Biomedical subjects

D Berger

Publications and source records attributed to D Berger.

At least 19 recordsLinked to original sources

PubMed2005

Quantification of dose perturbation by plaque in vascular brachytherapy.

BACKGROUND: Dose prescription and reporting in vascular brachytherapy (VBT) is based on the assumption that the vessel wall is water equivalent, which does not consider a possible dose perturbation by plaque. As the extent of this perturbation is unknown, we aimed to quantify dose attenuation by atherosclerotic plaque for beta- and gamma-radiation. MATERIAL AND METHODS: The dose delivered from Strontium-90/Yttrium-90 ((90)Sr/Y) and Iridium-192 ((192)Ir) sources with and without human peripheral arteries ((90)Sr/Y: n = 38, (192)Ir: n = 7) surrounding the respective delivery catheter was determined with radiochromic films. Plaque and vessel wall thickness were measured using light microscopy. From the ratio-attenuated doseunattenuated dose (dose perturbation factor: DPF) we determined averaged attenuation coefficients for atherosclerotic plaque (micro(P)) and the residual part of the vessel wall (micro(W)) by regression analysis based on the function DPF = exp(-micro(P) * plaque thickness -micro(W) * residual wall thickness). RESULTS: Attenuation in case of (192)Ir was less than the measurement uncertainties. For beta-radiation correlation was found by discrimination between calcified and noncalcified plaque. Classifying noncalcified plaque as normal arterial tissue, the regression coefficient was r = 0.845 at micro(P)= 0.5356 mm(-1) and micro(W) = 0.0663 mm(-1). CONCLUSIONS: Vascular brachytherapy with beta radiation in calcified arteries results in significant dose attenuation within the vessel wall, which can be calculated on knowing the vascular morphometry. Thus, plaque thickness should be taken into account in treatment planning and retrospective analyses.

Arteriosclerosis↗

PubMed2005

Hypophosphataemia in old patients is associated with the refeeding syndrome and reduced survival.

OBJECTIVES: Previous studies found that hypophosphataemia (HP) a common finding in hospitalised patients associated with unfavourable outcome, but they did not focus on old patients. The aim of the current study was to determine the prevalence, associated risk factors and potential clinical consequences of HP detected during hospitalisation in a geriatric medical centre. DESIGN: Case-control study. SETTING: A total of 312-bed geriatric division. SUBJECTS: We compared 325 patients aged >or=65 years with at least one episode of HP-group defined by serum phosphate <or=0.77 mmol L(-1) with 326 patients without HP (non-HP group). MEASUREMENTS: Evaluation included baseline anamnesis, demographic and laboratory data. Patients in both groups were followed up to 2.7 years and clinical outcome recorded included length of hospitalisation, in-hospital and long-term survival. RESULTS: About 14.1% of 2307 elderly had HP. Patients in the HP-group compared with the non-HP group had significantly more weight loss, lower albumin levels, more sepsis and received threefold more glucose-containing infusions and twofold more food supplementations (P < 0.0001). HP was detected on average on the 10.9 +/- 21.5 days of hospitalisation. Patients in the HP-group compared with the non-HP group, had significantly longer hospitalisation period (P < 0.0001) and reduced long-term survival (P = 0.003) with threefold increased mortality rates. In a multivariate analysis, HP was not found to be an independent predictor of mortality. CONCLUSIONS: The HP was common among old hospitalised patients. Clinical characteristics of the HP-group, the time-course and strong association with glucose and food supplementation, are compatible with the refeeding syndrome, described previously in malnourished patients. HP was associated with significantly reduced survival.

Aged↗

PubMed2003

Procalcitonin, C-reactive protein, and endotoxin after bone marrow transplantation: identification of children at high risk of morbidity and mortality from sepsis.

We prospectively evaluated the capacity of serum procalcitonin (PCT), compared with serum levels of C-reactive protein (CRP) and endotoxin, to identify children at high risk for mortality from sepsis after BMT. Of 47 pediatric bone marrow transplantation patients studied, 22 had an uneventful course post-transplant (Group 1), 17 survived at least one septic event (Group 2), and eight died from multiorgan failure (MOF) following septic shock (Group 3). Median concentrations of PCT over the course of the study were 1.3, 15.2, and 102.8 ng/ml, respectively, in each of the three groups (P<0.002 for each comparison). Median concentrations of CRP were 91, 213, and 260 mg/l, respectively (P<0.001 for Group 1 vs Group 2 and Group 3; P=NS for Group 2 vs Group 3). Median concentrations of endotoxin were 0.21, 0.30, and 0.93 U/l, respectively (P=NS for each comparison). Median concentrations of PCT, in contrast to serum CRP and endotoxin, correlated with the severity of sepsis (8.2 ng/ml in 'sepsis' and 22.3 ng/ml in 'severe sepsis', P=0.028) and provided useful prognostic information during septic episodes.

Adolescent↗

PubMed2003

Establishment of a high-efficiency SNP-based framework marker set for Arabidopsis.

The major goal of this project was the establishment of a tool for rapid mapping of new mutations and genotyping in Arabidopsis consisting of at least 100 evenly spaced framework markers. We assembled a single nucleotide polymorphism (SNP)-based marker set consisting of 112 polymorphic sites with average spacing of 1.15 Mbp derived from an SNP database that we recently developed. This information was used to set up efficient SNP detection reactions based on multiplexed primer extension assays. The 112 Columbia (Col-0)/C24 framework markers were used to assemble 18 multiplexed SNaPshot assays with which up to eight separate loci can be genotyped in a single-tube/single-capillary format. In addition, for 110 framework markers matrix-assisted laser desorption/ionization time of flight (MALDI-ToF) assays have been established for high throughput analyses. We demonstrated the usefulness and the robustness of both procedures of this tool by genotyping 48 BC3F1 individuals created between the accessions Col-0 and C24. Subsets of 10-62 of the established markers discriminate between various combinations of the accessions Col-0, C24, Landsberg erecta (Ler), Cape Verdi Islands (Cvi) and Niederzenz (Nd). Using a subset of 17 evenly distributed and established SNP markers that are also polymorphic between Ler and Col-0, we were able to rapidly map a mutant gene (tbr1) to an interval of 2.3 Mbp in an Ler (tbr1) x Col-0 cross.

Arabidopsis↗

PubMed2003

[Transarterial chemoperfusion of inoperable pancreas carcinoma and local recurrence].

BACKGROUND: To evaluate the side effects and tumor response of a locoregional transarterial chemoperfusion with Mitomycin C and Gemcitabine in advanced pancreatic cancer. MATERIALS AND METHODS: Between October 2001 and August 2002, 16 patients were treated in 80 transarterial chemoperfusion sessions with a mean of 5 sessions per patient and a pause of 4 weeks between the sessions. The chemotherapy consisted of a combination of Mitomycin C (8.5 mg/m 2) and Gemcitabine (500 mg/m 2), administered within 1 hour. The tumor response was evaluated by MRT and CT and the quality of life by a patient questionnaire. RESULTS: All patients tolerated the procedure well. The therapeutic outcomes were as follows: in 50 % (n=8) of patients, minor response with a decrease in size of the primary tumor and metastases up to 20 %; in 25 % (n = 4) of patients, stable disease; and in 25 % (n = 4) of patients, progressing metastases with stable primary tumor. Eleven patients (68.75 %) reported a good quality of life without impaired performance of their daily activities. Side effects were moderate and reversible between the treatment cycles. After one year 25 % of the patients were still alive. CONCLUSION: Transarterial chemoperfusion is a minimally invasive treatment for pancreatic carcinomas and local recurrences with little side-effects and can be delivered on an outpatient basis. It might be indicated as potential neoadjuvant treatment before surgery or as palliative treatment to provide clinical benefits and to improve the quality of life.

Activities of Daily Living↗

PubMed2003

Minimal adhesions to ePTFE mesh after laparoscopic ventral incisional hernia repair: reoperative findings in 65 cases.

BACKGROUND AND OBJECTIVES: Laparoscopic ventral incisional hernia repair involves intraabdominal placement of a synthetic mesh, and the possibility of formation of severe visceral adhesions to the prosthesis is a principal concern. Little clinical information based on reoperative findings is available about adhesions to biomaterials placed intraabdominally. We conducted a multi-institutional study of adhesions to implanted expanded polytetrafluoroethylene (ePTFE) mesh at reoperation in patients who had previously undergone laparoscopic incisional hernia repair done with the same mesh implantation technique. METHODS: Nine surgeons retrospectively assessed the severity of adhesions to ePTFE mesh at reoperation in 65 patients. For each case, adhesions were assigned a score of 0 to 3, with 0 indicating no adhesions and 3 severe adhesions. RESULTS: The mean time from mesh implantation to reoperation was 420 days (range, 2-1 739 days). No adhesions were observed in 15 cases. Forty-four cases received an adhesion score of 1, and 6 cases a score of 2; no scores of 3 were assigned. Thus, 59 patients (91 %) had either no or filmy, avascular adhesions. No enterotomies occurred during adhesiolysis. CONCLUSIONS: In this large series of reoperations after laparoscopic incisional hernia repair, no or minimal formation of adhesions to implanted ePTFE mesh was observed in 91 % of cases, and no severe cohesive adhesions were found. Comparative analyses of newer materials based on clinical reoperative findings are warranted to assess the safety of intraabdominally placed meshes.

Adult↗

PubMed2002

Postoperative complications after laparoscopic incisional hernia repair. Incidence and treatment.

BACKGROUND: The popularity of laparoscopic repair of incisional hernias is increasing due to the apparent advantages of laparoscopy. PATIENTS AND METHODS: A group of 150 consecutive patients with incisional hernias were treated by laparoscopic IPOM technique with a Goretex Dualmesh between September 1999 and September 2001 and subsequently followed up. Some minor and major complications could clearly identify advantages as well as drawbacks of the technique. RESULTS: No primary mesh infection were observed but 4 recurrences, 3 of them due to technical mistakes, and 1 case with ileus due to a volvolus at day 4 p.o. were recorded. Further major complications included 2 early and 2 later stage trocar hernias, which needed surgical correction. Two patients developed secondary bowel perforation after thermal injury and after primary enterotomy which was closed by laparotomy. CONCLUSIONS: All complications, except one recurrence due to failure of the material, were surgical mistakes and cannot be attributed to the laparoscopic procedure. Consequently, after taking into account the surgical mistakes and possible technical errors, the low recurrence rate justifies further application of laparoscopic ventral hernia repair.

Adult↗

PubMed2002

[Laparoscopic repair of incisional hernias].

The rationale for laparoscopic repair of incisional hernias lies in the fact that any kind of incisional hernia is caused by an intrinsic defect of wound healing. This means that the abdominal wall needs to be reinforced with foreign nonresorbable material. During laparoscopic repair a nonresorbable mesh with the characteristic feature that its two surfaces are quite different is used to completely cover the original incision. One surface is designed to ensure stable incorporation into the abdominal wall and the other, to keep adhesions between the mesh and the bowel to a minimum. Experience reported since its first description in 1993 has clearly shown that the main advantage of the laparoscopic technique over conventional methods is that it involves an extremely low risk of mesh infection. The reported recurrence rates of 1-11% are mainly attributable to technical error and demonstrate that in this way too, the laparoscopic technique is at least as good as the open techniques. Up to now, no mesh-related complications in the form of fistula or mesh migration have been described. In conclusion, then, laparoscopic repair of ventral hernia is an important addition to the surgical armamentarium, which at least in our hands has almost completely replaced conventional techniques.

Follow-Up Studies↗

PubMed2002

Genetic variants of insulin receptor substrate-1 (IRS-1) in syndromes of severe insulin resistance. Functional analysis of Ala513Pro and Gly1158Glu IRS-1.

AIMS: To define further the role of IRS-1 mutations in human syndromes of severe insulin resistance. METHODS: The IRS-1 gene was scanned for mutations in 83 unrelated affected subjects and 47 unaffected individuals using fluorescent single-strand conformation polymorphism (fSSCP) analysis. A novel heterozygous mutation, Gly1158Glu, was found in one affected subject. Four and two subjects were heterozygous for the previously reported variants Gly972Arg and Ala513Pro, respectively. The previously identified variant Gly819Arg was found in one affected and one unaffected subject. While Gly972Arg has been described to alter the signalling properties of IRS-1, no functional studies of Ala513Pro or Gly1158Glu have been reported. RESULTS: Chinese hamster ovary (CHO) cells stably over-expressing the insulin receptor were transiently transfected with vectors expressing either wild-type, Glu1158 or Pro513 IRS-1. A modest increase in insulin-stimulated tyrosine phosphorylation of Glu1158 IRS-1 was observed. However, this did not result in any significant change in the association of Grb2 or the p85 alpha subunit of PI3-kinase or of PI3-kinase activity. In parallel studies, the Pro513 IRS-1 variant was indistinguishable from wild-type IRS-1. CONCLUSIONS: While subtle effects of these variants cannot be excluded in this system, it is unlikely that these variants are responsible for the extreme insulin resistance seen in the subjects harbouring them. Although IRS proteins play a central role in insulin signalling, functionally significant mutations in the IRS-1 gene are a rare cause of human syndromes of severe insulin resistance.

Animals↗

PubMed2002

[School health education: practices and representations of primary school teachers].

A better understanding of primary school teachers' practices and representations toward health education (HE), and identification of individual or structural resistance as well as the partnership and training needs all constitute important goals in HE research. A quantitative study was conducted between April and December 2001 on a representative sample of the population of primary school teachers (n = 673) in the Auvergne region. The results demonstrate that the majority of teachers declare practicing and implementing HE. The approach is primarily thematic, essentially limited to a few lessons since it is only integrated into a broader project 20% of the time. 30% of teachers work in partnership, mainly with partners in school health; however, parents are rarely involved in HE activities. Parameters which influence the teachers' practices and representations are: (1) prioritizing work within an educational network and an inter-communal pedagogical regrouping, with the advantage that there are a greater number of teachers to do HE in these schools than in others, and (2) receiving initial or in-service training. These results suggest that a policy aiming to generalize the inclusion of HE in French primary schools must develop teacher training as well as support and accompany the collective dynamics within schools.

Attitude↗

PubMed2001

Endotoxemia and acute-phase proteins in major abdominal surgery.

BACKGROUND: Translocation of endotoxin is a controversial issue. The ability of plasma to inactivate endotoxin is an indirect measure of endotoxemia. Endotoxin is a potent stimulator of the inflammatory response and affects the innate immune system. OBJECTIVE: To elucidate the kinetics of endotoxemia and the ability of plasma to inactivate endotoxin in patients with major abdominal operations. To demonstrate the early time course of the acute-phase proteins C-reactive protein (CRP), serum amyloid A (SAA), alpha(1)-antitrypsin, alpha(2)-macroglobulin, transferrin, and interleukin 6 (IL-6), and to correlate them with the amount of endotoxemia. METHODS: Twenty patients with elective major abdominal operation and 10 healthy controls were investigated. Blood was collected preoperatively, during the operation and regularly up to 12 days after surgery. Endotoxin was measured by Limulus amebocyte lysate test (LAL), the ability of plasma to inactivate endotoxin by modified LAL, the acute-phase proteins nephelometrically, and IL-6 by enzyme-linked immunosorbent assay (ELISA). RESULTS: Preoperative endotoxin plasma level (0.026 +/- 0.004 EU/mL) did not differ from healthy volunteers but increased during operation (0.09 +/- 0.02 EU/mL, P = 0.02). Endotoxemia peaked 1 hour after the surgical procedure (0.16 +/- 0.03 EU/mL; P <0.0001 versus preoperative) and decreased to almost normal values after 48 hours. The capability of plasma to inactivate endotoxin was significantly reduced during (recovery, 0.16 +/- 0.03 EU/mL), 1 hour (0.25 +/- 0.04 EU/mL) and 24 hours (0.16 +/- 0.02 EU/mL) after the operation compared with preoperative (0.068 +/- 0.01 EU/mL) values. Plasma IL-6 was significantly increased for 48 hours with a peak 1 hour after surgery (470 +/- 108 pg/mL). CRP peaked at 210 +/- 19 mg/L (P <0.0001 versus preoperative) 48 hours after operation and was significantly elevated for the rest of the observation period. SAA was significantly increased 24 hours after surgery (249 +/- 45 mg/L) and peaked additional 48 hours later (456 +/- 86 mg/L). alpha(1)-Antitrypsin, although a positive acute-phase protein, decreased initially to 1.38 +/- 0.1 g/L (preoperative, 2.33 +/- 0.18 g/L; P <0.0001) and increased thereafter until day 12 (3.05 +/- 0.35 g/L, P = 0.11 versus preoperative). The same was true for alpha(2)-macroglobulin (preoperative, 2.2 +/- 0.16 g/L; intraoperative, 1.36 +/- 0.13 g/L; day 5, 2.8 +/- 0.4 g/L). Transferrin decreased already during surgery (1.6 +/- 0.1 g/L versus preoperative 2.8 +/- 0.17 g/L, P <0.0001) and remained on this level for 5 days. Correlation analysis revealed a relationship between endotoxemia and the ability of plasma to inactivate endotoxin (r = 0.67, P <0.0001) and also a relation between intraoperative endotoxemia on one hand and alpha(2)-macroglobulin (-0.53 > r > -0.6, P <0.05) as well as alpha(1)-antitrypsin (0.64 > r >0.55, P <0.05) on the other. CONCLUSION: Major abdominal surgery is associated with transient endotoxemia and a transient reduced endotoxin inactivation capacity of the plasma. Endotoxemia correlates with the endotoxin inactivation capacity. The surgical procedure causes substantial changes in plasma concentrations of acute-phase proteins. alpha(2)-Macroglobulin and alpha(1)-antitrypsin correlate moderately with endotoxemia.

Abdomen↗

PubMed2000

[A young woman with neurofibromatosis 1 (Recklinghausen disease), abdominal tumor and hypertension].

HISTORY AND ADMISSION FINDINGS: A 38-year-old woman, known to have type 1 neurofibromatosis (NF1; von Recklinghausen's disease) and recurrence of a malignant haemangiopericytoma in the lower abdomen developed hypertension. She also had headaches and marked perspiration. Physical examination revealed tachycardia and paleness of the distal digits, in addition to multiple neurofibromas and café-au-lait spots. INVESTIGATIONS: A tumour was found in the region of the right adrenal gland, in addition to the known haemangiopericytoma. The levels of epinephrine and dopamine were elevated, suggesting an orthotopic phaeochromocytoma as the cause of the hypertension. Mutation analysis confirmed the neurofibromatosis by demonstrating a splice mutation of the NF1 gene in exon 8. She also was found to have emphysema of the right upper and middle lobes of the lung. TREATMENT AND COURSE: Because of the extensive local changes the recurrent haemangiopericytoma was only partially resected. At the same time a right adrenalectomy was performed without complication. However, the patient's postoperative recovery was slow, but she was now normotensive. Planned radiotherapy was omitted because of her poor general state. Instead she was given weekly palliative chemotherapy with adriamycin, with little improvement. She died several weeks later from the malignancy. CONCLUSION: This case emphasizes that in a patient with NF1 a phaeochromocytoma must be considered as a possible cause of hypertension. It is likely that the patient's emphysema was associated with the NF1, while the haemangiopericytoma was presumably unconnected with the NF1.

Abdominal Neoplasms↗

PubMed2000

A subtilisin-like serine protease involved in the regulation of stomatal density and distribution in Arabidopsis thaliana.

Stomata are specialized cellular structures in the epidermis of aerial plant organs that control gas exchange (H(2)O release and CO(2) uptake) between leaves and the atmosphere by modulating the aperture of a pore flanked by two guard cells. Stomata are nonrandomly distributed, and their density is controlled by endogenous and environmental factors. To gain insight into the molecular mechanisms regulating stomatal distribution, Arabidopsis thaliana mutants with altered stomatal characteristics were isolated and examined. The sdd1-1 mutant exhibits a two- to fourfold increase of stomatal density and formation of clustered stomata (i.e., stomata that are not separated by intervening pavement cells), whereas the internal leaf architecture is not altered. The SDD1 gene was identified by map-based cloning. It encodes a subtilisin-like serine protease related to prokaryotic and eukaryotic proteins. We propose that SDD1 acts as a processing protease involved in the mediation of a signal that controls the development of cell lineages that lead to guard cell formation.

Amino Acid Sequence↗

PubMed2000

Release of endotoxin-binding proteins during major elective surgery: role of soluble CD14 in phagocytic activation.

Our previous study demonstrated that soluble CD14 (sCD14) modulates the biologic activity of circulating endotoxin, which appears after surgery. In this study, we examined the behavior of endotoxin-binding proteins, such as sCD14, lipopolysaccharide-binding protein (LBP), and bactericidal/permeability-increasing protein (BPI), in patients' plasma after major abdominal surgery and the phagocytic secretion of sCD14 from peripheral blood mononuclear cells (PBMCs) throughout the observation period. In a prospective study, 15 patients undergoing major abdominal surgery (gastrectomy, n = 3; pancreatectomy, n = 10: colectomy, n = 2) were involved in this study. The endotoxin-binding proteins were perioperatively (preoperatively; postoperative hour 6; days 1, 2, 3, 4, 5, 7, and 10) measured by an enzyme-linked immunosorbent assay (ELISA). To exclude the hemodilution effect of samples, each parameter was corrected by dividing the respective value by the albumin concentration. The phagocytic activity at each time point was tested as an ex vivo sCD14 secretion from PBMCs in the presence and absence of exogenously added endotoxin, Escherichia coli 055B5 (1 ng/ml). Significant endotoxemia (0.35 +/- 0.13 EU/ml; p < 0.05) was observed 6 hours after the beginning of surgery. The sCD14/albumin value rapidly increased at 6 hours after surgery, peaked on day 1, and sequentially declined, whereas the BPI/albumin and LBP/albumin ratios increased more gradually and peaked on day 2. The secretion of sCD14 from 2 x 10(6) PBMCs was significantly enhanced from 6 hours after operation. The increased plasma level of sCD14 may be explained by the parallel-enhanced sCD14 PBMC production. Activated secretion of these endotoxin-binding proteins may play a role in regulating the biologic activity of circulating endotoxin.

Acute-Phase Proteins↗

PubMed2000

Peritonitis in childhood: aspects of pathogenesis and therapy.

The pathogenesis of peritonitis due to hollow-viscus perforation is currently accepted as being mainly based on the local and systemic release of pro- and anti-inflammatory mediators triggered by the presence of bacteria and bacterial products in the abdominal cavity. Therefore, treatment consists in focal restoration, intraoperative debridement and lavage, and postoperative measures such as drainage, continuous peritoneal lavage, or scheduled reoperation aiming at the removal of infectious agents from the peritoneal cavity to prevent persisting peritonitis and sepsis. In order to evaluate the pathophysiologic relevance of the bacterial and endotoxin load of the peritoneal exudate, we examined the peritoneal fluid of 20 children with perforated appendicitis for qualitative and quantitative analysis of bacteria, antibiotic concentrations, and endotoxin content. The time period ranged in 12-h intervals from intraoperatively to day 5. Eighteen of 20 fluid specimens (90%) showed endotoxin levels above 1.5 endotoxin units EU/ml (standard <0.1 EU/ml). The most common bacterial species isolated was Escherichia coli, mostly in high concentrations. Despite persisting high endotoxin concentrations and bacterial loads in the peritoneal cavity during the 5 postoperative days, the children recovered uneventfully and the systemic signs of infection disappeared rapidly. In conclusion, neither the bacterial nor the endotoxin load of the peritoneal cavity proved to be associated with the clinical course. Therefore, we hypothesize that during peritonitis compartmentalization of the focus of infection prevents further systemic reactions and ultimately leads to removal of the infectious agents by endogenous mechanisms. At least in peritonitis due to perforated appendicitis in children, adjuvant surgical measures in addition to appendectomy and intraoperative debridement are not necessary.

Anti-Bacterial Agents↗

PubMed2000

Efficacy of Vitex agnus castus L. extract Ze 440 in patients with pre-menstrual syndrome (PMS).

In a prospective, multicentre trial the efficacy of an Vitex agnus castus L extract Ze 440 was investigated in 50 patients with pre-menstrual syndrome (PMS). The patients were treated daily with one tablet (20 mg native extract) during three menstrual cycles. 43 patients completed the study protocol which encompassed 8 menstrual cycles (2 baseline, 3 treatment and 3 post-treatment). 13/43 patients were receiving concomitant oral contraceptives. 6 patients did not complete the study for reasons not related to study medication, and one patient complained of fatigue possibly related to study medication. All evaluated patients took at least 85% of the prescribed medication. The main effect parameter was the validated Moos' menstrual distress questionnaire (MMDQ), and secondary parameters were a visual analogue scale (VAS; self-assessment) and a global impression scale (GI, self-assessment). The study population was homogenous in age (31.3+/-7.7 years) weight (58.9+/-6.9 kg) and cycle length (28.4+/-0.3 d). The diagnosis was according to DMS-III. At the end of the study, PMS-related symptoms were reduced by treatment. There was a significant score reduction (42.5%) of the MMDQ as the main effect parameter (p<0.001). Symptoms gradually returned after treatment cessation. However, a difference from baseline remained (20%; p<0.001) up to 3 cycles thereafter. 20/43 patients were considered "responders", with a reduction in MMDQ score by at least 50% relative to baseline. At baseline, the VAS score was elevated in the late luteal phase and low at the follicular phase, as expected. During treatment, VAS score decreased in the late luteal phase (47.2%; p<0.01) and remained 21.7% (p<0.001) below baseline after 3 cycles post-cessation of treatment. The low VAS score within the follicular phase remained unchanged over the whole observation period. 38 patients judged the global efficacy moderate to excellent, 5 patients indicated no global efficacy. The number of days patients sustained PMS symptoms was reduced slightly from 7.5 to 6. Resting levels of blood prolactin remained within the physiological range throughout. No differences were seen between patients on or off oral contraceptives. 20 patients reported 37 adverse events (AE). No serious AE were reported. One patint withdrew after four days of treatment due to fatigue and headache. Laboratory safety control parameters were not affected. In conclusion, patients with PMS can be treated successfully with Vitex agnus-castus extract Ze 440, as indicated by clear improvement in the main effect parameter during treatment and the gradual return after cessation of treatment. The main response to treatment seems related to symptomatic relief rather than to the duration of the syndrome.

Adult↗

PubMed2000

Pharmacological activities of Vitex agnus-castus extracts in vitro.

The pharmacological effects of ethanolic Vitex agnus-castus fruit-extracts (especially Ze 440) and various extract fractions of different polarities were evaluated both by radioligand binding studies and by superfusion experiments. A relative potent binding inhibition was observed for dopamine D2 and opioid (micro and kappa subtype) receptors with IC50 values of the native extract between 20 and 70 mg/mL. Binding, neither to the histamine H1, benzodiazepine and OFQ receptor, nor to the binding-site of the serotonin (5-HT) transporter, was significantly inhibited. The lipophilic fractions contained the diterpenes rotun-difuran and 6beta,7beta-diacetoxy-13-hydroxy-labda-8,14-dien . They exhibited inhibitory actions on dopamine D2 receptor binding. While binding inhibition to mu and kappa opioid receptors was most pronounced in lipophilic fractions, binding to delta opioid receptors was inhibited mainly by a aqueous fraction. Standardised Ze 440 extracts of different batches were of constant pharmacological quality according to their potential to inhibit the binding to D2 receptors. In superfusion experiments, the aqueous fraction of a methanolic extract inhibited the release of acetylcholine in a concentration-dependent manner. In addition, the potent D2 receptor antagonist spiperone antagonised the effect of the extract suggesting a dopaminergic action mediated by D2 receptor activation. Our results indicate a dopaminergic effect of Vitex agnus-castus extracts and suggest additional pharmacological actions via opioid receptors.

Animals↗

PubMed2000

Endotoxin and antiendotoxin antibodies in patients with acute pancreatitis.

OBJECTIVE: To elucidate the time course of endotoxaemia and antiendotoxin antibodies in patients with acute pancreatitis. DESIGN: Prospective clinical study. SETTING: University hospital, Germany. SUBJECTS: 25 patients with oedematous (n = 9) or necrotising (n = 16) pancreatitis, and 20 healthy controls. MAIN OUTCOME MEASURES: Concentrations of endotoxin and immunoglobulins (classes G, M, and A) directed at two lipid A molecules, four lipopolysaccharides, and alpha-haemolysin of Staphylococcus aureus measurements in plasma during a 12 day period. RESULTS: There were no differences in the degree of endotoxaemia between patients with oedematous and necrotising pancreatitis on admission. However, from the day after admission and throughout the observation period patients with necrotising pancreatitis had significantly higher concentrations of endotoxin than those with oedematous pancreatitis. Concentrations of IgM specific for endotoxin peaked at day 4, and then decreased in patients with oedematous pancreatitis while remaining high for those with necrotising pancreatitis. There was only a slight increase in IgA specific for endotoxin, and IgG and immunoglobulins to gamma-haemolysin remained steady throughout the observation period. There was strong cross-reactivity (r > 0.7) between IgM specific for endotoxin (70%), but this was less with IgA (52%), and IgG (20%). CONCLUSIONS: Necrotising pancreatitis is accompanied by persistent endotoxaemia with an extended rise in antiendotoxin antibodies. Patients with oedematous pancreatitis have a transient endotoxaemia with a temporary increase of Ig specific for endotoxin. Endotoxin stimulates the synthesis of specific antibodies (IgM) despite general immunosuppression.

Acute Disease↗