High dose combination chemotherapy with ifosfamide, cyclophosphamide or cisplatin, mitomycin C and mustine with autologous bone marrow support in advanced non-small cell lung cancer. A phase I/II study.

Twenty-three patients with advanced NSCLC were treated with high dose chemotherapy using four agents and autologous bone marrow reinfusion. Ten patients received two bolus doses of cyclophosphamide (maximum tolerated total dose 10 G m-2), ifosfamide as a 24 h infusion (11 G m-2) followed by mitomycin C (70 mg m-2) as a subsequent 24 h infusion and mustine as two boluses (total dose 30 mg m-2). Another 13 patients received the same agents except cisplatin was substituted for cyclophosphamide, two doses (total dose 100 mg m-2) being given in a 24 h period. The median time of recovery to greater than or equal to 20,000 platelets was 21 days and of neutropaenia greater than or equal to 500 was 12-15 days. Unusual non-haematological toxicity e.g. cardiomyopathy, colitis, veno occlusive disease was not noted, all patients being given regular selenium and other trace elements. Three patients died in the first 2 weeks. There were five complete responses (22%) and 12 partial responses (52%) with four patients (2CR, 2PR) still alive at 27, 48, 73 and 82 weeks. The patient's Karnofsky performance in the cisplatin regimen improved over pretreatment values when compared a month after the end of treatment. The high dose regimen was associated with a high (74%) response rate, but with an overall median survival of only 6 months. The regimen has no advantage over conventional doses with the same agents in patients with metastatic NSCLC.

Pseudo grey platelet syndrome--grey platelets due to degranulation in blood collected into EDTA.

We have studied a woman with a history of mild bruising and bleeding, with a normal platelet count and normal clotting factors, who had platelets that appeared grey when stained and viewed under the microscope. Unlike the grey platelet syndrome, the abnormality was only evident when blood had been collected into EDTA and not when citrate or heparin was used as anticoagulant. This 'pseudo grey platelet syndrome' was associated with platelet dense body and alpha granule secretion with no aggregation and occurred on removal of extracellular Ca2+. We discovered that a plasma factor was responsible which could be an immunoglobulin but which is clearly different from the EDTA-sensitive antibodies which cause platelet aggregation and agglutination. We were not able to demonstrate a relationship between the mild bleeding tendency and the in vitro abnormality.

[Sensitization to nickel sulfate in patients with ileitis terminalis (Crohn disease)]. / Sensibilisierung gegen Nickelsulfat bei Patienten mit Ileitis terminalis (Morbus Crohn).

The history of inpatients with Crohn's disease revealed several occurrences of contact dermatitis due to metal ions. Therefore, we considered the question as to whether allergic reactions to amalgam fillings or mercury, delivered in small amounts, could be a factor in the activity of regional enteritis. 23 patients with Crohn's disease (15 females, 8 males), aged from 20 to 44 years were screened by an extended standard patch test (following the rules of the ICDRG). Surprisingly, no case of hypersensitivity to amalgam and/or mercury was found. However, nickelsulfate yielded positive reactions in 39.1% of all tested patients (9/23). In comparison to the normal population this prevalence of nickelsulfate hypersensitivity is distinctly increased. It may be an epiphenomenon of Crohn's disease (sensitization via an enhanced permeability of the irritated mucous membranes for nutritive nickelsulfate) or an etiopathogenetic co-factor. In the latter case regional enteritis might be regarded as an allergic-irritative disease of the bowel.

Atrial natriuretic peptide binding properties of purified rat glomerular membranes.

125I-ANP (3-[125I] iodotyrosyl28) binding studies with purified rat glomerular membranes indicate two types of physiologically relevant hormonal receptors, Types I and II, Kd approximately 5 pM and approximately 2.5 nM, respectively. All preparations were essentially free of capsular and tubular contamination. Binding data indicated that Type I receptors were three times more concentrated than Type II receptors in purified membrane fractions. When purified membranes were cross-linked with 125I-rANP, using disuccinimidyl suberate and separated by SDS-PAGE, approximately 75- and approximately 140-kDa proteins were specifically labeled in a ratio of approximately 3:1, respectively. Thus, in purified renal glomerular membranes, Type I receptors with molecular weight of approximately 75-kDa appeared to predominate and would be detectably saturated at circulating ANP concentrations as low as 15 pg/ml. These findings could account for the exquisite sensitivity of natriuretic response to ANP.

'On line' data handling in a routine haematology department.

The use of a ;stand alone' mini computer, on line, data acquisition system is described utilising a microprocessor as an adjunct to the main central processor to increase data transmission rates. Visual display units (VDU) provide on line flexibility of data input. The system acquires, on line, the Coulter S generated parameters together with the associated patient identification data and other requested tests. Erythrocyte sedimentation rate, platelet count, and B12 and folate results are fed in at will via the VDUs, using rapid entry subroutines. Percentage differential white cell count results and the absolute leucocyte count are calculated by the microprocessor, on line input being facilitated by remote keyboards associated with the VDUs. Total editing of all requests and results is available on all ;current' (unfiled) reports via the VDUs, and this facility includes the entry of film appearances using plus symbols and predetermined comments available against a code number. This editing function is also used to enter all other results that can be made available on the computer-printed report form. The computer system also provides quality control data, immediate printout of Coulter S results outside given limits, cumulative filing for all routine and designated ;priority' results, and a daily alphabetical listing of all patients from whom specimens have been examined together with full blood count, ESR, and platelet results on specimens examined that day.

Evaluation of a rapid method for the determination of plasma fibrinogen.

In this study the method of Ellis and Stransky (1961) to determine plasma fibrinogen is evaluated, and modifications are described which have been introduced to improve the sensitivity and reduce the time taken for the test.

The Zollinger-Ellison syndrome in a child.

The Zollinger-Ellison syndrome was encountered in a boy aged 11 years who presented with a bulbar duodenal ulcer causing intractable pain and bleeding. The diagnosis was made by finding an overnight fasting gastric secretion of 1,300 ml containing 134 m-equiv/HCl, and little change of secretion after maximal histamine stimulus. A circumscribed non-beta islet cell pancreatic tumour was excised, with antrectomy. Postoperative acid secretion was normal and the boy was well after being followed up for 15 months. The diagnosis and management are discussed, as the view that total gastrectomy must be performed in all cases of the Zollinger-Ellison syndrome is questioned.