Ceftazidime improves hemodynamics and oxygenation in ovine smoke inhalation injury and septic shock.

OBJECTIVE: To investigate ceftazidime in acute lung injury (ALI) and sepsis. DESIGN AND SETTING: Prospective, randomized, controlled animal study in an investigational ICU at a university hospital. INTERVENTIONS: Eighteen female Merino sheep were prepared for chronic study and subjected to smoke inhalation and septic challenge according to an established protocol. MEASUREMENTS AND RESULTS: Whereas global hemodynamics and oxygenation remained stable in sham animals (no injury, no treatment), the injury contributed to a hypotensive-hyperdynamic circulation in the control group (smoke inhalation and sepsis, no treatment), as indicated by a significant increase in cardiac index) and heart rate and a drop in mean arterial pressure. Treatment with ceftazidime (smoke inhalation and sepsis, treatment group) stabilized cardiac index and heart rate and attenuated the decrease in mean arterial pressure. The deterioration in PaO2/FiO2 ratio and pulmonary shunt fraction (Qs/Qt) was significantly delayed and blunted by ceftazidime. At 24 h after injury a significant increase in airway obstruction scores of bronchi and bronchioles in both injured groups was observed. Ceftazidime significantly reduced airway obstruction vs. control animals. Whereas plasma nitrate/nitrite levels increased similarly in the two injured groups, lung 3-nitrotyrosine content remained at the baseline level in the ceftazidime group. CONCLUSIONS: In ovine lung injury ceftazidime improves global hemodynamics and oxygenation not only by bacterial clearance but also via reduction in toxic nitrogen species such as 3-nitrotyrosine. Therefore ceftazidime appears as a clinically relevant adjunct in the common setting of sepsis-associated lung injury.

Effects of severe smoke inhalation injury and septic shock on global hemodynamics and microvascular blood flow in sheep.

This prospective, randomized, controlled experimental study looks at the effects on global and regional microvascular blood flow (RMBF) in an ovine model of septic shock after severe smoke inhalation injury. Sixteen sheep were randomized into two groups, a control group (no injury, n = 8) and a smoke/sepsis (SS) group (n = 8), which received an insufflation of 4 sets of 12 breaths of cotton smoke (<40 degrees C) followed by instillation of live Pseudomonas aeruginosa into both lung lobes, according to an established protocol. All sheep were mechanically ventilated with 100% oxygen, and fluid resuscitated with lactated Ringer's solution for the entire duration of the 24-h experimental period to maintain hematocrit at baseline (BL) levels. Healthy control animals were not subjected to the injury and received only 4 x 12 breaths of room air and instillation of the vehicle (normal saline). Blood flow was analyzed using colored microspheres. Control animals remained hemodynamically stable and had no statistical changes from BL in visceral or cerebral blood flow during the entire experimental period. All SS animals developed a hypotensive, hyperdynamic circulation, characterized by a significant increase in heart rate and cardiac output with a simultaneous significant fall in mean arterial pressure, which, in combination, led to a fall in systemic vascular resistance index versus BL (P < 0.001, each). In visceral organs, the trachea showed a significant increase in RMBF (P < 0.001). In addition, skeletal muscle significantly increased versus BL and versus controls over time (P < 0.01). Whereas the pancreas displayed a significant drop in RMBF versus BL and controls (P < 0.05), no statistical differences occurred in the renal cortex, spleen, and ileum. All investigated cerebral structures, such as the cortex cerebri, basal ganglia, thalamus, hippocampus, pons, medulla oblongata, and cerebellum showed a significant increase in RMBF versus BL and versus control animals (P < 0.05, each). These data differ in areas of normal, increased, and decreased RMBF during septic shock after smoke inhalation injury and show differences to former studies of our group investigating RMBF in ovine models of either smoke inhalation or P. aeruginosa infusion. The results of this study reflect the complex pathophysiological variances of the combined injury and may provide a basis for future investigations for the treatment of this kind of injury.

Neoadjuvant treatment of gastric cancer with peritoneal dissemination.

AIMS: To report our experience of neoadjuvant intraperitoneal and systemic chemotherapy (NIPS) for patients having a complete resection of the primary gastric cancer and peritoneal carcinomatosis (PC). PATIENTS AND METHODS: Patients with advanced peritoneal dissemination of primary gastric cancer had the placement of a peritoneal port system. For intraperitoneal chemotherapy, 40 mg of docetaxel and 150 mg of carboplatin were introduced in 1000 ml of saline on a weekly basis. Simultaneously, 100 mg/m2 of methotrexate and 600 mg/m2 of 5-fluorouracil were infused via a peripheral vein. A minimum of two cycles and up to six cycles of NIPS were used prior to cancer resection. At surgery a complete removal of the primary gastric cancer and the peritoneal implants by peritonectomy was attempted. RESULTS: Sixty-one patients were enrolled in the study. Thirty-nine had positive intraperitoneal cytology which reverted to negative cytology after treatment in 22. Thirty-eight showed a partial response. Thirty patients came to resection and 14 patients could be made disease-free. Median survival time of all patients was 14.4 months. Patients who received a complete resection had a median survival time of 20.4 months. Grade III/IV toxicities were not found after two courses of NIPS, but did develop in seven patients after more than three courses of NIPS. CONCLUSION: NIPS can downstage large volume peritoneal dissemination of gastric cancer. When combined with gastrectomy including peritonectomy a complete surgical resection was possible in one-quarter of the patients and resulted in a prolonged survival. This combined intraperitoneal and systemic chemotherapy for PC from gastric cancer is worthy of consideration for phase III clinical investigations.

Intraoperative lavage for cytological examination in 1,297 patients with gastric carcinoma.

BACKGROUND: This study examined the clinical value of intraoperative peritoneal lavage for cytological examination in patients with gastric cancer. Peritoneal dissemination is the most frequent mode of recurrence for this tumor. METHODS: A retrospective of lavage findings, other factors, and outcome was performed in 1,297 patients with gastric cancer who underwent intraoperative peritoneal lavage. RESULTS: The 5-year survival rate of patients with positive lavage cytology was only 2%. Patients who underwent curative resection and had negative cytology had a significantly better 5-year survival rate (P < 0.001). Even among patients with macroscopic peritoneal dissemination, the survival rate was significantly better with negative cytology, which reflected fewer free cancer cells in the peritoneal cavity. Serum concentrations of carcinoembryonic antigen and carbohydrate antigen 19-9 were significantly higher in patients with positive cytology. Multivariate analyses indicated that intraoperative cytological findings was an independent prognostic factor for survival, and was the most important factor for predicting peritoneal recurrence. CONCLUSIONS: Intraoperative peritoneal lavage cytology is important in predicting survival and peritoneal recurrence in gastric cancer.

A new technique for variable-load cholangiomanometry. Implication for biliary tract surgery.

BACKGROUND/AIMS: Variable-load cholangiomanometry was performed to obtain data on terminal biliary function during the surgical treatment of cholelithiasis. The decision of whether or not to perform a definitive biliary drainage procedure was based on the results of this test. MATERIAL AND METHODS: The rate of perfusion was reduced in four steps from 15.3 ml/min to 1.2 ml/min, and the resultant perfusion pressures were plotted. The gradient produced by the straight line was considered the resistance, R. The baseline pressure without perfusion was regarded as the static pressure, P. RESULTS: A review of 444 patients with cholelithiasis who underwent intraoperative cholangiomanometry during the past 11 years led to the following indications for definitive biliary drainage: (1) R > 10 units and P > 200 mm H2O, (2) if only R or P is elevated, priority is given to R, and (3) if the elevation of R or P is borderline, the presence of a type I curvature in the segment of low flow rate is an indication for surgery. CONCLUSION: By performing an intraoperative cholangiomanometry concrete indications for a biliary drainage procedure can be defined.

[Effect of chemotherapy using irinotecan (CPT-11) against recurrent colorectal cancer].

Irinotecan (CPT-11) is a camptothecine derivative with antitumor activity and inhibitor of DNA topoisomerase I. CPT-11 showed a excellent and broad anticancer activity against several malignant tumors. In this study, as in the Japanese phase II study, CPT-11 was administered at 100 mg/m2 weekly by intravenous infusion against 10 patients with recurrent colorectal cancer. Median total dose was 513 mg. Partial responses were obtained in 4/10 patient (40%). Lung metastases showed a 33.3% response and lymphnode metastases showed a 60% response. However, liver metastases showed no response. The median duration to the onset of partial response was 20 days and the median overall response duration was 89 days. Adverse effects were leukopenia (40%), nausea, vomiting and diarrhea (80%), fever (20%), and general malaise (30%). These were generally well tolerated and reversible. From these results, CPT-11 seemed to become an effective drug for recurrent colorectal cancer. Further trials of combination chemotherapy utilizing CPT-11 seem to be warranted.

[A case of advanced gastric cancer showing complete disappearance of cancer cells in multiple liver metastases due to low-dose PMUE therapy].

A case of gastric cancer with liver metastasis who responded well to low-dose PMUE (CDDP, MMC, UFT, etoposide) therapy is reported. A 65-year-old man underwent distal partial gastrectomy with D2 lymph node dissection under the diagnosis of type 5 gastric cancer with multiple liver metastases. Pathological findings revealed papillary adenocarcinoma in the primary lesion and metastatic lymph nodes (No. 8a). Low-dose PMUE therapy after resection of primary lesion was effective for the liver metastases. Exacerbation was suspected, so the lesions of metastases were resected again after 2 years and 11 months postoperative course. All 4 resected lesions of metastases became old fibrous tissue with hyalinization, and 2 of 4 lesions were necrotic and surrounded by fibrous connective tissue. None of these 4 lesions included viable cancer cells. The patient has now been followed with no evidence of exacerbation. It was suggested that low-dose PMUE therapy was effective for liver metastasis of gastric cancer, especially the differentiated type.

[The clinicopathological analysis of lymph node metastasis of gastric cancer].

One hundred-twenty-one cases of curative resection for gastric cancer with lymph node metastasis were analyzed to determine the prognostic value of the nodal stage (n), number of metastatic lymph nodes, maximum diameter of metastatic lymph nodes, micrometastasis of lymph nodes, histological type of lymph node metastasis, extranodular invasion and infiltration into lymphatic vessels around metastatic lymph nodes. In patients with a higher nodal stage the survival rate was lower and the nodal stage was a good prognostic indicator. Inpatients who had 7 or more metastatic lymph nodes or in whom the maximum diameter of the metastatic lymph nodes was over 15 mm or who had not only micrometastasis of lymph nodes, the survival rate was lower. These results suggest that quantitative analysis of metastatic lymph nodes is necessary. In patients who had nudifferentiated type metastatic lesions of lymph nodes, the survival rate was lower than in those with the differentiated type and the difference was larger than for the primary lesion. In patients who had extranodular invasion or infiltration into lymphatic vessels around metastatic lymph nodes, the survival rate was decreased. These results suggest that histopathological analysis of metastatic lymph nodes is necessary.

[Clinical study of ten cases with acute abdomen after eating raw firefly squid (Watasenia scintillans, Hotaruika), which are probably due to type X larvae of the suborder spirurina].

We studied ten cases with abdominal pain after eating raw firefly squid, Watasenia scintillans, Hotaruika. Characteristic clinical features were abdominal pain, nausea, vomiting, diarrhea, creeping eruption and ileus with ascites. In ten patients, there were all cases with abdominal pain, nine with nausea and vomiting, four with diarrhea, one with creeping eruption, six with ileus. Laboratory examination revealed eosinophilia on peripheral blood in ten cases and high serum IgE value in nine cases. The infection rate of type X lavae of the suborder spirurina in Watasenia scintillans is almost 3%, so we measured the antibody to type X larvae of the suborder spirurina in nine patients by indirect fluorescent antibody method and the antibody titer was positive in seven cases. Most patients recovered in several days from first visit. But one patient was diagnosed peritonitis and operated with partial ileectomy. Pathological finding of resected specimen showed an erosion in the mucosal layer and an inflammation with marked eosinophilia in the submucosal layer. These results suggest that abdominal complaints after eating Watasenia scintillans are due to type X larvae of the suborder spirurina.

Light and electron microscopic observation of intracytoplasmic inclusion bodies in the locus coeruleus of the hamster.

The authors previously demonstrated that intracytoplasmic inclusion bodies (1-3 microm) in the mouse locus coeruleus under light and electron microscopy are characteristically stained using the Holmes modified method. We reported that one inclusion body existed in almost all neurons of the locus coeruleus. The present study examined whether similar inclusion bodies are present in the Syrian hamster (weight, about 60 g). Paraffin sections stained with the modified Holmes' method dis played numerous small inclusion bodies in the cytoplasm of cells in the locus coeruleus. Epon sections (1 microm thick) stained using toluidine blue were observed under light microscopy, and numerous small inclusion bodies were again observed. Under electron microscopy observation, inclusion bodies (<1 microm in diameter) predominantly comprised small granular materials, similar to those described by previous investigators. Although inclusion bodies were devoid of a limiting membrane, the relation ship to cytoplasmic organelles was unclear. However, free and polyribosomes were occasionally noted in close proximity to inclusion bodies. Inclusion bodies may thus be formed from ribosomes. Intracytoplasmic inclusion bodies in the hamster locus coeruleus differed in appearance compared with inclusion bodies in the mouse locus coeruleus.

Carbohydrate antigen 19-9 producing giant epithelial cyst of the spleen in a young woman.

We report a giant splenic epithelial cyst which produced carbohydrate antigen 19-9 (CA 19-9) in a 21-year-old woman with left abdominal pain. Imaging techniques revealed a huge cyst of the spleen, and laboratory data revealed elevated serum CA 19-9 (830 U/ml; normal, < 27 U/ml). After splenectomy, serum CA 19-9 level returned to normal. A unilocular splenic cyst measuring 16 x 14 x 13 cm contained brown fluid (900 ml) with a high level of CA 19-9 (10,150,000 U/ml). The wall of the splenic cyst was composed of inner stratified epithelium with mixed squamous and columnar differentiation; immunohistochemical analysis showed that the epithelial cells of the cyst showed strong immunoreactivity to CA 19-9. The inner connective tissue of the cyst wall devoid of epithelial cells was also strongly positive for CA 19-9. We suggest that epithelial cells of our splenic epithelial cyst produced a large amount of CA 19-9 which diffused into capillaries of the connective tissue of the cyst wall and entered into systemic circulation, resulting in the elevated serum CA 19-9.

Superoxide dismutase activity in rabbit reticulocytes.

Reticulocytosis was induced in rabbits by bleeding anemia and erythrocyte superoxide dismutase activity was determined. Reticulocytes were found to contain about 1.3 times as much activity as mature erythrocytes.

The role of 16,16-dimethyl prostaglandin E2 on the intrahepatic biliary branches in dogs.

We studied the effects of the oral administration of a stable prostaglandin E2 analog, 16,16-dimethyl prostaglandin E2, on the intrahepatic biliary branches in a canine model. Obstructive cholestasis with a bacterial infection was induced surgically in two liver lobes in healthy mongrel dogs, and 16,16-dimethyl prostaglandin E2 was administered orally. We examined the morphological changes in the intrahepatic biliary branches and quantitatively estimated density of mucus-producing glandular elements in the ductal wall by counting these glands per unit area. Dogs treated with 16,16-dimethyl prostaglandin E2 (group 1) demonstrated fibrous thickening of the ductal wall, moderate infiltration by inflammatory cells and severe adenomatous hyperplasia of the bile duct epithelium, including striking proliferation of the mucous glands. The mean number of these mucous glands per unit area (4 mm2) was 43.0 +/- 9.0 (mean +/- S.D.; range = 36 to 56). In contrast, in a control group whose members did not receive 16,16-dimethyl prostaglandin E2 (group 2), the mean number of mucous glands per unit area was 19.4 +/- 8.0 (range = 10 to 29), significantly lower than that in group 1, although histological examination revealed chronic inflammation in the region of the large bile duct similar to that in group 1. These findings suggest that the increase in the number of mucous glands that typically occur in the setting of bile stasis and biliary infection is enhanced by 16,16-dimethyl prostaglandin E2.

Stromal distribution of CA 19-9 as a predictor of lymph node metastases in gallbladder cancer without serosal invasion.

Gallbladder cancer without serosal invasion is often diagnosed during the pathologic examination of a gallbladder removed for presumed benign disease. The role of reoperative procedures in these patients is not well established, making it important to define prognostic factors that predict cancer spread. To determine if the pattern of immunohistochemical staining with a monoclonal antibody against CA 19-9 could predict lymph node spread of cancer, 23 patients with gallbladder cancer without serosal invasion were reviewed. CA 19-9 reaction was present in pathology specimens from all 23 patients. Twelve samples (52.2%) showed CA 19-9 in the stroma adjacent to cancer cells, while the remaining 11 did not show any stromal staining against CA 19-9. Lymph node development was found in only 2 (18.2%) of these 11 patients in the nonstromal staining group and 9 (75%) of the 12 patients in the stromal staining group. As these differences were statistically significant, we conclude that immunohistochemical localization of CA 19-9 in gallbladder cancer may be useful in predicting the presence or absence of lymph node involvement, and in developing a rational approach for a reoperative procedure.

Contrast is enhanced by yellow lenses because of selective reduction of short-wavelength light.

PURPOSE: Although many studies have shown a subjective preference for yellow lenses, there has been little success in determining the clinical nature of this benefit. METHOD: Contrast sensitivity, color vision, accommodative-convergence, and visual acuity were measured in a group of 20 young subjects along with subjective rating of their perception through clear control lenses (380-nm cut-off), yellow lenses (450-nm cut-off), dark yellow lenses (511-nm cut-off), and orange lenses (527-nm cut-off). RESULTS: A systematic detriment to color vision was found to occur with increasing cut-off wavelength of the yellow lenses (p < 0.001) and this was significantly correlated to subjective ratings of color (r = -0.66) and brightness (r = -0.34). Perceived brightness significantly improved for the yellow (450-nm cut-off) lens only (p < 0.001). Although tinted lenses reduced contrast sensitivity to a white on black grating, there was a significant improvement in low to midrange spatial frequencies when measured using a white-on-blue grating. CONCLUSIONS: The detriment in color vision caused by yellow-colored lenses enhances contrast when viewing bright objects against a blue-based background, such as the sky. Contrast of overlying objects is enhanced is due to the selective reduction of short-wavelength light by the yellow lenses.