Studies on the human metabolism of iproplatin

Summary We have previously shown that a significant portion of the total platinum in the plasma of patients receiving iproplatin is protein-bound [17]. We have also identifiedcis-dichloro-bis-isopropylamine platinum(II) (CIP) as a major metabolite of iproplatin [19]. To understand the nature of the bound platinum, we carried out in vitro comparative protein-binding studies for iproplatin and CIP. These studies indicate that when CIP is incubated in plasma, protein binding occurs, with a 2.7-h half-life for the disappearance of CIP; the parent complex does not bind and is stable in plasma for at least 48 h. The time dependence of protein binding with CIP suggests the formation of other chemical species from CIP that may be responsible for the observed protein binding. The results indicate that in patients receiving the drug, the reduction of iproplatin to CIP must take place intracellularly and that CIP or its protein-binding derivatives must efflux from the cells into the plasma. Efflux studies carried out to explore this possibility with cells in the whole blood showed that iproplatin was taken up into cells, but the efflux of protein-binding iproplatin metabolites did not occur. To understand further the nature of the metabolites of iproplatin, we carried out¹⁹⁵Pt-NMR (nuclear magnetic resonance) studies with urine from two patients who received a high dose of iproplatin (500 mg/m²). The predominant signals from the¹⁹⁵Pt-NMR corresponded to the divalent platinum complexes and not to quadrivalent complexes, indicating that the iproplatin metabolites in urine are divalent in nature.     

Acute hydrothorax complicating peritoneal dialysis.

Aim: To determine whether gradually increasing the peritoneal dialysate fill volume from 10 to 40 mL/kg over 6 days, rather than commencing at 40 mL/kg, prevents hydrothorax in children and reverses it if present. METHODS: A review of children peritoneally dialyzed in a single center. RESULTS: During the 20 years beginning June 1985, 416 children were peritoneally dialyzed, of which 327 (79%) had acute and 89 had end-stage renal failure. Among 253 children who had gradually increasing fill volumes, none developed acute hydrothoraces, but 13/163 (8%) who began with 40 mL/kg cycles did (p < 0.000, Fisher's exact test). These were diagnosed after a median (range) of 48 (6-72) hours and were predominantly right sided. Initially, we readily abandoned peritoneal dialysis; 2 were changed to hemodialysis. Subsequently, we found that peritoneal dialysis could be continued by using small volumes with the patients sitting up; cycle volumes were then gradually increased again. One pre-term baby died soon after developing an acute hydrothorax. One patient on chronic peritoneal dialysis developed an acute hydrothorax after forceful vomiting, but recovered after being dialyzed sitting up with low fills. CONCLUSION: Acute hydrothorax can be prevented and treated using graduated cycle volumes, and is not a contraindication for peritoneal dialysis.     

Resection and reanastomosis for the management of tracheal stenosis

Three cases of Cervical tracheal stenosis and One case of thoracic tracheal stenosis are managed by Resection and reanastomosis. Laryngealdrop by Suprahyoid-release, distal tracheal mobilisation and cervical flexion facilitate anastomosis without tension at the suture line. The pre-operative assessment, anaesthetic precautions, the operative technique and the problems encountered are discussed.     

Comparison of the efficacy of University of Wisconsin solution and Newcastle organ perfusion fluid in the preservation of livers for transplantation

Abstract University of Wisconsin solution (UW) is now used widely for the preservation of livers for transplantation. However, the use of commercial solutions has added considerably to the cost. We were able to produce a local version of organ perfusion fluid (NOPF) incorporating all the constituents of UW except for the hydroxyethyl starch and adenosine. We compared graft outcome using NOPF with imported grafts perfused with commercial UW solution. The two recipient groups (15 patients each) were similar with respect to age and sex distribution, urgency of transplantation, regraft status and patient and graft survival. Postoperative duration of ventilation, dialysis requirements, peak bilirubin, peak ALT and lowest unsupported prothrombin time were also similar in both groups. In conclusion, local perfusion fluids based on UW can be produced without detriment to graft outcome with considerable financial savings. At our institution, this represents a reduction of 33 % in the cost of perfusion fluids.     

Partial trisomy 22 (q11.2-q13.1) as a result of duplication and pericentric inversion.

A case of a 27 year old male with a duplication of part of the long arm of chromosome 22 (22q11.2-q13.1) together with a pericentric inversion of the same chromosome is reported. Particular phenotypic features of note include absence of speech, persistent self-injury, lack of daily living skills, colobomata, and very poor vision. Similarities between this case and other case reports of duplications of the long arm of chromosome 22 are discussed.     

Tuberculous infection of skeletal muscle in a case of dermatomyositis

A patient with dermatomyositis associated with carcinoma was treated with steroids and antibiotics for possible tuberculosis. Autopsy showed an overwhelming diffuse nongranulomatous infection of Mycobacterium tuberculosis involving only the skeletal muscles and one inguinal lymph node. The rare localization of tuberculosis to skeletal muscle in this case is possibly due to steroid immunosuppression and the humoral immune attack on muscle blood vessels that is a part of dermatomyositis. © 1994 John Wiley & Sons, Inc.     

Longitudinal stress fracture of the tibia: two cases.

Stress fracture of the tibia occurs in individuals who subject their extremities to repeated trauma. They can arise in otherwise healthy bone that is subjected to excessive loads (as in the marathon runner) or in abnormal bone that is subjected to minor loads (as in osteoporosis). These fractures may be anywhere along the tibial shaft and tend to be either transverse or oblique in orientation. We report two cases of stress fracture that ran longitudinally in the distal one third of the tibia. Both patients were healthy and did not describe excessive physical activity prior to fracture. Both describe a repetitive twisting action prior to fracture. Computed tomography was diagnostic in both cases following abnormal bone scans and normal plain radiographs. This unusual pattern of fracture has been reported on only four occasions in five patients in the literature.