Epitope specificity of CD44 for monoclonal antibody-dependent facilitation of marrow engraftment in a canine model

Primary graft rejection after marrow transplantation occurs more frequently in patients receiving HLA-haploidentical compared with HLA-identical sibling transplants. Both human and experimental animal data suggest that the cells responsible for this phenomenon are either host natural killer (NK) cells, T cells, or both. To investigate the mechanisms of graft rejection, we have developed a canine model of marrow transplantation, which uses DLA-nonidentical unrelated donors in the absence of postgrafting immunosuppression. In this model most animals rejected their marrow grafts after a preparative regimen of 9.2 Gy total body irradiation (TBI). However, engraftment of DLA-nonidentical marrow can be facilitated when the recipients are pretreated with monoclonal antibody (MoAb) S5, which recognizes CD44. In this report, we extended these observations by first cloning the canine CD44 and, next, mapping the epitope recognized by S5, which was located in a region conserved among human and canine CD44 and was distinct from the hyaluronan binding domain. However, in vitro binding of S5 caused a conformational change in CD44, which allowed increased hyaluronan binding. Then, we reexamined the in vivo model of marrow transplantation and compared results with MoAb S5 to those with two other anti-CD44 MoAbs, IM7 and S3. Only MoAb S5 significantly increased the engraftment rate of DLA-nonidentical unrelated marrow, whereas the two other anti-CD44 MoAbs were ineffective. The enhanced in vivo effect was not related to differences in the MoAbs' avidities, since both S5 and IM7 had equivalent binding to CD44, but most likely related to the specific epitope that S5 recognizes. Thus, this study shows that the effect of the anti-CD44 MoAb S5 in facilitating engraftment is epitope specific and if one is to use an anti-CD44 to facilitate engraftment of marrow in humans, one cannot assume that any anti-CD44 would work.     

The percutaneous endoscopic treatment of staghorn nephrolithiasis

Hyperferremia is shown to affect antioxidant system of the body, oxidation-reduction reactions in the cells seen as shifts in lymphocyte chemiluminescence. Dynamic changes in lymphocyte chemiluminescence reflect the level of hyperferremia.     

The meaning and impact of empathic relationships in hospice nursing

This naturalistic field study was designed to explore the patient's perspective of the nature, meaning, and impact of empathic relationships with hospice nurses. The findings are part of a larger study, focused on the meaning and impact of empathic relationships that develop between hospice nurses and their patients. Data were generated through in-depth interviews with 14 terminally ill adults receiving home-based hospice care. According to the hospice patient, an empathic relationship developed through a process of reciprocal sharing and revealing of personhood within a context of caring and acceptance. The experience of an empathic relationship meant being acknowledged as an individual, a person of value. The outcome of the empathic relationships between hospice nurses and their patients was the improvement and maintenance of patients' physical and emotional well-being. Understanding the patient's perspective is critical for effective nursing interventions and meaningful outcomes. Future research needs to explore empathic relationships between the nurse and family caregivers in various settings.     

Alpha blockaders--first or second line antihypertensive agents?

Alpha-receptor blockers reduce blood pressure by blocking of the alpha 1-receptors in the smooth muscle cells in the arteriolar walls. The heart pump function is not disturbed. Most studies have shown that the alpha-receptor blockers induce a reduction in plasma-triglycerides and an increase in the ratio between HDL- and LDL-cholesterol. They do not interfere with the metabolism of electrolytes, glucose or uric acid and have no negative effect on pulmonary function. Although long-term use does not induce a permanent increase in heart rate, some patients respond to initial therapy with faster heart rate and palpitations. The alpha-receptor blockers should not be used in patients with coronary heart disease if the patient is not on chronic beta-blockade. When these precautions are followed, the alpha-blockers can be used as first-line treatment--just like ACE-inhibitors and calcium-antagonists.     

Psychopharmacotherapy for addictive and comorbid disorders: current studies

Proper diagnosis of comorbid disorders is crucial in treatment planning for the dually diagnosed. Since psychoactive substance use can obfuscate the diagnosis, special care must be taken to exclude organically based syndromes. Adequate periods of abstinence should first be achieved and subsequently the patient re-examined for residual symptoms compatible with a nonaddictive, nonsubstance-induced psychiatric disorder. The integration of concurrent treatment of both the mental and the addictive disorders appears to be the best approach for treatment of comorbid psychiatric and addictive disorders. An abstinence-based model that typically utilizes a 12-step group therapy is often employed for the addictive illnesses. Other forms of psychosocial therapies such as case managers are being used as well. Presently, physicians' prescribing practices for comorbid addicted patients are based on traditional approaches to use of medications in psychiatric patients, and their attitudes towards addictive disorders may play a significant role in determining the overall success of treatment.     

Pharmacokinetic and pharmacodynamic effects of vaginal rings releasing levonorgestrel at a rate of 27 micrograms/24 hours: a pilot study

The pharmacokinetic and pharmacodynamic effects of vaginal rings releasing levonorgestrel (L-NOG) at an initial rate of 27 micrograms/24 h were studied in a group of 12 normally menstruating women during 90 days of continuous use (i.e., during three 30-day treatment segments). Blood samples were drawn immediately before insertion, 15 and 30 min, as well as 1, 2, 4, 8, 12 and 24 h after insertion of the rings, and thereafter three times weekly throughout the study for the analysis of L-NOG, estradiol, progesterone and sex hormone-binding globulin (SHBG). Endometrial biopsies were obtained for a morphometric analysis in a pre-treatment (control) cycle and in the 6th and 10th weeks of treatment. The peak of average L-NOG levels was reached within two hours after the insertion of rings. Until 24 h after insertion, the levels did not change significantly. Thereafter, a decrease at a rate of 0.2% per day was initiated. The L-NOG and SHBG levels were highly correlated. This was seen for both the pre-treatment SHBG vs L-NOG (r = 0.96) and the treatment SHBG vs L-NOG levels (r = 0.92). There was a significant (p < 0.001) decrease of SHBG levels due to treatment. During the total of 36 treatment segments, a normal ovarian function was seen in 47% of the segments. The women were anovulatory and had an inadequate lutal function in 28% and 25% of segments, respectively. No correlation between the L-NOG levels and ovarian reaction to treatment was found. The use of L-NOG induced significant changes in the endometrium; the number of glands/mm2 decreased after 6 (p < 0.02) and 10 weeks of use (p < 0.01). Also, the diameter of glands and the occurrence of vacuolated cells decreased significantly (p < 0.02 and p < 0.005, respectively). None of the endometrial parameters or dating was correlated with the ovarian reaction to treatment, indicating independent endometrial effects of L-NOG.