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Aims To examine the role of baseline depression, anxiety and stress symptoms on post-intervention diabetes self-efficacy and glycaemic control (HbA1c). Methods The current study analysed data from patients (n = 85) with treated but uncontrolled Type 2 diabetes who participated in a comparative effectiveness study of two diabetes self-management interventions. Hierarchical linear regression was used to examine the relationships between baseline affective symptoms and post-intervention diabetes self-efficacy and the moderating effects of baseline affective symptoms on the relationship between changes in diabetes self-efficacy and post-intervention HbA1c. Results Baseline depression was inversely associated with post-intervention diabetes self-efficacy (P = 0.0001) after adjusting for baseline characteristics including diabetes self-efficacy. In contrast, normal–mild levels of stress were associated with higher post-intervention diabetes self-efficacy (P = 0.04). Anxiety and stress symptoms significantly and independently moderated the relationship between changes in diabetes self-efficacy and post-intervention HbA1c (P = 0.02 and P = 0.03, respectively). Further evaluation of these interactions demonstrated that changes in diabetes self-efficacy were associated with lower post-intervention HbA1c, but only among those with higher baseline affective symptoms. Conclusions We found a moderating effect across affective symptoms on the relationship between diabetes self-efficacy changes and post-intervention HbA1c in the context of a self-management intervention. Results suggest that patients with poorly controlled diabetes who have higher levels of depression, anxiety and stress symptoms may derive greater benefits from self-management interventions known to improve diabetes self-efficacy.

Background Microwave ablation is an in situ method of tumour destruction used to treat patients with unresectable liver tumours. A new microwave generator and probe, designed to deliver high energy into solid tumours quickly has been developed at our institution. We report the results of its use in patients with unresectable liver tumours treated by a single surgeon in a single institution. Methods Thirty-one patients with 89 unresectable liver tumours were recruited into the study and underwent microwave ablation in a single procedure. Results There were no post-operative complications. At a median of 24 months post ablation, 15 patients were alive with 7 patients disease free. At a median of 26 months, 8 patients were alive with tumour recurrence but only 1 with local recurrence. The remaining 7 patients with recurrence were found to have new disease at locations remote from the ablation site. Fourteen patients died of disease progression at a median survival of 15 months, with only 1 patient with local and remote tumour recurrence. Of the total numbers of tumours treated (n = 89), a local tumour recurrence rate of 2% was observed. Overall median survival was 29 months with 3 year survival of 40%. Discussion Microwave tissue ablation using this novel generator and probe has a low local recurrence and complication rate. Overall survival is comparable to alternative ablation modalities and its ability to treat, even large tumours, with a single insertion of the probe makes it an extremely attractive treatment option.

Aims Surgical resection of combined hepatic and pulmonary metastases remains controversial in light of limited supportive evidence. This study aimed to audit our initial experience with this aggressive surgical strategy. Methods Between 1997 and 2006 we assessed 19 patients with colorectal cancer metastases for combined liver and lung metastasectomy, of whom 16 patients underwent surgery. We retrospectively reviewed perioperative and survival data. Results Synchronous liver metastases were present in three out of 16 patients at time of diagnosis of the primary tumour, and one out of 16 patients had synchronous lung and liver metastases with the primary tumour. Of those 12 patients who developed metachronous metastases five patients developed liver metastases first, one patient developed pulmonary metastases first, and six patients developed synchronous liver and lung metastases. Thirty nine operations were performed on 16 patients. The median hospital stay was 5.5 (2–10) days for the pulmonary and 7 (1–23) days for the hepatic resections. There were no in-hospital deaths. Chemotherapy was given to five patients prior to metastasectomy and nine received adjuvant chemotherapy following metastasectomy. Median survival from diagnosis of metastatic disease was 44 months (8–87 months). Estimated 1-year survival from diagnosis of metastatic disease was 94%, estimated 5-year survival was 20%. Conclusion We believe an aggressive but selective surgical approach to combined hepatic and pulmonary colorectal metastases is justified by limited resource requirements and encouraging survival.

Primary human hepatocytes are clinically used for transplantation or in bioartificial liver devices for the treatment of patients with liver failure. We aimed to assess whether an organ preservation solution containing trehalose, namely ET-Kyoto solution (ETK), could improve human liver cell viability when used for cryopreservation in comparison to the University of Wisconsin solution (UW). Our study showed beneficial effects of ETK when used in combination with other cryoprotectants on the viability of thawed hepatocytes. Indeed, no significant difference was seen between the viability of freshly isolated cells and cryopreserved cells when cryopreserved with ETK combined with other cryoprotectants. In contrast, a significant decrease of viability was observed in cells cryopreserved with UW or ETK combined with dimethysulfoxide (DMSO) only, or with UW combined with other cryoprotectants, compared to freshly isolated cells. No significant difference was observed between the four different groups of cryopreserved hepatocytes with regards to cell recovery rate or cell attachment after thawing. However, a significant decrease in cell metabolic activity was found in cells cryopreserved with UW 10% DMSO compared to the other groups. In conclusion, our study confirms the beneficial effect of ETK for the cryopreservation of human hepatocytes in combination with other cryoprotective agents.

Seroma are common early postoperative complications encountered in laparoscopic inguinal hernia repair. Previous anecdotal evidence from our surgical practice suggested a lower incidence of postoperative seroma formation with direct hernia repairs when the lax transversalis fascia (TF) is inverted by tacking to the pubic ramus. We undertook a study to investigate whether TF inversion in this way reduces the incidence of postoperative seroma.A total of 216 patients undergoing transabdominal preperitoneal (TAPP) laparoscopic inguinal hernia repairs from August 2003 to December 2005 were included in this prospective non-randomised controlled study. Surgeon 1 would routinely invert the TF whereas surgeon 2 would not. At follow-up the presence of postoperative seroma and pain was recorded.Mann-Whitney U test demonstrated no significant difference in terms of age, sex and time to follow-up between the surgeons' patient groups (P0.05), and Chi-square test demonstrated significantly that inversion of the TF is associated with a lower incidence of postoperative seroma (P0.05). There was no significant difference in terms of postoperative pain at follow-up.Inversion of the TF is associated with a statistically lower incidence of postoperative seroma, without increasing postoperative pain despite the use of one or two additional tacks.

INTRODUCTION The management of bile leaks following laparoscopic cholecystectomy has evolved with increased experience of ERCP and laparoscopy. The purpose of this study was to determine the impact of a minimally invasive management protocol. PATIENTS AND METHODS Twenty-four patients with a bile leak following laparoscopic cholecystectomy were recorded consecutively between 1993 and 2003. Between 1993–1998, 10 patients were managed on a case-by-case basis. Between 1998–2003, 14 patients were managed according to a minimally invasive protocol utilising ERC/biliary stenting and re-laparoscopy if indicated. RESULTS Bile leaks presented as bile in a drain left in situ post laparoscopic cholecystectomy (8/10 versus 10/14) or biliary peritonitis (2/10 versus 4/14). Prior to 1998, neither ERC nor laparoscopy were utilised routinely. During this period, 4/10 patients recovered with conservative management and 6/10 (60%) underwent laparotomy. There was one postoperative death and median hospital stay post laparoscopic cholecystectomy was 10 days (range, 5–30 days). In the protocol era, ERC ± stenting was performed in 11/14 (P = 0.01 versus pre-protocol) with the main indication being a persistent bile leak. Re-laparoscopy was necessary in 5/14 (P = 0.05 versus preprotocol). No laparotomies were performed (P < 0.01 versus pre-protocol) and there were no postoperative deaths. Median hospital stay was 11 days (range, 5–55 days). CONCLUSIONS The introduction of a minimally invasive protocol utilising ERC and re-laparoscopy offers an effective modern algorithm for the management of bile leaks after laparoscopic cholecystectomy.

Context: The physical hazards of farming have been extensively studied and reported upon. Far less studied are the social and emotional impacts of farmwork injuries and deaths. Purpose: To investigate and document broad but targeted issues regarding the impact on individuals, families, and communities of farmwork injuries and fatalities of farmer leaders. Methods: Ten incidents of farmwork injuries with disabilities or fatalities in Pennsylvania were used for a collective case study. Data were collected through a total of 47 interview sessions with 66 individuals including next of kin, other family members, injured persons, and community members. Thematic analysis was used to identify themes and issues in this descriptive study. Findings: Community members missed the rich, broad, and comprehensive skills, abilities, and perspectives that farmers brought to community service. Participants expressed that the community assistance and support provided to injured persons and families benefited not only the injured persons and their families and farms but also the community members. Participants reported emotional anguish and loss as well as positive transformations and consequences. As expressed by participants, God and religion play an important role in their beliefs regarding the occurrence and outcome of farmwork injury incidents. Conclusions: Social and emotional impacts on individuals, families, and communities are varied and multileveled. The role that religion and storytelling play in the process of dealing with serious injury incidents raises questions regarding agricultural injury prevention.

Background. An effective therapy is needed for patients with surgically unresectable liver tumors who have very limited life expectancy. One possible treatment is electrochemical tumor necrosis. This study investigated the natural history of electrochemical lesions in the normal rat liver. Materials and methods. A direct current generator, connected to platinum electrodes, was used to create controlled areas of liver necrosis. Animals were sacrificed 2 days, 2 weeks, 2 months, and 6 months after treatment and the macroscopic and histological appearance of the necrotic lesions was followed. Results. No animal died as a result of electrolysis; postoperatively, all gained weight normally. Liver enzymes were significantly (P < 0.001) elevated after treatment, but returned to normal after a week. Two days after electrolysis, histology confirmed an ellipsoidal area of coagulative necrosis at the site of the electrode tip and commonly a segment of peripheral necrosis. After 2 weeks there was histological evidence of healing. By 6 months, very little necrotic tissue remained within a small fibrous scar. Conclusions. Electrolysis is a safe method for creating defined areas of liver necrosis that heal well with no associated mortality. This study supports the potential of electrolysis for treating patients with unresectable liver tumors.

Background One of the most promising but unexplored methods for treating patients with irresectable liver tumours is electrolysis. This study examined the effect of increasing ‘current dose’ on the volume of the lesion induced in normal rat liver. Methods A direct current generator, connected to platinum electrodes implanted in the rat liver, was used to examine the effect of (1) varying current doses from 1 to 5 coulombs and (2) electrode separation (2 or 20 mm), on the volume of liver necrosis. Results There was a significant correlation (P < 0·001) between the current dose and the volume of necrosis produced for each electrode separation. Placing the electrodes 2 mm apart resulted in smaller total volumes of necrosis than placing them 20 mm apart when anode lesions were significantly larger than cathode lesions (P < 0·05). Liver enzymes (aspartate aminotransferase, alanine aminotransferase) were significantly raised 1 day after treatment (P < 0·001) and predicted the total volume of hepatic necrosis (P < 0·001). Conclusion Predictable and reproducible areas of liver necrosis are produced with electrolysis. If these results extrapolate to larger animal models, this technique has potential for patients with irresectable primary and secondary liver tumours.

Background Unilateral neck exploration for sporadic parathyroid adenomas remains a contentious policy. The morbidity is lower than for bilateral surgery, but the long-term outcome may be inferior. Methods The results of a policy of unilateral neck exploration for primary hyperparathyroidism based on preoperative localization are reviewed. Results Over a 10-year period, 89 patients were operated on, 57 undergoing unilateral neck exploration. Unilateral neck exploration significantly reduced operative time ( P P = 0.021). Over a mean biochemical follow-up of 38 months, recurrent hypercalcaemia occurred in 6% of patients, including 3.5% of those undergoing unilateral neck exploration, an additional 10% of patients were normocalcaemic with an inappropriately elevated parathormone level. Conclusions A policy of unilateral neck exploration can achieve comparable long-term results to more extensive bilateral surgery.

Laparoscopic surgery for the definitive treatment of gastroesophageal reflux (GOR) has become an accepted alternative to conventional techniques in adults. Although relatively rare, GOR in children represents an important clinical entity with symptoms including failure to thrive, nocturnal dyspnea, and vomiting. This paper details our experience in eight children who have undergone a laparoscopic Nissen fundoplication for failed medical treatment of severe GOR. Particular attention is paid to technical aspects of the procedure and the differences between adult and pediatric techniques are emphasized. The preliminary results suggest that a laparoscopic Nissen fundoplication is a safe procedure which significantly improves reflux symptoms in children and that these results are comparable to those obtained with conventional surgery.

The records of 149 patients who underwent testicular exploration for suspected malignancy were reviewed retrospectively. Malignancy was confirmed in 102 patients but benign pathology was noted in 47. Patients with benign disease were older, more likely to be Asian, gave a longer history and on examination were less likely to have a testicular mass. Increased levels of tumour markers, and ultrasonographic and operative appearance of the testis were highly predictive; with ultrasonography having a sensitivity of 100 per cent but a specificity of only 36 per cent for malignancy. Preoperative ultrasonography and an awareness of the potentially benign nature of many lesions with the use of frozen-section biopsy, where appropriate, may allow a decrease in the currently high rate of unnecessary orchidectomy without missing testicular malignancy.

Leflunomide (LEF) is a novel immunomodulator which has been reported to be efficacious in experimental models of systemic autoimmune diseases and in treating rheumatoid arthritis in man. Leflunomide's ability to ameliorate ocular disease processes was investigated in a model of autoimmune eye disease, experimental autoimmune uveitis (EAU). EAU was induced by the injection of retinal S-antigen (S-Ag) into the foot-pad of Lewis rats. Leflunomide, or the reference compound cyclosporin A (CSA), was administered orally or topically (to one eye) each day beginning on the day of S-Ag injection. Drug efficacy was measured by the suppression in clinical signs of ocular inflammation and confirmed by histology. Both oral and topical ocular treatment with LEF suppressed the ocular disease signs and symptoms and retinal necrosis and reduced the S-Ag antibody levels associated with EAU in a dose-dependent manner. Both LEF and CSA were able to inhibit totally the disease manifestations of EAU; however, a comparison of the IC50 and IC90 values indicate that LEF is more potent than CSA in inhibiting EAU. These results suggest that leflunomide may be useful for treating autoimmune diseases of the eye.

A simple modification for securing the omental patch during laparoscopic oversewing of perforated duodenal ulcers is presented. This new concept uses color coding of sutures to prevent confusion and suture "cut-out" during the tie-over of the omental patch. The concept of suture color-coding may be applicable to other laparoscopic procedures where identification of "suture pairs" is difficult.

To determine whether playing a wind or brass musical instrument is associated with reduced snoring or daytime fatigue.Cross-sectional, controlled, anonymous, questionnaire-based observational study.Rehearsal and performance halls.Three hundred and forty musicians from Scotland's five professional orchestras.Snore Outcomes Survey questionnaire and the Epworth Sleepiness Score.Hierarchical linear regression analysis.No significant difference was found between the snoring severity (Snore Outcomes Survey score) or daytime sleepiness (Epworth score) of wind/brass and other professional musicians. A regression model with snoring severity (Snore Outcomes Survey score) as the dependent variable and the three covariates of gender, age and body mass index as independent variables was significant [F(3, 206) = 28.77, P0.01, adjusted r(2) = 0.285]. Increasing age, body mass index and male gender were all significantly associated with lower Snore Outcomes Survey scores (i.e. worse snoring).The addition of instrument type did not significantly increase the fit of the model, and the regression coefficient for instrument type was not significant. There were similar results when the Epworth Sleepiness Score was used as the dependent variable.This study demonstrated no significant difference between the snoring severity or daytime sleepiness of brass/wind players and other professional orchestral musicians. This result may have been attributed to comparatively low levels of snoring/daytime sleepiness in the population studied. The findings contrast with previous studies examining the effects of singing and didgeridoo playing but concur with a recent similar study of orchestral musicians. A prospective interventional study would be required to determine whether playing a wind or brass instrument improves these variables in patients complaining of disruptive snoring.

The antiallergic compound, lodoxamide, was evaluated for its abilities to attenuate a local allergic reaction in rat conjunctiva in vivo and to inhibit rat conjunctival mast cell mediator release in vitro. Topically applied lodoxamide (0.01, 0.10 and 1.0%, w/v) dose-dependently reduced the allergic response (23, 43 and 72%, respectively) in vivo. Lodoxamide was more effective than cromolyn sodium, N-acetyl aspartyl glutamic acid (Naaxia) and levocabastine, and 25 (7-200) times more potent than nedocromil sodium in direct comparisons. Addition of lodoxamide (10 micrograms/ml) to sensitized conjunctival tissue in vitro immediately prior to antigen challenge significantly reduced the amount of histamine released by the tissue. These data suggest that lodoxamide's in vivo anti-allergic activity in the conjunctiva is associated with its ability to prevent allergic mediator release from mast cells contained in this same tissue.

The aetiology of urethral strictures in patients catheterised for short periods at the time of surgery is the subject of some debate. The occurrence of epidemics of strictures associated with certain batches of latex catheters, and the demonstrable in vitro cytotoxicity of latex in general, have supported the suggestion that catheter material (and in particular latex) has an important role. We have looked retrospectively at 299 patients undergoing transurethral resection of the prostate gland by 1 urologist, 135 of whom had a latex catheter and 164 a plastic one; 19 patients developed strictures over the next 12 months with no proven difference attributable to the catheter material. The study provides no evidence that the short-term use of latex catheters is associated with stricture formation.

Oesophageal intubation occasionally fails to palliate inoperable carcinoma: some tumours are unsuitable for this procedure and others overgrow the tube. This study reports a series of nine patients (median age 79 (range 55–87) years) in whom the argon beam monopolar coagulator via a flexible endoscopic probe was used to ablate such tumours. Fourteen ablation procedures were performed. The endoscope was passed to the stomach at the end of each procedure. There were no complications; the median hospital stay was 2 (range 1–13) days. Thirteen procedures rendered the patients completely asymptomatic for a median of 6 (range 4–12) weeks. Six patients died a median of 14 (range 4–38) weeks after the first ablation, reflecting their limited life expectancy. The argon beam coagulator provides an effective alternative to laser ablation, being considerably cheaper and safer, while maintaining the minimally invasive nature of the palliation.

Electrolytic ablation is a relatively new method for the local destruction of colorectal liver metastases. Experimental work in animal models has shown this method to be safe and efficacious. However, before proceeding to clinical trials it was necessary to confirm these findings in a pilot study of five patients.Five patients with colorectal liver metastases were studied prospectively. Each patient underwent a potentially curative liver resection. One of the metastases to be removed was treated using electrolysis before resection. Each patient was monitored closely during and after electrolysis to determine any morbidity associated with the treatment. Once resected, the metastases were examined histologically for completeness of ablation.All patients tolerated the electrolysis well; there were no deaths or complications related to the treatment. Histological examination of the resected metastases which had been treated electrolytically showed complete tissue destruction with no viable malignant cells remaining at the site of treatment.This pilot study of electrolytic ablation of liver metastases in five patients showed the treatment to be well tolerated and safe. Additionally, it demonstrated total destruction of the malignant tissue at the site of electrolysis. Based on these encouraging results, clinical trials can now begin.

Background/Aims: Patients with unresectable malignant liver tumours have a poor prognosis. A technique is needed which improves long-term survival. Previous studies in the rat have shown that electrolysis is a safe, predictable and reproducible method for creating areas of necrosis in the normal rat liver. This study examined the effects of electrolysis on colorectal liver ‘metastases’ in the rat. Methods: Tumours of colorectal origin were implanted into the livers of Wistar-WAG rats. Two weeks after implantation the tumours were treated with electrolysis. A direct current generator, connected to 2 platinum intrahepatic electrodes was used to examine the effects of various electrode configurations on the extent of tumour necrosis. Results: Significant (p

Summary Gallbladder disease due to stones is well recognised as falling into two categories, presenting with either chronic symptoms or developing acute cholecystitis or other complications. We describe an intermediate group of 14 patients (11 women, three men, median age 31 years) presenting with 4–14 days of at least daily attacks of resolving biliary colic, who underwent early laparoscopic cholecystectomy within 24 hours of presentation. None had any evidence of acute inflammation, either at laparoscopy or on histology. Their surgery was straightforward with operating times ranging from 35-80 minutes and no complications. Patients with ‘crescendo biliary colic’ are often young women who can rarely afford invalidity. Rather than the current practice of analgesia for each attack and elective surgery weeks later, they are optimally managed by urgent laparoscopic cholecystectomy, preventing the development of complications and minimising the need for further medical involvement.

Cholecystectomy is the most common surgical procedure performed in sickle cell anemia (SCA) patients. We investigated the effects of transfusion and surgical method on perioperative outcome. A total of 364 patients underwent cholecystectomy: group 1 (randomized to aggressive transfusion) 110 patients; group 2 (randomized to conservative transfusion) 120 patients; group 3 (nonrandomized nontransfusion) 37 patients; and group 4 (nonrandomized transfusion) 97 patients. Patients were similar except group 3 patients were more likely to be female, over 20 years old, smokers, and more healthy by American Society of Anesthesiologists (ASA) physical status score. Total complication rate was 39%: sickle cell events 19%; intraoperative or recovery room events 11%; transfusion complications 10%; postoperative surgical events 4%; and death 1%. Group 3 patients had the highest incidence of sickle cell events (32%). Open cholecystectomies were performed in 58% and laparoscopic in 42%. Laparoscopic patients were younger and more healthy by ASA score. Laparoscopic patients had longer anesthesia time (3.2 v 2.9 hours), but shorter hospitalization time (6.4 days v 9.8). Complications were similar between these two groups. We conclude that SCA patients undergoing cholecystectomy have a high perioperative morbidity, and the incidence of sickle cell events may be higher in patients not preoperatively transfused. We recommend a conservative preoperative transfusion regimen, and we encourage the use of the laparoscopic technique for SCA patients undergoing elective cholecystectomy.

Thoracoscopically assisted Ivor-Lewis oesophagectomy potentially combines the pulmonary advantages of transhiatal oesophageal dissection, with the visibility and control permitted by thoracotomy. This study reviewed 17 patients who underwent this procedure with an intrathoracic anastomosis. Five patients required conversion to thoracotomy, four because of technical difficulties with the anastomosis. After operation 13 patients had radiological evidence of atelectasis, six developed a left pleural effusion and five had clinically significant pneumonia. Three patients developed an anastomotic leak, two of whom died giving an in-hospital mortality rate of 12 per cent. Median postoperative hospital stay was 12 days. Four patients developed benign anastomotic strictures requiring dilatation. The 1- and 2-year survival rates were 73 per cent (11 of 15 patients) and 63 per cent (five of eight) respectively. The use of minimal access techniques in this context does not appear to reduce the postoperative incidence of either pulmonary or anastomotic complications.

The treatment of achalasia by laparoscopic Heller's cardiomyotomy may combine the minimally invasive advantages of pneumatic dilatation with the success rate and low risk of perforation of conventional surgery. The requirement for an antireflux procedure remains a contentious issue, as in conventional surgery. Nine patients underwent laparoscopic cardiomyotomy; excellent symptomatic relief was obtained in eight at follow-up between 12 and 21 months after operation. Four of these patients agreed to 24-h pH monitoring and showed no evidence of acid reflux. One patient, however, developed recurrent symptoms associated with significant acidityi on monitoring. Laparoscopic Heller's cardiomyotomy without an antireflux procedure produced effective symptomatic relief in this small group of patients.

This report describes the case of a 38-year-old man who, although he had undergone bilateral orchiopexy for cryptorchism at age 13 that had resulted in an atrophic left testis, had produced 2 children. An orchiectomy of the atrophic left testis, and a right vasectomy were performed. Histology confirmed the specimen as vas deferens and the testis as atrophic. However, motile spermatozoa were present in postoperative semen analyses nine months later. A second exploration found that the vas from the remaining "right" testis penetrated the scrotal septum and arose from the left side. It became obvious that he had undergone bilateral Ombredanne procedures at age 13. in which both testes were brought through the scrotal septum and placed on the opposite side. Following such a procedure, it is rarely evident that the testis is on the wrong side of the scrotum after 1-2 years. Because of this, greater care is required in vasectomies on men who have previously undergone orchiopexy.

Increasing demand for blood during elective surgery has led to attempts to rationalize routine preoperative crossmatching to those operations when there is a reasonable (greater than 30%) chance of it being required. Results of a questionnaire returned by 86% of the urology units in Great Britain show that 41% continue to crossmatch 2 units of blood before transurethral prostatectomy.A review of 301 transurethral prostatectomies performed with preoperative grouping and saving of blood showed that only 11% of the patients required transfusion. The need for transfusion was significantly associated with presentation in chronic or acute on chronic retention (p

The effect of a dose of alcohol on the kinetics of mandelic acid excretion in four volunteers exposed to 220 mg/m3 styrene has been investigated under controlled exposure chamber conditions. Ethanol inhibited the excretion of mandelic acid, so that the peak excretion was delayed from the end of the exposure period until three hours afterwards. One hour after administration of ethanol blood mandelic acid concentrations were 56% of the levels found during the alcohol-free control exposure, and this was paralleled by a 15-fold rise in phenylethane 1,2 diol, the metabolic precursor of mandelic acid. It is suggested that the inhibition of the oxidation of this diol is related to the change in NAD +/NADH ratio produced by ethanol metabolism. The implications of this ethanol effect on the interpretation of urinary mandelic acid excretion when monitoring workers exposed to styrene are discussed.

Infusion of the thromboxane A2 analogue U-46619 into isolated perfused rat livers resulted in dose-dependent increases in glucose output and portal vein pressure, indicative of constriction of the hepatic vasculature. At low concentrations, e.g. less than or equal to 42 ng/ml, glucose output occurred only during agonist infusion; whereas at concentrations greater than or equal to 63 ng/ml, a peak of glucose output also was observed upon termination of agonist infusion coincident with relief of hepatic vasoconstriction. Effluent perfusate lactate/pyruvate and beta-hydroxybutyrate/acetoacetate ratios increased significantly in response to U-46619 infusion. Hepatic oxygen consumption increased at low U-46619 concentrations (less than or equal to 20 ng/ml) and became biphasic with a transient spike of increased consumption followed by a prolonged decrease in consumption at higher concentrations. Increased glucose output in response to 42 ng/ml U-46619 was associated with a rapid activation of glycogen phosphorylase, slight increases in tissue ADP levels, and no increase in cAMP. At 1000 ng/ml, U-46619 activation of glycogen phosphorylase was accompanied by significant increases in tissue levels of AMP and ADP, decreases in ATP, and slight increases in cAMP. In isolated hepatocytes, U-46619 did not stimulate glucose output or activate glycogen phosphorylase. Reducing the perfusate calcium concentration from 1.25 to 0.05 mM resulted in a marked reduction of the glycogenolytic response to U-46619 (42 ng/ml) with no efflux of calcium from the liver. U-46619-induced glucose output and vasoconstriction displayed a similar dose dependence upon the perfusate calcium concentration. Thus, U-46619 exerts a potent agonist effect on glycogenolysis and vasoconstriction in the perfused rat liver. The present findings support the concept that U-46619 stimulates hepatic glycogenolysis indirectly via vasoconstriction-induced hypoxia within the liver.

SUMMARYStudies of the growth and composition of Q-strain mice selected over 20 generations for high and low body weight at 6 weeks of age, and their unselected controls, were made on livers and kidneys of males from the five selection replicates A, B, C, D and F. Differences in growth rate between Large and Small QD mice were confirmed from 2 to 9 weeks of age, but were greatest in the third, fourth, sixth and seventh weeks. Total amounts of dry matter, protein, free amino acids, bulk RNA and ribosomes were increased or decreased from control values in proportion to organ weight. A less-perfect relationship between DNA content and organ weight suggested that some small changes in average cell mass had accompanied the main change in cell number in organs from the selected lines. Absorbance profiles of polyribosomes from both organs were identical in selected and control mice: selection had not operated on the proportion of single (currently inactive) ribosomes. Attempts to relate the observed differences in growth rate in QD mice to differences in the rate of protein synthesis produced an unexpected result: incorporation of radioactively labelled amino acids was consistently higher in the organs of the Small mice. Measurements of rates of protein turnover, and calculated rates of protein degradation, suggested that protein might also be degraded more rapidly in the small mice.

Infusion of adenosine into perfused rat livers resulted in transient increases in glucose output, portal-vein pressure, the effluent perfusate [lactate]/[pyruvate] ratio, and O2 consumption. 8-Phenyltheophylline (10 microM) inhibited adenosine responses, whereas dipyridamole (50 microM) potentiated the vasoconstrictive effect of adenosine. The order of potency for adenosine analogues was: 5′-N-ethylcarboxamidoadenosine (NECA) greater than L-phenylisopropyladenosine greater than cyclohexyladenosine greater than D-phenylisopropyladenosine greater than 2-chloroadenosine greater than adenosine, consistent with adenosine actions modulated through P1-purine receptors of the A2-subtype. Hepatic responses exhibited homologous desensitization in response to repeated infusion of adenosine. Adenosine effects on the liver were attenuated at lower perfusate Ca2+ concentrations. Indomethacin decreased hepatic responses to both adenosine and NECA. Whereas adenosine stimulated glycogen phosphorylase activity in isolated hepatocytes, NECA caused no effect in hepatocytes. The response to adenosine in hepatocytes was inhibited by dipyridamole (50 microM), but not 8-phenyltheophylline (10 microM). The present study indicates that, although adenosine has direct effects on parenchymal cells, indirect effects of adenosine, mediated through the A2-purinergic receptors on another hepatic cell type, appear to play a role in the perfused liver.

Infusion of adenine nucleotides and adenosine into perfused rat livers resulted in stimulation of hepatic glycogenolysis, transient increases in the effluent perfusate [3-hydroxybutyrate]/[acetoacetate] ratio, and increased portal vein pressure. In livers perfused with buffer containing 50 microM-Ca2+, transient efflux of Ca2+ was seen on stimulation of the liver with adenine nucleotides or adenosine. ADP was the most potent of the nucleotides, stimulating glucose output at concentrations as low as 0.15 microM, with half-maximal stimulation at approx. 1 microM, and ATP was slightly less potent, half-maximal stimulation requiring 4 microM-ATP. AMP and adenosine were much less effective, doses giving half-maximal stimulation being 40 and 20 microM respectively. Non-hydrolysed ATP analogues were much less effective than ATP in promoting changes in hepatic metabolism. ITP, GTP and GDP caused similar changes in hepatic metabolism to ATP, but were 10-20 times less potent than ATP. In livers perfused at low (7 microM) Ca2+, infusion of phenylephrine before ATP desensitized hepatic responses to ATP. Repeated infusions of ATP in such low-Ca2+-perfused livers caused homologous desensitization of ATP responses, and also desensitized subsequent Ca2+-dependent responses to phenylephrine. A short infusion of Ca2+ (1.25 mM) after phenylephrine infusion restored subsequent responses to ATP, indicating that, during perfusion with buffer containing 7 microM-Ca2+, ATP and phenylephrine deplete the same pool of intracellular Ca2+, which can be rapidly replenished in the presence of extracellular Ca2+. Measurement of cyclic AMP in freeze-clamped liver tissue demonstrated that adenosine (150 microM) significantly increased hepatic cyclic AMP, whereas ATP (15 microM) was without effect. It is concluded that ATP and ADP stimulate hepatic glycogenolysis via P2-purinergic receptors, through a Ca2+-dependent mechanism similar to that in alpha-adrenergic stimulation of hepatic tissue. However, adenosine stimulates glycogenolysis via P1-purinoreceptors and/or uptake into the cell, at least partially through a mechanism involving increase in cyclic AMP. Further, the hepatic response to adenine nucleotides may be significant in regulating hepatic glucose output in physiological and pathophysiological states.