Ex vivo electrical impedance measurements on excised hepatic tissue from human patients with metastatic colorectal cancer.

Point-wise ex vivo electrical impedance spectroscopy measurements were conducted on excised hepatic tissue from human patients with metastatic colorectal cancer using a linear four-electrode impedance probe. This study of 132 measurements from 10 colorectal cancer patients, the largest to date, reports that the equivalent electrical conductivity for tumor tissue is significantly higher than normal tissue (p < 0.01), ranging from 2-5 times greater over the measured frequency range of 100 Hz-1 MHz. Difference in tissue electrical permittivity is also found to be statistically significant across most frequencies. Furthermore, the complex impedance is also reported for both normal and tumor tissue. Consistent with trends for tissue electrical conductivity, normal tissue has a significantly higher impedance than tumor tissue (p < 0.01), as well as a higher net capacitive phase shift (33° for normal liver tissue in contrast to 10° for tumor tissue).

Risk factors for catheter-related thrombosis (CRT) in cancer patients: a patient-level data (IPD) meta-analysis of clinical trials and prospective studies.

BACKGROUND: Knowledge of independent, baseline risk factors for catheter-related thrombosis (CRT) may help select adult cancer patients who are at high risk to receive thromboprophylaxis. OBJECTIVES: We conducted a meta-analysis of individual patient-level data to identify these baseline risk factors. PATIENTS/METHODS: MEDLINE, EMBASE, CINAHL, CENTRAL, DARE and the Grey literature databases were searched in all languages from 1995 to 2008. Prospective studies and randomized controlled trials (RCTs) were eligible. Studies were included if original patient-level data were provided by the investigators and if CRT was objectively confirmed with valid imaging. Multivariate logistic regression analysis of 17 prespecified baseline characteristics was conducted. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated. RESULTS: A total sample of 5636 subjects from five RCTs and seven prospective studies was included in the analysis. Among these subjects, 425 CRT events were observed. In multivariate logistic regression, the use of implanted ports as compared with peripherally implanted central venous catheters (PICCs), decreased CRT risk (OR, 0.43; 95% CI, 0.23-0.80), whereas past history of deep vein thrombosis (DVT) (OR, 2.03; 95% CI, 1.05-3.92), subclavian venipuncture insertion technique (OR, 2.16; 95% CI, 1.07-4.34) and improper catheter tip location (OR, 1.92; 95% CI, 1.22-3.02), increased CRT risk. CONCLUSIONS: CRT risk is increased with use of PICCs, previous history of DVT, subclavian venipuncture insertion technique and improper positioning of the catheter tip. These factors may be useful for risk stratifying patients to select those for thromboprophylaxis. Prospective studies are needed to validate these findings.

Design and benchtop validation of a handheld integrated dynamic breast imaging system for noninvasive characterization of suspicious breast lesions.

We have developed a portable, handheld, integrated, dynamic breast imaging system that integrates a near infrared tissue oximeter, clinical ultrasound, and two pressure sensors for noninvasive detection of pressure-induced structural and functional dynamics of suspicious breast lesions. A series of benchtop tests were conducted to validate multiple performance characteristics of the integrated dynamic near infrared/ultrasound breast imaging system (idNIRUS), including the reconstruction of the absorptive heterogeneities and the generation of the dynamic compression stimuli. In absorptive heterogeneity testing, we reconstructed the absorption coefficients of transparent polypropylene tubing circulated with a skim milk-India ink mixture and embedded in a gel wax tissue simulating phantom. High linear correlations (R(2) greater than 0.989) were observed between the reconstructed and the measured absorption coefficients of the embedded tubing. In dynamic compression testing, five volunteer operators generated ten successive compression sessions by compressing the idNIRUS imager on a breast self examination wearable model following the computer simulated pressure profile. The manually generated pressure profiles demonstrated an accuracy of 95.7% and operator-dependent variation of less than 5%. The results of the current benchtop tests will help to optimize the most appropriate testing conditions for our future planned clinical trial.

Partial tear of pectoralis major muscle masquerading as a breast mass in an 87-year-old woman. A case report.

We report on a case of a partial tear of the pectoralis major muscle mimicking a breast mass in an elderly patient. Breast MR was useful in identifying the traumatic muscular injury and in demonstrating the lack of any intraparenchymal breast lesion.

Novel applications of Endo GIA linear staplers during pancreaticoduodenectomy and total pancreatectomy.

Pancreaticoduodenectomy and total pancreatectomy remain a formidable challenge to many surgeons. This report describes the utilization of Endo GIA linear staplers for division of the proximal jejunal mesentery and division of the uncinate process during pancreatic surgery. Their use may help to reduce undue bleeding during surgery, reduce total operative time, and ultimately reduce postoperative morbidity and mortality.

Gastric schwannoma found incidentally 19 years after a horizontal gastroplasty for morbid obesity.

This report represents the first known case of a gastric schwannoma in a patient subsequent to a gastric stapling and partitioning procedure for morbid obesity. The submucosal tumor found in the collapsed distal portion of the stomach was merely an incidental finding and it appeared that all of the patient's ongoing symptomatology (nausea and vomiting after meals) was a reflection of the chronic obstruction that was present at the gastric partitioning staple-line. No correlation between gastric stapling and partitioning and the development of gastric schwannoma is known or is suggested in this report.

Recognition of intrabiliary hepatic metastases from colorectal adenocarcinoma.

Intrinsic involvement of bile ducts, by metastatic colorectal adenocarcinoma growing from within or invading the lumen of bile ducts, is not a well recognized pattern of tumor growth. Clinical, radiographic, operative, and histopathologic aspects of 15 patients with intrabiliary colorectal metastases were described. Fourteen patients were explored for possible hepatic resection. Two had jaundice, two radiographic evidence of an intrabiliary filling defect, 10 intraoperative evidence of intrabiliary tumor, and six microscopic evidence of intrabiliary tumor. Eleven patients underwent hepatic resection. Five of the resected patients developed hepatic recurrence. Four patients were explored for possible repeat resection. One had jaundice, one radiographic evidence of an intrabiliary filling defect, all had intraoperative evidence of intrabiliary tumor, and three microscopic evidence of intrabiliary tumor. Three patients underwent repeat hepatic resection. All patients with preoperative jaundice and radiographic evidence of an intrabiliary filling defect were unresectable. Overall, actuarial five-year survival is 33% for those patients resected versus 0% for those not resected. Intraoperative recognition of intrabiliary tumor at exploration for hepatic resection was more common than clinical, radiographic, or histopathologic recognition. More diligent examination of resected liver tissue by the surgeon and pathologist may increase identification of bile duct involvement and aid in achieving adequate tumor clearance.

A prospective analysis of the cephalic vein cutdown approach for chronic indwelling central venous access in 100 consecutive cancer patients.

BACKGROUND: Chronic indwelling central venous access devices (CICVAD) generally are placed by the percutaneous subclavian vein approach. The cephalic vein cutdown approach is used only infrequently. Although the technique has been well described, few prospective data are available on the cephalic vein cutdown approach. METHODS: From September 9, 1998, to July 20, 1999, the cephalic vein cutdown approach was attempted in 100 consecutive cancer patients taken to the operating room with the intention of placing CICVAD. Median patient age was 54.5 years (range 18-88), with 46 men and 54 women. Twenty-five patients had gastrointestinal malignancies, 17 had breast cancer, 15 had lymphoma, 13 had lung cancer, 12 had leukemia, 5 had multiple myeloma, and 13 had other malignancies. Patients were followed prospectively for immediate and long-term outcome. RESULTS: CICVAD placement via the cephalic vein cutdown approach was successful in 82 patients; the remaining 18 patients required conversion to a percutaneous subclavian vein approach. The reasons for inability to place CICVAD via cephalic vein cutdown approach were a cephalic vein that was too small (10 patients), an absent cephalic vein (7 patients), and inability to traverse the angle of insertion of the cephalic vein into the subclavian vein (1 patient). There were 56 subcutaneous ports and 26 tunneled catheters. Median operating time was 44 minutes (range, 26-79 minutes). No postoperative pneumothorax occurred. Median catheter duration was 198 days (range, 0-513 days). Long-term complications included catheter-related bacteremia (6%), site infection (2%), deep venous thrombosis (5%), port pocket hematoma (1%), and superior vena cava stricture (1%). Thirty-seven percent of patients have died since CICVAD placement. Twenty-nine percent of the CICVADs have been removed. CONCLUSIONS: The cephalic vein cutdown approach was successful in 82% of patients. This approach is a safe and useful alternative to the percutaneous subclavian vein approach.

Evaluation of percutaneous penetration of natural rubber latex proteins.

Latex allergy is recognized worldwide as a serious health risk. To date, exposure assessment and intervention strategies have focused primarily on respiratory protection; this work evaluates the potential role of dermal protein penetration in the development of latex allergy. In vitro penetration models using flow-through diffusion cells and both human surgical specimens and hairless guinea pig skin (CrL: IAF/HA) demonstrated iodinated latex proteins (ammoniated and non-ammoniated) penetrating into and through both intact and abraded skin. Although less than 1% penetration was observed with intact skin, up to 23% of latex proteins applied to abraded skin were recovered from receptor fluid within 24 h of exposure. Phosphoimaging of the concentrated effluent revealed proteins ranging in size from 3 to 26 kDa. Using a (3)H(2)O penetration assay to evaluate barrier integrity, the amount of latex protein penetration was found to positively correlate with the degree of dermabrasion. Immunohistochemistry of the skin localized latex proteins in the Langerhans cell-rich epidermis and in the dermis. Both in vitro penetration studies and immunohistochemistry supported the use of hairless guinea pig skin as a surrogate for human skin in evaluating latex protein penetration. In studies performed in vivo, 35% of hairless guinea pigs topically exposed to latex proteins (100 microg) 5 days per week for 3 months demonstrated elevations in latex-specific IgG1. The implication for these data is that the skin is not only a plausible route for latex sensitization but can be a major exposure route when the integument has been compromised.

Extended left hepatectomy.

Extended left hepatectomy (resection of Couinaud segments II, III, IV, V, and VIII of the liver) has only slowly been appreciated as a viable resectional technique for large, strategically placed, left-sided and central hepatic lesions that extend to involve the right anterior sectoral portal pedicular structures. We report on the preoperative, intraoperative, and postoperative findings of 51 patients undergoing extended left hepatectomy at Memorial Sloan-Kettering from 1992 to 1998. Median age was 58 years (range 1-85), with 28 males and 23 females. Altogether 34 patients had metastatic hepatic malignancies, 14 had primary hepatic malignancies, and 3 had benign hepatic lesions. Median postoperative length of stay was 10 days (range 6-52). Postoperative morbidity and mortality were 53% and 8%, respectively. Multivariate analysis of multiple preoperative variables disclosed that only the largest hepatic lesion of >8 cm (p = 0.033) was an independent predictor of a positive microscopic margin or tumor within one high power field. No preoperative, intraoperative, or postoperative variables were independent predictors of postoperative morbidity or mortality. Utilization of extended left hepatectomy allows resection of critically positioned hepatic lesions previously thought unresectable. It can be performed relatively safely, although it is not without somewhat increased postoperative morbidity and mortality compared to lesser anatomic hepatic resections. Patient selection, as dictated by factors associated with adequate tumor clearance (tumor size and proximity to the right sectoral portal pedicular structures), may be important for determining appropriate candidates for this aggressive resectional technique.

Preoperative biliary drainage: impact on intraoperative bile cultures and infectious morbidity and mortality after pancreaticoduodenectomy.

Whether it is necessary to perform biliary drainage for obstructive jaundice before performing pancreaticoduodenectomy remains controversial. Our aim was to determine the impact of preoperative biliary drainage on intraoperative bile cultures and postoperative infectious morbidity and mortality following pancreaticoduodenectomy. We retrospectively analyzed 161 consecutive patients undergoing pancreaticoduodenectomy in whom intraoperative bile cultures were performed. Microorganisms were isolated from 58% of these intraoperative bile cultures, with 70% of them being polymicrobial. Postoperative morbidity was 47% and mortality was 5%. Postoperative infectious complications occurred in 29%, most commonly wound infection (14%) and intra-abdominal abscess (12%). Eighty-nine percent of patients with intra-abdominal abscess (P = 0.003) and 87% with wound infection (P = 0.003) had positive intraoperative bile cultures. Microorganisms in the bile were predictive of microorganisms in intraabdominal abscess (100%) and wound infection (69%). Multivariate analysis of preoperative and intraoperative variables demonstrated that preoperative biliary drainage was associated with positive intraoperative bile cultures (P <0.001), postoperative infectious complications (P = 0.022), intra-abdominal abscess (P = 0.061), wound infection (P = 0.045), and death (P = 0. 021). Preoperative biliary drainage increases the risk of positive intraoperative bile cultures, postoperative infectious morbidity, and death. Positive intraoperative bile cultures are associated with postoperative infectious complications and have similar microorganism profiles. These data suggest that preoperative biliary drainage should be avoided in candidates for pancreaticoduodenectomy.

Association of preoperative biliary drainage with postoperative outcome following pancreaticoduodenectomy.

OBJECTIVE: To determine whether preoperative biliary instrumentation and preoperative biliary drainage are associated with increased morbidity and mortality rates after pancreaticoduodenectomy. SUMMARY BACKGROUND DATA: Pancreaticoduodenectomy is accompanied by a considerable rate of postoperative complications and potential death. Controversy exists regarding the impact of preoperative biliary instrumentation and preoperative biliary drainage on morbidity and mortality rates after pancreaticoduodenectomy. METHODS: Two hundred forty consecutive cases of pancreaticoduodenectomy performed between January 1994 and January 1997 were analyzed. Multiple preoperative, intraoperative, and postoperative variables were examined. Pearson chi square analysis or Fisher's exact test, when appropriate, was used for univariate comparison of all variables. Logistic regression was used for multivariate analysis. RESULTS: One hundred seventy-five patients (73%) underwent preoperative biliary instrumentation (endoscopic, percutaneous, or surgical instrumentation). One hundred twenty-six patients (53%) underwent preoperative biliary drainage (endoscopic stents, percutaneous drains/stents, or surgical drainage). The overall postoperative morbidity rate after pancreaticoduodenectomy was 48% (114/240). Infectious complications occurred in 34% (81/240) of patients. Intraabdominal abscess occurred in 14% (33/240) of patients. The postoperative mortality rate was 5% (12/240). Preoperative biliary drainage was determined to be the only statistically significant variable associated with complications (p = 0.025), infectious complications (p = 0.014), intraabdominal abscess (p = 0.022), and postoperative death (p = 0.037). Preoperative biliary instrumentation alone was not associated with complications, infectious complications, intraabdominal abscess, or postoperative death. CONCLUSIONS: Preoperative biliary drainage, but not preoperative biliary instrumentation alone, is associated with increased morbidity and mortality rates in patients undergoing pancreaticoduodenectomy. This suggests that preoperative biliary drainage should be avoided whenever possible in patients with potentially resectable pancreatic and peripancreatic lesions. Such a change in current preoperative management may improve patient outcome after pancreaticoduodenectomy.

Role of chest CT in patients with negative chest x-rays referred for hepatic colorectal metastases.

BACKGROUND: Hepatic resection is the standard treatment for hepatic colorectal metastases. The lung represents the next most likely site, after the liver, of metastatic disease. Computed tomography (CT) of the chest is more sensitive than is chest x-ray in detecting metastatic lung lesions. However, the usefulness of chest CT in the evaluation of patients before hepatic resection remains uncertain. METHODS: One hundred consecutive patients with negative chest x-rays and potentially resectable hepatic colorectal metastases underwent chest CT. Patients with CT findings suggestive of metastatic disease were subjected to thoracotomy or video-assisted thoracic surgery (VATS) before laparotomy and attempted hepatic resection. The operative findings and clinical course were analyzed. RESULTS: Eleven of 100 patients had a positive chest CT. Four of these 11 patients had malignant lesions of the lung (three metastatic colorectal cancers and one primary lung cancer). There was no difference in median total hospital stay (8.5 days [range 7 to 13 days] vs. 8.0 days [range 3 to 49 days]), number of perioperative deaths (0 vs. 2 deaths), or long-term outcome between those patients with a positive chest CT undergoing thoracotomy/VATS and those patients with a negative chest CT. Overall, chest CT provided a positive yield of 4% and a positive predictive value of 36% for the detection of malignant lesions of the lung. CONCLUSIONS: Chest CT only minimally improved detection of malignant lesions of the lung over chest x-ray. Thoracotomy/VATS and wedge resection of lung nodules did not adversely affect outcome. The low positive yield and low positive predictive value of chest CT in the setting of a negative chest x-ray places in question the usefulness of routinely performing chest CT as part of the extent-of-disease work-up before hepatic resection.

Autoradiographic localization of cholecystokinin (CCK) receptor expression during the development of azaserine-induced rat pancreatic carcinoma.

The peptide hormone cholecystokinin (CCK) has been shown to stimulate the growth of azaserine-induced preneoplastic nodules in the rat pancreas. Previously, our labortory demonstrated by classical binding studies that CCK receptors are overexpressed in azaserine-induced rat pancreatic neoplasms. In the present study, we utilized autoradiography to determine the temporal course of this increased receptor binding. Male Lewis rats were given azaserine or saline injections and sacrificed at 2, 4, 8, 12, and 18 months of age. Pancreatic tissue was harvested and autoradiography using 125l-labeled. CCK-8 was performed. Densitometry measurements of azaserine-induced pancreatic nodules, internodular pancreas, and normal pancreatic tissue (from saline-treated controls) of each age group were taken with an image analyzer. There was no statistically significant difference in CCK binding to internodular pancreas and normal pancreas at any age. At 2 months of age, there was no significant increase in CCK binding to azaserine-induced pancreatic nodules. However, at 4, 8, 12, and 18 months of age there was significantly greater CCK binding to azaserine-induced pancreatic nodules than to both internodular pancreas and normal pancreas (p < 0.001 for all groups). At 18 months of age, one azaserine-treated animal developed a pancreatic acinar cell carcinoma, which likewise exhibited significantly greater CCK binding than internodular pancreas or normal pancreas (p < 0.001 for both). These findings demonstrate increased CCK binding in azaserine-induced preneoplastic pancreatic nodules and pancreatic acinar cell carcinoma, compatible with our previous demonstration of receptor overexpression in these tissues. Increased CCK binding first becomes apparent by 4 months following exposure to azaserine. These result suggest that overexpression of CCK receptors, located specifically on preneoplastic and neoplastic pancreatic lesions, results in increased CCK binding and is involved in the mediation of CCK-stimulated growth during azaserine-induced pancreatic carcinogenesis.

Hematologic malignancies developing in Syrian golden hamsters during induction of pancreatic carcinoma.

We report 30 hematologic malignancies arising in 25 of 236 Syrian golden hamsters (SGH) that received combinations of N-nitrobis(2-oxopropyl)amine (BOP) and Streptozotocin (STZ). Lesions developed with morphological similarity to human small lymphocytic (n = 7), diffuse mixed (n = 2), diffuse large cell lymphoma (n = 13), follicular lymphoma (n = 2), anaplastic large cell lymphoma (n = 3), hairy cell leukemia (n = 2), malignant histiocytosis (n = 1) and discordant lymphomas (n = 5). The types and distribution of these lesions are different from epizootic lymphomas in SGH. We also report a higher percentage (12 versus 4.6%) and the earlier appearance (< or = 40 versus 80-112 weeks) compared with aging-associated spontaneous SGH lymphoma. The features of these hematologic malignancies have not been previously reported in epizootic or aging-associated spontaneous lymphomas and therefore suggest a new class of hematologic lesions in SGH. Benign and atypical hyperplasia correlated with STZ administration (r = 0.97, P = 0.03). The malignant lesions correlated with areas of lymphoid hyperplasia (r = 0.78, P= 0.004). Only one of the 21 untreated SGH spontaneously developed a low grade lymphoma. The unusual types, distribution and occurrence of these lesions may suggest a role for these carcinogens in their induction.

Gastrin receptor expression during azaserine-induced rat pancreatic carcinogenesis.

The hormone gastrin is thought to stimulate the growth of certain pancreatic carcinoma cell lines. We have previously detected the presence of the gastrin receptor in rat pancreatic carcinoma cell lines but not in normal rat pancreas. We had not, however, previously demonstrated that gastrin receptor is expressed in pancreatic carcinomas developing in the rat in vivo. Therefore, in the present study, we examined rat pancreatic tissue at various stages in azaserine-induced pancreatic carcinogenesis for gastrin binding and for the presence of gastrin receptor mRNA to determine the temporal expression pattern of the gastrin receptor during the in vivo development of pancreatic cancer. Autoradiography of pancreatic tissue using (125)I-gastrin-17-I from all azaserine-treated and control animals at 2, 4, 8, and 12 months of age demonstrated no specific gastrin binding. At 18 months of age, normal pancreas, azaserine-induced premalignant pancreatic nodules, and internodular pancreas demonstrated no specific gastrin binding. One of three azaserine-treated animals developed an area of pancreatic acinar cell carcinoma at 18 months of age which exhibited significant specific gastrin binding of 141.8 - 32.8 fmole/gm of tissue. Southern blot analysis of pancreatic RNA isolated from animals at 12 months of age revealed no gastrin receptor mRNA; however, by 18 months of age, gastrin receptor mRNA was present in all azaserine-treated animals but absent in control animals. In summary, specific gastrin binding is present in in vivo azaserine-induced pancreatic acinar cell carcinoma but absent in normal pancreas and azaserine-induced premalignant pancreatic nodules. Gastrin receptor mRNA is first expressed in azaserine-treated rat pancreas at some point between 12 and 18 months of age. These results demonstrate that expression of gastrin receptor is altered in azaserine-treated rat pancreas and may play a role in the development of pancreatic cancer.

Ki-ras and p53 mutations in pancreatic ductal adenocarcinoma.

Pancreatic adenocarcinoma involves activation of the Ki-ras oncogene, inactivation of the p53 tumor suppressor gene, and dysregulation of growth factors and perhaps metastasis genes. Ki-ras oncogene point mutations are known to be involved in pancreatic oncogenesis. The p53 tumor suppressor gene product plays a critical role in cell cycle regulation and also functions as a nuclear transcription factor. Point mutations in the p53 gene have been observed in a variety of malignancies. We determined the frequency of p53 protein overexpression and p53 point mutations in the conserved and nonconserved domains in pancreatic cancers as well as the coincidence of Ki-ras mutation in pancreatic ductal adenocarcinoma. Genomic DNA was isolated from 20 frozen pancreatic adenocarcinomas (14 primary, six metastases) along with six specimens of control pancreatic tissue and screened by single-strand conformation polymorphism (SSCP) analysis followed by direct genomic sequencing of SSCP variants. SSCP analysis was accomplished by incorporating 32P-dCTP in 12 separate polymerase chain (PCR) amplifications covering the p53 coding exons 2-11. All mobility shifts on SSCP were subjected to direct genomic sequencing by the modified dideoxy method. Immunoperoxidase (IP) staining was also done with a p53 monoclonal antibody. Ki-ras codon 12 mutational analysis was accomplished by incorporating 32P-dCTP by polymerase chain reaction amplification utilizing mismatched primers, which create a BstN1 restriction endonuclease site spanning codon 12; the products were digested by BstN1. Polyacrylamide gel electrophoresis allowed distinction between wild-type and mutant Ki-ras. p53 mutations were found in 5 of 20 pancreatic cancers (three of 14 primary tumors, two of six metastatic tumors). Point mutations were observed in three of 14 primary tumors, and one of six metastases, while a 2-base pair duplication resulting in a premature stop codon in exon 5 was found in one metastatic tumor. Point mutations were noted in conserved domains (exons 4, 5, 8) and in the nonconserved domain (exon 10). IP staining revealed that eight of 14 of the primary tumors and two of six metastases exhibited moderate to strong nuclear staining (> 30%), while no nuclear staining was evident in the controls. Ki-ras codon 12 mutations were found in 14 of 20 (70%) pancreatic cancers (nine of 14 primary tumors, five of six metastatic tumors) and none of the six controls. Fifty percent of the primary pancreatic tumors demonstrated moderate to strong nuclear staining. Extensive genetic analysis demonstrated mutations in 30% of the pancreatic cancers. One cancer had a nonsense mutation not detected by IP. Seven of 19 (37%) pancreatic cancers exhibited both Ki-ras point mutation and p53 protein overexpression or mutation. Both genetic analysis and IP are required to characterize all p53 mutations in pancreatic cancer. Ki-ras codon 12 mutations and p53 protein overexpression are important steps in pancreatic oncogenesis.

Efficacy of drug regimen exceeds electrostimulation in treatment of avian muscular dystrophy.

Autosomal-recessive dystrophic chickens were treated in three experimental groups with an intraperitoneal multicomponent drug mixture (50 mg/kg Ep475, 20 mg/kg Cinanserin, 10 mg/kg stanazolol, 100 mg/kg leucine, 0.1 mg/kg insulin, 100 mg/kg glucose, and 50 mg/kg carnitine), percutaneous high-frequency electrostimulation of the pectoralis muscle, or a combination of both drug and electrostimulation treatments. Therapeutic efficacy was determined in each group by measurements of strength, righting ability, and histomorphometric analyses of the pectoralis musculature. Drug treatment alone was found to significantly improve muscular strength, function, and relative myofiber necrosis compared with sham-injected controls. The efficacy of drug treatment was found to be equal to or better than singular electrostimulation treatment; there was no apparent additive effect of electrostimulation. As a result, these findings support the use of drug treatment as a useful nongenetic approach to the management of human muscular dystrophy where there is the potential risk of injury from exercise usage.

Characterization of cholecystokinin receptors and messenger RNA expression in rat pancreas: evidence for expression of cholecystokinin-A receptors but not cholecystokinin-B (gastrin) receptors.

It has been previously demonstrated that guinea pig pancreas possesses both cholecystokinin-A (CCK-A) receptors and CCK-B (gastrin) receptors. In contrast to guinea pig pancreas, it is not known whether CCK receptors in rat pancreas are CCK-A receptors, CCK-B (gastrin) receptors, or both. Thus, in the present study, we characterized CCK receptors in rat pancreas at the receptor and mRNA level. 125I-Bolton-Hunter-labeled CCK octapeptide (125I-BH-CCK-8), the specific CCK-A and CCK-B (gastrin) receptor antagonists L364,718 and L365,260, and 125I-labeled gastrin-I were utilized to characterize CCK receptors in normal rat pancreas. Additionally, we utilized 32P-labeled cDNA probes of the CCK-A receptor and CCK-B (gastrin) receptor coding regions in order to examine the expression of CCK receptor subtypes in normal rat pancreas at the mRNA level. The dose-inhibition curve of CCK-8 inhibiting binding of 125I-BH-CCK-8 was significantly best fit by a two-site model with a high-affinity site (Kd = 0.68 +/- 0.13 nM) and a low-affinity site (Kd = 656 +/- 289 nM). L364,718 inhibited binding of 125I-BH-CCK-8 with high affinity, whereas no high-affinity inhibition for L365,260 to inhibit binding of 125I-BH-CCK-8 was detected. L364,718 was 627 times as potent as L365,260 in inhibiting binding of 125I-BH-CCK-8. No saturable binding was present for 125I-labeled gastrin-I. Gastrin-17-I did not inhibit binding of 125I-BH-CCK-8.(ABSTRACT TRUNCATED AT 250 WORDS)