Pharmacokinetics of ethylenediaminemalonatoplatinum(II) (JM-40) during phase I trial

Pharmacokinetics of the cis-platin analog ethylenediaminemalonatoplatinum(II) (JM-410) was studied in 28 cycles of 19 patients during the phase I study of this drug. The drug was administered intravenously by short-term (10-60 min) infusion. Doses ranged from 20 to 1,200mg m-2. JM-40 was determined in plasma ultrafiltrate and urine by HPLC. Platinum (Pt) concentrations were determined in plasma, plasma ultrafiltrate, urine and red blood cells by atomic absorption spectrometry up to 5 days after administration of the drug. Ultrafilterable Pt could be determined up to 45 days after the infusion in one patient sampled over such a long period. Pharmacokinetics of JM-40 showed a linear behaviour. The final half-life of total Pt in plasma was 4.1 +/- 0.9 days. The disposition of JM-40 was similar to that of ultrafilterable Pt in respect to t1/2 alpha (10 and 13 min), t1/2 beta (44 and 57 min), volumes of distribution Vc (11 and 121) and Vss (17 and 201), systemic clearance (256 and 223 ml min-1), renal clearance (69 and 73 ml min-1) and metabolic clearance (183 and 154 ml min-1). During the first 6 h 27 +/- 9% of the administered dose was excreted as JM-40. Cumulative platinum excretion in the urine amounted to 29 +/- 13% and 60 +/- 13% over the first 6 h, 24 h and 5 days, respectively. The uptake of platinum in red blood cells was limited, comprising only 0.24 +/- 0.12% of the administered dose. Although JM-40 and carboplatin are structurally closely related, pharmocokinetics and toxicity of JM-40 were more similar to cis-platin than to carboplatin.     

Effects of emotion on perceptual asymmetry: interactions with personality

Perceptual asymmetry on a series of four specially constructed dichotic word tests was found to change as a function of the emotional quality of the words in the tests (P = 0.05). This was most pronounced in the case of positively valued words which produced an increase in asymmetry consistent with facilitated left-hemisphere function (P less than 0.004). Changes in asymmetry with emotion differed as a function of personality characteristics of the subjects, with repressors and high anxious subjects showing an increase with emotion while true low anxious subjects showed a decrease (P less than 0.02). Personality groups also differed in asymmetry on an emotionally neutral test (P less than 0.04) and in changes in asymmetry over time independent of emotion (P less than 0.001). These data suggest that emotion mediated activation of the left hemisphere may facilitate information processing within that hemisphere. Moreover, they indicate that dichotic listening tests may provide a non-invasive and inexpensive method for assessing emotion mediated changes in brain state that are clinically relevant.     

C-reactive protein levels predict postoperative septic complications

We studied 108 patients undergoing clean-contaminated and dirty surgical procedures to determine whether daily C-reactive protein (CRP) measurements for 14 days postoperatively could predict the occurrence of septic complications prior to clinical diagnosis. Diagnostic criteria for septic complications and positive CRP response were defined in advance of the study. The CRP assays were carried out using an automated laser nephelometer system after the patient's discharge from the hospital. Forty-six septic complications were diagnosed in 40 patients. These complications consisted of wound infection (23), urinary tract infection (11), pneumonia (six), upper respiratory tract infection (three), intra-abdominal abscess (one), and other (two). The CRP testing was found to have a positive predictive value of 69% and a negative predictive value of 78%. We conclude that serial CRP measurements may be a valuable adjunct to surgical care in patients at high risk of postoperative septic complications.     

Polymorphonuclear leukocyte function in psoriasis vulgaris

Polymorphonuclear leukocyte (PMN) migration was assessed in vitro using the agarose plate method in patients with psoriasis vulgaris, and compared with an age- and sex-matched control group. No significant difference was found between the two groups in the PMN response to the chemotactic substances F-Met-Leu-Phe (FMLP) or zymosan activated serum (ZAS). Equally, the chemokinetic or chemotactic potential of psoriatic serum did not differ from control serum. Our results do not support a primary abnormality of PMN function in psoriasis.     

Inhibition of vessel allograft rejection by endothelial removal. Morphologic and ultrastructural changes.

The vascular endothelium plays an important and complex role in vascular allograft rejection. Antigens expressed by the endothelium can act to promote and be the target of rejection reactions, which often lead to thrombosis and ischemic necrosis of the allograft. In this study, segments of femoral artery and femoral vein with or without endothelium were grafted between allogenic or autologous control rats. Immunocompetent Lewis (RT1(1] recipient rats were randomly selected for groups (N = 14 for each) receiving the following: ACI- (RT1a) allografts with intact endothelium, allografts with endothelium removed before operation, autografts with endothelium, and autografts with endothelium removed. Rejection was assessed by graft patency as well as morphologic and ultrastructural changes. At 5 days, the allografts with intact endothelium were totally occluded, whereas allografts without endothelium remained patent, as did autologous control grafts with or without endothelium. Two additional groups (N = 14 each) receiving the de-endothelialized allografts or autografts were examined at 120 days after operation, revealing that grafts in both groups were still patent and had been re-endothelialized. These findings indicate that physical removal of vascular endothelium may depress vessel allograft rejection without immunosuppressive therapy.     

Cancer patterns in Jordan 1975-1979

A total of 3,604 primary malignant tumours diagnosed histologically at the Departments of Pathology in Jordan during the period 1975-1979 were analysed. The relative frequency by age, sex and site of these tumours and age-standardised incidence rate are presented. Truncated standardised incidence rates for selected tumours were compared in Jordan and other countries. Except for the urinary bladder tumours, there is a striking resemblance between Jordan and other Middle Eastern countries in the pattern of tumour-occurrence in most sites. Skin malignancies are the dominant tumours in the general and male population, breast in female population and lymphomas in children. Noteworthy are the histologically advanced bladder cancers and the relatively young females affected by breast cancer at first diagnosis. Childhood tumours comprised 7.4% of the total cancers in the present study.     

Chylothorax after high translumbar aortography

Chlothorax is a rare complication of high translumbar aortography and a case is described here.