Vitamin E deficiency secondary to chronic intestinal malabsorption and effect of vitamin supplement: a case report.

We report the clinical, neurophysiological (comprehending electromyography, nerve conduction velocities, and multimodal evoked potentials), histological study of the nerve and muscle and the effect of vitamin E supplement in a 32-year-old case with chronic vitamin E deficiency subsequent to acquired intestinal malabsorption. An early diagnosis for an early treatment is essential in preventing severe neurological deterioration.     

Variations in ferritin levels in blood during physiological pregnancy

Iron deficiency anemia is the most frequent haematological pathology in pregnancy. Serum ferritin levels represent the state of iron deposits. Low levels are a sure sign of iron deficiency. At the University of Turin we studied the variations of serum ferritin levels during physiological pregnancy and the sensitivity of routine blood tests with respect to serum ferritin levels. Routine haematological blood values along with ferritin levels were measured in 115 patients throughout pregnancy. The mean serum ferritin level was 56 ng/ml in the first trimester, 27.2 ng/ml in the second and 11.8 ng/ml in the third. The incidences of anemia per trimester was 6.6%, 4.8% and 49% respectively (p less than 0.05, chi squared). Our results show that it is important to evaluate iron deposits early in pregnancy by measuring serum ferritin levels in order to determine the need for iron therapy.     

Reduced ACTH/cortisol responses to naloxone in men with Parkinson's disease

Summary In order to establish whether the inhibitory control exerted by endogenous opioid peptides on ACTH/cortisol secretion changes in patients affected by Parkinson's disease, ten parkinsonian male subjects and eight age matched normal controls were tested with naloxone (4 mg an i.v. bolus plus 10 mg infused in two hours). In a different occasion all subjects were tested with normal saline. Experiments started at 09.00 h. Plasma ACTH and cortisol concentrations showed a slight physiological decline during saline test in both groups. In the normal controls and in the parkinsonian patients both ACTH and cortisol levels were significantly higher after naloxone administration than during saline test. However, both naloxone induced ACTH and cortisol responses were significantly higher in normal than in parkinsonian subjects. In agreement with the well-known opioid deficiency characterizing the parkinsonian brain, these data show a reduced opioid inhibitory control of ACTH/cortisol secretion in patients with Parkinson's disease.     

Reduction of GH response to the GABA-B agonist baclofen in patients with major depression

In order to establish whether alterations in the GABAergic control of GH secretion occur in male patients with major depression, the GH response to the GABAergic-B agonist baclofen (10 mg at 0830h) or to placebo was tested in 9 depressed men and in 10 age- and weight-matched male normal controls.

The basal concentrations of GH were significantly lower in the depressed patients (0.87± 0.69 ng/ml) than in the normal controls (1.57±0.33 ng/ml) (p=0.011) and were not modified by the administration of placebo. The administration of baclofen induced a striking, significant increase in GH concentrations in the normal controls (mean peak at 90 MIN=6.4±1.5 ng/ml). In contrast, a slight, nonsignificant GH increase occurred in the depressed patients after baclofen (mean peak at 90 MIN=1.57±1.45 ng/ml). The GH response was significantly lower in the depressed than in the control subjects (p<0.001). These data indicate the presence of reduced GABAergic control of GH secretion in male depressed patients.     

Prognostic relevance of histological grade and its components in node-negative breast cancer patients.

Available results highlight the lack of good level of evidence studies on the pure prognostic value of histological grade. In the present study, the prognostic relevance of histological grade and of its three components, tubule formation, nuclear pleomorphism and mitotic count, was analyzed in a series of 372 patients with node-negative breast cancer treated with locoregional therapy alone until early relapse. Histological grade was determined blindly by two observers and discordance between evaluations was resolved after joint review using a multihead microscope. No relation was observed between histological grade and any of its three components and disease-free survival. Conversely, a significant relation was observed between histological grade and distant metastasis-free survival (at 6 years, 94, 86 and 76% for grades 1, 2 and 3, respectively, P=0.013) as well as overall survival (98, 90 and 86%, P=0.001). A breakdown analysis as a function of the three components showed that neither tubule formation nor nuclear pleomorphism was associated with prognosis, and only mitotic count strongly influenced both distant metastasis-free survival (91, 82 and 74%, P=0.014) and overall survival (97, 87 and 85%, P=0.011). Histological grade suffers from a much higher subjectivity than any other microscopic evaluation of biomarkers as it is the sum of three different morphological features. Within the Italian Network for Quality Assessment of Tumor Biomarkers program we observed that histological grade is an independent prognostic variable, but also that this role is ascribable only to the number of mitotic figures. In conclusion, due to the ever smaller size of diagnosed breast cancers, resulting in less cancer tissue for biofunctional and molecular analysis, mitotic count evaluated under strict quality control conditions seems to be an accurate and feasible prognostic variable.     

Lateral unicompartimental knee arthroplasty: indications,technique and short-medium term results

Lateral unicompartmental knee arthroplasty (UKA) is a valid alternative treatment in the event of arthritis confined to the lateral compartment. This paper examines its indications, technique and short to medium-term results. A total of 159 Miller–Galante cemented UKA prostheses (Zimmer, Warsaw, Indiana) were implanted consecutively (131 medial and 28 lateral) by the same surgeon. This study investigates 28 lateral UKAs in 27 patients. Twenty-five implants in 24 patients (including a subject operated bilaterally) were followed up for 12–60 months. Three patients were discarded on account of to short a follow-up period. The Hospital for Special Surgery (HSS) knee score was used to compare the pre- and post-operative results of the lateral UKA patients. The HSS score improved from a pre-op mean of 59.92 (range 48–68) to 88.04 (range 71–95) at the last follow-up. There was a positive increase in the pain, function and ROM components of the score. The lateral UKA prosthesis can be regarded as a sound alternative to total knee replacement. Correct patient selection on the basis of optimum surgical indications, however, is essential. No benefits of funds were received in support of the study.     

Six cases of travel-associated legionnaires' disease in Ischia involving four countries

Summary The detection of travel-associated legionellosis can be extremely difficult; hence, an extensive case investigation is recommended in pneumonia-striken travellers and tourists, who are particularly at risk of acquiring the disease. On the Island of Ischia (Isola d'Ischia, Naples, Italy) a total of six cases of Legionnaires' disease occurred from 1986 to 1990. All patients (one man and two women from Germany, one Austrian woman, one Swiss man, and one Italian woman) had taken thermal baths and stayed in local hotels; they all experienced severe pneumonia, and three of them died. These cases were associated with hotels, and the hot-water supply was presumed to have transmitted the infection. Remedial procedures were applied to the hot-water plumbing of the hotels according to the WHO recommendations and were proved to be effective. The occurrences described in this paper stress the importance of rapid and accurate reporting of diagnosed cases to the country where the infection was probably acquired, in order to ensure early detection of endemic foci and emerging clusters of legionellosis.

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Sechs Fälle von reiseassoziierter Legionärskrankheit in Ischia unter Beteiligung von vier Ländern

Zusammenfassung Der Nachweis reiseassoziierter Legionärskrankheit gestaltet sich häufig schwierig. Eine Überwachung von Touristen und Reisenden, die ein erhöhtes Legionellose-Risiko haben, ist daher zu empfehlen. Zwischen 1986 und 1990 traten auf der Insel Ischia (Neapel, Italien) insgesamt sechs Fälle von Legionärskrankheit auf. Alle Patienten (ein Mann und zwei Frauen aus Deutschland, eine Österreicherin, ein Schweizer und eine Italienerin), die in Hotels auf der Insel wohnten, hatten Thermalbäder besucht. Sie erkrankten an schweren Pneumonien, wobei drei Todesfälle auftraten. Die Ansteckungsquelle konnte mit Hotels in Verbindung gebracht werden, wobei die Übertragung der Infektion über die Warmwasserleitungsnetze als gesichert anzunehmen war. Desinfektionsmaßnahmen in den betreffenden Hotels, die nach den Empfehlungen der WHO ausgeführt wurden, erwiesen sich als wirksam. Das genannte Infektionsgeschehen weist auf die Notwendigkeit hin, Fälle von Legionärskrankheit so rasch wie möglich dem Ursprungsland unter Angabe der vermuteten Infektionsquelle zu melden, um sicherzustellen, daß eine Früherkennung endemischer Herde bzw. assoziierter Legionellosen bekannt gemacht wird.

     

An 11-year longitudinal study of the occupational dust exposure and lung function of polyvinyl chloride, cement and asbestos cement factory workers

Standardized questionnaires and lung function tests were administered in 1973, 1980, and 1984 to 126 workers occupationally exposed to polyvinyl chloride (PVC) dust, to cement dust, or to asbestos cement dust until 1974-1978 and to PVC thereafter. The workers in the last group were assigned to two asbestos exposure categories (heavy and slight). The decline in forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1.0) was analyzed with regard to the length of time since the data of first employment. After adjustment for age, height, and smoking status at the date of first employment, the decline in FVC and FEV1.0 among the nonsmokers-light smokers was slightly accelerated with length of employment in the PVC and slight asbestos exposure groups and markedly accelerated with time since first employment in the heavy asbestos exposure group. The heavy smokers in all the exposure groups had FVC and FEV1.0 predicted values that were lower than those of the nonsmokers-light smokers; these differences remained constant with length of employment. Cessation of asbestos exposure for about 10 years did not seem to change lung function decline.     

The role of resistance characteristics of viral strains in the prediction of the response to antiretroviral therapy in HIV infection

OBJECTIVE: To study the role of resistance characteristics of viral mutants in the prediction of virologic and immunologic response to antiretroviral therapy in HIV-infection. METHODS: This study is based on a mathematical model that generates viral and immunologic dynamics of HIV infection, taking into account drug-resistant mutants and therapy. We analyzed predictive factors of the increase in CD4 cell count and of the decrease in viral load from baseline after 6 months of HAART on a sample of 300 simulated individuals. The set of potential predictors was constituted by patients' state at initiation of therapy and by resistance characteristics of viral strains at that time. Predictive models, obtained by stepwise regression, were selected and compared using Mallows' Cp criterion. RESULTS: In addition to baseline viral load and CD4 cell count, known to influence response to therapy, baseline CD8 cell count and resistance characteristics of detectable strains are shown to improve the accuracy of the prediction. On the contrary, resistance parameters of low frequency viral mutants have no predictive value. CONCLUSIONS: Characteristics of preexisting detectable resistant mutants as determinants of virologic and immunologic response to antiretroviral therapy increase the capacity to predict the outcome of the treatment. Therefore, the use of phenotypic and genotypic testing could be crucial and should be considered for the choice of therapy.     

Nutrient signalling in the regulation of human muscle protein synthesis

The mammalian target of rapamycin (mTOR) and AMP-activated protein kinase (AMPK) are important nutrient- and energy-sensing and signalling proteins in skeletal muscle. AMPK activation decreases muscle protein synthesis by inhibiting mTOR signalling to regulatory proteins associated with translation initiation and elongation. On the other hand, essential amino acids (leucine in particular) and insulin stimulate mTOR signalling and protein synthesis. We hypothesized that anabolic nutrients would be sensed by both AMPK and mTOR, resulting in an acute and potent stimulation of human skeletal muscle protein synthesis via enhanced translation initiation and elongation.
We measured muscle protein synthesis and mTOR-associated upstream and downstream signalling proteins in young male subjects ( n = 14) using stable isotopic and immunoblotting techniques. Following a first muscle biopsy, subjects in the 'Nutrition' group ingested a leucine-enriched essential amino acid–carbohydrate mixture (EAC). Subjects in the Control group did not consume nutrients. A second biopsy was obtained 1 h later. Ingestion of EAC significantly increased muscle protein synthesis, modestly reduced AMPK phosphorylation, and increased Akt/PKB (protein kinase B) and mTOR phosphorylation ( P < 0.05). mTOR signalling to its downstream effectors (S6 kinase 1 (S6K1) and 4E-binding protein 1 (4E-BP1) phosphorylation status) was also increased ( P < 0.05). In addition, eukaryotic elongation factor 2 (eEF2) phosphorylation was significantly reduced ( P < 0.05). Protein synthesis and cell signalling (phosphorylation status) was unchanged in the control group ( P > 0.05).
We conclude that anabolic nutrients alter the phosphorylation status of both AMPK- and mTOR-associated signalling proteins in human muscle, in association with an increase in protein synthesis not only via enhanced translation initiation but also through signalling promoting translation elongation.