Occupational Health Services Have a Relevant Role in Protecting the Health and Safety of Paramedics.

In this Letter to the Editor, the authors point out occupational health and safety risks for paramedics, and highlight the relevant role carried out by multidisciplinary occupational health services in the prevention of occupational risks and the promotion of physical and mental well-being of these workers.

Dans cette lettre à l'éditeur, nous insistons sur les risques de sécurité et de santé encourrus par les personnels non médicaux ainsi que sur le rôle des services de santé au travail dans la prévention de ces risques et dans la promotion de leur santé physique et mentale.

Small Intestinal Bacterial Overgrowth Affects the Responsiveness to Colchicine in Familial Mediterranean Fever.

OBJECTIVE: Familial Mediterranean fever (FMF) is an autosomal recessive disease due to a MEFV gene mutation. Since Helicobacter pylori infection has been described to increase the severity and frequency of FMF attacks, we evaluate if overgrowth of small intestinal bacterial (SIBO), associated with a release of bacterial products, can affect the response to colchicine in FMF patients poorly responsive to colchicine. METHODS: We revised our Periodic Fever Centre database to detect FMF patients who were poorly responsive to colchicine, without a well-defined cause of drug resistance. They were evaluated for SIBO presence, then treated with decontamination therapy. RESULTS: Among 223 FMF patients, 49 subjects show colchicine resistance, and no other known causes of colchicine unresponsiveness has been found in 25 patients. All 25 patients underwent glucose breath test; 20 (80%) of them were positive, thus affected by SIBO. After a successful decontamination treatment, 11 patients (55%) did not show FMF attacks during the following three months (p < 0.01), while 9 of them revealed a significant reduction of the number of attacks compared to three months before (p < 0.01). CONCLUSION: The SIBO eradication improves laboratory and clinical features of FMF patients. Thus, patients with unresponsiveness to colchicine treatment should be investigated for SIBO.

Reversible Pulmonary Hypertension Associated with Whipple's Disease.

We describe a case of Whipple's disease with pulmonary hypertension in a 72-year-old woman in whom the pulmonary hypertension resolved completely after antibiotic therapy. She was admitted to study with a 2-months history of weight loss, diarrhoea, abdominal pain, asthenia, inappetence, and fever. She did not have dyspnoea or respiratory symptoms. A casual echocardiogram showed a pulmonary artery systolic pressure of 95 mmHg. Forty days after starting antibiotic therapy, an echocardiogram showed a complete normalisation of right ventricular involvement. Whipple's disease is a rare and multisystemic disorder in which pulmonary involvement is not a well-known finding. Although Whipple's disease is not generally considered as a possible cause of pulmonary hypertension, such awareness is important because it may be potentially resolved with antibiotic therapy.

Lower embryonic loss rates among twin gestations following assisted reproduction.

PURPOSE: To determine whether maternal age and number of transferred embryos influence early pregnancy losses in twin pregnancies compared to singletons following IVF/ICSI. METHODS: We compared the pregnancy loss rates in singleton (n = 549) and twin (n = 252) gestations, stratified by maternal age (< or = 35 and > 35 years) and the number of transferred embryos (1-3 and 4-9). RESULTS: Loss rates of singleton pregnancies were significantly higher than that in twins (OR 3.0, 95% CI 1.9, 4.9), especially among singletons conceived after transfer of 4-9 embryos (OR 5.0, 95% CI 2.2, 11.9). Younger mothers of twins had lower loss rates (OR 0.3, 95% CI 0.1, 0.9). CONCLUSION: Twins have a significantly reduced spontaneous miscarriage rate compared with singletons following IVF/ICSI. Higher implantation rates per cycle (i.e., development of twins rather than one live embryo) may represent a better capacity of the uterus for early embryonic development.

Rifaximin dose-finding study for the treatment of small intestinal bacterial overgrowth.

BACKGROUND: Few controlled studies assessing choice and duration of antibiotic therapy for small intestinal bacterial overgrowth are available. AIM: To assess efficacy, safety and tolerability of different doses of rifaximin, a broad spectrum non-absorbable antibiotic, for intestinal bacterial overgrowth eradication. METHODS: We enrolled 90 consecutive patients affected by small intestinal bacterial overgrowth. The presence of small intestinal bacterial overgrowth was based on the occurrence of a rise of H2 values >12 p.p.m. above the basal value after 50 g glucose ingestion. Patients were randomized in three 7-day treatment groups: rifaximin 600 mg/day (group 1); rifaximin 800 mg/day (group 2) and rifaximin 1200 mg/day (group 3). Glucose breath test was reassessed 1 month after the end of therapy. Compliance to the treatment and incidence of side-effects were also evaluated. RESULTS: No drop-outs were observed in the three groups. Glucose breath test normalization rate was significantly higher in group 3 (60%) with respect to group 1 (17%; P < 0.001) and group 2 (27%, P < 0.01). No significant differences in patient compliance and incidence of side-effects were found among groups. CONCLUSIONS: Higher doses of rifaximin lead to a significant gain in terms of therapeutic efficacy in small intestinal bacterial overgrowth eradication without increasing the incidence of side-effects.

Abnormal breath tests to lactose, fructose and sorbitol in irritable bowel syndrome may be explained by small intestinal bacterial overgrowth.

BACKGROUND: Small intestinal bacterial overgrowth and sugar malabsorption (lactose, fructose, sorbitol) may play a role in irritable bowel syndrome. The lactulose breath test is a reliable and non-invasive test for the diagnosis of small intestinal bacterial overgrowth. The lactose, fructose and sorbitol hydrogen breath tests are widely used to detect specific sugar malabsorption. AIM: To assess the extent to which small intestinal bacterial overgrowth may influence the results of hydrogen sugar breath tests in irritable bowel syndrome patients. METHODS: We enrolled 98 consecutive irritable bowel syndrome patients. All subjects underwent hydrogen lactulose, lactose, fructose and sorbitol hydrogen breath tests. Small intestinal bacterial overgrowth patients were treated with 1-week course of antibiotics. All tests were repeated 1 month after the end of therapy. RESULTS: A positive lactulose breath test was found in 64 of 98 (65%) subjects; these small intestinal bacterial overgrowth patients showed a significantly higher prevalence of positivity to the lactose breath test (P < 0.05), fructose breath test (P < 0.01) and sorbitol breath test (P < 0.01) when compared with the small intestinal bacterial overgrowth-negatives. Small intestinal bacterial overgrowth eradication, as confirmed by negative lactulose breath test, caused a significant reduction in lactose, fructose and sorbitol breath tests positivity (17% vs. 100%, 3% vs. 62%, and 10% vs. 71% respectively: P < 0.0001). CONCLUSIONS: In irritable bowel syndrome patients with small intestinal bacterial overgrowth, sugar breath tests may be falsely abnormal. Eradication of small intestinal bacterial overgrowth normalizes sugar breath tests in the majority of patients. Testing for small intestinal bacterial overgrowth should be performed before other sugar breath tests tests to avoid sugar malabsorption misdiagnosis.

Hypercreatininemia and hyperglycemia: diabetic nephropathy or "inverted peritoneal auto-dialysis"?

We describe a case of 51-year-old male with fever, abdominal pain and inguino-scrotal hernia. Laboratory examination revealed hypercreatininemia and hyperglycemia, firstly interpreted as diabetic nephropathy. US and CT scan showed a hernia of the bladder into the scrotum. Surgery revealed multiple bladder perforations with peritoneal diffusion of urine. So, hypercreatininemia was caused by peritoneal reabsorption of urea and creatinine, a condition that may be described as "inverted peritoneal auto-dialysis". Surgical reposition and repairment of the bladder led to rapid normalization of serum urea and creatinine. Discharged diagnosis was intraperitoneal rupture of inguino-scrotal hernia of the bladder in patient with recent onset of diabetes mellitus.

Pharmacological and clinical basis of treatment of Familial Mediterranean Fever (FMF) with colchicine or analogues: an update.

Familial Mediterranean Fever (FMF), an autosomal recessive disorder, is characterised by recurrent attacks of fever and serositis, lasting 24-72 hours. Since 1972 colchicine has become the drug of choice for prophylaxis against FMF attacks and amyloidosis FMF-associated. Colchicine, an alkaloid neutral, is absorbed in the jejunum and ileum. It metabolised by liver and only small amounts are recovered unchanged in the urine. Really plasma half-life is prolonged in patients with liver or renal failure. Colchicine is able to prevent activation of neutrophils, binding beta-tubulin and making beta-tubulin-colchicine complexes; this way inhibits assembly of microtubules and mitotic spindle formation; moreover its mode of action includes modulation of chemokines, prostanoids production, inhibition of neutrophil and endothelial cell adhesion molecules. The minimal daily dose in adults is 1.0 mg/die, but in children there is not a definite dose. Since in vitro high dosages of colchicine stop mitosis, this drug might interfere with male and female fertility and with children growth, but, according to current guidelines and because of rare side effects of the drug, FMF patients are recommended to take colchicine. Since colchicine treatment is often complicated by frequent gastrointestinal side effects, by our experience, in order to improve colchicine tolerance we recommend: lactose-free diet and treatment of intestinal bacterial overgrowth and/or Hp-infection, assessed by breath tests. Since our data showed that 10-15% of FMF patients seem are non-responders or intolerant to colchicine, today we are working in the design of colchicine analogues which may have lesser toxicities and a larger therapeutic window.

Effect of exogenous beta-galactosidase in patients with lactose malabsorption and intolerance: a crossover double-blind placebo-controlled study.

OBJECTIVE: To evaluate the efficacy of the addition to milk, 5 min and 10 h before its consumption, of a lactase obtained from Kluyveromyces lactis in lactose malabsorbers with intolerance. DESIGN: Double-blind, placebo-controlled, crossover study. SETTING: University Hospital. SUBJECTS: In total, 11 male and 19 female (aged from 18 to 65 y, mean age 43.3 y) lactose malabsorbers with intolerance participated. INTERVENTIONS: Each patient underwent three H(2) breath tests, in a random order. We used 400 ml of cow's semiskimmed milk as substrate and a beta-galactosidase obtained from K. lactis. The test A was carried out adding to the milk the enzyme (3000 UI), 10 h before its consumption; the test B was performed adding the beta-galactosidase (6000 UI) 5 min before milk ingestion and the test C was made using placebo. We evaluated the maximum breath H(2) concentration, the cumulative H(2) excretion and a clinical score based on intolerance symptoms (bloating, abdominal pain, flatulence and diarrhoea). RESULTS: Our study showed a significant reduction of the mean maximum H(2) concentration after both test A (12.07 +/- 7.8 p.p.m.) and test B (13.97 +/- 7.99 p.p.m.) compared with test C (51.46 +/- 16.12 p.p.m.) (ANOVA F = 54.33, P < 0.001). Similarly, there was a significant reduction of the mean cumulative H(2) excretion after both test A (1428 +/- 1156 p.p.m.) and test B (1761 +/- 966 p.p.m.) compared with test C (5795 +/- 2707 p.p.m.) (ANOVA F = 31.46, P < 0.001). We also observed a significant reduction of the mean clinical score after both test A (0.36 +/- 0.55) and test B (0.96 +/- 0.85) compared with test C (3.7 +/- 0.79) (ANOVA F = 106.81, P < 0.001). Moreover, with regard to the mean clinical score, there was a significant reduction after test A with respect to test B (Bonferroni's P = 0.03). CONCLUSIONS: Our study shows that in lactose malabsorbers with intolerance, the lactase obtained from K. lactis can represent a valid therapeutic strategy, with objective and subjective efficacy and without side effects.

A simple method for fallopian tube sperm perfusion using a blocking device in the treatment of unexplained infertility.

OBJECTIVE: To evaluate the efficacy of fallopian sperm perfusion (FSP) using a new method similar to the FAST system in comparison with standard intrauterine insemination (IUI) in patients with unexplained infertility. DESIGN: Prospective, randomized, controlled study. SETTING: Assisted conception service in a University Hospital. PATIENT(S): Women with unexplained infertility undergoing controlled ovarian hyperstimulation (COH). INTERVENTION(S): After hCG administration, patients were randomized to either standard IUI or FSP. The women received the same treatment in the first and all subsequent cycles. A maximum of three cycles was performed. Intrauterine insemination was performed using a standard method, and fallopian sperm perfusion was performed using a commercial device for hysterosalpingography and tubal hydropertubation. MAIN OUTCOME MEASURE(S): Clinical and ongoing pregnancy rates. RESULT(S): A total of 132 cycles was completed: 66 IUI cycles and 66 FSP cycles. In the IUI group, there were 5 ongoing pregnancies, giving a pregnancy rate of 7.6 per cycle and 15.6% per patient; in the FSP group, 14 ongoing pregnancies occurred, giving a pregnancy rate of 21.2% per cycle and 42.4% per patient. The prevalence of multiple pregnancies, miscarriages and ectopic pregnancies was similar in the two insemination groups. Fallopian sperm perfusion was easy to perform, and no case of sperm reflux was observed. The procedure was well tolerated and no complications were observed. The costs were comparable with standard IUI. CONCLUSION(S): In the treatment of couples with unexplained infertility, the method for fallopian sperm perfusion described yields higher pregnancy rates than IUI, with no significant increase in costs or complications. However, these results need to be confirmed in larger studies before replacing IUI with FSP as standard practice.

Pregnancy in hyperprolactinemic infertile women treated with vaginal bromocriptine: report of two cases and review of the literature.

Vaginal bromocriptine has proven safe and effective in treating hyperprolactinemic women. However, there has been no long-term clinical assessment regarding the influence of daily vaginal bromocriptine administration on the ability to conceive. This article presents two cases of successful pregnancy resulting from this alternative treatment. An infertile woman with an empty sella and hyperprolactinemia was treated with vaginal bromocriptine because of intolerance to oral administration. Prolactin levels were quickly normalized and no side effects occurred. Repeated postcoital tests during treatment proved normal. Twelve months later, the patient conceived. The therapy was discontinued during pregnancy, without complications. Although bromocriptine treatment was not resumed after delivery, postpartum prolactin levels were lower than before treatment and magnetic resonance imaging revealed an unchanged empty sella. Another patient with infertility and pituitary microadenoma with intolerance to oral dopaminergic agonists received the same treatment. Prolactin quickly fell to within the normal range. Vaginal bromocriptine was well tolerated and postcoital test results were not impaired. Tumor regression occurred and 10 months later the patient conceived. Despite bromocriptine withdrawal, no significant complications occurred during pregnancy. It can therefore be concluded that a couple's fertility does not appear to be significantly affected by the persistent local presence of bromocriptine.

Lipoprotein(a) changes during natural menstrual cycle and ovarian stimulation with recombinant and highly purified urinary FSH.

This prospective, randomized, controlled study compared the effects of recombinant human FSH (r-hFSH) and highly purified urinary FSH (u-hFSH HP) on lipoprotein(a) [Lp(a)] concentrations in women undergoing ovarian stimulation. Fifty infertile women were randomly allocated into two equally sized treatment groups (n = 25 per group). Thirty normal ovulation women were recruited as controls. The infertile women received u-hFSH or r-hFSH 150 IU/day starting on cycle day 2. From cycle day 6 the dose was adjusted according to ovarian response. Human chorionic gonadotrophin 10,000 IU was administered once there was at least one follicle > or =18 mm in diameter. The luteal phase was supported with progesterone 50 mg/day for at least 15 days. Repeated measurements of Lp(a) concentrations were performed during both stimulated and natural cycles. A significant increase in luteal phase Lp(a) concentrations was detected in the stimulated cycles, whereas no significant changes in serum Lp(a) concentrations were observed during natural cycles. There were no significant differences between the urinary and recombinant FSH effects on serum Lp(a). The luteal Lp(a) increase was transitory because after 1 month Lp(a) concentrations returned to baseline values if pregnancy failed to occur; in pregnant women persistent increased Lp(a) concentrations were found at the 8th week. The percentage changes in serum Lp(a) were positively correlated with the luteal progesterone increase (r = 0.40, P < 0.05), but not with follicular or luteal oestradiol increase. The women with low baseline Lp(a) (< or =5 mg/dl) had a greater increase of the Lp(a) concentrations at midluteal phase than women with baseline Lp(a) >5 mg/dl. In conclusion, the recombinant or urinary hFSH administration does not directly influence Lp(a) concentrations. The luteal Lp(a) increase in stimulated cycles is not related to gonadotrophin treatment per se, but appears to be related to the high luteal progesterone concentrations, physiologically or pharmacologically determined. Our results also suggest that the sensitivity to the progesterone changes could be related to apolipoprotein(a) phenotype.

Evaluation of a container closure integrity test model using visual inspection with confirmation by near infra-red spectroscopic analysis.

The objective of this study was to evaluate a novel test model involving an easy and rapid method to assess parenteral container/closure integrity. In this study, an extremely hygroscopic powder (methacholine chloride) was filled into the test vial/closure combination and served as an indicator of water vapor ingress into the package through either the stopper/glass interface and/or permeation through the closure. A visual means of detection was used initially, as the powder liquefies upon contact with a high-humidity environment. A further level of sensitivity was gained by using Near Infra-Red (NIR) spectroscopy to confirm that no additional water vapor was detectable in the test vials after being subjected to autoclave (worst-case water ingress) treatments. After two sequential autoclave cycles, none of the samples in the pilot study showed liquification of the indicator powder. This indicated that there was negligible ingress of water vapor, and therefore, the container/closure combination provided an adequate barrier to moisture ingress at the stress temperature and pressure conditions studied. The sensitivity of the NIR water ingress detection method was shown to be in the range needed for an acceptable vial integrity test. In conclusion, the model evaluated in this study can be used as an easy, rapid, and non-destructive closure integrity evaluation test. The use of such a NIR spectroscopy method would be immediately and directly amenable to the evaluation of vial integrity of dry powder-filled and lyophilized products, or can be used indirectly as shown in this study to assess container closure integrity for liquid-filled parenteral vial closure systems.