Imbalanced MHC class II molecule expression at surface of murine B cell lymphomas

To study the role of class II MHC expression in mouse lymphomagenesis, we examined the cell surface expression of I-A/E antigens on 24 spontaneous or murine leukemia virus (MuLV)-induced mouse B10.A (I-Ak, I-Ek) B cell lymphomas. Two primary B10.A B cell lymphomas were observed with strong I-Ek expression but with only minimal cell surface I-Ak expression. Both tumors are readily transplantable in syngeneic mice, with maintenance of their I-A-, I-E+ phenotype. Strikingly, one I-A-, I-E+ B cell lymphoma contains a (11; 17) translocation with a breakpoint on chromosome 17 that is localized within or very close to the H-2 complex. DNA of both tumors contains normal restriction enzyme fragments of the A alpha and A beta genes. Northern blot analyses indicated that one I-A-, I-E+ tumor strongly expressed A alpha, E alpha, and E beta mRNAs but possessed only a weak expression of A beta mRNA. The other B cell lymphoma showed A beta, E alpha, and E beta mRNA expression but only minimal A alpha mRNA expression. In 11 primary B10.A B cell lymphomas with a normal I-A+, I-E+ phenotype, no imbalances in A alpha/A beta mRNA levels were observed. The implications of these findings for the role of class II MHC expression in mouse B cell lymphoma-genesis are discussed.     

Sorption of various drugs in polyvinyl chloride, glass, and polyethylene-lined infusion containers

The sorption of chloroquine sulfate, diazepam, isosorbide dinitrate, lorazepam, midazolam, nitroglycerin, promethazine hydrochloride, thiopental sodium, and warfarin sodium to three types of containers was studied. Appropriate amounts of the drugs were added to 500 mL of 0.9% sodium chloride injection in polyvinyl chloride (PVC) bags, glass bottles, and Clear-Flex bags composed of a laminate of polyethylene, nylon, and polypropylene. The containers were stored in the dark at room temperature for 24 hours. Samples were taken at various intervals and assayed for drug concentration by high-performance liquid chromatography. There were no appreciable changes in pH after 24 hours, and all the admixtures remained clear and colorless. The potency of chloroquine sulfate, lorazepam, midazolam, promethazine hydrochloride, and thiopental sodium remained unchanged in glass, PVC, and Clear-Flex containers. Diazepam, isosorbide dinitrate, nitroglycerin, and warfarin sodium did not show any sorption to glass bottles and Clear-Flex bags. In PVC bags, however, up to 55% of diazepam, 23% of isosorbide dinitrate, 51% of nitroglycerin, and 24% of warfarin sodium was lost during the 24-hour study period. Diazepam, isosorbide dinitrate, nitroglycerin, and warfarin sodium in 0.9% sodium chloride injection showed a loss of potency when stored in PVC containers for 24 hours at room temperature, but none of the drugs studied lost potency when stored in glass bottles and Clear-Flex bags.     

Ecotropic and dualtropic mink cell focus-inducing murine leukemia viruses can induce a wide spectrum of H-2 controlled lymphoma types

Neonatal infection of C57BL and BALB/c mice by cloned ecotropic and dualtropic mink cell focus-inducing (MCF) murine leukemia viruses (MuLV) induces a wide spectrum of different lymphomas of T, B, and non-T/non-B cell types. Oncogenic dualtropic MCF viruses and poorly oncogenic ecotropic MuLV act synergistically in lymphomagenesis. Within one mouse strain virus-induced T-cell lymphomas arise earlier than B-cell lymphomas after neonatal inoculation of a single-cloned MuLV. The host genetic constitution, notably the H-2 complex has a marked influence on lymphoma type. This H-2 influence can be explained by an H-2-linked difference in penetration of the thymus early in life by oncogenic thymotropic MuLV, which in turn is correlated with, but not necessarily due to the magnitude of the anti-MuLV antibody response.     

Ältere Patienten in klinischen Studien

Advanced age is associated with a higher burden of illness. Nevertheless, elderly patients suffering from internal diseases are underrepresented in clinical trials; patient, physician and protocol-designed barriers in particular prevent the recruitment of older patients with impaired medical fitness (co-morbidity, co-medication, poor performance status, cognitive dysfunction etc.). Recommendations that are based on trials in younger subjects mostly cannot be generally adopted for the elderly. Treatment in clinical practice and clinical trials should be fitness-adapted rather than age-adjusted. Normally, standard regimens are effective and well tolerated in medically fit patients of advanced age. In contrast, it may be necessary to apply modified regimens for the medically unfit. Trials exploring novel treatment modalities in the young should always allow the inclusion of elderly patients with good medical fitness. The benefit of modifying a treatment regimen in medically unfit patients of advanced age has to be determined by separate trials.     

Abdominal wall bulging after thoracic surgery, an underdiagnosed wound complication

Background

Complications after thoracic surgery have well been established, pain being the most prominent. Intercostal nerves are mixed type nerves combining motor and sensory functions. This notion is not consistent with the incidence of PTPS compared to the incidence of muscle paresis or paralysis. We would hypothesize that abdominal wall paresis or paralysis is underdiagnosed.

Methods

In our hospital, three patients developed abdominal wall paralysis after thoracic surgery and consequent nerve damage. Their cases are discussed, and a review of the literature was conducted concerning (intercostal) nerve damage on a cellular level, the anatomy of the intercostal nerve, prevention of intercostal nerve damage and surgical techniques.

Results

A cellular cascade known as Wallerian degeneration and regeneration determine whether a damaged nerve can function again. The recovery of the nerve is highly dependent on the correct function of activated Schwann cells and macrophages and is related to the amount of damage that has taken place. The anatomy of the intercostal nerve makes it susceptible to injury. Retractor placement during open thoracic surgery has shown to effect compression injury and induced mechanical deformation and damage. Given the known factors of pathophysiology and anatomy, a number of preventive measures have been tested to reduce intercostal nerve damage. Several techniques have been proposed, but the most used technique, the video-assisted thoracic surgery, has been the most effective in reducing nerve damage.

Conclusion

Abdominal wall paralysis is an underdiagnosed complication after thoracic surgery. The amount of stress on the intercostal nerves could be reduced with less invasive techniques such as the VATS technique.     

Perioperative outcomes and costs of laparoscopic versus open inguinal hernia repair

Purpose

Studies comparing laparoscopic (LIHR) vs. open inguinal hernia repair (OIHR) have shown similar recurrence rates but have disagreed on perioperative outcomes and costs. The aim of this study is to compare laparoscopic vs. open outcomes and costs.

Methods

The National Surgical Quality Improvement Program (NSQIP) was used to compare durations of surgery, anesthesia time, and length of stay (LOS). The University HealthSystem Consortium (UHC) was used to review the cost and complications between approaches. Patients were matched on demographics, year of procedure and surgical approach between datasets for statistical analysis.

Results

A sample of 5468 patients undergoing OIHR (N = 4,693) or LIHR (N = 775) was selected from UHC from 2008–2011. An identical number of patients from NSQIP were matched to those from UHC resulting in a total of 10,936 records. LIHR patients had shorter duration of wait from admission to operation (p < 0.05). Conversely, LIHR patients had longer operating time (p < 0.05), duration of anesthesia (p < 0.05), and time in the operating room (p < 0.05).Overall complication rate was higher in open (3.1 vs. 1.8 %, p < 0.05). Cost favored open over LIHR ($4360 vs $5105). The cost discrepancy mainly stemmed from LIHR supplies ($1448 vs. $340; p < 0.05) and OR services ($1380 vs. $1080; p < 0.05).

Conclusion

This study demonstrates the LOS and perioperative outcomes were superior in the LIHR group; however, the overall cost was higher due to the supplies. Advancement in technology, surgeons’ skill level and preference of supplies are all factors in decreasing the overall cost of LIHR.

     

Altered mitochondrial metabolism in the insulin‐resistant heart

Obesity‐induced insulin resistance and type 2 diabetes mellitus can ultimately result in various complications, including diabetic cardiomyopathy. In this case, cardiac dysfunction is characterized by metabolic disturbances such as impaired glucose oxidation and an increased reliance on fatty acid (FA) oxidation. Mitochondrial dysfunction has often been associated with the altered metabolic function in the diabetic heart, and may result from FA‐induced lipotoxicity and uncoupling of oxidative phosphorylation. In this review, we address the metabolic changes in the diabetic heart, focusing on the loss of metabolic flexibility and cardiac mitochondrial function. We consider the alterations observed in mitochondrial substrate utilization, bioenergetics and dynamics, and highlight new areas of research which may improve our understanding of the cause and effect of cardiac mitochondrial dysfunction in diabetes. Finally, we explore how lifestyle (nutrition and exercise) and pharmacological interventions can prevent and treat metabolic and mitochondrial dysfunction in diabetes.