Homeopathic prescribing for chronic and acute periodontal conditions in 3 dental practices in the UK.

INTRODUCTION: This investigation extends our previous dental data collection pilot study with the following main aims: to gain insight into the periodontal complaints that dentists in the UK treat using individualised homeopathic prescription; to record patient-assessed change in severity of treated complaint (acute or chronic); to determine periodontal pocket depth (PPD). MATERIALS AND METHODS: Three dentists recorded data systematically at 249 homeopathic appointments in 51 patients over a period of 18 months. A spreadsheet enabled the data collection of the following records: date of appointment; anonymised patient identity; main periodontal problem treated; whether the condition was acute or chronic; patient-assessed clinical outcome on a 7-point Likert scale, ranging from -3 to +3, to compare the first and any subsequent appointments; whether any interventional dental surgery (IDS) had been carried out; clinician-assessed PPD measurements. RESULTS: At least one follow-up (FU) appointment was reported for each of 46 patients (22 chronic [6 with IDS, 16 without IDS]; 24 acute [10 with IDS, 14 without IDS]). In chronic cases, strongly positive outcomes (score of +2 or +3) were reported by 2 (33.3%) of 6 IDS patients and by 1 (6.3%) of 16 non-IDS patients. In acute cases, strongly positive outcomes were reported by 7 (70%) of 10 IDS patients and by 8 (57.2%) of 14 non-IDS patients (no statistically significant difference between sub-groups). The FU conditions most frequently treated with homeopathy were chronic periodontitis (19 patients) and acute periodontal abscess (11 patients). Analysis of PPD data was not feasible due to the small numbers of patients involved. CONCLUSION: Limited insight has been gained into the periodontal complaints treated by homeopathy in the UK. Due to small sample size and equivocal results, the interpretation of the patient-reported outcomes data is unclear. Positive findings obtained in the acute treatment setting suggest that this may be a promising area for research in periodontal homeopathy.

Veterinary clinical research database for homeopathy: placebo-controlled trials.

BACKGROUND: Veterinary homeopathy has led a somewhat shadowy existence since its first introduction. Only in the last three decades has the number of clinical trials increased considerably. This literature is generally not well perceived, which may be partly a consequence of the diffuse and somewhat inaccessible nature of some of the relevant research publications. The Veterinary Clinical Research Database for Homeopathy (VetCR) was launched in 2006 to provide information on existing clinical research in veterinary homeopathy and to facilitate the preparation of systematic reviews. OBJECTIVE: The aim of the present report is to provide an overview of this first database on clinical research in veterinary homeopathy, with a special focus on its content of placebo controlled clinical trials and summarising what is known about placebo effects in animals. RESULTS: In April 2012, the VetCR database contained 302 data records. Among these, 203 controlled trials were identified: 146 randomised and 57 non-randomised. In 97 of those 203 trials, the homeopathic medical intervention was compared to placebo. COMMENT: A program of formal systematic reviews of peer-reviewed randomised controlled trials in veterinary homeopathy is now underway; detailed findings from the program's data extraction and appraisal approach, including the assessment of trial quality (risk of bias), will be reported in due course.

Semi-standardised homeopathic treatment of premenstrual syndrome with a limited number of medicines: feasibility study.

BACKGROUND: Individualised homeopathy involves a large number of possible medicines. For clinical research purposes it is desirable to limit this number, create more consistency between prescribers and optimising the accuracy of prescription. Using a semi-standardised treatment protocol, we aimed to improve homeopathic management of targeted subgroups of women with premenstrual syndrome/symptoms (PMS/S). OBJECTIVES: To design a semi-standardised protocol for individualised prescribing in PMS/S with a limited number of homeopathic medicines, and to explore the feasibility of working with it in daily homeopathic practice. METHODS: With help of an expert panel, homeopathic medicines were selected, as well as predictive symptoms and characteristics (keynotes) for each medicine. With those, we designed a patient questionnaire and a diagnostic algorithm. The patient questionnaire contained 123 questions, representing potential predictive symptoms for 11 homeopathic medicines for PMS/S. The medicines selected (in rank order) were Sep, Nat-m, Lach, Cimic, Lac-c, Puls, Calc, Lil-t, Mag-p, Mag-c, Phos. In a feasibility study 20 homeopathic doctors used the protocol in daily practice. The diagnosis was confirmed by daily rating of pre-defined symptoms during two consecutive menstrual cycles. The acceptability and feasibility of the protocol were evaluated after 3 months follow-up, at which time we also measured changes in premenstrual symptom scores and patient-reported changes in symptoms and general health. RESULTS: The doctors mostly complied with the protocol and valued the computerised diagnostic algorithm as a useful tool for homeopathic medicine selection. 33 patients completed 3 months follow-up. By then, 19 patients still taking the first medicine on the basis of the algorithm. We received valid symptom records of 30 patients. Premenstrual symptom scores dropped by 50% or more in 12 patients and by 30-50% in 6 patients; scores dropped by less than 30% or increased in 12 patients. Recruitment of patients (n=38 in 9 months) proved difficult. Adherence to the diaries and the questionnaire was satisfactory. CONCLUSIONS: It is feasible to use a semi-standardised protocol for individualised homeopathic prescribing in PMS, in daily practice. Its predictive value and the percentage of women with PMS/S helped by the selected medicines remain to be evaluated in further research. In future research, active promotion will be needed to recruit patients.

Homeopathic prescribing for chronic conditions in equine veterinary practice in the UK.

Twelve Faculty of Homeopathy veterinarians recorded data systematically at 777 consecutive homeopathic appointments for horses over a period of 12 months. A spreadsheet enabled the recording of information, which included the date of appointment; horse and owner identity (anonymised); sex of horse; main medical problem treated; whether the condition was chronic or acute; whether the appointment was new or a follow-up; owner-assessed clinical outcome on a seven-point scale, ranging from -3 to +3, compared with the first appointment; homeopathic medicine(s) prescribed; and whether any conventional or other complementary/alternative medicine (CAM) was being used concurrently to treat the condition. Data from 289 horses comprised a total of 305 individual conditions identified as chronic in nature, of which 234 had a follow-up assessment. At the final appointment for chronic cases during the study period, 4.3 per cent were receiving conventional medication and 17.1 per cent were being given another CAM treatment in addition to homeopathy. The eight chronic conditions most frequently treated with homeopathy were: arthritis, headshaking, laminitis, chronic obstructive pulmonary disease, sweet itch, dermatitis, sarcoidosis and Cushing's syndrome.

Pilot study of the effect of individualised homeopathy on the pruritus associated with atopic dermatitis in dogs.

Twenty dogs with confirmed atopic dermatitis were treated with homeopathy. In the first phase of this pilot study, all of the dogs were treated by a veterinary homeopath with individualised remedies prescribed on the basis of the dog's cutaneous signs and constitutional characteristics. The response to treatment was assessed by scoring the severity of pruritus from 0 to 10 on a validated scale. The dogs were evaluated at monthly intervals for at least two months. In 15 cases, the owners reported no improvement following homeopathic treatment. In the other five cases, the owners believed that the homeopathic treatment was associated with a substantial improvement, and reported reductions in pruritus scores ranging from 64 to 100 per cent. These five dogs were selected for the second phase of the study, in which homeopathic remedies were tested against placebos in a randomised and blinded trial. In one of these dogs, atopic dermatitis resolved completely and so this dog could not participate in phase 2; another dog was euthanased because of status epilepticus before phase 2 could be started. In the remaining three cases, the owners correctly distinguished between the placebo and homeopathic remedies, and reported reductions in the pruritus score of 0, 0.2 and 0.8 following placebo treatment and 4.3, 2.4 and 3.0, respectively, following the remedy.

Outcomes from homeopathic prescribing in dental practice: a prospective, research-targeted, pilot study.

BACKGROUND AND AIMS: A base for targeted research development in dental homeopathy can be founded on systematic collection and analysis of relevant data obtained by dentists in clinical practice. With these longer-term aims in mind, we conducted a pilot data collection study, in which 14 homeopathic dentists collected clinical and outcome data over a 6-month period in their practice setting. METHODS: A specifically designed Excel spreadsheet enabled recording of consecutive dental appointments under the following main headings: date; patient identity (anonymised), age and gender; dental condition/complaint treated; whether chronic or acute, new or follow-up case; patient-assessed outcome (7-point Likert scale: -3 to +3) compared with first appointment; homeopathic medicine/s prescribed; whether any other medication/s being taken for the condition. Spreadsheets were submitted monthly via e-mail to the project co-ordinator for data synthesis and analysis. RESULTS: Practitioners typically submitted data regularly and punctually, and most data cells were completed as required, enabling substantial data analysis. The mean age of patients was 46.2 years. A total of 726 individual patient conditions were treated overall. There was opportunity to follow-up 496 individual cases (positive outcome in 90.1%; negative in 1.8%; no change in 7.9%; outcome not recorded in 0.2%). Sixty-four of these 496 patients reported their outcome assessment before the end of the homeopathic appointment. Strongly positive outcomes (scores of +2 or +3) were achieved most notably in the frequently treated conditions of pericoronitis, periodontal abscess, periodontal infection, reversible pulpitis, sensitive cementum, and toothache with decay. CONCLUSIONS: This multi-practitioner pilot study has indicated that systematic recording of practice data in dental homeopathy is both feasible and capable of informing future research. A refined version of the spreadsheet can be employed in larger-scale research-targeted data collection in the dental practice setting.

Outcomes from homeopathic prescribing in veterinary practice: a prospective, research-targeted, pilot study.

BACKGROUND AND AIMS: Targeted research development in veterinary homeopathy is properly informed by the systematic collection and analysis of relevant clinical data obtained by its practitioners. We organised a pilot data collection study, in which 8 Faculty of Homeopathy veterinarians collected practice-based clinical and outcomes data over a 6-month period. METHODS: A specifically designed Excel spreadsheet enabled recording of consecutive clinical appointments under the following headings: date; identity of patient and owner (anonymised); age, sex and species of patient; medical condition/complaint treated; whether confirmed diagnosis, chronic or acute, new or follow-up case; owner-assessed outcome (7-point Likert scale: -3 to +3) compared with first appointment; homeopathic medicine/s prescribed; other medication/s for the condition/complaint. Spreadsheets were submitted monthly by e-mail to the project organisers for data checking, synthesis and analysis. RESULTS: Practitioners submitted data regularly and punctually, and most data cells were completed. 767 individual patients were treated (547 dogs, 155 cats, 50 horses, 5 rabbits, 4 guinea-pigs, 2 birds, 2 goats, 1 cow, and 1 tortoise). Outcome from two or more homeopathic appointments per patient condition was obtained in 539 cases (79.8% showing improvement, 6.1% deterioration, 11.7% no change; outcome not recorded in 2.4% of follow-ups). Strongly positive outcomes (scores of +2 or +3) were achieved in: arthritis and epilepsy in dogs and, in smaller numbers, in atopic dermatitis, gingivitis and hyperthyroidism in cats. CONCLUSIONS: Systematic recording of data by veterinarians in clinical practice is feasible and capable of informing future research in veterinary homeopathy. A refined version of the spreadsheet can be used in larger-scale research-targeted veterinary data collection.

Outcomes from homeopathic prescribing in medical practice: a prospective, research-targeted, pilot study.

BACKGROUND AND AIMS: A base for targeted research and development in homeopathy can be founded on systematic collection and analysis of relevant clinical data obtained by doctors in routine practice. With these longer-term aims in mind, we conducted a pilot data collection study, in which 14 homeopathic physicians collected clinical and outcomes data over a 6-month period in their practice setting. METHODS: A specifically designed Excel spreadsheet enabled recording of consecutive clinical appointments under the following main headings: date, patient identity (anonymised), age and gender, medical condition/complaint treated, whether chronic or acute, new or follow-up case, patient-assessed outcome (7-point Likert scale: -3 to +3) compared with first appointment, homeopathic medicine/s prescribed, whether any other medication/s being taken for the condition. Spreadsheets were submitted monthly via email to the project co-ordinator for data synthesis and analysis. RESULTS: Practitioners typically submitted data regularly and punctually, and most data cells were completed as required, enabling substantial data analysis. The mean age of patients was 41.5 years. A total of 1,783 individual patient conditions were treated overall. Outcome from two or more homeopathic appointments per patient condition was obtained in 961 cases (75.9% positive, 4.6% negative, 14.7% no change; 4.8% outcome not recorded). Strongly positive outcomes (scores of +2 or +3) were achieved most notably in the frequently treated conditions of anxiety, depression, and irritable bowel syndrome. CONCLUSIONS: This multi-practitioner pilot study has indicated that systematic recording of clinical data in homeopathy is both feasible and capable of informing future research. A refined version of the spreadsheet can be employed in larger-scale research-targeted clinical data collection in the medical practice setting--particularly in primary care.

Hepatic and mesenteric nitric oxide synthase expression in a rat model of CCl(4)-induced cirrhosis.

BACKGROUND: Cirrhosis and portal hypertension are frequently linked with changes in expression of nitric oxide synthase (NOS) and/or endotoxaemia. AIMS: This study tested the following hypothesis: that inducible (i)NOS activity is increased within the visceral circulation concurrently with decreased constitutive (c)NOS activity in the hepatic sinusoids and that the concentration of NO metabolites in portal blood is consequent on endotoxin concentration. MATERIALS AND METHODS: Plasma concentrations of (nitrite + nitrate) and endotoxin, together with hepatic and mesenteric NOS activity (arginine/citrulline method) and protein expression (histochemistry) plus portal and arterial blood pressure, were determined in rats made severely cirrhotic by intragastric CCl(4) over 14 weeks (n = 6) compared with age-matched controls (n = 5). The concentrations of [nitrite + nitrate] and endotoxin in portal plasma were also directly compared in rats made cirrhotic for a period of 8-14 weeks (n = 10). RESULTS: In rats with advanced cirrhosis, arterial [nitrite + nitrate] was 93.1 (22.4) micromol/L (mean, SEM) compared with 29.1 (6.1) micromol/L in controls (P < 0.05); portal plasma [NO(2)(-) + NO3(-)] was 127.1 (27.2) compared with 24.7 (4.7) micromol/L in controls (P < 0.05). Cirrhotic rats had higher endotoxin concentration in plasma compared with controls (systemic: 85.0 (24.5) versus 1.7 (0.2) EU/ml, P < 0.05; portal: 180.3 (47.9) versus 1.7 (0.2) EU/ml, P < 0.05). The same severely cirrhotic rats possessed decreased cNOS activity in liver (2.95 [0.40] versus 5.29 [0.85] pmol/min/g; P < 0.05) and increased iNOS activity in mesentery (4.83 [1.23] versus 1.47 [0.15] pmol/min/g; P < 0.05) compared with controls. Histochemical observations confirmed these findings. Rats given CCl(4) for a period of 8-14 weeks possessed high endotoxin concentration in portal plasma, with correspondingly high [nitrite + nitrate] (r(2) = 0.954; P < 0.001). CONCLUSIONS: An endotoxin-induced increase in mesenteric iNOS activity and a decrease in hepatic cNOS activity may account for, respectively, the hyperdynamic visceral circulation and the increased intrahepatic resistance of cirrhosis.

The research evidence base for homeopathy: a fresh assessment of the literature.

BACKGROUND: The claims made for the clinical effects of homeopathy are controversial. The results of several meta-analyses of clinical trials are positive, but they fail in general to highlight specific medical conditions that respond well to homeopathy. AIMS: This review examines the cumulative research from randomised and/or double-blind clinical trials (RCTs) in homeopathy for individual medical conditions reported since 1975, and asks the question: What is the weight of the original evidence from published RCTs that homeopathy has an effect that is statistically significantly different from that in a comparative group? METHOD: Analysis of the 93 substantive RCTs that compare homeopathy either with placebo or another treatment. RESULTS: 50 papers report a significant benefit of homeopathy in at least one clinical outcome measure, 41 that fail to discern any inter-group differences, and two that describe an inferior response with homeopathy. Considering the relative number of research articles on the 35 different medical conditions in which such research has been carried out, the weight of evidence currently favours a positive treatment effect in eight: childhood diarrhoea, fibrositis, hayfever, influenza, pain (miscellaneous), side-effects of radio- or chemotherapy, sprains and upper respiratory tract infection. Based on published research to date, it seems unlikely that homeopathy is efficacious for headache, stroke or warts. Insufficient research prevents conclusions from being drawn about any other medical conditions. CONCLUSIONS: The available research evidence emphasises the need for much more and better-directed research in homeopathy. A fresh agenda of enquiry should consider beyond (but include) the placebo-controlled trial. Each study should adopt research methods and outcome measurements linked to a question addressing the clinical significance of homeopathy's effects.

The research evidence base for homeopathy: a fresh assessment of the literature

The claims made for the clinical effects of homeopathy are controversial. The results of several meta-analyses of clinical triasl are positive, bur they fail in general to highlight specific medical conditions... (AU)

Rapid flow carbon dioxide laparoscopy disperses cancer cells into the peritoneal cavity but not the port sites in a new rat model.

BACKGROUND: The role of carbon dioxide (CO2) in the pathogenesis of tumor recurrence after laparoscopy remains controversial. Using a new rat model, we studied the effect of different CO2 flow rates on the dispersal of free cancer cells. METHODS: A novel model of desufflation without trocar was developed, and 55 Fischer rats were randomized into three flow groups: group A (rapid, 0.67 l/min; n = 20), group B (slow, 0.44 l/min; n = 20), and group C (gasless, n = 15). We vented CO2 via a portless surgical valve that filtered cells. After the abdominal wall had been suspended to create space, half of the animals in each group (nonrecovery) received 7.5 x 10(6) immunolabeled rat colon cancer cells (RCC2) intraperitoneally, whereas the other half (recovery) received 7.5 x l0(6) viable RCC2 before insufflation or gasless laparoscopy. Nonrecovery animals were killed after 20 l of insufflation. Parietal peritoneal and port-site specimens were examined for RCC2 by fluorescence microscopy (FM) and flow cytometry (FC). The recovery animals were killed at 4 weeks for evidence of wound recurrence. RESULTS: Nine of 10 nonrecovery animals in A had RCC2 on FM or FC, as compared with 2 animals in each of the nonrecovery groups B and C (p = 0.018, Fisher's exact test). Two of the nine animals in group A also had RCC2 in their portless valves. Two recovery (A) animals developed wound recurrence as compared with none in the other groups (p = 0.315). CONCLUSION: In this model, rapid CO2 flow dispersed free cancer cells into the peritoneal cavity, but not into the port sites, thus supporting a role for CO2 in the intraperitoneal dispersal of free cancer cells, but not in wound recurrence.

Expression of inducible nitric oxide synthase contributes to the development of pancreatitis following pancreatic ischaemia and reperfusion.

BACKGROUND: Inducible nitric oxide synthase (iNOS) activity is increased in experimentally induced acute pancreatitis. Increased expression of this isoform of nitric oxide synthase has been demonstrated in several organs subjected to ischaemia-reperfusion injury. The present experiment investigated the expression of iNOS and the effect of selective iNOS inhibition in pancreatic ischaemia-reperfusion. METHODS: Wistar rats (n = 40) were randomly and equally assigned to four groups. Groups 2 and 4 underwent 60 min of total pancreatic ischaemia followed by 6 h of reperfusion (I-R). Groups 1 and 3 underwent sham operation. The selective iNOS inhibitor L-N(6)-(1-iminoethyl)-lysine (L-NIL) was administered to groups 3 and 4. Expression of iNOS was examined by immunohistochemistry. Other investigations included measurement of serum amylase activity and pancreatic wet : dry weight ratio, and histopathological examination. RESULTS: Eight of ten rats in group 2 (I-R only) expressed iNOS but none of the ten animals in group 1 (sham laparotomy) did so. Group 4 (I-R + L-NIL) animals had significantly lower serum amylase levels and wet : dry weight ratios than those in group 2 (I-R only). Microscopic evidence of pancreatic injury was present only in rats in group 2 (I-R only). CONCLUSION: Expression of iNOS during reperfusion following pancreatic ischaemia contributes significantly to the development of acute pancreatitis.

The effect of N(G)-monomethyl-L-arginine and tamoxifen on nitric oxide production in breast cancer cells stimulated by oestrogen and progesterone.

OBJECTIVE: To examine the capacity of oestrogen, or progesterone, or both to elicit the release of nitric oxide (NO) from T47D breast cancer cells in vitro. DESIGN: Prospective, longitudinal, controlled in vitro experiment. SETTING: University Medical School, United Kingdom. MATERIAL AND INTERVENTIONS: T47D breast cancer cells were stimulated by micromolar to picomolar doses of 17beta-oestradiol, or progesterone, or both, with or without inhibition of NO or tamoxifen at 24 and 48 hours. MAIN OUTCOME MEASURES: Concentration of NO metabolites (nitrite + nitrate) in the culture medium measured by chemiluminescence. RESULTS: Both hormones dose-dependently increased the proliferation of T47D without toxic effects over the range 10(-12)-10(-6) M. Both stimulated NO production at 24 hours, micomolar doses producing a pronounced (2-4 fold) increase in the concentration of NO metabolites in culture medium (p = 0.002 and p < 0.001 for oestradiol and progesterone, respectively). By contrast, incubation with hormones for 48 hours had little effect on the concentrations of NO metabolites. NO production induced by hormones was completely inhibited by the NO synthesis inhibitor N(G)-monomethyl-L-arginine (10(-5)-10(-3) M) and by tamoxifen (10(-8)-10(-4) M) (p < 0.001 in each case). CONCLUSIONS: Oestrogen and progesterone have a role in stimulating NO production in T47D breast cancer cells. Inhibition of NO synthesis might be a novel therapeutic approach for reducing hormone-associated angiogenesis in breast cancer.

The effect of augmenting portal venous inflow on intrahepatic pressure and resistance in the isolated perfused porcine liver.

BACKGROUND/AIMS: The literature regarding the relationship between portal venous flow and pressure is controversial. The aim of this study was to examine the effects of doubling portal venous inflow on hepatic hemodynamics. METHODOLOGY: Portal venous pressure, intrahepatic portal venous resistance, hepatic arterial pressure and intrahepatic arterial resistance were assessed during basal portal venous inflow (756 +/- 142 mL/min; mean +/- SD) and enhanced portal venous inflow (1512 +/- 284 mL/min) in an isolated perfused normal porcine liver model (n = 6). Hepatic arterial flow was maintained constant throughout the experiments. RESULTS: During the period of enhanced portal venous flow there was an increase in: portal venous pressure (from 9 +/- 2 to 22 +/- 7 mm Hg, P = 0.0076); the difference between portal venous and hepatic venous pressures (from 2 +/- 2 to 10 +/- 5 mm Hg; P = 0.0289); hepatic arterial pressure (from 84 +/- 9 to 151 +/- 33 mm Hg, P = 0.0019); and intrahepatic arterial resistance (from 0.3488 +/- 0.0637 to 0.6387 +/- 0.2020, P = 0.0046). CONCLUSIONS: The increases in hepatic artery pressure and intrahepatic arterial resistance are a result of the hepatic arterial 'buffer response', a phenomenon not previously demonstrated in vitro. The magnitude of the observed changes in portal venous and hepatic venous pressure leads to the conclusion that, in the porcine liver, the intrahepatic venous resistance sites react by constricting to increases in portal venous inflow.

Hepatic ischemia-reperfusion injury.

BACKGROUND: The morbidity associated with liver transplantation and major hepatic resections is partly a result of ischemia-reperfusion injury. DATA SOURCES: The entire world literature on the subject was searched via Medline. Keywords included reperfusion injury, transplantation, liver resection, nitric oxide, endothelin, cytokines, Kupffer cells, ischemic/ischaemic preconditioning, and nuclear factor-kappa B. CONCLUSIONS: An imbalance between endothelin and nitric oxide levels results in failure of the hepatic microcirculation at the onset of reperfusion. Activation of nuclear factor-kappa B in the liver promotes proinflammatory cytokine and adhesion molecule synthesis. These result in oxygen-derived free radical production and neutrophil recruitment, further contributing to cellular injury. Various therapeutic modalities acting on the above mediators have been successfully used to attenuate reperfusion injury in animal models of hepatic transplantation and resection. Application of the knowledge gained from animal models of hepatic ischemia-reperfusion to the clinical setting will improve the outcome of hepatic surgery.

Nitric oxide induction in a rat model of selective pancreatic ischemia and reperfusion.

BACKGROUND/AIMS: Ischemia and reperfusion of the pancreas may be important in aggravating the course of acute pancreatitis. In a rat model of selective pancreatic ischemia and reperfusion, we studied plasma levels of nitric oxide and expression of nitric oxide synthase in the pancrease and lung. METHODOLOGY: Pancreatic ischemia was achieved by occlusion of the 4 main pancreatic arteries for 40 min; this was followed by a 7-hour reperfusion period (group A, 10 rats). Outcome measures were compared with those of animals undergoing a sham operation (group B, 10 rats). RESULTS: Pancreatic damage in group A animals was demonstrated by increased serum alpha-amylase and by macroscopic and microscopic evidence. Total nitric oxide synthase activity in pancrease and lung was higher than in shams [median: 0.73 vs. 0.54 pmol/mg protein/min in the pancreas (P = 0.0082); 1.38 vs. 0.68 pmol/mg protein/min in the lung (P = 0.023)]; this was mainly due to activation of the inducible isoform of the enzyme. There was an associated 58.2% increase in plasma levels of nitric oxide metabolites [from mean 55.0 to 131.6 mumol/L (P < 0.001)]. Immunohistochemistry confirmed expression of inducible nitric oxide synthase and nitric oxide-mediated oxidative damage (nitrotyrosine) in both pancreas and lung. CONCLUSIONS: Ischemia and reperfusion of the pancreas induces pancreatic damage, overexpression of inducible nitric oxide synthase and oxidative damage within the pancreas and lung.

Portal flow augmentation for liver cirrhosis.

BACKGROUND: Portal hypertension due to chronic liver disease is a major cause of death worldwide. Orthotopic liver transplantation offers the best therapeutic option but is available to only a minority of patients. In the past few years mechanically pumping portal venous inflow has been reported to reduce portal hypertension and improve liver function. METHODS: A review of the published data on augmented portal perfusion for the treatment of portal hypertension in cirrhosis was carried out by searching Medline and other online databases. From each published study portal pressure and blood flow data before and after augmented portal perfusion were used to calculate the change in mean intrahepatic portal vascular resistance (IHPR). The standardized data were then combined to allow meta-analysis. RESULTS: Seven papers were identified on normal and cirrhotic animal and human livers with augmented flow (50% to fourfold over baseline) for 30-180 min. Meta-analysis revealed that the increased portal venous inflow was associated with a significant rise in portal venous pressure on the hepatic side (P < 0.001), a significant reduction on the mesenteric side (P < 0.001) and a significant reduction in IHPR (P = 0.013). Limited data were available to support improved liver function. CONCLUSION: Detailed in vivo cirrhotic liver studies on augmented portal flow in experimental models assessing haemodynamic and functional changes are required before clinical evaluation.

Attenuation of reperfusion injury by renal ischaemic preconditioning: the role of nitric oxide.

OBJECTIVE: To determine the effect on nitric oxide (NO) release and renal NO synthase (endothelial, eNOS and inducible, iNOS) activity of renal ischaemia-reperfusion (I/R) in vivo in an animal model, and to examine the possible involvement of NO in ischaemic preconditioning (IP) of the kidney. MATERIALS AND METHODS: In a right-nephrectomized rat model, 42 animals were randomized in four groups: controls; IP-only (4 min of ischaemia followed by 11 min of reperfusion, total of four cycles); renal warm ischaemia (45 min) and 6 h reperfusion; ischaemia (45 min) preceded by IP pretreatment. Serum NO metabolites were assayed 2 and 6 h after ischaemia or the control equivalent. NOS expression in the kidney was detected immuno-histochemically, and damage assessed morphologically in sections stained with haematoxylin and eosin. Kidney function was assessed by the levels of serum creatinine, urea and electrolytes. RESULTS: Compared with before ischaemia, the concentration of serum NO metabolites at 6 h was increased in the IP-only animals (P = 0. 016) and in the IP + I/R group (P = 0.002). There was greater eNOS expression in the IP-only group (P = 0.009) and in the IP + I/R group than in controls (P = 0.050). iNOS expression was greater in the IP-only animals than in the control group (P = 0.050). Histological assessment showed less evidence of cellular damage in IP + I/R animals than in the I/R-alone group (P = 0.020). Serum creatinine level was not significantly different between the IP-only group and the control. There were no differences after 2 h of reperfusion. CONCLUSION: Ischaemic preconditioning has a protective effect on renal structure and function, which may be produced by increased NO release arising from increased NOS expression by 6 h after reperfusion.

Nitric oxide and hepatic ischemia-reperfusion injury.

A number of surgical maneuvers require a period of liver ischemia. On reperfusion, hepatic injury results from a failure of the microcirculation and an excessive inflammatory response. Within the liver, sinusoidal cells produce a basal level of nitric oxide from endothelial nitric oxide synthase activity. During the early reperfusion period, increased concentrations of cytokines and oxygen free radicals result in expression of the inducible form of nitric oxide synthase, via activation of nuclear transcription factor-kappa B, in hepatocytes and Kupffer cells. This results in increased production of nitric oxide after 4 to 6 h from the onset of reperfusion. Nitric oxide generation attenuates the inflammatory response by counteracting endothelin, reducing inflammatory cell activity and decreasing the expression of cytokines and adhesion molecules. In animal models, therapeutic strategies that increase endogenous nitric oxide concentrations in the liver significantly decrease reperfusion injury. Such treatment modalities may have important clinical implications for the future, particularly in view of the increasing use in hepatic transplantation programs of marginal donor livers with their greater susceptibility to ischemia-reperfusion injury.