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Bone marrow aspirates from patients with cerebral malaria were studied with the light and electron microscopes. Various abnormalities were found including: (1) an increase in plasma cells and macrophages, sometimes to a marked degree; (2) phagocytosis of parasitized red cells by macrophages and of merozoites by neutrophil metamyelocytes, neutrophil granulocytes and macrophages; (3) an increase in the proportion of eosinophil granulocytes and their precursors; (4) the presence of giant metamyelocytes; and (5) morphological abnormalities of erythroblasts, particularly irregularly-shaped nuclei and karyorrhexis. A high percentage of the red cells within marrow sinusoids were parasitized and the parasitized cells were attached to the endothelium. Some marrow sinusoids were packed with and completely obstructed by parasitized cells. Strands of electron-dense material were sometimes found connecting the knobs of parasitized red cells to endothelial cells or to the knobs of adjacent parasitized red cells. A striking finding was a complex interdigitation between cytoplasmic processes developed by some of the parasitized red cells and those developed by the endothelial cells to which they were attached. Occasionally, cytoplasmic processes arising from marginated parasitized red cells completely penetrated the endothelial cell and emerged extravascularly. Several parasitized red cells were also found extravascularly between haemopoietic cells. Sequestration of parasitized red cells within small blood vessels may play a part in the pathogenesis not only of the encephalopathy of cerebral malaria but also of the bone marrow dysfunction in severe malaria.

The evolution of coagulation abnormalities was studied in Russell's viper bite victims who, on admission to hospital, showed no clinical signs of systemic envenoming. Based on the laboratory results and subsequent clinical course, three groups were distinguished. The first group, consisting of five cases, showed no activation of coagulation at any stage. The second group, consisting of six cases, developed mild to moderate abnormalities in some tests, particularly in the aPTT and factor V assay, which corrected to normal without treatment. The third group, consisting of nine patients, developed haemostatic abnormalities as early as 1-2 h after the bite, which progressed to severe defibrination 4-8 h later at which time antivenom was given. Comparison of the haemostatic abnormalities in the three groups suggested that serial monitoring of the serum FDP concentration may be of value in predicting the likelihood of systemic envenoming and progression to complete defibrination.

Uncoagulable blood and life-threatening bleeding can result from the action of some snake venom toxins on haemostatic components of blood and vessel walls. Although envenoming by Micropechis ikaheka primarily affects neurones and muscle cells causing post-synaptic neuromuscular blockade and rhabdomyolysis, disturbances of haemostasis also occur. Therefore, the present study explored the effects of M. ikaheka venom on platelets and endothelium, which are important components of the haemostatic mechanism. The venom inhibited platelet aggregation in response to ADP and collagen, and also delayed clotting dependent on platelet activation or endothelial cell tissue factor expression. Some of these effects were reduced by the incubation of venom with a phospholipase A2 (PLA2) inhibitor and could be reproduced by a 17 kDa venom fraction containing a PLA2. In addition, an 11 kDa fraction containing a long-chain neurotoxin reduced ADP-induced aggregation. The venom was also found to reduce endothelial cell adherence to vitronectin-, fibronectin- and collagen-coated surfaces. These results suggest that, by inhibiting procoagulant activities of platelets and endothelial cells, a 17 kDa PLA2 plays an important role in the anticoagulant action of M. ikaheka venom.

Summary Background Stings from bees and wasps can cause systemic reactions which can be fatal in some individuals. In these venom-sensitive patients, specific IgE to the venom is produced and is considered to participate in the adverse reactions. This immune response requires antigen presentation by human leucocyte antigens (HLA) class II molecules, which includes DR and DP, which are present on antigen presenting cells. Objective To test for associations between HLA class II DRB1 and DPB1 alleles and life- threatening sensitivity to both bee and wasp venoms. To establish further whether any associations are independent of the atopy phenotype. Methods A total of 33 bee- and 44 wasp-venom-sensitive patients was studied. DRB1 genotypes were determined by single stranded oligonucleotide (SSO) probing of PCR products, and DPB1 genotypes by amplified fragment length polymorphism (AFLP) analysis. Total and specific IgE were measured using the Pharmacia Immunocap, FEIA. Patients with specific IgE to the venom antigens only were termed monosensitive and those with additional specific IgE to HDM and/or GP were termed polysensitive. Results Allele frequencies were compared to an unrelated control population. The 33 bee- sensitive patients had a greater prevalence of DRB 1*07 alleles than the control subjects, 26% vs 14%, with an odds ratio (OR) of 2.1 (95%CI, 1.2–3.7, P= 0.015, corrected for multiple comparisons, pc > = ns). This association was confined to the 15 monosensitive bee patients, who had a 43% DRB 1*07 allele frequency when compared with 11% in the 18 polysensitive bee patients, OR 6.1 (95%CI, 1.73–22, P= 0.004, pc= 0.05), and when compared with a control group of non-venom subjects, 43% vs 16%, OR 3.9 (95% CI, 1.72–9.0, P= 0.002, pc= 0.02). The 44 wasp-sensitive patients had an increase in the DRB1*11 allele when compared with the control subjects, 13% vs 6%, with an OR 2.2 (95%CI, 1.0–4.6, P= 0.04, pc= NS), and a decreased prevalence of DRB 1*04 alleles, 10% vs 19%, with an OR 0.33 (95%CI, 0.24–0.99, P= 0.04, pc= NS), but these were not significant when multiple comparisons were taken into account. The DPB1 alleles were not significantly different between the venom sensitive patients and the controls. Conclusion Patients monosensitive to bee venom had a significantly greater prevalence of DRB 1 *07 alleles than the non-venom, control population suggesting that IgE responses in these patients may, in part be controlled by immune response HLA class II genes. These results are also suggestive of wasp-sensitive patients having a higher prevalence of DRB1*11 and a lower prevalence of DRB 1*04 than the control population.

IN 2011, the Veterinary Poisons Information Service (VPIS) reviewed 422 telephone inquiries concerning dogs with adder ( Vipera berus ) bites received between 1985 and 2010 (Sutton and others 2011). European adder antivenom was used in 56 per cent of cases, steroids in 51 per cent, antibiotics in 56 per cent and antihistamines in 20 per cent. Among dogs treated with antivenom, case fatality was slightly lower than in the rest (0.3 per cent versus 0.5 per cent, though not statistically significant) and swelling resolved more rapidly (47 hours on average versus 94 hours). Although antivenom is not required for the management of every case of adder bite, it is usually recommended for potentially serious cases, …

In a new approach to the specific labelling of organic compounds with tritium use is made of isotope exchange with tritium of certain specific hydrogen atoms in organic molecules when stirred with tritium gas in solution at room temperature in the presence of a metal hydrogen transfer catalyst. Specifically labelled tritiated compounds of high specific activity and radio-chemical purity are obtained. The method can be used for labelling a wide variety of organic compounds including purines, purine nucleosides and nucleotides, aromatic amines and amino acids, carbohydrates and steroids. Numerous examples are cited and possible mechanisms discussed.

Chloroquine diphosphate (3 mg base kg-1) was given by constant rate intravenous injection over 10 min to 12 healthy adult male volunteers. Plasma concentrations of chloroquine and the principal metabolite desethylchloroquine, electrocardiograph intervals, and arterial blood pressure were measured at frequent intervals to determine the relationship between cardiovascular effects and plasma concentrations. Peak plasma concentrations ranged between 784 and 6649 (mean 2913) ng ml-1. The decline in plasma concentrations was multiexponential with an initial rapid distribution phase; mean (+/- s.d.) first order rate constant 0.65 +/- 0.14 min-1, and an estimated apparent volume of the central compartment of 0.18 +/- 0.15 l kg-1. There was no serious toxicity, but subjective side effects were reported in all patients and there was a significant fall in systolic blood pressure (110 +/- 9.5 to 101 +/- 12.5 mm Hg; P = 0.03) and rise in heart rate which paralleled the change in plasma chloroquine concentrations. Coincident with changes in blood pressure, there was a significant prolongation of the electrocardiograph QRS interval; 81 +/- 15 to 92 +/- 13 ms (P less than 0.01) but no change in the QTc interval. These findings suggest that the cardiovascular toxicity of parenteral chloroquine is related to transiently high plasma concentrations occurring early in the distribution phase. This results from incomplete distribution from a central compartment that is approximately one thousand times smaller than the eventual total apparent volume of distribution at steady state. Rate of administration is therefore a major determinant of toxicity.

Labelling patterns in tritiated folic acid and methotrexate have been examined by tritium nuclear magnetic resonance spectrometry. The results indicate that oxidative degradation with permanganate can give a false tritium distribution.

A series of 50 neurochemicals, important for the investigation of neurotransmission processes, has been labelled with tritium, using in all 8 methods. Tritium nuclear magnetic resonance spectroscopy has been employed to determine the positions and extent of labelling in these neurochemicals which can be important for their use in tracer studies. The specificity of the labelling processes is discussed.

The complete analysis of the tritium distribution in tritiated methyl groups in labelled compounds is achieved by a direct method for the first time, through 3H NMR spectroscopy aided by resolution enhancement.

The position of the tritium label in DL-[G-3H] phenylalanine prepared by platinum catalysed exchange in tritiated water at elevated temperatures has been determined by chemical degradation and by tritium nuclear magnetic resonance speotroscopy. There is good agreement between the results of the two methods : analysis of the product of two separate preparations showing 73 ± 3% of the activity in the aromatic nucleus and 27 ± 3% in the side chain.

SUMMARY Eighty-one patients who continued to be incontinent of urine after repair of prolapse have been investigated, treated and followed up from one to six years. Cases have been classified by investigation as having mechanical faults of the urethral sphincter mechanism or faults of bladder action. Fifty-two patients were considered to have anatomical abnormalities of the urethral sphincter mechanism usually due to fixity by scar tissue. Forty-two patients have been cured by freeing the urethra and bringing in fresh tissue. Twenty-nine cases were found to have abnormal bladder action usually due to chronic cystitis or urethro-trigonitis and only one-half have been cured.

The influence of lung shrinkage on the breath holding time was studied in three normal males. The rate of shrinkage was increased two to three fold either by slow expiration or by reducing gas density in a hypobaric chamber. For any given lung volume the relationship between breath holding time and pCO2 was defined by a rebreathing method which allowed breath holds to be performed at progressively increasing levels of pCO2. Hypoxia was avoided throughout and the ventilatory response to CO2 remained constant irrespective of ambient pressure. The breath holding time for any given pCO2 was usually longer the larger the lung volume. Increasing the rate of lung shrinkage by either method did not alter the relationship between breath holding time and pCO2. There was no constant relationship between the pCO2 and the lung volume at the breaking point of a breath hold. These findings are discussed in the light of previous work and it is concluded that the sensation arising during breath holding cannot be fully explained in terms of any combination of pCO2, lung volume and lung shrinkage.

Case report of urinary incontinence during menstruation in a 18 year-old healthy women. Urodynamics investigations at mid-cycle were normal but a detrusor instability was found during menstruation. Physiopathology, involving probably prostaglandins, is discussed