ON HOOKWORM ANEMIA: (APLASTIC ANEMIA IN HOOKWORM DISEASE)

We have discussed three types or stages of blood changes in hookworm disease.Attention is directed to a severe irreversible aplastic anemia which occurs not infrequently in hookworm disease. The pathogenesis is obscure, but we believe thatit is due to bone marrow exhaustion following continuous blood loss in the presenceof various factors, including dietary deficiency.

The symptomatology, hematologic and bone marrow findings are described.

     

A Three-Dimensional Display for Cardiac Activation Mapping

A three-dimensional display is described that allows activation sequences from the epicardium and endocardium to be shown simultaneously on the same image. Three electrode arrays (epicardial sock, left ventricular balloon, right ventricular balloon) are represented in a three-dimensional perspective by an array of dots that are intensified when activated. This arrangement requires fewer calculations and is easier to interpret than siiced-isochronal maps but cannot represent a complete heart cycle in one image. The three-dimensional display eliminates the distortion caused by two-dimensional diagrams and facilitates activation correlation between electrode arrays. A standard, low cost microcomputer has been used to implement the activation display.     

The Eosinophilia of Magnesium Deficiency

Experimental magnesium deficiency has been produced by dietary means inintact and adrenalectomized rats. The numbers and distributions of eosinophiles and mast cells were studied.

1. Adrenal ablation produced a mild blood eosinophilia and the numbers ofmast cells were reduced in peritoneal fluid. Tissue eosinophilia was not observed.

2. Magnesium deficiency in both intact and adrenalectomized rats isaccompanied by an extremely high blood eosinophilia. Concurrently the numbers of peritoneal fluid eosinophiles increased while the numbers of peritonealmast cells decreased.

3. Massive infiltration of eosinophiles into the lung, submaxillary gland andmesenteric lymph nodes were observed in all magnesium deficient groups.Mast cells were found in the liver sinusoids and spleen of adrenalectomized,magnesium deficient animals of the chronic phase where these cells are notnormally present.

Submitted on May 3, 1960 Accepted on July 25, 1960     

Mycosis fungoides, nitrogen mustard and skin cancer

The prevalence of epithelial cancer was determined in 202 patients with mycosis fungoides and the Sézary syndrome and was found to be 10.5%. In an attempt to establish a possible association with topically applied nitrogen mustard, it was noted that 4.0% of these patients had lesions prior to nitrogen mustard therapy (although over half subsequently developed further lesions) and 6.5% of the patients developed them de novo after therapy. In two patients in this latter group, malignancies developed in are as not usually associated with solar-induced cancer. These findings indicate that epidermal neoplasia is not uncommon in these patients and that nitrogen mustard may function as a carcinogen or a co-carcinogen.     

Protected amino acid tetrafluorophenyl esters for peptide synthesis

New 2,3,5,6-tetrafluorophenyl active esters of protected amino acids useful for peptide synthesis were prepared in high yield. For certain amino acid derivatives such as Boc-Pro-OH, Boc-Ile-OH, and Boc-Val-OH, their tetrafluorophenyl esters have significantly higher melting points than the corresponding pentafluorophenyl esters. Kinetic studies were carried out to compare the racemization rate constants (with triethylamine) and coupling rate constants (with valine methyl ester) of the tetrafluorophenyl and pentafluorophenyl esters of protected histidine and tyrosine. Results of the second-order kinetics showed similarly large k_coupling/k_racemization ratios for both tetra- and pentafluorophenyl esters. In particular, the use of 2,3,5,6-tetrafluorophenyl or pentafluorophenyl ester prevents extensive racemization of the N-tert.-butyloxycarbonyl-N^im-benzyl-histidine.     

THE METABOLIC EFFECTS OF CHRONIC HYPERGLUCAGONAEMIA

A subject with a benign glucagonoma was studied before and after complete resection of his pancreatic tumour. Studies were undertaken pre- and post-operatively to determine the effects of chronic hyperglucagonaemia on glucose tolerance and glucose kinetics both in the fasting state and during physiological insulin infusions, employing the [3H]-3-glucose technique. In addition the plasma cyclic AMP response to an acute infusion of glucagon was studied pre- and post-operatively. The basal immunoreactive glucagon levels pre- and post-operatively were 10492 +/- 1296 and 149 +/- 15 pg/ml respectively. Pre- and post-operative oral glucose tolerance tests did not differ but were abnormal. Pre-operatively basal hepatic glucose production was normal and it was suppressed rapidly by the low dose insulin infusion, despite continuing hyperglucagonaemia. The metabolic clearance rate of glucose was slightly reduced. There was no plasma cyclic AMP response to a glucagon infusion, suggesting down-regulation of the glucagon receptor by the chronic hyperglucagonaemia. Post-operatively the hepatic glucose production and clearance rate of glucose fell, whereas the plasma cyclic AMP responses to the glucagon infusion reverted to a normal pattern. It is concluded that chronic hyperglucagonaemia is not a major factor in the development of the glucose intolerance, but it may lead to down-regulation of the biological action of glucagon.