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Introduction: The effect of burns surgery that requires intraoperative transfusion of five or more units of blood on serum vancomycin levels was assessed., Methods: Serum vancomycin levels were measured 10 min and 6 h after vancomycin administration with surgery being performed in the interval. The following day the same dose of vancomycin was given and serum vancomycin levels measured at the same times without intervening surgery., Results: Thirteen operations involving nine patients who required a mean blood transfusion of 9.2 units were studied. There was very little difference between 10-min levels, 6-h levels and the change over interval (absolute and percentage) on the day of surgery and the following day. The recorded serum levels were often at the lower end of the desired range, especially in patients who underwent the larger operations. This was the case on both day of surgery and the control day., Conclusions: Large volume blood loss and replacement during burns surgery did not significantly affect perioperative vancomycin levels. 1998 Elsevier Science Ltd for ISBI.

Background: Reliable reporting of chemotherapy-induced neurotoxicity is important. The objectives of the current study were to evaluate the differences in the peripheral neurotoxicity sections of several widely used chemotherapy-related toxicity grading systems, and the differences in the way in which observers interpret these scales., Patients and Methods: Two neurologists independently rated the severity of chemotherapy-induced peripheral neuropathy, according to WHO, ECOG, Ajani, and NCIC-CTC criteria in 37 patients., Results: The highest percentage grade 1, grade 2 and grade 3 peripheral neurotoxicity was noted when employing the WHO, Ajani and NCIC-CTC scales, respectively. Percentage inter-observer agreement across all grades of severity ranged from 45.9 (NCIC-CTC) to 83.8 (WHO). The degree of agreement varied from 'poor to fair' to 'substantial'. Percentage inter-observer agreement for the dichotomy grade < or = 2 and grade 3 ranged from 81.1 (NCIC-CTC) to 94.6 (Ajani and WHO), however, exact agreement on grade 3 peripheral neurotoxicity ranged from 0 (Ajani and WHO) to 42% (NCIC-CTC). Percentage interscale agreement for the dichotomy grade < or = 2 and grade 3 varied from 67.6 (WHO and NCIC-CTC) to 100 (WHO and ECOG). Interobserver disagreement of severity grading was partly due to different interpretation of scale parameters., Conclusions: Our results suggest that caution should be used in interpreting results across studies using different scales for neurotoxicity grading in chemotherapy-related peripheral neuropathy. When (multicentre) trials are to be undertaken with potential neurotoxic or neuroprotective agents, consensus should be sought regarding the toxicity rating scale used, and its interpretation by participating physicians.

Background: Although high-dose chemotherapy is rapidly gaining acceptance as a treatment option for a number of cancers, the long-term toxic effects of such therapy are a concern. Cognitive deficits (e.g., problems with memory and concentration) are not uncommon after chemotherapy, but they have not been documented systematically. In this study, we assessed the prevalence of cognitive deficits in a group of patients with high-risk breast cancer who were randomly assigned to receive either high-dose or standard-dose adjuvant chemotherapy plus tamoxifen, and we investigated whether high-dose chemotherapy impaired cognitive functioning more than standard-dose chemotherapy., Methods: Cognitive functioning was evaluated by use of a battery of neuropsychologic tests. In addition, patients were interviewed with regard to cognitive problems, health-related quality of life, anxiety, and depression. Results from patients who received adjuvant systemic therapy were compared with results from patients who had early stage breast cancer not treated with such therapy (control patients)., Results: The study population consisted of 34 patients treated with high-dose chemotherapy plus tamoxifen, 36 patients treated with standard-dose chemotherapy plus tamoxifen, and 34 control patients. For all patients, the average time since the completion of last nonhormonal therapy was 2 years. Cognitive impairment was found in 32% of the patients treated with high-dose chemotherapy, in 17% of the patients treated with standard-dose chemotherapy, and in 9% of the control patients. In comparison with the control patients, patients treated with high-dose chemotherapy appeared to have an 8.2-times higher risk of cognitive impairment (odds ratio; 95% confidence interval [CI] = 1.8-37.7); in comparison with the patients who received standard-dose chemotherapy, this risk of impairment was 3.5-times higher (95% CI = 1.0-12.8)., Conclusion: High-dose chemotherapy appears to impair cognitive functioning more than standard-dose chemotherapy. Central nervous system toxicity may be a dose-limiting factor in high-dose chemotherapy regimens.

Exposure keratitis can lead to infectious keratitis, corneal perforation, blindness and disfigurement. Chronic exposure of the cornea can occur following facial burns that cause eyelid ectropion. This complication can be difficult to diagnose in the unconscious patient. Five patients have undergone lid ectropion release to 11 eyelids in the early postburn period over the past 5 years. One patient required repeat release. Full-thickness skin grafts were used for the lower eyelid and no graft failure occurred. Operations were performed between 30-50 days postburn. Plastic wrap was used in one patient as a temporary dressing to maintain corneal hydration until surgery could be performed. All the patients were noted to have exposure keratitis on ophthalmological review. Patients most at risk are those with large area burns that include the face, who require prolonged intensive care support. It is important to look out for the development of eyelid ectropion, which should be corrected when first diagnosed to prevent disabling, sight-threatening eye injury.

Objectives: The use of self-report questionnaires for the assessment of health-related quality of life (HRQOL) is increasingly common in clinical research. This method of data collection may be less suitable for patient groups who suffer from cognitive impairment, however, such as patients with brain cancer. In such cases, one can consider employing the patients' significant others as proxy raters of the patients' health-related quality of life. The authors examined the response agreement between patients with brain cancer and their significant others on a health-related quality of life instrument commonly used in cancer clinical trials, the EORTC QLQ-C30, and on a brain cancer-specific questionnaire module, the QLQ-BCM., Methods: The study sample consisted of 103 pairs of patients, with either recently diagnosed or recurrent brain cancer, and their significant others (75% spouses, 22% relatives, and 3% friends). Patients and proxies independently completed the EORTC QLQ-C30 and the QLQ-BCM at three different times., Results: Approximately 60% of the patient and proxy scores were in exact agreement, with more than 90% of scores being within one response category of each other. For most HRQOL dimensions assessed, moderate to good agreement was found. Statistically significant differences in mean scores were noted for several dimensions, with proxies tending to rate the patients as having a lower quality of life than the patients themselves. With the exception of fatigue ratings, this response bias was of a limited magnitude. Less agreement and a more pronounced response bias was observed for the more impaired patients, and particularly for patients exhibiting mental confusion. This finding was confirmed by longitudinal analyses, which indicated lower levels of patient-proxy agreement at follow-up for those patients whose physical or neurologic condition had deteriorated over time., Conclusions: In general, patients and their significant others provide similar ratings of the patients' quality of life. Lower levels of agreement and more biased ratings can be expected among those patients for whom the need for proxies is most salient. It is argued, however, that discrepancies between patient-proxy ratings should not be interpreted, a priori, as evidence of the inaccuracy or biased nature of proxy-generated data. Future studies are needed to examine the relative validity and reliability of patient-versus proxy-generated health-related quality of life scores.

Objectives: To assess and compare the quality of life of men with advanced prostate cancer who are in remission receiving treatment with a luteinizing hormone-releasing hormone (LHRH) agonist and flutamide or who are in progression., Methods: We conducted a cross-sectional survey to measure health-related quality of life in a cohort of 113 patients with metastatic prostate cancer, 60 in remission and 53 with disease progression, using a battery of questionnaires, including the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30, the Medical Outcomes Study Short Form Health Survey SF-36, and a prostate cancer-specific module., Results: Patients in remission receiving an LHRH agonist and flutamide reported a significantly better quality of life compared with patients with disease progression (P < 0.011). Men with hormone-sensitive cancer had significantly less bodily pain, more vitality, more social interactions, and better mental health than patients with hormone-resistant disease. No differences were noted between the two groups concerning treatment-related problems such as diarrhea, constipation, urinary symptoms, sexual function, sexual satisfaction or hot flashes, although men in remission tended to rate each of these items more favorably than did men with disease progression. Men in remission have a health-related quality of life that is similar to an equivalent norm for men in the United States general population as compared with men with disease progression, who demonstrate significant compromise in all domains measured., Conclusions: Patients in remission receiving an LHRH agonist and flutamide have a quality of life that is indistinguishable from a matched male population without prostate cancer and a quality of life significantly better than that of men with androgen-resistant disease. Among patients who respond to total androgen ablation, flutamide and an LHRH agonist provide significant, measurable benefits to recipients independent of any possible improvement in longevity.

The process of wound healing represents a series of complex physicochemical reactions requiring different nutritional microcomponents at each stage. In patients with extremely grave diseases and injuries the course of wound healing is impaired because of a hypermetabolic reaction to stress, leading to protein catabolism. The hypothalamus responds to cytokine stimulation by changes of thermoregulation (increase of heat production) and increased production of stress hormones (catecholamines, hydrocortisone, and glucagon). In turn, stress hormones trigger the thermogenous (unproductive) metabolic cycle and the lipolysis and proteolysis processes. Hyperproduction of glucose at the expense of skeletal muscle tissue degradation leads to the formation of amino acid substrate for liver glyconeogenesis. Additional nutrients are obligatory for wound healing in such patients. Protein catabolism cannot be arrested by amino, acids alone partly because amino acid transport is impaired; it can be normalized by anabolics, such as growth hormone and insulin-like growth factor 1. Treatment with growth hormone yields a dramatic positive effect in severely burned children. Proteins and vitamins, specifically arginine and vitamins A, B, and C provide the optimal nutritive support during wound treatment.

Activation of endothelial cells by vasoactive mediators, such as endothelins, may be an early, strategically important step in the initiation of inflammation in the intestine. In view of recent evidence that inflammatory bowel disease is associated with elevated intestinal concentrations of endothelins and upregulated expression of endothelin receptors on vascular endothelium in intestine, endothelins may become therapeutic targets in inflammatory bowel disease. The recent availability of an orally active, mixed endothelin receptor antagonist, bosentan, allowed us to examine the role of endothelins in a rat model of colitis. Colitis was induced by intra-rectal administration of trinitrobenzene sulphonic acid. In each treatment group, rats were treated with bosentan (10-60 mg/kg p.o.) 24 and 2 h prior to (pre-dose) or 1 h after the induction (post-induction) of colitis and all animals were treated every 24 h thereafter for 5 days. On day 6, stool consistency and the presence of adhesions in the peritoneal cavity were accessed. Colonic tissue samples were removed for determination of macroscopic and microscopic tissue injury, and myeloperoxidase activity. Colitis was typified by tissue ulceration in the distal colon and a corresponding 35-fold increase in myeloperoxidase activity compared to non-inflamed controls. Daily treatment with bosentan dose-dependently reduced colonic damage and myeloperoxidase activity when bosentan was given prior to induction of colitis. In the pre-dose group, the greatest beneficial effect of bosentan was observed at 60 mg/kg; colonic damage and granulocyte infiltration were attenuated by > 80%. A partial therapeutic effect of bosentan was also observed at 60 mg/kg when the pre-treatment regimen was excluded. These findings demonstrate that an orally active, mixed endothelin receptor antagonist has marked protective and therapeutic effects in an animal model of colitis.

Purpose: To investigate the effects of medroxyprogesterone acetate (MPA) on appetite, weight, and quality of life (QL) in patients with advanced-stage, incurable, non-hormone-sensitive cancer., Patients and Methods: Two hundred six eligible patients were randomized between double-blind MPA 500 mg twice daily or placebo. Appetite (0 to 10 numerical rating scale), weight, and QL (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire [EORTC-QLQ-C30]) were assessed before the start of treatment (t = 0), and 6 weeks (t = 6) and 12 weeks (t = 12) thereafter., Results: One hundred thirty-four patients (68 MPA and 66 placebo) were assessable at t = 6 and 99 patients (53 MPA and 46 placebo) at t = 12. A beneficial effect of MPA on appetite was observed after both 6 weeks (P = .008) and 12 weeks (P = .01) of treatment. After 12 weeks, a mean weight gain of 0.6 +/- 4.4 kg was seen in the MPA, versus an ongoing mean weight loss of 1.4 +/- 4.6 kg in the placebo group. This difference of 2.0 kg was statistically significant (P = .04). During the study, several areas of QL deteriorated in the total group of patients. With the exception of an improvement in appetite and possible also a reduction in nausea and vomiting, no measurable beneficial effects of MPA on QL could be demonstrated. The side effects profile of MPA was favorable: only a trend toward an increase in (usually mild) peripheral edema was observed., Conclusion: In weight-losing, advanced-stage non-hormone-sensitive cancer patients, MPA exhibits a mild side effects profile, has a beneficial effect on appetite, and may prevent further weight loss. However, general QL in the present study was not measurably influenced by MPA treatment.

The purpose of the present study was to assess patients' anxiety level and information requirement in the preoperative phase. During routine preoperative screening, 320 patients were asked to assess their anxiety and information requirement on a six-item questionnaire, the Amsterdam Preoperative Anxiety and Information Scale (APAIS). Two hundred patients also completed Spielberger's State-Trait Anxiety Inventory (STAI-State). Patients were able to complete the questionnaire in less than 2 min. On factor analysis, two factors emerged clearly: anxiety and the need for information. The anxiety scale correlated highly (0.74) with the STAI-State. It emerged that 32% of the patients could be considered as "anxiety cases" and over 80% of patients have a positive attitude toward receiving information. Moreover, results demonstrated that 1) women were more anxious that men; 2) patients with a high information requirement also had a high level of anxiety; 3) patients who had never undergone an operation had a higher information requirement than those who had. The APAIS can provide anesthesiologists with a valid, reliable, and easily applicable instrument for assessing the level of patients' preoperative anxiety and the need for information.

Purpose: Here we report the results of a randomized study undertaken to test the efficacy of a supplementary, telephone-based nursing intervention in increasing patients' awareness and understanding of the clinical trials in which they are asked to participate., Methods: During a 12-month period, 180 cancer patients who were approached to participate in a phase II or III clinical trial were randomized to undergo either of the following: (1) standard informed consent procedures based on verbal explanations from the treating physician plus written information (controls); or (2) standard informed consent procedures plus a supplementary, telephone-based contact with an oncology nurse (intervention). For purposes of evaluation, face-to-face interviews were conducted with all patients approximately 1 week after the informed consent process had been completed., Results: The two groups were comparable with regard to sociodemographic and clinical variables. Both groups had a high level of awareness of the diagnosis and of the nature and objectives of the proposed treatments. The intervention group was significantly (P < .01) better informed about the following: (1) the risks and side effects of treatment; (2) the clinical trial context of the treatment; (3) the objectives of the clinical trial; (4) where relevant, the use of randomization in allocating treatment; (5) the availability of alternative treatments; (6) the voluntary nature of participation; and (7) the right to withdraw from the clinical trial. The intervention did not have any significant effect on patients' anxiety levels or on rates of clinical trial participation. Patients reported high levels of satisfaction with the intervention., Conclusion: The use of a supplementary, telephone-based nursing intervention is a feasible and effective means to increase cancer patients' awareness and understanding of the salient issues that surround the clinical trials in which they are asked to participate.

Previously, we have shown that adenosine inhibits release of acetylcholine (ACh) by acting at A1 presynaptic receptors in guinea pig submucosal synapses. In this study, intracellular recordings were made to investigate the actions of ATP and some analogs on the synaptic release of ACh. Superfusion of these substances decreased the amplitude and duration of electrically induced fast excitatory postsynaptic potentials (EP-SPs) in about 90% of the tested neurons. ATP (0.1-30 microM) effects were concentration dependent with an EC50 of 1.4 microM. ADP, AMP and ATP-gamma-S mimicked ATP inhibitory effects and were equally potent and efficacious. beta,gamma-Methylene-ATP seemed to act as a partial agonist, causing less than 50% of the inhibition obtained with ATP. 2-Methyl-thio-ATP was only active at the highest concentration tested whereas alpha,beta-methylene-ATP and UTP were inactive (0.3-30 microM). ATP-gamma-S did not alter depolarizations induced by exogenous application of ACh, indicating that ATP analogs inhibit EPSPs by acting at a presynaptic site. Although the EC50 values were similar for ATP and adenosine, the maximum responses (76 +/- 4.5% and 40 +/- 1.6%) were different. Adenosine deaminase (which inactivates adenosine) and alpha,beta-methylene-ADP (an ecto-5'-nucleotidase inhibitor) did not alter ATP-induced inhibition of these EPSPs. Inhibition of EPSPs by 30 microM adenosine (maximal concentration) and 1 microM ATP (submaximal concentration) were additive. Suramin or reactive blue 2 (30 microM), antagonists of ATP actions in several tissues, did not modify the effects of ATP on the fast EPSPs. 8-Cyclopentyltheophylline inhibited, in a competitive manner, these ATP inhibitory effects. In conclusion, ATP inhibits synaptic release of ACh by acting at receptors similar to those previously identified as P3-purinoceptors.

Ascaris pneumonitis in areas of endemic infestation is considered a benign condition. Smoke inhalation with any burn injury can be potentially fatal. A heavy infestation of Ascaris could further exacerbate the smoke-induced lung injury. After ingested eggs hatch in the small intestine, the larvae penetrate the mucosa and invade the blood stream and are then carried to the lungs. The larvae break out into the aveolar spaces as they are too large to cross the capillary bed and are carried up the bronchial tree and eventually swallowed. This study describes three cases of Ascaris infection in thermally injured children. While the burns were < 30 per cent total body surface area, two patients who were injured in the same fire had a further complication of smoke inhalation which necessitated sophisticated therapy in order to promote survival. All patients were treated initially with Vermox. The one patient without smoke inhalation did not develop ascariasis pneumonitis even with positive stool samples and was discharged with no complications, whereas the two with smoke inhalation developed severe pneumonitis. One patient was placed on ECMO and did not receive a full course of the Vermox treatment. This patient died after several weeks of ECMO treatment. The third patient received a full course of Vermox, slowly recovered, and went home. Supportive therapy only is recommended during the lung migration phase of the Ascaris lifecycle. We feel that continuation of chemotherapy (Vermox) would have been beneficial in the fatal case based on the survival of the second patient.(ABSTRACT TRUNCATED AT 250 WORDS)

Accidental burn injury is common among children. Contact burns are the second most frequent cause of burns in children and electric iron contact burns constitute a substantial proportion of this group. A prospective analysis of electric iron burns presenting from 1988 to 1991 was conducted. The 38 iron burns treated during this period represented 19% of contact burns treated. The mean age of injury was 19 months. The male to female ratio was 1.1:1 and 80% involved the upper limb. Twenty-five per cent required operation. All burns occurred in the child's own home with the majority (74%) occurring in the central living areas while the child was supervised (45%). The child was most likely to be injured by touching the iron directly or pulling the cord. A substantial number of burns occurred even after the iron was switched off. Education should be directed towards the caregivers of young children emphasizing the need to use and store irons in areas to which children do not have free access. Powerpoints should be placed so that children cannot reach the cord. Manufacturers should provide insulated pads in which to store the iron and a retracting cord to help prevent the cord being within a child's reach.

Wound healing is a series of complex physicochemical interactions that require various micronutrients at every step. In the critically ill or severely injured patient, wound healing is impaired by the protein-catabolic, hypermetabolic response to stress. The hypothalamus responds to cytokine stimulation by increasing the thermoregulatory set-point and by augmenting elaboration of stress hormones (catecholamines, cortisol, and glucagon). In turn, the stress hormones induce thermogenic futile substrate cycling, lipolysis, and proteolysis. Increased glucose production results at the expense of skeletal muscle degradation, producing amino acid substrate for hepatic gluconeogenesis. Nutritional support of the hypermetabolic state is an essential part of ensuring efficient wound healing in these patients. Protein catabolism cannot be reversed by increased amino acid availability alone, due partly to a defect in amino acid transport. This defect can be reversed by anabolic agents, such as growth hormone and insulin-like growth factor-1. Growth hormone treatment dramatically improves wound healing in severely burned children. Supplementation with protein and vitamins, specifically arginine and vitamins A, B, and C, provides optimum nutrient support of the healing wound.

Chronic active type B gastritis is invariably the result of Helicobacter pylori infection and is an important factor in duodenal ulcer disease. The actions of mediators produced (a protein factor, a lipid soluble "pore-forming factor" and urease) or induced (immune/inflammatory cell mediators) by this bacterium on the control of gastric acid secretion are currently being investigated. These studies are reviewed in light of our current knowledge of the physiological control of gastric acid secretion.

In vitro contractility studies were conducted in canine gastric muscularis mucosae muscle strips with the adenosine analogues 2-chloroadenosine (CIAD), 5'-N-ethylcarboxamidoadenosine (NECA), 5'-(N-cyclopropyl)-carboxamidoadenosine (CPCA), R-N6-(2-phenylisopropyl)adenosine (R-PIA), S-PIA, N6-cyclohexyladenosine (CHA) and (2-p-carboxyethyl)phenylamino-5'-N-carboxamidoadenosine (CGS21680) as well as the A1-selective antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX). Adenosine analogues contracted the muscle strips with the following rank order of potency: CPCA > NECA > CIAD > R-PIA > CHA > S-PIA > CGS21680. CPCA, R-PIA, and CHA were partial agonists. At a concentration selective for adenosine A1 receptors (50 nM), DPCPX did not alter the concentration-response curves to CIAD or CHA. However, at higher concentrations (1-10 microM), DPCPX antagonized CIAD-mediated contractions in a competitive manner (pA2 = 6.96; slope = 0.93). CIAD-mediated contraction was not altered by treatment of the muscle strips with tetrodotoxin (1 microgram/ml) or mepyramine (1 microM). Our results indicate that adenosine A1 receptors, nerves or mast cells are not involved in contraction of canine gastric muscularis mucosae by adenosine analogues.

Histamine had two effects on the contractility of canine gastric muscularis mucosae in vitro: relaxation at or below 10 microM and contraction at higher concentrations. Selective agonists and antagonists were used to test the possibility that these effects were mediated by different receptor subtypes. The H1-selective agonist 2-pyridylethylamine (2-PEA) and the H2-selective agonist dimaprit contracted and relaxed this muscle, respectively, while the H3-selective agonist R-alpha-methylhistamine had no effect. The H1- and H2-selective antagonists mepyramine and ranitidine selectively blocked 2-PEA-mediated contractions and dimaprit-mediated relaxations, respectively. Agonist responses, were unaltered by tetrodotoxin, suggesting a site of action other than nerves. Our results indicate that canine gastric corpus muscularis mucosae possesses both contractile H1 and relaxant H2 receptors.

The heterogeneous group of proteinases known as pepsinogens are synthesized, stored, and upon appropriate stimulation released from gastric mucosal chief cells. Under the acidic conditions of the lumen of the stomach, the proenzymes, pepsinogens, are converted to "pepsin", which plays an important physiologic role as a digestive enzyme. The potential roles for pepsin in upper gastrointestinal diseases such as gastric or duodenal ulcer and gastroesophageal reflux disease along with the recent development of in vitro gastric gland and isolated chief cell preparations have renewed interest in the study of the control of pepsinogen synthesis and secretion. In this article the authors briefly summarize current knowledge of the biology of pepsinogens and emphasize more recent findings concerning the control of the chief cell, which is related to the synthesis and secretion of pepsinogens in vitro.

We examined changes in membrane function underlying the increased contractility of jejunal longitudinal muscle to carbachol in rats infected 6 days previously with Trichinella spiralis. Muscarinic receptor characteristics were examined in particulate fractions using [N-methyl-3H]scopolamine (NMS). There was a significant reduction in the total number of binding sites on muscle from infected rats, but the affinity for NMS was unchanged. Similarly, in competition studies, the binding of carbachol to high or low affinity sites was not significantly different in tissue from control or infected rats. However, we observed an 89% suppression of the activity of K+ -stimulated ouabain-sensitive p-nitrophenylphosphatase (pNPPase), an enzyme marker for the Na+ -K+ pump, in plasma membranes from infected compared with control rats. Similar results were obtained in 86Rb uptake studies. In contractility studies, evidence for the electrogenicity of the Na+ -K+ pump was obtained by demonstrating that pump activation by K+, Rb+, or Cs+ was associated with tissue relaxation with a rank order of potency that was identical to that for stimulation of pNPPase activity by these ions. Conversely, pump inhibition by vanadate increased tone and abolished phasic contractions in muscle from control or infected rats. This was accompanied by an increased response to carbachol in muscle from control but not infected rats. In addition, pump inhibition by removing extracellular K increased tone in control tissue but decreased tone in muscle from T. spiralis-infected rats, presumably because of preexisting pump suppression. These results are consistent with the hypothesis that suppression of electrogenic Na-pump activity contributes to the increased contractility of jejunal muscle in rats infected with T. spiralis.

In the isolated rat vas deferens, various 2-substituted adenosine derivatives and adenosine inhibited contractions elicited by field stimulation but had little effect on responses to exogenous noradrenaline. 2-Chloroadenosine, 2-bromoadenosine, 2-hydroxyadenosine and 2-fluoroadenosine were all more potent than adenosine. Theophylline antagonized the action of the 2-substituted derivatives. The inhibitory action of adenosine was potentiated by dipyridamole, 2-amino-6-[(2-hydroxy-5-nitro)benzylthio]-9-beta-D-ribofuranosylpurine (HNBTG) or 2'-deoxycoformycin while that of 2-choloroadenosine was not altered by any of these drugs or by phenoxybenzamine, atropine or indomethacin. Pretreatment of the vas deferens with both HNBTG and 2'-deoxycoformycin eliminated the difference in inhibitory potency between adenosine and 2-chloroadenosine. These results indicate that 2-substituted adenosine derivatives, like adenosine, produce inhibition of transmission by acting on a presynaptic site which can be blocked by theophylline. The high apparent potency of 2-chloroadenosine compared to adenosine appears to be due to the former being neither taken up nor deaminated, while the apparent potency of adenosine is masked by uptake and deamination in this tissue.

Two of the 5 serotypes of bluetongue virus (BTV) known from Australia have been isolated from field collected insects. Serotype 20 was isolated in 1975 from a mixed pool of 214 insects containing several Culicoides species. Serotype 1 has been isolated from C. (Avaritia) fulvus Sen & Das Gupta collected at Beatrice Hill in the Northern Territory and from C. (Avaritia) brevitarsis Kieffer collected at Peachester in southeast Queensland. All other isolates of bluetongue (BT) group viruses have been made from sentinel cattle. An additional 2 species of the subgenus Avaritia, C. wadai Kitaoka and C. actoni Smith, 1 species of the subgenus Culicoides, C. peregrinus Kieffer and 1 species of the Schultzei group, C. oxystoma Kieffer have been infected in the laboratory. Serotype 20 was transmitted from sheep to sheep by C. fulvus and serotype 1 by C. fulvus and C. actoni. The infection rates established for Culicoides fed on sheep infected with serotype 20 were C. fulvus 62%; C. wadai 11%; C. actoni 2% and C. brevitarsis 0.3%. All species of insects successfully infected are widely distributed in the Oriental region. Attempts to infect species that are restricted in range to the Australasian region have been unsuccessful. The 3 species with highest experimental infection rates: C. fulvus, C. wadai and C. actoni, are confined in Australia to areas with an annual summer rainfall in excess of 800 mm, and do not penetrate to the drier areas where sheep are commercially husbanded. C. brevitarsis is the vector responsible for transmission in the coastal dairying areas, and although it does occur where sheep are reared, it is an inefficient vector. It breeds in discrete cow dung pats on pasture and is more closely associated with cattle than with sheep when the 2 hosts occur together. More than 1 species of Culicoides is responsible for the transmission of BT group viruses in Australia and no BT disease of sheep has been recorded because the more efficient vector species are not present in sheep rearing areas.

Forskolin was found to cause concentration dependent, reversible relaxations of isolated smooth muscle preparations including rat aorta, bovine coronary artery, canine coronary artery, guinea pig taenia caeci and rabbit small intestine. The relaxant effects of forskolin in guinea pig taenia caeci and rabbit small intestine were potentiated by cyclic nucleotide phosphodiesterase inhibitors Ro 20-1724 and MIX. In rabbit small intestine, Ro 20-1724 also potentiated the relaxant effects of isoproterenol but not those of verapamil or 2-chloroadenosine. However, in bovine coronary arteries the phosphodiesterase inhibitors had to be used at concentrations of 100 nM or below because of relaxant effects and did not alter forskolin-induced relaxations. Forskolin caused a concentration dependent activation of adenylate cyclase in broken cell preparations from guinea pig taenia caeci and rabbit small intestine, exceeding the stimulatory effect of 10 mM NaF. These results indicate that relaxations of smooth muscle by forskolin are mediated by cyclic AMP and, in turn, that cyclic AMP may well serve as an intracellular mediator of physiological relaxant stimuli.

A case of a large bone cyst in the tibial condyle of a patient with rheumatoid arthritis is reported. The etiology and pathology are discussed, and preventive surgical treatment is recommended.

Adult female Culicoides brevitarsis Kieffer, important vectors of arboviruses affecting livestock in Australia, were fed on penned Hereford yearling cattle which had been given a single subcutaneous injection of ivermectin at a dose of 200 mcg/kg. The mean mortality of engorged females 48 hr after feeding on the treated cattle was 99% for 10 days posttreatment and in excess of 40% for 18 days posttreatment. Based on these results, it appears that ivermectin administered subcutaneously could be a useful tool for the control of Culicoides-transmitted diseases and would provide an attractive alternative to "slaughter out" programs in the case of a major exotic disease threat.

125I-Tyr8-substance P binding was examined in a plasma membrane enriched fraction from the circular muscle of canine small intestine. The binding was quick in onset, reversible and saturable to a single high affinity binding site; KD and maximum receptor concentration were 0.50 = 0.06 nM and 742 +/- 173 fmol/mg of protein, respectively. KD values from kinetic and saturation studies were in agreement. The rank order of potency of the tachykinins and related compounds in displacing this binding was consistent with that of a neurokinin (NK)-P (NK-1) type binding site. 125I-eledoisin did not bind specifically to these membranes and eledoisin was relatively ineffective in displacing the 125I-Tyr8 substance P. Kassinin was totally ineffective. Based on relative agonist potencies, the tachykinins appeared to contract the circular muscle of canine small intestine in vitro by a mechanism which also could be considered to be a NK-P (NK-1) type receptor. However, a comparison of data obtained by these two techniques suggests that the NK-P (NK-1) type binding site and the receptor(s) responsible for contractile responses are not identical. There were discrepancies in relative orders of potency and in absolute potencies. The simplest explanation is that there is also an NK-A (NK-2) receptor which is functional but not labeled by our ligands. Possible reasons for these discrepancies are discussed.

Between October 1974 and May 1976, 57 596 mosquitoes, 169 957 Culicoides, 5923 Lasiohelea and 1043 phlebotomines were collected for virus isolation at Beatrice Hill (lat. 12 degrees 39'S.,long. 131 degrees 20'E.) in the Northern Territory of Australia. A total of 94 viruses belonging to 22 different serological groupings was isolated. The following species of insect yielded viruses which were identified and those viruses marked with an asterisk represent a new record of insect host: Culex annulirostris: Ross River, Kokobera, Barmah Forest, Corriparta, Eubenangee*, Wongorr; Anopheles amictus: Mapputta*; An bancroftii: bovine ephemeral fever*; An farauti: Eubenangee*; An annulipes: Mapputta; Culicoides marksi: Barmah Forest*, Belmont, Eubenangee*, Wallal, Warrego, Leanyer*, Parker's Farm*, Humpty Doo*; C. peregrinus: Beatrice Hill*; C. oxystoma: Bunyip Creek*, Marrakai*; C. pallidothorax: Wongorr*; C. histrio: Thimiri*; Lasiohelea spp.: Humpty Doo*. Pools of mixed species of Culicoides yielded bluetongue, Belmont, CSIRO Village, Warrego and Facey's Paddock viruses. Filter-passing agents not yet identified, were isolated from Cx annulirostris and An bancroftii. As well as providing new locality records for all but one of the 22 viruses isolated, the study yielded five new viruses (bluetongue serotype 20, CSIRO Village, Marrakai, Beatrice Hill and Humpty Doo viruses) and a new record for Thimiri virus which had not been recorded previously in Australia nor had it been isolated from an arthropod. Nine of the viruses isolated occur in more than one family of Diptera.

A case of sciatica with partial paralysis of both lower limbs is reported. At operation a prolapse of the L4/5 intervertebral disc on the right side was associated with an anomaly of the left fifth lumbar root which was lower and more horizontal than normal. The authors give a short review of the literature.

Apamin, a peptide of bee venom, was shown to inhibit the relaxant responses of guinea-pig taenia caeci to ATP, noradrenaline, adenosine and, less effectively, to stimulation of noradrenergic inhibitory nerves. Thus apamin acts nonspecifically and, contrary to the suggestion of Vladimirova and Shuba (1978), the fact that inhibitory responses due to nerve stimulation and ATP are blocked by the toxin does not allow conclusions as to the possible transmitter role of ATP in these nerves.