Characterization of a novel seed protein of Prosopis cineraria showing antifungal activity.

An antifungal protein with a molecular mass of 38.6 kDa was isolated from the seed of Prosopis cineraria. The protein was purified using ammonium sulphate precipitation, ion exchange chromatography and gel filtration. The antifungal activity of purified protein was retained up to 50 °C for 10 min. The MALDI TOF mass spectroscopy revealed 15 assorted peptides. The molecular weight of the antifungal protein is different from antifungal proteins reported in seeds of other leguminous plants. The purified protein exerted antifungal activity against post-harvest fruit fungal pathogens Lasiodiplodia theobromae and Aspergillus fumigatus, isolated from the rotten fruits. The antifungal properties of this novel antifungal protein can be potentially exploited to manage post-harvest fungal disease of fruits through alternative means to reduce use of hazardous chemicals.

Randomized controlled trial of honey versus mupirocin to decolonize patients with nasal colonization of meticillin-resistant Staphylococcus aureus.

BACKGROUND: Mupirocin is used specifically for the eradication of nasal meticillin-resistant Staphylococcus aureus (MRSA), but increasing mupirocin resistance restricts its repeated use. The antibacterial effects of manuka honey have been established in vitro; antibacterial activity of other honeys has also been reported. AIM: To describe the learning experience from a randomized controlled trial (RCT) comparing the efficacy of medical-grade honey (MGH) with mupirocin 2% for the eradication of nasal MRSA. METHODS: Patients colonized in the nose with MRSA and age ≥18 years were recruited. Participants received either one or two courses of MGH or mupirocin 2%, three times per day for five consecutive days. FINDINGS: The proportion of patients who were decolonized after one or two courses of treatment was not significantly different between MGH [18/42; 42.8%; 95% confidence interval (CI): 27.7-59.0] and mupirocin 2% (25/44; 56.8%; 95% CI: 41.0-71.7). Non-nasal MRSA colonization was significantly associated with persistent nasal colonization (odds ratio: 5.186; 95% CI: 1.736-5.489; P = 0.003). The rate of new acquisition of mupirocin resistance was 9.75%. CONCLUSION: Although not significant, a decolonization rate of 42.8% for MGH was impressive. Our findings suggest that this strategy, which has the potential to combat antimicrobial resistance, should be assessed in similar but larger studies.

Integrated total pelvic floor ultrasound in pelvic floor defaecatory dysfunction.

AIM: Imaging for pelvic floor defaecatory dysfunction includes defaecation proctography. Integrated total pelvic floor ultrasound (transvaginal, transperineal, endoanal) may be an alternative. This study assesses ultrasound accuracy for the detection of rectocele, intussusception, enterocele and dyssynergy compared with defaecation proctography, and determines if ultrasound can predict symptoms and findings on proctography. Treatment is examined. METHOD: Images of 323 women who underwent integrated total pelvic floor ultrasound and defaecation proctography between 2011 and 2014 were blindly reviewed. The size and grade of rectocele, enterocele, intussusception and dyssynergy were noted on both, using proctography as the gold standard. Barium trapping in a rectocele or a functionally significant enterocele was noted on proctography. Demographics and Obstructive Defaecation Symptom scores were collated. RESULTS: The positive predictive value of ultrasound was 73% for rectocele, 79% for intussusception and 91% for enterocele. The negative predictive value for dyssynergy was 99%. Agreement was moderate for rectocele and intussusception, good for enterocele and fair for dyssynergy. The majority of rectoceles that required surgery (59/61) and caused barium trapping (85/89) were detected on ultrasound. A rectocele seen on both transvaginal and transperineal scanning was more likely to require surgery than if seen with only one mode (P = 0.0001). If there was intussusception on ultrasound the patient was more likely to have surgery (P = 0.03). An enterocele visualized on ultrasound was likely to be functionally significant on proctography (P = 0.02). There was, however, no association between findings on imaging and symptoms. CONCLUSION: Integrated total pelvic floor ultrasound provides a useful screening tool for women with defaecatory dysfunction such that defaecatory imaging can avoided in some.

Intrathecal ziconotide and baclofen provide pain relief in seven patients with neuropathic pain and spasticity: case reports.

Seven cases of combination of intrathecal (IT) ziconotide and baclofen therapy in patients with refractory neuropathic pain and spasticity were reviewed. Five of the seven adult patients were receiving IT baclofen treatment when ziconotide was initiated. All five patients had experienced at least one previous failed IT treatment regimen. Pain intensity scores improved by a mean of 50.3% with the use of ziconotide-baclofen therapy. Mean time to onset of pain relief was 15 weeks, at a mean ziconotide dose of 3.7 microg/day. Within this group of patients, adverse events were observed in one patient, but they were not considered to be ziconotide related and subsequently resolved. The remaining two patients were receiving ziconotide treatment when baclofen was initiated. Pain intensity scores improved by 75% and 30%, respectively. Pain relief was evident at two weeks and one week, with corresponding ziconotide doses of 2.4 microg/day and 14.4 microg/day, respectively. One patient in this group reported adverse events, but all resolved during continued treatment with the study drugs. Treatment regimens varied between patients in these case series; each regimen used a different titration strategy and different concentrations of ziconotide and baclofen. Combination IT ziconotide and baclofen therapy may be a treatment option for patients with neuropathic pain and spasticity. Future studies are warranted to determine the optimal dosing and titration schedules for ziconotide-baclofen usage.

Vancomycin administration: the impact of multidisciplinary interventions.

BACKGROUND: The clinical microbiology team observed that patients were not receiving all prescribed doses of vancomycin. Ward staff was confused about ordering and interpreting vancomycin therapeutic drug monitoring (TDM) levels. AIM: To audit the incidence of vancomycin dose omission. To implement a series of interventions to improve vancomycin dose administration, and to repeat the audit process to assess these interventions. METHODS: Three prospective audits were conducted to assess the impact of vancomycin TDM on administration of vancomycin. After the first audit, a number of changes in the TDM process were undertaken. After review of the second audit, a senior pharmacist coordinated ward-based pharmacists in assisting staff to interpret levels, and TDM interpretative charts were designed for drug charts. Following the third audit, feedback to hospital management and a plan for ongoing education were undertaken. RESULTS: There was a significant reduction in the number of vancomycin doses held inappropriately in the third (10% (78/782) of prescribed doses) when compared to the first audit (16% (161/1007) of doses) (p<0.01). Of doses that were held inappropriately, there was a significant decrease in doses held for no apparent reason in audit 3 (16% (27/170) of prescribed doses) when compared to audit 1 (25% (69/282) of doses) (p<0.05). CONCLUSIONS: The interventions resulted in a 37.5% reduction in inappropriately held vancomycin doses over a one-year period; 10% of doses are still being held inappropriately. This study highlights the difficulties in identifying barriers to change and changing healthcare worker behaviour.

Investigation of faecal incontinence.

Most patients with faecal incontinence require only a full history (information about other predisposing causes) and examination (assessment for faecal impaction and evaluation of sphincter function and structure). When necessary, anorectal physiological studies, endoanal ultrasound and magnetic resonance imaging allow accurate characterization of sphincter function and structure.

Effect of hemodilution on tissue perfusion and blood coagulation during radical hysterectomy.

OBJECTIVE: The goal of this study was to evaluate the safety of hemodilution on global and splanchnic perfusion and blood coagulation during radical hysterectomy. METHODS: A pulmonary artery catheter and a gastric tonometry catheter were placed in 16 patients with cervical carcinoma. Global perfusion indices, splanchnic perfusion index, and coagulation tests were obtained. Blood was removed to achieve a hemoglobin measurement of 8-9 9 g/dL. Three more measurements were repeated after hemodilution, at the end of surgery, and after the retransfusion of blood. Analysis of variance was used to determine statistical significance. RESULTS: Sixteen patients with cervical carcinoma had 1.0 +/- 0.3 L (mean +/- SD) of blood removed and had a blood loss of 0.8 +/- 0.7 L. Hemodiluted preoperative hemoglobin was 8.7 +/- 1 g/dL. All of the global perfusion indices, except for arterial pH and oxygen consumption, decreased after hemodilution and recovered with the retransfusion of blood (P < or = 0.004). Splanchnic perfusion and coagulation tests were unchanged (P > or = 0.1). Major complication was pulmonary edema in one patient. CONCLUSION: Hemodilution during radical hysterectomy, in this select group of patients, does not appear to compromise tissue perfusion or coagulation.

Preconditioning the human myocardium with intracoronary adenosine.

This study was designed to study the role of adenosine in ischaemic preconditioning. The clinical, electrocardiographic and metabolic parameters of ischaemia were compared before and after intracoronary adenosine during percutaneous transluminal coronary angioplasty in 15 patients with significant stenosis of the left anterior descending artery. Baseline ischaemia was demonstrated by inflating the balloon of appropriate size at its nominal pressure for 30 seconds. Intracoronary adenosine was then administered in dose of 1000 to 6000 mgm/ml. The balloon was repositioned and inflated at nominal pressure for 180 seconds. As compared to 1st balloon inflation, the 2nd balloon inflation produced less severe chest pain, less ST segment deviation on the intracoronary ECG (7.40 +/- 3.94 vs 4.30 +/- 2.15 mm; p < 0.05) and lower coronary sinus lactate levels as compared to the first (0.28 +/- 0.06 vs 0.22 +/- 0.04 mmol/lit; p < 0.05). In conclusion, this study proves that by injecting intracoronary adenosine it is possible to precondition the human myocardium.

A prospective evaluation of clinical tests for placement of laryngeal mask airways.

BACKGROUND: Reliable tests of correct anatomic placement of the laryngeal mask airway (LMA) may enhance safety during use and minimize the need for fiberoptic instrumentation during airway manipulation through the device. This study assessed the correlation between the outcomes of nine clinical tests to place the LMA and the anatomic position of the device as graded on a standard fiberoptic scale. METHODS: During 150 anesthetics, the outcome of nine clinical tests of correct placement was individually scored as satisfactory (positive) or unsatisfactory (negative) for clinical use of the LMA. Anatomic placement was assessed (by fiberoptic evaluation) by an anesthesiologist, who was blinded to the placement of the device, as grade 1, vocal cords not seen; grade 2, cords plus the anterior epiglottis seen; grade 3, cords plus the posterior epiglottis seen; and grade 4, only vocal cords seen. The outcomes of clinical tests were correlated with fiberoptic grade. RESULTS: Tests that correlated with the fiberoptic grade were the ability to generate an airway pressure of 20 cm water, the ability to ventilate manually, a black line on the LMA in midline, anterior movement of the larynx, outward movement of the LMA on inflation of the cuff, and movements of the reservoir bag with spontaneous breathing. Two tests, ability to generate airway pressure of 20 cm water and ability to ventilate manually, correlated with fiberoptic grades 4 and 3 combined (i.e., the epiglottis was supported by the LMA) and grade 2 (the epiglottis was not supported by the LMA). Tests with poor correlation with fiberoptic grade were the presence of resistance at the end of insertion, inability to advance LMA after inflation of the cuff, and presence of a capnographic trace. CONCLUSIONS: The outcome of clinical tests correlates with the anatomic placement of LMAs, as judged by fiberoptic examination. Two tests that best correlated with the fiberoptic grade were the ability to generate airway pressure of 20 cm water and the ability to ventilate manually.

Augmented autologous transfusions in major reconstructive spine surgery.

Intraoperative autologous transfusion during major reconstructive spine surgery decreased allogeneic red blood cell transfusions, but patients were exposed to significant numbers of allogeneic blood products. This study reports a prospective study of 160 randomized patients undergoing major reconstructive spine surgery. Without delaying start of surgery, 80 patients underwent hemapheresis with coincidental normovolemic hemodilution in the operating room to sequester autologous blood components. A therapeutic dose plateletpheresis product and an average of 2 U each of freshly collected autologous red cells and fresh plasma were prepared prior to surgical incision. The same supplies and equipment were used subsequently to carry out intraoperative autologous transfusion (IAT). Autologous plasma and platelets were transfused to Sequestration patients, contributing to a significant decrease of total allogeneic donor exposures. One or more autologous red blood cell unit equivalents were cost effectively salvaged and retransfused to 78% of the Sequestration patients. Altogether, autologous red cells comprised 87% of the total red cells transfused. During the same time period, 80 age-, sex-, and weight-matched controls, who received IAT only, were accrued for comparison with Sequestration patients. Of all red cells transfused to control patients, autologous units comprised 47%. Both patient groups received the same total perioperative red blood cell support. The per patient cost for IAT, with or without sequestration, was competitive with supplying one unit of cross-matched allogeneic red cells. IAT only patients had greater allogeneic blood donor exposures than Sequestration patients, in whom the numbers of allogeneic red cells, plasma and platelet transfusions were decreased. Compared with IAT alone, the hospital post-operative stay of Sequestration patients was 23% less than IAT only patients.

Audit of autotransfusion in spine surgery.

A prospective evaluation has been undertaken of 382 patients undergoing reconstructive spine surgery during a thirty-six month period. Acute normovolaemic haemodilution and haemapheresis for blood component sequestration was used in 80 patients in the operating theatre. An average of two units each of freshly collected autologous red cells and fresh plasma together with a therapeutic dose of a plateletpheresis product were prepared for each patient prior to surgical incision. The same supplies and equipment were subsequently used for conventional blood salvage and autotransfusion. The other 302 patients received salvaged blood only. Of the total blood transfused, autologous red cells comprised 87% of sequestration and 49% of autotransfusion-only patients. Each group received the same total perioperative red blood cell support. The cost for one red cell equivalent by intraoperative autologous transfusion was competitive with that of providing one unit of cross-matched allogeneic red cells. As compared with salvage alone, sequestration combined with salvage was even more cost effective and decreased reliance on allogenic products and preoperative autologous blood donations. The rate of transfusing autologous blood products was markedly increased.

Hemodynamic effects of isovolemic hemodilution during descending thoracic aortic cross clamping and lower torso reperfusion.

BACKGROUND: Isovolemic hemodilution has been suggested for blood conservation and to improve hemodynamic tolerance to abdominal aortic cross clamping. However, the hemodynamic effects of hemodilution during descending thoracic aortic cross clamping (DAC) have not been established. We evaluated them in anesthetized swine. METHODS: Hemodilution (n = 7) was produced by the isovolemic exchange of blood for 6% hetastarch to a target hematocrit of 20%. Hematocrit in control pigs (n = 7) remained at 30%. DAC was performed at the T9 level for 45 minutes. During a 60-minute reperfusion period, control pigs were infused with lactated Ringer's solution; shed blood was returned to hemodilution pigs, followed by lactated Ringer's. If hypotension occurred despite left atrial pressure of 10 mm Hg or greater, boluses of phenylephrine were given to keep mean arterial pressure above 60 mm Hg. RESULTS: Hemodilution caused a marked reduction in hematocrit and in global oxygen delivery (DO2). DAC produced a significant increase in proximal arterial pressure, cardiac index, and DO2 and oxygen consumption (VO2) was markedly reduced in both groups. A significant increase in systemic vascular resistance during DAC occurred only in control pigs. After reperfusion, vascular resistance was significantly lower than baseline in hemodilution pigs, requiring a sixfold greater dose of phenylephrine to avoid hypotension. A lower global DO2 and supply-limited VO2 were also observed in hemodilution pigs. CONCLUSIONS: Isovolemic hemodilution maintains hemodynamic stability during DAC. During lower torso reperfusion, however, hemodilution caused hemodynamic instability, decreased global DO2, and limited VO2, which may offset its potential benefits.

Pulmonary hypertension and systemic vasoconstriction may offset the benefits of acellular hemoglobin blood substitutes.

OBJECTIVE: We tested the hypothesis that the pharmacologic properties of a small volume of alpha alpha-cross-linked hemoglobin (alpha alpha Hb) could effectively resuscitate pigs subjected to hemorrhage. METHODS: Fourteen pigs hemorrhaged to a mean arterial pressure (MAP) of 40 mm Hg for 60 minutes were treated with a 4-mL/kg 2-minute infusion of 10 g/dL alpha alpha Hb or 7 g/dL human serum albumin, an oncotically matched control solution. RESULTS: The removal of blood (17 +/- 1.5 mL/kg) caused the typical physiologic responses to hemorrhagic hypovolemia. Infusion of alpha alpha Hb restored mean arterial pressure and coronary perfusion pressure, but cardiac output and mixed venous O2 saturation did not improve significantly. Pulmonary arterial pressure and pulmonary vascular resistance increased markedly and were higher than baseline levels after alpha alpha Hb. Infusion of human serum albumin produced only minor hemodynamic changes. Brain blood flow did improve to baseline values after alpha alpha Hb, but was the only tissue to do so. In the human serum albumin group, superior mesenteric artery blood flow recovered to baseline values, whereas brain blood flow did not. Blood flows to other tissues were similar in both groups. CONCLUSION: Small-volume infusion of alpha alpha Hb restored mean arterial pressure and brain blood flow, but pulmonary hypertension and low peripheral perfusion may offset benefits for trauma patients.

Adenosine-induced chest pain: is it due to myocardial ischaemia? Clinical, electrocardiographic, haemodynamic and metabolic study.

Adenosine has recently been demonstrated to be a mediator of angina in human beings. The present study was undertaken to document the presence or absence of myocardial ischaemia on clinical, haemodynamic, electrocardiographic and metabolic evidences after intracoronary administration of adenosine. Fifteen patients with chronic stable angina (12 males and 3 females), positive exercise stress test and documented significant stenosis of the left anterior descending coronary artery (LAD) were included in the study. The surface and intracoronary electrocardiograms (ECGs), pulmonary artery diastolic pressure and coronary sinus lactate levels were monitored at baseline and after intracoronary administration of adenosine in all patients. Adenosine was administered intracoronary in doses of 1000-8000 microgram depending on the provocation of chest pain. Typical angina was observed in all patients. There were no signs of ischaemia on surface or intracoronary ECG. There was no statistically significant difference between the pulmonary artery diastolic pressure and coronary sins lactate levels at baseline and post-adenosine administration (p > 0.05). It is concluded that intracoronary administration of adenosine produces chest pain in patients with chronic stable angina by mechanism other than myocardial ischaemia.

Coronary artery stenting in acute myocardial infarction.

Little information is available on the use of coronary stents to treat suboptimal results during direct angioplasty in acute myocardial infarction (AMI). In this study, we report 16 cases of AMI who underwent stent implantation in infarct-related artery for suboptimal results and their 6 months angiographic follow-up. Immediate angiographic success was achieved in all patients. The minimal luminal diameter increased from 0.06 +/- 0.12 mm to 2.89 +/- 0.12 mm (p < 0.001). One patient died in the hospital on day 8 due to subacute stent thrombosis. No patient required emergency bypass surgery. Two patients required blood transfusion for groin haematoma and one required intracoronary thrombolysis. All patients underwent exercise stress test at 1 month and at 3 months and coronary angiography at 4 months or earlier it indicated. At the end of 6 months follow-up, 4 patients had a positive exercise test and coronary angiography revealed angiographic restenosis in 3 and progression of disease in other vessels in 1 patient. We conclude that stent deployment is a viable option to treat suboptimal results after direct angioplasty in AMI.

Inhaled nitric oxide reverses cell-free hemoglobin-induced pulmonary hypertension and decreased lung compliance. Preliminary results.

BACKGROUND: In order to test the hypothesis that inhaled nitric oxide (NO) reverses the pulmonary hypertension induced by alphaalpha-diaspirin crosslinked hemoglobin (alphaalphaHb), were studied anesthetized pigs that were administered with a total dose of 200 mg/kg of 10% alphaalphaHb. Inhaled NO (5 ppm) was administered for 10 min, and then discontinued for 10 min. This cycle was then repeated with 10 ppm inhaled NO. RESULTS: alphaalphaHb caused pulmonary arterial pressure (PAP) to increase from 27 +/- 1.7 to 40 +/- 3.0 mmHg (P<0.05) and dynamic lung compliance to decrease from 29+/- 1.5 to 23+/- 1.6 ml/cmH2O (P < 0.05). After both doses of inhaled NO, but particularly 10 ppm, PAP was reduced (P < 0.05) and lung compliance increased (P < 0.05) from the alphaalphaHb levels. When inhaled NO was discontinued PAP again increased and lung compliance decreased to levels significantly different from baseline (P < 0.05). CONCLUSION: We conclude that cell-free hemoglobin-induced pulmonary hypertension and decreased lung compliance can be selectively counteracted by inhaled NO.

A phase III, multicenter, open-label, randomized, comparative study evaluating the effect of sevoflurane versus isoflurane on the maintenance of anesthesia in adult ASA class I, II, and III inpatients.

STUDY OBJECTIVE: To compare the clinical efficacy and safety of sevoflurane and isoflurane when used for the maintenance of anesthesia in adult ASA I, II, and III inpatients undergoing surgical procedures of at least 1 hour's duration. DESIGN: Phase III, randomized, open-label clinical trial. SETTING: 12 international surgical units. PATIENTS: 555 consenting inpatients undergoing surgeries of intermediate duration. INTERVENTIONS: Subjects received either sevoflurane (n = 272) or isoflurane (n = 283) as their primary anesthetic drug, each administered in nitrous oxide (N2O) (up to 70%) and oxygen (O2) after an intravenous induction using thiopental and low-dose fentanyl. The concentration of volatile drug was kept relatively constant but some titration in response to clinical variable was permitted. Comparison of efficacy was based on observations made of the rapidly and ease of recovery from anesthesia and the frequency of untoward effects for the duration of anesthesia in the return of orientation. Safety was evaluated by monitoring adverse experiences, hematologic and non-laboratory testing, and physical assessments. In 25% of patients (all patients 171 both treatment groups at selected investigational sites), plasma inorganic fluoride concentrations were determined preoperatively, every 2 hours during maintenance, at the end of anesthesia, and at 1, 2, 4, 8, 12, 24, 48, and 72 hours postoperatively. MEASUREMENTS AND MAIN RESULTS: Emergence, response to commands, orientation, and the first request for postoperative analgesia were all more rapid following discontinuation of sevoflurane than following discontinuation of isoflurane (sevoflurane, 11.0 +/- 0.6, 12.8 +/- 0.7, 17.2 +/- 0.9, 46.1 +/- 3.0 minutes, respectively, versus isoflurane, 16.4 +/- 0.6, 18.4 +/- 0.7, 24.7 +/- 0.9, 55.4 +/- 3.2 minutes). The incidence of adverse experiences was similar for sevoflurane and isoflurane patients. Forty-eight percent of patients on the sevoflurane group had no untoward effect versus 39% in the isoflurane group. Three patients who received sevoflurane had serum inorganic fluoride levels 50 microM/I. or greater though standard tests indicated no evidence of associated renal dysfunction. CONCLUSION: Sevoflurane anesthesia, as compared with isoflurane, may be advantageous in providing a smoother clinical course with a more rapid recover.

Adjuvant chemotherapy with 5-FU, adriamycin, and mitomycin-C (FAM) versus surgery alone for patients with locally advanced gastric adenocarcinoma: A Southwest Oncology Group study.

PURPOSE: To evaluate FAM [5-FU (5-fluorouracil), doxorubicin, mitomycin C] chemotherapy as adjuvant therapy for patients with resected TNM stage I, II, or III gastric carcinoma. PATIENTS AND METHODS: One hundred ninety-three eligible patients were accrued from 1978 to 1991 in a phase III trial comparing six cycles (1 year) of postoperative FAM chemotherapy with observation only. RESULTS: The median follow-up on this study was 9.5 years. For all patients, no differences (log-rank analysis) in disease-free survival (p = 0.45) and overall survival (p = 0.57) between FAM therapy (93 cases) and surgery (100 cases) were observed. Quality of surgical resection affected survival irrespective of FAM use. Cases with curative resection, defined in a retrospective review of pathology and surgical reports as cases having no evidence of residual disease in the abdomen and tumor-free margins > 1 cm, had superior survival compared to cases not meeting these requirements (p < 0.001). FAM was well tolerated with 6% (five of 90) of cases demonstrating grade IV hematologic toxicity. There were two drug-related fatalities (one cardiomyopathy, one hematolytic uremic syndrome). CONCLUSION: FAM is not effective adjuvant therapy for TNM stage I, II, and III patients with resected gastric cancer. Future adjuvant studies must emphasize prospective surgical quality control to assure enrollment of appropriately staged and resected cases and wide participation to assure adequate case accrual over a reasonable period.