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Biomedical subjects

Rainer Koch

Publications and source records attributed to Rainer Koch.

47 records · Page 3Linked to original sources

CARD15 genotype and phenotype analysis in 55 pediatric patients with Crohn disease from Saxony, Germany.

OBJECTIVES: Crohn disease is a chronic inflammatory bowel disorder that is caused by environmental and genetic factors. Mutations in the CARD15 gene have been recently identified to be associated with the disease. Until now no genetic study has focused directly on a pediatric population. METHODS: The authors sequenced all 12 exons of the CARD15 gene in 55 pediatric patients with Crohn disease from Saxony. Their average age at onset was 11.2 years (1-17.5 years). The authors also evaluated the genotype-phenotype relationship in the patients. RESULTS: Fourteen different polymorphic and/or disease-related nucleotide alterations have been identified in the patients. Sixty-five percent of their genomic DNA samples harbored at least one of six mutations within the CARD15 gene, which previously has been identified as being associated with Crohn disease. The authors found that the cytosine insertion mutation 3020insC was significantly more common in their pediatric population than in patients with Crohn disease (26% versus 11% of the alleles) whose results were reported in the literature. The genotype-phenotype analysis showed that the authors' patients with at least one of the six CARD15 disease-associated mutations had a high risk of inflammation located in the terminal ileum and ascending colon. In 10 of 19 patients with two mutations, intestinal resection surgery was necessary because of stricturing. CONCLUSIONS: In the authors' pediatric patients, the genetic influence on Crohn disease was more pronounced than that reported in any other study, and it strongly affected the clinical phenotype.

Adolescent↗

Autoantibodies to thyroperoxidase (TPOAb) in a large population of euthyroid subjects: implications for the definition of TPOAb reference intervals.

OBJECTIVE: Measurement of autoantibodies against thyroperoxidase (TPOAb) plays an important role in the diagnosis of autoimmune thyroid disease. The assessment of reference intervals for TPOAb, however, is a controversial issue since elevated TPOAb values are sometimes found in subjects without other evidence of thyroid disease. METHODS: TPOAb were measured in 1,295 euthyroid individuals using a highly sensitive, fully automated chemiluminescence assay (Advantage A-TPO, Nichols Institute Diagnostics, CA, USA). The study subjects participated in a population study on the prevalence of thyroid disorders in the German federal state of Saxony, an area of mild iodine deficiency. RESULTS: TPOAb above the detection limit of 0.45 IU/ml were found in 1,277/1,295 euthyroid individuals. TPOAb values in the low measurable range below 1.1 IU/ml followed a normal distribution, and this was independent of age and sex. When using a cut-off value of 1.1 IU/ml, which corresponds to a sensitivity of 79% and a specificity of 95% resulting from the receiver-operator characteristic plot for discrimination between a main type and other types with a higher mean value of TPOAb, elevated TPOAb were found in 14.4% of euthyroid men and in 25.8% of euthyroid women. CONCLUSIONS: The results demonstrate for the first time that TPOAb are detectable in nearly all euthyroid individuals and that TPOAb values in the low measurable range are normally distributed. The distribution of TPOAb values in the low range is independent of age and sex. Based on these data, reference intervals for TPOAb can be defined that are independent of the population investigated. The clinical significance of slightly elevated TPOAb, however, has still to be defined by prospective studies.

Adult↗

Comparative study of Venostasin and Pycnogenol in chronic venous insufficiency.

The aim of this study was to compare the efficacy of Venostasin (horse chestnut seed extract) and Pycnogenol (French maritime pine bark extract) in the treatment of chronic venous insufficiency (CVI). In an open, controlled comparative study 40 patients with diagnosed CVI were treated either with 600 mg chestnut seed extract per day or 360 mg Pycnogenol per day over a period of 4 weeks. The following parameters were investigated before the start of treatment and after 2 and 4 weeks of treatment: circumference of the lower legs and rating of subjective symptoms (scores) of pain, cramps, night-time swelling, feeling of "heaviness", and reddening of the skin. In addition, blood levels of cholesterol LDL and HDL were determined before and at the end of treatment. Pycnogenol significantly reduced the circumference of the lower limbs and significantly improved subjective symptoms. Furthermore, Pycnogenol significantly decreased cholesterol and LDL values in the blood, whereas HDL remained unaffected. Venostasin only moderately but not significantly, reduced the circumference of the lower limbs and marginally improved symptoms. Venostasin had no influence on the determined lipid values. Both medications were equally well tolerated. In conclusion, Pycnogenol was found to be more efficacious than Venostasin for the treatment of CVI.

Adult↗

Primary closure techniques in chronic pilonidal sinus: a survey of the results of different surgical approaches.

PURPOSE: Pilonidal sinus is a common disease and surgical removal and subsequent wound closure is crucial for lasting cure. To evaluate the outcome of different primary closure techniques we performed a pooled analysis of data published in the past 35 years. METHODS: We identified reports on wound infection, early failure, and late recurrence status in relation to treatment modality. Surgical techniques were classified into five groups: simple closure technique in the midline, asymmetric or oblique closure techniques, and full-thickness flap techniques like rhomboid flaps, vy-plasty, and z-plasty. Estimations of the incidences resulted from the quotient of number of responses and the number of patients for each study, and these quotients were summarized over all studies. RESULTS: The MEDLINE search identified 74 publications including 10,090 patients. Pooled data analysis revealed an inhomogeneous effect of the surgical techniques on the infection rate. In contrast, there was a significantly lower early failure rate and late recurrence rate of both the asymmetric-oblique closure techniques and the full-thickness flap techniques when compared with the midline repair technique. No difference was found between the asymmetric repairs and the full-thickness flap techniques. CONCLUSION: Beside the various statistical considerations when using a pooled data analysis combining results from the literature, this overview suggests a significant benefit of asymmetric-oblique closure techniques or flap techniques in comparison with simple closure in the midline. Thus, we recommend an asymmetric closure technique for primary closure of a chronic pilonidal sinus. These asymmetric procedures provide better results than the simple closure in the natal midline. Furthermore, they are not as sophisticated as the full-thickness plasty techniques.

Humans↗

Lobe-sparing resection of multiple pulmonary metastases with a new 1318-nm Nd:YAG laser--first 100 patients.

BACKGROUND: A new 1318-nm Nd:YAG laser has been developed to utilize the second wavelength (1318 nm; 40 watt) to more precisely cut, coagulate, and seal lung tissue adjacent to pulmonary nodules. This laser allows a precise intraparenchymal nodulectomy with a 5-mm rim of tissue destruction and subsequent lung parenchymal reapproximation to avoid lobar distortion. Resection of multiple, bilateral, and recurrent tumors in the lung is facilitated by this laser technique. METHODS: In 100 consecutive patients (53 men, mean age 60 years; 47 women, mean age 61 years) with various primaries (most commonly renal and colorectal), 155 laser resections were performed via anterolateral thoracotomy (staged 3 to 4 weeks, if bilateral) using a new 1318-nm Nd:YAG laser. All palpable and visible masses were removed with 2 to 3-mm visible tumor margins (plus a 5-mm rim of residual lung necrosis secondary to laser energy dispersal) if the tumor or residual lung ratio was judged favorable. No stapling devices or bioadhesives were used. RESULTS: Six hundred thirty-two metastases (6.3 per patient, range 1 to 124) were resected. Despite 41% centrally located metastases, tumor resections were possible in 95% of patients with only a 5% lobectomy rate. Of the 100 patients, 67 were considered "curative" with complete metastasectomy by inspection and palpation, and 23 were judged incomplete from too extensive tumor or residual lung, miliary lung spread, or pleural studding. There were no associated mortalities and two complications, including bleeding (1) and a prolonged airleak (1), both treated conservatively. Follow-up was complete in all patients for a median of 26.5 months with clinic visits and chest computed tomographic scan every 3 to 6 months. Nine recurrences were detected and underwent reoperation. Overall survival in the completely resected "curative" group was 85% at 1 year, 71% at 2 years, 69% at 3 years, 57% at 4 years, and 32% at 5 years; in the completely resected "palliative" group, they were 70% at 1 year, 36% at 2 years, 12% at 3 years, and 0 at 4 years; in the incomplete group, they were 56% at 1 year, 30% at 2 years, and 0 at 3 years. CONCLUSIONS: The new 1318-nm Nd:YAG laser is parenchyma-sparing, improves complete resection rates, and potentially improves survival with fewer required lobectomies.

Aged↗

N-Mesityl-C-acylketenimines: 1,5-Sigmatropic Shifts and Electrocyclization to Quinolines.

Flash vacuum thermolysis (FVT) of triazoles 6a-c generates alpha-oxoketenimines 10, the ester 10a being isolable. FVT of pyrroledione 8 generates the isomeric imidoylketene 9a. Ketenes 9 and ketenimines 10 undergo thermal interconversion by 1,3-shifts of methoxy and dimethylamino groups under mild FVT conditions (ca. 350-400 degrees C). Both 9 and 10 are directly observable by IR spectroscopy at either 77 K or on Ar matrix isolation at 12 K. On FVT at temperatures above ca. 400 degrees C, the ketenimines 10 undergo a 1,5-H shift to o-quinoid imines 12/13, followed by electrocyclization to dihydroquinolines 14 (unobserved) and 15 (observed by NMR). The latter are easily oxidized to alkylquinoline-3-carboxylates or quinoline-3-carboxamides 16 by atmospheric oxygen. Ab initio calculations on model compounds 18-23 predict an energy barrier of ca. 38 kcal mol(-)(1) (161 kJ mol(-)(1)) for the 1,5-H shift in N-(o-methylphenyl)ketenimines via the transition state TS19 followed by an electrocyclization barrier to dihydroquinoline 23a via TS22a of ca. 16 kcal mol(-)(1).

Journal Article↗

Retro-Ene Reactions in Acylallene Derivatives.

Allenic esters and amides 4 undergo a retro-ene reaction to vinylketene (6) and an aldehyde or imine (5) under the conditions of flash vacuum thermolysis (FVT). The same products are obtained by FVT of cyclobutenones 7 via electrocyclic ring opening to alkoxy- or aminovinylketenes 3 and 1,3-rearrangement of ketenes 3 to allenes 4. All the intermediates and products were characterized by matrix isolation IR spectroscopy, and in the case of 4c the reaction was also monitored by online mass spectrometry. A lower temperature for the retro-ene reaction of 4c, eliminating an imine, than for 4a, eliminating formaldehyde, is in agreement with a lower calculated activation barrier (167 and 181 kJ mol(-1), respectively, at the G2(MP2,SVP) level of theory). The allenic amide 11 undergoes an analogous retro-ene reaction to the (unobserved) vinylketene 13, the latter isomerizing to cyclohexenylacrolein 16 in a 1,5-H shift (calculated barrier 125 kJ mol(-1); G2 (MP2, SVP)).

Journal Article↗

Facile 1,3- and 1,5-Chlorine Migration.

High-level ab initio molecular orbital calculations, using the G2(MP2,SVP) theory (and semiempirical methods) have been used to examine several 1,3- and 1,5-chlorine migrations. It is found that the interaction of chlorine lone pair electrons with a low-lying LUMO accelerates the Cl shift dramatically (lone pair-LUMO-mediated pericyclic reaction). The activation barriers for the 1,3-migration in chloro oxo ketene 1 (Cl(C=O)CH=C=O) and the 1,5-migration in (2-(chlorocarbonyl)vinyl)ketene 2 (Cl(C=O)CH=CHCH=C=O) are only 53 and 61 kJ mol(-)(1), respectively, compared to the 216 and 173 kJ mol(-)(1) barriers for the corresponding unassisted 1,3- and 1,5-sigmatropic shifts of Cl in 3-chloro-1-propene and 5-chloro-1,3-pentadiene. The transition structures for 1 and 2 reveal that migration of the chlorine atoms takes place in the molecular planes. The 1,5-chlorine shift in 6-chlorocyclohexa-2,4-dienone (3) has a significantly higher barrier due to a lack of appropriate orbital interaction. The related 1,3-shift in the (chlorocarbonyl)imine-alpha-chloro isocyanate system is also dramatically accelerated compared with conventional pericyclic 1,3-Cl migration.

Journal Article↗

Changing comorbidity classification patterns at radical prostatectomy during a 10-year period.

OBJECTIVE: To investigate the consistency of several comorbidity classifications and concomitant diseases at radical prostatectomy (RP) during a 10-year period. METHODS AND MATERIALS: In 1,297 patients who underwent RP between 1993 and 2002, age and several comorbidity classifications were derived from patient records and assigned to the year of surgery. Trends were evaluated using the Cochran-Armitage trend test. RESULTS: Parallel to an increasing frequency of RPs and a shift toward more organ-confined tumors (P = 0.0094), the proportion of patients aged > or =70 years increased (P = 0.0077). The proportion of the American Society of Anesthesiologists (ASA) Physical Status class 3 increased (P < 0.0001), whereas that of ASA class 1 decreased (P < 0.0001). A Charlson score > or =1 has been assigned with an increasing frequency (P = 0.0008), whereas the trend with a Charlson score of > or =2 did not reach statistical significance (P = 0.07). In contrast to the latter 2 classifications, no significant trends were observed with classifications related to diabetes mellitus and heart disease. CONCLUSIONS: This study shows that the application of the ASA classification may change significantly over time, whereas cardiac and diabetes-related conditions, as well as the Charlson score were apparently less sensitive to changing classification standards in the RP setting.

Aged↗

Mentalizing language development in a longitudinal attachment sample: implications for alexithymia.

BACKGROUND: The construct of alexithymia implies a deficit in symbolization for emotional, somatic, and mental states. However, the etiologic factors for alexithymia have not yet been fully elucidated. The present study investigated the use of mentalizing language, i.e. the utterance of internal states, from a developmental perspective according to attachment organization and disorganization. METHODS: A longitudinal design across 4 time points was applied to a volunteer sample of 42 children. At 12 months, children were tested with the strange situation procedure, the standard measure of attachment at the optimal age, and attachment classifications were taken of videotapes. At ages 17, 23, 30 and 36 months, mother and child were observed in simplified separation episodes of 30 min duration. Transcripts of the sessions were subject to coding of internal state words. RESULTS: During the investigated span, securely attached children rapidly acquired emotion, physiology, cognition and emotion-regulatory language, whereas insecurely attached and disorganized children either completely lacked internal state language or displayed a considerable time lag in the use of emotion and cognition vocabulary. CONCLUSION: The results raise the possibility that alexithymia might be a consequence of deficits in the development of internal state language in the context of insecure or disorganized childhood attachment relationships.

Affective Symptoms↗