Successful treatment of life-threatening Evans syndrome due to antiphospholipid antibody syndrome by rituximab-based regimen: a case with long-term follow-up.

An association of antiphospholipid antibody syndrome with antibodies directed against either phospholipids or plasma proteins strongly suggest that B-cell dysfunction may be involved in its pathogenesis. Antiphospholipid antibody syndrome with autoimmune cytopenias shows a poor response rate to conventional treatment with anticoagulants, glucocorticosteroids, immunosuppressive agents, intravenous immunoglobulin or plasmapheresis. We report a case of life-threatening antiphospholipid antibody syndrome with Evans syndrome receiving successful multimodal treatment including anti-CD20 monoclonal antibody rituximab with long-term follow-up.

Sequencing, high-level expression and phylogeny of the pyrophosphate-dependent phosphofructokinase from the thermophilic spirochete Spirochaeta thermophila.

The full-length gene encoding a 554-amino-acid, active pyrophosphate-dependent phosphofructokinase from Spirochaeta thermophila was cloned and sequenced using a combination of degenerate and inverse PCR, and the enzyme expressed to a high level in Escherichia coli. The recombinant enzyme, with a calculated molecular mass of 61 kDa, was purified to near homogeneity and found to be similar to the purified native enzyme for most properties examined. Phylogenetic analysis demonstrated a close relationship between the thermophilic S. thermophila phosphofructokinase and the large beta-subunits of the phosphofructokinases from Borrelia burgdorferi and Treponema pallidum.

Early magnetic resonance imaging of brainstem lesions after severe head injury.

OBJECT: The availability of magnetic resonance (MR) imaging data obtained in comatose patients after head injury is scarce, because MR imaging is somewhat cumbersome to perform in patients requiring ventilation and because, in the first hours after injury, its relevance is clearly inferior to computerized tomography (CT) scanning. The authors assessed the value of MR imaging in the early postinjury period. METHODS: In this prospective study MR imaging was performed in 61 consecutive patients within 7 days after they suffered a severe head injury. An initial CT scan had already been obtained. To understand the clinical significance of the lesions whose morphological appearance was identified with MR imaging, brainstem function was assessed by registration of somatosensory and auditory evoked potentials. Brainstem lesions were visualized in 39 patients (64%). Bilateral pontine lesions proved to be 100% fatal and nonbrainstem lesions carried a mortality rate of 9%. In singular cases circumstances allowed for a clear clinical distinction between primary and secondary brainstem lesions. On MR imaging all lesions were hyper- and hypointense after intervals longer than 2 days. Within shorter intervals (< 2 days) after the injury, primary lesions appeared isointense on MR imaging. In one secondary brainstem lesion there were no traces of blood. CONCLUSIONS: Because mean intracranial pressure (ICP) levels in patients without brainstem lesions were similar to those in patients with brainstem lesions, the authors conclude that it was not mainly increased ICP that accounted for the high mortality rates in patients with brainstem lesions. The authors also conclude that brainstem lesions are more frequently found in severe head injury than previously reported in studies based on neuropathological or CT scanning data. Early MR imaging after head injury has a higher predictive value than CT scanning.

Phosphorus-32-chromic phosphate for ovarian cancer: I. Fractionated low-dose intraperitoneal treatments in conjunction with platinum analog chemotherapy.

UNLABELLED: For many years, 32P-chromic phosphate (32P-CP) intraperitoneal instillations and platinum analogue chemotherapy have been used to treat disseminated ovarian cancer. To investigate possible enhancement of 32P-CP irradiation due to the concomitant administration of chemotherapy, in vitro studies were undertaken. Based on those laboratory investigations, a clinical regimen of combined 32P-CP and platinum analogue chemotherapy was developed. METHODS: In vitro enhancement of 32P-CP cytotoxicity by cisplatin was studied in cultured human ovarian adenocarcinoma (CHOA) cell lines and in a fibroblast cell strain. In addition, ovarian cancer cells obtained from the malignant abdominal ascites and pleural effusions of 10 individual patients were also studied ex vivo. As part of routine clinical care, 30 patients with disseminated ovarian adenocarcinoma underwent up to eight monthly cycles of platinum analogue chemotherapy with concomitant intraperitoneal instillation of 5 mCi of 32P-CP at each monthly chemotherapy cycle. RESULTS: There was an enhanced and possibly supra-additive effect of cisplatin on the cytotoxicity from 32P-CP irradiation. For the 30 patients, the survival rate at 3 yr was 63%. CONCLUSION: Phosphorus-32 CP low-dose intraperitoneal treatments in conjunction with platinum analogue chemotherapy is a promising approach for the treatment of disseminated intraperitoneal ovarian cancer.

Influence of starch fermentation on bile acid metabolism by colonic bacteria.

Secondary bile acids (BA) may be involved in the pathogenesis of colorectal cancer. In vivo, starch malabsorption has been shown to reduce fecal excretion of secondary BA. The present in vitro study was performed to investigate the effect of starch fermentation on BA metabolism by colonic bacteria. Fecal samples of healthy volunteers were incubated in anaerobic batch cultures for 48 hours with the primary bile acids cholic (0.6 g/l) and chenodeoxycholic acid (0.4 g/l). Media were starch free or enriched with starch (10 g/l). The pH was controlled and held at 6 or 7. In the starch-free incubations, secondary BA were rapidly formed, and degradation of primary to secondary BA was complete within 24 hours. The formation of secondary BA was partially inhibited by the addition of starch to the media. This effect was stronger at pH 6 than at pH 7. Starch was rapidly and completely fermented. In conclusion, this study showed that formation of secondary BA by fecal bacteria is inhibited when starch is simultaneously fermented, an effect that is mainly, but not completely, explained by reduction of pH.

Ergonomic research study on aircraft luggage handling.

In this study, the lifting and carrying of freight and luggage at a large German airport is classified by typical conditions of performance. These manual load handling tasks take place in height-restricted workplaces. Different methods for an ergonomic evaluation of these tasks are used. The results of the epidemiological, physiological, and biomechanical studies indicated a strain bottleneck during loading tasks in aircraft holds. Therefore, an additional laboratory study was done, in order to analyse the influence of work weight and weight of work object on heart rate, subjective RPE, and number of work objects handled. As a result of the study, the airport has developed a special lifting and carrying training for the aircraft handlers which aims to reduce strain on the postural and locomotor apparatus by an appropriate technique of work. The training programme consists of theoretical instruction by a company doctor and practical exercises under the supervision of a specially-trained sports teacher.

Ergonomic evaluation of a wheelchair for transfer of disabled passengers at a large airport.

Transferring disabled passengers to the aircraft, both arriving and departing, is one passenger service at a big airport. We use different ergonomic research methods (registration of heart rate, AET job analysis as well as a standardized questionnaire) to evaluate the present wheelchair design. Due to e.g. the high wheelchair backrest, the forces needed to handle the chair and other facts, the current wheelchair causes a strain bottleneck. The results of the AET analysis and the rating of the perceived exertion confirm this finding. A redesigned wheelchair based on ergonomic principles, which reduces stress on the employees and offers more comfort to disabled passengers, is presented.

Optimization of the production of hCG beta-like material by CaSki human cervical carcinoma cells in roller bottle culture.

This study was aimed at optimizing large-scale roller bottle culture conditions for CaSki human cervical carcinoma cells, to produce ectopic hCG beta-like material in quantities sufficient for subsequent characterization studies. Several cell culture techniques contributed to the achievement of this goal: (1) use of serum-free culture medium; (2) use of intermittent recovery periods in presence of serum; and (3) ultrafiltration of the serum-free medium pool for initial concentration of 100-fold.

Choriocarcinoma: blocking factor and monoclonal antibody iodine 131 imaging.

Postoperative iodine 131 monoclonal antibody localization in metastatic choriocarcinoma was accomplished in this study. The monoclonal antibody was prepared to male choriocarcinoma which cross reacted with gestational choriocarcinoma. The antibody was raised against whole choriocarcinoma cells and human chorionic gonadotropin (hCG) cross reactivity was excluded. The purified antibody was iodinated with 131I and successfully imaged BeWo choriocarcinoma transplanted in nude mice; however, imaging of choriocarcinoma in a patient was verified only after resection. It is our belief that failure to sufficiently concentrate the antibody in the tumor before operation was due to blocking factor in the serum of the patient. Blocking factor and hCG dropped postoperatively. Blocking factor activity in 15 patients with metastatic trophoblastic disease was monitored and, like hCG, was found to be a sensitive indicator of the presence of disease. Its efficacy may be in the small number of patients without hCG but with persistent disease.

A human parathyroid carcinoma that produces parathyroid hormone: long term maintenance in tissue culture.

Parathyroid carcinoma cells from a pulmonary metastasis of a patient with a serum Ca of 17 mg/dl and an immunoreactive parathyroid hormone (PTH) of 6.4 ng eq bovine (b) PTH/ml (normal 40--400 pg/ml) have been maintained in tissue culture for more than 2 1/2 years. The cells secrete PTH into the culture media that 1) during immunoassay dilutes in parallel to human hyperparathyroid serum, 2) has a molecular weight similar to intact highly purified bPTH, and 3) stimulates bone resorption in a manner that is equivalent and additive to synthetic bPTH-(1--34).

Human chorionic gonadotropin in BeWo trophoblastic cells after 12 years in continuous culture: retention of intact human chorionic gonadotropin secretion in mechanically versus enzyme-dispersed cells.

Gel filtration and radioimmunological studies were used to demonstrate that BeWo malignant trophoblastic cells, subcultured for more than 12 yr as roller tube colonies using dissection by scalpel, retained the ability to secrete large quantities of intact hCG. By contrast, BeWo cells that had been subcultured weekly for 12 hr using proteolytic enzyme dispersion lost their ability to secrete intact hCG. Rather, a large form of hCG-alpha was the major secretory product, along with lesser amounts of heterogeneous low molecular weight forms of hCG-beta. The gradual loss of hormone secretory ability and fidelity of hormone product by cells in continuous culture is a well known phenomenon. Our results suggest that the habitual use of trypsin-EDTA to subculture cells may accelerate this process.

Immunodiagnosis in ovarian cancer: blocking factor activity.

Tumor immunology studies have been utilized for development of a blocking factor assay for therapy monitoring in ovarian cancer. The blocking factor index was defined as the arithmetic difference between assays conducted in the presence and absence of the patient's serum compared to incubations with normal control lymphocytes. Eighteen advanced ovarian epithelial malignancies have shown blocking factor activity during treatment. Blocking factor has abated in eight patients whose clinical disease completely regressed. Chemotherapy was discontinued after 18 to 24 months. In 10 patients, blocking factor persisted and chemotherapy has been continued. Some of these patients showed decreasing blocking factor; others have shown increases, which led to death due to disseminated disease in four cases. Blocking factor activity was found to correlate with tumor growth.

Expression of cell-mediated immunity and blocking factor using a new line of ovarian cancer cells in vitro.

A cell-mediated cytotoxicity test, quantitated by postlabeling with tritiated thymidine, was used to asses immune reactivity of cancer patients to the HeW cell line derived from serous cystadenocarcinoma of the ovary. Lymphocytes from 71.4% of serous and mucinous cystadenocarcinoma patients demonstrated a cytotoxic response towards the HeW cells, whereas no reactivity was observed towards target cells derived from nonovarian cancer. These observations indicated that the HeW cells express tumor-associated antigen. In some patients bearing similar tumors, cytotoxicity was blocked by ascitic fluid from other patients with cystadenocarcinoma. In addition, antigen obtained from the spent culture fluid of HeW cells exhibited blocking activity in a typical dose-response fashion, suggesting that blocking factor may be free tumor-associated antigen or an antigen-specific suppressor molecule. Thus, blocking of the lymphocytotoxic response of cystadenocarcinoma patients towards HeW cells may be utilized to monitor the isolation of ovarian carcinoma-associated antigen.

Tumor antigen and human chorionic gonadotropin in CaSki cells: a new epidermoid cervical cancer cell line.

Epidermoid cervical carcinoma cells (CaSki line) have been established in continuous culture. When leukocytes from cervical cancer patients were incubated with CaSki culture fluid concentrates, inhibition of leukocyte migration was observed in more than 70 percent of the patients tested. By contrast, significantly less inhibition was observed with normal donor leukocytes or leukocytes from patients with other types of cancer. These results were consistent with the expression of tumor-associated antigen by CaSki cells. Analysis of the serum from the donor of the cell line at the time of tumor biopsy, and of CaSki culture fluids, demonstrated the presence of the beta subunit of human chorionic gonadotropin.