Both melphalan and cyclophosphamide increase life expectancy in patients with myelomatosis, but few large randomised studies have compared combination chemotherapy regimens with these single agents. In the Vth MRC myelomatosis trial, the survival of 314 patients randomised to receive ABCM (adriamycin, BCNU, cyclophosphamide, and melphalan) as first-line treatment was significantly longer than that of 316 patients given intermittent melphalan (M7) (p = 0.0003). The 75%, median, and 25% survivals were 7, 24, and 42 months, respectively, with M7 and 10, 32, and 56 months, respectively, with ABCM. Stable disease with few symptoms (plateau) was achieved by 61% of patients given ABCM and 49% of those given M7 (p = 0.004). Myelotoxicity was comparable between regimens. Cross-trial analysis suggests that M7 is comparable to melphalan and prednisone or melphalan, prednisone, and vincristine; that the efficacy of ABCM in the Vth trial and VIth MRC trials is comparable; and that ABCM gave better survival than intermittent melphalan regimens in the prognostic groups analysed. The results indicate that ABCM is an acceptable regimen that is more effective than melphalan, with or without prednisone, for first-line treatment of myelomatosis.

Falls in gastric intramucosal pH (pHi) are associated with morbidity and mortality in patients admitted to intensive-care units (ICU). We tested the hypothesis that ICU outcome can be improved by therapy guided by changes in pHi and aimed at improving systemic oxygen availability. We studied 260 patients admitted to ICUs with APACHE II scores of 15-25. After insertion of a gastric tonometer, each patient was randomly assigned to a control or protocol group within the admission pHi category (normal = 7.35 or higher; low = below 7.35). The control groups were treated according to standard ICU practices. The protocol groups received, in addition, treatment to increase systemic oxygen transport or to reduce oxygen demand, whenever the pHi fell below 7.35 or by more than 0.10 units from the previous measurement. The protocol was used, because pHi fell, in 67 (85%) of the protocol group with normal pHi on admission. There were no significant differences between protocol and control groups in demographic characteristics, admission blood gases or haemoglobin concentration, number or type of organ system failures, or the intensity of ICU care. For patients admitted with low pHi, survival was similar in the protocol and control groups (37% vs 36%), whereas for those admitted with normal pHi, survival was significantly greater in the protocol than in the control group (58% vs 42%; p less than 0.01). Therapy guided by pHi measurements improved survival in patients whose pHi on admission to ICU was normal. pHi-guided resuscitation may help improve outcome in such patients by preventing splanchnic organ hypoxia and the development of a systemic oxygen deficit.

Whether antibiotic prophylaxis can prevent bacterial endocarditis is hotly debated. In an attempt to settle this issue, we have assessed the efficacy of prophylaxis for bacterial endocarditis on native valves in a nationwide, case-control study in the Netherlands. Cases were patients with known cardiac disease in whom endocarditis developed within 180 days of a medical or dental procedure for which prophylaxis was indicated. Of a total of 438 patients with endocarditis diagnosed during 2 years, 48 were eligible for the study. Controls were patients with the same cardiac status in whom endocarditis did not develop within 180 days of a similar procedure; of a total of 889 controls from five hospitals, 200 were eligible. Overall, about 1 in 6 patients in both groups had received prophylaxis. The best estimate of protective efficacy was 49% for first-ever endocarditis occurring within 30 days of a procedure. Endocarditis developed within 30 days of a procedure in only 13% of patients with a previously diagnosed heart lesion which predisposed to the disease. The findings suggest that strict adherence to generally accepted recommendations for prophylaxis might do little to decrease the total number of patients with endocarditis in the community.

Cutaneous wheal and flare responses to increasing concentrations of calcitonin gene-related peptide, substance P, neurokinin A, vasoactive intestinal polypeptide (VIP), compound 48/80, and phosphate-buffered saline were measured in 10 patients with chronic idiopathic urticaria and 10 healthy controls. A significant increase in VIP-induced wheal, but not flare or cutaneous blood flow, was seen in urticarial patients compared with controls (p less than 0.001). No significant differences in responses to other tested compounds were found between these groups. These data point to an increased sensitivity of microvasculature to VIP in patients with chronic idiopathic urticaria.

Most fetuses in developed countries are exposed in utero to diagnostic ultrasound examination. Many pregnant women express concern about whether the procedure harms the fetus. Since most routine ultrasound examinations are done at weeks 16-22, when the fetal brain is developing rapidly, effects on neuronal migration are possible. We have sought an association between routine ultrasonography in utero and reading and writing skills among children in primary school. At the age of 8 or 9 years, children of women who had taken part in two randomised, controlled trials of routine ultrasonography during pregnancy were followed-up. The women had attended the clinics of 60 general practitioners in central Norway during 1979-81. The analysis of outcome was by intention to treat: 92% of the "screened" group had been exposed to ultrasound screening at weeks 16-22, and 95% of controls had not been so exposed, but there was some overlap. 2428 singletons were eligible for follow-up, and the school performance of 2011 children (83%) was assessed by their teachers on a scale of 1-7; the teachers were unaware of ultrasound exposure status. A subgroup of 603 children underwent specific tests for dyslexia. There were no statistically significant differences between children screened with ultrasound and controls in the teacher-reported school performance (scores for reading, spelling, arithmetic, or overall performance). Results from the dyslexia test sample showed no differences between screened children and controls in reading, spelling, and intelligence scores, or in discrepancy scores between intelligence and reading or spelling. The test results classified 21 of the 309 screened children (7% [95% confidence interval 3-10%]) and 26 of the 294 controls (9% [4-12%]) as dyslexic. The risk of having poor skills in reading and writing was no greater for children whose mothers had been offered routine ultrasonography than for those whose mothers had not been offered the procedure.

To reduce the likelihood of thrombophlebitis during intravenous feeding through a peripheral vein, the osmolality of the solution is usually reduced by disproportionately raising the lipid content and lowering the carbohydrate, electrolyte, and aminoacid concentrations. The possibility that delivery system rather than feed is the main influence on the development of thrombophlebitis was examined in a randomised comparison of a fine-bore silicone catheter against a short 'Teflon' cannula. The nutrient solution given through a peripheral vein was a standard feed used for infusion into a central vein (osmolality 1250 mOsmol/kg, 13 g nitrogen, 200 g glucose [800 kcal], and lipid emulsion [1000 kcal]). 27 patients received the infusion through a fine-bore silicone rubber catheter (diameter 23 G, length 15 cm) and 23 through a teflon catheter (diameter 20 G, length 3.2 cm). The median duration of feeding was 5 days in each of the two groups. Thrombophlebitis developed in all patients in the teflon group but in only 2 (7%) of the silicone group. The first silicone catheter for a patient lasted a median of 128.5 h, compared with 40 h for the first teflon cannula (p less than 0.001). The results show that when a nutrient solution of osmolality 1250 mOsmol/kg is delivered through a peripheral vein with an ultrafine-bore silicone catheter, the risk of thrombophlebitis is low. For many patients intravenous feeding may thus be given through a peripheral instead of a central vein without compromising the nutritional adequacy of the feed.

Under international humanitarian law, the Hague Declaration of 1899 forbids the use of small arms ammunition that disrupts in the body after impact. However, assessment of whether bullets have undergone disruption is subjective and accusations that one or both sides of a conflict have used such ammunition cannot be substantiated. We describe a method by which disruption of bullets after impact can be assessed objectively. We reviewed 1287 wound radiographs of 1201 patients in four International Committee of the Red Cross hospitals. Radiographs were scored according to the F (fracture) and M (presence of metallic bodies) variables of the Red Cross wound classification; bullet disruption is evidenced by metallic fragments on the radiograph. One hospital had a significantly higher proportion of patients wounded by bullets that disrupted after impact; these wounds were associated with comminuted fractures. The findings show that the presence of metallic fragments on a radiograph is a reliable indicator of wound severity and bullet disruption. The study has important implications for the upholding of international humanitarian law, because with our method the use and manufacture of bullets that contravene the Hague Declaration can be identified.

S-carboxy-L-methylcysteine was used to assess the activity of the S-oxidation pathway of sulphur metabolism in 35 patients with systemic lupus erythematosus (SLE); 25 (71%) showed impaired sulphoxidation and 21 (60%) produced virtually no sulphoxides, compared with 17 (36%) and 2 (4%), respectively, of 47 healthy controls. The substrate/product ratio of cysteine oxygenase (plasma cysteine/sulphate) was significantly higher in SLE patients than in controls (median [interquartile range] 362 [224-588] vs 65 [44-111]; p less than 0.00001). The alternative pathway of sulphur metabolism, S-methylation, catalysed by thiolmethyltransferase, was not impaired in the SLE patients. There is a biochemical difference in sulphur metabolism between SLE and rheumatoid arthritis, since both pathways are impaired in the latter disorder.

A randomised, phase I/II, double-blind, placebo-controlled study was designed to assess the effect of topically applied recombinant human BB homodimeric platelet-derived growth factor (rPDGF-BB) on healing of chronic pressure ulcers. Twenty patients were randomly allocated daily treatment for 28 days with 1, 10, or 100 micrograms/ml rPDGF-BB (0.01, 0.1, or 1.0 micrograms per cm2 ulcer area) or placebo. Patients treated with 100 micrograms/ml rPDGF-BB showed a greater healing response than the placebo group, but the lower doses had little effect. After 28 days, ulcers treated with 100 micrograms/ml rPDGF-BB were smaller than those treated with placebo (mean [SE] volume 6.4 [4.0] vs 21.8 [5.6]% of day 0 volume). There were no toxic effects. These preliminary findings suggest that rPDGF-BB is a potent wound-healing agent in soft tissue.

Laparoscopy is frequently associated with postoperative shoulder pain that may last several days. We have assessed the analgesic effect of intraperitoneal local anaesthetics during day-case diagnostic laparoscopy. 80 young women were randomly assigned to one of four groups of 20 patients each: group 1, no peritoneal administration; group 2, 80 ml saline injected under direct vision in the right subdiaphragmatic area at the start of the procedure; group 3, 80 ml 0.5% lignocaine with adrenaline (320,000 dilution); group 4, 0.125% bupivacaine with adrenaline (800,000 dilution). Scapular pain was assessed with a visual analogue pain scale, and information about nausea, vomiting, abdominal pain, and analgesic requirements during the first 48 h was sought. Both local anaesthetics were more effective in reducing postoperative shoulder pain than either control or saline. Analgesic requirements were greater in the non-treatment groups than in the local anaesthetic groups. Intraperitoneal local anaesthetic administration during laparoscopy is both a non-invasive and an efficient method of reducing the intensity of scapular pain.