Cognitive deficits in first-degree relatives of bipolar patients: the use of homogeneous subgroups in the search of cognitive endophenotypes.

Previous studies have demonstrated impairments in attention, memory and executive functions in euthymic bipolar patients (BP) as well as their unaffected first-degree relatives, albeit in an attenuated form. Subsequently, cognitive deficits are discussed as a possible endophenotype of bipolar disorder. However, recent studies showed that only a subgroup of BP shows cognitive impairments. The aim of the present study was to investigate cognitive functioning in relatives compared to BP, to find out if the differentiation in a cognitive deficit vs. non-deficit subgroup is valid for relatives of BP, too. Therefore, the performance of 27 unaffected relatives of BP, 27 euthymic BP and 27 HC were compared using a neuropsychological test battery. The results showed that BP exhibited a reduced psychomotor speed and deficits in working memory compared to relatives and HC. Relatives performed significantly slower (psychomotor speed) as compared to HC (p = 0.024); performance in the other test measures lie between BP and HC. Furthermore, a detailed evaluation of the data indicated that only subgroups of BP and relatives exhibited cognitive impairments in the implemented tests. However, the deficit and non-deficit groups did not differ in sociodemographic and clinical variables from each other, possibly due to the small sample size. In conclusion, our results suggest that reduced psychomotor speed could serve as a potential endophenotype for bipolar disorder which should be investigated along the developmental trajectory of this disorder, also to examine whether abnormalities therein precede onset of the first mood episode. Furthermore, the division of relatives into subgroups aids in the identification of stable trait markers and high-risk bipolar groups and could enable early prevention strategies. As to that more research using distinct and homogeneous subgroups is necessary.

Prosthetics in antiquity-An early medieval wearer of a foot prosthesis (6th century AD) from Hemmaberg/Austria.

Even though the earliest prosthetic devices date to the Ancient Egyptian Empire and iconographic sources attest their use in the Greco-Roman world, archaeological evidence for this practice prior to 2nd millennium AD is very scant. In 2013, a skeleton dating to the Frankish period (6th century AD) was excavated at the Hemmaberg in southern Austria. The middle adult male was missing his left foot from above the ankle. In its place, an iron-ring and wooden remains were recovered and interpreted as a prosthesis replacing the lost foot. This represents one of the oldest examples of prosthetic limb replacement associated with the skeleton of its wearer in Europe to date. Analysis through macroscopic assessment, radiography and CT-scanning revealed healing of the lesion even though it may have initially been complicated by osteomyelitis. Atrophy of the left lower leg further indicates immobilisation and suggests survival of several years. Osteoarthritis in the knees and shoulder girdle provides tentative indications towards the functionality of the prosthesis, perhaps aided through a crutch. These findings are set against the historic, archaeological, bioarchaeological and social context of the man in order to discuss whether removal of the foot was due to medical, punitive or traumatic causes.

Evidence for cognitive subgroups in bipolar disorder and the influence of subclinical depression and sleep disturbances.

Recent research in bipolar disorder (BD) points to the relevance and persistence of cognitive deficits even in euthymia. Up to now, the mechanisms behind why some bipolar patients (BP) do not reach their former level of cognitive performance and psychosocial functioning while others remit completely, are not understood. In this study we aimed to identify a "cognitive deficit" vs. "non-deficit" subgroup within BD by using an extensive neuropsychological test battery. The test performance of 70 euthymic outpatients (BD-I and II, recruited as a sample of convenience from our bipolar disorder programme) was compared to 70 matched, healthy controls (HC). Furthermore, we investigated the association between demographic/clinical variables and the cognitive performance of BP. As expected, our sample of euthymic BP performed significantly worse than HC in psychomotor speed, divided attention, working memory, verbal memory, word fluency and problem solving. However, 41.4% of the patients did not have any neurocognitive deficits at all, and whether or not a patient belonged to the non-deficit group was not influenced by disease severity. Instead, our results demonstrate that patients suffering from persistent sleep disturbances and sub-threshold depressive symptomatology show more severe cognitive dysfunctions. In addition, antipsychotic treatment and comorbid anxiety disorder were associated with cognitive deficits. In sum, these results suggest that a major part of cognitive impairment is due to current symptomatology, especially sleep disorder and sub-syndromal depression. Rigorous treatment of these symptoms thus might well improve cognitive deficits and, as a consequence, overall functioning in BD.

Synchronization of the Drosophila circadian clock by temperature cycles.

The natural light/dark and temperature cycles are considered to be the most prominent factors that synchronize circadian clocks with the environment. Understanding the principles of temperature entrainment significantly lags behind our current knowledge of light entrainment in any organism subject to circadian research. Nevertheless, several effects of temperature on circadian clocks are well understood, and similarities as well as differences to the light-entrainment pathways start to emerge. This chapter provides an overview of the temperature effects on the Drosophila circadian clock with special emphasis on synchronization by temperature cycles. As in other organisms, such temperature cycles can serve as powerful time cues to synchronize the clock. Mutants that specifically interfere with aspects of temperature entrainment have been isolated and will likely help to reveal the underlying mechanisms. These mechanisms involve transcriptional and posttranscriptional regulation of clock genes. For synchronization of fly behavior by temperature cycles, the generation of a whole organism or systemic signal seems to be required, even though individual fly tissues can be synchronized under isolated culture conditions. If true, the requirement for such a signal would reveal a fundamental difference to the light-entrainment mechanism.

[Pulmonary infiltrates in a 19 year old patient with dysuria and hypercalcemia]. / Pulmonale Infiltrate bei einem 19-jährigen Patienten mit Dysurie und Hyperkalziämie.

A 19 year old patient presented with the typical constellation of sarcoidosis. In the presence of indefinable pulmonary infiltrates, hypercalcemia, raised angiotensin converting enzyme and even evidence of giant and epitheloid cell granulomas, cocaine abuse should be considered. Chronic inhalative cocaine abuse can cause foreign body associated granulomatosis of the lung and other organs. It is important to establish this differential diagnosis by confidential interview and systematic polarisation microscopy to detect foreign material in tissues: unnecessary therapies with potential side effects should be avoided and drug weaning with rehabilitation of the patient should be initiated. However the potential for rapid progressive respiratory failure should not be underestimated.

Effect of dose and dose-distribution in damage to the kidney following abdominal radiotherapy.

PURPOSE: To define the effects of abdominal radiotherapy on the kidney with regard to dose-distribution parameters. MATERIALS AND METHODS: Ninety-one patients with abdominal radiotherapy were included in the study, and the minimum follow-up was 1 year. Conventional fractionation, 5 x 1.8-2.0 Gy week(-1) to total doses of 30.6-62.5 Gy, was employed. Assessment of organ function was performed before, immediately after, and at 6 months and 1 year after radiotherapy. In cases with a significant radiation response at 1 year, subsequent follow-ups were done at 6-month intervals. Documented parameters included clinical examination, static and sequential scintigraphy of the kidneys, abdominal computed tomography, and sonography. RESULTS: Twenty-one patients (23%) developed a reduction in kidney function detected by static scintigraphy. Only in 15 of these patients was impairment of renal function observed by sequential scintigraphy. The contribution of the irradiated kidney to overall renal function decreased progressively to 34-40% by the third year after treatment. Hypertension was seen in two patients. No changes were found in laboratory parameters. ED(50) for scintigraphic changes decreased from 27 Gy for 10% of the volume to 7.6 Gy for 100%. ED(5) were in the range of 3-6 Gy, and this was independent of volume. CONCLUSIONS: Sophisticated imaging techniques allow the identification of radiation effects in partial volumes of the kidneys. A dose-response relationship in relation to the volume of kidney irradiated can thus be established for scintigraphic changes. As in a number of other organs, such changes do not relate directly to loss of renal function due to the reserve capacity of unirradiated kidney tissue.

The promoter of the human sodium/iodide-symporter gene responds to retinoic acid.

It was shown previously that hNIS mRNA expression is stimulated by retinoic acid (RA) in human follicular thyroid carcinoma cell lines FTC-133 and FTC-238, and patients with thyroid carcinomas lacking iodide uptake respond to RA treatment with increased radioiodide transport. Here, in transient transfection experiments using FTC-238 cells, hNIS promoter/luciferase reporter constructs showed an up to 2.5-fold increase in transcriptional activity after incubation with 1 microM RA. Stimulation by 10 nM T3 was up to 2.4-fold. Deletion or block mutation of a putative nuclear receptor recognition site, 'DR10', abolished RA and T3 responses. Four copies of the DR10 cloned 5' to the thymidine kinase promoter gave a 2.6-fold and a 1.4-fold increase in transcriptional activity after RA and T3 stimulation, respectively. In electrophoretic mobility shifts, a wildtype DR10 oligonucleotide, but not block mutants of either DR10 halfsite, interacted with nuclear receptors. Thus, RA redifferentiation of advanced thyroid carcinomas may reinduce iodide uptake by stimulating hNIS expression and thereby make tumours accessible for radioiodide therapy again.

Laparoscopic extraction of a swallowed fork in a patient first diagnosed with bulimia nervosa.

Swallowed foreign bodies are relatively common problem. The first reports date back about 3000 years. The first medical report was done by Mestivier in 1759. Several studies show that up to 90% of the foreign bodies (FBs) pass spontaneously and 10% to 20% require an endoscopic removal. Surgical intervention is only indicated in approximately 1% of the cases. Surgical intervention is only necessary, for example, when large or sharp FBs are involved because of the potential risk of perforation and obstruction. The surgical therapy can be carried out by means of laparotomy or laparoscopy; laparoscopy has to be given the first priority whenever possible. The advantages of a laparoscopic procedure are well-known: reduced postoperative pain, better lung function, less postoperative bowel obstruction, shorter hospital stay, and faster reconvalescence. We report an unusual case of an unintentional ingested fork, which required a laparoscopic extraction using three trocars. The 20-year-old female patient was then subsequently diagnosed with bulimia nervosa for the first time during her hospital stay. The patient was discharged home on the fourth postoperative day after an unremarkable course.

Modeling the 3D structure of GPCRs from sequence.

G-protein-coupled receptors (GPCRs) are a large and functionally diverse protein superfamily, which form a seven transmembrane (TM) helices bundle with alternating extra-cellular and intracellular loops. GPCRs are considered to be one of the most important groups of drug targets because they are involved in a broad range of body functions and processes and are related to major diseases. In this paper we present a new technology, named PREDICT, for modeling the 3D structure of any GPCR from its amino acid sequence. This approach takes into account both internal protein properties (i.e., the amino acid sequence) and the properties of the membrane environment. Unlike competing approaches, the new technology does not rely on the single known structure of rhodopsin, and is thus capable of predicting novel GPCR conformations. We demonstrate the capabilities of PREDICT in reproducing the known experimental structure of rhodopsin. In principle, PREDICT-generated models offer new opportunities for structure-based drug discovery towards GPCR targets.

[Internet presence in surgical departments in Germany. II. Legal bases of medical Internet presence]. / Chirurgische Internetpräsenz in Deutschland, Teil II. Rechtliche Grundlagen ärztlicher Internetpräsenz.

In recent years, the Internet has generally been growing throughout the world, and physicians have taken to the Web as well. Besides its use for medical data research, physicians and hospitals are increasingly discovering the Internet as a vehicle for the presentation of their scope of practice. In this regard, the legal frameworks in Germany are strictly regulated. This article presents current legal standards and consequences to be faced when the law on prohibited advertising is broken. Included are references to specific laws concerning Internet pages.

MYO6, the human homologue of the gene responsible for deafness in Snell's waltzer mice, is mutated in autosomal dominant nonsyndromic hearing loss.

Mutations in the unconventional myosin VI gene, Myo6, are associated with deafness and vestibular dysfunction in the Snell's waltzer (sv) mouse. The corresponding human gene, MYO6, is located on chromosome 6q13. We describe the mapping of a new deafness locus, DFNA22, on chromosome 6q13 in a family affected by a nonsyndromic dominant form of deafness (NSAD), and the subsequent identification of a missense mutation in the MYO6 gene in all members of the family with hearing loss.

Residue frequencies and pairing preferences at protein-protein interfaces.

We used a nonredundant set of 621 protein-protein interfaces of known high-resolution structure to derive residue composition and residue-residue contact preferences. The residue composition at the interfaces, in entire proteins and in whole genomes correlates well, indicating the statistical strength of the data set. Differences between amino acid distributions were observed for interfaces with buried surface area of less than 1,000 A(2) versus interfaces with area of more than 5,000 A(2). Hydrophobic residues were abundant in large interfaces while polar residues were more abundant in small interfaces. The largest residue-residue preferences at the interface were recorded for interactions between pairs of large hydrophobic residues, such as Trp and Leu, and the smallest preferences for pairs of small residues, such as Gly and Ala. On average, contacts between pairs of hydrophobic and polar residues were unfavorable, and the charged residues tended to pair subject to charge complementarity, in agreement with previous reports. A bootstrap procedure, lacking from previous studies, was used for error estimation. It showed that the statistical errors in the set of pairing preferences are generally small; the average standard error is approximately 0.2, i.e., about 8% of the average value of the pairwise index (2.9). However, for a few pairs (e.g., Ser-Ser and Glu-Asp) the standard error is larger in magnitude than the pairing index, which makes it impossible to tell whether contact formation is favorable or unfavorable. The results are interpreted using physicochemical factors and their implications for the energetics of complex formation and for protein docking are discussed. Proteins 2001;43:89-102.

Effects of hydrogen peroxide scavenger Catalase on villous microcirculation in the rat small intestine in a model of inflammatory bowel disease.

This study was conducted to quantify the effect of systemic Catalase, a hydrogen peroxide scavenger, on villous microcirculation in the inflamed small intestine of the rat. Intestinal inflammation was induced with s.c. application of Indomethacin. Intravital fluorescence microscopy and FITC-labeled erythrocytes were used to quantify erythrocyte velocity and arteriolar diameter in the main arteriole of the villi in the terminal ileum following i.v. application of Catalase in the inflamed intestine, and the blood flow was calculated. Control groups were formed for Ringer's lactate, Catalase and Indomethacin, respectively. We found that villous blood flow was significantly increased in the in the inflamed intestine. Application of Catalase led to a significant decrease in villous perfusion, but had no effect in the control group. The increase in villous blood flow was accompanied by changes in the diameter of the main arteriole. This effect on arteriolar diameter was reversed by i.v. Catalase. Our results provide evidence that systemic application of Indomethacin leads to vasodilatation of the main arteriole of the villus in the rat ileum and hyperemia in the mucosa. Hyperemia and the vascular diameter of the main arteriole were significantly reduced by H(2)O(2)-scavenger Catalase, suggesting that endogenous H(2)O(2) may be one of the mediators of hyperemia in the mucosa in this animal model of intestinal inflammation.

[Prevention of radiation-induced diarrhea by smectite. Results of a double-blind randomized, placebo-controlled multicenter study]. / Prophylaxe der strahleninduzierten Diarrhö durch Smektit. Ergebnisse einer doppelblind randomisierten, plazebokontrollierten Multicenterstudie.

PURPOSE: Diarrhea and abdominal pain are well-known side effects abdominal or pelvic of radiation therapy that may lead to interruption of treatment in serious cases. In recent trials the silicate smectite has proven a promising drug in the prophylaxis of these adverse events. The presented trial aimed at the verification of earlier studies and the evaluation of a dose-effect relationship. PATIENTS AND METHODS: Between April 1994 and May 1995, a total of 176 patients obtaining radiotherapy of the pelvis or the abdomen were evaluated in a double-blind, randomized placebo-controlled investigation regarding the prophylactic effect of smectite (= Colina) against radiotherapy-induced diarrhea. During the whole period of radiotherapy 85 patients obtained 2 x 6 g smectite daily and 91 patients received 2 x 6 g placebo. The primary end point of the analysis was the time to the first appearance of diarrhea (> or = 3 pappy stools). RESULTS: All 176 patients were evaluated according to an intent-to-treat analysis. There was no significant difference between the prophylactic effects of smectite and placebo. For an explorative post-hoc analysis the total study group was split up into 2 subgroups, one with an irradiated small bowel volume < or = 837.5 ml, the other with a small bowel volume > 837.5 ml (median); the analysis indicated that the first subgroup showed a benefit for the smectite-treated patients in contrast to the placebo treatment (32 vs. 18 calendar days to the first appearance of diarrhea). This benefit was statistically not significant. CONCLUSION: Prophylactic application of smectite during irradiation of the pelvis and the abdomen can delay the development of radiotherapy-induced diarrhea, a statistical significance could not be verified neither in the total study group nor in the post-hoc subgroup analysis.

Current practice of temporary vena cava filter insertion: a multicenter registry.

PURPOSE: To evaluate the current practice of temporary vena cava filter placement and its complications. MATERIALS AND METHODS: A multicenter registry was conducted from May 1995 until May 1997 using a standardized questionnaire. One hundred eighty-eight patients were evaluated. Patient characteristics, filter indications, filter characteristics, and complications were registered. RESULTS: Deep vein thrombosis was proven in 95.2% of the patients. Main filter indication was thrombolysis therapy (53.1%). Average filter time was 5.4 days. An Antheor filter was inserted in 56.4%, a Guenther filter in 26.6%, and a Prolyser filter in 17.%. Transfemoral filter implantation was slightly preferred (54.8%). Four patients died of pulmonary embolism (PE) during filter protection. Major filter problems were filter thrombosis (16%) and filter dislocation (4.8%). When thrombus was found in or at the filter before explantation, additional thrombolysis was performed in 16.7%, additional filter implantation in 10%, and thrombus aspiration in 6.7%; 4.8% of filters were replaced with permanent filters. DISCUSSION: Temporary vena cava filters are placed to prevent PE in a defined patient population. Despite their presence, PEs still occur in a small percentage. Problems of filter thrombosis and dislocation have to be solved. CONCLUSION: The results of this multicenter registry support the need for innovative filter design, as well as a randomized, prospective study.

[Laparoscopic adhesiolysis - results following prospective surveillance]. / Die laparoskopische Therapie des Adhäsionsbauchs. Ergebnisse einer prospektiven Beobachtungsstudie.

INTRODUCTION: About 90 % of the patients have abdominal surgery develop adhesions afterward. Studies analyzing complications and follow-up even in emergency cases are rare. METHODS: Intra- and postoperative findings and complications and follow-up were analyzed in a prospective trial between January 1994 and June 1998. RESULTS: We performed laparoscopic procedures in 56 patients with complaints of obstructing adhesive bands or adhesions. Ninety-six percent of the patients have had abdominal surgery; 51.8 % were treated as emergency cases with acute pain, 48.2 % with chronic abdominal pain. Intraoperatively, 37.5 % of the patients showed single adhesive bands; 62.5 % showed adhesions. Mean operation time was 60 min, conversion rate: 5.4 %. Complications were recorded according to the "Cologne classification": class I: 78.6 %, class II: 8.9 %, class III: 1.8 %, class IV: 10.8 %, class V: 0 %. The postoperative hospital stay was 6 days on average. CONCLUSION: Our study suggests that laparoscopic adhesiolysis can be done safely in emergency cases and in patients with extensive adhesions as well.