Effects of general anaesthesia in dorsal recumbency with and without vatinoxan on bronchoalveolar lavage cytology of healthy horses.

Pneumonia is one of the potential complications of general anaesthesia in horses. Anaesthesia is known to increase neutrophils in bronchoalveolar lavage fluid (BALF) of horses after lateral recumbency, but studies after dorsal recumbency are lacking. Our primary aim was to determine when lung inflammation reaches its maximum and how rapidly BALF cytology returns to baseline after anaesthesia in dorsal recumbency. A secondary aim was to investigate the possible effect of vatinoxan, a novel drug, on the BALF cytology results. Six healthy experimental horses were enrolled in this observational crossover study. The horses were subject to repeated BALF and blood sampling for 7 days after general anaesthesia with two treatment protocols, and without anaesthesia (control). During the two treatments, the horses received either medetomidine-vatinoxan or medetomidine-placebo as premedication, and anaesthesia was induced with ketamine-midazolam and maintained with isoflurane for 1h in dorsal recumbency. The differences in BALF and blood variables between the two anaesthesia protocols and control were analysed with repeated measures analysis of variance models. In this study, anaesthesia in dorsal recumbency resulted in no clinically relevant changes in airway cytology that could be differentiated from the effect of repeated BALF sampling. No differences in BALF matrix metalloproteinase gelatinolytic activity could be detected between the two treatments or the control series. Marked increase in serum amyloid A was detected in some animals. Vatinoxan as premedication did not consistently affect lung cytology or blood inflammatory markers after anaesthesia.

Effects of diet-induced obesity on motivation and pain behavior in an operant assay.

Obesity has been associated with multiple chronic pain disorders, including migraine. We hypothesized that diet-induced obesity would be associated with a reduced threshold for thermal nociception in the trigeminal system. In this study, we sought to examine the effect of diet-induced obesity on facial pain behavior. Mice of two different strains were fed high-fat or regular diet (RD) and tested using a well-established operant facial pain assay. We found that the effects of diet on behavior in this assay were strain and reward dependent. Obesity-prone C57BL/6J mice fed a high-fat diet (HFD) display lower number of licks of a caloric, palatable reward (33% sweetened condensed milk or 30% sucrose) than control mice. This occurred at all temperatures, in both sexes, and was evident even before the onset of obesity. This diminished reward-seeking behavior was not observed in obesity-resistant SKH1-E (SK) mice. These findings suggest that diet and strain interact to modulate reward-seeking behavior. Furthermore, we observed a difference between diet groups in operant behavior with caloric, palatable rewards, but not with a non-caloric neutral reward (water). Importantly, we found no effect of diet-induced obesity on acute thermal nociception in the absence of inflammation or injury. This indicates that thermal sensation in the face is not affected by obesity-associated peripheral neuropathy as it occurs when studying pain behaviors in the rodent hindpaw. Future studies using this model may reveal whether obesity facilitates the development of chronic pain after injury or inflammation.

Obesity increases nociceptive activation of the trigeminal system.

BACKGROUND: Obesity is a risk factor associated with several pain syndromes. However, the mechanisms underlying the association between obesity and pain are not known. The aim of this study was to test the hypothesis that obesity enhances neuronal responses to nociceptive stimulation within the trigeminal nucleus caudalis (TNC). METHODS: Male and female C57BL/6J mice were fed a high-fat or regular diet from the time of weaning until 20 weeks of age. We then quantified neuronal activation by measuring Fos immunoreactivity within the TNC in response to a facial injection of a low dose of capsaicin (1 µg/10 µL). RESULTS: We found that 0.01% capsaicin did not significantly increase Fos immunoreactivity in control mice fed a regular diet. In contrast, this low dose of capsaicin caused a 3.3-fold increase in Fos in the TNC in obese mice (p < 0.001). CONCLUSIONS: These results support the hypothesis that diet-induced obesity in mice enhances nociceptive processing within the TNC. Diet-induced obesity may be a useful model for mechanistic studies. Future studies will improve our understanding of how obesity may contribute to trigeminal pain by sensitizing the trigeminal nociceptive system.

Characterization of bilateral trigeminal constriction injury using an operant facial pain assay.

In order to better understand and treat neuropathic pain, scientific study must use methods that can assess pain processing at the cortical level where pain is truly perceived. Operant behavior paradigms can accomplish this. We used an operant task to evaluate changes following chronic constriction injury to the trigeminal nerves. We also relate these behavioral changes to immunohistochemistry of transient receptor potential channels vanilloid 1 and melastatin 8 (TRPV1 and TRPM8) in the trigeminal ganglia. Following nerve injury, successful performance of the operant task was reduced and aversive behaviors were observed with 10 and 37 °C stimulation, indicating cold allodynia and mechanical allodynia respectively. In contrast, while aversive behaviors were observed with 48 °C stimulation, successful performance of the operant task was not substantially hindered following injury. These behavioral changes were accompanied by an increase in TRPV1 positive cells and an increased intensity of TRPM8 staining at 2 weeks post-injury, when cold allodynia is maximal. These findings suggest that the incorporation of operant behavioral assessment in the study of pain may provide insight into the relationship among peripheral changes, motivational drive, and pain. Understanding this relationship will allow us to better treat and prevent chronic neuropathic pain.

[Severe acute hepatic failure and haemophagocytic syndrome: cause or consequence?]. / Insuffisance hépatique aiguë sévère et syndrome d'activation macrophagique: cause ou conséquence?

Haemophagocytic syndrome corresponds to an unconnected macrophagic activity with haemophagocytosis. We report the case of a haemophagocytic syndrome in a 49-year-old woman with initially a severe acute hepatic failure. This syndrome is probably underestimated in ICU patients. Haemophagocytic syndrome should be suspected in patients with fever and jaundice without infection.

High-dose cyclophosphamide, BCNU, and VP-16 (CBV) conditioning before allogeneic stem cell transplantation for patients with non-Hodgkin's lymphoma.

Allogeneic stem cell transplantation (SCT) has been shown to be a curative therapy for some patients with non-Hodgkin's lymphoma (NHL). Total-body irradiation and high-dose cyclophosphamide combinations are the most established conditioning regimens used in this setting. We examined the efficacy and toxicity of cyclophosphamide, BCNU, and VP-16 (CBV) as a suitable chemotherapy-only regimen for NHL patients. In total, 18 patients, median age 42 years, with NHL were treated with CBV followed by allotransplant. Patients had received a median of two prior chemotherapy regimens. Median times to neutrophil and platelet recovery were 19 and 15 days, respectively. Interstitial pneumonitis occurred in one patient. There have been four relapses after a median follow-up of 39 months. Overall, there were four deaths, one because of relapse. The 2-year estimates of relapse-free and overall survival are 56 and 76%, respectively. CBV is a safe and an effective alternative to TBI-containing regimens before allogeneic SCT for NHL.

[Training for adult subclavian venous catheterization: use of real-time echography]. / Apprentissage du cathétérisme de la veine sous-clavière chez l'adulte: apport de l'assistance échographique en temps réel.

OBJECTIVE: To assess the training in adult subclavian venous catheterization of an inexperienced operator, with two different procedures: ultrasound guidance vs anatomic landmark technique. STUDY DESIGN: Prospective, comparative study. PATIENTS AND METHODS: After informed consent, 50 adults were divided in two groups, with an original method of inclusion, designed to assess the training of the operator, which alternated ultrasound guidance (n = 25) and Aubaniac's landmark technique (n = 25). RESULTS: All the catheterizations have been completed. The success rate at first attempt was higher in ultrasound group than in landmark group, without reaching significance (76 vs 56%). Two arterial punctures were reported in landmark group. With ultrasound guidance, there were 21 puncture sites at the external third and 4 at the medial third of the clavicle. Average access time (skin to vein) was 15 +/- 8 seconds in ultrasound group and 63 +/- 78 seconds in landmark group (p < 0.01), with a significant relation between access time and patient rank in landmark group (r2 = 0.42, p < 0.01). CONCLUSION: Ultrasound guidance makes the training in adult subclavian venous catheterization easier, and allows inexperimented operator to be rapidly efficient. The use of ultrasound would decrease the incidence of complications by a real time visualization of anatomical structures, and by a more external approach of the vein than in the Aubaniac's technique.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) priming with successive concomitant low-dose Ara-C for elderly patients with secondary/refractory acute myeloid leukemia or advanced myelodysplastic syndrome.

Patients with advanced MDS and secondary AML respond poorly to chemotherapy. Granulocyte-macrophage colony-stimulating factor (GM-CSF) can stimulate proliferation of leukemic blasts and sensitize these cells to the cytotoxic effects of S-phase-specific drugs. This is the first report of safety and efficacy of GM-CSF prior to and during cytarabine in a low-dose, intermittent regimen for elderly patients with poor risk acute myelogenous leukemia or myelodysplastic syndrome. Twenty patients, age 68 to 86 years, each received 250 microg/m2 of GM-CSF (Sargramostatin; Immunex, Seattle, WA, USA) subcutaneously (s.c.) or intravenously (i.v.) for 3 days followed by GM-CSF at the same dose and cytarabine 100 mg/m2 i.v. for 3 days. GM-CSF and cytarabine were both administered for 3 days during weeks 2 and 3 followed by a 3-week rest period. Rates of CR and PR were 20% and 40%, respectively. These included clinically significant resolution of cytopenias and transfusion requirements. Many of the responding patients had been heavily pretreated prior to enrollment. One- and 2-year survival estimates are 44% and 19%, respectively. Myelosuppression was the most significant toxicity. Our findings suggest that this novel combination of GM-CSF with sequential and concomitant low-dose cytarabine can benefit patients with poor risk myeloid malignancies.

The effect of glucagon-like peptide 2 on intestinal permeability and bacterial translocation in acute necrotizing pancreatitis.

BACKGROUND: Acute pancreatitis (AP) initiates a generalized inflammatory response that increases intestinal permeability and promotes bacterial translocation (BT). Impairment of the intestinal epithelial barrier is known to promote BT. Glucagon-like peptide 2 (GLP-2), a 33 residue peptide hormone, is a key regulator of the intestinal mucosa by stimulating epithelial growth. The purpose of this study was to determine whether GLP-2 decreases intestinal permeability and BT in AP. METHODS: To examine whether GLP-2 can decrease intestinal permeability and thereby decrease BT in acute necrotizing pancreatitis, 34 male Sprague-Dawley rats (200 to 300 g) were studied. AP was induced in group I and group II by pressure injection of 3% taurocholate and trypsin into the common biliopancreatic duct (1 mg/kg of body weight). The potent analog to GLP-2 called ALX-0600 was utilized. Group I rats received GLP-2 analog (0.1 mg/kg, SQ, BID) and group II rats received a similar volume of normal saline as a placebo postoperatively for 3 days. Group III and group IV received GLP-2 analog and placebo, respectively. At 72 hours postoperatively, blood was drawn for culture of gram-negative organisms. Specimens from mesenteric lymph nodes (MLN), pancreas and peritoneum were harvested for culture of gram-negative bacteria. Intestinal resistance as defined by Ohm's law was determined using a modified Ussing chamber to measure transepithelial current at a fixed voltage. A point scoring system for five histologic features that include intestinal edema, inflammatory cellular infiltration, fat necrosis, parenchymal necrosis, and hemorrhage was used to evaluate the severity of pancreatitis. Specimens from MLN, pancreas, jejunum, and ileum were taken for pathology. RESULTS: All group I and group II rats had AP. The average transepithelial resistance in group I was 82.8 Omega/cm(2) compared with 55.9 Omega/cm(2) in group II (P <0.01). Gram-negative BT to MLN, pancreas, and peritoneum was 80%, 0%, and 0%, respectively in group I compared with 100%, 30%, and 20% translocation in group II. CONCLUSION: GLP-2 treatment significantly decreases intestinal permeability in acute pancreatitis.

Intraoperative sestamibi scanning in reoperative parathyroidectomy.

BACKGROUND: Reoperative neck exploration for hyperparathyroidism is often difficult even for experienced surgeons. Recent advances in preoperative and intraoperative localization techniques have improved successful resection rates. This prospective study evaluates the accuracy and clinical utility of intraoperative technetium 99m sestamibi scanning for localizing hyperfunctioning parathyroid tissue in reoperative neck explorations. PATIENTS AND METHODS: Eleven patients underwent reoperative neck exploration for hyperparathyroidism. Two patients had 3 prior neck explorations, 1 had 2 prior neck explorations, and 8 patients had 1 prior neck operation. Preoperative studies included sestamibi scintigraphy and ultrasound in all patients, magnetic resonance imaging in 4, computed tomography scan in 3, parathyroid arteriogram in 1, and selective venous sampling in 1. All patients underwent intraoperative technetium 99m sestamibi scanning and parathyroid hormone assay. RESULTS: Preoperative technetium 99m sestamibi scanning and ultrasound each successfully localized 7 of 11 hyperfunctioning glands (64%). Intraoperative technetium 99m sestamibi scanning correctly localized 10 of 11 hyperfunctioning glands (91%). Intraoperative parathyroid hormone assay confirmed successful excision of hyperfunctioning tissue in all 11 patients. Postoperatively, all 11 patients had low-normal or normal calcium levels. CONCLUSIONS: Intraoperative technetium 99m sestamibi correctly localized 91% of hyperfunctioning glands compared with 64% localization for preoperative technetium 99m sestamibi and preoperative ultrasound. Intraoperative technetium 99m sestamibi scanning and parathyroid hormone monitoring are useful in reoperative neck explorations for hyperparathyroidism.

Laparoscopic ultrasound enhances diagnostic laparoscopy in the staging of intra-abdominal neoplasms.

Routine laparoscopy and laparoscopic ultrasound (LUS) for staging intra-abdominal malignancies remains controversial. Thus, we undertook a prospective study to assess the value of preoperative laparoscopy with LUS for patients with intra-abdominal tumors judged resectable by preoperative studies. Laparoscopy was successfully performed in 76 of 77 patients, and 60 underwent LUS. Of 33 patients with presumed pancreatic cancer, laparoscopic findings changed the operative management of 11 patients, and LUS altered the management of an additional 6 patients. Laparotomy was avoided in 9 patients (27%). Among 14 patients with hepatobiliary tumors, laparotomy was avoided in 9 patients in whom laparoscopy and/or LUS revealed either benign or advanced disease. Operative management was altered in 4 of 18 patients with gastric or esophageal cancer by laparoscopic findings. LUS did not add to the management of these patients. Of 12 patients with presumed intra-abdominal lymphoma, 9 were diagnosed with lymphoma and 3 with benign disease, without laparotomy in all but 1 case. Laparoscopy and LUS are valuable tools for evaluating the resectability of pancreatic and hepatobiliary tumors. Laparoscopy, and to a lesser degree LUS, greatly facilitates diagnosing patients with intra-abdominal lymphomas and spares an occasional patient with esophagogastric carcinoma from undergoing laparotomy.

The effect of lexipafant on bacterial translocation in acute necrotizing pancreatitis in rats.

Bacterial translocation (BT) from the gastrointestinal tract to mesenteric lymph nodes (MLNs) and other extra intestinal organs is an important source of infection in acute pancreatitis (AP). Lexipafant (BB-882) is a potent platelet-activating factor receptor antagonist that has an anti-inflammatory effect. To examine whether BB-882 could affect BT in acute necrotizing pancreatitis, 48 male Sprague Dawley rats (250-350 g) were studied. AP was induced in Group I and Group II by pressure injection of 3% taurocholate and trypsin into the common biliopancreatic duct (1 mL/kg of body weight). Group I rats received BB-882 (10 mg/kg, i.p. qd) and Group II rats received a similar volume of normal saline as a placebo postoperatively for 2 days. Group III and Group IV received BB-882 and placebo, respectively, after an exploratory laparotomy. At 48 hours postoperatively, blood was drawn for culture, serum amylase, and tumor necrosis factor (TNF)-alpha determinations. Specimens from MLNs, spleen, liver, pancreas, and cecum were harvested for culture of gram-positive, gram-negative, and anaerobic bacteria. Quantitative cecal cultures of gram-positive, gram-negative, and anaerobic bacteria were obtained. A point scoring system for five histological features that include interstitial edema, inflammatory cellular infiltration, fat necrosis, parenchymal necrosis, and hemorrhage was used to evaluate the severity of pancreatitis. There was no difference in serum amylase levels (2415 +/- 127 IU/L versus 2476 +/- 170 IU/L), serum TNF-alpha levels (7820 +/- 1396 pg/mL versus 7318 +/- 681 pg/mL), and the mean pancreatic histology score (5.9 +/- 1.2 versus 6.5 +/- 1.1) between Group I and Group II, respectively (P > 0.05). Seven of 12 Group I rats had BT to MLNs, compared with 11 of 12 rats in Group II (P > 0.05). Five of 12 Group I rats had BT to distant sites such as pancreas, spleen, liver, and/or blood, compared with 11 of 12 rats in Group II (P < 0.05). BB-882 treatment decreases bacterial spread to distant sites, but does not reduce serum amylase levels and serum TNF-alpha levels or ameliorate pancreatic damage in rats with AP.

Definitions of physical and biological low dose.

The concept of 'low dose' may be understood to refer to an average frequency of microdosimetric events (charged-particle traversals) that is substantially less than unity in cells or their nuclei. An important consequence is that in this case the probability of any effect on autonomous cells must be proportional to the absorbed dose and independent of dose rate. However, this definition may be unnecessarily restrictive because--especially in the case of low-LET radiation--only a small fraction of events may cause the effects under consideration (e.g. cell lethality). This results in larger 'biological' rather than 'physical' 'small doses'. From a pragmatic viewpoint, one may consider the fact that in the linear-quadratic model deviations from proportionality between effect probability and absorbed dose are attributed to a term that depends on the square of the absorbed dose. This permits the selection of a criterion which establishes as 'small doses' those in which such deviations are less than a chosen value which in the examples given here is 10%. Different applications of this criterion to the inactivation of V 79 hamster cells are considered.

Clinical and radiological predictors of complete excision in breast-conserving surgery for primary breast cancer.

BACKGROUND: Local recurrence after conservative surgery for breast cancer usually results from growth of residual cancer adjacent to the excised primary tumour or from multicentric disease. Complete local excision (CLE) confirmed histologically is essential to ensure that the risk of local recurrence is minimal. This study was undertaken to determine that clinical or radiological factors may assist the surgeon at the time of surgery to achieve this aim. METHODS: A retrospective review of 101 cases treated by conservative surgery identified 70 cases of CLE and 31 of incomplete local excision (ILE). Clinical, surgical and histopathological data were taken from hospital records. Mammographic features and those of specimen X-rays were evaluated without knowledge of the histopathological outcome of surgery. RESULTS: Complete excision was significantly associated with type of operation (lumpectomy vs wide local excision/quadrantectomy, P < 0.003), absence of calcification (P < 0.03) and the presence of a mass on mammography (P = 0.05). Tumour size (> 2.5 cm) and the presence of extensive ductal carcinoma in situ (DCIS) were associated with incomplete excision (P = 0.0005). No relationship was demonstrated with patient age, breast size, breast density, tumour grade, receptor status, axillary nodal status or spicules on X-ray and completeness of excision. Specimen X-ray had a positive predictive value of 94% with CLE. CONCLUSIONS: Clinical and pre-operative mammographic parameters are important for predicting CLE for breast cancers treated by breast-conserving surgery. Specimen radiology for palpable lesions can confirm excision of the cancer and permit re-excision of breast tissue at the time of initial surgery. Its role in determining CLE should be further evaluated.

Inactivated whole-cell bacterial vaccines: current status and novel strategies.

Inactivated bacterial whole-cell vaccines have been the most widely studied prophylactic treatment for infectious diseases. They offer an economical, and potentially safe, effective means of preventing disease. The disadvantages of these vaccines have been that parenteral administration, while effective in some instances, may have caused adverse reactions in vaccinees, while oral administration often required high doses and resulted in short-term immunity. More recent studies describing new approaches for improving antigenicity of inactivated whole-cell vaccines and the enhancement of immune responses to oral immunization offer great hope for improving the efficacy of these agents. Promising whole cell vaccines include those against Vibrio cholerae, enterotoxigenic Escherichia coli, and more recently Campylobacter jejuni.

Effect of bile on Vibrio parahaemolyticus.

Many enteric pathogens are thought to enter a viable but nonculturable state when deprived of nutrients. Virulent strains of the enteric pathogen Vibrio parahaemolyticus are rarely isolated from their low-nutrient aquatic environments, possibly due to their nonculturability. Host factors such as bile may trigger release from dormancy and increase virulence in these strains. In this study, the addition of bile or the bile acid deoxycholic acid to estuarine water-cultured bacteria led to an increase in the direct viable count and colony counts among the virulent strains. This effect was not demonstrated in the nonvirulent strains, and it was reversed by extraction of bile acids with cholestyramine. Bile-treated V. parahaemolyticus had lower levels of intracellular calcium than untreated cells, and this effect coincided with an increase in the number of metabolically active cells. Chelation of intracellular calcium with BAPTA/AM (R. Y. Tsien, Biochemistry 19:2396-2402, 1980) produced similar results. Addition of bile to V. parahaemolyticus cultures in laboratory medium enhanced factors associated with virulence such as Congo red binding, bacterial capsule size, and adherence to epithelial cells. These results suggest that a bile acid-containing environment such as that found in the human host favors growth of virulent strains of V. parahaemolyticus and that bile acids enhance the expression of virulence factors. These effects seem to be mediated by a decrease in intracellular calcium.

Radiogenic lung cancer: the effects of low doses of low linear energy transfer (LET) radiation.

A critical review of the literature leads to the conclusion that at the radiation doses generally of concern in radiation protection (< 2 Gy), protracted exposure to low linear energy transfer (LET) radiation (x- or gamma-rays) does not appear to cause lung cancer. There is, in fact, indication of a reduction of the natural incidence.