Long-term survival after autologous bone marrow transplantation for follicular lymphoma in first remission.

The role of autologous stem cell transplantation (ASCT) in the treatment of follicular lymphoma is still being defined in the era of antibody therapy. Here we report the long-term 12-year clinical outcomes of patients treated with autologous bone marrow transplantation (ABMT) for follicular non-Hodgkin's lymphoma (NHL) in first remission. Between 1988 and 1993, advanced-stage follicular NHL patients in need of initial therapy were enrolled in 2 consecutive prospective treatment trials of either standard-dose CHOP induction (83 patients) or high-dose CHOP plus granulocyte-colony stimulating factor (G-CSF) (20 patients). Patients who achieved an adequate remission with induction therapy underwent conditioning with cyclophosphamide and total body irradiation (TBI) followed by ABMT in first remission using bone marrow (BM) purged in vitro with anti-B cell monoclonal antibodies and rabbit complement (96 patients). At 12-year follow-up, 61% of the patients are alive and 43% remain in continuing complete remission. The only predictors of decreased progression-free survival proved to be histologic BM involvement at time of harvest (hazard ratio [HR] 2.27, 95% confidence interval [CI] 1.3-3.9, P<.004) and PCR detectable disease in the BM product after purging (HR 4.18, 95% CI 1.99-8.8, P=.0002). No significant predictors of overall survival were identified. These results at 12-year follow-up suggest that a subset of follicular lymphoma patients can experience prolonged survival with ABMT in first remission.     

Experimental studies of the historheology of the liver capsule (author's transl)

We have performed histomechanical experiments with historheological methods on the liver capsule of men and cattle. The liver capsule is a non linear viscoelastic tissue. The force-extension diagram or the force-time curve under increase in length shows a flat initial part with a large strain reserve, then an arched domain and subsequently a steep increase in force with a coordination of a small increase in length. The hysteresis loop is represented. When the tissue is in a viscoelastic steady state (preconditioned), the force-extension curves respectively the force-time curves are identical one with another and under certain presuppositions reproducible. This is also the case with the static relaxation curve and the force recovery curve (inverse relaxation). With a ramp shaped extension time input function and an additional, superimposed sinus length-time input function we can observe the following dynamical force-time output functions: Non linear dynamical force increase, amplitude increment phenomenon, dynamical force recovery (dynamical inverse relaxation). Various dynamical-statical transients are demonstrated in diagrams. The mechanical properties of the liver capsule are interacting with the ligaments of the liver, with the intrahepatic connective tissue, and with the liver parenchyma. Aspects of the functional anatomy and the tension of the capsule in an acute increase of he liver parenchyma are discussed.     

Biased immunoglobulin variable region gene expression by Ly-1 B cells due to clonal selection

Most, if not all, autoantibodies specific for bromelain-treated mouse erythrocytes recognize the common membrane phospholipid, phosphatidyl choline (PtC). Anti-PtC antibodies are produced by 5%-15% of CD5+ Ly-1 B cells of normal unimmunized mice, but not by detectable numbers of conventional CD5- B cells. At 1 week of age PtC-specific B cells are undetectable but then increase dramatically over the next 3 to 4 weeks to reach adult numbers. We report here that PtC-specific Ly-1 B cells in B10.H-2aH-4bp/Wts mice predominantly express either of two heavy and kappa chain variable (V) region gene combinations. In addition, the sequence and length of DH genes are conserved among cells expressing the same V gene combination, and the V kappa-J kappa junctions of one group involve unusual splice sites. Preferential V gene rearrangement models are insufficient to explain the DH and V kappa-J kappa junctional sequences or the delayed appearance of this specificity, and so they cannot solely account for the high frequency of PtC-specific cells. These characteristics are more consistent with antigen selection. We therefore attribute the frequent use of the two V region gene combinations to selection for cells that express them and conclude that the expressed V gene repertoire of Ly-1 B cells in adult mice is influenced by antigen selection. Apparently, there is no selection for mutant anti-PtC antibodies of higher affinity during the formation of the Ly-1 B repertoire because the V region genes expressed by PtC-specific cells are unmutated. Our findings are consistent with an important, germ line-encoded function for the immunoglobulin products of these gene combinations.     

Corynebacterium endocarditis. Difficult diagnosis in an elderly woman

Physicians have been reminded repeatedly of the many faces of bacterial endocarditis. In this case, Corynebacterium endocarditis presented as an occult malignancy and eluded diagnosis for six months. The coryneform isolates found in cultures are often considered to be contaminants because of their ubiquitous nature, sometimes causing a delay in diagnosis. Patients with culture-negative endocarditis or Corynebacterium "contamination" should be treated as having Corynebacterium endocarditis pending results of microbiologic isolation tests.     

Ethical issues in a drug information center

The frequency and nature of ethical issues faced by pharmacists have not been well documented. To address these issues a retrospective study of the potential ethical problems encountered by pharmacists in a drug information center was conducted. Of the 744 calls received over a 13-month period, 50 raised ethical issues. Consumer calls were more likely to raise ethical issues than were health-provider calls. The calls mainly fell into five categories: drug identification, assessment of a physician's recommendations for consumers, conflict between callers' needs and legal or public-health considerations, therapeutic issues in the pharmacist-patient relationship, and paternalistic treatment of "difficult" callers. These questions raised ethical issues related to confidentiality, truth telling, and pharmacists' societal obligations. Pharmacists may confront an increased number of ethical issues as more drug information centers provide consumer services. Although there is no empirical evidence regarding pharmacists' ability to deal with ethical issues, there are reasons to believe that training in medical ethics will better equip pharmacists to recognize, analyze, and resolve ethical dilemmas.     

Dialysis arthropathy: complication of long term treatment with haemodialysis

Twenty eight patients who had received haemodialysis for more than 10 years were reviewed to establish the incidence of joint problems. Only six patients had no joint symptoms, one had avascular necrosis, one had had recent septic arthritis, and four had hyperparathyroidism. The remaining 16 patients had no evidence of hyperparathyroidism yet had an arthropathy causing pain and stiffness in many joints, particularly the shoulders. Ten of these 16 patients had a recurrent carpal tunnel syndrome requiring repeated surgical decompressions, which resulted in only partial improvement. Of the eight patients who had received dialysis for more than 15 years, seven had this "dialysis arthropathy" and six had recurrent carpal tunnel syndrome. Dialysis arthropathy is a common and often severe and disabling complication of long term treatment with haemodialysis. The cause is not known, but amyloid was found in a synovial biopsy specimen from one patient.     

Short-termin vivo stability of endothelial-lined polyester elastomer and polytetrafluoroethylene grafts

A fibronectin substrate will significantly enhance the strength of endothelial cell attachment on grafts constructed of polyester elastomer (PE) and polytetrafluoroethylene (e-PTFE). This experiment was undertaken to determine the short-termin vivo stability of endothellum on these fibronectin coated surfaces. Eight mongrel dogs underwent bilateral carotid artery replacement with both graft materlals. All grafts were inoculated with 2,000 cells/mm² using cultured autogenous venous endothelium labelled with Indium-111-oxine. The Indium-111 label in the grafts was measured immediately prior to implantation, after 1 hour ofin vivo perfusion, and at explantation after 24 hours. The percentage of inoculated cells attached to the grafts before perfusion was simillar for both materials, 93.3±3.0% versus 92.2±7.2%, for PE and e-PTFE respectively. All grafts were patent at one hour after implantation. PE grafts were found to have 93.8±3.9 % of the attached cells present at one hour while e-PTFE grafts had only 54.5 ± 10.8 % remaining, p<.001. After 24 hours, 5/8 (62.5%) e-PTFE grafts and 2/8 (25.0 %) PE grafts remained patent, p=.13. Of the patent grafts however, endothelial cell retention was still superior on the PE grafts with 78.0±0.6% of the attached cells remaining compared to only 24.5±6.1% on e-PTFE, p<.001. Occluded PE grafts had fewer cells remaining at 24 hours than patent ones, 78.0±0.6% versus 31.1±32.8%, respectively, p=.13. Histologically, patent PE grafts demonstrated nearly confluent endothelial monolayers while e-PTFE had patches of endothelial cells surrounded by, a platelet-fibrin carpet. We conclude that short-term patency appears to be determined by the extent of endothelial retention on PE but not e-PTFE.     

Is obsessive–compulsive disorder an autoimmune disease?

OBSESSIVE–COMPULSIVE DISORDER (OCD) IS A COMMON and debilitating neuropsychiatric disorder. Although it is widely believed to have a genetic basis, no specific genetic factors have been conclusively identified as yet, leading researchers to look for environmental risk factors that may interact with an underlying genetic susceptibility in affected individuals. Recently, there has been increasing interest in a possible link between streptococcal infections and the development of OCD and tic disorders in children. It has been suggested that OCD in some susceptible individuals may be caused by an autoimmune response to streptococcal infections, that is, a similar biological mechanism to that associated with Sydenham's chorea. The term “pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections” (PANDAS) has been used to describe a subset of children with abrupt onset or exacerbations of OCD or tics, or both, following streptococcal infections. Affected children have relatively early symptom onset, characteristic comorbid symptoms and subtle neurological dysfunction. Neuroimaging studies reveal increased basal ganglia volumes, and the proposed cause involves the cross-reaction of streptococcal antibodies with basal ganglia tissue. Vulnerability to developing PANDAS probably involves genetic factors, and elevated levels of D8/17 antibodies may represent a marker of susceptibility to PANDAS. Prophylactic antibiotic treatments have thus far not been shown to be helpful in preventing symptom exacerbations. Intravenous immunoglobulin therapy may be an effective treatment in selected individuals. Further understanding of the role of streptococcal infections in childhood-onset OCD will be important in determining alternative and effective strategies for treatment, early identification and prevention of this common and debilitating psychiatric disorder.     

Translation and psychometric validation of the traditional Chinese version of patient-reported outcomes measurement information system Pediatric-25 Profile version 2.0 (PROMIS-25) in Chinese Children with Cancer in Hong Kong

Quality of Life Research - To translate and cross-cultural validate the PROMIS Pediatric-25 Profile 2.0 (PROMIS-25) into traditional Chinese, and to investigate its psychometric properties in...     

Iterative reconstruction algorithms

In this paper a survey of recent results on iterative reconstruction algorithms is given. These results, many of which have not yet appeared elsewhere, are applicable to a very general formulation of the reconstruction problem based on the series expansion approach. A set of optimization criteria and a number of iterative reconstruction algorithms are stated, together with theorems on the convergence of the algorithms to optimum images. The efficacy of the algorithms is compared to that of the convolution method. In particular, the falseness of the claim that ART and the backprojection method are the same is demonstrated.