Thrombolysis and mechanical cardiopulmonary resuscitation for pulmonary embolism complicated by hepatic and splenic lacerations resulting in major haemorrhage.

Thrombolysis with prolonged cardiopulmonary resuscitation may be required for the successful resuscitation of patients presenting with massive pulmonary embolism leading to cardiac arrest. A rare, recognised complication of cardiopulmonary resuscitation is traumatic hepatic and splenic laceration. The incidence of complications is believed to be increased in those who receive automated mechanical cardiopulmonary resuscitation, compared to those who receive standard chest compressions. We present a case of a patient with massive pulmonary embolism leading to cardiac arrest which was successfully treated with thrombolysis and mechanical automated cardiopulmonary resuscitation. The patient suffered hepatic and splenic lacerations resulting in major haemorrhage. This required emergency resuscitation with blood products and splenic embolisation. This case highlights the importance of continual re-assessment of patients, the early recognition of complications and an awareness of the potential complications of treatments we deliver.

beta-Adrenergic regulation of IL-6 release from adipose tissue: in vivo and in vitro studies.

UNLABELLED: Circulating IL-6 levels are elevated in obesity. Although IL-6 is expressed in adipose tissue, neither its regulation nor cell of origin is well characterized. Here we investigated the beta-adrenergic regulation of IL-6 release in a combination of studies on humans and animals in vivo and cultured adipocytes in vitro. Human in vivo study: Human volunteers were infused with isoproterenol, norepinephrine, or saline [4 M:4F; mean (SD) age 35.5 (5.8) yr; body mass index 24.6 (4.2) kg/m(-2)]. Plasma IL-6 levels increased during a 3-h infusion of isoproterenol (P = 0.01) and fell 2 h post infusion (P = 0.05). IL-6 levels did not change significantly with either norepinephrine or saline. Murine in vivo study: C57BL6/J male mice were injected ip with dobutamine (beta(1) agonist), clenbuterol (beta(2)), CL316243 (beta(3)), or saline placebo. Plasma IL-6 levels at 3 h were increased by clenbuterol (P = 0.02) and CL316243 (P = 0.02) but not dobutamine (P = 0.51), compared with placebo. IN VITRO STUDIES: In human peripheral blood cells, lipopolysaccharide treatment enhanced secretion of IL-6 (vs. controls; P < 0.001), whereas isoproterenol inhibited IL-6 secretion (P = 0.012) and norepinephrine had no significant effect. In contrast, isolated human adipocytes and differentiated 3T3F442A adipocytes all rapidly secreted IL-6 in response to adrenergic agonists (P < 0.01, compared with untreated cells). We conclude that beta 2/beta 3 adrenoceptor stimulation on adipocytes, rather than macrophages, may be responsible for the increases in plasma IL-6 concentrations observed during sympathetic activation and in obesity.

Control of hypertensive emergencies.

Although uncommon, hypertensive emergencies require prompt recognition and treatment to reduce very high morbidity and mortality rates. Admission to an intensive care unit for treatment and monitoring is essential for optimal care. A Swan-Ganz catheter is often helpful in management. Intravenous nitroprusside sodium (Nipride, Nitropress) is probably the drug of choice for hypertensive emergencies other than those due to eclampsia or pheochromocytoma.

Effects of sample handling on the stability of interleukin 6, tumour necrosis factor-alpha and leptin.

Detected levels of IL-6, TNF-alpha and leptin may be affected by methods of storage, anticoagulant or repeated freezing-thawing. Blood samples from 22 healthy subjects were: (i) allowed to stand for 1, 2, 4 or 6 h prior to, or after separation, before freezing at -70 degrees C; (ii) taken into tubes with lithium heparin, sodium citrate, EDTA or no anticoagulant, separated and frozen; and (iii) separated, and plasma repeatedly freeze-thawed for up to six cycles prior to assay. Leptin was assayed by RIA, and IL-6 and TNF-alpha by high-sensitivity ELISA. (i) IL-6 and TNF-alpha levels were not altered significantly in separated samples but IL-6 declined by mean (SEM) 14.3% (3.7%) and TNF-alphaincreased by 9.6% (2.3%) in samples left unseparated for 4 h (P=0.003 and 0.002, respectively). Leptin remained unchanged. (ii) Serum and EDTA-plasma samples gave comparable results for all three cytokines, but levels in the other anticoagulant samples were highly variable. (iii) IL-6 and leptin levels were not altered by up to 6 cycles of freeze-thawing, but TNF-alpha increased by 17.0% (3.7%) after 3 cycles. Concentrations of these molecules are significantly altered by storage conditions, therefore they need to be standardized for epidemiological and clinical studies, and between-study comparisons of levels may not be reliable.

Acute mental stress elicits delayed increases in circulating inflammatory cytokine levels.

The influence of acute mental stress on cardiovascular responses and concentrations of inflammatory cytokines up to 2 h later was assessed in 12 subjects exposed to stress and in eight control subjects. Beat-by-beat recordings of finger blood pressure and heart rate were made at rest and during two behavioural tasks (colour-word interference and mirror tracing). Blood was drawn after adaptation and at 45 min and 2 h after the tasks, and assayed for interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-alpha), interleukin-1 receptor antagonist (IL-1Ra), C-reactive protein (CRP) and haematocrit. Saliva was sampled periodically and assayed for free cortisol. The tasks were rated as stressful by the participants. The stress group showed significant increases in systolic and diastolic blood pressure (mean rises of 16.4+/-12.3 and 12.6+/-6.9 mmHg respectively) and heart rate (5.39+/-5.3 beats/min); these values returned to baseline during the recovery period. The IL-6 concentration was increased by 56% at 2 h after the tasks (P<0.05), while IL-1Ra was increased by 12.3% (P<0.01). No changes in cardiovascular variables or cytokine concentrations were observed in the control subjects, and haematocrit did not change. The magnitude of blood pressure responses during tasks was correlated positively with the IL-6 concentration after 45 min (r=0.70, P<0.05), and with the IL-1Ra concentration after 2 h (r=0.63, P<0.05). Increases in TNF-alpha after 2 h were correlated with heart rate responses to tasks (r=0.66, P<0.05). Associations between IL-6 and IL-1Ra concentrations were also recorded. This study indicates that inflammatory cytokines respond to acute mental stress in humans with delayed increases, and suggest that individual differences in cytokine responses are associated with sympathetic reactivity.

Evaluation of compounds for insecticidal activity on adult mosquitos. 1. Responses of adult mosquitos to some new insecticides.

Responses shown by female mosquitos to topical applications of solutions, to deposits from water-dispersible-powder formulations, or to exposure to the vapour from such deposits, are described for a number of compounds that have shown promise as residual contact insecticides.The behaviour of Anopheles stephensi females in laboratory tests indicates that departures of mosquitos from treated buildings, and their survival rates, are likely to be increased as a result of irritation and consequent activity after only a brief period of contact with phthalthrin (OMS-1011) and other synthetic pyrethroids but not with dieldrin (OMS-18) and lindane (OMS-17) or the carbamates and organophosphorus compounds tested. Mosquitos were not disturbed by exposure to the vapour from deposits of any of the compounds.The rates of action of the different compounds following their application in solution directly to the insect cuticle or contact of the mosquitos with deposits on plywood and plaster emphasize the importance of the lipid-solubility and partitioning properties of an insecticide in determining its passage from a surface deposit into, and through, the cuticle to the site of action.

Evaluation of compounds for insecticidal activity on adult mosquitos. 2. Toxicity to adult mosquitos and the physical properties of some new carbamates.

The N,N-dimethylcarbamates are much less toxic and much more volatile than the corresponding N-methylcarbamates. N-acylation of N-methylcarbamates is also generally accompanied by a loss in intrinsic toxicity to adult mosquitos by topical application, but the reduction in toxicity may be relatively small and in some N-acetyl derivatives may not occur at all. N-acylation is also accompanied by changes in physical properties such as lipid solubility and partition coefficient, which influence contact toxicity, and volatility, which affects residual activity. In the series of compounds examined, contact toxicity is maximal in the N-acetyl derivatives but their volatility is often so high that they lack the persistence required of residual insecticides. This does not apply, however, to the N-acetyl derivatives of OMS-597 and OMS-708 because the volatility of the parent compound is so low that some degree of persistence can be sacrificed to obtain some improvement in contact activity.OMS-1064 is the only N-chloroacetyl derivative tested so far that shows promise as a residual insecticide.

Evaluation of compounds for insecticidal activity on adult mosquitos. 3. Properties of some N-methylthiolcarbamates.

N-methylcarbamates derived from thiophenols possess negligible insecticidal activity against the mosquitos Anopheles stephensi and Aedes aegypti. The probable basic reason for the inactivity is that these compounds are much less efficient inhibitors of cholinesterase than the oxygen analogues.

Evaluation of compounds for insecticidal activity on adult mosquitos. 4. Insecticidal activity and physical properties of some halogenated organophosphorus esters.

The effects of changes in structure upon toxicity to adult mosquitos and upon physical properties which are important in determining contact effectiveness and residual activity are described for a group of O,O-dialkyl O-halogenated-phenyl phosphates, phosphorothionates and phosphamido(thio)ates. This group includes such established insecticides as fenchlorphos, bromophos and iodofenphos.

Evaluation of compounds for insecticidal activity on adult mosquitos. 5. Toxicity to adult mosquitos and residual properties of some pyrethroids.

New pyrethrin-like compounds are compared with earlier synthetic pyrethroids and natural pyrethrins for intrinsic toxicity to adult mosquitos and for residual contact activity. Two of the compounds are at least as toxic as pyrethrin I to female Anopheles stephensi and Aedes aegypti. Residues of these compounds are very persistent in the dark or in very subdued lighting but they decompose on exposure to normal intensities of daylight and rapidly lose their insecticidal activity.