Idiopathic CD4+ T lymphocytopenia presenting as mycetoma in a patient with a mutation in the cystic fibrosis transmembrane regulator gene.
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Biomedical subjects
Publications and source records attributed to B Neumeister.
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OBJECTIVE: To investigate the potential role of endogenous prostacyclin (PGI2) released after mesenteric traction during major abdominal surgery on perioperative endotoxemia and bacterial translocation. DESIGN: Prospective, randomized, double-blind clinical study. SETTING: Operating room and surgical intensive care unit in a university hospital. PATIENTS: Fifty consecutive patients scheduled for major abdominal surgery (pancreas resection, abdominal aortic surgery). INTERVENTIONS: Fifteen minutes before skin incision, either 400 mg of ibuprofen or a placebo equivalent were administered intravenously. Immediately after peritoneal incision, eventration and action of the small bowel was intentionally performed in a uniform fashion. MEASUREMENTS AND MAIN RESULTS: Baseline values were obtained before induction of anesthesia. Additional measurements, along with assessments of hemodynamics and gas exchange, were performed before incision of the peritoneum and at 5, 30, and 45 mins and 3, 6, and 24 hrs after mesenteric traction. Arterial plasma concentrations of 6-keto-prostaglandin F1 alpha and thromboxane B2 (stable metabolites of PGI2 and thromboxane A2) were determined by radioimmunoassay. Endotoxin was measured by limulus amebocyte lysate test. Mesenteric lymph nodes were sampled in 31 patients (ibuprofen n = 14, placebo n = 17) and sent for culture under sterile conditions. Transient hypotension and a marked increase of plasma 6-keto-prostaglandin F1 alpha concentrations occurred up to 6 hrs after mesenteric traction in untreated patients with median peak concentrations (2243 vs. 72 ng/L [p < .0001, placebo vs. ibuprofen], observed 5 mins after mesenteric traction). Endotoxemia occurred in both study groups. However, after mesenteric traction, plasma endotoxin concentrations were significantly higher in the ibuprofen group. Median peak concentrations (0.12 vs. 0.27 EU/mL [p < .001, placebo vs. ibuprofen]) were observed 3 hrs after mesenteric traction. Gram-negative bacteria in mesenteric lymph nodes were detected exclusively in the ibuprofen group (n = 5, p < .01). CONCLUSIONS: In ibuprofen-pretreated patients, significantly higher endotoxin concentrations as well as bacterial translocation to mesenteric lymph nodes occurred, despite the absence of a transient decrease in mean arterial pressure that had been associated with PGI2 release. Therefore, we hypothesized that during major abdominal surgery, endogenous PGI2 released in response to mesenteric traction may play a crucial role in maintaining splanchnic microcirculation and thus preserving gut mucosal barrier function.
Several lines of evidence suggest that surfactant and surfactant proteins may have direct effects on inhaled bacteria and are able to interact with lung defence mechanisms in many ways. We examined the effect of three different surfactant preparations (Alveofact, Survanta and Exosurf) approved for treatment of the infant respiratory distress syndrome on different strains of Escherichia coli, Staphylococcus aureus, Staphylococcus epidermidis and Streptococcus agalactiae which are important neonatal pathogens and on Legionella pneumophila serogroup I as a frequent cause of pneumonia in adults. Addition of Survanta to saline seemed to delay the reduction of viable bacteria in sterile saline and induced a considerably accelerated growth of all examined E. coli strains. As opposed to this, addition of surfactant did not influence the kinetics of bacterial growth in brain-heart infusion or buffered yeast extract both with the exception of Exosurf which exerted an inhibitory effect on the multiplication of group B streptococci. Though the exact mechanisms underlying these effects remain to be determined, the influence of surfactant therapy on the growth of bacteria within the respiratory tract should be taken into account.
Flagella of Legionella pneumophila serogroup 1, strain Philadelphia (ATCC 33152), were isolated and used as antigen to detect antibodies by enzyme immunoassay (EIA) in sera of patients with significant titers against Legionella as determined by the indirect immunofluorescence assay (IFA). Healthy blood donors served as a control group. Whereas the sera of blood donors were negative in both assays, sera of patients showed two patterns of reactivity. Sera with elevated titers against Legionella pneumophila serogroup 1 or Legionella gormanii in IFA usually demonstrated high titers in EIA. However, high IFA titers against Legionella bozemanii were associated with low titers in EIA. The data show that flagella protein of Legionella pneumophila serogroup 1 strain Philadelphia is of limited value for the detection of antibodies against Legionella other than Legionella pneumophila serogroup 1, although in vitro studies revealed genus-specific epitopes. This might be due to unpredictable variabilities in the expression of flagella in vivo.
The species spectrum, antibiotic susceptibility, and genomic profile of coagulase-negative staphylococci (CNS) isolated from infected preterm infants were compared with those obtained in CNS from nursery personnel. Staphylococcus epidermidis was the predominant species in the 66 investigated preterm infants (171 isolates), accounting for 64% of all isolates. A high proportion of Staphylococcus haemolyticus (32%) could be detected. In contrast to the results in patients, the spectrum in nursery personnel was broad and included more species of CNS. All isolates of CNS from preterm infants demonstrated a low rate of susceptibility to the beta-lactam antibiotics (2% sensitivity to penicillin and 6% sensitivity to oxacillin). Sensitivity to gentamicin (9%) was also rare. An unexpected observation was susceptibility to teicoplanin in only 70% of all CNS isolated from patients due to the high proportion of Staphylococcus haemolyticus. Analysis of the genomic profile of 33 isolates of Staphylococcus haemolyticus by pulsed-field gel electrophoresis revealed a relationship between the strains. An outbreak of one particular strain of Staphylococcus haemolyticus in the neonatal intensive care unit investigated can therefore not be excluded.
OBJECTIVES: To investigate at what time the peak level should be determined under conventional thrice daily (t.i.d.) administration of the aminoglycoside netilmicin and to study its serum concentrations under once daily (od) treatment to define the required daily dose and to gain information about convenient drug monitoring. DESIGN: The design of the study was a consecutive sample trial. SETTING: The study took place in a university hospital. PATIENTS: 41 intubated patients of a surgical ICU who received netilmicin as a short-term infusion over 30 min for life-threatening infections were included in the study. INTERVENTIONS: In 21 patients netilmicin was administered t.i.d. The virtual peak levels which had been determined by pharmacokinetic dosage calculation were compared with the serum concentrations obtained directly after the administration as well as after 15, 30, 60 and 180 min. In 20 patients the netilmicin serum concentrations during od treatment were determined directly before and immediately after the application as well as 0.5, 1, 3, 7 and 12 h later. To achieve a virtual peak level of 25 mg/l and a trough level of 0.5 mg/l individual adjustment of the dosage based on pharmacokinetic calculations was performed. MEASUREMENTS AND RESULTS: In t.i.d. treatment the serum concentration measured after 30 min was closest to the virtual peak level; therefore, this is the best time to determine the peak level. In od treatment the required daily dose was 7.86 mg/kg body weight (median) in patients with normal renal function. During od dosing the trough level was extremely important in drug monitoring, whereas determination of the high peak level was of doubtful value. CONCLUSIONS: The peak level should be determined during t.i.d. administration at 30 min. In od treatment the initial daily dose should be 7 mg/kg body weight; in drug monitoring the trough level is very important.
One of the problems in histopathology of ovarian tumors is differential diagnosis between the poorly differentiated carcinomas and granulosa cell tumors of the sarcomatoid type. Hence we evaluated the expression of various cytokeratins (CK 1-19; CK 10, 13, 14, 15, 19; CK 8, 18, 19; CK HMW 1, 5, 10, 11; CK 8; CK 1-19 Stähli; CK AE1/AE3) immunohistochemically in 53 ovarian malignancies (11 of them poorly differentiated carcinomas and 12 granulosa cell tumors). CK HMW was not detected in granulosa cell tumors, and in only half of the carcinomas. AE1/AE3 was expressed by more than 90% of ovarian carcinomas but by one granulosa cell tumor only. The other keratins we investigated showed higher expression rates in granulosa cell tumors and/or lower expression rates in ovarian carcinomas. We think that cytokeratin immunohistochemistry is of value in differentiating between granulosa cell tumors and ovarian carcinomas.
Estrogen and progesterone receptors were immunohistochemically recorded from 426 cases of primary mammary carcinoma. Immunohistochemical detection was based on monoclonal antibodies to estrogen receptor (H222) and progesterone receptor (KD68). Immunohistochemical and biochemical tests were correlated to each other with significance (p less than 0.0001) for either receptor. Some of the histological parameters exhibited relationships with the immunohistochemical receptor status. Receptor positivity of lobular, mucoid, tubular, and papillary carcinomas was more frequent than that of ductal carcinoma, whereas that of medullary carcinoma fell below ductal cases. A straight forward correlation of statistical significance was found to exist between histological tumor grade and steroid hormone receptor status. Receptor positivity of carcinomas with sizeable stroma components proved to be more frequent than that of carcinomas with lower stroma levels. Steroid hormone receptors can be immunohistochemically identified from cytological specimens, as well, though some limiting factors are implied in the latter. Thirteen percent of fine-needle aspirates provided falsely negative steroid hormone receptor findings, as compared to histological biopsy. This problem was encountered primarily in cases of low receptor positivity and high stroma content of carcinoma, factors for which only minor amounts of cell material could be obtained from puncturing. Clinical follow-up checks and evaluation of survival data revealed the immunohistochemically determined steroid hormone receptor status to be of significant importance to prognostication (ER-ICA p less than 0.00001; PgR-ICA p = 0.004). The prognosis of patients with negative estrogen and progesterone receptors was found to be worse than that of patients with positive receptor status. These studies are likely to confirm immunohistochemical determination of steroid hormone receptors, using monoclonal antibodies, to be a reliable method of great prognostic importance.
An immunocytochemical assay (ICA) for the measurement of estrogen receptor (ER) and progesterone receptor (PgR) has been evaluated in 426 human primary breast carcinomas. For estrogen receptor determination ER ICA was used. PgR ICA was performed using the monoclonal antibody KD 68. Assay results for progesterone receptor immunocytochemistry were in agreement (P less than 0.0001) with those of biochemical determination in 74%. Progesterone receptor positivity determined with a semiquantified approach based on intensity and heterogeneity of immunocytochemical staining correlated significantly with biochemically determined progesterone receptor levels (P = 0.0001). Survival data showed a significantly better overall survival for patients with either ER ICA- or PgR ICA-positive carcinomas (ER ICA, P less than 0.00001; PgR ICA, P = 0.004). Patients with both negative ER ICA and PgR ICA showed a poorer prognosis than patients with only one negative receptor. In ER ICA- and PgR ICA-positive carcinomas a trend could be found that patients whose carcinomas contained high numbers of receptor-positive tumor cells had a better survival. This study demonstrates that ER ICA and PgR ICA are strong prognostic indicators and that the proportion of steroid hormone receptor-positive tumor cells seems to be of clinical importance.
Forty-one patients with Stage III and IV squamous cell carcinomas (SCC) of the head and neck were treated preoperatively with mitomycin C and 5-fluorouracil and concomitant radiotherapy. Operation specimen were examined histologically, the percentage of vital tumor cells and devitalized tumor cells were graduated. The grade of regression was classified according to a four-stage scale. Tumor regression was elevated as good (Grades 1, 2) and bad (3, 4) response to combined preoperative therapy. After a follow-up of 18 to 30 months, 14 of 41 patients have experienced a locoregional recurrence; all these patients were bad responders (Grades 3, 4) to preoperative radiochemotherapy. There was a statistically significant correlation between tumor regression grade and probability of survival (P less than 0.001). The authors conclude that the prognosis of patients with pretreated SCC of head and neck depends on the histologic grade of tumor regression.
The diagnostic value of immunocytochemical tests was analysed for 19 cases of pulmonary histiocytosis X (PHX) and eight of other types of fibrosing pulmonary disease (sarcoidosis, 3; exogenous allergic alveolitis, 3; chronic pneumonia, 1; fibrosing alveolitis, 1). The cellular, proliferative-fibroblastic and fibrocystic stages in the course of pulmonary changes were differentiated. PHX cells reacted with anti-S 100 protein in all stages. In three cases for which unfixed tissue was available, all PHX cells reacted with antibody Leu-6, and 35% of these cells also reacted with the proliferation marker Ki-67. The few S-100 positive cells from the eight controls were limited to peribronchial tissue. Thus the antibodies Leu-6 and S-100 are useful aids in the diagnosis of PHX.
Squamous cell carcinomas in the oral cavity and the oropharynx were diagnosed in 84 patients. After verification by biopsy, 79 of these patients were treated preoperatively with mitomycin C and 5-fluro-uracil, radiated and operated 3-5 weeks later. The effectiveness of adjuvant preoperative radio-chemotherapy was evaluated histologically. Serial sections of the entire tumor specimen were investigated and the percentage of vital cancerous tissue in the total tumor area was assessed. Regression was classified into four grades. Grades I and II were regarded as good response to adjuvant preoperative radio-chemotherapy, while grades III and IV stood for bad or no response. Morphologically questionable residual tumor infiltrates could be clarified by immunohistochemical methods with antibodies against vimentin, desmin and Lu-5. The histological assessment of the regression grade of operated tumor specimens allows a clinically relevant, morphologically exact and reproducible evaluation of the effect of preoperative radiochemotherapy.
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The tumor-specificity of tumor-clostridia-phenomenon in the model of Jensen-sarcoma of the white rat was detected with the help of humoral and cell-mediated immune reactions of the host towards intravenous application of 5 X 10(8) spores of clostridia, which do not dissolve the tumor. Contrary to weak responses in Widal-agglutination the MAI showed characteristic values of inhibition of peritoneal-cell-adherence in tumor-bearing animals after incubation with soluble clostridia antigens.
In the present report investigations for cellular sensitization against Jensen-sarcoma of the white rat are performed. Macrophage-Adherence-Inhibition-Test according to Halliday and Miller in a modification according to Schimke was the applied test. A significant adherence-inhibition of peritoneal cells of tumor-bearing rats was found in comparison to control animals with a plateau on day 12 after transplantation and a praemortal eclipse phenomenon from day 19 after inoculation with tumor cells. The concentration of immune complexes shows the same manner, but was especially high in animals with small or not-taken tumors, whereas MAI-index was similar to that of the control group. Antibody production against the tumor could not be detected with Ouchterlony-precipitation. Non-specific immunotherapy with DNCB and BCG as well as therapy with soluble tumorantigen in KFA and insoluble polymerized extracts in 2 TU PPD were unsuccessful to prevent the development of tumors in the model.