Laparoscopic posterior sectoral bile duct injury: the emerging role of nonoperative management with improved long-term results after delayed diagnosis.

BACKGROUND: Right posterior sectoral bile duct (RPSD) anomalies seen in up to 8% of the population rarely are injured at laparoscopic cholecystectomy. Paucity of data on the management of these injuries led the authors to conduct this study aimed at reviewing management strategies for laparoscopic RPSD injuries at a specialist center. METHODS: Of 221 patients, 15 (6.7%; 4 men; mean age, 51 years; range, 21-75 years) treated between 1992 and 2009 for injuries to the RPSD were followed up for a median of 58 months (range, 7-208 months). Case notes, imaging, and follow-up data were reviewed. RESULTS: The RPSD injury was immediately recognized in 3 (20%) of the 15 patients, whereas in the remaining patients, biliary injury was suspected on day 1 (range, 1-18 days) due to bile leak/biloma. The diagnosis of RPSD injury was made by a combination of investigations including endoscopic retrograde cholangiopancreatography (ERCP) (n = 11), drain tube cholangiogram (n = 10), on-table cholangiogram (n = 3), and nuclear scan (n = 3). An intact common bile duct and absence of RPSD were identified on cholangiography (ERCP and on-table cholangiogram), whereas drain tube cholangiogram demonstrated a leaking RPSD in all cases. The majority of the patients (8/15, 53%) were managed nonoperatively with combined percutaneous drainage and endoscopic stenting, whereas six patients (40%) were managed with biliary reconstruction (immediate: n = 2; delayed 14-87 days: n = 4). Clinical and radiologic confirmation of complete cessation of bile leak was demonstrated 56 days (range, 7-62 days) after injury. The long-term outcome included a dilated right duct system with transient elevation of liver function tests in two patients (1 each in the nonoperative and surgical management groups), whereas the remaining patients all remain well at this writing. CONCLUSION: Bile leak in the presence of an intact common duct shown on cholangiogram should raise the suspicion of an RPSD injury. Expertise is needed to interpret the absence of RPSD in these cases. Drain tube cholangiogram is an important adjunctive investigation. In selected cases, the results of nonoperative management alone is comparable with the results of reconstruction.

Delayed introduction of reduced-dose tacrolimus, and renal function in liver transplantation: the 'ReSpECT' study.

We report a multicenter, prospective, randomized, open-label trial investigating the effect of lower levels and delayed introduction of tacrolimus on renal function in liver transplant recipients. Adult patients with good renal function undergoing primary liver transplant were randomized to either: group A (standard-dose tacrolimus [target trough levels >10 ng/mL] and corticosteroids; n = 183); group B (mycophenolate mofetil [MMF] 2g/day, reduced-dose tacrolimus [target trough levels

Orthotopic liver transplantation for epithelioid haemangioendothelioma.

AIMS: To report seven cases of epithelioid haemangioendothelioma (EHE) of the liver, a rare, low-grade malignant neoplasm of vascular origin that have been treated in our institution. MATERIALS AND METHODS: Patients with ages ranging from 25 to 60 years presenting mainly with non-specific symptoms, such as right upper quadrant abdominal pain or weight loss. The tumours presented as multiple, nodular lesions involving both lobes of the liver. This type of tumour is often difficult to diagnose, with the final diagnosis being established only by histological examination. The key to diagnosis was the demonstration of cells containing factor VIII-related antigen. RESULTS: Five patients underwent orthotopic liver transplantation (OLT), four of whom are alive at a median follow up 38 months (11-88 months). One patient died of recurrent of disease at 88 months. Two patients did not receive an OLT since they presented with extrahepatic metastatic disease; they died at 21 and 25 months from diagnosis. CONCLUSION: Orthotopic liver transplantation may be considered as a potentially curative treatment for this rare form of tumour when the disease is confined to the liver.

Is serum gentamicin level a good predictor of graft injury in intestinal transplantation?

INTRODUCTION: Following intestinal transplant (SBT), the early diagnosis and treatment of rejection is a major management aim. The diagnosis of rejection is based on histology of stomal biopsies. Oral gentamycin (2.5 mg/kg) was used for selective decontamination of the digestive system. Our hypothesis was that gentamycin might be absorbed in the presence of graft dysfunction. AIM: Our goal was to assess the correlation between serum gentamycin level and the health of the intestinal graft. SUBJECTS AND METHODS: Among 33 SBT performed from 1993 to 2005, serum gentamycin levels were performed once weekly or more often when there was a suspicion of rejection. All data were analyzed retrospectively. RESULTS: Adequate trough levels were achieved for only 23 patients, six of whom had histologically proven rejection and only one did not have a raised gentamycin content. Five patients with raised levels but no rejection included two with severe intestinal ischemia and three with bowel obstruction/ileus. Four of the five patients required laparotomies. CONCLUSION: We concluded that in our study raised serum gentamycin levels were a good predictor of rejection or significant injury to the graft.

Surgical treatment of metastases to the pancreas.

BACKGROUND AND AIMS: Metastases to the pancreas are rare and their surgical treatment is not well reported. We present a considerable experience from a single centre analysing various prognostic factors. METHODS: Data were collected on 13 cases who underwent surgery between 1988 and 2002. Since 1997, data have been recorded prospectively on a dedicated database. Clinical and histopathological factors were reviewed. RESULTS: There were two women and 11 men with a median age of 62 years (range 40-73). There were seven cases of renal cell carcinomas, three colorectal carcinomas, two sarcomas and one lung carcinoma. A prolonged disease-free interval from primary surgery was characteristic for renal cell carcinoma cases (median = 10.8 years). The operative procedures performed included seven pancreatoduodenectomies, four total and two distal pancreatectomies. The operative mortality and morbidity was 7.7% and 46.1% respectively. The overall one- and two-year survival was 78.8% and 54% respectively. Median survival for renal cell carcinoma was 30.5 months and for non-renal cell carcinoma was 26.4 months (p = 0.76). CONCLUSIONS: Pancreatectomy should be considered for metastases to the pancreas in the absence of generalised metastatic disease. However, decision making and experience should be concentrated in centres with significant familiarity of this approach.

Liver transplantation in patients over sixty years of age.

BACKGROUND: Although some centers have reported very good patient and graft survival in liver allograft recipients, reports from both North America (United Network of Organ Sharing) and Europe (European Liver Transplantation Registry) have failed to confirm this. AIM: We have reviewed our experience of liver transplantation in older recipients and compared their clinical outcome to a younger group. METHODS: Retrospective analyses were conducted on 875 consecutive adult patients undergoing liver transplantation for chronic liver disease, between 1990 and 1999. Group I consisted of patients under 60 years of age (n=701; 80.2%) and group II of patients over 60 years (n=174; 19.8%). RESULTS: The proportion of older patients transplanted increased from 10.15% between 1990-1991 to 20.85% (1997-1999). Actuarial graft survival at 1, 3, and 5 years was 78%, 74%, and 69% and 78%, 73%, and 66% for groups I and II, respectively (P=0.49). The overall actuarial patient survival tended to be better in the younger group (1-, 3-, and 5-year survival of 83%, 79%, and 76% for group I and 81%, 75%, and 69% for group II (P=0.07). Crude mortality probability shows a stable trend until 45 years, a gradual increase in mortality between 45 and 60 years, and then the risk of death is accelerated. The same analysis shows the risk of death is between 1.5 and 2 times greater in Child C patients; this is greater in patients aged more than 66 years. CONCLUSION: There is no statistically significant difference in patient or graft survival in patients aged over 60 compared to younger recipients. However, when age is assessed as a continuous variable, an adverse effect of older age is seen on outcome and this effect is more marked in sicker patients.

Donor thyroid function does not affect outcome in orthotopic liver transplantation.

Brainstem death is associated with endocrine and metabolic alterations that can result in donor hemodynamic instability. It has been suggested that these changes can be reversed through hormonal manipulation of the donor. We measured thyroid hormone levels (free triiodothyronine [fT3], free tetraiodothyronine [fT4], reverse triiodothyronine) and thyroid-stimulating hormone (TSH) in 50 consecutive adult brain dead multiorgan donors. Recipient graft function was assessed using peak and day 5 aspartate aminotransferase, peak serum bilirubin, and minimum prothrombin time during the first week after OLT. Free T3 was low in 32/50 donors and was associated with a low fT4 in 24 cases. TSH was normal in 35 donors and we found no correlation between TSH levels and fT3 or fT4. Reverse triiodothyronine was normal or high in 96% of donors. Patient and graft survival were 96% for both the low and high fT3 groups. These data suggest that euthyroid sick syndrome is the most likely cause for the endocrine and metabolic alterations seen in brainstem-dead donors. This does not appear to influence liver recipient or graft survival.

Acute liver allograft rejection--is treatment always necessary?

A group of 195 consecutive adult patients who received a primary orthotopic liver allograft were reviewed retrospectively to analyze the incidence of rejection, the response to antirejection therapy, and the impact of acute rejection on the development of ductopenic rejection. The diagnosis of acute rejection (AR) was based on a combination of clinical and histological criteria, and 69.7% of the patients had at least one episode of acute rejection. Only 6.7% of the patients failed to respond to steroids and were treated with OKT3. Four (2.3%) patients developed acute vanishing bile duct syndrome (within 60 days) and 6 (3.5%) patients developed chronic rejection. Eight patients who spontaneously recovered from AR without additional immunosuppression are described in detail. In addition to histological damage, all developed significant hepatic dysfunction. Except for one patient who died from disseminated fungal infection, the 7 remaining patients are alive with excellent graft function 7 to 21 months posttransplant. While severe AR and recurrent AR should be treated without delay, some patients with mild-to-moderate rejection and hepatic dysfunction may resolve without additional immunosuppression.

The role of dynamic and morphological studies in the assessment of potential liver donors.

In a prospective study, 66 donor livers were evaluated by monoethylglycinexylidide (MEGX) dynamic clearance and semiquantitative scoring of pathological changes in liver biopsies. The median MEGX level in 63 donors was 89 mcg/L (range 16-250 mcg/L); fifteen had MEGX levels < 50 mcg/L, 17 between 50 and 90 mcg/L, and 31 > 90 mcg/L. There were no cases of primary nonfunction, and no deaths were related to poor graft function. There was no statistically significant difference in peak aspartate aminotransferase (AST), day 5 AST, peak bilirubin, or lowest prothrombin time among the 3 groups. Liver biopsies were assessed in 61 donors: 33 (54%) were normal and 17 (28%) showed mild, 8 (13%) showed moderate, and 3 (5%) showed severe steatosis. Postperfusion biopsy assessing the extent of preservation injury was essentially normal or showed minimal change in 16 (26%), mild change in 29 (48%), moderate in 13 (21%) and severe abnormalities in 3 (5%). The latter 3 biopsies all had severe steatosis. There was no significant difference in early graft function or outcome between moderate/severe groups and normal/minimal groups, although the former had a higher peak AST (P < 0.02) and peak bilirubin (P < 0.004). This detailed prospective analysis suggests that MEGX and the morphological studies may assist in the assessment of potential liver donors but they do not provide a basis on which grafts should be discarded.

En block combined reduced-liver and small bowel transplants: from large donors to small children.

BACKGROUND: The critical shortage of size-matched donor organs for infants and small children in need of combined liver and intestinal transplantation has lead to long waiting times and a high risk of dying before transplantation. Utilizing grafts from larger donors could alleviate this problem, but using larger composite grafts in small children has been challenging and unsuccessful in the past. METHODS: We conducted a pilot study for evaluating the results of transplanting into small recipients a composite graft (reduced-size liver and whole small bowel, including duodenum and pancreas head) procured from large donors. Liver size reduction was performed ex situ using the extrahilar approach, which leaves the liver hilum untouched. Straightforward implantation of the graft was performed by simple, two-step vascular anastomoses. The preservation of the donor duodenum in continuity with the combined graft avoided the need for biliary reconstruction, thus preserving maximal bowel length for gut continuity restoration in the recipient. RESULTS: Two children, weighing 7.6 and 9.8 kg, respectively, underwent transplantation of a composite graft procured from donors weighing 35 kg. Their waiting time (68 and 97 days, respectively) was shorter compared with our previous experience with conventional techniques. Both are currently alive and well, at home and on full enteral feeds, 15 and 11 months after transplantation, respectively. CONCLUSION: This new technique has extended the range of possible donors for small candidates waiting for combined grafts and was successful in two patients. It should be considered for small recipients in the future.

Randomized trial of cyclosporine microemulsion (neoral) versus conventional cyclosporine in liver transplantation: MILTON study. Multicentre International Study in Liver Transplantation of Neoral.

BACKGROUND: The new microemulsion formulation of cyclosporine (Neoral) has been developed in an effort to improve the reliability of drug absorption. The objectives of this study were to assess the efficacy, safety, and tolerability of Neoral compared to the original formulation (Sandimmun) in liver transplant recipients. METHODS: In a double-blind, parallel group study conducted in 28 centers across Europe and the United States, patients receiving primary orthotopic liver allografts were randomized within 24 hr of transplantation, 198 to Neoral and 192 to Sandimmun. Patients with and without T-tube biliary drainage were included. Postoperatively, all patients also received intravenous (i.v.) cyclosporine, together with prednisolone and azathioprine. Antibody induction was excluded. Efficacy measures were rejections, graft failure, patient survival, and the efficacy of the study medication in achieving the desired cyclosporine blood levels. Safety was assessed by reported adverse events, blood pressure, serum creatinine, and other routine laboratory measurements. RESULTS: Kaplan-Meier analyses showed that the Neoral group performed better than the Sandimmun group, with the estimates for patients free of treated rejection and histologically confirmed rejection either showing or approaching statistical significance at the 5% level. By 52 weeks, 5.8% (95% confidence limits: -4.4-15.9%) fewer patients required treatment of acute rejection in the Neoral group. The proportion of patients experiencing at least one treated rejection episode by 2 weeks was 29.8% for Neoral and 43.2% for Sandimmun. For histologically confirmed rejection, these proportions were 32.8% and 44.3%, respectively. The proportion of patients experiencing at least one steroid-resistant rejection was 2.0% for Neoral and 6.3% for Sandimmun at week 2, and 3.0% and 9.9%, respectively, at week 3. All these differences were significant at P<0.05. By 52 weeks, graft failure was 6.3% on Neoral and 11.4% on Sandimmun, with respective patient survival figures of 85.4% and 85.8%. The median duration of the initial episode of i.v. cyclosporine was 4.0 days for Neoral, compared to 6.5 days for Sandimmun (P<0.001). Within the first 2 weeks, a larger percentage of patients in the Neoral group reached the lower target level of cyclosporine (P< or =0.01). The weight-adjusted daily doses of study medication were lower in the Neoral group (median dose: 4.86 vs. 5.42 mg/kg/day, P=0.001), but the blood levels of cyclosporine showed no difference. For those with a T-tube, more of the patients on Neoral remained free of treated rejection throughout the study period (P=0.042, Wilcoxon). By week 2, 44.9% of these patients in the Sandimmun group required treatment for rejection compared to 30.2% in the Neoral group (P=0.007). There was no significant difference between the groups for serum creatinine, blood pressure, other biochemical and hematological variables, or reported adverse events. CONCLUSIONS: In liver transplantation in the normal clinical setting, the pharmacokinetic advantages of Neoral translate into clinical superiority over Sandimmun without a negative impact on safety. Recent data indicate that it is not optimal to use i.v. cyclosporine initially in this type of study, but the benefit was seen despite this. In keeping with the previous pharmacokinetic studies, patients managed by T-tube biliary drainage, and hence with no or limited bile available in the gastrointestinal tract, did particularly well with Neoral.

The use of liver grafts from donors with bacterial meningitis.

BACKGROUND: The shortage of suitable donors for transplantation is a worldwide problem. The use of cadaveric donors with bacterial meningitis may be associated with an increased risk of sepsis. We report the results of orthotopic liver transplantation (OLT) from 33 such donors between 1989 and 1999. METHODS: The hospital records of recipients from cadaveric donors with meningitis (study group) were retrospectively reviewed and compared with matched recipients from cadaveric donors dying from causes other than meningitis (recipient-matched control group). RESULTS: A total of 34 recipients underwent 21 whole, 10 reduced, and 3 split liver transplants from 33 cadaveric donor livers with bacterial meningitis. The donor meningitis pathogens were Neisseria meningitidis (n=14), Streptococcus pneumoniae (n=4), Haemophilus influenzae (n=1), Streptococcus species (n=2), and unknown (n=12). Twenty-seven patients had an elective OLT and seven patients had an emergency OLT. Adequate antimicrobial therapy before organ procurement and after transplant was administrated. The mean posttransplant follow-up was 37 months (range: 1 day-106 months). There was no difference in recipient and graft survival rates between the study and the recipient-matched groups. In the study group, there were no infectious complications caused by the meningeal pathogens. Overall patient survival rates were 79%, 76%, 72%, and 72% at 1, 6, 12, and 60 months, respectively. Graft survival was 77%, 70%, 65%, and 65% at 1, 6, 12, and 60 months, respectively. The survival rate in elective cases was significantly better than emergency cases (P<0.05). CONCLUSION: Liver transplantation from donors with bacterial meningitis is a safe procedure provided both donors and recipients receive adequate antimicrobial therapy.

Extended preservation of the liver with UW solution--is it justifiable?

The outcome of 228 liver grafts in 208 elective adult recipients was assessed to identify any adverse effects of extending the length of cold preservation with UW solution beyond 12 hr. A total of 114 grafts had been preserved < 12 hr--median 9.5 (group I) and 114 > 12 hr--median 14.5 (group II). Intraoperative blood and blood product usage, graft function, hospital stay, and graft and patient survival were identical in the two groups. Biliary strictures occurred in 5.7% of grafts (8 anastomotic (3 group I, 5 group II; 5 hilar/nonanastomotic: 3 group I, 2 group II). There was no graft or patient loss due to the hilar strictures but 1 patient died following reconstruction of an anastomotic stricture (0.4%). It is concluded that extending the cold preservation to approximately 15 hr does not adversely affect outcome after liver transplantation.

Improved clinical outcomes for liver transplant recipients using cyclosporine monitoring based on 2-hr post-dose levels (C2).

BACKGROUND: A prospective, open-label, study was conducted at 29 centers in 9 countries, involving 307 de novo liver transplant patients to compare the clinical usefulness of monitoring 2-hr post-dose cyclosporine (CsA) levels (C2) with conventional trough cyclosporine blood levels (pre-dose) (C0). METHODS: Neoral oral therapy was initiated at 15 mg/kg/day and dose adjusted according to predetermined C2 or C0 target level ranges. The primary efficacy variable was treatment failure at 3 months, where evaluation was based on a composite endpoint of biopsy-proven rejection, treatment for rejection, graft loss, death, or premature withdrawal/discontinuation from the study. RESULTS: Baseline characteristics were similar between groups. Graft loss at 12 weeks (retransplantation or death) occurred in 6.8% C2 and in 7.0% C0 patients. Overall incidence of treated acute rejection was lower for C2 (23.6%) than C0 patients (31.6%) (P=0.144, Cochran-Mantel-Haenszel [CMH] test). In hepatitis C virus (HCV)-negative patients, the incidence of rejection in the C2 group was significantly less than in the C0 group (21.2% vs. 33.0%; P<0.05), whereas in HCV-positive patients, the rejection rate was similar in both groups (26.7% for C2 group vs. 27.3% for C0 group: P=0.81). C2 patients (n=16) who reached minimum target CsA levels by day 3 had a notably low incidence of rejection (12.5%), whereas there was no difference in the incidence of rejection in C0 patients, irrespective of time to reach target level. For biopsy-proven acute rejections (21.6% for C2 vs. 30.4% for C0), the incidence of moderate and severe histological diagnosis was significantly lower in the C2 group than in the C0 group (47% vs. 73%; P=0.01). Safety profiles were similar between the two groups, with few patient withdrawals due to adverse events (9.5% for C2; 7.0% for C0). CONCLUSIONS: Using C2 monitoring, the overall incidence of acute cellular rejection was lower compared with the C0 group, and the histological severity of acute rejections was shown to be significantly milder for the C2 group, indicative of good long-term prognosis. These data demonstrate that the use of C2 monitoring is superior to C0 and results in a reduction in the incidence and severity of acute cellular rejection without detrimental effect on the drug safety profile.

Multicenter randomized trial comparing tacrolimus (FK506) and cyclosporine in the prevention of renal allograft rejection: a report of the European Tacrolimus Multicenter Renal Study Group.

BACKGROUND: To confirm the results of a number of studies conducted in Europe, the United States, and Japan, this multicenter, randomized trial compared the 12-month efficacy and safety of tacrolimus- and cyclosporine-based immunosuppressive regimens in the prevention of renal allograft rejection. METHODS: A total of 448 renal transplant recipients were recruited from 15 centers and assigned to receive triple-drug therapy consisting of tacrolimus (n=303) or cyclosporine (n=145) in conjunction with azathioprine and low-dose corticosteroids. RESULTS: At 12 months after transplantation, tacrolimus therapy was associated with a significant reduction in the frequency of both acute (tacrolimus 25.9% vs. cyclosporine 45.7%; P<0.001 [absolute difference: 19.8%, 95% confidence interval: 10.0-29.6%]) and corticosteroid-resistant rejection (11.3% vs. 21.6%; P=0.001 [absolute difference: 10.3%, 95% confidence interval: 2.5-18.2%]). Actuarial 1-year patient (tacrolimus 93.0% vs. cyclosporine 96.5%; P=0.140) and graft survival rates (82.5% vs. 86.2%; P=0.380) did not differ significantly between the two treatment groups. Overall, the safety profiles of the tacrolimus- and cyclosporine-based regimens were quite comparable. Infections, renal impairment, neurological complications, and gastrointestinal complaints were frequently reported but were mostly reversible in both groups. Higher incidences of elevated serum creatinine, tremor, diarrhea, hyperglycemia, diabetes mellitus, and angina pectoris were reported in the tacrolimus treatment group, whereas acne, arrhythmia, gingival hyperplasia, and hirsutism were more frequent with cyclosporine treatment. CONCLUSIONS: The significant reduction in the incidence of episodes of allograft rejection observed with tacrolimus therapy may have important long-term implications given the prognostic influence of rejection on graft survival.

Hormonal basis during pregnancy for the onset of maternal behavior in the rat.

This article reviews the current state of our knowledge about the hormonal basis of maternal behavior in the rat. Considered are the ovarian hormones estrogen and progesterone, the pituitary hormones beta-endorphin and prolactin, and the hormone oxytocin, secreted by several hypothalamic nuclei and associated brain regions. The hormones of pregnancy, estrogen and progesterone, prime the female to respond to a terminal rise in estrogen that stimulates a high level of maternal responsiveness even before parturition begins. Studies on the role of prolactin, using hypophysectomy, prolactin release blockers and anterior pituitary and prolactin replacement, indicate that prolactin is required for the ovarian hormones to be effective in stimulating maternal behavior. During the latter half of pregnancy, placental lactogen may displace prolactin in this role. Although prolactin serves as a chronic stimulus for maternal behavior, it also may act over a short period. Oxytocin stimulates maternal behavior in a specific strain of rat, but not in other strains, and only when administered introcerebroventricularly (ICV) in estrogen-primed females. The decline in the high brain levels of beta-endorphin around parturition has been proposed as a requirement for the onset of maternal behavior; morphine blocks the onset of maternal behavior and disrupts ongoing maternal behavior and maternal aggression in lactating females. However, blocking beta-endorphin action at parturition interferes with pup cleaning and eating of the placenta as well.

Bedside percutaneous tracheostomy in critically ill patients.

Bedside percutaneous dilational tracheostomy was performed by critical care attending physicians or supervised pulmonary and critical care fellows on 100 patients in the ICU at Cook County Hospital, Chicago, over a 3-year period. A needle is inserted in the first or second tracheal interspace followed by a guidewire. The tract is enlarged with a series of dilators to allow placement of a standard tracheostomy tube. Average procedure duration for 46 patients was 6.7 +/- 2.9 min. The intraoperative complication rate was 8 percent: transient oxygen desaturation (4 percent), transient hypotension (3 percent), and paratracheal insertion (1 percent). The postoperative complication rate was 10 percent: bleeding (5 percent), stomal infection (3 percent), and subcutaneous emphysema (2 percent). One patient died of presumed innominate artery rupture. Fifteen of 37 patients who survived hospitalization were decannulated. Stomal closure occurred in 13 of these 15 patients within 3 days with a minimal residual scar. Comparison of percutaneous dilational tracheostomy with two other techniques of percutaneous tracheostomy reveals a similar success rate with a lower incidence of serious complications. Bedside percutaneous dilational tracheostomy can be performed in the ICU by trained physicians with a low complication rate. We believe it to be the procedure of choice for many critically ill patients who require tracheostomies.

Peripeduncular nucleus lesions in the rat: I. Effects on maternal aggression, lactation, and maternal behavior during pre- and postpartum periods.

Bilateral peripeduncular (PPN) lesions made on the seventh postpartum day (L7) with either radiofrequency (RF) current or N-methyl-d,l-aspartic acid (NMDA)/phosphate buffered saline (PBS) reduced maternal aggression (MA) and partially inhibited lactation without producing significant deficits in other items of maternal behavior (MB). RF-PPN lesions did not interfere with prolactin secretion, which suggests that there was deficient oxytocinergic activity. The deficit in MA was not due to interruption of afferent suckling input to the PPN: either thelectomizing females (day L6) or producing bilateral knifecuts in the mesencephalon (placed caudal to the level of the PPN; Day L7) had no effect on MA, but both procedures impaired lactation. Deficits in MA produced by RF-PPN lesions developed gradually between Days L4 and L7; lesions made either prepartum or on Day L1 did not impair MA or MB. Deficits in lactation first appeared after RF-PPN lesions on Day L1.

C reactive protein: an aid to assessment and monitoring of acute pancreatitis.

An evaluation of C reactive protein as an indicator of the progress of acute pancreatitis has been made, and the data have been compared with the information given by the white cell count, erythrocyte sedimentation rate, and temperature and by two antiproteases--alpha 1 protease inhibitor and alpha 1 antichymotrypsin. The main value of C reactive protein is to provide a guide to the severity of the inflammation and to increase clinicians' awareness of the patient's enhanced risk of developing pancreatic collections when the C reactive protein concentration remains high (greater than 100 mg/l) at the end of the first week of the illness. In this respect C reactive protein concentrations are superior to white cell count, erythrocyte sedimentation rate, and temperature and the concentrations of antiproteases.

Peritoneal fluid in human acute pancreatitis blocks hepatic mitochondrial respiration.

Peritoneal fluid may be the source of multi-system failure during the initial stages of acute pancreatitis. The toxicity of human pancreatic ascitic fluid (HPAF) collected under sterile conditions from 12 patients with acute pancreatitis was investigated with the use of an in vitro preparation of mitochondria. Hepatocyte mitochondria from Sprague-Dawley rats were prepared by standard techniques. Mitochondrial oxidative activity was determined in glutamate-malate medium, with micromodification of the YSI Model 53 (Yellow Springs, Ohio) oxygen electrode system. The oxygen uptake of 150 to 200 microliter samples of mitochondria suspension (20 to 25 mg/ml) was monitored for 3 minutes, after which 3 microliter of 0.1 M adenosine diphosphate (ADP) was added to the chamber to induce state 3 respiration. Two minutes after the oxygen trace returned to state 4 respirations, 20, 40, or 80 microliter of the HPAF sample was introduced into the reaction vessel and the oxygen measurement continued for an additional 3 minutes. After this, 3 microliter of 0.1 M ADP again was added to the reaction chamber and the oxygen measurement continued. Control runs were made with reconstituted pooled human serum used in place of the HPAF samples. A significant (p less than 0.05) increase in state 4 respiration occurred in all 12 samples of HPAF. Addition of ADP showed a significant decline (p less than 0.05) in respiratory control ratio in all specimens. A dose-response curve was observed in 8 of 12 HPAF samples tested.(ABSTRACT TRUNCATED AT 250 WORDS)