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Biomedical subjects

V Mann

Publications and source records attributed to V Mann.

At least 19 recordsLinked to original sources

Validation of a 7-point Global Overall Symptom scale to measure the severity of dyspepsia symptoms in clinical trials.

BACKGROUND: Currently there is no consensus on the optimal method to measure the severity of dyspepsia symptoms in clinical trials. AIM: To validate the 7-point Global Overall Symptom scale. METHODS: The Global Overall Symptom scale uses a 7-point Likert scale ranging from 1 = no problem to 7 = a very severe problem. Validation was performed in two randomized-controlled trials (n = 1121 and 512). Construct validity: Global Overall Symptom was compared with the Quality of Life in Reflux And Dyspepsia, Gastrointestinal Symptom Rating Scale, Reflux Disease Questionnaire and 10 specific symptoms using Spearman correlation coefficients. Test-retest reliability: The Intraclass Correlation Coefficient was calculated for patients with stable dyspepsia defined by no change in Overall Treatment Effect score over two visits. Responsiveness: effect size and standardized response mean were also calculated. RESULTS: Construct validity: Change in Global Overall Symptom score correlated significantly with Quality of Life for Reflux And Dyspepsia, Gastrointestinal Symptom Rating Scale, Reflux Disease Questionnaire and specific symptoms (all P < 0.0002). Reliability: The Intraclass Correlation Coefficient was 0.62 (n = 205) and 0.42 (n = 270). Responsiveness: There was a positive correlation between change in Global Overall Symptom and change in symptom severity. The effect size and standardized response mean were 1.1 and 2.1, respectively. CONCLUSION: The Global Overall Symptom scale is a simple, valid outcome measure for dyspepsia treatment trials.

Adolescent↗

Association of COLIA1 Sp1 alleles with defective bone nodule formation in vitro and abnormal bone mineralization in vivo.

Previous work identified a G/T polymorphism affecting a Sp1 binding site in a regulatory region of the COLIA1 gene that predisposes to osteoporotic fractures by affecting bone strength through mechanisms that are partly independent of differences in bone mineral density (BMD). To clarify the mechanisms by which COLIA1 Sp1 alleles influence bone strength we used quantitative backscattered electron imaging (qBEI) to characterize bone mineralization in biopsy samples from subjects of different COLIA1 genotype and studied the ability of osteoblast-like cells cultured from subjects of different genotypes to form mineralized bone nodules. The qBEI analysis showed a significant (P = 0.014) reduction in mineralization in bone biopsies from G/T heterozygotes (n = 6) compared with G/G homozygotes (n = 7) and a significant increase in heterogeneity of mineralization (P = 0.017). The in vitro studies showed that osteoblasts derived from G/T heterozygotes (n = 5) were significantly less able to produce mineralized bone nodules than G/G homozygotes (n = 10) at all time-points examined (P < 0.0001). We conclude that carriage of the COLIA1 Sp1 "T" allele is associated with an impaired ability of osteoblast-like cells to form mineralized bone nodules in vitro and with abnormalities of bone mineralization in vivo. This suggests that the increased bone fragility in carriers of the COLIA1 Sp1 allele may result in part from defects in bone mineralization.

Aged↗

[Human biomonitoring investigations of organochlorine compounds -- PCB, DDE, HCB, beta- and gamma-HCH, PCDD/PCDF, Dioxin-like PCB's and polybrominated biphenyl ethers].

Although PCB and PCB-containing materials are not processed for a long time, PCB is under discussion again and again caused by the pollution of indoor environments. To objectify the discussion, the dates of the PCB-biomonitoring, the organochlorine-compounds (DDE, HCB, beta-/gamma -HCH, PCDD/PCDF) and the polybrominated biphenyl ethers concerning the investigations within the project "Sentinel Health Departments" in Baden-Wurttemberg are represented. Additionally results from children from Kazakhstan (Aral-Sea area) and from teachers which are working in PCB polluted schools as well as from a long term investigated test person are reported. Blood concentrations of the following compounds decreased from 1996/97 to 2002/03: the sum of the concentration of PCB 138,153 and 180 decreased from 0.46 microg/L to 0.20 microg/L, DDE from 0.32 microg/L to 0.17 microg/, HCB from 0.20 microg/L to 0.08 microg/L, beta-HCH below the level of detection, I-TEQ NATO to 4.8 pg/g blood fat, TEQ WHO (without PCB) to 5.5 pg/g blood fat, PCB 126 to 18,8,pg/g blood fat and PCB 169 to 12.8 pg/g blood fat. The influence of breast feeding and the gender on the level of the pollution is conspicious. No local correlations were found in Baden-Wurttemberg, but they were found in comparison with the results of Kazakhstan (Aral-Sea area). The difficulty to produce time series while the analyzing pollutants are more and more decreasing, as well as the change of the calculation base of the summation of parameters like I-TEQ NATO to TEQ WHO are discussed.

Adult↗

Fas/CD95 is associated with glucocorticoid-induced osteocyte apoptosis.

Prolonged use of glucocorticoids is associated with decreased bone formation, increased resorption and osteonecrosis, through direct and indirect effects on the activity and viability of bone effector cells, osteoblasts and osteoclasts, and osteocytes. This study has investigated molecular pathways implicated in Dexamethasone-induced apoptosis of osteocytes, using a cell line and primary chicken cells. MLO-Y4 osteocytes were pre-treated with several bisphosphonates representing a range of anti-resorptive activities and conformation/structure relationships, and were subsequently challenged with Dexamethasone. Apoptotic cells were detected at various times after treatment using morphological and biochemical criteria. Dex was shown to induce apoptosis associated with the Fas/CD95 death receptor and in a caspase 8 dependent manner. The apoptotic response was inhibited by all variants of the BP molecules, including those with reduced anti-resorptive activity, indicating that Dex-induced apoptosis is independent of anti-osteoclastic activity. Dex-induced apoptosis was associated with a transient increase in phosphorylated ERK 1/2 and was blocked by the ERK inhibitor UO126. In addition, both UO126 and BPs decreased localization of Fas to the cell membrane. ERK activation by PMA did not induce death or Fas upregulation, suggesting that Fas may be important for the induction of apoptosis and the existence of an additional factor activated by Dex which enables the cooperation between the Dex-activated ERK and Fas pathways, during apoptosis of osteocytes. Furthermore, upregulation of death and Fas was not accompanied by upregulation of FasL, pointing to the possible existence of FasL-independent Fas-associated death in these cells.

Analysis of Variance↗

Meta-analysis of COL1A1 Sp1 polymorphism in relation to bone mineral density and osteoporotic fracture.

Genetic factors play an important role in the pathogenesis of osteoporosis and several candidate gene polymorphisms have been implicated in the regulation of this process. One of the most widely studied is the Sp1 binding site polymorphism in the COL1A1 gene. This polymorphism has been associated with BMD and osteoporotic fracture in several studies, but the data from different studies have been conflicting. Here we have attempted to clarify the association between COL1A1 Sp1 alleles, BMD, and osteoporotic fracture by conducting a meta-analysis of 26 published studies including 7849 participants. Under a fixed effects model, BMD values at the lumbar spine (6800 subjects) were significantly lower in the "Ss" genotype group when compared with "SS" homozygotes (standardized mean difference = 0.131 [95% CI, 0.06,0.16], P = 0.00005) but the difference was not significant for the "ss" comparison (0.09 [-0.03,0.21], P = 0.13). At the femoral neck (6750 subjects) BMD values were lower in the "Ss" genotype (0.14 [0.08,0.19], P < 0.00001) and lower still in the "ss" genotype group (0.19 [0.07,0.31], P = 0.001). Similar results were found when the data were analyzed under a random effects model. Analysis of fracture data (6961 subjects) showed an increased odds ratio for any fracture in "Ss" subjects (1.26 [95% CI 1.09,1.46], P = 0.002) and an even greater increase in "ss" subjects (1.78 [1.30,2.43], P = 0.0003). Subgroup analysis showed that increased risk was largely attributable to vertebral fracture where the odds ratio was 1.37 [1.15,1.64] for "Ss" (P = 0.0004) and 2.48 [1.69,3.65] for "ss" (P < 0.00001). The risk of nonvertebral fracture was not increased in relation to the COL1A1 genotype, although power to detect an effect was limited by the fact that fewer studies had analyzed nonvertebral fracture. We conclude that the COL1A1 Sp1 alleles are associated with a modest reduction in BMD and a significant increase in risk of osteoporotic fracture, particularly vertebral fracture.

Bone Density↗

Inhalational induction of anaesthesia with 8% sevoflurane in children: conditions for endotracheal intubation and side-effects.

BACKGROUND AND OBJECTIVE: This study was designed to assess the conditions for endotracheal intubation or insertion of a laryngeal mask airway following an inhalational induction using 8% sevoflurane and nitrous oxide without the use of muscle relaxants or opioids. METHODS: There were two groups: 30 children had endotracheal intubation and 30 children had a laryngeal mask airway inserted. Induction of anaesthesia was accomplished using an inspiratory concentration of sevoflurane 8% in a nitrous oxide and oxygen mixture. After an end-expiratory concentration of sevoflurane of at least 4% had been reached, when the pupils were miotic and centred, the trachea was intubated or a laryngeal mask inserted. The time to loss of consciousness and successful airway management was recorded. Jaw relaxation, movements, visibility, and position of the vocal cords and vital parameters were monitored. RESULTS: Jaw relaxation was complete in all children. The vocal cords were completely visible in all patients of the tracheal intubation group, whereas vocal cord relaxation was incomplete in five children. Nevertheless, all children had an atraumatic intubation or insertion of the laryngeal mask without the use of a muscle relaxant. Vital signs were stable in both groups. There were no cases of restlessness and/or postoperative shivering. Four patients in the endotracheal group (13.3%) were nauseous and three (10%) vomited, while two children (6.6%) in the laryngeal mask group experienced nausea and vomiting. CONCLUSIONS: Induction with sevoflurane in nitrous oxide and oxygen leads to fast loss of consciousness and provides ideal conditions for managing the airway without supplemental opioids or muscle relaxants. Furthermore, sevoflurane using this technique was very well tolerated, indicated by high haemodynamic stability and a reduced rate of postoperative restlessness, shivering, nausea and vomiting.

Anesthesia, Inhalation↗

[Changes in the cytokine network through escalating SIRS after heart surgery].

Changes in the Cytokine Network Through Escalating SIRS After Heart Surgery. Cardiopulmonary bypass is associated with an injury that may cause pathophysiological changes in form of systemic inflammatory response syndrome (SIRS) or multiple organ dysfunction syndrome (MODS). There is a lot of information about the immunologic alterations in patients undergoing cardiopulmonary bypass, but only little is known about the expression of cytokines in patients with severe SIRS or MODS following cardiovascular surgery. In the present study, we investigated the inflammatory response of patients with an escalating SIRS following open heart surgery. Plasma levels of cytokines (IL-1beta, IL-6, IL-8, IL-10, IL-12, IL-18, GM-CSF and TGF-beta) were measured at the first four postoperative days in 12 adult male patients with severe SIRS (SIRS-group), and 15 patients with uncomplicated course (control-group) following myocardial revascularization. All cytokines (except IL-1beta) were significantly elevated in SIRS-patients, the analysis of differences between the survivors and non-survivors within the SIRS-group showed dramatically elevated levels of IL-8 and IL-18 in non-survivors. From the results of our investigation we can conclude that monitoring of immunologic parameters, e.g. IL-8 and/or IL-18 may be helpful for the early detection and prognosis of high-risk patients with severe SIRS and MODS following cardiac surgery.

Aged↗

A COL1A1 Sp1 binding site polymorphism predisposes to osteoporotic fracture by affecting bone density and quality.

Osteoporosis is a common disease with a strong genetic component. We previously described a polymorphic Sp1 binding site in the COL1A1 gene that has been associated with osteoporosis in several populations. Here we explore the molecular mechanisms underlying this association. A meta-analysis showed significant associations between COL1A1 "s" alleles and bone mineral density (BMD), body mass index (BMI), and osteoporotic fractures. The association with fracture was stronger than expected on the basis of the observed differences in BMD and BMI, suggesting an additional effect on bone strength. Gel shift assays showed increased binding affinity of the "s" allele for Sp1 protein, and primary RNA transcripts derived from the "s" allele were approximately three times more abundant than "S" allele--derived transcripts in "Ss" heterozygotes. Collagen produced from osteoblasts cultured from "Ss" heterozygotes had an increased ratio of alpha 1(I) protein relative to alpha 2(I), and this was accompanied by an increased ratio of COL1A1 mRNA relative to COL1A2. Finally, the yield strength of bone derived from "Ss" individuals was reduced when compared with bone derived from "SS" subjects. We conclude that the COL1A1 Sp1 polymorphism is a functional genetic variant that predisposes to osteoporosis by complex mechanisms involving changes in bone mass and bone quality.

Aged↗

Metabolic engineering of astaxanthin production in tobacco flowers.

Using metabolic engineering, we have modified the carotenoid biosynthesis pathway in tobacco (Nicotiana tabacum) to produce astaxanthin, a red pigment of considerable economic value. To alter the carotenoid pathway in chromoplasts of higher plants, the cDNA of the gene CrtO from the alga Haematococcus pluvialis, encoding beta-carotene ketolase, was transferred to tobacco under the regulation of the tomato Pds (phytoene desaturase) promoter. The transit peptide of PDS from tomato was used to target the CRTO polypeptide to the plastids. Chromoplasts in the nectary tissue of transgenic plants accumulated (3S,3'S) astaxanthin and other ketocarotenoids, changing the color of the nectary from yellow to red. This accomplishment demonstrates that plants can be used as a source of novel carotenoid pigments such as astaxanthin. The procedures described in this work can serve as a platform technology for future genetic manipulations of pigmentation of fruits and flowers of horticultural and floricultural importance.

Bacterial Proteins↗

Recombinant chimeric proteins generated from conserved regions of Plasmodium falciparum merozoite surface protein 2 generate antiparasite humoral responses in mice.

The merozoite surface protein 2 of P. falciparum is highly polymorphic in nature, but has regions of almost complete conservation at its N- and C-termini. We produced a chimeric recombinant protein comprising these regions only (hereafter termed NC). Mice immunized with the NC antigen produce antibodies at levels comparable to those immunized with 1624, a full-length recombinant protein representing MSP2 from P. falciparum. Antisera raised against NC recognized P. falciparum schizonts by IFA and a P. falciparum protein of Mr 45 kDa by Western blot. However, antibody specificities were observed to differ between anti-NC and anti-1624 sera, and this resulted in differences in parasite recognition, despite similar levels of antibodies having been produced. The response to the NC antigen was also shown to be restricted in some mice (H2-d), but this was overcome by including appropriate T-cell help, which was accomplished by creating recombinant protein chimeras that contained NC and T-helper epitopes from Tetanus toxoid, or MSP119 from P. berghei.

Adolescent↗

Laparoscopic subtotal cholecystectomy: a review of 56 procedures.

BACKGROUND AND PURPOSE: The essential surgical steps in laparoscopic cholecystectomy remain similar to those of open cholecystectomy. Positive identification of the biliary anatomy, safe clipping or ligature of the cystic duct and artery, and dissection of the gallbladder from the liver bed form the basis of cholecystectomy. Subtotal cholecystectomy is a definitive and safe operation under certain adverse conditions intraoperatively for dissection of the gallbladder from the liver bed. We reviewed our experience with laparoscopic cholecystectomy over a 2-year period between June 1996 and May 1998, when 1,680 operations were performed. The objective was to analyze the pathology, review surgical procedures, and trace the outcome of laparoscopic subtotal cholecystectomy. PATIENTS AND METHODS: In 56 of 1,680 patients, laparoscopic subtotal cholecystectomy was performed, which constituted 3.33% of the laparoscopic cholecystectomies performed at our institution. Dense fibrosis and adhesions were present in 32 patients; 12 patients had Mirizzi syndrome, 6 patients had a sessile gallbladder, and 6 patients had a gangrenous gallbladder. The Endo-GIA 30 stapler was used in 40 patients, sequential clips were used in 9 patients, and a suture for stump closure was used in 5 patients. A subhepatic drain was inserted in 50 patients. RESULTS: Two conversions to open surgery were needed because of gangrene of the gall bladder wall and one conversion as a result of continued bleeding from the cystic artery after application of the Endo-GIA 30 stapler. The mean postoperative stay in hospital was 2.5 days. One patient had a solitary bile duct calculus extracted at endoscopic retrograde cholangiopancreatography 3 months after surgery. Three patients had biliary drainage that lasted for a week, and four patients had epigastric port-site infections that resolved with antibiotics, dressings and postural drainage. CONCLUSION: Laparoscopic subtotal cholecystectomy is safe, feasible, and effective and may help prevent conversion to open surgery in carefully selected patients with difficult cholecystectomies.

Cholecystectomy, Laparoscopic↗

Laparoscopic ventral hernia repair.

PURPOSE: A retrospective study was carried out of patients who underwent laparoscopic ventral abdominal wall hernia repair (excluding groin hernias) between January 1994 and January 1999. PATIENTS AND METHODS: Laparoscopic ventral hernia repair was performed on 202 patients for defects ranging from 1.5 cm to 12 cm in diameter. Of these, 35 patients had multiple hernial defects. After reduction of the hernial contents and adhesiolysis, a polypropylene mesh was used intraperitoneally in all patients, such that there was a margin of at least 3 cm from the edge of the defect as well as the previous scar. RESULTS: The mean operating time decreased from 90 minutes in the initial 3 years to 50 minutes in the last 2 years. Postoperatively, the mean hospital stay was 1.8 days. Patients complained of somatic abdominal pain at the site of mesh insertion for a mean of 7 days. There were two postoperative hernia recurrences at a mean follow-up of 2.9 years. The incidence of seroma formation postoperatively was 32% in the first 3 years but declined to 18% subsequently with postoperative abdominal-wall pressure dressings. There were no postoperative sequelae related to bowel adhesions. Negligible wound sepsis (superficial wound infection in five patients), decreased morbidity, and all the other advantages of a minimally invasive surgical approach were evident in this group of patients. CONCLUSION: These promising early results need to be confirmed by a prospective controlled trial, especially recurrence rates and incidence of postoperative adhesions.

Adult↗

The management of Mirizzi syndrome in the laparoscopic era.

Mirizzi syndrome is a rare complication of long-standing gallstone disease resulting in obstructive jaundice. Careful perioperative management is of utmost importance because of an increased risk of bile duct injury intraoperatively. Experience with Mirizzi syndrome over a period of 3 years, from January 1996 to December 1998, was reviewed. Twenty-seven patients were operated upon, which constituted 0.9% of 2840 patients who underwent laparoscopic cholecystectomy in the authors' department. There were 12 patients with Mirizzi type I syndrome and 15 patients with Mirizzi type II syndrome, according to McSherry classification. Six (22%) conversions were reported, all because of unclear anatomy and inherent limitations of the laparoscopic approach. For the remaining 21 (78%) patients, the procedure was completed laparoscopically. No bilioenteric anastomosis was required. A preoperative stent insertion in the common bile duct (CBD) during endoscopic retrograde cholangiopancreatography (ERCP) enabled us to achieve primary closure of CBD in every case. There was no perioperative mortality, and patients remained well for an average 2.1-year follow-up. It is highly desirable to have a preoperative diagnosis of Mirizzi syndrome, and the laparoscopic approach is not a contraindication in specialized centers. Our current management protocol to treat Mirizzi syndrome consists of a high degree of suspicion at ERCP, with stenting preoperatively and a complete stone clearance with subtotal cholecystectomy intraoperatively.

Cholangiopancreatography, Endoscopic Retrograde↗

Complete penoscrotal transposition and associated malformations.

Complete transposition of the penis and scrotum, or prepenile scrotum, is an uncommon congenital malformation. Concomitant genitourinary abnormalities, often life-threatening in nature, are frequently seen, and major malformations involving other organ systems may also be present. We report a newborn in whom complete penoscrotal transposition was accompanied by urethral atresia and radial dysgenesis.

Abnormalities, Multiple↗

Plasma levels of selectins and interleukins in cardiovascular surgery using cardiopulmonary bypass.

BACKGROUND: Cardiovascular surgery with cardiopulmonary bypass (CPB) leads to activation of a variety of inflammatory pathways, including the release of cytokines and selectins. METHODS: In 20 patients undergoing elective coronary artery bypass grafting, plasma levels of interleukins IL-2, -6, -8, -10, -12 and of P-, E-, and L-selectins were measured at eight time points before, during, and after CPB using a standardized ELISA technique. RESULTS: IL-2 plasma levels decreased significantly after the start of CPB and remained low until the second postoperative day. IL-6 and IL-8 levels increased significantly after weaning off CPB, with mean peak values six hours postoperatively. Very low IL-10 plasma levels were detectable preoperatively. They remained low during CPB and peaked significantly after weaning off CPB until skin closure. The IL-12 levels decreased after weaning off CPB (p < 0.05) until 6 hours postoperatively. The plasma levels of P-selectin showed no alterations, but concentrations of E- and L-selectin decreased after the start of CPB (p < 0.05). There were no adverse postoperative events. CONCLUSIONS: The results of our study demonstrate a dysregulation of cytokine and selectin production during and up to 48 h after CPB, which may be a "normal" stress reaction to CPB.

Adult↗

Endoscopic neck surgery: expanding horizons.

There have now been several attempts at neck exploration using minimally invasive surgery. These encouraging reports paved the way for the authors to attempt endoscopic neck surgery. Having the necessary technical expertise in minimally invasive surgery with an experience of more than 6000 laparoscopic procedures, they attempted endoscopic parathyroidectomy in three patients with hyperparathyroidism. Of these, two had a hyperfunctioning adenoma and one had parathyroid hyperplasia. The hyperfunctioning tissue was accurately localized using a 99Tc-thallium subtraction scan. It was possible to localize and dissect the parathyroid tissue in two of the three patients. One patient required an open hemithyroidectomy before the adenoma could be localized and excised. The total operative time averaged 113 min. The working space was found to be adequate provided good hemostasis was maintained. The magnification proved excellent in identifying and defining important neck structures. Sufficient mobilization of the lateral thyroid lobe for access to the tracheoesophageal groove was found to be technically very difficult. No subcutaneous emphysema was observed beyond the neck region, and none lasted beyond 24 h. Cosmesis was acceptable to both the patient and the surgeon.

Adenoma↗

Lexical familiarity and English-language experience affect Japanese adults' perception of / / and /l/.

This study assessed the influence of subjective lexical familiarity and English-language experience on Japanese adults' accuracy in identifying singleton word-initial tokens of English [symbol: see text] and /l/. The inexperienced Japanese (IJ) subjects had lived in the U.S. for 2 years, whereas the experienced Japanese (EJ) subjects had lived there for 21 years, on average. The native Japanese subjects correctly identified English [symbol: see text] and /l/ tokens less often than did a group of native English (NE) subjects, but they did not differ from the NE subjects in identifying the control consonants /w/ and /d/. The NE subjects, who were at ceiling, showed no effect of subjective lexical familiarity. However, the EJ and IJ subjects correctly identified [symbol: see text] and /l/ tokens more often in words that were more familiar than their minimal pairs than in words that were less familiar than their minimal pairs. The EJ subjects identified liquids more often than did the IJ subjects, but usually less often than the NE subjects. However, the EJ subjects managed to identify [symbol: see text] tokens at rates comparable to the NE subjects' rates in words that wer matched in subjective familiarity to their minimal pair (experiment 1), and when identifying [symbol: see text] tokens that had been edited out of their original word or nonword context (experiment 2).

Humans↗