ABSTRACT
BACKGROUND: Histopathologic regression following neoadjuvant treatment (NT) of oesophageal cancer is a prognostic factor of survival, but the nodal status is not considered. Here, a score combining both to improve prediction of survival after neoadjuvant therapy is developed. METHODS: Seven hundred and fifteen patients with oesophageal squamous cell (SCC) or adenocarcinoma (AC) undergoing NT and esophagectomy were analysed. Histopathologic response was classified according to percentage of vital residual tumour cells (VRTC): complete response (CR) without VRTC, major response with <10% VRTC, minor response with >10% VRTC. Nodal stage was classified as ypN0 and ypN+. Kaplan-Meier and Cox regression were used for survival analysis. RESULTS: Survival analysis identified three groups with significantly different mortality risks: (1) low-risk group for CR (ypT0N0) with 72% 5-year overall survival (5y-OS), (2) intermediate-risk group for minor/major responders and ypN0 with 59% 5y-OS, and (3) high-risk group for minor/major responders and ypN+ with 20% 5y-OS (p < 0.001). Median survival in AC and SCC cohorts were comparable (3.8 (CI 95%: 3.1, 5.3) vs. 4.6 years (CI 95%: 3.3, not reached), p = 0.3). CONCLUSIONS: Histopathologic regression and nodal status should be combined for estimating AC and SCC prognosis. Poor survival in the high-risk group highlights need for adjuvant therapy.
Subject(s)
Adenocarcinoma , Esophageal Neoplasms , Humans , Neoadjuvant Therapy , Neoplasm Staging , Esophageal Neoplasms/pathology , Prognosis , Combined Modality Therapy , Adenocarcinoma/pathology , Esophagectomy , Treatment Outcome , Retrospective StudiesABSTRACT
Introduction The inflammatory microenvironment has emerged as one of the focuses of cancer research. Little is known about the immune environment in esophageal adenocarcinoma (EAC) and possible tumor-escape mechanisms to avoid immune cell attack. Patients and methods We measured T cell inflammation (CD3, CD8) in the microenvironment using a standardized software-based evaluation algorithm considering different predefined tumor areas as well as expression of MHC class 1 and PD-L1 on 75 analyzable primarily resected and locally advanced (≥ pT2) EACs. We correlated these findings statistically with clinical data. Results Patients with high amounts of T cell infiltration in their tumor center showed a significant survival benefit of 41.4 months compared to 16.3 months in T cell poor tumors (p = 0.025), although CD3 fails to serve as an independent prognostic marker in multivariate analysis. For the invasion zone, a correlation between number of T-cells and overall survival was not detectable. Loss of MHC1 protein expression on tumor cells was seen in 32% and PD-L1 expression using the combined positive score (CPS) in 21.2%. Most likely due to small numbers of cases, both markers are not prognostically relevant, even though PD-L1 expression correlates with advanced tumor stages. Discussion Our analyses reveal an outstanding, though not statistically independent, prognostic relevance of T-cell-rich inflammation in our group of EACs, in particular driven by the tumor center. For the first time, we describe that the inner part of the invasion zone in EACs shows significantly fewer T-cells than other tumor segments and is prognostically irrelevant. We also demonstrate that the loss of antigen presenting ability via MHC1 downregulation by the carcinoma cells is a common escape mechanism in EACs. Future work will need to show whether tumors with MHC class 1 loss respond less well to immunotherapy (AU)
Subject(s)
Humans , Male , Female , Middle Aged , Aged , Tumor Microenvironment/immunology , Tumor Escape/immunology , Lymphocytes, Tumor-Infiltrating , Esophageal Neoplasms/immunology , Adenocarcinoma/immunology , Neoplasm Invasiveness/immunology , Esophageal Neoplasms/mortality , Esophageal Neoplasms/pathology , Down-Regulation , Adenocarcinoma/mortality , Adenocarcinoma/pathology , Time Factors , PrognosisABSTRACT
INTRODUCTION: The inflammatory microenvironment has emerged as one of the focuses of cancer research. Little is known about the immune environment in esophageal adenocarcinoma (EAC) and possible tumor-escape mechanisms to avoid immune cell attack. PATIENTS AND METHODS: We measured T cell inflammation (CD3, CD8) in the microenvironment using a standardized software-based evaluation algorithm considering different predefined tumor areas as well as expression of MHC class 1 and PD-L1 on 75 analyzable primarily resected and locally advanced (≥ pT2) EACs. We correlated these findings statistically with clinical data. RESULTS: Patients with high amounts of T cell infiltration in their tumor center showed a significant survival benefit of 41.4 months compared to 16.3 months in T cell poor tumors (p = 0.025), although CD3 fails to serve as an independent prognostic marker in multivariate analysis. For the invasion zone, a correlation between number of T-cells and overall survival was not detectable. Loss of MHC1 protein expression on tumor cells was seen in 32% and PD-L1 expression using the combined positive score (CPS) in 21.2%. Most likely due to small numbers of cases, both markers are not prognostically relevant, even though PD-L1 expression correlates with advanced tumor stages. DISCUSSION: Our analyses reveal an outstanding, though not statistically independent, prognostic relevance of T-cell-rich inflammation in our group of EACs, in particular driven by the tumor center. For the first time, we describe that the inner part of the invasion zone in EACs shows significantly fewer T-cells than other tumor segments and is prognostically irrelevant. We also demonstrate that the loss of antigen presenting ability via MHC1 downregulation by the carcinoma cells is a common escape mechanism in EACs. Future work will need to show whether tumors with MHC class 1 loss respond less well to immunotherapy.
Subject(s)
Adenocarcinoma/immunology , Esophageal Neoplasms/immunology , Lymphocytes, Tumor-Infiltrating/cytology , Tumor Escape/immunology , Tumor Microenvironment/immunology , Adenocarcinoma/mortality , Adenocarcinoma/pathology , Aged , B7-H1 Antigen/analysis , B7-H1 Antigen/metabolism , Down-Regulation , Esophageal Neoplasms/mortality , Esophageal Neoplasms/pathology , Female , HLA-A Antigens/analysis , HLA-A Antigens/metabolism , HLA-B Antigens/analysis , HLA-B Antigens/metabolism , Humans , Immunity, Cellular , Inflammation/immunology , Lymphocyte Count , Male , Middle Aged , Neoplasm Invasiveness/immunology , Prognosis , Time FactorsABSTRACT
BACKGROUND: Ivor-Lewis esophagectomy (ILE) is the standard surgical care for esophageal cancer patients but postoperative morbidity impairs quality of life and reduces long-term oncological outcome. Two-stage ILE separating the abdominal and thoracic phase into two distinct surgical procedures has proven to enhance microcirculation of the gastric conduit and therefore most likely reduces complications. However, two-stage ILE has not been evaluated systematically in selected groups of patients scheduled for this procedure. This investigation aims to demonstrate the feasibility of two-stage ILE in high-risk patients. PATIENTS AND METHODS: In this retrospective analysis of data obtained from a prospective database, a consecutive series of 275 hybrid ILE (hILE) were included. Patients were divided into two groups based on one- or two-stage hILE. Postoperative complications were assessed according to ECCG (Esophageal Complication Consensus Group) criteria and compared using the Clavien-Dindo score. Indication for two-stage esophagectomy was classified as pre- or intraoperative decision. RESULTS: 34 out of 275 patients (12.7%) underwent two-stage hILE. Patients of the two-stage group were significantly older. In 21 of 34 patients (61.8%) the decision for a two-stage procedure was made prior to esophagectomy, in 13 (38.2%) patients intraoperatively after completion of the laparoscopic gastric mobilization. The most frequent preoperative reason to select the two-stage procedure was a stenosis of the coeliac trunc and superior mesenteric artery (n = 10). The predominant cause for an intraoperative change of strategy was a laparoscopically diagnosed hepatic fibrosis/cirrhosis (n = 5).Overall morbidity and major' complications (CD > IIIa) were comparable for both groups (11.7% in both groups). The overall anastomotic leak rate was 12.4% and was non-significant lower for the two-stage procedure. CONCLUSION: Two-stage hILE is a feasible concept to individualize the surgical treatment of patients with well-defined clinical risk factors for postoperative morbidity. It can also be applied after completion of the abdominal phase of IL esophagectomy without compromising the patient safety.
Subject(s)
Esophagectomy/methods , Morbidity/trends , Plastic Surgery Procedures/methods , Postoperative Complications/etiology , Quality of Life/psychology , Aged , Esophageal Neoplasms/surgery , Female , Humans , Male , Middle Aged , Retrospective StudiesABSTRACT
T-cell prolymphocytic leukemia (T-PLL) is a poor-prognostic neoplasm. Differentiation stage and immune-effector functions of the underlying tumor cell are insufficiently characterized. Constitutive activation of the T-cell leukemia 1A (TCL1A) oncogene distinguishes the (pre)leukemic cell from regular postthymic T cells. We assessed activation-response patterns of the T-PLL lymphocyte and interrogated the modulatory impact by TCL1A. Immunophenotypic and gene expression profiles revealed a unique spectrum of memory-type differentiation of T-PLL with predominant central-memory stages and frequent noncanonical patterns. Virtually all T-PLL expressed a T-cell receptor (TCR) and/or CD28-coreceptor without overrepresentation of specific TCR clonotypes. The highly activated leukemic cells also revealed losses of negative-regulatory TCR coreceptors (eg, CTLA4). TCR stimulation of T-PLL cells evoked higher-than-normal cell-cycle transition and profiles of cytokine release that resembled those of normal memory T cells. More activated phenotypes and higher TCL1A correlated with inferior clinical outcomes. TCL1A was linked to the marked resistance of T-PLL to activation- and FAS-induced cell death. Enforced TCL1A enhanced phospho-activation of TCR kinases, second-messenger generation, and JAK/STAT or NFAT transcriptional responses. This reduced the input thresholds for IL-2 secretion in a sensitizer-like fashion. Mice of TCL1A-initiated protracted T-PLL development resembled such features. When equipped with epitope-defined TCRs or chimeric antigen receptors, these Lckpr-hTCL1Atg T cells gained a leukemogenic growth advantage in scenarios of receptor stimulation. Overall, we propose a model of T-PLL pathogenesis in which TCL1A enhances TCR signals and drives the accumulation of death-resistant memory-type cells that use amplified low-level stimulatory input, and whose loss of negative coregulators additionally maintains their activated state. Treatment rationales are provided by combined interception in TCR and survival signaling.
Subject(s)
Immunologic Memory , Leukemia, Prolymphocytic, T-Cell/immunology , Proto-Oncogene Proteins/immunology , Receptors, Antigen, T-Cell/immunology , Signal Transduction/immunology , T-Lymphocytes/immunology , Animals , Humans , Leukemia, Prolymphocytic, T-Cell/genetics , Leukemia, Prolymphocytic, T-Cell/pathology , Mice , Mice, Knockout , Proto-Oncogene Proteins/genetics , Receptors, Antigen, T-Cell/genetics , Signal Transduction/genetics , T-Lymphocytes/pathologyABSTRACT
BACKGROUND: Pretransplant psychosocial evaluation of living-donor kidney transplantation (LDKT) candidates identifies recipients with potentially inferior posttransplant outcomes. Rating instruments, based on semi-standardized interviews, help to improve and standardize psychosocial evaluation. The goal of this study was to retrospectively investigate the correlation between the Transplant Evaluation Rating Scale (TERS) and transplant outcome in LDKT recipients. METHODS: TERS scores were retrospectively generated by 2 raters based on comprehensive interviews of 146 LDKT recipients conducted by mental health professionals (interrater reliability, 0.8-0.9). All patients were eligible for transplantation according to pretransplant psychosocial evaluation. Patients were classified into 2 groups according to their TERS scores, in either two thirds excellent risk (TERS <29) and one third at least moderate risk (TERS ≥29) candidates. Analyzed medical parameters were change in estimated glomerular filtration rate and acute rejection (AR) episodes within the first year posttransplant. In addition, a subgroup of 65 patients was tested for de novo donor-specific HLA antibodies (DSA) posttransplant. RESULTS: There was no significant difference between the excellent (n = 97) and at least moderate (n = 49) risk candidates according to TERS in terms of organ function (estimated glomerular filtration rate decline >25%: 17 of 97 vs 11 of 49; P = .51) and episodes of AR (19 of 97 vs 15 of 49; P = .15). Patients developing de novo DSA (n = 18 [28%]) did not have higher pretransplant TERS scores (DSA positive, 11 of 42 vs 7 of 23; P = .78). CONCLUSIONS: Classifying LDKT recipients according to TERS score did not predict medical outcome at 1 year posttransplant or the occurrence of de novo DSA.
Subject(s)
Graft Rejection/psychology , Kidney Transplantation/psychology , Living Donors , Postoperative Complications/psychology , Psychiatric Status Rating Scales/statistics & numerical data , Adult , Antibodies/blood , Antibodies/immunology , Female , Glomerular Filtration Rate , HLA Antigens/immunology , Humans , Male , Middle Aged , Postoperative Period , Reproducibility of Results , Retrospective Studies , Treatment OutcomeABSTRACT
Outbreaks of highly pathogenic avian influenza A virus (HPAIV) subtype H5N8, clade 2.3.4.4, were first reported in January 2014 from South Korea. These viruses spread rapidly to Europe and the North American continent during autumn 2014 and caused, in Germany, five outbreaks in poultry holdings until February 2015. In addition, birds kept in a zoo in north-eastern Germany were affected. Only a few individual white storks (Ciconia ciconia) showed clinical symptoms and eventually died in the course of the infection, although subsequent in-depth diagnostic investigations showed that other birds kept in the same compound of the white storks were acutely positive for or had undergone asymptomatic infection with HPAIV H5N8. An exception from culling all of the 500 remaining zoo birds was granted by the competent authority. Restriction measures included grouping the zoo birds into eight epidemiological units in which 60 birds of each unit tested repeatedly negative for H5N8. Epidemiological and phylogenetical investigations revealed that the most likely source of introduction was direct or indirect contact with infected wild birds as the white storks had access to a small pond frequented by wild mallards and other aquatic wild birds during a period of 10 days in December 2014. Median network analysis showed that the zoo bird viruses segregated into a distinct cluster of clade 2.3.4.4 with closest ties to H5N8 isolates obtained from mute swans (Cygnus olor) in Sweden in April 2015. This case demonstrates that alternatives to culling exist to rescue valuable avifaunistic collections after incursions of HPAIV.
Subject(s)
Disease Outbreaks/veterinary , Influenza A Virus, H5N8 Subtype/isolation & purification , Influenza in Birds/epidemiology , Animal Culling , Animals , Animals, Zoo , Birds , Germany/epidemiology , High-Throughput Nucleotide Sequencing/veterinary , Influenza A Virus, H5N8 Subtype/genetics , Influenza A Virus, H5N8 Subtype/immunology , Influenza A Virus, H5N8 Subtype/pathogenicity , Influenza in Birds/pathology , Influenza in Birds/virology , Phylogeny , Sequence Analysis, DNA/veterinaryABSTRACT
Immunosuppressive strategies applied in renal transplantation traditionally focus on T cell inhibition. B cells were mainly examined in the context of antibody-mediated rejection, whereas the impact of antibody-independent B cell functions has only recently entered the field of transplantation. Similar to T cells, distinct B cell subsets can enhance or inhibit immune responses. In this study, we prospectively analyzed the evolution of B cell subsets in the peripheral blood of AB0-compatible (n = 27) and AB0-incompatible (n = 10) renal transplant recipients. Activated B cells were transiently decreased and plasmablasts were permanently decreased in patients without signs of rejection throughout the first year. In patients with histologically confirmed renal allograft rejection, activated B cells and plasmablasts were significantly elevated on day 365. Rituximab treatment in AB0-incompatible patients resulted in long-lasting B cell depletion and in a naïve phenotype of repopulating B cells 1 year following transplantation. Acute allograft rejection was correlated with an increase of activated B cells and plasmablasts and with a significant reduction of regulatory B cell subsets. Our study demonstrates the remarkable effects of standard immunosuppression on circulating B cell subsets. Furthermore, the B cell compartment was significantly altered in rejecting patients. A specific targeting of deleterious B cell subsets could be of clinical benefit in renal transplantation.
Subject(s)
ABO Blood-Group System/immunology , Blood Group Incompatibility/immunology , Graft Rejection/etiology , Graft Survival/immunology , Kidney Failure, Chronic/surgery , Kidney Transplantation/adverse effects , Transplant Recipients , Adult , B-Lymphocyte Subsets/immunology , Female , Follow-Up Studies , Graft Rejection/blood , Humans , Immunosuppressive Agents/therapeutic use , Living Donors , Male , Postoperative Complications , Prognosis , Prospective Studies , Risk Factors , Transplantation, HomologousABSTRACT
BACKGROUND: During neurosurgery intraoperative imaging of vital neural structures on a cellular level would facilitate the development of new strategies for diagnosis and treatment. In vivo imaging would permit the detection of the tumour centre and infiltration zone. With targeted biopsies the lesion of interest could be determined before performing the biopsy, facilitating the final pathological diagnosis. In this study we present confocal neurolasermicroscopy as a new method in neurosurgery. METHODS: A miniaturised confocal neurolasermicroscope (NLM) was used ex vivo immediately after tumour resection of glioblastoma multiforme (GBM). NLM was performed with subcellular magnification up to a tissue depth of 100 microm. NLM images were compared to conventional histological images of the same tumour. RESULTS: The application of the method in nine patients allowed adequate diagnosis of a malignant glioma fulfilling the WHO criteria when compared to conventional histology. In one patient with glioblastoma multiforme NLM allowed the correct diagnosis of GBM to be made, demonstrating the high mitotic rate and cell pleomorphy of the tumour cells. Additional characteristics such as pleomorphic cells, mitotic figures, fibrillary matrix and the distinction between tumour centre and infiltration zone could be shown. CONCLUSIONS: NLM is a tool which could be adapted for neurosurgical intraoperative applications with the potential to diagnose tumours and recognise the tumour centre and infiltration zone in vivo. Further applications of NLM to characterise subcellular structures and vascular architecture are possible.
Subject(s)
Brain Neoplasms/pathology , Brain Neoplasms/surgery , Brain/pathology , Brain/surgery , Glioblastoma/pathology , Glioblastoma/surgery , Microscopy, Confocal/methods , Microsurgery/methods , Neurons/pathology , Neurosurgical Procedures/methods , Apoptosis , Humans , Image Processing, Computer-Assisted , Immunohistochemistry , Microscopy, Confocal/instrumentation , Microsurgery/instrumentation , Mitosis , Neurosurgical Procedures/instrumentation , Pilot Projects , Subcellular Fractions/ultrastructureABSTRACT
PURPOSE: The effect of transcranial duplex ultrasound (US) on the intraventricular temperature in patients was analyzed. Temperature increases during examination have been identified as a potential risk factor but only data from model studies is currently available. MATERIALS AND METHODS: Patients who had an intracranial pressure/temperature transducer implanted and underwent US assessment were included. In an examination series (B-mode, combined B- and color mode, combined B- and color mode plus Doppler, 3 min for each mode), the intracranial thermodilution thermistor was focused while intraventricular temperature and body temperature (bladder catheter or rectal probe) were recorded continuously and temperature changes were analyzed. RESULTS: Thirty-one US examinations were performed in 14 patients. Twenty-six examinations in 9 patients in which the intracranial temperature probe was depicted were included. Initial patient temperatures ranged from 35.1dgC to 38.7dgC. No significant increase or decrease in intracranial temperature was seen after the first (B-mode), second (B- and color mode) and third (B- and color mode plus Doppler) duplex US examination. T-test for paired samples showed a constant temperature throughout US examination (two-sided significance: 1.000, 1.000, 0.731). CONCLUSION: Routine transcranial duplex ultrasound does not increase the intracranial temperature in patients.
Subject(s)
Brain/physiopathology , Hot Temperature/adverse effects , Ultrasonography, Doppler, Transcranial/adverse effects , Body Temperature , Cerebral Ventricles/diagnostic imaging , Female , Humans , Intracranial Hypertension/diagnostic imaging , Male , Ultrasonography, Doppler, Color/adverse effects , Ultrasonography, Doppler, Color/methods , Ultrasonography, Doppler, Transcranial/methodsABSTRACT
AIMS/HYPOTHESIS: Polycystic ovary syndrome (PCOS) is a risk factor of type 2 diabetes. Screening for impaired glucose metabolism (IGM) with an OGTT has been recommended, but this is relatively time-consuming and inconvenient. Thus, a strategy that could minimise the need for an OGTT would be beneficial. MATERIALS AND METHODS: Consecutive PCOS patients (n=118) with fasting glucose <6.1 mmol/l were included in the study. Parameters derived from medical history, clinical examination and fasting blood samples were assessed by decision tree modelling for their ability to discriminate women with IGM (2-h OGTT value >/=7.8 mmol/l) from those with NGT. RESULTS: According to the OGTT results, 93 PCOS women had NGT and 25 had IGM. The best decision tree consisted of HOMA-IR, the proinsulin:insulin ratio, proinsulin, 17-OH progesterone and the ratio of luteinising hormone:follicle-stimulating hormone. This tree identified 69 women with NGT. The remaining 49 women included all women with IGM (100% sensitivity, 74% specificity to detect IGM). Pruning this tree to three levels still identified 53 women with NGT (100% sensitivity, 57% specificity to detect IGM). Restricting the data matrix used for tree modelling to medical history and clinical parameters produced a tree using BMI, waist circumference and WHR. Pruning this tree to two levels separated 27 women with NGT (100% sensitivity, 29% specificity to detect IGM). The validity of both trees was tested by a leave-10%-out cross-validation. CONCLUSIONS/INTERPRETATION: Decision trees are useful tools for separating PCOS women with NGT from those with IGM. They can be used for stratifying the metabolic screening of PCOS women, whereby the number of OGTTs can be markedly reduced.
Subject(s)
Glucose Intolerance/etiology , Polycystic Ovary Syndrome/blood , Adult , Blood Glucose/metabolism , Body Mass Index , Cohort Studies , Decision Trees , Female , Glucose Intolerance/blood , Glucose Tolerance Test , Hormones/blood , Humans , Models, Statistical , Predictive Value of TestsABSTRACT
OBJECTIVE: Hydrostatic devices have considerable advantages compared to "conventional" differential-pressure-valves concerning overdrainage, but are thought to imply a tendency to underdrain or to clog. The aim of this study was to evaluate the ability of the hydrostatic gravitational Dual-Switch-Valve (DSV) to minimize overdrainage-related complications without increasing the danger of underdrainage. RESULTS: In a series of 202 adult patients with different etiologies treated with a ventriculo-peritoneal shunt including the hydrostatic Dual-Switch-valve (DSV), 21 cases were suspected of suffering from underdrainage. Using a new algorithm we were able to differentiate obstruction in 6 patients from functional underdrainage in 15 cases, thus we saw an indication to reimplant a DSV with a lower opening pressure in the latter. CONCLUSION: The reasons for functional underdrainage were multifold in our series, especially the intraperitoneal pressure is still a "black box". Despite the ability of the DSV to avoid clogging and to minimize overdrainage by its high-pressure-chamber, it remains difficult to determine the optimal opening pressure of the low-pressure-chamber of the DSV for ideal clinical improvement. Therefore a new hydrostatic gravitational "programmable" valve (proGAV), entitled on avoiding the disadvantages of other adjustable devices, has been developed and implanted in 16 patients with promising results.
Subject(s)
Cerebrospinal Fluid Shunts/instrumentation , Equipment Failure Analysis , Hydrocephalus/diagnosis , Hydrocephalus/surgery , Adolescent , Adult , Aged , Aged, 80 and over , Cerebrospinal Fluid Shunts/methods , Female , Humans , Male , Middle Aged , Prosthesis Failure , Prosthesis Fitting/methods , Treatment OutcomeABSTRACT
PURPOSE: The efficacy of anthracyclin-containing adjuvant chemotherapy of node-positive breast cancer can be further improved by adding sequential paclitaxel (T). There is also clinical evidence that replacing cyclophosphamide (C) with vinorelbin (V) might further reduce toxicity. In order to assess the safety of these options, we initiated a clinical cohort study of epirubicin/cyclophoshamide and epirubicin/vinorelbine with or without sequential paclitaxel. METHOD: Patients with node-positive (1-3) breast cancer were assigned to open-label epirubicin/vinorelbine (EV), epirubicin/vino-relbine and sequential paclitaxel (EV/T), epirubicin/cyclophosphamide (EC) or epirubicin/cyclophosphamide plus sequential paclitaxel (EC/T) therapy. RESULTS: Fifty four outpatients received a total of 304 chemotherapy cycles. There were significant differences in grade III/IV anemia only between the EV/T and EC/T groups, in favor of the EC/T group (P=0.002). CONCLUSIONS: The safety of paclitaxel is not impaired when given sequentially after administration of the two anthracyclin-containing regimens. The exchange of cyclophosphamide against vinorelbine leads to deteriorating safety of the EC/T regimen.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Breast Neoplasms/drug therapy , Vinblastine/analogs & derivatives , Adult , Aged , Chemotherapy, Adjuvant , Cyclophosphamide/administration & dosage , Drug Administration Schedule , Epirubicin/administration & dosage , Female , Humans , Lymphatic Metastasis , Middle Aged , Paclitaxel/administration & dosage , Vinblastine/administration & dosage , VinorelbineABSTRACT
Neurons of the caudal fastigial nucleus were investigated by means of single unit recordings. Natural vestibular stimuli were applied as well as galvanic labyrinth polarization. One-third of the neurons showed a convergence of vertical and horizontal canals. More than 80% of the neurons responded to polarization of both the ipsilateral and contralateral canals (binaural responders). Most neurons had a limited response range. Two classes of neurons could be distinguished: up to 1 Hz responders and up to 10 Hz responders. In addition a group of fastigial cells showed a tuning within a small range of frequencies (sharp-tuning responders).
Subject(s)
Action Potentials/physiology , Cerebellar Nuclei/physiology , Neurons/physiology , Postural Balance/physiology , Semicircular Canals/physiology , Vestibular Nerve/physiology , Vestibular Nuclei/physiology , Animals , Cerebellar Nuclei/cytology , Electric Stimulation/methods , Electrophysiology/methods , Eye Movements/physiology , Female , Functional Laterality/physiology , Male , Physical Stimulation , Rats , Vestibular Nerve/cytology , Vestibular Nuclei/cytologyABSTRACT
Efficiency of animal waste sterilization prescribed by the European Union and Switzerland was verified using a pork-based ELISA and two PCR assays (tRNA(Glu)/cytochrome b specific for vertebrates; bovine species-specific cytochrome b mitochondrial genome). A total of 204 samples of feedingstuffs were analysed including reference materials subjected to known heat treatments. Both ELISA and PCR assays were able to detect poorly heat-treated feedingstuffs if there was enough pork-based material present. The proposed species-specific PCR test, however, showed a higher sensitivity and specificity as it specifically detected bovine material. Nevertheless, the PCR assay will not detect bovine material in properly heat-treated feeds as the DNA is too fragmented. It is, however, very useful as a rapid, sensitive, and specific method for the routine screening of animal meals with regard to prophylaxis of BSE.
ABSTRACT
Ejaculatory disorders can interfere with the fertility of young adults who suffer from spinal cord injury, have type I diabetes mellitus or have undergone retroperitoneal or intrapelvic operations. Following an overview of causes and treatment of ejaculatory disorders, the data of our centre are presented. From a group of 37 patients with genuine loss of seminal emission, 15 men and their wives were offered a combined treatment of rectal probe electro-ejaculation and artificial reproductive techniques. No serious complications occurred. During 40 cycles with intracorporeal insemination and 11 cycles with extracorporeal fertilization techniques, seven pregnancies were achieved, representing a pregnancy rate of 46% per couple and 14% per cycle for all cycles. Five healthy children were born, all following extracorporeal insemination. The 'take-home baby rate' for this population and for this technique is 45%. In vitro fertilization (IVF) led to one birth, intracytoplasmic sperm injection (ICSI) achieved four live births out of three pregnancies, one being a twin gestation. Since our successes are due to the use of extracorporeal insemination techniques, these are now incorporated in a new, more rational treatment protocol.
Subject(s)
Ejaculation , Reproductive Techniques , Sexual Dysfunction, Physiological/therapy , Electric Stimulation , Female , Humans , Male , Pregnancy , Sexual Dysfunction, Physiological/etiologyABSTRACT
For the diagnostic evaluation of infertility it is crucial to obtain information on potential abnormalities of the uterus or the fallopian tubes. At present, the following diagnostic methods are available: CO2-pertubation, hysteroscopy, hysterosalpingography (HSG) and chromolaparoscopy (CLP). For the latter procedure, general anaesthesia is required. In a clinical trial 103 patients from our infertility clinic were examined for fallopian tube patency using the contrast agent SH U 454 (Echovist). The new technique hystero-contrast sonography (Hy-Co-Sy) was carried out in an outpatient setting without requiring general anaesthesia. Informed consent was obtain from all patients. A Foley catheter was inserted into the uterine cavity, the balloon was inflated and the contrast medium injected. Distribution of the contrast agent as well as the uterine cavity, the fallopian tubes as well as in the pouch of Douglas was then observed by sonography. In addition to Hy-Co-Sy, 58 patients underwent HSG or CLP. Hy-Co-Sy findings could confirmed by HSG and CLP in 90.6% and 91.6%, respectively. Patients were asked to describe their discomfort on a scale of one to hundred. The average time required for the assessment to tubal patency was 9 minutes. Within 12 months of the Hy-Co-Sy study, 23 out of 60 patients (38.3%) became pregnant. Our study shows that Hy-Co-Sy is a valuable and reliable procedure to assess the uterine cavity and the fallopian tubes in patients undergoing treatment for infertility. The procedure can be performed safely in the office without the need for general anaesthesia.(ABSTRACT TRUNCATED AT 250 WORDS)
Subject(s)
Contrast Media , Fallopian Tube Diseases/diagnostic imaging , Infertility, Female/diagnostic imaging , Polysaccharides , Adult , Ambulatory Care , Fallopian Tube Diseases/therapy , Fallopian Tube Patency Tests , Female , Follow-Up Studies , Humans , Infertility, Female/therapy , Pregnancy , UltrasonographyABSTRACT
Forty-six patients (28 boys, 18 girls) were treated with growth hormone (GH) for short stature. Twenty-eight patients had total growth hormone deficiency (GHD), 12 partial GHD and 6 patients had short stature without GHD. Brain tumours were the cause of GHD in 8 patients and multiple pituitary hormone deficiency was present in 9 children. All patients received GH with subcutaneous injections only, 6-7 times/week. Mean final height for all patients was -1.11 SDS and was similar in boys (-1.09 SDS) and girls (-1.13 SDS). Target height SDS was -0.80 SDS in 42 patients, comparing favourably with a final height SDS of -1.05. Similar results were obtained in all patient sub-groups. Height velocity during the last year of therapy was between 2.1 and 9.9 cm/year in 34 patients and below 2 cm in 12 patients. As further growth is to be expected, target height will probably be reached by most patients.
Subject(s)
Body Height/physiology , Growth Hormone/deficiency , Adolescent , Bone Development/drug effects , Brain Neoplasms/complications , Child , Female , Growth Disorders/drug therapy , Growth Disorders/etiology , Growth Hormone/administration & dosage , Growth Hormone/therapeutic use , Humans , Injections, Subcutaneous , Male , Pituitary Hormones/deficiency , Retrospective StudiesABSTRACT
A prospective study was performed to analyse the relationship between urogenital infections caused by Chlamydia trachomatis and occlusions of the fallopian tubes with histologically confirmed chronic salpingitis and salpingitis isthmica nodosa. 110 infertile patients were tested for C. trachomatis infection. 23 patients with tubal occlusions and histologically confirmed chronic salpingitis (group 1) and eight patients with salpingitis isthmica nodosa (group 2) were compared to 13 patients with tubal occlusions after tuboligation (group 3), and to 66 patients with patent fallopian tubes as demonstrated by laparoscopy or hysterosalpingography (group 4). The prevalence of infections of the endocervix or urethra and the presence of Chlamydia in urine was low in all four groups. However, in groups 1 and 2, the median Chlamydia IgG and IgA serum antibody titres were significantly higher (p < or = 0.0002) than in groups 3 and 4. This result illustrates the association between urogenital infections with Chlamydia and tubal occlusions with histologically documented chronic salpingitis and salpingitis isthmica nodosa.