Biomedical subjects
J Mueller
Publications and source records attributed to J Mueller.
Extranodal connective tissue invasion and the expression of desmosomal glycoprotein 1 in squamous cell carcinoma of the oesophagus.
We investigated extranodal connective tissue involvement (ECTI) in 39 patients with oesophageal carcinoma. Both the primary tumour and ECTI were immunohistochemically examined using the monoclonal antibody 32-2B for desmosomal glycoprotein 1 (DG1). Connective tissue carcinoma deposits were identified as cells within small lymph nodes, as lymphatic or venous vessel invasion or as widespread invasion beyond the capsule of metastatic lymph nodes. These histological findings were present in at least one area in 20 of 39 patients (51.3%). DG1 immunostaining intensity by tumour was graded as DG1 (++), DG1 (+) or DG1 (-). DG1 (+) or DG1 (-) primary tumours demonstrated lymph node metastases and ECTI more frequently than DG1(++) tumours (P<0.05). Among 17 patients in whom DG1 immunohistochemistry was performed on ECTI, there were three DG1(++), five DG1(+) and nine DG1(-) patients. The DG1 expression of ECTI was equal to or less intense than the primary tumour. These results indicate that reduction or loss of DG1 expression may promote ECTI and lymph node metastases. One should be aware of the potential for ECTI in oesophageal carcinomas. In the future, adjuvant therapy may be advisable for some oesophageal carcinomas based on the phenotype of individual cancer cells, including expression of DG1.
Synchronous and metachronous carcinomas of the esophagus and head and neck.
We retrospectively analyzed the clinicopathologic findings, treatment and outcome of 22 patients with synchronous or metachronous carcinomas of the esophagus and head and neck. The patients with metachronous cancers in whom esophageal cancer occurred first had either an early-stage esophageal carcinoma or only one positive lymph node. Similarly, five of 10 patients with metachronous cancers in whom head and neck cancer was the first tumor had early-stage esophageal carcinomas. The esophageal lesion was mucosal carcinoma in four patients which was found by endoscopy with the iodine dye method. In the patients with synchronous cancers either one or both carcinomas were advanced, and the prognosis of these patients was poor compared with those of patients with metachronous carcinomas. Accordingly, endoscopic surveillance for early detection of metachronous lesions are encouraged.
The effect of respiration on the performance of the total artificial heart.
An electromechanical driven pusher plate type total artificial heart (TAH) has been developed in the Department of Surgery at Baylor College of Medicine. The control of this TAH is based upon Frank-Starling's law, and the output is likely to be affected by the respiration cycle. The necessity of an averaging system for the pumping to avoid this drifting of the output has been discussed in several papers. In this study, the effect of respiration on the performance of the TAH was evaluated in both in vitro and in vivo conditions. This TAH was driven without an averaging system in its control system. The results indicated that the mean output pressure was stable with minute changes in both the heart rate and outflow. This verifies that the electromechanical driven pusher plate type TAH, which is under development in our laboratory, compensated for the effect of respiration without an averaging system.
Hemolysis test of a centrifugal pump in a pulsatile mode: the effect of pulse rate and RPM variance.
Centrifugal pumps are generally employed as nonpulsatile blood flow pumps; however, these pumps can produce pulsatile flow by periodically alternating the impeller rotation speed. This study investigates blood trauma due to the effect of pulse frequency and various ranges of pump speed. The hemolysis tests were conducted using the Gyro C1E3 pump. The study was divided into the following categories: Group 1 in a nonpulsatile mode; Group 2 operated at 40 bpm with 30% of speed variance; Group 3, 60 bpm with 30% of speed variance; Group 4, 40 bpm with 70% of speed variance; and Group 5, 60 bpm with 70% of speed variance. A flow rate of 3 L/min and a total pressure head of 200 mm Hg were employed in all groups to simulate a percutaneous cardiopulmonary support condition. There were no significant differences in the hemolysis levels among Groups 1, 2, and 3. However, Groups 4 and 5 exhibited a significantly higher hemolysis rate compared to the other groups. These results indicate that a high rate of speed variance increases hemolysis; however, a range of less than 30% does not affect hemolysis. The pulse rate has no significant effect on hemolysis. In conclusion, the higher speed variance increases the hemolysis level when a pulsatile mode is applied with a centrifugal pump at the given test conditions. However, a speed variance of less than 30% or a pulse rate of less than 60 bpm does not affect hemolysis.
The hemolysis test of the Gyro C1E3 pump in pulsatile mode.
While a centrifugal pump is generally used for nonpulsatile blood flow, it can also produce a pulsatile flow by alternating the impeller rotational speed (rpm) periodically. However, there is a concern that this centrifugal pump pulsatile mode may induce added hemolysis as a result of the repeated acceleration and deceleration of rpm. Thus, a hemolysis study of the pulsatile modes of the Gyro C1E3 centrifugal pump (Gyro-P) was conducted. The results were then compared with the nonpulsatile mode of the same pump (Gyro-N) and the nonpulsatile BioMedicus BP-80 (Bio-N) pump. Three different conditions were simulated: left ventricular assist device (LVAD), cardiopulmonary bypass (CPB), and percutaneous cardiopulmonary support (PCPS). The beating rate of the Gyro-P was set at 40 bpm, with repetition of two different impeller speed (the lower being 70% of the higher speed). The 2 impeller speeds were set to obtain the same average flow as that of the nonpulsatile mode. The hemolysis results of the Gyro-P were comparable to or better than those of Bio-N, and no excessive hemolysis was observed, compared to the Gyro-N. In conclusion, The Gyro-P had an excellent hemolytic characteristic and generated no excessive hemolysis in most clinical usage conditions. With the concern of hemolysis eliminated, this pulsatile mode may have various possible mode advantages.
Bombesin-like peptides stimulate somatostatin release from rat fundic D cells in primary culture.
In several species, bombesin-like neuropeptides stimulate somatostatin release in in vitro preparations of gastric mucosa. We sought to determine if this response is due to a direct effect on fundic D cells. Rat fundic mucosal cells were isolated by pronase E (1% D cells). D cells were separated by counterflow elutriation and subsequent density-gradient centrifugation (Nycodenz) (15% D cells) and grown in primary culture for 48 h (46% D cells). Cultured cells were double stained with affinity-purified rabbit-anti-gastrin-releasing peptide (GRP) receptor antibody and mouse monoclonal antibody to human somatostatin. After incubation with rhodamine-labeled anti-rabbit and fluorescein isothiocyanate-labeled anti-mouse antibodies, reactions were visualized by fluorescence microscopy. All cells positive for somatostatin had GRP receptors, whereas all non-D cells showed no expression in this G cell-free culture system. Somatostatin release from cultured cells was stimulated by sulfated cholecystokinin octapeptide (CCK-8; EC50 3 X 10(-10) M) and epinephrine (EC50 4 X 10(-8) M), which are established stimuli for canine fundic D cells. Bombesin (EC50 6 X 10(-11) M), its mammalian analog GRP-27, and neuromedin C (GRP-10) (EC50 1 X 10(-10) M, for both) were almost equally potent stimuli of somatostatin release, eliciting maximal response at 10(-9) M (400-550% above basal). Neuromedin B was less potent and effective (maximal response at 10(-8) M, 230% above basal). [D-Phe6]bombesin-(6-13)-OMe, a specific bombesin receptor antagonist, inhibited bombesin-stimulated somatostatin release in a competitive manner (IC50 9 X 10(-8) M). Potentiating interactions were observed between bombesin and dibutyryladenosine 3',5'-cyclic monophosphate (DBcAMP) or epinephrine, but not between bombesin and CCK-8. We conclude that bombesin-like peptides directly stimulate somatostatin release by interacting with specific receptors on rat fundic D cells. Bombesin-like peptides appear to induce Ca(2+)-phospholipid-dependent signal-response transduction, as is indirectly suggested by potentiating interactions with DBcAMP or epinephrine.
Ductuloendocrine cell proliferation in the pancreas of two young dogs with diabetes mellitus.
Two cases of diabetes mellitus in juvenile dogs (a 3-4 month-old Golden Retriever and a 2-month-old Labrador Retriever) are described here in terms of their clinical, histologic, and immunohistologic findings. Only very few insulin-positive cells were demonstrated immunohistochemically in one dog. In the second dog, the alterations of the pancreas consisted of hydropic vacuolar degeneration of B cells in the islets of Langerhans. In both cases, hyperplasia of the vacuolated cells was prominent. These cells formed tubular structures and were immunohistochemically positive for cytokeratin and proliferating cell antigen (MIB-1). Furthermore, within these vacuolated areas, some cells were positive to varying degrees for insulin, glucagon, somatostatin, and pancreatic polypeptide. Apoptotic cells could be seen in the exocrine pancreas, in vacuolated areas, and occasionally in the islets of both dogs. We interpret these alterations as ductuloendocrine cell proliferation, probably as an idiopathic compensatory response.
Analysis for microsatellite instability and mutations of the DNA mismatch repair gene hMLH1 in familial gastric cancer.
We examined 30 gastric-cancer patients with a varying degree of family history of stomach cancer and/or synchronous gastric tumors for microsatellite instability. We observed microsatellite instability at at least 1 of 8 loci tested in tumors of 14/30 patients; of these 14, 8 had single locus alterations and 6 had alterations at at least half of the 8 loci. Among the patients with microsatellite instability at > or = 4 loci, 3 patients showed a strong familial clustering of gastric cancer. Mutation analysis of the DNA mismatch repair gene hMLHl on paired non-tumorous and tumor DNA from 10 patients, 6 with microsatellite instability at > or = 4 loci and 4 with an alteration at one locus, revealed a novel missense mutation, present in the normal and tumor DNA of one patient with microsatellite instability at multiple loci in his tumor. His family history of cancer included one second-degree relative affected with gastric cancer. These data suggest that germline mutations in the hMLHl gene occur in some gastric-cancer patients and that in the majority of cases microsatellite instability in gastric tumors may be due to defects in other genes responsible for DNA replication fidelity than the hMLHl.
Expression of bcl-2 and p53 in de novo and ex-adenoma colon carcinoma: a comparative immunohistochemical study.
The development of colorectal carcinoma from adenomas is recognized as the dominant mechanism of colon carcinogenesis. However, early colon carcinomas are being increasingly detected which have no adenomatous elements in their vicinity, and which, despite their small size, already show submucosal invasion. Such tumours (so-called 'de novo' carcinomas) have renewed consideration of the de novo colorectal carcinogenesis pathway. The goal of this study was to evaluate the expression of tumour suppressor gene p53 and apoptosis control gene bcl-2 in de novo carcinomas, compared with early carcinomas developing in the background of an adenoma (ex-adenoma). Fifty cases each of de novo and ex-adenoma carcinomas (pT1) were studied. p53 expression was significantly higher in the de novo carcinomas than in the ex-adenoma carcinomas (62 per cent vs. 42 per cent), while bcl-2 tended to be weaker in the de novo than in the ex-adenoma carcinomas. These differences' support the concept that de novo carcinomas are a unique pathological entity, with a phenotype reflecting their more aggressive behaviour.
Epidemiology of erythema exsudativum multiforme majus, Stevens-Johnson syndrome, and toxic epidermal necrolysis in Germany (1990-1992): structure and results of a population-based registry.
The severe skin reactions erythema exsudativum multiforme majus (EEM with mucosal involvement, EEMM), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN) are difficult to study as they are very rare diseases with an incidence of about two cases per 1 million inhabitants per year. We report on the structure of a registry with the aim of ascertaining all hospitalized cases of EEMM, SJS, and TEN in western Germany and Berlin. The registry is structured as an intensive reporting system, regularly contacting more than 1500 departments including 100% of the burn units (n = 34), departments of pediatrics (n = 241), departments of dermatology (n = 106), and 100% of all internal medicine departments in hospitals with intensive care facilities or with more than 200 beds (n = 1161). With a coverage rate up to 95% based on the number of responding departments between April 1, 1990 and December 31, 1992, from a total of 767 reported cases 353 patients with EEMM, SJS, and TEN were finally included in the registry. Most of these patients were directly reported to the registry; only 2.54% (9 of 353) were primarily registered by the German spontaneous reporting systems. Assuming an average population of 64.5 million for western Germany and Berlin an incidence up to 1.89 per 1 million inhabitants per year could be calculated for SJS and TEN.
Three teams improving thrombolytic therapy.
BACKGROUND: The American Heart Association (AHA) standard for delivering thrombolytic therapy to chest pain patients is 30 to 60 minutes after patient presentation to the emergency department. Three acute care hospitals in an integrated health system in northern California shortened the time of administration of thrombolytic agents to appropriate patients presenting with chest pain in the emergency department. FINDING THE SOLUTIONS: Physician-led multidisciplinary teams developed algorithms to reduce variation and decrease the thrombolytic administration process to 30 minutes. Changes were made to prehospital and hospital thrombolytic policies and staff practices. REALIZING RESULTS: Each of the three acute care hospitals reduced their thrombolytic administration time by 48% to 59% to levels within the AHA standard. LEARNING FROM THE PROCESS: Internal benchmarking for clinical processes promotes a synergy between hospitals and medical staffs for the improvement of patient care. Multidisciplinary teams, which include community representatives, achieve a thorough understanding of a process, which in turn reduces variation in practice and improves quality.
Miserable minority: emotional risk factors that influence the outcome of a mild traumatic brain injury.
Emotional risk factors are explored in four case studies, each of whom had sustained a mild traumatic brain injury (MTBI). Selected pre-existing personality traits that compounded the symptom presentation included over-achievement, dependency, grandiosity and borderline personality traits. Premorbid risk factors are described and their influence on co-morbid and post-morbid difficulties is discussed. We also touched upon the therapeutic issues involved in our cases. General treatment considerations are highlighted for dealing with grandiosity, narcissistic features and borderline traits. Over-achievement and perfectionism are discussed in the context of providing treatment for stress management. Finally, the effect of pre-existing emotional trauma combined with the MTBI is discussed.
Stromelysin-3 (ST-3) mRNA expression in colorectal carcinomas. Localization and clinicopathologic correlations.
Stromelysin-3 (ST-3) mRNA expression was studied in 28 colorectal carcinomas and compared with that of adjacent nontumorous tissue. By Northern blot analysis, levels of ST-3 mRNA were significantly increased in the carcinomas compared with ST-3 expression was seen with degree of invasion, nodal or distant metastases, or histologic grade. In situ hybridization of nontumorous tissue showed no significant ST-3 expression. In tumor tissue, ST-3 mRNA was localized adjacent to colon carcinoma cells in irregular foci within the stoma. No significant difference in ST-3 expression was found between the center and periphery of the colon tumors. Most of the colon carcinomas (26 of 28) induced an expression of ST-3 in the directly adjacent stroma. No significant correlation between ST-3 mRNA expression and tumor stage and grade was seen. By Northern blot, we also saw expression of ST-3 in noncarcinomatous tissue, further supporting the concept that ST-3 expression is a tumor-induced but not a tumor-specific phenomenon.
[Gamma-linolenic acid in atopic patients?].
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[Treatment of allergy with calcium?].
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Liver transplantation for treatment of giant hepatocellular adenomas.
Giant hepatocellular adenomas are associated with a high incidence of rupture with intra-abdominal hemorrhage and may also undergo malignant transformation. If resection is not technically feasible, liver transplantation should be a treatment option. The aim of this report is to describe the indications, feasibility, and outcome of liver transplantation for hepatocellular adenomas. A 66-year-old man with a 17-cm hepatocellular adenoma originating in the left lobe but involving nearly the entire liver and a 35-year-old woman with a 20-cm tumor involving the right lobe of the liver and compressing the left lobe underwent liver transplantation without complication. In both cases, a histological diagnosis was made by core needle biopsy preoperatively, and resection was technically not possible. Hepatocellular adenoma involving nearly all of the liver with no evidence of malignant change was confirmed in the explant liver from both cases. Giant hepatocellular adenomas may be unresectable and require liver transplantation for complete removal to prevent potential rupture with hemorrhage or malignant transformation.
School-based AIDS education for adolescents.
PURPOSE: To describe a program which utilizes medical students and persons with AIDS (PWAs) to provide for adolescents school-based education about acquired immunodeficiency syndrome (AIDS). METHODS: Two 1.5 hour classroom sessions were conducted by medical students and persons with AIDS for seventh and eighth grade students (n = 1,161 students) at two urban middle schools. In addition, a two hour informational session was provided for parents. A 49 question student health survey was used to evaluate adolescents' HIV knowledge, tolerance of persons with AIDS, and intentions to engage in human immunodeficiency virus (HIV) safe behaviors. RESULTS: Significant (p < 0.01) increases in HIV knowledge and tolerance of persons with AIDS were observed, which persisted for three months. A significant (p < 0.01) improvement in intention to engage in HIV-safe behaviors was observed but did not persist for three months. CONCLUSIONS: Medical students and persons with AIDS can provide school-based AIDS education to early adolescents.