Biomedical subjects

M Schreiber

Publications and source records attributed to M Schreiber.

At least 37 records · Page 2Linked to original sources

PubMed2001

Low dose clonidine premedication accentuates the hyperglycemic response to surgery.

PURPOSE: To investigate the influence of low dose clonidine premedication on perioperative glucose homeostasis. METHODS: Sixteen patients undergoing abdominal hysterectomy for benign uterine myoma were randomly assigned to receive either iv clonidine (1 microg x kg(-1)) 30 min before induction of general anesthesia (clonidine, n=8) or saline (control, n=8). Plasma concentrations of glucose, insulin, cortisol, epinephrine and norepinephrine were measured before, during and two hours after surgery. At the same time heart rate, mean arterial pressure and cardiac output were recorded. RESULTS: In both groups, glucose concentrations significantly increased during and after surgery. Intraoperative glucose plasma concentration in the clonidine group was higher than in the control group (clonidine: 6.8 +/- 0.6 mmol x L(-1) vs control: 5.7 +/- 0.8 mmol x L(-1), P < 0.05). This was accompanied by a lower insulin plasma concentration (clonidine: 3.9 +/- 1.9 microU x mL(-1) vs control: 6.5 +/- 2.8 microU x mL(-1), P <0.05). Heart rate, mean arterial pressure and cardiac output remained unchanged throughout the study period without any differences between the groups. While norepinephrine plasma concentrations increased in the control group only (P <0.05), the plasma concentrations of epinephrine and cortisol increased in both groups (P <0.05). Clonidine significantly attenuated the cortisol response as reflected by lower intra- and postoperative cortisol plasma concentrations than in the control group (P <0.05). CONCLUSION: Premedication with clonidine 1 microg x kg(-1) accentuates the hyperglycemic response to lower abdominal surgery caused by the decrease in insulin plasma concentrations.

Adult↗

PubMed2001

Laparoscopic-assisted vaginal hysterectomy and the hyperglycemic response to surgery: an observational study.

PURPOSE: To test the hypothesis that laparoscopic-assisted vaginal hysterectomy (LAVH) attenuates the hyperglycemic response to surgery when compared to vaginal hysterectomy (VH). METHODS: Fourteen patients received either LAVH (n=7) or VH (n=7). Whole body glucose production was measured before and three hours after surgery using [6.6-2H2] glucose. Before, during and after the operation, plasma concentrations of glucose, insulin, glucagon, cortisol, epinephrine and norepinephrine were determined. RESULTS: Plasma glucose concentration increased in both groups during and after surgery showing a significantly higher value after VH than after LAVH (VH: 8.3 +/- 1.4 mmol x L(-1); LAVH: 6.6 +/- 0.9 mmol x L(-1), P <0.05). The postoperative increase in glucose production was comparable in both groups. While plasma concentrations of insulin and glucagon remained unchanged, intra- and postoperative plasma cortisol concentrations were significantly higher in the VH group than in the LAVH group. Plasma catecholamine concentrations significantly increased after both types of surgery to the same extent. CONCLUSION: In this observational study, LAVH appears to blunt the hyperglycemic and cortisol response to surgery when compared to VH.

Adult↗

PubMed2001

Key regulatory transcription factors involved in placental trophoblast development--a review.

Specification of the trophoblast cell lineage comprising the outermost epithelial cell layer of the blastocyst occurs early in development and is a prerequisite for implantation of the embryo and subsequent formation of the placenta, a multifunctional organ which is indispensable for the proper development of the fetus. Trophoblast stem cells of the placenta give rise to distinct highly differentiated trophoblast subtypes which build the functional units of the organ. These specialized cells assure anchorage of the embryo to the mother, establishing a vascular connection transporting nutrients and gases and expression of hormones that are required for the successful progression of pregnancy. Developmental processes of the trophoblast occur in a spatially and temporally highly organized manner. Despite these facts, little is known on the key regulatory factors which commit and differentiate trophoblast cells in humans. Recent studies in mice, however, provided evidence that various cell-type specific transcription factors play crucial roles in the developmental programme of the trophoblast. In this review we will focus on the function of these major regulatory factors in murine trophoblast/placental development and discuss the potential role of their homologues in the human system.

Adult↗

PubMed2001

A probabilistic method for identifying start codons in bacterial genomes.

As the pace of genome sequencing has accelerated, the need for highly accurate gene prediction systems has grown. Computational systems for identifying genes in prokaryotic genomes have sensitivities of 98-99% or higher (Delcher et al., Nucleic Acids Res., 27, 4636-4641, 1999). These accuracy figures are calculated by comparing the locations of verified stop codons to the predictions. Determining the accuracy of start codon prediction is more problematic, however, due to the relatively small number of start sites that have been confirmed by independent, non-computational methods. Nonetheless, the accuracy of gene finders at predicting the exact gene boundaries at both the 5' and 3' ends of genes is of critical importance for microbial genome annotation, especially in light of the important signaling information that is sometimes found on the 5' end of a protein coding region. In this paper we propose a probabilistic method to improve the accuracy of gene identification systems at finding precise translation start sites. The new system, RBSfinder, is tested on a validated set of genes from Escherichia coli, for which it improves the accuracy of start site locations predicted by computational gene finding systems from the range 67-77% to 90% correct.

Algorithms↗

PubMed2001

Loss of N-linked glycans in the V3-loop region of gp120 is correlated to an enhanced infectivity of HIV-1.

We describe mutants of human immunodeficiency virus type-1 (HIV-1) strain NL4-3, which are lacking the thirteenth, fifteenth, or seventeenth sites for N-linked glycosylation (g13, g15, g17) of the envelope protein gp120. All three sites are located within the hypervariable V3 loop region of gp120. Those mutants lacking carbohydrates g15 or combinations of g15/g17 showed markedly higher infectivity for GHOST cells (human osteosarcoma cells) expressing CXCR4 (GHOST-X4), compared to the fully glycosylated NL4-3 wild type virus. In addition, these mutants could also infect cells which exhibits low background expression of CXCR4, corresponding to <10% of that observed for GHOST-X4 cells. In addition to the enhanced infectivity observed, mutants lacking g15 and g17 showed increased resistance to inhibition by SDF-1, the natural ligand of CXCR4. Thus, loss of the oligosaccharides g15 and g17 in the V3 region of gp120 markedly influences CXCR4-specific infection.

Amino Acid Sequence↗

PubMed2001

A simple, efficient and inexpensive program for preventing prematurity.

Prevention of prematurity and of low birth weight is--because of the associated increased risk of mortality and morbidity--one of the most urgent tasks of perinatal medicine. Whereas the rate of prematures all over the world does not vary very much (5-10%), the rate of infants born with low birth weight lies between 3.6% and 10% in the industrial countries and between 9.8% and 43% in the developing countries, where the main cause of low birth weight is intrauterine malnutrition. As there are different causes for prematurity and low birth weight, but also because various countries have different resources and have therefore to set their priorities differently, there is no global solution. The situation in each country must be considered individually. However, as far as basic means are available for the majority--such as basic health care, monitoring the nutritional state of the mothers and acting to prevent infectious diseases (malaria in particular can cause prematurity)--determined prevention of prematurity should take the form of screening and the treatment of disturbances of the vaginal milieu or genital infections. This policy can be recommended because one of the most important avoidable causes of prematurity is ascending genital infection (mostly combined with bacterial vaginosis), which very frequently starts with a disturbance of the vaginal milieu and then often takes its course asymptomatically. Regular screening for signs of such a disturbance using vaginal pH-measurements (and if necessary further diagnostics and therapy) makes possible the detection of an "early marker" to prevent prematurity in an effective and inexpensive way. Our prematurity-prevention-program, which has been successful for many years, is based on an anamnestic assessment of prematurity risk, the early detection of warning signs (including regular measurement of the vaginal pH) and, if necessary, the appropriate therapeutic measures. In cases of disturbance of the vaginal milieu, the latter consists of a therapy with lactobacillus preparations or in a combination of lactobacillus preparation with an acidifying therapy which may lead to earlier normalization of the vaginal milieu. In cases of bacterial vaginosis local therapy, for example with metronidazol or clindamycin, is undertaken, and in other infections specific treatment. It is encouraging to note that particularly the rate of the very small prematures is reduced when pregnant patients take part in our self-care-program, measuring their own vaginal pH-value twice a week, and also searching for any other warning signs. In this way in our collective the rate of very small low birth weight infants could be reduced from 7.8% in the immediate previous pregnancy to 1.3%. In a prospective study performed in Erfurt the rate of very early premature births (< 32 + 0 gw) amounted to only 0.3% in contrast to 3.3% in a control group who had not taken part in the self-care activity. According to a differentiated classification of the control group the success of the self-care activity was even clearer: In patients who did not take part because their doctors did not support the self-care activity, the rate of very early premature births amounted to 4.1%. In patients who did not take part in the self-care activity, but who were in the care of doctors who were interested and had taken part in the prevention-program, the rate was 2.2%; in the group with active participation in the self-care activity it was only 0.3%. To date measurement of the vaginal pH-value was performed intravaginally using either indicator strips or pH-measuring test gloves. A short time ago we developed a panty liner coated with an indicator strip, which enables reading of the pH-value by just checking the indicator on the panty liner. First results with this panty liner are very promising.

Abortion, Spontaneous↗

PubMed2000

The mammalian UV response: c-Jun induction is required for exit from p53-imposed growth arrest.

The mammalian UV response results in rapid and dramatic induction of c-jun. Induction of a protooncogene, normally involved in mitogenic responses, by a genotoxic agent that causes growth arrest seems paradoxical. We now provide an explanation for the role of c-Jun in the UV response of mouse fibroblasts. c-Jun is necessary for cell-cycle reentry of UV-irradiated cells, but does not participate in the response to ionizing radiation. Cells lacking c-Jun undergo prolonged cell-cycle arrest, but resist apoptosis, whereas cells that express c-Jun constitutively do not arrest and undergo apoptosis. This function of c-Jun is exerted through negative regulation of p53 association with the p21 promoter. Cells lacking c-Jun exhibit prolonged p21 induction, whereas constitutive c-Jun inhibits UV-mediated p21 induction.

Animals↗

PubMed2000

Prospective analysis of the value of 24-hour ambulatory blood pressure on renal function after kidney transplantation.

BACKGROUND: No prospective study has been performed to determine the prognostic value of 24-hr ambulatory blood pressure (24-hr ABP) versus casual blood pressure (CBP) in patients after kidney transplantation. We have addressed this issue by analyzing renal graft function in patients for the first 5 years after transplantation. METHODS: The 24-hr ABP (SpaceLabs 90207) was monitored 6 and 18 months after transplantation in 46 renal transplant recipients without any acute episodes of rejection. Combined study endpoints were death of patients, need for dialysis, second transplantation, and doubling of serum creatinine. RESULTS: Six months after transplantation systolic and diastolic 24-hr ABP correlated with serum creatinine (r=0.41, P=0.005 and r=0.37, P<0.01, respectively) although CBP did not. Divided into tertiles according to average 24-hr ABP (lower tertile: < or =91 mmHg; middle tertile: 92-97 mmHg; upper tertile: > or =98 mmHg) serum creatinine significantly differed between the three groups (1.26 +/- 0.38 vs. 1.32 +/- 0.25 vs. 1.65 +/- 0.39 mg/dl, respectively; analysis of variance, P< 0.01). Confounding factors of renal function such as age, body weight, cold and warm ischemic time, cytomegaly virus status, methylprednisone and cyclosporine dosages, cyclosporine concentrations, as well as concomitant antihypertensive medication did not differ among the three groups. In the long-term follow-up (5 years), combined endpoints were reached in 3 of 15 of the lower tertile group, in 3 of 15 of the median tertile group, and in 8 of 16 of the upper tertile group (log-rank test, P<0.01). No relation to long-term out come was found when patients were stratified according to their CBP. CONCLUSION: In our small but homogenous study cohort 24-hr ABP was more closely related to renal function in patients after transplantation than CBP suggesting that 24-hr ABP is superior for evaluation of hypertension-related renal graft dysfunction.

Adult↗

PubMed2000

[Lesions of peripheral structures of cadaver fingers caused by Kirschner wires].

Fractures of the hand skeleton are common injuries. These are or are associated with phalangeal fractures. Kirschner wires can be used for osteosynthesis, but can cause lesions of peripheral finger structures. The aim of our study was to record the incidence of lesions in peripheral structures of the fingers caused by retrograde crossed inserted Kirschner wires of 1.0, 1.25, 1.4 and 1.6 mm diameter into the middle and proximal phalanges of the long fingers and the proximal phalanx of the thumb of 120 fresh cadaver hands. We found an increase of insertion attempt frequency and an increasing number of lesions with increasing Kirschner wire diameter. Because of these findings Kirschner wires of 1.0 or 1.25 mm diameter should be preferred to prevent the peripheral functional finger structures.

Bone Wires↗

PubMed2000

Prognostic value of the Banff classification.

UNLABELLED: We evaluated whether classification of renal allograft biopsies according to the Banff schema is a predictive parameter for graft survival. All patients who received renal transplants between 1980 and 1994 at the University of Erlangen-Nuremberg (n = 1141) were included. Patients who had undergone a renal biopsy (n = 306) were divided into groups according to the Banff classification. We observed a correlation (P < 0.05) between biopsy findings and the following patient characteristics: donor/recipient age, donor/recipient gender, panel reactive antibodies, maintenance immunosuppression, and primary renal disease. Compared to patients who did not undergo renal biopsy (55.9%), 5-year graft survival was reduced in patients with moderate acute rejection defined by tubulitis (20.6%, P = 0.03) or arteritis (0%; P < 0.0001) and in patients with severe acute rejection (24.4%, P < 0.0001). CONCLUSIONS: (1). The Banff classification is a predictive parameter for renal allograft survival. (2). Certain characteristics predispose patients to certain biopsy findings.

Adult↗

PubMed2000

Prolonged use of intraluminal arterial shunts without systemic anticoagulation.

BACKGROUND: Temporary arterial shunts maintain perfusion while surgeons postpone arterial repairs. The common indications are combined orthopedic and vascular injuries and damage control. The duration of patency and the need for systemic anticoagulation remain in question. We examined our experience for answers. METHODS: We searched for patients who had temporary arterial shunts and collected the following: mechanism, artery injured, shunt time, blood loss and transfusions, injury severity score (ISS,) mangled extremity severity score (MESS,) and anticoagulation. RESULTS: Of 19 patients, 10 had shunts for damage control (group 1,) and 9, for orthopedic/vascular injuries (group 2.) group 1 had significantly higher shunt time, mortality, ISS, and MESS. Shunt time ranged from 47 to 3,130 minutes (52 hours.) Two patients, 1 in each group, required amputations. CONCLUSION: Temporary arterial shunts can be use for combined orthopedic and vascular injuries and for damage control. Shunts can stay open for 52 hours without systemic anticoagulation.

Adolescent↗

PubMed2000

Age-matching in renal transplantation.

BACKGROUND: So far, the combined influence of donor age and recipient age on renal allograft survival has not been investigated sufficiently. In this retrospective single-centre study we analysed whether the influence of donor age and recipient age on renal allograft survival are dependent on each other. METHODS: Data from 1269 cadaveric renal allograft transplantations were evaluated. Paediatric donors (<15 years) and paediatric recipients (<15 years) were excluded. Donors and recipients were divided by age: young donors (yd, </=55 years, n=1093), old donors (od, >55 years, n=176), young recipients (yr, </=55 years, n=1058), and old recipients (or, >55 years, n=211). Functional and actual long-term graft survival (8 years) within the four resulting groups was determined: yd/yr (n=926), yd/or (n=167), od/yr (n=132), and od/or (n=44). RESULTS: Univariate analysis showed that long-term graft survival of both, kidneys from young donors (functional, 66.1 vs 52.2%, P=0.004; actual, 53.3 vs 46.2%, P=0.065) and kidneys from old donors (functional, 68.7 vs 22.5%, P=0.07; actual, 57.1 vs 20.8%, P=0.15) was better in old recipients as compared to young recipients. Multivariate regression analysis revealed that actual graft survival of kidneys from old donors was significantly reduced in young recipients (od/yr) as compared to all other groups (P=0.001; RR, 1. 97; 95% CI, 1.32-2.94). In this group of patients, graft loss was mainly due to acute (33.7%) and chronic (24.0%) rejection. CONCLUSION: Transplantation of kidneys from 'old' donors into 'young' recipients should be avoided, and these kidneys should be given to age-matched recipients.

Acute Disease↗

PubMed2000

Propofol/sufentanil anesthesia suppresses the metabolic and endocrine response during, not after, lower abdominal surgery.

UNLABELLED: We investigated the influence of propofol/sufentanil anesthesia on metabolic and endocrine responses during, and immediately after, lower abdominal surgery. Twenty otherwise healthy patients undergoing abdominal hysterectomy for benign myoma received either continuous infusions of propofol supplemented with sufentanil (0.01 microg. kg(-1). min(-1), n = 10) or enflurane anesthesia (enflurane, n = 10). Plasma concentrations of glucose, lactate, free fatty acids, triglycerides, insulin, glucagon, cortisol, epinephrine, and norepinephrine were measured before, during, and 2 h after surgery. Pre- and postoperative endogenous glucose production (R(a) glucose) was analyzed by an isotope dilution technique by using [6,6-(2)H(2)] glucose. Propofol/sufentanil anesthesia prevented the increase in plasma cortisol and catecholamine concentrations and attenuated the hyperglycemic response during surgery without showing any difference after the operation. Mediated through a higher glucagon/insulin quotient (propofol/sufentanil 15 +/- 7 versus enflurane 8 +/- 4 pg/microU, P < 0.05), the R(a) glucose postoperatively increased more in the propofol/sufentanil than in the enflurane group (propofol/sufentanil 15.6 +/- 2.0 versus enflurane 13.4 +/- 2.2 micromol. kg(-1). min(-1), P < 0.05). IMPLICATIONS: The concept of stress-free anesthesia using propofol combined with sufentanil is valid only during surgery. The metabolic endocrine stress response 2 h after the operation is more pronounced than after inhaled anesthesia.

Anesthesia, Intravenous↗

PubMed2000

c-Jun-dependent CD95-L expression is a rate-limiting step in the induction of apoptosis by alkylating agents.

Mouse 3T3 fibroblasts derived from fetuses lacking c-Jun were used to define an essential role of c-Jun, a main component of the transcription factor AP-1, in the cellular response to the alkylating agent methyl methanesulfonate (MMS). MMS represents the most potent and selective activator of the stress-induced kinases JNK/SAPK and p38, resulting in very efficient induction of c-Jun hyperphosphorylation and c-jun transcription. This agent induced apoptosis with high efficiency in wild-type cells but not in c-jun(-/-) cells. Resistance to apoptosis was accompanied by impaired expression of CD95 ligand (CD95-L), a well-known inducer of apoptosis. The addition of recombinant CD95-L restored apoptosis sensitivity in c-jun(-/-) fibroblasts. MMS-induced apoptosis in wild-type fibroblasts or human lymphocytes was strongly reduced by neutralizing CD95-L antibodies or transdominant negative FADD, confirming the importance of CD95 signalling in MMS-induced apoptosis. The loss-of-function approach in fibroblasts allowed the identification and dissection of c-Jun-dependent and -independent processes upstream or downstream of CD95 activation. We have found that c-Jun can act as a proapoptotic regulator in cells exposed to DNA damage via induction of CD95-L. Once activated, CD95-induced death signalling is not affected by the loss of c-Jun, demonstrating that only the initiation and not the execution of stress-induced apoptosis depends on c-Jun.

Activating Transcription Factor 2↗

PubMed2000

Placental vascularisation requires the AP-1 component fra1.

Fra1 is an immediate-early gene encoding a member of the AP-1 transcription factor family, which has diverse roles in development and oncogenesis. To determine the function of Fra1 in mouse development, the gene was inactivated by gene targeting. Foetuses lacking Fra1 were severely growth retarded and died between E10.0 and E10.5, owing to defects in extra-embryonic tissues. The placental labyrinth layer, where X-gal staining revealed expression of Fra1, was reduced in size and largely avascular, owing to a marked decrease in the number of vascular endothelial cells, as shown by the lack of Flk1 expression. In contrast, the spongiotrophoblast layer was unaffected and expressed the marker genes 4311 (Tpbp) and Flt1. Furthermore, mutant foetuses exhibited yolk-sac defects that may contribute to their growth retardation and lethality. Importantly, when the placental defect was rescued by injection of Fra1(-)(/)(-) ES cells into tetraploid wild-type blastocysts, Fra1(-)(/)(-) pups were obtained that were no longer growth retarded and survived up to 2 days after birth without apparent phenotypic defects. These data indicate that a defect in the extra-embryonic compartment is causal to the observed lethality, and suggest that Fra1 plays a crucial role in establishing normal vascularisation of the placenta.

Animals↗

PubMed2000

Extracorporal therapy with AN69 membranes in combination with ACE inhibition causing severe anaphylactoid reactions: still a current problem?

The negatively charged membrane AN69 is known to evoke anaphylactoid reactions both without and with concomitant ACE inhibition. Underlying reasons are mainly the induction of bradykinin release due to the negatively charged membrane and the reduced degradation of bradykinin due to ACE inhibition. This complication has been reported repeatedly, but anaphylactoid reactions still occur in clinical practice. We recently had to treat two patients who suffered anaphylactoid reactions during extracorporal therapy with an AN69 membrane and simultaneous ACE inhibition. The first incident occurred in a patient on hemodialysis, the second was in a patient on continuous venovenous hemofiltration. An anaphylactoid reaction induced by an AN69 membrane during continuous, extracorporal treatment in combination with ACE inhibition has not been reported so far. Our report intends to serve as a reminder that the potentially lethal combination of AN69 membranes with ACE inhibitor treatment should be avoided.

Acrylic Resins↗

PubMed2000

Preliminary findings from the National Pre-ESRD Education Initiative.

Regardless of age or race, more patients preferred peritoneal dialysis (PD) than would be expected from the current ratio of patients treated with PD in the U.S. The percent of patients choosing PD seems to be largely influenced by the scope of information they receive prior to therapy initiation. In the absence of thorough treatment option education, a significant number of patients may be assigned a therapy when, in reality, they would have selected an alternative option. There is a need to further understand the correlation between a practice's PD utilization rate and the extent to which patients are given dialysis treatment options.

Adult↗

PubMed1999

Comparison of the effectiveness of adenovirus vectors expressing cyclin kinase inhibitors p16INK4A, p18INK4C, p19INK4D, p21(WAF1/CIP1) and p27KIP1 in inducing cell cycle arrest, apoptosis and inhibition of tumorigenicity.

Cell cycle regulatory proteins are important candidates for therapeutic tumour suppressors. Adenovirus vectors were constructed to overexpress cyclin kinase inhibitors p16INK4A, p18INK4C, p19INK4D, p21(WAF1/CIP1) and p27KIP1 under the control of the murine cytomegalovirus immediate early gene promoter. These vectors directed the efficient expression of each of the cyclin kinase inhibitors and induced growth arrest, inhibited DNA synthesis, and prevented phosphorylation of the retinoblastoma protein (pRb) in cell lines expressing functional pRb. In pRb-deficient cells, expression of the cyclin kinase inhibitors was not effective in inhibiting DNA replication or growth arrest. Interestingly, three of the cyclin kinase inhibitors, p16, p18 and p27 were found to induce apoptotic death in transduced HeLa and A549 cells. When the vectors were tested for their ability to inhibit tumorigenicity in a polyomavirus middle T antigen model of murine breast carcinoma, expression of the cyclin kinase inhibitors resulted in a delay in tumour formation that varied from several weeks for the p19 expressing vector to greater than 25 weeks for the p27 expressing vector. When tumours were injected directly with the adenovirus vectors expressing the cyclin kinase inhibitors, only treatment with the vector expressing p16 resulted in a delay in tumour growth.

Adenocarcinoma↗