Nebulized voriconazole in infections with Scedosporium apiospermum--case report and review of the literature.

Scedosporium infections are rare complications in immunocompromised patients or patients with chronic pulmonary disease. While Scedosporium prolificans is resistant to most antimycotics, Scedosporium apiospermum is usually sensitive to voriconazole and posaconazole. Pharmacokinetics and efficacy of nebulized voriconazole have been described in a murine model previously. We report for the first time the safe and effective use of nebulized voriconazole for the treatment of severe pulmonary infection with Scedosporium apiospermum in an adolescent with cystic fibrosis.

Refractory focal epilepsy in a patient with methylmalonic aciduria: case report on positive and long-lasting effect of rufinamide.

We report on a 5-year-old boy with methylmalonic aciduria, an autosomal recessive inborn error of metabolism leading to accumulation of methylmalonic-CoA and thereby causing intoxication with leading symptoms of hyperammonaemia and metabolic acidosis. Hyperammonemia itself causes brain oedema. In our patient, this led to a vast metabolic stroke of the left hemisphere and subsequent pharmacoresistant epilepsy. Guided by his main seizures--drop attacks--the orphan drug rufinamide (RUF) was introduced as "off-label use" and led to freedom of drop attacks and tonic-clonic seizures over a period of 14 months as well as normalisation of the electroencephalogramm. Only once during an episode of fever and diarrhoea with reduced level of RUF did some provoked seizures with focal complex semiology for the time period of infection occur. In the 16 months follow-up, the patient also improved in his development, showing a more stable gait with the hemiparesis and understanding more complex sentences.

Controlling a vancomycin-resistant enterococci outbreak in a Brazilian teaching hospital.

The purpose of this article was to describe a 2.5-year interventional program designed to control the dissemination after a large hospital outbreak of vancomycin-resistant enterococci (VRE) in a tertiary-care university hospital. A VRE working group was designated to work specifically on controlling VRE intrahospital dissemination after the detection of the first VRE infection at in our hospital in June 2007. The intervention consisted in the interruption of new admissions during a period of 15 days and closure of the index case unit, microbiological surveillance of rectal swabs for VRE, cohorting patients and staff, immediate application of contact precautions, and continuous education. From July 2007 to December 2009, 8,692 rectal swabs were cultured for VRE and 321 (3.7%) were positive. An expressive reduction of the detection of new positive rectal swabs cultures was seen during the year 2009 (1.5%) when compared to 2008 (4.2%) and 2007 (7.2%) (p < 0.005). The annual ratio of VRE per 1,000 admissions reduced from 20.3 in 2007 to 10.07 and 3.82 in 2008 and 2009, respectively (p < 0.001). The continuous microbiologic surveillance for VRE and strict and prompt contact precautions for VRE patients were the fundamental aids in the control of VRE.

[Pancytopenia, fever, and splenomegaly in a 2-year-old boy]. / Panzytopenie, Fieber und Splenomegalie bei 2-jährigem Jungen.

HISTORY: Suspected of having a systemic malignancy a 22-month-old boy was admitted to hospital with fever, pancytopenia and hepatosplenomegaly. The boy was of ethnically German origin and no travel abroad was reported. DIAGNOSIS: Intensive search for a focus of infection, laboratory tests and bone marrow microscopy failed to be diagnostic. Serological findings and detection of Leishmania DNA in bone marrow by polymerase chain reaction (PCR) led to the diagnosis of visceral leishmaniasis. On explicit questioning the child's parents reported a stay in Greece 18 months before onset of symptoms. TREATMENT AND COURSE: On the fourth day of i.v. therapy with liposomal amphotericin B, 3mg/kg/d for 10 days, the fever subsided. Platelets and leukocytes regained normal levels. The child was discharged after 10 days of treatment and received two more doses on days 14 and 21. CONCLUSION: Negative results on microscopic bone marrow inspection do not rule out visceral leishmaniasis. Detection of anti-Leishmania antibodies may support the suspected diagnosis and provide the indication for PCR technique.

MEDIANOVO - a media database for medical education, research and health care.

MEDIANOVO provides a high quality, scientifically indexed multi-media database with comfortable authoring and download functions through a web-based frontend. Currently, MEDIANOVO is used by medical teachers as a repository for storing and sharing media for educational purposes. However a database was created which could also serve with training and further education, in computer based learning systems as well as medical publishers and for individual patient information. Through the web-frontend the content is available worldwide.

[Pulmonary nodular amyloidosis mimicking multiple pulmonary metastases of carcinoma of the corpus uteri]. / Pulmonal noduläre Amyloidose--Imitation einer multiplen pulmonalen Metastasierung nach Carcinom des Corpus uteri.

INTRODUCTION: Pulmonary nodular amyloidosis (PNA) is a phenomenon that is rarely diagnosed anywhere in the world. METHODS: We report a case of a 63-year-old woman who smoked in whom a chest X-ray examination 5 years after diagnosis and radical treatment of a highly differentiated carcinoma of the corpus uteri showed multiple lung metastasis. To elucidate these findings by bronchoscopy and thoracoscopy we took a specimen from the right pleura and from one of the suspicious nodules, which were up to 3 cm in diameter; we also obtained some of the bronchial secretion. RESULTS: The nodules were histopathologically diagnosed as PNA. CONCLUSION: Even if it is rare, PNA also belongs in the differential diagnosis of metastatic cancers. For us evidence of Pseudomonas fluorescens in the sputum is a reason for discussing a chronic, clinical unobtrusive local inflammation with hyperactivity of the B-cells as the hypothetical etiology of the amyloidomas.

Carotenoid supply in breast-fed and formula-fed neonates.

UNLABELLED: Carotenoids have various biological functions including their role as antioxidants. For humans fruits and vegetables are the only source of carotenoids. In the first months breast milk and/or formula preparations are the only nutrition for infants. To study the influence of nutrition on the plasma carotenoid profile in newborns, breast milk, different formula preparations, and the plasma of breast-fed (BF) and formula-fed (FF) newborns were analyzed by high-performance liquid chromatography. The method used allowed beta-carotene, alpha-carotene, lycopene, and beta-cryptoxanthine to be detected and all four were found in breast milk. In colostrum carotenoids were up to five times higher than in mature breast milk (P<0.05). In contrast, not all carotenoids could be found in formula preparations. Beta-carotene was detected in four out of eight, and beta-cryptoxanthine in three out of eight formula preparations. Lycopene and alpha-carotene were not detectable in any of the formula preparations. Four formula preparations did not contain any carotenoids. FF infants had different plasma carotenoid profiles compared to BF infants. beta-carotene was significantly lower in FF infants [14 (0-32) microg/l, median and interquartile ranges] than in infants after birth [24 (19-310) microg/l, P<0.05], and BF infants [32 (22-63) microg/l, P<0.05]. While newborns after birth had measurable plasma concentrations of lycopene (16 [14-18] microg/l) and of alpha-carotene [5 (0-8) microg/l), these carotenoids were no longer detectable in FF infants after day 14. CONCLUSION: FF and BF infants show significant biochemical differences in plasma carotenoid concentrations.

Transmission dynamics of tuberculosis in a high-incidence country: prospective analysis by PCR DNA fingerprinting.

We have prospectively analyzed the DNA fingerprints of Mycobacterium tuberculosis strains from a random sample of patients with newly diagnosed tuberculosis in Windhoek, Namibia. Strains from 263 smear-positive patients in whom tuberculosis was diagnosed during 1 year were evaluated, and the results were correlated with selected epidemiological and clinical data. A total of 163 different IS6110 fingerprint patterns were observed among the 263 isolates. Isolates from a high percentage of patients (47%) were found in 29 separate clusters, with a cluster defined as isolates with 100% matching patterns. The largest cluster included isolates from 39 patients. One predominant strain of M. tuberculosis caused 15% of cases of smear-positive pulmonary tuberculosis in Windhoek. That strain was also prevalent in the north of the country, suggesting that in contrast to other African countries with isolates with high levels of diversity in their DNA fingerprint patterns, only a restricted number of different strains significantly contribute to the tuberculosis problem in Namibia.

Effects of dietary supplementation of saturated fatty acids and of n-6 or n-3 polyunsaturated fatty acids on plasma and red blood cell membrane phospholipids and deformability in weanling guinea pigs.

The fatty acid composition of plasma cholesteryl esters, plasma phospholipids, red blood cell (RBC) membrane phosphatidylcholine (corresponding to the outer membrane leaflet), and phosphatidylethanolamine (corresponding to the inner membrane leaflet) was investigated in weanling guinea pigs fed with diets of cacao (saturated fatty acids), sunflower oil [n-6 polyunsaturated fatty acids (PUFA)] or fish oil (n-3 PUFA) for 20 wk. RBC deformation was measured by means of a cell-transit analyzer (filtration) and a cone-plate rheoscope. The contents of saturated fatty acids in plasma phospholipids and RBC membrane leaflets were similar in all three groups. Diets with sunflower oil resulted in a high content of linoleic acid in plasma cholesteryl esters and in the outer leaflet of RBC membranes. Fatty acids of fish oil were mainly incorporated in plasma phospholipids and in the inner leaflet of RBC membranes. The arachidonic acid content was high in all groups in the plasma phospholipids and in the inner leaflet. The n-6 and n-3 PUFA were mainly incorporated in the inner leaflet. In all groups the polyunsaturated/saturated fatty acid ratio and the total PUFA content were similar in the inner RBC membrane. The RBC filtration times and the RBC deformation indices were not affected by the dietary treatment.

Childhood tuberculosis in Germany between 1985 and 1994: comparison of three selected patient groups.

SETTING: Clinical and epidemiologic features of childhood tuberculosis in Germany are unknown for recent years. The characteristics of patient groups may show typical differences, depending on the source of data. OBJECTIVE: To identify typical features of childhood tuberculosis in Germany, and to relate the characteristics of patient groups to the purpose of the reporting centres. DESIGN: Comparative, retrospective, descriptive analysis of clinical and notification records by standardized data sheet. Evaluation of cases of active tuberculosis in children recorded between 1985 and 1994 at three study centres. RESULTS: One clinical study centre was a referral centre for sick children with an unclear diagnosis, the second specialized in tuberculosis, and the third was a public health office. Almost two thirds (64%) of the 285 evaluated patients were four years of age and under. Between 73% and 96% of children suffered from pulmonary disease and 17% to 58% were culture positive (range between study centres). Source cases had been found for 23% to 52% of children, and the primary reason for clinical evaluation was a positive tuberculin test for between 12% and 57%. Foreign-born children showed characteristic differences. CONCLUSION: The characteristics of reported childhood tuberculosis differ depending on the reporting centre. A significant number of notified cases were probably wrongly diagnosed.

Long-chain polyunsaturated fatty acids in plasma and erythrocyte membrane lipids of children with phenylketonuria after controlled linoleic acid intake.

It has been reported that children with classical phenylketonuria (PKU) have reduced levels of arachidonic acid (AA, 20:4 n-6) and docosahexaenoic acid (DHA, 22:6 n-3) in plasma and membrane phospholipids compared to controls and may therefore require supplementation. However, it is not established that these changes are specific for PKU. They may as well be attributed to the specific composition of a largely vegetarian diet used for dietary PKU treatment. We therefore investigated the fatty acid composition of plasma phospholipids (PL), plasma cholesterol esters (CE), red blood cell phosphatidylcholine (PC), and red blood cell phosphatidylethanolamine (PE) in two groups of PKU patients including 8 children between 1 and 6 years (group A), 9 adolescents between 11 and 18 years (group B), and 20 age-matched healthy controls. Group A had good dietary control (median plasma phenylalanine 272 mumol/L during the last 6 months before phospholipid analysis) while median phenylalanine in group B was 714 mumol/L (p < 0.001). When compared to age-matched controls, group A showed significantly lower DHA levels in PE (4.21 vs 5.85 weight% (wt%), p < 0.01), in PC (1.02 vs 1.25 wt%, p < 0.05) and in CE (0.25 vs 0.54 wt%, p < 0.05). There was no significant difference of DHA between group B and controls. AA levels were similar in phospholipids of all groups. We conclude that reduced levels of long-chain polyunsaturated fatty acids in PKU patients occur only in those patients with strict dietary therapy with respect to n-3 fatty acids, most probably caused by reduced intake of n-3 fatty acids.

High incidence of epilepsy related to onchocerciasis in West Uganda.

The incidence of epilepsy was assessed in an onchocerciasis endemic area in West Uganda over a period of 4 years. A high overall crude incidence rate of 215 per 100000 person-years was found (age-adjusted: 156 per 100000 person-years) and the incidence in zones of high onchocerciasis endemicity was significantly higher than in low endemic zones (age adjusted rates: 232 per 100000 person-years versus 77 per 100000 person-years; Yates corrected chi2: P < 0.01). The data constitute a baseline for an ongoing intervention study on the effects of onchocerciasis control on epilepsy incidence in the study area. If a causal relationship between onchocerciasis and epilepsy can be confirmed, this would have significant implications for the concept of morbidity due to onchocerciasis and for the prevention of epilepsy in the endemic areas.

The clinical manifestation of the kwashiorkor syndrome is related to increased lipid peroxidation.

Along with the onset of severe kwashiorkor symptoms, a 20-month-old child showed biochemical signs of markedly increased lipid peroxidation, with a decrease of plasma antioxidants and decreased proportions of polyunsaturated fatty acids in plasma and red cell phospholipids. Additionally, plasma concentrations of the lipid peroxidation products malondialdehyde and hexanal, as well as the urinary excretion of leukotriene E4, were found to be increased. All biochemical alterations normalized along with subsequent clinical improvement. These findings suggest that the extent of lipid peroxidation is strongly related to the severity of the kwashiorkor syndrome.

Childhood tuberculosis: an index measuring the ability to detect cases early.

SETTING: Tuberculosis control programmes are conventionally monitored using data from sputum smear positive adult patients. Good overall results may mask significant and avoidable shortcomings with tuberculosis control in children. OBJECTIVE: To develop a specific surveillance tool for child patients, using the ability to detect cases early as a parameter for the impact of control measures. DESIGN: A simple index of early detection was compiled with values ranging from 0 to 100. Three groups of tuberculous children diagnosed in Germany between 1985 and 1994 (n = 303), and five other groups from the literature, were used to make a preliminary assessment of the validity of the index. RESULTS: The index values of 10, 13 and 24 for the German groups correlate well with other analysed patient data and the different functions of the institutions where the patients were diagnosed. Comparable characteristics could be found when applying the index to published data of other cases, with values of between 12 and 74. CONCLUSION: The proposed index seems suitable for monitoring early detection of child cases. Unexpected trends can be disclosed or effects of changed programme activities assessed. Routine use of the index would help the health services focus their attention on problem areas and specific patient groups with extremely low or falling index values. Conclusions can be drawn regarding the overall impact of the control programme.

Influence of n-6 and n-3 polyunsaturated fatty acids on the resistance to experimental tuberculosis.

It has previously been shown that the n-3 polyunsaturated fatty acids (PUFAs) eicosapentaenoic acid (20:5(n-3)) and docosahexaenoic acid (22:6(n-3)) possess antiinflammatory properties and can interfere with immune functions. To evaluate whether this would affect resistance to infection, we studied the influence of different types of fatty acids (FAs) on experimental tuberculosis in an animal model. Three groups of 26 weanling guinea pigs were fed isocaloric diets with 26 cal% fat that differed in FA composition with respect to saturated FAs, linoleic acid (18:2(n-6)), eicosapentaenoic acid (20:5(n-3)), and docosanexaenoic acid (22:6(n-3)) as follows: (1) reference (REF) group: 14.8 cal% saturated FAs and 2.8 cal% linoleic acid; (2) n-6 group: 4.6 cal% saturated FAs and 15.4 cal% linoleic acid; (3) n-3 group: 6.3 cal% saturated FAs, 10 cal% linoleic acid, 1.4 cal% eicosapentaenoic acid, and 0.9 cal% docosahexaenoic acid. After 13 weeks, 18 animals from each group were intramuscularly injected with 180 colony-forming units (CFU) Mycobacterium tuberculosis strain H37Rv. Eight noninfected animals per group served as controls. Seven weeks later, the mean number of mycobacteria recovered from the spleens of the n-3 group (log 4.34 CFU, standard error of the mean [SEM], 0.12) was significantly higher than from the REF group (log 3.90 CFU; SEM, 0.15) and the n-8 group (log 3.93 CFU; SEM, 0.13; P < .05). In addition, the Root Index of Virulence (RIV) showed the most pronounced progression of the disease in the n-3 group. The mean size of the tuberculin reaction was larger in the n-3 group than in the other groups (P < .05). There was no significant difference between the n-6 group and the REF group. We conclude that supplementing the diet with n-3 FAs eicosapentaenoic acid and docosahexaenoic acid can affect resistance to M tuberculosis, whereas supplementing with n-6 FAs does not.

Plasma carotenoids in German children and adolescents.

UNLABELLED: Carotenoids are important antioxidants and precursors of vitamin A, but only few studies have been carried out on plasma carotenoid levels in paediatric age groups. Using high-performance liquid chromatography we analysed concentrations of four important carotenoids (alpha-carotene, beta-carotene, cryptoxanthin, lycopene) in 129 healthy German children and adolescents (81 boys, 48 girls; age 1-18 years). For all carotenoids analysed, no significant differences between girls and boys were found. alpha-Carotene values ranged from 0 mumol/l (below detection limits) to 0.73 mumol/l (0-395 micrograms/l), beta-carotene from 0.09 mumol/l to 2.68 mumol/l (48-1443 micrograms/l), lycopene from 0 mumol/l to 1.51 mumol/l (0-815 micrograms/l), and cryptoxanthin from 0 mumol/l to 0.30 mumol/l (0-164 micrograms/l), respectively. Data analyses according to age groups showed a tendency towards higher levels of alpha- and beta-carotene, and lower levels of lycopene in young children. These differences were significant when children younger than 4 years were compared with those above 8 and 12 years, respectively. The data presented may serve as reference values for studies on children with nutritional disorders and diseases associated with a risk of vitamin deficiencies. CONCLUSION: Carotenoids are important antioxidants and singlet oxygen scavengers. Plasma levels of alpha-carotene, beta-carotene, lycopene and cryptoxanthin were determined in 129 healthy German children and adolescents. Highest values were found for beta-carotene and lycopene.

Influence of dialysis on plasma lipid peroxidation products and antioxidant levels.

In patients with end-stage renal failure (ESRF), the incidence of atherosclerosis and cancer is increased. The importance of lipid peroxidation (LPO) products in the pathogenesis of these complications has recently been emphasized. The LPO products malondialdehyde (MDA) and hexanal, lipophilic antioxidants and erythrocyte glutathione (GSH) were estimated in 10 pediatric hemodialysis (HD) patients before and after HD and in 11 peritoneal dialysis (CPD) patients. Before HD, MDA was elevated [median (interquartile range): 384.5 (110 to 501) nM; normal < 150 nM], whereas plasma hexanal levels were normal in all patients [130.5 (88 to 222) nM; < 320 nM]. HD decreased MDA concentrations on average by 88% but did not change hexanal levels. CPD patients exhibited high plasma MDA concentrations [371 (287 to 468) nM], whereas hexanal was in the low normal range [56 (51 to 81) nM]. Antioxidants were normal in both groups and unchanged during HD. GSH decreased slightly during HD. We hypothesize that MDA may accumulate in ESRF due to reduced plasma clearance. Our results argue against a general increase of LPO in uremia.

The Nakalanga syndrome in Kabarole District, Western Uganda.

An acquired condition resulting in arrested growth was reported in the 1950s and 1960s from along the Nile near Jinja in eastern Uganda. This became known as Nakalanga dwarfism, and an association with onchocerciasis was postulated. After control of onchocerciasis through larvaciding in this area some 30 years ago, no new cases have been noted. We now report this condition from western Uganda where its appearance seems to be a relatively recent event. Thirty-one persons with short stature, 15 years of age and older, were identified through household surveys in an area of Kabarole district with a high prevalence of onchocerciasis. Cases identified were matched with controls selected for age and sex from the nearest household. Cases of Nakalanga syndrome weighed significantly less and were shorter than controls. The Z scores for weight-for-age, weight-for-height, height-for-age, and body mass index were significantly less among cases. Other clinical features observed among cases included absence of secondary sexual characteristics, skeletal deformities, dental caries, and mental retardation. All cases and 22 (79%) controls had microfilariae of Onchocerca volvulus in skin snips. All community members interviewed were aware of the Nakalanga syndrome, and 93% believed it to be acquired sometime after birth. The possible association with onchocerciasis is discussed.

The prevalence of epilepsy follows the distribution of onchocerciasis in a west Ugandan focus.

Epidemiological surveys indicate that the prevalence of epilepsy is higher in developing countries than in industrialized countries. Except for neurocystocercosis due to Taenia solium, little is known about possible underlying causes. This article reports the relationship between epilepsy and onchocerciasis in an Onchocerca volvulus endemic area in West Uganda. Individuals complaining of seizures were identified by means of a population census in 12 villages. Active epilepsy was confirmed in 61 of 4743 inhabitants (crude prevalence rate = 1.3%; age-standardized rate = 1.1%). Distribution of epilepsy in the study area was clustered, ranging from a prevalence of 0.2% to 3.4% in different villages. Age-specific prevalence was highest between 10 and 19 years, with a rate of 3.6% for the study are as a whole, and up to 10.0% in villages of high epilepsy prevalence. The prevalence of onchocerciasis in the 10-19-year-old age group was assessed by skin-snip biopsy and ranged from 15% to 85% in different villages. Epilepsy was significantly more frequent in the three villages with the highest levels of O. volvulus endemicity than in other villages (P < 0.0001). Serological testing for T. solium infection was positive in one and borderline in three of 53 epilepsy patients tested. The significant correlation between epilepsy and onchocerciasis did not change when these four patients were excluded from the analysis. These findings suggest a strong association between epilepsy and onchocerciasis in this area. This could have significant implications for the concept of morbidity due to O. volvulus.