Artificial dialysis membranes: from concept to large scale production

The development of hemodialysis from an experimental concept to a routine medical therapy is closely related to research, manufacturing and availability of dialysis membranes. Collodion, a cellulose-trinitrate derivative, was the first polymer to be used as an artificial membrane and played a central role in further investigations and applications. Basic studies on the mechanism of solute transport through membranes, like diffusion, were done by A. Fick and T. Graham using collodion as a membrane material. In vivo dialysis in animals and humans was performed with collodion by J. Abel in the USA and G. Haas in Germany. Cellophane and Cuprophan membranes replaced collodion later, because of their better performance and mechanical stability. However, due to its alleged lack of hemocompatibility, membranes made from unmodified cellulose lost their market share. They have been replaced by modified cellulosic and synthetic dialysis membranes which show a better hemocompatibility than unmodified cellulose membranes. Most of the new membrane materials are also available in high-flux modifications and for this reason suitable as well for more effective therapy modes, such as hemodiafiltration and hemofiltration. The success of hemodialysis as a routine therapy is also the success of membrane development, because both, a reproducible membrane production and an unlimited availability of dialysis membranes have increased the number of dialyzed patients to about 1 million patients worldwide in 1999.     

Sequential vapour ablation of adjacent segments in canine lung

Introduction: Vapour ablation is used to create lung volume reduction for emphysema patients to improve lung function and quality of life. This study characterises effects of vapour ablation treatment in lung segments within a lobe that are adjacent to lung segments previously treated with vapour in a healthy canine model. Because emphysema is a progressive disease, subsequent treatments could offer continued benefit to the patient. Method: Six healthy canines were treated with vapour at 8.5?cal/g in one upper lobe segment. After a 4-week healing period, the adjacent segment was treated. After a second 4-week healing period, necropsy was performed and the tissue inspected. Clinical effects were monitored during each healing period. Results: Each treatment was well tolerated and no significant abnormalities were observed during the healing phases, including death, pneumothorax, or major decline in health status. Animal health, oxygenation changes, pathology, and airway changes were monitored during the study. Analysis of these end points showed no difference in changes after treatment 2 as compared to changes after treatment 1. Conclusion: In this model, there was no evidence of increased or different clinical observations after a second adjacent vapour ablation. It was not possible to differentiate between the clinical effects of treatment 1 and the clinical effects of treatment 2. These results support investigation of sequential adjacent segmental vapour treatments in humans.     

The genome sequence of Clostridium tetani,the causative agent of tetanus disease

Tetanus disease is one of the most dramatic and globally prevalent diseases of humans and vertebrate animals, and has been reported for over 24 centuries. The manifestation of the disease, spastic paralysis, is caused by the second most poisonous substance known, the tetanus toxin, with a human lethal dose of approximately 1 ng/kg. Fortunately, this disease is successfully controlled through immunization with tetanus toxoid; nevertheless, according to the World Health Organization, an estimated 400,000 cases still occur each year, mainly of neonatal tetanus. The causative agent of tetanus disease is Clostridium tetani, an anaerobic spore-forming bacterium, whose natural habitat is soil, dust, and intestinal tracts of various animals. Here we report the complete genome sequence of toxigenic C. tetani E88, a variant of strain Massachusetts. The genome consists of a 2,799,250-bp chromosome encoding 2,372 ORFs. The tetanus toxin and a collagenase are encoded on a 74,082-bp plasmid, containing 61 ORFs. Additional virulence-related factors could be identified, such as an array of surface-layer and adhesion proteins (35 ORFs), some of them unique to C. tetani. Comparative genomics with the genomes of Clostridium perfringens, the causative agent of gas gangrene, and Clostridium acetobutylicum, a nonpathogenic solvent producer, revealed a remarkable capacity of C. tetani: The organism can rely on an extensive sodium ion bioenergetics. Additional candidate genes involved in the establishment and maintenance of a pathogenic lifestyle of C. tetani are presented.     

Rupture of ectopic pregnancy with minimally detectable beta-human chorionic gonadotropin levels: a report of 2 cases

BACKGROUND: Several studies have demonstrated that 25-77% of ectopic pregnancies spontaneously resolve with expectant management. However, expectant management is controversial and should be considered only for patients with small, unruptured gestational sacs, low beta-human chorionic gonadotropin (beta-hCG) levels and absence of symptoms. There is no consensus on how long to follow such patients. CASES: Two patients with beta-hCG levels < 10 mIU/mL presented with ruptured ectopic pregnancy and hemoperitoneum. CONCLUSION: While expectant management of a suspected ectopic pregnancy may allow spontaneous resolution of such an ectopic pregnancy, rupture may occur at any time and even with extremely low beta-hCG levels. Patients need to be counseled about the risks of rupture and symptoms, immediate action should be taken if symptoms develop, and serum beta-hCG levels should be followed to zero.     

The beta2-microglobulin/cystatin C ratio--a potential marker of post-transplant lymphoproliferative disease

BACKGROUND: As a consequence of more intensified immunosuppression, post-transplant lymphoproliferative disease (PTLD) is increasingly observed in patients after solid-organ transplantation. Beta2-microglobulin, a low-molecular weight protein (MW 11.8 kDa), is produced by all nucleated cells as part of the HLA complex. Its serum concentration is directly correlated with prognosis in patients with lymphatic neoplasms. Like other low-molecular weight proteins, beta2-microglobulin is eliminated by glomerular filtration. This complicates its use as a tumor marker in renal insufficiency. Cystatin C, a low-molecular weight protein of 13.3 kDa, is a new marker of kidney function largely unaffected by extrarenal disease. We, therefore, sought to assess the potential of the beta2-microglobulin/cystatin C ratio (beta2M/Cys) as a marker of lymphoproliferation. PATIENTS AND METHODS: Beta2M/Cys was determined by particle-enhanced immunonephelometry in sera from 132 children with different degrees of renal insufficiency, 5 of whom had lymphoproliferative disease. Renal function was assessed using the Schwartz formula. RESULTS: Beta2M/Cys was constant between 1.2 and 2.4 mg/mg for Schwartz GFR > or = 40 ml/min x 1.73 m2. With lower GFR, beta2M/Cys rose progressively, maximum values being found in the hemodialysis patients (4.85-11.73). Healthy renal transplant recipients had beta2M/Cys comparable to controls. With acute lymphoproliferative disease, all but one patient had significantly elevated beta2M/Cys between 2.68 and 3.68 mg/mg, which returned to normal in remission (1.67-2.35 mg/mg). The sensitivity of a beta2M/Cys ratio > 2.4 mg/mg for the detection of PTLD was 80%, the specificity 100%, positive predictive value 100%, negative predictive value 90%. CONCLUSION: The beta2-microglobulin/cystatin C ratio is a promising parameter of lymphoproliferation in patients with normal or mildly impaired renal function.     

Uterine position at real embryo transfer compared with mock embryo transfer

BACKGROUND: The purpose of this study was to determine the consistency in the uterine position between mock and real embryo transfer. METHODS: We reviewed 996 consecutive embryo transfer cycles (585 patients); 74% of patients had an anteverted (AV) uterus and 26% had a retroverted (RV) uterus at mock embryo transfer. All mock and real embryo transfers were performed under abdominal ultrasound guidance. RESULTS: Of 623 fresh embryo transfers in patients with an AV uterus at mock embryo transfer, only 2% became RV, while 55% of 213 embryo transfers in patients with an RV uterus on mock embryo transfer converted to AV at real embryo transfer (P < 0.0001). For frozen-thawed embryo transfer, 12% of AV uteri at mock embryo transfer became RV, while 33% of RV uteri became AV (P = 0.01). CONCLUSIONS: Our data suggest that an RV uterus at mock embryo transfer will often change position at real embryo transfer. Misdirecting the embryo transfer catheter can be avoided by accurate knowledge of the uterine position at the time of embryo transfer, which can be more accurately assessed by routine ultrasound guidance. Additionally, patients with an RV uterus at mock embryo transfer should still present with a full bladder for embryo transfer, since a significant number will convert to an AV position.     

Breast cancer: patient information needs reflected in English and German web sites

Individual belief and knowledge about cancer were shown to influence coping and compliance of patients. Supposing that the Internet information both has impact on patients and reflects patients' information needs, breast cancer web sites in English and German language were evaluated to assess the information quality and were compared with each other to identify intercultural differences. Search engines returned 10 616 hits related to breast cancer. Of these, 4590 relevant hits were analysed. In all, 1888 web pages belonged to 132 English-language web sites and 2702 to 65 German-language web sites. Results showed that palliative therapy (4.5 vs 16.7%; P=0.004), alternative medicine (18.2 vs 46.2%; P<0.001), and disease-related information (prognosis, cancer aftercare, self-help groups, and epidemiology) were significantly more often found on German-language web sites. Therapy-related information (including the side effects of therapy and new studies) was significantly more often given by English-language web sites: for example, details about surgery, chemotherapy, radiotherapy, hormone therapy, immune therapy, and stem cell transplantation. In conclusion, our results have implications for patient education by physicians and may help to improve patient support by tailoring information, considering the weak points in information provision by web sites and intercultural differences in patient needs.