermatogonia, spermatocytes, and round spermatids. The authors analyzed the expression of the RBM gene in germ cell tumors and in the seminiferous tubules in the vicinity of these tumors to identify the presence of IGCN. Sections from testicular germ cell tumors of 21 patients were stained with anti-RBM antibody by using an immunohistochemical method. Distal tubules showing spermatogenesis were immunopositive for RBM protein. All of the germ cell tumors studied were completely immunonegative for RBM. Defined areas of IGCN also showed an absence of RBM expression. Tubules with spermatocyte-like cells, which were expected to express RBM, did not express this protein. This result enabled the identification of tubules as being IGCN. RBM is a novel marker consistently expressed in normal male germ cells but not in malignant germ cell tumors or IGCN. Thus, the absence of RBM expression in germ cells provides a new diagnostic tool of preinvasive malignancy of the testis.

Fluctuating parkinsonism: a pilot study of single afternoon dose of levodopa methyl ester.

Thirty-four patients with idiopathic fluctuating Parkinson's disease and early afternoon "delayed on" or severely resistant "off" periods, in spite of long-term antiparkinsonian therapy, were studied. The first afternoon levodopa administration was substituted with an equimolar dosage of the liquid formulation levodopa methyl ester (LDME). The major end-points for efficacy were latency to "on" and duration of "on" periods. The patients were divided into five subgroups according to their baseline treatment and they were evaluated monthly for 6 months using the Unified Parkinson's Disease Rating Scale. The patients completed weekly self-evaluation using an "on-off" chart. LDME was well tolerated by all the patients. A statistically significant reduction in latency to "on" was observed in all patients. The clinical effect of LDME remained stable during the treatment period (repeat measures ANOVA). The more rapid clinical effect of LDME and its stable and predictable antiparkinsonian activity represents a new and useful approach for treating patients with complicated Parkinson's disease.

QT interval and QT dispersion in multiple system atrophy (Shy-Drager syndrome).

To evaluate the influence of autonomic function on the QT interval and QT dispersion, 18 patients (10 males and 8 females; mean age 61 +/- 9 years) with multiple system atrophy (MSA, Shy-Drager syndrome) were studied. Cardiovascular tests were performed to assess the degree of autonomic dysfunction. The QT interval, corrected QT (QTc), QT dispersion (QTd), corrected and adjusted QTd were calculated from a standard 12-lead electrocardiogram. Fifteen healthy subjects matched for sex and age were studied as controls. Nine MSA patients showed severe autonomic dysfunction with orthostatic hypotension. In the remaining patients definite autonomic impairment was found. No statistically significant difference was found in QTd and only a trend towards higher values of maximal QTc was found in patients compared with controls. QTc prolongation, defined as greater than the mean +/- 2 SD of the controls, was detected only in three out of the 18 MSA patients (17%). No correlation was found between the severity of autonomic impairment and repolarization parameters. Our data suggest that chronic autonomic impairment in patients with MSA does not significantly affect ventricular repolarization and ventricular dispersion.

The clinical efficacy of a single afternoon dose of levodopa methyl ester: a double-blind cross-over study versus placebo.

Levodopa methyl ester (LDME) is a highly water soluble derivative produced by esterification of the carboxilic acid moiety of the L-Dopa molecule that is rapidly hydrolyzed to L-Dopa and can be administered orally in an easily dosable liquid form. In this study the relative efficacy and tolerability of a single dose of an oral solution of 250 mg of LDME was compared to that of placebo in reversing afternoon off period. A controlled double-blind cross-over study versus placebo had previously been carried out in 25 idiopathic parkinsonian patients with predictable fluctuations in motor performances. The study design stipulated the sequential administration of LDME and placebo in group A and placebo and LDME in group B on two consecutive days. All patients turned "on" with LDME and none with placebo solution. The mean latency to "on" was 25.3 +/- 13.5 min for the A group and 27.6 +/- 3.9 min for group B (Fig. 2) and the "on" duration was 147.7 +/- 50.3 min and 163.3 +/- 39.3 min for the A and B groups respectively. Five patients suffering from drug resistant "off" phenomena turned "on" with LDME solution showing a mean latency to "on" of 31.4 +/- 6.2 min.

Prevalence of cryptosporidiosis in HIV-infected patients with diarrhoeal illness.

Protozoans of the genus Cryptosporidium may cause serious diarrhoeal illness in immunocompromised hosts and especially in HIV-infected patients. In this study we have evaluated the frequency of Cryptosporidium in stools of 51 HIV-infected patients with diarrhoea. Laboratory diagnosis of cryptosporidiosis was performed of faecal samples concentrated by a formalin-ether sedimentation technique and stained by a modified cold Ziehl-Neelsen method. Results demonstrated that 17 (33.3%) of these patients were infected with Cryptosporidium. Moreover, Cryptosporidium infection was the first clinical marker of AIDS in 7 cases. Our data show that the prevalence of this parasitosis in HIV-infected people seems to be higher in our region (Apulia, South Italy), compared to other areas of the world.

The clinical efficacy of single morning doses of levodopa methyl ester: dispersible Madopar and Sinemet plus in Parkinson disease.

For many patients with Parkinson disease and levodopa-related motor fluctuations, the latency to onset of action of a single dose of a levodopa preparation may be both long and variable. In an effort to find a more rapidly acting and reliable preparation of levodopa, we therefore studied the efficacy of single doses of an oral solution of 250 mg of levodopa methyl ester (ME) with benserazide, 50 mg and of a molar equivalent dose of dispersible Madopar (DM) (50/200) in 13 patients in the fasting state after overnight drug withdrawal. The response of seven of these patients was compared to that after two Sinemet 25/100. The latency to "on" was equally fast with ME and DM, and significantly faster than after standard Sinemet. The duration of "on" was similar with all three. Because of this more rapid relief of "off" periods, both ME and DM offer a potential clinical advantage over standard preparations of levodopa.

[Adherence to a diet and the social aspects of patients with celiac disease]. / Aderenza alla dieta ed aspetti sociali dei pazienti con malattia celiaca.

We studied the social behaviour and dietary habits of 335 coeliacs older than 6 yrs diagnosed in our paediatric gastroenterology unit by a mailed questionnaire, 156 patients (45.2%) answered all questions; their median age was 14.7 yrs (range 6-29). We found that the disease does not compromise educational achievement and working capacity of patients. A majority of our coeliacs are students (from primary school to university) and rather successful ones since 55% of them passed their previous year examinations. Some are already employed and work as clerks, artisans, masons or skilled workers. 89.6% of our patients reported to be on a strict gluten-free diet, 9% introduce small amounts of gluten and 1.4% are on a normal diet by their own decision. Coeliac patients originating from Northern Italy have more of their gluten-free foods home made and use more gliadin free cereals (rice, maize), whereas coeliacs originating from the Southern regions consume more ready made gluten-free foods. We have assessed the amount of gluten-free products consumed monthly by our patients and their food preferences. Females eat less than males and prefer bread and flour based dishes, whereas males east more pasta and biscuits.

[Clinical data on celiac disease with an early or late onset]. / Dati clinici nella malattia celiaca ad esordio precoce o tardivo.

Typical symptoms in celiac disease (CD) are usually associated with early onset of the disease, whereas an atypical symptomatology has more often a later onset. The aim of this study was to evaluate the prevalence of some clinical signs and symptoms in children whose CD started before one year of age ("early onset" 135 children, M/F 50/85, mean age at onset 6.9 +/- 1.9 months) and in children whose disease started later ("late onset", M/F 14/26, mean age at onset 26.3 +/- 26.7 months). We analyzed: a) time lapse between gluten introduction and onset of symptoms, b) prevalence of patients with gastrointestinal symptoms alone and that of patients with gastrointestinal plus extraintestinal symptoms, c) frequency of each symptom. We then evaluated the influence of breast feeding and age of gluten introduction on time lapse. Our results showed that typical gastrointestinal symptoms, like diarrhea anorexia and abdominal distension prevailed both in children with early and late onset; whereas failure to thrive was significantly more frequent in children with an early onset CD (p < 0.01). Breast feeding delayed onset of symptoms: time lapse was significantly longer in children breast fed for a longer time (p < 0.001). On the contrary, age at first gluten ingestion seemed to have no influence on age at onset, since it was similar in both groups.