Biomedical subjects

M Seibel

Publications and source records attributed to M Seibel.

At least 19 recordsLinked to original sources

PubMed2002

Is the predictive power of previous fractures for new spine and non-spine fractures associated with biochemical evidence of altered bone remodelling? The EPOS study. European Prospective Osteoporosis Study.

BACKGROUND: In the European Prospective Osteoporosis Study (EPOS), a past spine fracture increased risk of an incident fracture 3.6 - 12-fold even after adjusting for BMD. We examined the possibility that biochemical marker levels were associated with this unexplained BMD-independent element of fracture risk. METHODS: Each of 182 cases in EPOS of spine or non-spine fracture that occurred in 3.8 years of follow-up was matched by age, sex and study centre with two randomly assigned never-fractured controls and one case of past fracture. Analytes measured blind were: osteocalcin, bone-specific alkaline phosphatase, total alkaline phosphatase, serum creatinine, calcium, phosphate and albumin, together with the collagen cross-links degradation products serum CTS and urine CTX. Most subjects also had bone density measured by DXA. RESULTS: Cases who had recent fractures did not differ in marker levels from cases who had their last fracture more than 3 years previously. No statistically significant effect of recent fracture was found for any marker except osteocalcin, which was 17.6% lower in recent peripheral cases compared to unfractured controls (p<0.05) and this was independent of BMD. CONCLUSION: Past fracture as a risk indicator for future fracture is not strongly mediated through increased bone turnover.

Aged↗

PubMed2001

Antithrombin III enhances inducible nitric oxide synthase gene expression in vascular smooth muscle cells.

Evidence suggests that antithrombin III (ATIII) exerts anti-inflammatory properties in addition to its anti-coagulative mechanisms. In animal models of sepsis, ATIII affected cytokine plasma concentrations with a decrease of pro-inflammatory cytokines. In addition to cytokines, excessive production of nitric oxide (NO) derived from inducible nitric oxide synthase (iNOS) might represent another important mediator of the cytotoxic events during sepsis. Regarding ATIII as a potential anti-inflammatory modulator, one may speculate that ATIII inhibits the synthesis of iNOS-derived NO. However, our data demonstrate that ATIII further stimulates iNOS gene expression when applied together with either interleukin-1 beta or the combination of lipopolysaccharide plus interferon-gamma. The most prominent synergistic effects on NO synthesis were found when ATIII was given at higher concentrations (1, 5, and 10 U/ml). Although the mechanisms of ATIII signal transduction remain to be established, intensification of interleukin-1 beta or interferon-gamma/lipopolysaccharide-induced NO synthesis by ATIII does not attribute to the anti-inflammatory properties of ATIII.

Animals↗

PubMed2001

Inability of an "energy transfer diagnostician" to distinguish between fertile and infertile women.

CONTEXT: Various forms of "energy healing" have become popular in the United States. OBJECTIVE: To test the assertion that an energy healer can, without physical contact, distinguish the presence or absence of internal organ pathology in individuals who lack overt physical findings. DESIGN: Observational randomized study, in which we tested the assertion by a well-recognized alternative healer that he had particular skill in using energy transfer to detect the presence or absence of fertility disorders in women. PATIENTS: Convenience sample of 37 women, 28 of whom had documented pathology resulting in infertility, and 9 of whom were fertile. OUTCOMES: The healer was provided with no medical history and performed diagnostic evaluations without physical contact with the blindfolded, clothed, and silent subjects. We compared to random chance the ability of the healer to establish a diagnosis of fertility or fertility disorder. SETTING: Teaching hospital. MAIN RESULTS: The healer was unable to distinguish the presence or absence of fertility disorders in the study subjects. CONCLUSION: This study points to further need for fair yet rigorous assessment of claims that energy transfer can lead to accurate clinical diagnoses.

Energy Transfer↗

PubMed2001

Nitric oxide-dependent apoptosis in ovarian carcinoma cell lines.

OBJECTIVE: In a recent study, we found different profiles of inducible nitric oxide synthase (iNOS) gene expression in the ovarian carcinoma cell lines OVCAR-3, HOC-7, and 2774 following stimulation by proinflammatory cytokines. The present study was performed to determine whether nitric oxide (NO) synthesis correlates with programmed cell death in these cells. METHODS: NO-Dependent apoptosis was detected by DNA fragmentation analysis and fluorescence-activated cell sorter analysis. RESULTS: NO formation in response to interferon gamma (IFN-gamma), interleukin-1beta (IL-1beta), and tumor necrosis factor alpha (TNF-alpha) was correlated with programmed cell death in the investigated cells. DNA fragmentation was most prominent in OVCAR-3 (34.17 +/- 1.81%), less pronounced in HOC-7 (12.86 +/- 0.45%), and undetectable in 2774 (4.54 +/- 0.40%) cells. The rate of apoptosis correlated with the amount of NO formation in cytokine-treated cells. Moreover, coincubation of OVCAR-3 and HOC-7 with the specific iNOS inhibitor aminoguanidine suppressed apoptosis induced by IFN-gamma, IL-1beta, and TNF-alpha. CONCLUSION: Our data indicate that in OVCAR-3 and HOC-7 cells, NO synthesis induced by IFN-gamma, IL-1beta, and TNF-alpha is correlated with the degree of apoptotic cell death. In clinical situations, this might in part explain the benefit of cytokine application in ovarian carcinoma patients (e.g., documented for IFN-gamma).

Apoptosis↗

PubMed2001

In vitro modulation of inducible nitric oxide synthase gene expression and nitric oxide synthesis by procalcitonin.

OBJECTIVE: Serum procalcitonin (PCT) concentration was recently introduced as valuable diagnostic marker for systemic bacterial infection and sepsis. At present, the cellular sources and biological properties of PCT are unclear. During sepsis and septic shock, inducible nitric oxide synthase (iNOS) gene expression is stimulated followed by the release of large amounts of nitric oxide (NO). We investigated the possible association between PCT and iNOS gene expression in an in vitro cell culture model. DESIGN: Prospective, controlled in vitro cell culture study. SETTING: University research laboratories. INTERVENTIONS: Confluent rat vascular smooth muscle cells (VSMC) were incubated for 24 hrs and 48 hrs with PCT (1 ng/mL, 10 ng/mL, 100 ng/mL, 1,000 ng/mL, 5,000 ng/mL) alone or with the combination of tumor necrosis factor-alpha (TNF-alpha, 500 U/mL) plus interferon-gamma (IFN-gamma, 100 U/mL). iNOS gene expression was measured by qualitative as well as quantitative polymerase chain reaction analysis, NO release was estimated by the modified Griess method. MEASUREMENTS AND MAIN RESULTS: PCT in increasing concentrations had no effect on iNOS gene expression and nitrite/nitrate release for 24 hrs and 48 hrs, respectively. However, PCT ameliorated TNF-alpha/IFN-gamma-induced iNOS gene expression in a dose-dependent manner (maximal inhibition at PCT 100 ng/mL by -66% for 24 hrs and -80% for 48 hrs). This was accompanied by a significantly reduced release of nitrite/nitrate into the cell culture supernatant (maximal reduction at PCT 100 ng/mL by -56% and -45% for 24 hrs and 48 hrs, respectively). CONCLUSIONS: We conclude that recombinant PCT inhibits the iNOS-inducing effects of the proinflammatory cytokines TNF-alpha/ IFN-gamma in a dose-dependent manner. This might be a counter-regulatory mechanism directed against the large production of NO and the concomitant systemic hypotension in severe sepsis and septic shock.

Animals↗

PubMed2000

Impaired bone metabolism following augmentation cystoplasties in growing rats.

OBJECTIVE: The aim of this study was to evaluate the possible risk of impaired bone metabolism following augmentation cystoplasties with different gastrointestinal segments. METHOD: 60 young rats underwent augmentation cystoplasties using gastric, ileal or sigma segments, or sham operations. An additional group undergoing sigma-cystoplasty received the bisphosphonate ibandronate to inhibit osteoclast-mediated bone resorption. Bone mass in the lumbar spine and tibia was analyzed monthly by in vivo densitometry. Bone turnover was assessed monthly using current bone metabolism markers for a period of 16 weeks. Bone ashing and serum analyses of the osteotropic hormones parathyroid hormone (PTH), and 25-OH vitamin D3 were performed at study conclusion. RESULTS: Following ileocystoplasty, reduced bone mineral density (BMD) was seen throughout the observation period; this was pronounced in the trabecular bone. The decline in BMD was associated with decreased serum 25-OH vitamin D3 levels. Following sigmacystoplasty, bone calcium content was significantly decreased; this could be prevented by ibandronate. No skeletal changes occurred in the gastrocystoplasty group. Serum pH was not altered in any group, and markers of bone resorption indicated normal bone resorption rates. CONCLUSION: There is a significant correlation between impaired bone metabolism and the type of segment used for bladder augmentation. While the use of the ileum (and probably the colon too) causes osteopenia, gastrocystoplasties seem to have little influence on bone turnover.

Absorptiometry, Photon↗

PubMed1999

Inhibition of inducible nitric oxide synthase gene expression and nitric oxide synthesis in vascular smooth muscle cells by granulocyte-colony stimulating factor in vitro.

Clinical and experimental evidence suggests that granulocyte-colony stimulating factor (G-CSF) acts as an anti-inflammatory modulator with beneficial effects in severe inflammatory diseases, e.g., sepsis and septic shock. Excessive production of nitric oxide (NO) is regarded as a potent mediator of the vascular changes leading to systemic hypotension that occurs during sepsis. Therefore, the aim of the present study was to investigate the influence of G-CSF on inducible nitric oxide synthase (iNOS) gene expression and NO synthesis in vascular smooth muscle cells (VSMC). Qualitative and quantitative analyses of iNOS cDNA revealed that G-CSF significantly reduced interferon-gamma/lipopolysaccharide (IFN-gamma/LPS) dependent iNOS gene expression (P < 0.05) following 6, 18, 24, and 48 h incubation periods. In addition, the co-application of G-CSF resulted in a decreased IFN-gamma/LPS mediated iNOS protein generation as detected by immunoblotting methods after 24 and 48 h. Measurement of the stable NO metabolites showed a significant reduction of nitrite/nitrate concentrations following co-incubation of VSMC with G-CSF + IFN-gamma/LPS (242.57 +/- 10.73 nmol NO2-/NO3-/mg cell protein, n = 8) as compared to IFN-gamma/LPS treatment (306.20 +/- 19.26 nmol NO2-/NO3-/mg cell protein, n = 8, P < 0.05) following a 24-h incubation protocol. This inhibitory effect of G-CSF was still present after a 48 h incubation period (G-CSF + IFN-gamma/LPS: 319.56 +/- 6.26 nmol NO2-/NO3-/mg cell protein; IFN-gamma/LPS: 489.20 +/- 27.15 nmol NO2-/NO3-/mg cell protein (P < 0.05), n = 8, respectively). The present findings suggest that inhibition of iNOS gene expression and NO generation in VSMC might be one of the protective anti-inflammatory effects of G-CSF during sepsis.

Animals↗

PubMed1999

Neopterin-induced expression of intercellular adhesion molecule-1 (ICAM-1) in type II-like alveolar epithelial cells.

Production and release of proinflammatory mediators such as tumour necrosis factor-alpha and neopterin are common events following the activation of the cellular immune system. Concerning inflammatory disorders of the lung, e.g. sepsis or sarcoidosis, high serum neopterin levels have been reported to correlate well with the severity of the disease. These situations are often associated with an increased expression of ICAM-1 reported to be induced in type II alveolar epithelial cells. In our study we investigated the potential effects of neopterin on ICAM-1 synthesis in the type II-like pneumocyte cell line L2. Detection of ICAM-1 gene expression by reverse transcriptase-polymerase chain reaction revealed a dose-dependent effect of neopterin, with maximum impact following 12-h incubations. Comparable results were obtained when ICAM-1 protein synthesis was measured via a cell-based ELISA. In a second set of experiments we were able to show that coincubation of L2 cells with pyrrolidine dithiocarbamate (PDTC) significantly suppressed neopterin-induced ICAM-1 synthesis. Since PDTC is known to be a potent inhibitor of NF-kappaB, the stimulating effects of neopterin on ICAM-1 gene expression and protein generation may be mediated by activation of this transcription factor. From these data we conclude that neopterin stimulates ICAM-1 production in L2 cells. In vivo, these effects may contribute to the prolongation of the inflammatory response, including cytotoxic cell host defence mechanisms that impair the functions of the airway epithelium.

Animals↗

PubMed1999

Human dermal microvascular endothelial cells express inducible nitric oxide synthase in vitro.

Stimulation of inducible nitric oxide synthase with subsequent release of nitric oxide in large amounts may play a critical part either in host defense reactions or in the pathophysiology of the inflammatory response syndrome leading to septic shock. The aim of the present study was to investigate whether human dermal microvascular endothelial cells exhibit the typical characteristics of an inducible nitric oxide synthase expressing cell. A strong effect on inducible nitric oxide synthase gene expression could be detected when the cells were coincubated with the proinflammatory cytokines interferon-gamma and tumor necrosis factor-alpha with inducible nitric oxide synthase cDNA concentrations averaging 11.7 +/- 0.6 amol per microg total RNA at 24 h, and 25.0 +/- 1.4 amol per microg total RNA at 48 h, respectively. Intracellular staining with an antibody recognizing inducible nitric oxide synthase protein and subsequent analysis by flow cytometry revealed a 4-fold increase of inducible nitric oxide synthase protein in human dermal microvascular endothelial cells treated with interferon-gamma/tumor necrosis factor-alpha. This was accompanied by a significant elevation in nitrite/nitrate concentrations in the cell-free culture supernatants. Our results indicate that human dermal microvascular endothelial cells are provided with an inducible nitric oxide synthase system and can be regarded as an appropriate cell model for investigating inducible nitric oxide synthase gene expression and nitric oxide properties in microvascular endothelial cells.

Cells, Cultured↗

PubMed1995

Increased urinary excretion of collagen crosslinks in girls with Ullrich-Turner syndrome.

Skeletal abnormalities and "osteoporosis" are frequent features of Ullrich-Turner syndrome (UTS), but their cause remains largely unknown. In this study, we compared the urinary excretion of hydroxyproline (OHP), pyridinoline (PYD) and deoxypyridinoline (DPD) in 28 girls (bone age 3.5-11.0 years, mean 7.4 years) with UTS and 30 healthy prepubertal children (chronological age 3.9-10.9 years, mean 7.6 years). Expressed relative to the square of the height, the excretion of both collagen crosslinks was significantly higher in UTS than in controls (23.4% for PYD, 33.6% for DPD, p < 0.05). In contrast, no significant difference was found for OHP. The molar PYD/DPD ratio was significantly lower in UTS children than in controls (mean (+/- SD) 3.4 (+/- 0.41) versus 3.8 (+/- 0.55); p = 0.004). While the higher excretion of collagen crosslinks reflects enhanced bone resorptive activity in UTS, the lower PYD/DPD ratio might be due to structural alterations in collagen.

Adolescent↗

PubMed1994

The natural resolution of a lumbar spontaneous epidural hematoma and associated radiculopathy.

This is a report of a 37-year-old man who, while lifting a heavy box, developed severe low-back pain radiating into the right anterior thigh. The only clinical signs were paraspinal muscle spasm and a positive femoral nerve stretch test on the right. An electromyographic study demonstrated denervation in the right L2, L3, and L4 myotomes and paraspinal muscles. Magnetic resonance imaging (MRI) showed a large L1-2 anterior epidural hematoma compressing the spinal cord. The patient's pain gradually improved with conservative management and he returned to light work after 4 weeks. Repeat electromyographic and MRI studies were normal, indicating a resolution of the radiculopathy and hematoma. The diagnosis and management of spontaneous epidural hematomas are discussed.

Adult↗

PubMed1994

Urinary excretion of hydroxy-pyridinium cross-links of collagen reflects skeletal growth velocity in normal children.

Two new markers of bone resorption, the collagen cross-linking amino acids pyridinoline (PYD) and deoxypyridinoline (DPD), were measured in 24-h urine collections from 88 healthy children (45 females, 43 males; age 4 to 18 years) and 17 adults. Normal values for pediatric use were established for these parameters. Related to daily excretion of creatinine PYD and DPD were about 3 to 6 fold higher in the pediatric groups than in adults. The collagen cross-links showed a highly significant correlation to the urinary excretion of hydroxyproline (OHP): r = 0.65 for PYD and r = 0.60 for DPD (p < 0.001). Both collagen cross-links and OHP excretion related to creatinine were significantly correlated to growth velocity (r = 0.67, 0.62 and 0.51 for PYD, DPD and OHP respectively; p < 0.001 in each case). PYD and DPD may be useful for the monitoring of growth in children.

Adolescent↗

PubMed1993

Estrogen protection against bone resorbing effects of parathyroid hormone infusion. Assessment by use of biochemical markers.

OBJECTIVE: Because parathyroid hormone (PTH) stimulates bone resorption, resistance to its actions might help maintain bone mass. We tested the hypothesis that the effects of estrogen on bone are accomplished in part by decreasing the sensitivity of the skeleton to the resorbing effects of PTH. STUDY DESIGN: Comparison of response to PTH infusion in untreated and estrogen-treated postmenopausal women with osteoporosis. INTERVENTION: (1-34) human PTH, 0.55 U/(kg.h), was infused intravenously over 20 hours. SETTING: The inpatient clinical research unit of a referral hospital. PATIENTS: Women with primary postmenopausal osteoporosis who were untreated (n = 15) or treated with estrogen (n = 17). MAIN OUTCOME MEASURES: Skeletal turnover indices including hydroxyproline, deoxypyridinoline, pyridinoline, tartrate-resistant acid phosphatase, alkaline phosphatase, bone Gla protein, and insulin-like growth factor-1. RESULTS: All basal indices were higher in untreated than in estrogen-treated women, but statistical differences were seen only for deoxypyridinoline and pyridinoline. During the 20-hour infusion, hydroxyproline/creatinine increased 0.023 mumol/mumol in untreated women but only 0.010 mumol/mumol in estrogen-treated women (P < 0.05). Corresponding changes for deoxypyridinoline/creatinine were 14.6 mumol/mumol and 3.5 mumol/mumol (P = 0.06). Tartrate-resistant acid phosphatase and pyridinoline increased only in untreated group. A circadian rhythm in circulating bone Gla protein was seen in both groups without clear PTH-induced effects or differences between groups. Alkaline phosphatase levels decreased and insulin-like growth factor-1 levels increased in both groups with no distinction between untreated and estrogen-treated women [corrected]. CONCLUSION: The estrogenized postmenopausal osteoporotic skeleton is less sensitive to the bone resorbing effects of acutely administered PTH. There are no differential effects on bone formation.

Aged↗

PubMed1992

Pathways of destruction in metacarpal and metatarsal joints of patients with rheumatoid arthritis.

219 metatarsal (MTP) and 69 metacarpal (MCP) capitulae obtained during surgery from patients with definite rheumatoid arthritis (RA) were histologically evaluated. This evaluation, focussing on primary pathways of joint destruction by tumor-like proliferated synovial cell masses revealed 3 pathways of aggression: Pathway A: In 15% aggression onto the articular cartilage only. Pathway B: In 49% direct invasion exclusively into the cortical bone. Pathway C: In 36% a "forceps-like" aggression, a combination of A and B in which the joint is attacked from both sides. In contrast to the hitherto conventional concepts, the findings of this study reveal a clear preference of the synovial aggression for the cortical bone rather than for the articular cartilage. The different concepts of joint destruction in RA are being discussed in the light of our findings. Thus, future pathogenetic considerations with regard to joint destruction in RA should take this fact into consideration.

Adult↗

PubMed1992

Coping with infertility: a new nursing perspective.

Infertility is a major life stressor, and reproductive failure is difficult to accept. Many couples become trapped in a cycle of repeated medical treatment, repeating painful patterns without developing insight or growth, feeling powerless to achieve their goal or move on. The causes of inappropriate coping behaviors are not well understood, and there is little direction for the nurse clinician's efforts to assist the couple with decision making. The use of superstition and ritual (magical thinking or magical ideation) by couples with infertility is discussed, and its role as a potential barrier to resolution is evaluated. A clinical tool for assessing the extent of magical ideation is described and its potential clinical utility explored. Women who have experienced a previous pregnancy may be more likely than nulliparas to substitute magical thinking for coping behaviors that might bring them closer to resolution. Problems with current research in this area are discussed, and directions for developing clinical nursing interventions are suggested.

Adaptation, Psychological↗

PubMed1992

The prevalence and predictability of depression in infertile women.

OBJECTIVE: To determine the prevalence, severity, and predictability of depression in infertile women compared with a control sample of healthy women. DESIGN: Subjects were assessed while waiting to see their physician: infertility patients before a visit with an infertility specialist and control subjects before seeing either a gynecologist or internist for a routine gynecological examination. Subjects completed a demographic form and two depression scales. SETTING: A group infertility practice affiliated with an academic medical center, a hospital-based gynecology practice, and a health maintenance organization internal medicine clinic. PARTICIPANTS: 338 infertile women and 39 healthy women. INTERVENTIONS: None. MAIN OUTCOME MEASURES: The Beck Depression Inventory and the Center for Epidemiological Studies Depression Scale. RESULTS: The infertile women had significantly higher depression scores and twice the prevalence of depression than the controls; women with a 2- to 3-year history of infertility had significantly higher depression scores compared with women with infertility durations of < 1 year or > 6 years; women with an identified causative factor for their infertility had significantly higher depression scores than women with unexplained or undiagnosed infertility. CONCLUSIONS: Depressive symptoms are common in infertile women. Psychological interventions aimed at reducing depressive symptoms need to be implemented, especially for women with a definitive diagnosis and for those with durations of 2 to 3 years of infertility.

Depression↗

PubMed1992

Hysteroscopic resection of fibroid with thermal injury to sigmoid.

BACKGROUND: Hysteroscopy is being used increasingly, especially as a means of performing uterine surgery. Uterine perforation is the most frequent complication of hysteroscopy. CASE: A 31-year-old woman sustained uterine perforation with a resectoscope during hysteroscopic resection of a pedunculated myoma. The perforation was identified laparoscopically, but laparotomy was necessary to assess the pelvic viscera fully. Perforation of the sigmoid was discovered and the defect was repaired primarily. CONCLUSION: Laparoscopy may be insufficient to evaluate fully the possible sequelae of uterine perforation. Penetrating thermal injury to the colon can be managed successfully with primary repair.

Adult↗

PubMed1992

Psychological improvement in infertile women after behavioral treatment: a replication.

OBJECTIVE: To replicate previously reported psychological improvements in infertile women attending a group behavioral treatment program. DESIGN: Psychological and demographic data were collected before entering and again upon completion of a behavioral medicine program on a second cohort of patients. SETTING: The program was offered in the Division of Behavioral Medicine, an outpatient clinic of the Department of Medicine at New England Deaconess Hospital. All patients were receiving care from infertility specialists not affiliated with this hospital. PATIENTS: Fifty two self-referred women receiving medical treatment for infertility attended the program. INTERVENTION: A 10-week group behavioral treatment program. MAIN OUTCOME MEASURES: Three validated psychological instruments. RESULTS: Psychological improvement was statistically significant (Profile of Mood States Tension/Anxiety: P less than 0.0001; Depression/Dejection: P less than 0.0122; Vigor/Activity: P less than 0.0431; Confusion/Bewilderment: P less than 0.0057; Spielberger Anger Expression: P less than 0.0013; Spielberger State Anxiety: P less than 0.0037, and Trait Anxiety: P less than 0.0001). CONCLUSIONS: Behavioral treatment is associated with significant decreases in negative psychological symptoms.

Adult↗