Atelosteogenesis I and boomerang dysplasia: a question of nosology

We report a patient whose clinical, radiologic and histopathologic findings are compatible with severe atelosteogenesis (AT-I). The patient is compared with previously reported cases of AT-I, as well as with patients reported as having "boomerang" dysplasia. We conclude that it is reasonable to consider AT-I and boomerang dysplasia as part of a spectrum, probably reflecting a common etiology. More and detailed clinical, radiologic and histopathologic reports are needed to further clarify the relationship of AT-II and AT-III in this family of skeletal dysplasias.     

6-125I-iodo-2-methyl-1,4-naphthoquinol bis (diammonium phosphate) as a potential radio-halogenated anti-cancer agent: In vitro investigations and possible clinical implications

6-¹²⁵I-iodo-2-methyl-1,4-naphthoquinol bis (diammonium phosphate) (6-¹²⁵I-iodo-MNDP) has been synthesised and studied as the prototype of a class of potential radio-halogenated anti-cancer agents. The incorporated ¹²⁵I provides Auger electron radiations which behave like high LET radiations in the treatment of tumours, though the accompanying X- and -radiations make an undersirable contribution to the total body dose. The in vitro experiments reported show that 6-¹²⁵I-iodo-MNDP is selectively concentrated in the cells of some human malignant tumours by factor of about 15 to 20 or more in relation to the cells of normal origin studied. On the basis of dosimetric considerations and comparison with clinical treatment with tritiated methylnaphthoquinol diphosphate, practical dosage of 6-¹²⁵I-iodo-MNDP is suggested and clinical indications and safety of use are discussed. The types of tumour of particular interest are inoperable cases of carcinoma of the colon, carcinoma of the pancreas, malignant melanoma and osteosarcoma. Further investigations are in progress.Beit Memorial Fellow for Medical Research     

Antibody-dependent lymphocyte-mediated cytotoxicity (Ab-LMC), definition of the "K cell" in the rat.

The nature and membrane characteristics of the "K cell" of antibody-dependent lymphocyte-mediated cytotoxicity (Ab-LMC) were investigated in a widely used rat model of transplantation. Treatment of sensitized effector cell populations with anti-immunoglobulin and complement eliminated K cell cytotoxicity without diminishing the component of T cell-mediated injury. EA and EAC depletion experiments, although demonstrating no loss of K cell cytotoxicity after removal of complement receptor-bearing lymphocytes, produced a marked abrogation of cytotoxicity following the removal of the Fc receptor-bearing lymphocyte pool. Studies on phagocytic properties showed K cell activity to be shared by an adherent as well as a nonadherent cell population. Thus, the Fc receptor emerged as the only constant surface marker of the rat K cell in Ab-LMC.     

The evolution of drug development in schizophrenia: past issues and future opportunities.

Schizophrenia is a disease syndrome with major public health implications. The primary advance in pharmacotherapeutics was in 1952 with the introduction of antipsychotic medications (ie, chlorpromazine, dopamine D2 antagonism). Barriers to progress have been substantial, but many will be subject to rapid change based on current knowledge. There are attractive psychopathology indications for drug discovery (eg, impaired cognition and negative symptoms), and drugs with efficacy in these domains may have application across a number of disease classes. These pathologies are observed prior to psychosis raising the possibility of very early intervention and secondary prevention. Success in drug discovery for cognition and negative symptom pathologies may bring forth issues in ethics as the potential for enhancing normal function is explored.     

Severe hypervitaminosis A in siblings: evidence of variable tolerance to retinol intake

A 2-year-old boy had signs and symptoms of chronic hypervitaminosis A. A course of increasing severity led to eventual death. A younger brother later had similar clinical features. Chicken liver spread containing up to 420 IU/g vitamin A was the likely source of intoxication. Markedly elevated circulating retinyl ester levels have persisted in the surviving sibling for 3 subsequent years despite severe restriction of vitamin A intake. A therapeutic trial of the carbohydrate-derived complexing agent 2-hydroxypropyl-beta-cyclodextrin was initiated. Circulating retinyl esters transiently increased during the infusion (from 407 to 4791 micrograms/dL), and urinary total vitamin A excretion, undetectable before infusion, increased to 23 micrograms/dL after infusion. The frequency of hypervitaminotic episodes has decreased somewhat in the 2 years since the infusion, probably related to dietary vitamin A restriction. The occurrence of this syndrome in two brothers, while a sister ingesting the same diet remains completely healthy, suggests an inherited variance in tolerance to vitamin A intake.     

New strategies for glucose control in patients with type 1 and type 2 diabetes mellitus in pregnancy

Over the past 5 decades, perinatal outcome in pregnancies complicated by diabetes mellitus has improved dramatically due in large part to better maternal glycemic control. Self-blood glucose monitoring in combination with flexible or intensive insulin treatment including the use of newer insulin analogs and insulin pump therapy has dramatically improved glucose control in most pregnancies complicated by diabetes. In developing an insulin regimen, careful attention must be paid to both basal and prandial insulin needs. Every effort must be made to avoid hypoglycemia and prevent ketoacidosis. A team approach including the patient, diabetes nurse educator, nutritionist, and social worker is ideal.