Improved selective medium for the isolation of lipase-positive Clostridium botulinum from feces of human infants.

Isolation of lipase-positive Clostridium botulinum from fecal specimens establishes the diagnosis of infant botulism, contributes to the diagnosis of food-borne botulism, and is most easily accomplished by use of selective media. Modification of an available selective medium, C. botulinum inhibitory medium (CBI), enabled more rapid isolation of C. botulinum. The modified medium (botulinum selective medium [BSM] contained (per liter) 25 g of dehydrated heart infusion broth, 20 g of agar, 30 ml of egg yolk suspension, 250 mg of cycloserine, 76 mg of sulfamethoxazole, 4 mg of trimethoprim, and 100 IU of thymidine phosphorylase at pH 7.4. The two media were compared by using 15 fresh fecal specimens from infant botulism patients (10 type A and 5 type B) and a C. botulinum isolate that had been obtained from an infant botulism patient and that was mixed into a fresh stool specimen from a healthy human infant. In comparison to CBI, BSM always provided better suppression of the nonbotulinum fecal flora and earlier emergence of lipase-positive colonies. Diagnosis of infant botulism was accomplished sooner with BSM than with CBI because isolation of lipase-positive C. botulinum was easier.     

Childhood Cancer and the Risk of ESKD

BackgroundIncreasing cancer incidence among children alongside improved treatments has resulted in a growing number of pediatric cancer survivors. Despite childhood cancer survivors’ exposure to various factors that compromise kidney function, few studies have investigated the association between childhood cancer and future kidney disease.MethodsTo assess the risk of ESKD among childhood cancer survivors, we conducted a nationwide, population-based, retrospective cohort study that encompassed all Israeli adolescents evaluated for mandatory military service from 1967 to 1997. After obtaining detailed histories, we divided the cohort into three groups: participants without a history of tumors, those with a history of a benign tumor (nonmalignant tumor with functional impairment), and those with a history of malignancy (excluding kidney cancer). This database was linked to the Israeli ESKD registry to identify incident ESKD cases. We used Cox proportional hazards models to estimate the hazard ratio (HR) of ESKD.ResultsOf the 1,468,600 participants in the cohort, 1,444,345 had no history of tumors, 23,282 had a history of a benign tumor, and 973 had a history of malignancy. During a mean follow-up of 30.3 years, 2416 (0.2%) participants without a history of tumors developed ESKD. Although a history of benign tumors was not associated with an increased ESKD risk, participants with a history of malignancy exhibited a substantially elevated risk for ESKD compared with participants lacking a history of tumors, after controlling for age, sex, enrollment period, and paternal origin (adjusted HR, 3.2; 95% confidence interval, 1.3 to 7.7).ConclusionsChildhood cancer is associated with an increased risk for ESKD, suggesting the need for tighter and longer nephrological follow-up.     

The association between melatonin and sleep stages in normal adults and hypogonadal men

The role of melatonin in normal sleep-wake regulation has been inferred from the temporal relationships between its cycle and the 24 h cycle in sleep propensity. Pharmacological doses of melatonin were reported to have sleep-inducing effects in insomniacs. The current study investigated the relationship between melatonin and sleep stages in groups of hypogonadal men with abnormal melatonin levels. We were also interested in examining what would happen to these relationships during testosterone replacement therapy. Male patients with hypogonadotropic hypogonadism (IGD, n = 6), constitutional delayed puberty (DP, n = 6), and Klinefelter's syndrome (KS, n = 5) before and during testosterone replacement therapy were studied. Six patients with KS and normal testosterone levels were also studied. Results were compared with those obtained in normal controls (n = 6). Serum samples were obtained at 15 min intervals from 1900-0700h in a controlled light-dark environment with simultaneous polysomnographic sleep recordings. Serum melatonin levels were the highest in IGD and DP and lowest in KS patients. A lower percentage of sleep stage 2 and higher percentage of stage 3/4 were observed in IGD and DP groups while KS patients had higher percentage of stage 2 and lower percentage of stage 3/4 as compared to controls. Slow wave sleep was the highest in IGD and the lowest in KS groups. Serum melatonin levels were lowest in KS groups. Serum melatonin levels were lowest in sleep stage 3/4, higher in stage 2 and highest in REM sleep when all groups were combined and averaged together. However, in the IGD group, melatonin levels were actually lowest in REM sleep. Also in the KS group, melatonin levels were lower in REM than during sleep stage 2. Serum melatonin levels were lowest in sleep stage 3/4 in all groups, higher in stage 2, and highest in REM sleep. During waking periods, melatonin levels were the highest in untreated IGD, DP and KS patients. Testosterone treatment given to these patients, although normalized, their melatonin levels did not statistically significantly change these correlations. These data demonstrate that relative melatonin concentrations are associated with sleep stages in hypogonadal and normal men. The results also indicate that the association between melatonin and the reproductive hormones are independent of the synchronizing effects of melatonin on sleep homeostasis.     

Nidovirus infections: experimental model systems of human neurologic diseases

The presence of terminally differentiated slow- and non-dividing cells in the central nervous system (CNS) provides a safe harbor for viral persistence and latency and constitutes a unique immunologic environment for viral infections. Studies of experimental model systems of viral infections of the CNS provide insight into mechanisms of viral persistence and immune-mediated pathology. Nidoviruses are comprised of 2 families of viruses, coronaviruses and arteriviruses, and are common pathogens of humans and a variety of animal species. Both families of viruses contain neurotropic strains that produce experimental neurologic diseases in rodents. These include acute meningitis and encephalitis; acute poliomyelitis; and chronic inflammatory, immune-mediated, demyelination. Coronavirus-induced demyelinating disease mimics many of the pathologic features of Multiple Sclerosis (MS).     

Increased risk of salivary gland tumors after low-dose irradiation

Objective: To assess the risk of neoplastic development among persons exposed to scalp irradiation. Study Design: Historical cohort study initially; prospective follow-up subsequently. Method: Two control groups—population and siblings—matched for age, sex, ethnic origin, and year of immigration. Follow-up from time of irradiation (1950s) until the end of 1991. Linkage with nationwide cancer registry. Results: A 4.5–fold incidence of cancer (P < .01) and a 2.6–fold increase of benign tumors were noted. The mean length of latency period until tumor development was 11 years for malignant tumors and 21.5 years for benign. A clear dose response effect for both cancer and benign tumors was demonstrated. Conclusions: The study confirms the role of radiation in salivary gland carcinogenesis. It indicates a need for better awareness, a comprehensive examination, and long-term follow-up of patients who have been subjected to head and neck radiation.     

Role of Immunosuppressive Therapy for the Treatment of Multiple Sclerosis

Immunosuppressives have been used in multiple sclerosis (MS) since 1966. Today, we have many treatments for the relapsing forms of the disease, including 8 US Food and Drug Administration-approved therapies, with more soon to be introduced. Given the current treatment landscape what place do immunosuppressants have in combating MS? Trial work and our experience suggest that immunosuppressives still have an important role in treating MS. Cyclophosphamide finds use in treating patients with severe, inflammatory relapsing remitting MS or those suffering from a fulminant attack. We tend to employ mycophenolate mofetil as an add-on to injectable therapy for patients experiencing breakthrough activity. Some progressive (primary progressive multiple sclerosis or secondary progressive multiple sclerosis) patients may stabilize after treatment with either cyclophosphamide or mycophenolate. We rarely employ mitoxantrone because of potential cardiac or carcinogenic effects. We prefer to use cyclophosphamide or mycophenolate mofetil in preference to methotrexate because evidence of efficacy is limited for this drug. We have less experience with azathioprine, but it may be an alternative for patients with limited options who are unable to tolerate conventional therapies.     

Thiotepa‐based versus total body irradiation‐based myeloablative conditioning prior to allogeneic stem cell transplantation for acute myeloid leukaemia in first complete remission: a retrospective analysis from the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation

Thiotepa is an alkylating compound with an antineoplastic and myeloablative activity and can mimic the effect of radiation. However, it is unknown whether this new regimen could safely replace the long‐established ones. This retrospective matched‐pair analysis evaluated the outcome of adults with acute myeloid leukaemia in first complete remission who received myeloablative conditioning either with a thiotepa‐based (n = 121) or a cyclophosphamide/total body irradiation‐based (TBI; n = 358) regimen for allogeneic hematopoietic stem cell transplantation from an HLA‐matched sibling or an unrelated donor. With a median follow‐up of 44 months, the outcome was similar in both groups. Acute graft‐versus‐host disease grade II‐IV was observed in 25% after thiotepa‐containing regimen versus 35% after TBI (P = 0.06). The 2‐yr cumulative incidence of chronic graft‐versus‐host disease was 40.5% for thiotepa and 41% for TBI (P = 0.98). At 2 yrs, the cumulative incidences of non‐relapse mortality and relapse incidence were 23.9% (thiotepa) vs. 22.4% (TBI; P = 0.66) and 17.2% (thiotepa) vs. 23.3% (TBI; P = 0.77), respectively. The probabilities of leukaemia‐free and overall survival at 2 yrs were not significantly different between the thiotepa and TBI groups, at 58.9% vs. 54.2% (P = 0.95) and 61.4% vs. 58% (P = 0.72), respectively. Myeloablative regimens using combinations including thiotepa can provide satisfactory outcomes, but the optimal conditioning remains unclear for the individual patient in this setting.     

Mortality in bullous pemphigoid: A systematic review and meta‐analysis of standardized mortality ratios

There are inconsistent data on mortality rates in patients with bullous pemphigoid (BP). Trends in mortality in BP throughout the years are yet to be established. The aim of the present study was to study the mortality in BP patients relative to the general population and to estimate trends in standardized mortality over the past 30 years. We performed a systematic review and meta‐analysis of observational studies in Medline, Embase and Scopus (1823–2017). Reference lists of included studies were also searched for eligible studies. Quality of evidence was assessed using the Newcastle–Ottawa Scale (NOS). A meta‐analysis was performed using random‐effects models to estimate pooled standardized mortality ratios (SMR) with 95% confidence intervals (CI). Meta‐regression models were used to investigate the secular trends in SMR. Ten studies were included covering the period 1960–2015 (1736 patients, 746 deaths). Pooled all‐cause SMR was 3.6 (95% CI, 2.6–5.0). There was no trend in all‐cause SMR across the last three decades (regression coefficient 0.02 [change in logSMR/year]; 95% CI, 0.04–0.08; P = 0.545). In conclusion, there is a 3.6‐fold increased mortality among patients with BP as compared with the age‐matched general population. The excess mortality in BP has not changed significantly over the past 30 years.     

Adolescents on the Front Line: Exposure to Shelling Via Television and the Parental Role

Objectives: Research suggests that exposure to traumatic content via television inadvertently increases posttraumatic stress symptoms (PTSS) as well as psychological distress, especially among adolescent viewers. The aim of the current study was to assess the effect of news consumption on PTSS and general distress among adolescents who live in a war area, as well as to examine the role of parents as intermediaries of news broadcasting. Method: A total of 65 adolescents who live in a war zone filled out the Child Post Traumatic Stress Reaction Index, the Brief Symptoms Inventory, and a scale measuring the level of real-life exposure, news broadcast consumption, and parents as intermediaries of news broadcasting. Results: A main effect for real-life exposure on both PTSS and general distress was revealed. Interestingly, a three-way interaction between real-life exposure, television exposure, and parents as intermediators was found for general distress. Only under low real-life exposure did parents as intermediaries buffer the effect of television exposure on general distress. Conclusions: Parental intermediation of news broadcasting of traumatic events, especially in situations of continuous, real-life exposure, is essential.