Surveillance of Salmonella spp. in the environment of public hospitals in KwaZulu-Natal, South Africa.

AIM: To investigate the dissemination of Salmonella spp. within four levels of government hospitals in KwaZulu-Natal, South Africa. METHODS: The identification of Salmonella spp. was performed by amplification of the invA gene. Isolates were subjected to antimicrobial susceptibility testing and molecular characterization of eight resistance genes (qnrA, qnrB, qnrS, tetA, tetB, tetC, tetG, ermB) and three virulence genes (sitC, spvA, spv). Genetic relatedness between isolates was determined using enterobacterial repetitive intergenic consensus (ERIC) polymerase chain reaction. FINDINGS: Ninety-four isolates were obtained. The largest source of isolates was the regional hospital. Paediatric wards had the highest prevalence of isolates. Nurses' tables contained the most isolates out of all sites sampled. Twenty-two clusters indicating diverse isolates were obtained via molecular typing. Four main ERIC types were identified, each unique to a specific hospital. A possibility of dissemination across the wards was noted as highly related isolates were present at various sites within the wards. Many of these sites were highly trafficked areas by healthcare staff. Ten multi-drug-resistant isolates were found. CONCLUSIONS: This study suggests that infection prevention and control strategies that involve environmental cleaning and decontamination may not be enough, or adhered to sufficiently, to prevent the dissemination of Salmonella spp.

In vitro potentiation of carbapenems with tannic acid against carbapenemase-producing enterobacteriaceae: exploring natural products as potential carbapenemase inhibitors.

AIMS: We hypothesized and confirmed that tannic acid (TA) reverses carbapenem resistance by inhibiting carbapenemases in class A and B carbapenemase-producing Enterobacteriaceae. METHODS AND RESULTS: Minimum inhibitory concentrations of carbapenems in the presence and absence of TA and other efflux pump inhibitors, TA-carbapenemases inhibition assays and computational studies showed that TA had the greatest effect on metallo-ß-lactamases (MBLs) followed by class A serine-ß-lactamases (SBLs). TA completely reversed the MICs of MBL producers from between 32 and ≥512 mg l-1 to susceptible values (<4 mg l-1 ) while substantially reducing the MICs of SBLs from between 16 and >512 mg l-1 to <4 to 16 mg l-1 . Tolerable cytotoxic effect was observed for the concentrations tested (8-1024 mg l-1 ). TA inhibited enzymes with a marked difference of ≈50% inhibition (IC50 ) for NDM-1 (270 µmol l-1 ) and KPC-2 (15  µmol l-1 ). CONCLUSION: TA inhibited both MBLs and SBLs by targeting their hydrophobic sites. Moreover, TA had a stronger binding affinity for MBLs than SBLs as the MBLs, specifically VIM-1 (-43·7220 ± 0·4513 kcal mol-1 ) and NDM-1(-44·2329 ± 0·3806 kcal mol-1 ), interact with a larger number of their catalytic active-site residues than that of OXA-48 (-22·5275 ±  0·1300 kcal mol-1 ) and KPC-2 (-22·1164 ± 0·0111 kcal mol-1 ). SIGNIFICANCE AND IMPACT OF THE STUDY: Tannic acid or its analogues could be developed into carbapenemase-inhibiting adjuvants to restore carbapenem activity in CRE infections, save many lives and reduce healthcare associated costs.

Molecular characterization of methicillin-resistant Staphylococcus aureus isolates from a hospital in Ghana

Background: Methicillin-resistant Staphylococcus aureus (MRSA) are a major cause of hospital- and community-acquired infection. They can colonize humans and cause a wide range of infections including pneumonia, endocarditis and bacteraemia. We investigated the molecular mechanism of resistance and virulence of MRSA isolates from a teaching hospital in Ghana. Methodology: A total of 91 S. aureus isolates constituted the initial bacterial sample. Identification of S. aureus was confirmed by the VITEK 2 system. The cefoxitin screen test was used to detect MRSA and antibiotic susceptibility was determined using the VITEK 2 system. The resistance (mecA, blaZ, aac-aph, ermC, and tetK) and virulence (lukS/F-PV, hla, hld and eta) genes were amplified by polymerase chain reaction (PCR) and positive samples subjected to DNA sequencing. Pulsed field gel electrophoresis (PFGE) was used to ascertain the relatedness of the isolates. Results: Fifty-eight of 91 (63.7%) isolates were putatively methicillin resistant by the phenotypic cefoxitin screen test and oxacillin MICs. However, 43 (47%) of the isolates were genotypically confirmed as MRSA based on PCR detection of the mecA gene. Furthermore, 37.9% of isolates displayed resistance to tetracycline, 19% to trimethoprim-sulphamethoxazole, 15.5% to clindamycin, 12.1% to gentamicin, 13.8% to ciprofloxacin and erythromycin, 6.9% to moxifloxacin and 7.0% to rifampicin. None of the isolates was positive for inducible clindamycin resistance. The prevalence of resistance (mecA, blaZ, aac(6')-aph(2''), tetK, and ermC) and virulence (hla and lukS/F-PV) genes respectively were 74%, 33%, 22%, 19%, 3%, 5% and 3%, with isolates organized in two highly related clades. Conclusion: Results indicate a fairly high occurrence of MRSA, which can complicate the effective therapy of S. aureus infections, necessitating surveillance and stringent infection control programmes to forestall its spread

Colistin and tigecycline resistance in carbapenemase-producing Gram-negative bacteria: emerging resistance mechanisms and detection methods.

A literature review was undertaken to ascertain the molecular basis for tigecycline and colistin resistance mechanisms and the experimental basis for the detection and delineation of this resistance particularly in carbapenemase-producing Gram-negative bacteria. Pubmed, Google Scholar and Science Direct were searched with the keywords colistin, tigecycline, resistance mechanisms and detection methods. Trans-complementation and comparative MIC studies, mass spectrometry, chromatography, spectrofluorometry, PCR, qRT-PCR and whole genome sequencing (WGS) were commonly used to determine tigecycline and colistin resistance mechanisms, specifically modifications in the structural and regulatory efflux (acrAB, OqxAB, kpgABC adeABC-FGH-IJK, mexAB-XY-oprJM and soxS, rarA robA, ramRAB marRABC, adeLRS, mexRZ and nfxb) and lipid A (pmrHFIJFKLM, lpxA, lpxC lpxD and mgrB, pmrAB, phoPQ,) genes respectively. Mutations in the ribosomal 16S rRNA operon rrnBC, also yielded resistance to tigecycline through target site modifications. The mcr-1 gene conferring resistance to colistin was identified via WGS, trans-complementation and a murine thigh infection model studies. Common detection methods are mainly antibiotic sensitivity testing with broth microdilution while molecular identification tools are mostly PCR and WGS. Spectrofluorometry, MALDI-TOF MS, micro-array and real-time multiplex PCR hold much promise for the future as new detection tools.

In vitro evaluation of metal chelators as potential metallo- ß -lactamase inhibitors.

AIMS: This study aimed at investigating the use of metal chelators as potential metallo-ß-lactamase inhibitors (MBL). METHODS AND RESULTS: The minimum inhibitory concentration (MIC) of meropenem was ascertained alone and in combination with various concentrations of macrocyclic (1,4,7- triazacyclononane-1-glutaric acid-4,7-diacetic acid = NODAGA) peptide derivatives and acyclic (N,N,N',N'-Tetrakis(2-pyridylmethyl)ethylenediamine = TPEN and di-(2-picolyl)amine = DPA) metal chelators using the broth microdilution method. MICs of meropenem against carbapenem-resistant enterobacteriaceae (CRE) producing MBLs were decreased to concentrations as low as 0·06 mg l(-1) in the presence of some metal chelators. TPEN at 4 and 8 mg l(-1) showed the best activity by decreasing meropenem MICs to 0·5 and 0·06 mg l(-1) , respectively, for some New Delhi Metallo-beta-lactamase (NDM) and Verona integron-encoded metallo-ß-lactamase (VIM) -producing enterobacteriaceae. DPA at 8 and 16 mg l(-1) was also able to decrease meropenem MICs to 1 and 0·125 mg l(-1) , respectively, for these CREs. NODAGA peptide derivatives showed the least inhibition as 32 mg l(-1) was required for meropenem MICs to be decreased to 0·06 mg l(-1) against an NDM-1 producing isolate. CONCLUSION: The various metal chelators, TPEN, DPA and NODAGA peptide derivatives were able to inhibit the MBLs in decreasing order of activity, rendering CREs susceptible to meropenem. SIGNIFICANCE AND IMPACT OF THE STUDY: In the absence of new antibiotics, this study evaluated metal chelators as potential MBL inhibitors.

Determination of the minimum infusion rate of alfaxalone during its co-administration with midazolam in goats.

INTRODUCTION: The minimum infusion rate (MIR) of alfaxalone when co-administered with midazolam in goats was evaluated. MATERIALS AND METHODS: Eight goats (four does and four wethers) were anaesthetised, on separate occasions, with alfaxalone at an initial dose of 9.6 mg/kg/hour combined with one of three midazolam treatments: a bolus of 0.1 mg/kg followed by constant rate infusion (CRI) of 0.1 mg/kg/hour (treatment LMID), 0.3 mg/kg followed by CRI of 0.3 mg/kg/hour (MMID), 0.9 mg/kg followed by CRI of 0.9 mg/kg/hour (HMID), intravenously. Responses to stimulation (clamping on the proximal part of one digit of the hoof with Vulsellum forceps for 60 seconds) were tested every 30 minutes. In the absence or presence of a response to stimulation, the infusion rate was reduced or increased by 1.9 mg/kg/hour. Alfaxalone MIR was calculated as the mean of the infusion rates that allowed and abolished movement. Cardiopulmonary parameters were measured. RESULTS: Alfaxalone MIR was 6.7 (6.7-8.6) mg/kg/hour, 6.7 (4.8-6.7) mg/kg/hour and 2.9 (1.0-4.8) mg/kg/hour for LMID, MMID and HMID respectively. Cardiopulmonary function was minimally affected, with hypoxaemia observed two minutes into anaesthesia during all treatments. Recovery from anaesthesia was excitement-free. CONCLUSIONS: Midazolam causes a dose-dependent reduction of alfaxalone MIR in goats. Oxygen supplementation is recommended during anaesthesia with alfaxalone and midazolam in goats.

Cost-effectiveness of selective internal radiation therapy using yttrium-90 resin microspheres in treating patients with inoperable colorectal liver metastases in the UK.

OBJECTIVE: Selective internal radiation therapy (SIRT) using SIR-Spheres(®) (90)Y-labeled resin microspheres has been shown to be a well-tolerated, effective treatment in patients with inoperable liver-dominant chemotherapy-refractory metastatic colorectal cancer (mCRC). This study estimated the cost-effectiveness of (90)Y-resin microspheres compared to best supportive care (BSC) from a UK perspective. METHODS: Survival data from a comparative retrospective cohort study was analyzed and used in a state-transition cost-effectiveness model, using quality-adjusted life years (QALYs) gained as the measure of effectiveness. The model incorporated costs for the SIRT procedure, monitoring, further treatment, adverse events, and death. Utility values, reflecting patient quality-of-life, were taken from a published source. RESULTS: SIRT using (90)Y-resin microspheres compared to BSC improved overall survival by a mean of 1.12 life years and resulted in a cost per QALY gained of £28,216. In sensitivity analysis, this varied between £25,015-£28,817. CONCLUSION: In an area of large unmet need, treatment with (90)Y-resin microspheres offers a clinically effective and cost-effective treatment option.

Stewart-Bluefarb syndrome: Report of five cases and a review of literature.

Stewart-Bluefarb syndrome is a rare angioproliferative disorder characterised by acroangiodermatitis associated with an underlying arteriovenous shunt. This condition should be differentiated from acroangiodermatitis of Mali classically described in association with chronic venous insufficiency. Patients with Stewart-Bluefarb syndrome typically present with lower leg pigmented macules, papules and plaques that can coalesce to form larger confluent patches of pigmentation. Recognition of Stewart-Bluefarb syndrome may be difficult or delayed as the cutaneous manifestations may resemble a variety of other dermatological conditions. Most commonly, acroangiodermatitis may be confused with Kaposi's sarcoma and the condition is often referred to as 'Pseudo-Kaposi's sarcoma'. Acroangiodermatitis may also resemble or coexist with pigmentation of chronic venous insufficiency. As seen in this report, acroangiodermatitis may also be clinically confused with the 'cavernous' form of a capillary malformation. Here, we describe five patients with Stewart-Bluefarb syndrome. In one female and two male patients the diagnosis was delayed as the acroangiodermatitis closely resembled other conditions. All underlying arterio-venous communications were initially diagnosed on duplex ultrasound and confirmed with magnetic resonance angiography. Four patients were found to have a congenital arterio-venous malformation while one was diagnosed with a post-thrombotic arterio-venous fistula. Management included observation and intervention using a variety of techniques including percutaneous or trans-catheter embolisation, endovenous laser, radiofrequency ablation and foam ultrasound guided sclerotherapy. This case series highlights the challenges involved in the diagnosis and management of Stewart-Bluefarb syndrome. Given the local and systemic sequelae of high flow shunts, correct diagnosis and early detection of the underlying arterio-venous abnormality is crucial in the long-term management of these patients and in preventing the associated complications.

Use of near-infrared spectroscopy to identify trends in regional cerebral oxygen saturation in horses.

REASONS FOR PERFORMING STUDY: Alterations in cerebral haemodynamics may contribute to perianaesthetic complications in horses. Near-infrared spectroscopy (NIRS) is frequently used intraoperatively in man to provide information regarding cerebral perfusion. OBJECTIVES: To determine whether NIRS can identify trends in regional cerebral oxygen saturation (rSO2) in horses and whether there is a correlation between rSO2 and venous oxygen tensions. METHODS: A cerebral oximeter sensor recorded rSO2 from the dorsal sagittal sinus of 6 healthy horses. Values for rSO2, arterial and venous oxygen and carbon dioxide tensions (PaO2, PvO2, PaCO2 and PvCO2 respectively), along with arteriovenous oxygen saturations (SavO2) were recorded in unsedated (recording period [RP] 1), sedated (RP2) and anaesthetised horses (RP3-5) and during recovery (RP6-8). During anaesthesia, horses were ventilated to achieve states of normo- (RP3), hyper- (RP4) and hypocapnoea (RP5). Data were evaluated descriptively and analysed using linear mixed-effects models and Pearson's correlation coefficient. RESULTS: Overall mean ± s.d. values for rSO2, PaO2, PvO2, PaCO2, SavO2 and mean arterial pressure varied significantly by RP (P<0.001). Significant decreases in rSO2 were identified between RP1 and the post anaesthetic periods (P<0.001). No significant differences in rSO2 values were identified between RP1 and the intra-anaesthesia periods or between RP3, RP4 and RP5. Significant correlations were identified between rSO2 and PaO2 (r = 0.448, P<0.001), rSO2 and PvO2 (r = 0.512, P<0.001) and rSO2 and SavO2 (r = 0.469, P<0.001). CONCLUSIONS: This is the first study to identify trends in rSO2 in horses using NIRS. A positive correlation was identified between rSO2 and PvO2, suggesting that alterations in cerebral oxygenation may be reflected in PvO2 . POTENTIAL RELEVANCE: Near-infrared spectroscopy may be used to monitor trends in rSO2 during equine anaesthesia. Decreasing rSO2 values may act as an early warning signal, alerting clinicians to potential cerebral desaturation events and indicating a need for intervention.

Barbiturate ingestion in three adult captive tigers (Panthera tigris) and concomitant fatal botulism of one.

Zoo animals, including tigers, have been reported to suffer from barbiturate intoxication, with pentabarbitone being most commonly recorded. Clinical signs range from mild ataxia to general anaesthesia with recovery over hours to days with several factors affecting hepatic barbiturate metabolism and tissue partitioning. Botulism is an often fatal intoxication in man, animals, birds and certain fish. The occurrence in carnivores is uncommon to rare, with only 2 reports found of botulism in felids. This report relates to 3 adult captive cohabiting tigers that simultaneously developed signs of abdominal discomfort, progressive ataxia, recumbency and comatose sleep resembling stage 2 anaesthesia, alternating with periods of distracted wakefulness and ataxic movements. These signs occurred 4 days after being fed the carcass of a horse that had ostensibly died of colic and not been euthanased. The male tiger that was the dominant animal in the feeding hierarchy was worst affected and had to be given intravenous fluids. The female that was lowest in hierarchy was unaffected. After 48-72 hours of treatment at the Onderstepoort Veterinary Academic Hospital the females could eat and made an uneventful recovery. The male tiger showed partial recovery but died during the night a few hours after drinking water on his return to the owner. Necropsy revealed severe oesophageal dilation and impaction with decaying grass; some of this material and water were present in the pharynx and trachea, and had been aspirated causing acute widespread bronchopneumonia. Colon content tested negative for common pesticides but, together with liver, tested positive for barbiturate. Serum taken on the day of admission had tested negative for barbiturate and the residual serum from the 3 animals later tested negative for botulinum toxin. Colon and oesophageal content from the male at necropsy were positive for Clostridium botulinum toxin type C by the mouse bioassay neutralisation test, confirming that this male had had concomitant barbiturate toxicity and botulism, and had succumbed to aspiration bronchopneumonia secondary to pharyngeal, laryngeal and oesophageal paralysis and oesophageal

Clinical care and technical recommendations for 90yttrium microsphere treatment of liver cancer.

Selective internal radiation therapy (SIRT) with (90)yttrium microspheres is a relatively new clinical modality for treating non-resectable malignant liver tumours. This interventional radiology technique employs percutaneous microcatheterisation of the hepatic arterial vasculature to selectively deliver radioembolic microspheres into neoplastic tissue. SIRT results in measurable tumour responses or delayed disease progression in the majority of eligible patients with hepatocellular carcinoma or hepatic metastases arising from colorectal cancer. It has also been successfully used as palliative therapy for non-colorectal malignancies metastatic to the liver. Although most adverse events are mild and transient, SIRT also carries some risks for serious and--rarely--fatal outcomes. In particular, entry of microspheres into non-target vessels may result in radiation-induced tissue damage, such as severe gastric ulceration or radiation cholecystitis. Radiation-induced liver disease poses another significant risk. By careful case selection, considered dose calculation and meticulous angiographic technique, it is possible to minimise the incidence of such complications to less than 10% of all treatments. As the number of physicians employing SIRT expands, there is an increasing need to consolidate clinical experience and expertise to optimise patient outcomes. Authored by a panel of clinicians experienced in treating liver tumours via SIRT, this paper collates experience in vessel mapping, embolisation, dosimetry, microsphere delivery and minimisation of non-target delivery. In addition to these clinical recommendations, the authors propose institutional criteria for introducing SIRT at new centres and for incorporating the technique into multidisciplinary care plans for patients with hepatic neoplasms.

Radioembolization with yttrium microspheres for neuroendocrine tumour liver metastases.

BACKGROUND: (90)Y microsphere radioembolization is performed by injecting the microspheres through a hepatic artery catheter placed percutaneously via the femoral or brachial artery. This study assessed the efficacy of (90)Y microsphere therapy for patients with unresectable neuroendocrine tumour liver metastases (NETLMs). Potential prognostic factors were analysed for their impact on overall survival. METHODS: A prospectively collected database for patients with NETLMs treated by (90)Y microspheres in two centres from 2003 to 2008 was examined retrospectively. Serial radiographic evidence was collected during follow-up to assess response. RESULTS: Fifty-eight patients were included, 51 of whom had evaluable disease at most recent follow-up. Six patients achieved a complete response, 14 a partial response, 14 had stable disease and 17 had disease progression. Overall survival rates at 1, 2 and 3 years were 86, 58 and 47 per cent respectively; median survival was 36 (range 1-61) months. Extent of tumour involvement, radiographic response to treatment, extrahepatic disease and tumour grade were significant prognostic factors for overall survival. CONCLUSION: (90)Y microsphere radioembolization achieved a radiographic response in a significant proportion of patients with NETLMs.

After-hours equine emergency admissions at a university referral hospital (1998-2007): causes and interventions.

Medical records of equine after-hours admissions from 1998 to 2007 are reviewed. Data extracted from the medical records included signalment, reason for admission, pre-admission treatment, clinical presentation, procedures performed, final diagnoses, complications occurring in hospital, length of stay and outcome. Eight hundred and twenty after-hours admissions were available of which 75% were classified as emergencies. Most horses originated from Gauteng province (82%), with Thoroughbred, Arabian, and Warmbloods representing 46%, 10% and 7% of horses. Horses had a median age of 7 years and were predominantly male (60%). Gastrointestinal (64%) and musculoskeletal (19%) disorders were the primary reasons for admission. Anti-inflammatories, sedation and antibiotics were given in 51%, 20% and 15% of cases respectively prior to referral. On admission, 23% of horses had surgical intervention. Intravenous catheterisation (64%), rectal examination (61%), nasogastric intubation (56%), abdominocentesis (33%) and ultrasonography (19%) were the procedures performed most frequently. Surgical and medical colics constituted 28% and 27% respectively of the overall diagnoses, while piroplasmosis was diagnosed in 5% of horses. Post-admission complications occurred in <2% of horses. The median length of stay was 4 days (95% CI: 1 to 21 days). Overall survival to discharge was 74%. This study demonstrates that the majority of after-hours equine admissions to a university referral hospital required medical intervention and were mostly due to gastrointestinal disorders. Information obtained from this study can be used in emergency referral planning.

Prevalence of antibiotic resistance in Campylobacter isolates from commercial poultry suppliers in KwaZulu-Natal, South Africa.

OBJECTIVES: Campylobacter jejuni isolated from broiler and layer chickens from registered abattoirs in KwaZulu-Natal, South Africa, were tested for their susceptibility to eight antibiotics. METHODS: Using agar dilution, susceptibility to eight antibiotics was determined for C. jejuni recovered from the caeca. RESULTS: A total of 155 isolates were collected of which 77 were identified as C. jejuni (broilers n = 56 and layers n = 21). Resistance was highest to tetracycline (broilers 98.2% and layers 100%) and ceftriaxone (broilers 96.4% and layers 100%). High susceptibility was found to ciprofloxacin (broilers 91% and layers 76%) and gentamicin (broilers 98% and layers 81%). Susceptibilities to each of the antibiotics for the broilers and layers, respectively, were: 50% and 57% for erythromycin, 45% and 24% for clarithromycin, 68% and 43% for ampicillin and 64% and 48% for nalidixic acid. Statistically significant differences were detected for the MIC(50) of gentamicin, ciprofloxacin and tetracycline between broilers and layers (P < 0.001) with the MIC(90) of gentamicin also of significant difference (P = 0.01). Multiresistance was detected in 23% and 43% of the isolates from broiler and layer chickens, respectively. CONCLUSIONS: Mass therapy procedures used in animal husbandry have a potential impact on antibiotic resistance development in C. jejuni.

Limb fracture during recovery from general anaesthesia: an often tragic complication of equine anaesthesia.

A 10-year-old Thoroughbred mare was presented for lameness of the left hindlimb as a result of an apical fracture of the lateral proximal sesamoid bone. The mare was ultimately euthanased after suffering catastrophic fractures of the 3rd and 4th metatarsal bones of the contra-lateral hindlimb during an uncoordinated attempt to rise during recovery from general anaesthesia after undergoing arthroscopic surgery. The case report focuses mostly on horse anaesthesia-related mortality, anaesthetic procedure in the horse, possible causes of fractures in horses during recovery and ways in which rate of occurrence of these fractures can be minimised.

Some cardiopulmonary effects of midazolam premedication in clenbuterol-treated bitches during surgical endoscopic examination of the uterus and ovariohysterectomy.

Midazolam was administered intravenously to 8 bitches in a randomised, placebo-controlled clinical trial before propofol induction of surgical anaesthesia. Anaesthesia was maintained with isoflurane-in-oxygen during surgical endoscopic examination of the uterus and ovariohysterectomy. Clenbuterol was administered at the start of surgery to improve uterine muscle relaxation, and to facilitate endoscopic examination of the uterus. Ventilation was controlled. Induction of anaesthesia with propofol to obtain loss of the pedal reflex resulted in a statistically significant (P < 0.05) decrease in minute volume and arterial oxygen partial pressure in the midazolam group. Apnoea also occurred in 50% of dogs in the midazolam group. The dose for propofol in the midazolam group was 7.4 mg/kg compared to 9.5 mg/kg in the control. Minute volume was significantly (P < 0.05) higher in both groups during isoflurane maintenance, compared to the value after incremental propofol to obtain loss of the pedal reflex. Propofol induction resulted in a 25-26% reduction in the mean arterial blood pressure in both groups, and the administration of clenbuterol at the start of surgery resulted in a transient, but statistically significant (P < 0.05), decrease in mean arterial blood pressure in the midazolam group during isoflurane anaesthesia. It is concluded that intravenous midazolam premedication did not adversely affect cardiovascular function during propofol induction, but intra-operative clenbuterol during isoflurane maintenance of anaesthesia may result in transient hypotension. Midazolam premedication may increase adverse respiratory effects when administered before propofol induction of anaesthesia.

Some clinical effects of midazolam premedication in propofol-induced and isoflurane-maintained anaesthesia in dogs during ovariohysterectomy.

In a randomised, placebo-controlled clinical trial, anaesthesia was induced with propofol (4 mg/kg) after intravenous premedication with or without midazolam (0.1 mg/kg), in a group of 8 dogs scheduled for ovariohysterectomy. Midazolam administration induced acute behavioural changes, and increased reflex suppression after propofol induction. Compared to the control group, the dose required to obtain loss of the pedal reflex was significantly reduced by 37%, and the end-tidal isoflurane concentration during maintenance, reduced by 23%.

Sedative-hypnotic effects of midazolam in goats after intravenous and intramuscular administration.

OBJECTIVE: To examine the effect of dose and route of administration on the sedative-hypnotic effects of midazolam. DESIGN: Prospective randomized controlled study ANIMALS: Six indigenous, African bred goats. METHODS: Pilot studies indicated that the optimum dose of midazolam for producing sedation was 0.6 mg kg-1 for intramuscular (IM) injection, while the optimum intravenous (IV) doses causing hypnosis without, and with loss of palpebral reflexes were 0.6 mg kg-1 and 1.2 mg kg-1, respectively. These doses and routes of administration were compared with a saline placebo in a randomized block design in the main experiment, and the sedative-hypnotic effects evaluated according to pre-determined scales. RESULTS: Intramuscular midazolam produced sedation with or without sternal recumbency in all animals with the peak effect occurring 20 minutes after administration. The scores for IM sedation with midazolam were significantly different (p < 0.05) from placebo. Intravenous midazolam at 0.6 mg kg-1 resulted in hypnosis, and at 1.2 mg kg-1 increased reflex suppression was observed. The maximum scores for hypnosis at both doses were obtained 5 minutes after IV injection. The mean (± SD) duration of lateral recumbency was 10.8 (± 3.8) minutes after IV midazolam (0.6 mg kg-1) compared to 20 (± 5.2) minutes after midazolam at 1.2 mg kg-1. Compared to baseline, the heart rate increased significantly (p < 0.05) after high dose IV midazolam. CONCLUSION: Intramuscular midazolam (0.6 mg kg-1) produced maximum sedation 20 minutes after injection. Intravenous injection produced maximum hypnosis within 5 minutes. Increasing the IV dose from 0.6 to 1.2 mg kg-1 resulted in increased reflex suppression and duration of hypnosis. CLINICAL RELEVANCE: For a profound effect with rapid onset midazolam should be given IV in doses between 0.6 and 1.2 mg kg-1.

External bacterial contamination of local anaesthetic cartridges.

In this study external bacterial contamination of local anaesthetic cartridges from newly opened and open containers was examined. Colonies of mainly Gram-positive cocci and Gram-positive rods were grown from cartridges from both the freshly opened and open containers. However, the total number of colonies grown from open containers was significantly higher than that from freshly opened ones. It was concluded that where local anaesthetic cartridges are bulk-packed in containers, strict infection control measures are to be instituted in clinical practice. We suggest that these include keeping containers tightly capped, removing cartridges only when needed, using forceps to handle cartridges and swabbing cartridges with alcohol prior to loading into syringes.

Plasma leukotriene C4 and reactions to contrast media.

Forty-five patients were randomly divided into three groups of 15 and within each group patients were given iothalamate, iopamidol or ioxaglate intravenously during radiological investigations. The plasma leukotriene C4 level was measured before and 30 s and 3 min after the administration of the respective contrast media. In patients demonstrating non-idiosyncratic contrast reactions, a consistent decrease in plasma leukotriene concentration was noted at both 30 s and 3 min following the administration of all three contrast media. A statistically significant decrease in plasma leukotriene occurred at 30 s with ioxaglate, but not with the other two agents. In the limited number of patients who experienced idiosyncratic reactions, the decrease in plasma leukotriene concentration was less apparent. This decrease in plasma leukotriene concentration has been attributed to changes in plasma volume following administration of hyperosmolar contrast media. The inability to demonstrate an increase in plasma leukotriene levels following the administration of both conventional and new, low-osmolar radiographic contrast media supports the cumulative evidence against an allergic mechanism in the majority of non-idiosyncratic and some idiosyncratic contrast reactions.