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Biomedical subjects

Andreas Koch

Publications and source records attributed to Andreas Koch.

At least 37 records · Page 2Linked to original sources

Configuration and E/Z interconversion mechanism of O(S)-allyl-S(O)-methyl-N-(acridin-9-yl) iminothiocarbonate.

The configuration and dynamic behavior of O-allyl-S-methyl-N-(acridin-9-yl)iminothiocarbonate (1) and its S-allyl-O-methyl regioisomer (2) were studied using quantum chemical calculations and by applying a novel graphical method to scatter maps obtained from MD simulations for evaluation of an NOE-weighted internuclear distance (r(NOE)). Energy calculations indicated that the Z configuration was predominant for each compound and, further, this was supported both by the calculated chemical shifts and the r(NOE). Both N-inversion- and rotation-type transition-state structures were also calculated for the E/Z isomerization process, the results indicating that the preferred interconversion mechanism for 1 is N-inversion, but contrastingly, interconversion via rotation is equally as probable as N-inversion for 2. This supports the notion that one or the other or both pathways can be active and each system needs to be assessed on a case-by-case basis.

Journal Article↗

Benzoate hydroxylation: a measure of oxidative stress in divers.

Hyperoxia may facilitate the formation of reactive oxygen species. Recent experiments indicated signs of oxidative stress after 3.5 h hyperoxic diving. We analyzed in the urine of healthy, 100% O2-breathing male volunteers before and after 45 min seawater diving (170 kPa) or 30 min resting at 280 kPa in a pressure chamber (HBO) for sub-fractions of hydroxybenzoate (HB), monohydroxybenzoate (MHB), and of dihydroxybenzoate (DHB). Measurements were performed by HPLC and electrochemical or UV-detection. Additionally, urinary concentrations of thiobarbituric acid-reactive substances (TBARS) and of creatinine (CREA) were analyzed by standard colorimetric assays. During HBO treatment, TBARS, DHB, 2,4-DHB, and 3,4-DHB increased significantly. MHB and CREA did not change. 2,4- and 3,4-DHB-alterations correlated with changes in TBARS. Diving induced urine dilution and stimulated oxygen consumption. Urinary TBARS and HB rose significantly higher during diving at 170 kPa than during HBO at 280 kPa. A different pattern in urinary sub-fractions of DHB could be observed in divers: 2,6 > 2,3 > 2,5 > 3,4. Changes in 2,6- and 2,5-DHB correlated significantly with alterations in TBARS. 2,6-DHB probably indicated renal oxidant stress similar to previously described animal experiments. It is concluded that analyzing urinary HB may provide a sensitive measure to quantify and qualify oxidant stress in divers.

Adult↗

The significance of Meckel's diverticulum in appendicitis--a retrospective analysis of 233 cases.

Conflicting reports are found in the literature concerning whether to remove an incidentally discovered Meckel's diverticulum (MD). Between 1.1.1974 and 31.12.2000, at a single center, the perioperative data associated with appendectomy (AE) were recorded consecutively and analyzed retrospectively. All patients in whom an MD was discovered during an AE were included in the study. The clinical presentation, postoperative course, and follow-up in all MDs left in place were analyzed. During the course of 7927 AE, 233 MD (2.9%) were detected. Of these 80.7% (n = 188) were removed and 19.3% (n = 45) were left untouched. In 9% (n = 21) of all detected diverticula pathological changes were found. Ectopic tissue was seen in 12.2% (n = 23) of the MDs removed. The postoperative complication rates did not differ significantly between patients in whom the MD was removed (9.5%; n = 18) and those in whom it was not (17.7%; n = 8); in the latter group the appendicitis was of the more acute type (gangrenous or perforated) (24.4% vs. 4.3%). In 18 patients (40.0%) with non-removed MDs, a follow-up period of 14.1 5.8 years was achieved. Complications associated with a non-removed MD were not observed. If during the course of an AE a MD is detected, the present data, as well as those in the literature, suggest that an individualized approach should be taken. Meckel's diverticulum with obvious pathology should always be removed. In cases of gangrenous or perforated appendicitis, an incidentally discovered MD should be left in place, whereas in an only mildly inflamed appendix it should be removed.

Adolescent↗

The impact of the risk factor "age" on the early postoperative results of surgery for colorectal carcinoma and its significance for perioperative management.

The risks and benefits of surgery for colorectal cancer in old patients have not been unequivocally defined. The present investigation was carried out in 309 hospitals as a prospective multicenter study. In the period between 1 January 2000 and 31 December 2001, a total of 19,080 patients were recruited for the study; 16,142 (84.6%) patients were younger than 80 years (<80) and 2932 (15.4%) were 80 years and older (> or =80). Significant differences between the age groups were observed for general postoperative complications (22.3% for <80 years; 33.9% for > or =80). Specific postoperative complications were identical in both groups. Overall, significantly elevated morbidity and mortality rates were found with increasing age (morbidity: 33.9% vs. 43.5%; mortality: 2.6% vs. 8.0%). The distribution of tumor stages revealed a significantly higher percentage of locally advanced tumors in the older age group (stage II: 28.0% vs. 34.4%). In contrast, no increase in metastasizing tumors was found in the older age group (stage IV: 17.4% vs. 14.1%). Logistic regression showed that, in concert with a number of other parameters, age is a significant influencing factor on postoperative morbidity and mortality. The increase in postoperative morbidity and mortality rates associated with aging is a result of the increase in general postoperative complications, in particular, pneumonia and cardiovascular complications. Age as such does not represent a contraindication for surgical treatment. The short-term outcome and quality of life are of overriding importance for the geriatric patient.

Age Factors↗

Cerebral autoregulation is temporarily disturbed in the early recovery phase after dynamic resistance exercise.

AIM: To determine cerebral blood-flow velocity (CBFV) and parameters of dynamic cerebral autoregulation (CA) during and after exhausting resistance exercise. METHODS: Strength endurance (23 repetitions) and maximal strength training (8 repetitions) in 16 female and 16 male athletes on a leg curler (m. quadriceps training; approx. 2 s contraction) in the upright position. Registration of ECG, blood pressure by Finapres, CBFV by transcranial Doppler (TCD), and breathing by a Zak breathing-belt. Additional repetitive ergospirometry (O2-uptake, CO2-elimination, ventilation) and blood gas analyses were performed in a subgroup of seven athletes. From BP and CBFV cerebrovascular resistance (CVR), pulsatility index (PI) as well as LF-power, gain and phase-angle (frequency analysis) were derived. RESULTS: All athletes showed significant (p<0.01) 15 % to 30 % increases in CBFV during both training sets without signs of flow depression due to Valsalva maneuvers. In the early recovery, when blood pressure rapidly decreased, CBFV amplitude significantly (p<0.01) increased for 60-80 seconds with mean flow (Vm) at the exercise level, while CVR and PI showed conflicting results, similar to a presyncopal reaction. Ergospirometry and blood gas analyses revealed no evidence of major changes in pCO2, but phase angle was reduced (p<0.001) after exercise, together with an LF power increase (p<0.001). CONCLUSION: An unexpected increase in CBFV amplitude and in Vm occurs directly after dynamic resistance exercise without increased pCO2, which is comparable to a maximum leg press with hypercapnia. CVR and PI results as well as data from frequency analysis show similarities to presyncopal reactions, on the one hand, and point towards a temporarily disturbed cerebral autoregulation, on the other.

Adult↗

7a-O-methyldeguelol, a modified rotenoid with an open ring-C, from the roots of Derris trifoliata.

From the acetone extract of the roots of Derris trifoliata an isoflavonoid derivative, named 7a-O-methyldeguelol, a modified rotenoid with an open ring-C, representing a new sub-class of isoflavonoids (the sub-class is here named as rotenoloid), was isolated and characterised. In addition, the known rotenoids, rotenone, deguelin and alpha-toxicarol, were identified. The structures were determined on the basis of spectroscopic evidence. Rotenone and deguelin were identified as the larvicidal principles of the acetone extract of the roots of Derris trifoliata.

Animals↗

Intrauterine torsion of a testicular teratoma: a case report.

Neonatal testicular tumors and intrauterine testicular torsions are very rare. The presented case is the first describing intrauterine torsion of a descended testis with a teratomatous tumor. Immediately after birth, right hemiscrotal swelling was seen in a preterm male newborn. Surgical intervention showed extravaginal testicular torsion and a highly differentiated testicular teratoma with haemorrhagic infarction. The testis was removed (orchiectomy). Over a period of twelve months no signs of tumor recurrence were found. While being extremely rare, testicular tumors should be included in the differential diagnosis of neonatal scrotal swelling.

Female↗

Oral capecitabine plus subcutaneous interferon alpha in advanced squamous cell carcinoma of the skin.

PURPOSE: Squamous cell carcinoma of the skin (SSC) is a UV-damage-related skin tumor. The first-line treatment is surgery, which has a high cure rate. In advanced cases, however, the established treatment is often not curative and shows a high rate of side effects. Improved treatment modalities are necessary. METHODS: Oral capecitabine plus subcutaneous interferon alpha were used in a prospective case series in advanced SSC of the skin at an academic teaching hospital for dermatology. Four patients with advanced SCC were included. Capecitabine 950 mgm(-2) body surface on days 1 to 14 was combined with interferon alpha 3x3 mioU s.c. three times a week. The chemotherapy was repeated on day 22. Clinical response, histology, monitoring of side effects and health performance status were assessed. RESULTS: Four patients (two females and two males) with advanced SCC were included (age range: 19 to 75 years). Complete remission (CR) was obtained in two and partial response (PR) in two. The final outcome was CR in two and progressive disease in one. One patient died of an unknown cause. Side effects were mild. Adjuvant treatment was unnecessary. Health performance status was not affected by the treatment. CONCLUSIONS: The treatment protocol with a combination of capecitabine and interferon alpha seems to be effective and well tolerated in patients with advanced SCC. Controlled trials are necessary to prove the benefit we observed in this case series.

Adult↗

Laterality of the aortic arch and anomalies of the subclavian artery-reliable indicators for 22q11.2 deletion syndromes?

UNLABELLED: A variety of cardiac defects, encompassing truncus arteriosus, tetralogy of Fallot, pulmonary atresia with ventricular septal defect and interrupted aortic arch, are generally summarised as conotruncal malformations. Patients with these cardiac defects were frequently found to have a common microdeletion on chromosome 22, the so-called monosomy 22q11.2. The aim of our study was to determine whether the laterality of the aortic arch or the presence of subclavian artery anomalies (SAA) represent markers for monosomy 22q11.2 in these patients. 170 patients with these cardiac anomalies were recruited at presentation in the paediatric cardiology units of two tertiary referral centres from 1994 until 2003. Of the 170 children and young adults, 33 had interrupted aortic arch, 35 tetralogy of Fallot, 31 truncus arteriosus communis and 71 pulmonary atresia with ventricular septal defect. All were screened for monosomy 22q11.2 and the results were correlated with the laterality of the aortic arch and the presence of SAA contralateral to the aortic arch (aberrant origin from the descending aorta, isolation, distal ductal origin from the pulmonary artery and cervical origin of the right subclavian artery). Monosomy 22q11.2 was present in 59/170 patients (35%). A left aortic arch (LAA) was found in 118 (69%), a right aortic arch (RAA) in 52 (31%) patients. Almost 50% of the patients with RAA (46%), but only 30% of the patients with LAA had monosomy 22q11.2 ( P=0.054). A total of 47 patients (28%) had an anomaly of the subclavian artery, 81% of whom had monosomy 22q11.2. This deletion was found in decreasing percentage in patients with LAA+SAA (85%) >RAA+SAA (75%) >RAA without SAA (28%) >LAA without SAA (13%). CONCLUSION: In patients with conotruncal malformations, anomalies of the subclavian arteries are the most important anatomical marker for the presence of monosomy 22q11.2, independent of the laterality of the aortic arch. Therefore, we recommend cytogenetic testing for this microdeletion in all patients with subclavian artery anomalies and conotruncal malformations.

Adolescent↗

Stereoelectronic effects in ring-chain tautomerism of 1,3-diarylnaphth[1,2-e][1,3]oxazines and 3-alkyl-1-arylnaphth[1,2-e][1,3]oxazines.

The disubstitution effects of X and Y in 1-(Y-phenyl)-3-(X-phenyl)-2,3-dihydro-1H-naphth[1,2-e][1,3]oxazines on the ring-chain tautomerism, the delocalization of the nitrogen lone pair (anomeric effect), and the (13)C NMR chemical shifts were analyzed by using multiple linear regression analysis. Study of the three-component equilibrium B<==>A<==>C revealed that the chain<==>trans (A<==>B) equilibrium constants are significantly influenced by the inductive effect (sigma(F)) of substituent Y on the 1-phenyl ring. In contrast, no significant substituent dependence on Y was observed for the chain<==>cis (A<==>C) equilibrium. There was an analogous dependence for the epimerization (C<==>B) constants of 1-(Y-phenyl)-3-alkyl-2,3-dihydro-1H-naphth[1,2-e][1,3]oxazines. With these model compounds, significant overlapping energies of the nitrogen lone pair was observed by NBO analysis in the trans forms B (to sigma*(C1-C1'), sigma*(C1-C10b), and sigma*(C3-O4)) and in the cis forms C (to sigma*(C1-H), sigma*(C1-C10b), and sigma*(C3-O4)). The effects of disubstitution revealed some characteristic differences between the cis and trans isomers. However, the results do not suggest that the anomeric effect predominates in the preponderance of the trans over the cis isomer. When the (13)C chemical shift changes induced by substituents X and Y (SCS) were subjected to multiple linear regression analysis, negative rho(F)(Y) and rho(F)(X) values were observed at C-1 and C-3 for both the cis and trans isomers. In contrast, the positive rho(R)(Y) values at C-1 and the negative rho(R)(X) values at C-3 observed indicated the contribution of resonance structures f (rho(R) > 0) and g (rho(R) < 0), respectively. The classical double bond-no-bond resonance structures proved useful in explaining the substituent sensitivities of the donation energies and the behavior of the SCS values.

Journal Article↗

Ninety-four appendectomies for suspected acute appendicitis during pregnancy.

Acute appendicitis during pregnancy is a rare event, and large numbers of cases reported in the literature stem entirely from data stored in national registers. Between 1974 and 2000 relevant perioperative data on the treatment of appendicitis were collected consecutively and analyzed retrospectively. Surgical and obstetric data relating to the medical history, the clinical, intraoperative, and histologic findings, and the course of the pregnancy were recorded. Altogether, 9793 appendectomies were performed, 94 of which were in pregnant women (24.5% during the first trimester, 51% during the second trimester, and 24.5% during the third trimester). This represents 0.2% of the 46,960 deliveries during the period under observation. Fifty percent of the case histories during the second trimester were atypical. The overall perforation rate was 14.9%; it was 8.7%, 12.5%, and 26.1% during the three trimesters, respectively. Maternal mortality was 0%; the combined miscarriage/abortion rate was 8.5% (n = 8); and infant mortality was 3.2% (n = 3). The postoperative spontaneous abortion rate was 13.0% and the additional therapeutic/requested abortion rate 21.7% during the first trimester. In view of the elevated postoperative abortion rate and the facility of the clinical diagnosis during the first trimester, the indication for invasive diagnostic measures and surgery requires careful consideration. During the second and third trimesters the difficulty of establishing a clinical diagnosis makes it necessary to undertake exploratory surgery early.

Acute Disease↗

Search for somatic 22q11.2 deletions in patients with conotruncal heart defects.

A wide range of clinical variability in patients with 22q11.2 deletions has been demonstrated in numerous studies. Nevertheless, it is still an open question if major genetic factors contribute to clinical expression. Therefore one aim of this study was to investigate, if patients with 22q11.2 deletion and conotruncal heart defects show a "second hit" somatic 22q11.2 deletion in tissue from the conotruncus, heart vessels or thymus. The second aim was to analyse patients with conotruncal heart defects without 22q11.2 deletion in blood cells for somatic deletion mosaicism. We were able to study tissue samples from heart surgery from 23 patients, 9 of whom had 22q11 deletions by FISH analysis on metaphase spreads from peripheral lymphocytes. Analysis of 18 polymorphic markers from the 22q11.2 region in DNA prepared from thymus and/or heart vessels and/or conotruncus tissue and peripheral lymphocytes in each patient did not show any allelic loss. Thus somatic 22q11.2 deletions apparently do not play a major role in conotruncal heart defects in patients with or without germ line 22q11.2 deletion.

Child↗

Electronic influences on 3J(C,H) coupling constants via -S-, -S(O)- and -SO2-: their determination, calculation and comparison of detection methods.

3J(C,H) coupling constants via a sulfur atom in two series of compounds, both including a sulfide, a sulfoxide and a sulfone, were detected experimentally and calculated by quantum mechanical methods. In the first series (1-3) the coupling between a hydrogen, bonded to an sp3 carbon, and an sp2 carbon is treated; the second series (4-6) deals with the coupling between a hydrogen, bonded to an sp3 carbon, and an sp3 carbon. Different pulse sequences (broadband HMBC, SelJres, 1D HSQMBC, J-HMBC-2, selective J-resolved long-range experiment and IMPEACH-MBC) proved to be useful in determining the long-range 3J(C,H) coupling constants. However, the dynamic behaviour of two of the compounds (4 and 6) led to weighted averages of the two coupling constants expected (concerning equatorial and axial positions of the corresponding hydrogens). DFT calculations proved to be useful to calculate not only the 3J(C,H) coupling constants but also the different contributions of FC, PSO, DSO and SD terms; the calculation of the Fermi contact term (FC) was found to be sufficient for the correct estimation of 3J(C,H) coupling constants.

Journal Article↗

Resection of the spleen using the Water Jet dissection technique.

Today, spleen-preserving or splenic-tissue-conserving surgery is both an accepted and desirable principle in the surgical treatment of injuries to the spleen as well as nontraumatic benign splenic lesions. In the rare case of benign tumorous lesions of the spleen, the question whether splenectomy or resection is the preferred successful therapeutic option is still being discussed. We present a case in which a high-pressure water jet dissector (Helix Hydro-Jet, A. Pein Medizintechnik, Schwerin, Germany) was used to perform an elective resection in a 13-year-old boy with a hamartoma of the spleen. The postoperative course was free of complications. The case illustrates the excellent features of water jet dissection in terms of transection of the parenchymal tissue and safe and selective hemostasis, which has also made the Hydro-Jet our preferred instrument for surgery on the splenic parenchyma.

Adolescent↗

Beneficial Effects of Estrogens on Indices of Renal Damage in Uninephrectomized SHRsp Rats.

Renal diseases tend to be less severe among premenopausal female patients, compared with male patients. Experimental data on the effects of estrogens on renal damage are controversial, and potential underlying mechanisms have not been fully clarified. Three-month-old, female, uninephrectomized (UNX), sham-operated or ovariectomized (OVX) SHRsp rats were left untreated or received either 17beta-estradiol 3-benzoate (25 micro g/d) or estriol (0.02 mg/d) daily. After 3 mo, indices of renal damage (glomerulosclerosis index and tubulointerstitial damage index) and glomerular geometric parameters were investigated. The expression of desmin, TGF-beta, endothelin-1, collagen IV, endothelial nitric oxide synthase, and estrogen receptors alpha and beta in the glomeruli and tubulointerstitium was immunohistochemically evaluated. Estradiol and estriol did not significantly affect kidney weights or BP. Estradiol and estriol caused significant reductions in albuminuria (vehicle-treated UNX/OVX animals, 25.4 +/- 8.52 mg/24 h; estradiol-treated UNX/OVX animals, 15.37 +/- 6.12 mg/24 h; estriol-treated UNX/OVX animals, 6.54 +/- 2.24 mg/24 h). The glomerulosclerosis index was significantly lower in estriol- and estradiol-treated animals (estradiol-treated UNX/OVX animals, 0.69 +/- 0.16; estriol-treated UNX/OVX animals, 0.21 +/- 0.12; P < 0.05), compared with vehicle-treated animals (1.46 +/- 0.09); the tubulointerstitial damage index exhibited a similar pattern. The mean glomerular volume was significantly less in estrogen-treated animals. UNX/OVX animals demonstrated significantly greater expression of TGF-beta and endothelin-1 in immunohistochemical, in situ hybridization, and reverse transcription-PCR assays. This increase was abrogated by estriol but not estradiol. Similarly, significantly higher glomerular and tubulointerstitial expression of proliferating cell nuclear antigen and collagen IV was observed in UNX/OVX animals, and expression was decreased by estriol but not estradiol. It was concluded that, in the UNX model of spontaneous renal damage, glomerular lesions and glomerular hypertrophy were reduced by estriol but less consistently by estradiol. In parallel, loss of podocytes, evidence of podocyte injury (i.e., desmin expression), and expression of mediator systems of glomerular damage were decreased, pointing to a major renoprotective action of estriol.

Animals↗

Reversal of glomerulosclerosis after high-dose enalapril treatment in subtotally nephrectomized rats.

Interventions to block the renin-angiotensin system (RAS) halt the progression of renal lesions in renal damage models. It has recently also been reported that established glomerulosclerosis can be reversed by pharmacologic blockade of the RAS. It was the aim of this study to confirm that high doses of angiotensin-converting enzyme (ACE) inhibitors reverse established glomerulosclerosis and to extend the findings by providing quantitative information on glomerular geometry, podocytes and other glomerular cells, renal vessels and tubulointerstitial tissue. Male Sprague Dawley rats were subjected to subtotal surgical renal ablation (SNX) (n = 27) or sham operation (n = 31) and fed using a pair-feeding protocol. Eight weeks after surgery, rats were either sacrificed or allocated to two arms: enalapril treatment (48 mg/kg body wt per day administered in the drinking fluid for 4 wk) or no treatment. Renal morphology was evaluated after 8 or 12 wk, respectively, by stereology in tissue fixed by pressure-controlled perfusion. Both systolic BP and albumin excretion rate were significantly higher in SNX compared with sham-operated controls. They were significantly reduced in SNX after delayed enalapril treatment. The glomerulosclerosis (GSI), tubulointerstitial (TII), and vascular (VI) damage indices were significantly higher in all SNX groups than in sham-operated controls. At the end of the experiment (12 wk after SNX) GSI, TII, and VI were significantly lower in SNX with delayed enalapril treatment (0.77 +/- 0.18, 0.63 +/- 0.19 and 0.43 +/- 0.16, respectively) compared with untreated SNX (1.64 +/- 0.14, 1.16 +/- 0.34 and 0.67 +/- 0.29, respectively). GSI, TII, and VI were also significantly lower in SNX with delayed enalapril treatment compared with SNX sacrificed without treatment 8 wk after SNX. The same was true for glomerular volume. The number of podocytes was not affected by SNX, but podocyte volume was increased. Both indices remained unaffected by treatment. The numbers of cells within the mesangium and endothelial cells per glomerulus were significantly lower in SNX after delayed enalapril treatment compared with untreated SNX. These results strongly suggest regression of preexisting lesions, i.e., glomerular, tubular, and vascular remodeling as well as reversal of glomerular hypertrophy by ACE inhibitor treatment. The study confirms that high-dose ACE inhibitor treatment causes partial reversal of glomerular as well as interstitial lesions in subtotally nephrectomized rats.

Angiotensin-Converting Enzyme Inhibitors↗