Use of an antibody-ricin A-chain conjugate to delete neoplastic B cells from human bone marrow

Affinity-purified rabbit antibody to human lambda and kappa chains (R alpha H lambda kappa) was conjugated to the A-chain of the plant toxin, ricin. The resulting immunotoxin (R alpha H lambda kappa-A) killed cells from the tumor cell line Daudi, which bears surface immunoglobulin, but was nontoxic to the CFU-E, BFU-E, and CFU-GM of human bone marrow. R alpha H lambda kappa-A eliminated 99% of clonogenic Daudi cells that had been mixed with marrow cells in vitro, without demonstrable toxicity to hematopoietic cells. Thus, in vitro treatment of marrow with R alpha H lambda kappa-A may increase the incidence of cure following autologous bone marrow transplantation for the treatment of human B-cell malignancies.     

The D-allele of the ACE gene polymorphism predicts a stronger antiproteinuric response to ACE inhibitors

SUMMARY: Angiotensin converting enzyme (ACE) inhibitors have additional renoprotective effects over other antihypertensive drugs in retarding the development and progression of diabetic and non-diabetic nephropathies. This additional beneficial effect has been attributed to their antiproteinuric action. However, individual antiproteinuric responses to ACE inhibitors vary considerably. the mechanism underlying the variable response is unresolved. the role of the insertion/deletion (I/D) polymorphism of the ACE gene in this response was examined. the case series consisted of 96 patients (69 males, median age 46.5 years) on ACE inhibitors with an initial proteinuria in excess of 1.0 g/24h. A control series consisted of 103 patients (43 males, median age 40 years) with autosomal polycystic kidney disease. A second control series consisted of 82 patients (52 males, median age 39 years) with a diagnosis of insulin-dependent diabetes mellitus (IDDM) without microalbuminuria after more than 15 years of IDDM. Angiotensin converting enzyme genotyping was performed by polymerase chain reaction (PCR) analysis of chromosomal DNA. the ACE genotype distribution (DD 44%, ID 28%, II 28%) in the case series was not in accordance with the Hardy-Weinberg equilibrium (χ²= 17.2, P<0.001), whereas it was in both control series. the difference in ACE genotype distribution between the case series and both control series combined was significant as a result of an overrepresentation of patients with the DD genotype (χ²=9.2, P=0.01). the allele frequencies were compared in patients with a reduction of proteinuria above and below the median value of 45%. the antiproteinuric effectiveness of ACEI therapy in the whole group was greater in the presence of the D-allele (OR 1.6, 95% CI 0.9-2.9). the effect of the D-allele was more pronounced in the subgroup of patients with an initial proteinuria in the non-nephrotic range (relative risk 2.8, 95%CI 1.0-8.0) and in patients not receiving diuretics (relative risk 2.3, 95% CI 1.1–4.5). In conclusion, the DD genotype seems to predispose the development of proteinuria in the presence of a kidney disorder. the presence of the D-allele predicts a stronger antiproteinuric efficacy of ACE inhibitor therapy in patients with an initial proteinuria in the non-nephrotic range and in the patients not requiring comedication with diuretics.     

Spontaneous Regression of Cardiac Tumors

The authors report a case of an asymptomatic 3-day-old baby with multiple biventricular tumors detected 2 years ago by echocardiography. In spite of the major anatomical anomaly, no functional abnormality was found. There was no outflow tract obstruction and, therefore, an expectant and noninterventional approach was recommended. Serial echocardiographic follow-up revealed spontaneous and progressive regression of the tumors. Today the child remains asymptomatic and only three small masses persist.     

Piaget's Approach to Problems of Intellectual Development

In an attempt to demonstrate the way in which Jean Piaget looks at intelligence and its development, a comparison was made with the more usual psychometric approach. Two subtests of the Terman-Merrill revision of the Stanford Binet intelligence test were taken as a basis for this comparison, and it was shown that Piaget's interests in this field are directed towards the development of the thought processes which lie behind apparently simple tasks. He is not primarily concerned with the allocation of abilities to various age levels, but rather with the development of the internalised structures and mechanisms which enable the child to understand and solve various intellectual problems.     

Is there a relationship between antipsychotic blood levels and their clinical efficacy? An analysis of studies design and methodology

Summary— There are now more than 50 studies concerning neuroleptic blood levels and clinical outcome relationships. Haloperidol, the most studied, is the only antipsychotic permitting some conclusions. A number of authors suggest that the striking lack of agreement between different studies results from heterogeneity of their quality. Here, we have used a scoring system for assessing the quality of those studies. According to this system, none (0/14) of the studies having a score <0.60 was able to show a therapeutic window, as compared to 53% (10/19) of those having a score ≥0.60 (p = 0.002, Fisher exact test). Also, the studies able to identify the presence of a therapeutic window during haloperidol treatment were those having sample sizes >20 ( p = 0.06) and those whose patients were treated with fixed doses ( p = 0.02). The diagnosis of schizophrenia in the studies seems not to be an exclusive condition, as compared with those also including schizophreniform and schizoaffective disorders (p = 0.12). Our qualitative analysis of haloperidol blood level publications seem to indicate that an upper limit may exist for haloperidol efficacy; values above this limit seem not to provide any supplementary clinical improvement and may even reduce therapeutic effect.