Differential immunologic effects of language-dominant and nondominant cerebral resections.

OBJECTIVE: To demonstrate whether the cerebral hemispheres (language dominant versus nondominant) affect immune function differentially in humans by delineating the effects of resections for epilepsy surgery on T-cell indices. BACKGROUND: Cerebral lateralization has been postulated to affect immunomodulation. Differential effects of left versus right cerebral lesions on T-cell numbers and responsiveness have been demonstrated in animals, but the effects in humans are unclear. METHODS: Pre- and postoperative changes in T-cell indices were examined in relation to side of language dominance in patients undergoing epilepsy surgery. RESULTS: Absolute lymphocyte count, total T cells (CD3+), helper T cells (CD3+4+), cytotoxic/suppressor cells (CD3+8+), and total suppressor cells (CD8+) were reduced after language-dominant resections, but were increased after nondominant resections. CONCLUSIONS: Although the mechanisms are not fully elucidated, the results demonstrate differential immunologic responses in humans to focal cerebral lesions as a function of cerebral lateralization.

HLA antigens in lichen sclerosus et atrophicus.

Several reports have found conflicting data regarding the association between lichen sclerosus et atrophicus (LSA) and HLA types. Association with HLA-A31 and -B40 has been noted, whereas another report found no correlation. We are the first to specifically examine HLA types in white patients in the United States. We have found a significant association between LSA and HLA-A29 and -B44 individually and an even stronger association with the combination of A29 and B44. A review of previous LSA-HLA studies, as well as several reports of HLA typing in familial LSA, is discussed, with consideration given to possible reasons for the discrepancies among the various studies.

Acute activation of peripheral lymphocytes during treatment of diabetic ketoacidosis.

Activated peripheral T-lymphocytes are increased in both pre-insulin-dependent diabetes mellitus (IDDM) patients and in recently diagnosed IDDM patients, as well as in various forms of acute stress. We studied the in vivo T-lymphocyte activation in six patients in severe diabetic ketoacidosis (DKA) prior to treatment, after 24 h of treatment and > or =5 days after admission. Five of the six patients showed an increased percentage of activated T-lymphocytes based on the expression of HLA-DR at 24 h of treatment when compared to the admission percentage of activation (P<.05). There was no correlation to the admission serum glucose, osmolality, or electrolytes. Serum pH showed a trend toward an inverse correlation, but was not statistically significant. We speculate that T-lymphocyte activation plays a role in the progression of the acute complications of subclinical brain edema and interstitial pulmonary edema of DKA. This process could also be another factor in the progression of the chronic complications of IDDM in addition to the well-established effects of hyperglycemia and hypertension.

Differential regulation of the immune response to SRBC by monoclonal antibodies to interferon-gamma.

Three monoclonal antibodies against different epitopes of interferon-gamma (IFN-gamma) were used to assess its role as a normal immunomodulatory molecule. Two of these antibodies were able to reduce significantly the primary antibody response to sheep erythrocytes in an in vitro culture system. One of these two antibodies has been reported to suppress both the antiviral and macrophage activation factor activities of IFN-gamma by binding to its carboxyl terminus. These findings indicate that IFN-gamma is an important lymphokine for the maximum expression of the immune response and that it acts via the carboxyl terminus of the molecule. This antibody suppressed the immune response only when added at the initiation of culture, suggesting that the action of IFN-gamma is on an early component of the response. The third monoclonal antibody, which binds to the amino end of IFN-gamma, did not suppress the in vitro response. However, it was able to block the effects exerted by an immunosuppressive dosage of exogenous IFN-gamma on in vitro antibody production. These results indicate that the immunosuppression vitro antibody production. These results indicate that the immunosuppression induced by the addition of IFN-gamma to a primary antibody response and the role that it plays in that response are mediated through different sites on the molecule and, therefore, probably by different mechanisms.

High-dose chemotherapy followed by reinfusion of a high number of CD34+ progenitor cells is frequently associated with development of fever in the postengraftment period.

Twenty-nine patients received high-dose chemotherapy and autologous stem cell transplantation from June 1997 to December 1998. The number of CD34+ cells reinfused was 2.4 x 10(6) to 69.0 x 10(6)/kg. Twelve patients developed a fever in the immediate postengraftment period. One patient had a documented infection that could account for the fever; a second patient had a rash and biopsy proven acute graft-versus-host disease (GvHD) that responded to steroids. In the other 10 patients (30%) there was no identifiable cause of the fever. One of these patients received 4.2 x 10(6) CD34+ cells/kg. The other nine received 22.0 x 10(6) to 69.0 x 10(6) CD34+ cells/kg. In our series of 29 patients, 9 of the 11 (82%) patients who received > 20 x 10(6) CD34+ cells/kg developed fever in the postengraftment period. There was a significant association between the number of CD34+ cells (<20 vs. >20 x 10(6)) and occurrence of fever (odds ratio = 76.5; p = 0.00005). Even though they engrafted promptly (7 to 9 days), the fever required evaluation for infection, blood cultures, antibiotic treatment, and observation. This required additional hospitalization of 1 to 7 days. These data suggest that a high number of CD34+ cells is frequently associated with post-engraftment fever and prolongation of the hospital stay. Should there be an upper limit in the number of reinfused CD34+ cells is a question that has to be addressed and possibly studied.

Phenotypic evolution of classic 21-hydroxylase deficiency.

We describe a female patient who was diagnosed and treated at birth for a classic form of salt-losing congenital adrenal hyperplasia. At 17 years of age, against medical advice, she discontinued both mineralocorticoid and glucocorticoid replacement with no resulting clinical symptoms other than the occurrence of amenorrhoea. Steroid metabolites revealed significant abnormalities of the renin-angiotensin-aldosterone axis, as well as of pituitary-adrenal function. Analysis of our patient's DNA showed only one deleterious CYP21 mutation, an intron 2 base pair change activating a cryptic splice site. We speculate that expression of this patient's CYP21 genes may be altered by the effects of ageing or by changes in the steroid milieu.