Prospective study of the occurrence of monoclonal gammapathies following bone marrow transplantation in young children

We have prospectively studied the occurrence of monoclonal serum immunoglobulins in 38 recipients of BMT. Patients were young children with primary immunodeficiencies (n = 31), other inherited diseases (n = 4), leukemia (n = 2), or aplastic anemia (n = 1). Twenty-nine received an HLA-nonidentical marrow and nine an HLA-identical marrow. Serum monoclonal immunoglobulins were detected by the immunofixation method. Monoclonal immunoglobulins were found in 26 patients. Monoclonal components were more frequently detected in patients with primary severe T cell deficiencies (21/25) rather than in the other patients (6/13). In 7 of 29 recipients of HLA-nonidentical transplants, versus 0 out of 9 recipients of HLA-identical transplants, serum monoclonal immunoglobulins were found associated with a B lymphocyte proliferation syndrome due to an Epstein-Barr virus infection. In this group, monoclonal immunoglobulins were detected early, prior to the onset of the clinical syndrome. The simultaneous occurrence of several monoclonal immunoglobulins was more frequent in these patients, while monoclonal immunoglobulin concentrations increased faster, especially those of IgM isotype. These characteristics may allow in patients at risk (recipients with primary T cell immunodeficiencies and receiving HLA-nonidentical transplantation) an earlier diagnosis of B lymphocyte proliferative syndrome that may eventually lead to early and more efficient therapy.     

RELATIONSHIP BETWEEN PLATELET CYTOSOLIC FREE CALCIUM CONCENTRATION AND PLASMA RENIN ACTIVITY

1. Plasma renin activity (PRA) and platelet cytosolic free calcium concentration ([Ca2+]i) were simultaneously determined in 18 untreated essential hypertensive subjects and 17 normotensive controls. A significant positive correlation was found between [Ca2+]i and PRA (slope = 42 nmol/l/ng/ml/h) in these 35 subjects. 2. Two determinations more than one week apart in nine subjects confirmed the parallel fluctuations of [Ca2+]i and PRA. A strict sodium restriction produced a progressive PRA elevation associated with a parallel rise in [Ca2+]i in one subject. 3. These results are consistent with the hypothesis that angiotensin II causes a concentration-dependent calcium mobilization.     

Further phenotypic evidence that nodular, lymphocyte-predominant Hodgkin's disease is a large B-cell lymphoma in evolution

Five cases of nodular, lymphocyte predominant Hodgkin's disease (nLP HD), in which an association with (n = 3) and transformation to (n = 2) large cell lymphoma (LCL) were found, were studied with monoclonal antibodies against B-, T-, and Reed-Sternberg (R-S) cell-associated antigens and epithelial membrane antigen (EMA) on paraffin sections. Both lymphocytic (L) and histiocytic (H) cells of nLP HD and lymphoma cells of LCL expressed multiple B-cell-associated antigens (detected by LN-1/CDw75, L26, MB2, DBB.42, DBA.44, DND.53, DNA.7 antibodies) but did not react with antibodies against T-cell-associated (MT1, UCHL1/CD45RO) (one exception for CD45RO in LCL) and R-S cell-associated (Leu-M1/CD15, Ber-H2/CD30) antigens. EMA was expressed by L and H cells in all cases and conserved in LCL cells, emphasizing the frequent expression of EMA by the diagnostic cells of nLP HD. An antibody (BNH9) against blood group-related antigens (H and Y oligosaccharide antigens) that does not normally react with lymphoid cells was found to be reactive with few L and H cells in two of five and most LCL cells in four of five cases. The finding might be indicative of abnormal activation of lymphoid cells. The data reinforce current implications that nLP HD is a B-cell malignancy in evolution and that it is not truly representative of Hodgkin's disease in terms of biological and clinical behavior.     

Different clinical types of degenerative aphasia

The authors report 3 cases of slowly progressive aphasia with different language disturbances: anomia, pure word deafness and Broca's aphasia. All patients were independent in daily life activities. Insight, judgement and overall behaviour were intact. There was no major disturbance of other cognitive functions, but psychometric tests showed mild deficits suggesting widespread involvement. CT scans and magnetic resonance imaging showed focal dilatation of the left sylvian fissure. A positron emission tomographic study showed left perisylvian hypometabolism. A review of the literature yielded an increasing number of cases of this degenerative syndrome affecting dominant hemisphere language areas. Our cases confirm the clinical heterogeneity of degenerative aphasia. Postmortem neuropathological examinations are rare and many causes are found: Pick's disease, Alzheimer's disease or aspecific gliosis.     

The overwhelmed intestine syndrome

We studied 54 patients who, after small intestinal resection, developed a massive protracted diarrhea with a daily fecal loss greater than 2 kg, status we defined as the "overwhelmed intestine syndrome" (OIS). Median length of residual small bowel was 120 cm, 19 patients had a definitive stoma (jejunostomy, n = 9; colostomy, n = 10), 26 patients had a provisional jejunostomy. Fecal weight greater than 2 kg was related to enteral hyperalimentation (greater than 3,500 Kcal) in 19 patients (induced OIS) and was clearly independent in 16 others who had fecal weight over 3 kg while receiving approximately 2,000 Kcal (obligatory OIS); the last 19 patients had fecal weight between 2 and 3 kg during normoalimentation. Hypocalcemia and hypomagnesemia were common in the three groups. The other complications were seen mostly in patients with obligatory OIS: in those patients, parenteral nutrition was maintained in 9 cases out of 16 (vs. 0 in other groups), nutritional gain was scanty, sodium equilibrium was difficult to obtain in spite of a large sodium intake (380 mmol/day), hospitalization lasted several months and autonomy via the enteral route could not be achieved in 7 out of the 9 patients with definitive short bowel (vs. 0 in other groups). This study shows that the OIS is an unique functional entity. Complications and prognosis are dependent on the obligatory or induced pattern of the syndrome. Only patients with obligatory OIS require definitive home parenteral nutrition.     

A 13-year longitudinal analysis of risk factors and clinic visitation patterns of patients with repeated gonorrhea

A retrospective study of 2498 patients who made multiple visits to a sexually transmitted disease clinic over a 13-year period analyzed risk factors, default patterns, and repeated infections associated with gonococcal urethritis. An analysis of visitation patterns found that being young, black, and male and having a history of gonococcal urethritis before visiting the clinic was positively related to the total time a patient remained involved with the clinic. Default rates for all patients increased with successive clinic visits. A focused analysis was carried out on the records of 146 patients who returned to the clinic within 12 months with a second diagnosis of gonococcal urethritis. It was found that this group of "repeaters," who comprised 15% of the total population with gonococcal urethritis, accounted for approximately 29% of all diagnoses of this infection over the 13-year study period. Repeaters were found to be more frequently male, black, single, and to be less likely to return for a test-of-cure culture. Longitudinal analysis found that the median time repeaters remained involved with the clinic was approximately 130 days. The relatively brief clinic "half-life" and rapid rates of removal of repeaters are discussed in terms of the development of strain-specific immunity to Neisseria gonorrhoeae in a closed population of patients.     

A study on OX39, a murine anti-rat interleukin 2 receptor antibody

OX39, a murine IgG1 monoclonal antibody (MoAb) that recognizes the 55 kDa alpha chain of the rat interleukin 2 receptor (R-IL2), was studied in vitro for its ability to interfere with IL2 binding and IL2-induced proliferation on rat concanavalin A (ConA) blasts and in vivo in a model of rat heart allografts. In vitro studies indicated that OX39 MoAb interacts with a single class of sites on the alpha chain of the rat R-IL2 with a high affinity (K_D=0.8 nm) and competes with IL2 binding on this chain (K_I=0.53 nm). In contrast, OX39 MoAb was found to be 10–20 times less efficient in competing with IL2 binding to the high-affinity R-IL2 (K_I10 nm). It is proposed that the epitope recognized by OX39 on the alpha chain (low-affinity R-IL2) is modified on (or buried in) the high-affinity R-IL2 configuration. Accordingly, OX39 was found to be a weak inhibitor in vitro on IL2-induced proliferation and in vivo on allograft rejection. Allograft survival was unaffected by doses of OX39 of 20 and 50 g/rat for 9 days; only a borderline effect was noted when doses as high as 250 g/rat were used. A significant, but restricted, effect of OX39 could be further detected when combined with low doses of cyclosporine A (1.5 mg/kg), which were ineffective by themselves. Together, our data suggest that in order to be efficient in vivo, anti-R-IL2 MoAbs must bind with high affinity to epitopes involved in the high-affinity IL2 binding site.