Comparison of FK-506 and cyclosporine regimens in pediatric renal transplantation

Clinical aspects of FK-506 or cyclosporine immunosuppression regimens were evaluated in 48 consecutive pediatric renal transplant recipients. Tapering and discontinuation of prednisone was employed only in children receiving FK-506 who experienced minor or no rejection episodes during the 1st posttransplant month. At 1 year follow-up, 17 of 22 (77%) of all children with functioning allografts were receiving no prednisone (n=13) or a mean dosage of 0.07 mg/kg per day (n=4). During the 1st month, acute cellular rejection was more common in the FK-506 group (0.58 vs. 0.21 rejections per patient,P<0.05) but allograft survival (92%) and renal function at 1 year posttransplant were identical in both groups. Compared with the cyclosporine regimen, FK-506 immunosuppression may be associated with a higher incidence of cytomegalovirus or reversible Epstein-Barr virus-induced lymphoproliferative disease. However, the FK-506 group had less hirsutism and gingival hypertrophy and required fewer antihypertensive medications independent of steroid use. Height standard deviation scores and weight-for-height index improved only in preadolescents receiving FK-506 but no prednisone (P<0.02 andP<0.05, respectively), but did not differ between children on FK-506 plus prednisone and those in the cyclosporine group. We conclude that the major advantages of FK-506 over cyclosporine immunosuppression are a reduced severity of hypertension and an improved cosmetic appearance which may improve long-term medical compliance. When used as monotherapy, FK-506 also shows promise in relieving the growth retardation associated with cyclosporine regimens that include prednisone.     

Considerations for the Use of Cytokine-Secreting Tumor Cell Preparations for Cancer Treatment

Limited efficacy of chemotherapy in most solid tumors has revived interest in immunotherapeutic approaches for cancer. One novel form of immunotherapy is the use of cancer vaccines consisting of tumor cells genetically engineered to secrete cytokines. The rationale for this immunization strategy is based on the existence of tumor-specific antigens, on the importance of the cellular arm of the immune system in mediating an effective antitumor response, and on the role of cytokines in regulating the cellular immune response. Such tumor vaccines showed considerable promise in various animal models and induced potent antitumor immunity in the host, which led to regression of established tumors and, moreover, produced immunological memory protecting animals from a subsequent tumor challenge at a distant site. Translated to the human patient, this implies that genetically modified tumor vaccines may be able to eradicate or reduce existing tumor deposits to subclinical levels as well as provide long-term protection from regrowth of tumor cells. This report will review and discuss the concept and rationale for the use of cytokine-secreting tumor vaccines for the treatment of human malignancies.     

Ruminative Response Style and Vulnerability to Episodes of Dysphoria: Gender, Neuroticism, and Episode Duration

A number of recent laboratory and prospectivefield studies suggest that the tendency to ruminateabout dysphoric moods is associated with more severe andpersistent negative emotional experiences (e.g., Morrow & Nolen-Hoeksema, 1990;Nolen-Hoeksema & Morrow, 1991). The current paperreports two studies that tested the hypotheses that (a)ruminative response styles act as a trait vulnerabilityto dysphoria, particularly to relativelypersistent episodes of dysphoria; (b) aspects ofrumination that are not likely to be contaminated withthe presence and severity of previous symptomatology(introspection/self-isolation, self-blame) demonstrate vulnerability effects;and (c) rumination mediates the effects of gender andneuroticism on vulnerability to dysphoria. Consistentsupport was found for each of these hypotheses. Overall, our data suggest that rumination mightreflect an important cognitive manifestation ofneuroticism that increases vulnerability to episodes ofpersistent dysphoria.     

Effect of contaminated preprocessed semen on fertilization rate and embryo quality in assisted reproductive techniques.

We aimed to identify the sources and prevalence of semen contamination from mastrubation and determine the effect of bacterospermia on fertilization rate and embryo quality in standard in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). This was a prospective controlled study, in an IVF unit of a university teaching hospital, of 93 consecutive couples undergoing IVF-embryo transfer cycles. We evaluated handwashing; semen collection and processing; and assisted reproductive technology using semen provided by masturbation. The main outcome measures were presence and type of micro-organisms in the semen samples and embryo culture medium; the effect of hand washing on rate of contamination; and the effect of semen contamination on fertilization rate and embryo quality. The first consecutive 52 men of the 93 couples were not instructed to wash their hands before masturbation, and the remainder were so instructed. Forty-nine semen cultures (94.2%) in the first group were contaminated compared to only 16 (39%) in the second (p < 0.016); 27 of the 65 positive cultures (41.5%) were contaminated by more than one organism. The most common contaminators were bacteria usually found on the skin. All but four embryo medium cultures were negative. There was no significant difference in fertilization rate and embryo quality by culture findings in either the IVF or the ICSI procedures. We found that a high percentage of manually obtained semen for standard IVF or ICSI procedures was contaminated, but this had no effect on fertilization rate and embryo quality.     

Semantic memory recognition is supported by intrinsic recollection-like processes: “The butcher on the bus” revisited

Dual-process models suggest that recognition memory is independently supported by recollection and familiarity. Current theories attribute recollection solely to hippocampally mediated episodic memory (EM), and familiarity to both episodic and semantic memory (SM) supported by medial temporal lobe cortex (MTLC) and prefrontal cortex. We tested whether, contrary to this view, recollection-like processes also intrinsically support SM recognition and whether MTL structures are involved in their execution. A semantic Process Dissociation Procedure (PDP) with famous and non-famous names was used in three experiments. Experiment 1 revealed that recollection-like processes in semantic memory were not associated with episodic memory for the public events, were predicted by performance on standard SM tasks and were independent of EM tasks, suggesting they are intrinsic to SM. Experiment 2 demonstrated the independence of the two process estimates by showing only familiarity was affected by shifting response criterion while only recollection estimates were significantly altered under divided-attention. Finally experiment 3 tested amnesic patients with varying degrees of hippocampal and MTLC damage. Despite normal overall fame recognition performance, recollection estimates were specifically affected by MTL damage. When damage was primarily hippocampal, only retrograde recollection estimates were reduced, while more extensive MTLC damage led to both retrograde and anterograde recollection deficits. We conclude that recognition of semantic information is supported by at least two independent processes akin to the ones that support EM recognition. Recollection-like processes are intrinsic to SM and likely do not reflect EM contribution to SM performance. Together with previous studies of recollection in remote memory, these data suggest that recollection is not a unitary phenomenon. In EM it involves autonoetic re-experiencing, and is supported by interaction of fronto-temporal networks; in EM and SM it supports retrieval of contextual/associative information regardless of consciousness type, and is dependent on intact MTL function. Familiarity processes and neural substrates may also differ between lifetime familiarity and within-session familiarity.     

Prevalence of mitral valve prolapse in chronic lymphocytic thyroiditis and nongoitrous hypothyroidism

An increased prevalence of mitral valve prolapse has been found in Graves' disease and a common autoimmune etiology has been suggested for both disorders. We investigated the prevalence of mitral valve prolapse in 87 patients with autoimmune chronic lymphocytic thyroiditis, 50 patients with nongoitrous hypothyroidism and 111 healthy control subjects. Mitral valve prolapse was found in 16.09% of patients with chronic lymphocytic thyroiditis compared to 6 and 5.4% in nongoitrous hypothyroidism and normal controls, respectively. The result is statistically significant, p less than 0.02, and confirms that the prevalence of mitral valve prolapse is significantly increased in patients with autoimmune disorders of the thyroid gland, when compared to normals and nonautoimmune conditions.