Laparoscopic incisional and ventral hernia repair in a district general hospital.

INTRODUCTION: The laparoscopic approach to repairing ventral and incisional hernias has gained increasing popularity worldwide. We reviewed the experience of laparoscopic ventral hernia repair at a district general hospital in the UK with particular reference to patients with massive defects (diameter ≥15cm) and the morbidly obese. METHODS: A total of 144 patients underwent laparoscopic ventral (incisional or umbilical/paraumbilical) hernia repair between April 2007 and September 2012. RESULTS: The prevalence of conversion to open surgery was 2.8%. The prevalence of postoperative complications was 3.5%. Median postoperative follow-up was 30.2 months. A total of 5.6% cases suffered late complications and 2.8% developed recurrence. Thirty-four patients underwent repair of defects ≥10cm in diameter with a prevalence of recurrence of 5.6%. Sixteen patients underwent repair of 'massive' incisional hernia (diameter ≥15cm) with a prevalence of recurrence of 12.5%. Sixteen patients with a body mass index (BMI) ≥40kg/m(2) (range, 40-61kg/m(2)) underwent laparoscopic repair with a prevalence of recurrence of 6.3% (p>0.05 vs BMI <40kg/m(2)). CONCLUSIONS: Laparoscopic ventral hernia repair can be carried out safely with a low prevalence of recurrence. It may have advantages in morbidly obese patients in whom open repair would represent a significant undertaking. Laparoscopic ventral hernia repair may be used in cases of large and massive hernias, in which the risk of recurrence increases but is comparable with open repair and associated with low morbidity.

Cellular and plasma uptake of parenteral omega-3 rich lipid emulsion fatty acids in patients with advanced pancreatic cancer.

BACKGROUND & AIMS: Omega-3 rich fatty acids (n-3FA) have powerful anti-inflammatory and anti-neoplastic properties. Previous studies have investigated plasma and cellular uptake of oral and parenteral n-3FA regimens. These have shown that n-3FA undergo rapid uptake into cells which is sustained for the length of the treatment course. The aim of this study was to investigate long-term uptake of prolonged, regular treatment courses of parenteral n-3FA which has not been previously reported. METHODS: As part of a phase II single-arm trial, patients with advanced pancreatic cancer were treated with gemcitabine plus parenteral n-3FA rich lipid emulsion (up to 100 g) each week for three consecutive weeks with a subsequent rest week. This was repeated for up to six months in total for each patient. Pre-treatment serum and erythrocyte cell membrane (ECM) pellet samples were obtained each week for the entire treatment course of each patient. Post-treatment samples were obtained for the first two cycles only to assess rapid uptake. Fatty acid methyl esters (FAME) were produced and analysed using gas chromatography. FAME proportions as a total of sample lipid composition for each class were plotted and the results analysed using a linear regression coefficient model. RESULTS: There was rapid and significant uptake of EPA and DHA FAME into plasma Non-Esterified Fatty Acids (NEFA) and EPA into ECM pellets in post-treatment samples (median increase of 1.06%, 0.65% and 0.05% respectively). There was significant reduction in n-6 fatty acid FAMEs and DHA in ECM pellets (decrease of 0.31% and 0.8% respectively- p = 0.031 for all). There was significant sustained uptake of EPA and DHA FAME into ECM pellets over the cohort's pooled treatment course with corresponding reduction in the n-6:n-3 ratio. CONCLUSIONS: Prolonged regular parenteral n-3FA administration results in rapid and sustained cellular uptake. This regimen is appropriate for therapies aimed at increasing n-3FA content of cellular membranes and reduction of the n-6:n-3 ratio.

Management and outcome of prosthetic patch infection after carotid endarterectomy: a single-centre series and systematic review of the literature.

OBJECTIVES: Outcomes following prosthetic patch infection after carotid endarterectomy (CEA). METHODS: Retrospective audit and systematic review. RESULTS: 22 patients were treated between January 1992 and April 2012, 5 having undergone their original CEA at another institution. The commonest infecting organism was Staphylococcus. One patient was treated by antibiotic irrigation, one was stented, while 20 underwent debridement and patch excision plus; carotid ligation (n = 3), vein patching (n = 3) or vein bypass (n = 14). There was one peri-operative stroke, but no peri-operative deaths. There were no reinfections at a median follow-up of 54 months. A systematic review identified 123 patients with prosthetic patch infection in the world literature. Thirty-six (29%) presented <2 months, 78 (63%) presented >6 months after the original CEA. Seventy-nine of/87 patients (91%) with a positive culture yielded Staphylococci or Streptococci. Seventy-four patients were treated by patch excision and autologous reconstruction. Four (5%) developed reinfection <30 days, but later reinfections have been reported. Seven of nine patients (78%) undergoing prosthetic reconstruction either died or suffered reinfection. Five patients were treated with a covered stent, none developing reinfection (median followup 12 months). CONCLUSION: Patch infection following CEA is rare. Few have undergone stenting and long term data are awaited. For now, patch excision and autologous reconstruction remains the 'gold standard'.

Nonresectional palliative abdominal surgery for patients with advanced colorectal cancer.

OBJECTIVE: Nonresectional palliative abdominal surgery (e.g. defunctioning stoma/bypass) may be appropriate for patients unsuitable for curative resection, to deal with complications of advanced colorectal malignancy such as obstruction. Our aim was to review the outcome of surgery in these patients within our institution. METHOD: All patients undergoing palliative surgery without resection for colorectal carcinoma between July 1998 and January 2007 were identified from our prospectively compiled colorectal cancer database. Data were extracted related to patients' demographics, presentation, tumour site, operative intervention, complications, oncological therapies, length of hospital stay and postoperative survival. RESULTS: One hundred and ninety-three patients were identified with a median age of 79 years (31-94 years). Fifty per cent were operated on an emergent basis for obstruction or perforation, and 50% on an elective basis. One hundred and sixty-nine patients had defunctioning stomas formed of which 156 were loop stomas. Twenty-four patients underwent bypass procedures. Thirty-day mortality rate was 13.5% and postoperative morbidity rate 47%. Median survival was 247 days, with 1-year survival of 38%. Patients undergoing operation on an emergent basis had poorer long-term survival (127 vs 320 days, P = 0.002). CONCLUSION: Nonresectional palliative abdominal surgery is associated with relatively high morbidity and mortality, particularly when performed in the emergency setting. However, in this patient group with a very poor outlook, it may be offered with reasonable survival expectations.

Combined percutaneous-endoscopic stenting of malignant biliary obstruction: results from 106 consecutive procedures and identification of factors associated with adverse outcome.

BACKGROUND: In patients in whom attempted endoscopic stenting of malignant biliary obstruction fails, combined percutaneous-endoscopic stenting and percutaneous stenting using expandable metallic endoprostheses offer alternative approaches to biliary drainage. Despite the popularity of the percutaneous route, there is no available evidence to support its superiority over combined stenting in this patient group. The objective of this study was to present the short- and long-term results of a large series of combined percutaneous-endoscopic stenting procedures and identify factors associated with adverse outcome. METHODS: Data were retrospectively collected on patients undergoing combined percutaneous-endoscopic biliary stenting for malignant biliary obstruction between January 2002 and December 2006. Short- and long-term outcomes were recorded, and pre-procedure variables correlated with adverse outcome. RESULTS: Combined biliary stenting was technically successful in 102 (96.2%) of 106 patients. Procedure-associated mortality rate was 0%. In-hospital morbidity and mortality rates were 24.5% and 16.7%, respectively, with the majority of deaths resulting from biliary sepsis. Median survival was 100 days, with a 13.7% stent occlusion rate. On multivariable analysis, baseline American Society of Anaesthesiologists (ASA) grade, decreasing serum albumin and increasing leucocyte count were independently associated with in-hospital mortality following combined stenting. CONCLUSION: Combined biliary stenting is associated with short- and long-term outcomes equal to those reported in recent series of percutaneous transhepatic stenting. Randomised control trials, including cost-effectiveness analyses, are required to further compare these techniques. Outcomes following combined stenting may be further improved by early recognition and treatment of sepsis and scrupulous management of co-morbid disease.

Defining ductal anatomy using CT cholangiography in a patient with gallbladder duplication.

Duplication of the gallbladder is a rare congenital abnormality. Pre-operative diagnosis is challenging and, with the almost universal use of laparoscopic cholecystectomy, the scope for missing the second intrahepatic gallbladder is increased. Here we report the use of CT cholangiography to define ductal anatomy successfully in a patient with gallbladder duplication.

Colorectal cancer: presentation and outcome in British South Asians.

AIM: Colorectal cancer (CRC) has a lower incidence in patients of South Asian origin compared with British Caucasians. There are however little data available regarding the demographics of these patients, their presentation and outcome. Leicester has a high South Asian immigrant population, and we aim to define any potential differences in presentation, pathogenesis and outcome between our Caucasian and South Asian ethnic groups. METHOD: All patients of South Asian origin were identified from the Leicester CRC database between June 1998 and April 2007. Data were analysed regarding the patients' demographics, the presentation and treatment details, tumour characteristics and clinical outcome. Data were compared with Caucasian patients from the same database. Patients from an ethnic background other than South Asia or Caucasians were excluded from analysis. RESULTS: 3435 patients were included in the analysis, of which 134 (3.9%) were of South Asian ethnicity. 61.9% of South Asian patients were male compared with 56% of Caucasians. South Asians were significantly younger at presentation (61.4 vs 70.6 years, P < 0.001). South Asian patients had significantly more rectal tumours than their Caucasian counterparts (P = 0.002). South Asian patients were more likely to require initial oncological therapy, and were less likely to have resectional surgery than Caucasians (P = 0.006). Of the patients undergoing resectional surgery, the ASA grade, mode of surgery, tumour characteristics and Dukes' stage were similar. There was no difference in 5-year survival between the South Asian and Caucasian patients. CONCLUSION: Patients of South Asian ethnicity are younger at their age of presentation and have a higher proportion of rectal tumours compared with British Caucasian patients. They are more likely to require initial oncological treatment and are less likely to undergo resectional surgery, therefore suggesting more advanced disease at presentation. Overall 5-year survival is the similar.

Introduction of a day-case laparoscopic cholecystectomy service in the UK: a critical analysis of factors influencing same-day discharge and contact with primary care providers.

INTRODUCTION: The objective of this study was to determine the safety and acceptability of the implementation of a day-case laparoscopic cholecystectomy (LC) service in a large UK teaching hospital, and analyse factors influencing contact with primary care providers. Wide-spread introduction of day-case LC in the UK is a major target of healthcare providers. However, few centres have reported their experience. In the US, out-patient surgery for LC has been reported, though many groups have utilised 24-h observation units to facilitate discharge. Concerns remain amongst surgeons regarding the feasibility and acceptability of the introduction of day-case LC in the UK. PATIENTS AND METHODS: Comprehensive care and operative data were prospectively collected on the first 106 consecutive day-case procedures in our hospital. Postoperative recovery was monitored by telephone questionnaire on days 2, 5 and 14, including complications, satisfaction and general practitioner consultation. RESULTS: A total of 106 patients were admitted for day-case LC, of whom 84% were discharged on the day of surgery. Patient satisfaction rate was 94% in both the successful day-case and the admitted patients. Mean operation time was 62 min, with an average total stay on the day-care unit of 426 min. Training-grade surgeons performed 31% of operations. Both the readmission rate after surgery and rate of conversion to open surgery were 2%. Advice from primary healthcare providers was sought by 33% of patients within the first 14 postoperative days. CONCLUSIONS: Introduction of day-case LC in the UK is feasible and acceptable to patients. The potential burden to primary care providers needs further study.

The inguinal release procedure for groin pain: initial experience in 73 sportsmen/women.

OBJECTIVE: To assess the impact of the laparoscopic inguinal release procedure with mesh reinforcement on athletes with groin pain. DESIGN: Prospective cohort study. SETTING: Private sector. PATIENTS: Professional and amateur sportsmen/women undergoing the inguinal release for groin pain. MAIN OUTCOME MEASUREMENTS: Change in patient's symptoms, functional limitation and time to resuming sporting activity following surgery. RESULTS: 73 sportsmen/women underwent laparoscopic inguinal release in the study period, 37 (51%) of whom were professionals. 95% were male with a median age of 30 years. Following operation, patients returned to light training at a median of 1 week, full training at 3 weeks (professionals-2 weeks) and playing competitively at 4 weeks (professionals-3 weeks). 74% considered themselves match-fit by 4 weeks (84% of professionals). Following surgery, there was a highly significant improvement in frequency of pain, severity of pain and functional limitation in both the whole cohort and professional group. 88% reported a return to full fitness at follow-up, with 73% reporting complete absence of symptoms. 97% of the cohort thought the operation had improved their symptoms. CONCLUSIONS: This study shows that the laparoscopic inguinal release procedure may be effective in the treatment of a subgroup of athletes with groin pain.

Restorative proctocolectomy. Does ethnicity affect outcome?

OBJECTIVE: Restorative proctocolectomy (RPC) with ileal pouch-anal anastomosis (IPAA) is well-established in the management of ulcerative colitis (UC) and familial adenomatous polyposis (FAP). We review outcome of pouch surgery from a single centre, comparing non-South Asian and South Asian Caucasian populations. METHOD: Patients undergoing RPC for UC and FAP during a 10-year period between January 1997 and January 2007 were identified from hospital records. Data were collected retrospectively from case notes on early and long-term results. RESULTS: A total of 107 patients underwent pouch formation for UC (94%) or FAP (6%) and 22 (21%) were from the Asian subcontinent. Eighty-seven (81%) underwent a three-stage procedure and 20 (19%) a two-stage procedure. Postoperative complications occurred in 40 (37%) patients, being major in 11 (10%) patients with relaparotomy required in 9 (8%) with no difference between South Asian and non-South Asian Caucasian patients. Long-term pouch function, with a median of five times over 24 h (range 2-15), was similar between the two groups. The incidence of pouchitis was 57 (53%) and this was significantly greater in the South Asian population [17/21 (77%); 39/86 (46%); P = 0.006]. CONCLUSION: Surgical results were similar in South Asian and non-South Asian Caucasian patients, but the incidence of pouchitis was greater in the former group.

Evaluation of the prognostic value of systemic inflammation and socioeconomic deprivation in patients with resectable colorectal liver metastases.

BACKGROUND: There is increasing evidence that the presence of a pre-operative systemic inflammatory response (SIR) independently predicts poor long-term outcome in patients with colorectal cancer (CRC). Socioeconomic deprivation was reported to correlate with the presence of the SIR and to independently predict poor outcome following primary CRC resection. The aim of this study was to determine the prognostic value of pre-operative systemic inflammatory biomarkers and socioeconomic deprivation in patients undergoing resection of colorectal liver metastases (CLM) and to examine correlations between these variables in this context. PATIENTS AND METHODS: Clinicopathological data, including the Memorial Sloan-Kettering Cancer Centre Clinical Risk Score (CRS), were obtained from a prospectively maintained database for 174 patients who underwent hepatectomy for CLM between January 2000 and December 2005 at a single United Kingdom (UK) tertiary referral hepatobiliary centre. Inflammatory biomarkers (total and differential leucocyte counts, neutrophil-lymphocyte ratio, platelet count, haemoglobin, and serum albumin) were measured from routine pre-operative blood tests. Socioeconomic deprivation was measured using the Carstairs deprivation score. RESULTS: On multivariable analysis, poor CRS (3-5), high neutrophil count (>6.0 x 10(9)/l) and low serum albumin (<40g/dl) were the only independent predictors of shortened overall survival following metastasectomy, with neutrophil count representing the greatest relative risk of death. These factors were also the only independent predictors of shortened disease-free survival following hepatectomy. Socioeconomic deprivation was associated with neither systemic inflammation nor long-term outcome in this context. CONCLUSIONS: The presence of a pre-operative systemic inflammatory response, but not socioeconomic deprivation, independently predicts shortened survival following resection of CLM.

Surrogate markers of resectability in patients undergoing exploration of potentially resectable pancreatic adenocarcinoma.

Despite extensive preoperative staging, a significant number of pancreatic cancers are unresectable at surgical exploration. Patients undergoing pancreatic exploration with a view to resection were studied and comparisons are then made between those undergoing resection and a bypass procedure to identify surrogate markers of unresectability. One hundred thirteen consecutive patients underwent pancreatic exploration for head-of-pancreas (HOP) adenocarcinoma with curative intent. Fifty-five underwent pancreaticoduodenectomy and 58 underwent a bypass procedure. Student's t test, receiver operator characteristics (ROC) and logistic regression were used to compare the predictive value of preoperative patient variables collected retrospectively. The bypass group had a significantly higher median CA19.9 than the resection group (P = 0.003). Platelet count and neutrophil-lymphocyte ratio (NLR) were also significantly different (P = 0.013 and P = 0.026, respectively). ROC analysis indicated that age < or =65, platelet count >297 x 10(9)/l, CA19.9 < or =473 Ku/l, and CA19.9-bilirubin ratio were predictive variables for resectable disease. NLR and CA19.9-bilirubin ratio had specificity values of 92.9 and 97.0%, respectively. From logistic regression, a raised CA19.9 was found to be an independent risk factor for unresectable disease (P = 0.031). A significant proportion of patients with HOP adenocarcinoma are understaged preoperatively. Preoperative serology including platelet count, NLR, CA19.9, and CA19.9-bilirubin ratio may be used as additional discriminators of resectability particularly for high-risk patients.

Major resection of hepatic colorectal liver metastases in elderly patients - an aggressive approach is justified.

AIMS: With a progressively ageing population, increasing numbers of elderly patients will present with colorectal metastases and be referred for surgical resection. The aim of this study was to assess the safety of hepatic resection in patients over 70 years of age by comparing outcomes with those of a younger cohort of patients. METHODS: Forty-nine patients over 70 years of age who underwent hepatic resection of colorectal liver metastases were compared to 142 patients less than 70 years of age in terms of pre-, peri- and post-operative results, as well as long-term survival. RESULTS: Major resections were performed in 61% of the elderly group and 68% of the younger group. The two groups were comparable in terms of operative duration, transfusion rate, length of HDU stay and post-operative hospital stay. The elderly group had a non-significant increase in post-operative morbidity. The 30-day and 60-day/inpatient mortality rates were similar between the two groups (elderly 0% and 4%; younger 2% and 3%). Long-term disease-free survival was similar between elderly and younger patients. CONCLUSION: This study confirms that an aggressive surgical policy towards colorectal metastases in elderly patients is associated with low peri-operative morbidity and mortality, as well as good long-term outcomes.

Role of ultrasonography in the detection of resectable recurrence after hepatectomy for colorectal liver metastases.

BACKGROUND: Recurrence develops in most patients after hepatectomy for colorectal liver metastases. Repeat resection is feasible in some of these patients. The aim of this study was to evaluate an ultrasound-based follow-up protocol in the detection of resectable recurrent disease. METHODS: All patients undergoing hepatectomy for colorectal liver metastases at a single hepatobiliary referral centre in the UK from January 1999 to December 2004 were identified. Variables reviewed included rates of recurrence, mode and timing of detection, rates of repeat hepatectomy and survival. RESULTS: During the study period 191 patients underwent initial resection of colorectal liver metastases, of whom 109 developed recurrent disease. In total, 21 patients underwent potentially curative intervention, including 16 hepatic resections, four pulmonary resections and one staged pulmonary/hepatic resection. Ten of 72 patients who presented with recurrent disease within 12 months after initial resection were amenable to curative resection, compared with 11 of 37 patients presenting after 12 months. Sonographic surveillance identified all of the potentially resectable recurrent hepatic disease in the series. CONCLUSION: Ultrasonography is effective in the detection of potentially resectable hepatic recurrence after hepatectomy for colorectal liver metastases; however, routine chest imaging is needed.

Tumour characteristics predictive of survival following resection for ductal adenocarcinoma of the head of pancreas.

AIMS: We have maintained a highly conservative policy in selecting patients with carcinoma of the head of pancreas for resection. This has been based on tumour size, evidence of lymph node involvement or local invasion outside of the gland at laparotomy, laparoscopy or CT imaging. This study investigated our survival rates following pancreatic resection and examined clinicopathological predictors of survival. METHODS: Sixty-two consecutive patients undergoing pancreatic resections for malignancy were identified from 1999 onwards. Thirty-three underwent resection for pancreatic ductal adenocarcinoma and were included in our analysis, the remainder included resections for ampullary adenocarcinoma (n=20) or other malignancies (n=9). Patient, tumour and operative characteristics were analysed to assess predictors of survival following resection (Kaplan-Meier survival curves). RESULTS: Median survival following resection for ductal pancreatic adenocarcinoma was 54 months (ampullary adenocarcinomas achieved a median survival of 62 months) and thirty-day mortality was 2.7% (n=1). Survival was not associated with any demographic or intraoperative factors, such as blood loss, operative duration or anaesthetic technique. Survival curves were significantly worse when perineural or vascular invasion was evident histologically (p=0.023 and 0.0023 respectively). Patients with positive lymph nodes had a significantly shorter survival (p=0.0030) especially when lymph node status was expressed as a percentage of total lymph node yield. If more than 20% of retrieved lymph nodes were positive for tumour, this was a clear predictor of survival (p<0.0001). A positive resection margin was also associated with shortened survival (p=0.0291). CONCLUSION: Despite the advances made in the management of pancreatic cancer, tumour biology still dictates long-term survival. A highly selective surgical approach to the management of these patients results in good long-term survival.

Clinical Risk Score predicts yield of staging laparoscopy in patients with colorectal liver metastases.

BACKGROUND: Resection offers the only realistic chance of cure for hepatic colorectal metastases. The aim of this study was to examine the potential of laparoscopy and laparoscopic intraoperative ultrasonography (IOUS) for detecting incurable disease, and to determine whether the Clinical Risk Score (CRS) is useful in selecting patients for laparoscopy before hepatic resection. METHODS: All patients with potentially curable colorectal liver metastases who underwent staging laparoscopy and laparoscopic IOUS before planned hepatic resection between January 2000 and December 2004 were included. A preoperative CRS was determined for each patient and correlated with curability. RESULTS: Two hundred patients were identified, of whom 133 were found to have resectable disease at laparotomy. Laparoscopy detected 39 (58 per cent) of 67 patients with incurable disease, changing the management in 19.5 per cent of the 200 patients. The CRS correlated with the likelihood of detecting incurable disease; incurable disease was present in two of 31 patients with a CRS of 0-1, 35 of 129 with a score of 2-3 and 30 of 40 with a score of 4-5. The potential benefit of laparoscopy increased progressively with increasing CRS, changing management in none of 31 patients with a CRS of 0-1, 18 of 129 with a score of 2-3 and 21 of 40 with a score of 4-5. CONCLUSION: Staging laparoscopy and IOUS detected more than half of the incurable disease in this cohort. Laparoscopy had a low diagnostic yield in patients with a CRS of 0-1 and its routine use in this group of patients is therefore not recommended.

Cholecystobronchial fistula secondary to adenomyomatosis of the gallbladder.

A case of cholecystobronchial fistula secondary to adenomyomatosis of the gallbladder is described. A cholecystobronchial fistula is a very unusual cause of fistulation between the bronchial and biliary tree. This is only the fifth reported case in the English language literature.

Protein kinase C in rat brain cortex and hippocampus: effect of repeated administration of fluoxetine and desipramine.

1. Recent evidence indicates that changes in the activity of cyclic AMP-dependent protein kinase may be involved in neuroadaptive mechanisms after chronic treatment with antidepressants. The aim of this study was to investigate the effect of repeated administration of fluoxetine (FL) and desipramine (DMI) on the distribution and activity of protein kinase C (PKC) in subcellular fractions of rat cortex (Cx) and hippocampus (Hc) under basal conditions and in response to a single in vivo administration of 5-HT2A/2C agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI). 2. Rats were treated for 21 days with FL (5 mg kg-1 day-1, i.p.) or DMI (10 mg kg-1 day-1, i.p.). DOI was injected to groups of rats receiving repeated doses of antidepressants or to control rats 1 h before ex vivo PKC assay. Distribution of PKC was determined by [3H]-phorbol-12,13-dibutyrate ([3H]-PDBu) binding and PKC activity by the Amersham enzyme assay system. 3. Autoradiography of tissue sections revealed decreased [3H]-PDBu binding in CA1 region of hippocampus (by 18%) and paraventricular thalamic nucleus (by 28%) of rats after repeated administration of FL. 4. In vitro exposure of brain sections to 50 microM FL resulted in significant decreases (by 23-32%) of [3H]-PDBu binding in six out of seven regions examined; exposure to 100 microM FL reduced [3H]-PDBu binding (by 36-52%) in all regions. In contrast, exposure of brain sections to 100 microM DMI failed to alter specific [3H]-PDBu binding in brain sections. 5. The activity of PKC in subcellular fractions of Cx and Hc was significantly (by 40-50%) decreased in rats given repeated doses of FL or DMI. A single administration of either drug was without effect.6. A single in vivo administration of DOI to control rats resulted in reduced PKC activity (by 30-40%)in the particulate fraction of both Cx and Hc. This response to DOI was similar in DMI-treated rats but was not seen in rats given repeated doses of FL. A single administration of DOI to animals given repeated doses of FL resulted in PKC activities higher than those seen in rats treated with FL alone.7. The results indicate that repeated administration of FL and DMI produced similar changes in basal PKC activity but differentially affected the PKC response to the 5-HT2A/2c receptor agonist, DOI. The effect on basal PKC activity may result from a post-receptor action of antidepressants; the alteration of PKC response to DOI after fluoxetine could be due to receptor-mediated desensitization of the signalling system.