Corrective osteotomy of distal radial deformities: a new method of guided locking fixed screw positioning.

Corrective osteotomy for distal radial malunion is a valuable but at times technically challenging operation. We have developed a new device to aid in the performance of the operation. We compared clinical use of the new technique with the standard technique. In 11 patients treated with the new technique the volar locking plate needed repositioning only once. With the standard technique in 17 patients the plate was repositioned in nine cases and needed bending in six cases. The new method corrected radial inclination (SD of 3° vs. 9°) and ulnar variance (SD of 0.9 mm vs. 1.4 mm) more predictably than the standard technique but there was no advantage in correction of volar tilt (SD of 6° vs. 4°). In our experience the new device makes corrective osteotomy of the distal radius easier and more reliable.

Toxicological properties of metaflumizone.

Metaflumizone is a new insecticide developed for crop protection and urban pest control by BASF. Its mammalian toxicological profile was assessed by conducting multiple toxicity studies in the rat, mouse, and dog, covering all relevant endpoints. Metaflumizone is characterized by very low acute toxicity, is not irritating to the eye or the skin and does not possess a potential to induce skin sensitization. The substance also shows relatively low toxicity following subchronic oral or dermal exposure to mammals. In addition, metaflumizone demonstrates low toxicological potential following chronic oral exposure to rats, mice, and dogs. Overall, the lowest no observed adverse effect level (NOAEL) is 12mg/(kgday) from the 1-year chronic dog study. In a battery of in vitro and in vivo mutagenicity assays, the weight-of-the-evidence indicates a lack of potential genotoxicity for metaflumizone. Furthermore, the compound demonstrated a lack of potential oncogenicity in long-term toxicity studies in rats and mice. Results from the rat multi-generation reproductive toxicity study as well as the rat and rabbit developmental toxicity studies indicate that metaflumizone is not selectively toxic to the offspring or fetus, as compared to the parents. Also, metaflumizone is not teratogenic in the rat or rabbit. Lastly, no neurotoxicity could be detected in acute and subchronic neurotoxicity studies in rats.

[A rare splenic involvement by Echinococcus multilocularis - case report]. / Ein aussergewöhnlicher Milzbefall durch Echinococcus multilocularis - eine Kasuistik.

In the present case an 81-year-old patient was operated upon for a suspected atraumatic spleen rupture. During the operation a spleen abscess was found. Histological examination of the removed spleen revealed an Echinococcus multilocularis infection. There was no sign of further organ involvement: surprisingly the liver was not affected. Case history, clinical outcome and the prescribed treatment are described. A short overview of the Echinococchus multilocularis syndrome is presented.

Challenges and perspectives of computer-assisted instruction in medical education: lessons learned from seven years of experience with the CAMPUS system.

OBJECTIVES: In this paper we discuss solutions to the problem that medical teachers and students do not use modern computer-assisted instruction systems in medical education as much as expected by their developers. METHODS: As an example for a modern problem-based CAI system we introduce the CAMPUS shell system for case-based training in medicine. RESULTS: CAMPUS has received several awards and positive evaluation results. Nevertheless, the usage of such systems in courses and for self-study could be increased. CONCLUSIONS: Curricular integration of CAI as well as further improvements on existing CAI systems to increase the usage in medical education is essential.

Integrin-linked kinase interacts with caspase-9 and -8 in an adhesion-dependent manner for promoting radiation-induced apoptosis in human leukemia cells.

Integrin-mediated adhesion of leukemia cells to extracellular matrix proteins reduces apoptosis following radiation-induced genotoxic injury. To evaluate the role of integrin-linked kinase (ILK) in this process, HL60 human acute promyelocytic leukemia cells were stably transfected with ILK wild-type or kinase-hyperactive overexpression vectors. Suspension or fibronectin (FN) adhesion cultures were irradiated with X-rays and processed for measurement of apoptosis, mitochondrial transmembrane potential and caspase activation. Adhesion to FN pronouncedly reduced radiation-induced apoptosis of HL60 cells and vector controls. Intriguingly, overexpressed ILK enhanced apoptosis after irradiation by combined activation of caspase-3 through caspase-8 and -9 in irradiated FN cultures. Irradiation of ILK suspension cultures lacked caspase-8 activation, but showed serial cleavage of caspase-9, -3 and poly (ADP-ribose) polymerase. These findings further characterize the cell death-promoting function of ILK in DNA-damaged cells. Moreover, ILK might represent a potential therapeutic target for innovative chemo- and radiooncological approaches in hematological malignancies.

In situ hybridization using riboprobes on free-floating brain sections.

A method is described for in situ hybridization of riboprobes to free-floating brain sections. Brain sections are hybridized and processed free-floating in buffer, i.e., without attachment to a support such as a slide. To withstand the extra wear compared with sections processed on-slide, the brain tissue must be well fixed (4% paraformaldehyde) and sections cut at thickness of typically 40 microm. Sections were exposed to a prehybridization treatment before a riboprobe is added to form the hybridization solution. Riboprobes were prepared from cDNA via an in vitro transcription reaction and are labeled with digoxigenin. The sections are subsequently processed to remove nonspecific binding and the digoxigenin label detected via an antibody conjugated to alkaline phosphatase. This method may be readily combined with neuronal tracing and is ideal for further processing by immunohistochemistry to detect specific proteins.

Transdiaphragmatic pleural lavage in penetrating thoracoabdominal trauma.

BACKGROUND: The purpose of this study was to determine the incidence of thoracic sepsis following a systematic thoracic cavity washout through the injured diaphragm in patients with penetrating thoracoabdominal trauma. METHODS: Prospectively collected data on all patients presenting with penetrating thoracoabdominal trauma between July 1999 and July 2002 were analysed. Patients with peritoneal biliary-gastroenteric (BGE) contamination and a diaphragmatic laceration were managed by laparotomy and transdiaphragmatic thoracic lavage. RESULTS: A total of 217 patients had penetrating thoracoabdominal injuries, of whom 110 had BGE contamination of the peritoneal cavity with spillage into the pleural cavity. The mean Injury Severity Score was 38.1. Gunshot and stab wounds occurred in 79 (71.8 per cent) and 31 (28.2 per cent) respectively. Contamination was from the stomach (55.4 per cent), large bowel (37.3 per cent), small bowel (29.1 per cent), gallbladder and bile ducts (9.1 per cent) and pancreas (6.4 per cent). Thoracic complications occurred in six patients (5.5 per cent): empyema in two, Escherichia coli-related pneumonia in three and pleuritis in one. There were no deaths. CONCLUSION: A thoracic washout through the injured diaphragm in patients with penetrating thoracoabdominal trauma and BGE contamination was associated with a low rate of intrathoracic septic complications.

Obstacle avoidance during human walking: H-reflex modulation during motor learning.

The goal of this study was to investigate changes of H-reflex amplitudes during a motor learning task. Subjects with reduced vision were instructed to step over an obstacle on a treadmill as low as possible, while the soleus H-reflex was elicited. Acoustic warning and feedback signals about performance were provided. Performance improvement was associated with a decrease of muscle activity, needed to step over the obstacle (rectus femoris, biceps femoris, tibialis anterior and gastrocnemius medialis muscles), and of foot clearance, while joint angle trajectories from knee and ankle became more stable. The experiment consisted of five runs, three with normal treadmill walking and two with randomly stepping over the obstacle (100 times). H-reflexes were elicited at early and late stance phase before stepping over the obstacle. H/M ratio, latency and duration were determined. The values of these measures were calculated for the onset and end of a run and their course over time was evaluated using a correlation coefficient. The largest adaptations with a significant increase of reflex amplitude occurred during the first obstacle run. This increase lasted only briefly and the reflex amplitudes decreased to their previous values. During the later obstacle run, no H-reflex modulation occurred. It is concluded that a motor learning task causes adaptational effects not only on performance, but also on H-reflex responses. The results indicate that most of the modulation of H-reflexes is probably due to supraspinal influences on reflex transmission. The observations made are probably less specific for this motor task (stepping over the obstacle), but rather associated with the increased attention required by the motor learning task during the first obstacle run.

Complexity of sensory environment drives the expression of candidate-plasticity gene, nerve growth factor induced-A.

Exposure of animals to an enriched environment triggers widespread modifications in brain circuitry and function. While this paradigm leads to marked plasticity in animals chronically or acutely exposed to the enriched environment, the molecular mechanisms that enable or regulate such modifications require further characterization. To this end, we have investigated the expression profiles of both mRNA and protein products of a candidate-plasticity gene, nerve growth factor induced-A (NGFI-A), in the brains of rats exposed to increased environmental complexity. We found that NGFI-A mRNA is markedly up-regulated throughout the brains of animals exposed to the enriched environment, but not in the brains of either handled-only or undisturbed control groups. The most pronounced effects were observed in the somatosensory and visual cortices, in layers III and V, while more modest increases were observed in all other cortical layers, with the exception of layer I. A striking NGFI-A mRNA up-regulation was also observed in the striatum and hippocampal formation, notably in the CA1 subfield, of animals exposed to the enriched environment paradigm. Immunocytochemistry was also used to investigate the distribution of NGFI-A protein in response to the environmental enrichment protocol. A marked increase in the number of NGFI-A positive nuclei was identified in the enriched environment condition, as compared to undisturbed and handled-only controls, throughout the rat brain. While the greatest number of NGFI-A immunolabeled neurons was found in cortical layers III and V, up-regulation of NGFI-A protein was also detectable in layers II, IV and VI, in both the somatosensory and visual cortices. NGFI-A immunopositive neurons were also more numerous in the CA1 subfield of the hippocampal formation of animals exposed to the enriched environment, but remained at basal levels in both control groups. Our results implicate NGFI-A as one of the possible early genetic signals that ultimately lead to plastic changes in the CNS.

LDL-receptor-related proteins in Wnt signal transduction.

The Wnt family of secreted signalling molecules are essential in embryo development and tumour formation. The Frizzled (Fz) family of serpentine receptors function as Wnt receptors, but how Fz proteins transduce signalling is not understood. In Drosophila, arrow phenocopies the wingless (DWnt-1) phenotype, and encodes a transmembrane protein that is homologous to two members of the mammalian low-density lipoprotein receptor (LDLR)-related protein (LRP) family, LRP5 and LRP6 (refs 12-15). Here we report that LRP6 functions as a co-receptor for Wnt signal transduction. In Xenopus embryos, LRP6 activated Wnt-Fz signalling, and induced Wnt responsive genes, dorsal axis duplication and neural crest formation. An LRP6 mutant lacking the carboxyl intracellular domain blocked signalling by Wnt or Wnt-Fz, but not by Dishevelled or beta-catenin, and inhibited neural crest development. The extracellular domain of LRP6 bound Wnt-1 and associated with Fz in a Wnt-dependent manner. Our results indicate that LRP6 may be a component of the Wnt receptor complex.

Distribution of NADPH-diaphorase cells in visual and somatosensory cortex in four mammalian species.

The distribution of the well-labeled nicotinamide adenine dinucleotide phosphate diaphorase (NADPHd) Type I neurons was evaluated in the isocortex of four mammalian species: the Didelphis opossum, the Monodelphis opossum, the rat and the marmoset. In Didelphis opossum, laminar distribution was examined in tangential and non-tangential sections. The density increases from superficial to deep layers of the gray matter. In rats' tangential sections, infragranular and supragranular layers have higher density than layer IV. Cell density measurements in the visual and the somatosensory cortices were compared in tangential sections from flattened hemispheres of the four species. Somatosensory areas were identified histochemically in rat (barrel fields) and marmoset (S1 and S2/PV). In the opossums, areas S1 and S2/PV were identified by multiunit recording. Except in the rat, primary visual cortex (V1) was labeled histochemically by NADPHd and/or cytochrome oxidase. In the four species, cell density in somatosensory cortex was significantly higher than in visual cortex. Taken together these results demonstrate that NADPHd Type I neurons are not homogeneously distributed in the isocortex of these mammals. In conclusion, the tangential distribution of Type I neurons in the sensory areas examined, but not its laminar distribution, was similar in the four species. Given that rats, marmosets and opossums are distantly related species, and that the latter are considered to have more 'generalized' brains, it is conceivable that this pattern of tangential distribution of Type I neurons is a general feature of mammalian isocortex.

Sensitive ELISA dipstick test for the detection of chloroquine in urine under field conditions.

OBJECTIVE: To evaluate a new enzyme-linked immunosorbent assay (ELISA) dipstick test for detecting chloroquine (CQ) in urine in a malaria-endemic region of north-western Namibia. METHOD: Urine samples from 92 patients attending the outpatient department of Kamhaku Hospital with suspected malaria infection were tested for CQ with both the Dill-Glazko test and the ELISA dipstick test. Results were compared to the history of CQ intake as documented in the patients' health passes. RESULTS: The dipstick test proved an easy-to-handle and very sensitive tool for the detection of CQ with a lower limit of detection at 120 nmol/l. It showed high agreement with the history of CQ intake within the last 6 months. The specificity in a negative control group was 100%. The Dill-Glazko test was far less sensitive and specific with a lower detection limit of 150 micromol/l. CONCLUSION: The dipstick test can be used in pharmacological studies to evaluate the use of CQ, and as an inclusion criterion for in vivo and in vitro sensitivity tests, whereas the Dill-Glazko test is appropriate to test compliance during and a few days after CQ intake.

Anti-malarial drug resistance, malnutrition and socio-economic status.

To investigate the relationship between nutritional status and resistance to chloroquine treatment, we designed a nested case-control study prospective with respective to the outcome of Plasmodium falciparum-infected school children aged 5-14 years from Honiara, Solomon Islands. 38 chloroquine-resistant cases were compared with treatment-susceptible controls with respect to current nutritional status, behavioural characteristics, medical and demographic data. The overall prevalence of moderate malnutrition was 28%. The incidence rate of chloroquine resistance was 23%. Malnourished children were generally at higher risk for treatment failure than well-nourished ones (OR: 3.6; 95% CI: 1.6-8.4; P = 0.001). This effect was modified by socio-economic status. Stratified analysis by logistic regression resulted in an eightfold risk of resistance for malnourished children in the higher socio-economic category (OR: 8.1; 95% CI: 2.4-27.9; P = -.0001). In children from the lower socio-economic group, the effect of malnutrition was not significant (OR: 1.5; 95% CI: 0.4-5.6). Socio-economic differences may affect the immune status. The treatment response in children of lower socio-economic status, which are more exposed to malaria, may therefore be less affected by malnutrition.

Pharmacology of kinins in the arterial and venous mesenteric bed of normal and B2 knockout transgenic mice.

We have tested the vasoactive effects of kinins in addition to various other endothelium-dependent or independent agonists in the arterial and venous perfused mesenteric circuits of the mouse. Bradykinin (0.1 pmol-100 nmol), but not des-Arg9-bradykinin (10 nmol) induced a dose-dependent vasodilation of the precontracted arterial and venous mesenteric vasculature of the mouse. Furthermore, acetylcholine (2.5 nmol) also induced a marked arterial vasodilation but was without effect on the venous side. Other endothelium-dependent vasodilators, such as platelet-activating factor (PAF) (1 nmol), tachykinin NK1 selective agonist ([Sar9,Met(O2)(l1) ]substance P) (0.5 nmol) and adenosine diphosphate (5 nmol), were without effect on either side of the mesenteric bed of the mouse. The bradykinin B2 receptor selective antagonist (HOE 140) abolished the arterial and venous vasodilation induced by bradykinin without affecting that of acetylcholine or sodium nitroprusside. In addition, the bradykinin B1 receptor antagonist des-Arg9-[Leu8]bradykinin was without effect on the responses induced by bradykinin. A nitric oxide synthase inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME) markedly reduced, whereas removal of the endothelium with 3-[3-cholamidopropyl)dimethylammonio]-1-propane sulfonate (CHAPS) abolished dilatation to bradykinin and acetylcholine (arterial side only) without affecting that induced by sodium nitroprusside in the mouse arterial and venous mesenteric circuits. In the same two circuits of transgenic B2 knockout mice, the vasodilatory responses to bradykinin were absent, whereas the arterial circuit still responded to acetylcholine by a L-NAME-sensitive vasodilation. Our results suggest the exclusive contribution of B2 receptors located on the endothelium in the vasodilatory effects of bradykinin in the arterial and venous mesenteric circuits of the mouse.

Geographic differences in the sensitivity of a polymerase chain reaction for the detection of Plasmodium falciparum infection.

The amplification of target DNA by highly specific probes using the polymerase chain reaction (PCR) provides a highly sensitive and specific method for the detection of malaria infection. The use the of PCR in settings with varying endemicity within one survey area has not been investigated intensively. Therefore, a cross-sectional study was conducted in the districts of Kabarole and Bundibugyo in western Uganda using material from three villages with different epidemiologic situations regarding malaria and DNA primers for a PCR that had shown satisfactory sensitivity and specificity in previous trials. The sensitivity of the PCR varied significantly (P < 0.001) in the three survey villages (between 63.2% and 83.9% for the primer pair K1-14-1 and between 37.9% and 69.9% for the primer pair MSP-1) and was highly linked to geographic differences and social exchanges of the inhabitants with other areas of the district. According to the results of this investigation, it is advisable not to use a single primer pair in epidemiologic field studies for the detection of falciparum malaria. The use of combined primer pairs and the frequent confirmation of the results by microscopy are recommended.

Risk factors of chloroquine resistance in Plasmodium falciparum malaria.

OBJECTIVE: To identify patient-related risk factors of chloroquine resistance. DESIGN: A case control study. SUBJECTS: Plasmodium falciparum infected school children were followed prospectively for 7 days for the detection of chloroquine resistance. Cases were 38 individuals with chloroquine resistant infections. Controls were 125 individuals with chloroquine sensitive infections. Cases were compared with controls with respect to previous or current study factor levels. Subjects were recruited from randomly selected schools which were stratified for area. Study location was in North Guadalcanal, Solomon Islands. OUTCOME MEASURE: Treatment failure of chloroquine in standard dosage (25 mg/kg). Follow-up period was 7 days. RESULTS: Logistic regression resulted in 5 independent significant predictors of chloroquine resistance, obtained simultaneously with the diagnosis of malarial infection: (i) Young age (odds ratio (OR) for age < 7 years: 7.1; 95% confidence interval (CI): 2.5-25.0; OR per year increase after the age of 5 years: 0.8; 95% CI: 0.6-0.9). (ii) High parasite density (OR for > 1000/microliters: 5.0; 95% CI: 2.0-10.6; OR per 500 parasites/microliters increase: 1.3; 95% CI: 1.1-1.7). (iii) Normal spleen size (OR: 4.0, 95% CI; 1.5-10.8). (iv) Malnutrition (OR: 4.9; 95% CI: 1.8-13.2). (v) Presence of gametocytes in the thick smear (OR: 3.0; 95% CI: 1.1-8.0). CONCLUSION: The identified risk factors are easily measurable without special equipment. They may be useful for health workers in the Solomon Islands, even in remote areas, to identify Plasmodium falciparum infected individuals at high risk for chloroquine resistance before a treatment decision is made.

Salt-sensitive hypertension in bradykinin B2 receptor knockout mice.

The kallikrein-kinin system regulates water and sodium excretion and thus plays a role in blood pressure (BP) homeostasis. We tested the hypothesis that mice lacking the gene encoding for the bradykinin B2 receptor (B2-KO) have a greater hypertensive response to chronic high Na+ intake (salt sensitivity) compared to controls. We also obtained dose-response curves for different vasoactive substances in both groups. The hypertensive effect of high Na+ intake was almost doubled in B2-KO mice compared to controls. A high-Na+ diet increased heart and kidney weight in B2-KO, but not in controls, suggesting an increased afterload in B2-KO mice. The BP response to bradykinin was completely abolished in B2-KO, but that to acetylcholine was conserved. The hypertensive response to angiotensin II was not exaggerated in B2-KO mice. This study describes a new salt-sensitive animal model and suggests that in mice kinins play a role in preventing salt-sensitive hypertension.

[Total skin electron beam irradiation in cutaneous T-cell lymphoma]. / Ganzhautelektronenbestrahlung des kutanen T-Zell Lymphoms.

PURPOSE: Patients with cutaneous T-cell lymphoma are treated in Germany mostly by dermatological local therapy like corticosteroids or PUVA-irradiation. Total skin electron beam irradiation is used rarely, even though it has a potentially curative character. We present an analysis of patients, who received a total skin electron beam irradiation after having progressive disease following other treatment modalities. PATIENTS AND METHODS: Twenty-one patients (mean age 58.9 years) in different stages were treated (stage IB and IIA n = 4, stage IIB n = 8, stage III n = 3, stage IV n = 6). All patients had progressive disease under other forms of local therapy. The irradiation was performed from 6 directions per hemibody using 2 axial fields which have each an 18 degree angle to the horizontal level. Six and 7 MeV fast electrons were used. Total dose was between 8 and 36 Gy in single dosis of 1 x 4 up to 5 x 2 Gy per week. In underdosed areas and areas of tumors of the skin boost irradiation with small fields was given. RESULTS: All patients had a good tumor regression (complete remission: n = 10, partial remission: n = 11). With the follow-up between 4 and 93 months total- and recurrence-free survival was 18 and 7 months (median). Patients in early stages with slow but complete remission of the symptoms had the best prognosis. Because of the small case number there was no significant difference between the groups. There were no severe side effects of the radiotherapy noted. CONCLUSION: Our analysis shows on a small patient number, that total skin electron beam irradiation has a good palliative effect on patients who have progressive disease following other types of treatment like PUVA or corticosteroids. The recurrence-free survival of 2 out of 4 patients with early stage disease (I-IIA) up to 93 month shows the potentially curative character of the treatment.

Stand-by treatment of suspected malaria in travellers.

Travellers to malarious areas are increasingly advised to carry an emergency medication for self-treatment of suspected malaria in absence of medical attention. However, no data are available so far how travellers cope with self-diagnosis and stand by treatment (SBT). We therefore investigated the frequency, circumstances and outcome of emergency self-treatment for suspected malaria in German travellers. 3434 travellers were recruited for an open prospective study by 28 different travel clinics in Germany. 2867 travellers (90.1%) who returned questionnaires after their journey were analyzed. 40 travellers (1.4%) reported about SBT during their journey. Significant Plasmodium falciparum antibody levels could be demonstrated in only 4 of 37 SBT users (10.4%). In another 127 travellers with febrile episodes but without SBT use, no malaria was indicated by follow-up and/or serology.