A myeloproliferative disease in two infants associated with eosinophilia and chromosome t(1;5) translocation

Two children are described who presented at the age of 5 and 7 months with anaemia, a high white cell count with eosinophilia and thrombocytopenia. Both children had an identical balanced translocation t(1;5)(q23;q33) and no evidence of a constitutional abnormality. The response to treatment of one child was poor, the other remains well on therapy. This translocation has not been previously reported and is likely to represent a subclass of myeloproliferative disorder analogous to the monosomy 7 syndrome, although less common. The previous literature of acquired chromosome abnormalities involving chromosomes 1 and 5 is reviewed.     

Pitfalls in the use of clinical algorithms

The algorithm is a very useful tool in medical practice. Like any other tool, it has advantages and disadvantages. The wise physician avoids a modality until he has learned how to use it. The same should be true of algorithms. Obtain some computer primers that explain the writing of algorithms. Experiment with algorithms of your own creation. When you reach the level where you can easily write your own algorithms, you are ready to use those written by others, making any modifications necessary to suit your own philosophy and experience.     

1H NMR studies of urine during fasting: excretion of ketone bodies and acetylcarnitine

High-resolution 1H NMR spectroscopy has been applied to a study of urine from five normal human subjects during a 48-h period of fasting and for 22 h thereafter. The excretion rates of all three ketone bodies (acetoacetate, 3-D-hydroxybutyrate, and acetone), acetylcarnitine, creatinine, and sarcosine during this period were measured. Parallel increases in the excretion of the ketone bodies and acetylcarnitine were observed during fasting with little change in the output of creatinine and sarcosine.     

In vivo antitumor activity and in vitro cytotoxic properties of bis[1,2-bis(diphenylphosphino)ethane]gold(I) chloride

We have previously reported the cytotoxicity and antitumor activity of bis(diphenylphosphino)ethane (DPPE) and a variety of its transition metal complexes. During studies of the chemistry of a gold complex of this group [(AuCl)2(DPPE)], it was observed that this complex readily underwent ring closure on reaction with DPPE to form the tetrahedral complex [Au(DPPE)2]+. Various counterion forms (e.g., Cl-) of this cation were isolated and were found to exhibit a remarkably high stability in solution. Evaluation of [Au(DPPE)2]Cl in mice bearing i.p. P388 leukemia demonstrated that the compound produced an average of 87% increase in life span at its maximally tolerated dose (2-3 mumol/kg/day for 5 days). Activity was also seen in i.p. M5076 reticulum cell sarcoma (60% increase in life span) and s.c. mammary adenocarcinoma 16/c. Modest activity was evident in i.p. B16 melanoma and L1210 leukemia. A subline of P388 leukemia resistant to cisplatin was not cross-resistant to [Au(DPPE)2]Cl. In addition, combination therapy of [Au(DPPE)2]Cl and cisplatin against i.p. P388 demonstrated an advantage over single-agent therapy. In vitro studies of [Au(DPPE)2]Cl showed that the compound: is cytotoxic to tumor cell lines; is only minimally inhibited in its cytotoxic activity by the presence of serum; produces DNA protein cross-links and DNA strand breaks in cells; and inhibits macromolecular synthesis with a preferential inhibitory effect on protein synthesis relative to DNA and RNA synthesis. 31P nuclear magnetic resonance spectroscopy indicated that the compound is stable in the presence of serum proteins, thiols, or disulfides and that it reacts with Cu(II) resulting in the formation of a Cu(I)DPPE complex. The results of these in vivo and in vitro experiments suggest that the contrasting pharmacological profile of [Au(DPPE)2]Cl with respect to other gold(I) phosphine complexes may be related to both the kinetic stability of the complex and its stability in the presence of thiols.     

Use of paramagnetic chelated metal derivatives of polysaccharides and spin-labeled polysaccharides as contrast agents in magnetic resonance imaging.

Soluble and insoluble polysaccharides were derivatized with diethylenetriaminepentaacetic acid (DTPA) and/or spin-labeled with 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO). Polysaccharides derivatized with DTPA were prepared via cyanogen bromide activation, coupling to a diamine linker, and to DTPA anhydride. Spin-labeled polysaccharides were also prepared via cyanogen bromide activation. The extent of derivatization for dextran (18 kDa) was about 120 glucose units per DTPA, and for cellulose and starch about 15-30 units per DTPA. For spin-labeled polysaccharides, the average loading ranged from 1 nitroxide per 16 glucose units for starch to 181 for dextran (82 kDa). These derivatized paramagnetic polysaccharides were shown to be more effective relaxants than the small paramagnetic molecules alone. Both soluble and insoluble polysaccharide-linker-DTPA-Gd(III) complexes were effectively cleared from the body (rats) after oral administration. After intravenous administration, the biodistribution of dextran-linker-DTPA-Gd(III) complexes differed significantly from that of GdDTPA. Reduction of the nitroxide by ascorbic acid was retarded in the polysaccharide derivatives, particularly in starch derivatized with both nitroxide and linker-DTPA-Cu(II). These agents showed contrast enhancement in the gastrointestinal tract of rabbits.