Studies on experimental diabetes in the Wellesley hybrid mouse

Summary A hybrid of C3Hf and I strains of mice (the Wellesley mouse) results in an animal with a predisposition to diabetes mellitus. In this study it was found that animals that developed the diabetic syndrome had elevated levels of immunoreactive insulin in their serum, and peripheral tissues thatin vitro were less responsive to insulin. Dietary restriction prevented the diabetes from occurring as well as maintaining insulin sensitivity in peripheral tissue.Paper I of this series isLike et al., 1965.     

Experiments to vaccinate marmoset monkeys against malignant lymphoma.

Humoral antibodies can be induced in cotton topped (CT) marmosets with killed Herpesvirus saimiri (HVS) vaccines. The serum antibodies delayed, but did not prevent, malignant lymphoma in actively and passively immunized monkeys after inoculation with 10(3.8)TCID50 of cell-free HVS. Experiments are in progress to determine whether the vaccines are able to protect against smaller challenge dosages of HVS. The immunized monkeys were not resistant against transplantation of tumor cells. Infection with Epstein-Barr virus (EBV) and Marek's disease virus (MDV) did not protect against the tumors caused by superinfection with HVS. Attenuation of HVS was not achieved by passaging the HVS genome through different monkey species.     

Prospective randomised trial of endobronchial ultrasound-guide sheath versus computed tomography-guided percutaneous core biopsies for peripheral lung lesions

Aim: To determine diagnostic rate, complications and patient tolerability of endobronchial ultrasound‐guide sheath (EBUS‐GS) and computed tomography (CT)‐guided percutaneous core biopsy for peripheral lung lesions. Methods: Lesions >1 cm diameter on CT were randomised to either EBUS‐GS or CT‐guided biopsy. Excluded were patients with severe chronic obstructive airway disease, lesions touching visceral pleura or hilum, and patients with symptoms needing bronchoscopic evaluation. Patients completed preprocedure and postprocedure questionnaires on tolerability. Results: Of 64 participants (mean lesion size 29 ± 16 mm), 57 completed the study. Diagnostic sensitivity was 67% for EBUS‐GS and 78% for CT‐guided biopsy (P= not significant). In those with negative results, in the EBUS group, nine had a CT‐guided biopsy as a cross‐over, seven of which were positive. In the CT group, four had cross‐over EBUS‐GS of which three were diagnostic. Sensitivity for malignancy was 17/23 for EBUS‐GS (74%) and 23/26 (88%, P= not significant). For lesions <2 cm, CT‐guided biopsy had a significantly better diagnostic yield (80% vs 50%, P= 0.05). In EBUS‐GS cases, for lesions with an air bronchogram, sensitivity was 89%. Pneumothorax and intercostal catheter insertion occurred in three and two cases, respectively, for EBUS, and 10 and 3 cases for CT‐guided biopsy (P= 0.02 for pneumothorax). Nine unexpected admissions occurred after CT‐guided biopsy compared with three after EBUS‐GS. Overall, tolerability was high for both groups; however three patients had moderate‐to‐severe pain after CT‐guided biopsy. Conclusions: In lesions <2 cm, CT‐guided biopsy had higher yields; however, EBUS‐GS had better tolerability and fewer complications.     

Miniaturized HIA microdiagonal pump as left ventricular assist device in a sheep model

We evaluated the newly developed miniaturized HIA microdiagonal blood pump (MDP) as a continuous flow left ventricular assist device. In a sheep model (n = 6), the MDP was implanted through left lateral thoracotomy and placed paracorporeally with inflow conduit to left atrium and outflow conduit to descending aorta. The sheep were pumped at a mean flow rate of 2.5 L/min for 7 days. Anticoagulation was applied by intravenous heparin administration. Postoperatively, activated clotting time was held stable with values of 200 seconds. During follow-up, blood samples (creatinine kinase, creatinine, glutamic-oxaloacetic transaminase (aspartate aminotransferase) (GOT), glutamate dehydrogenase (GLDH), gamma-GT, plasma-free hemoglobin, and hemoglobine) were taken daily. After 7 days, the sheep were killed for macroscopic examination. Systemic artery pressures remained stable during the whole test period. Because of operative reasons, the hemoglobin value (7.5 +/- 0.61 g/dl) decreased perioperatively, but recovered within the test period, whereas creatinine kinase increased initially after thoracotomy, but decreased to normal within days. Renal and liver functions were slightly impaired perioperatively, indicated by temporarily enhanced values of GOT, gamma-GT, GLDH, and creatinine. The MDP did not produce significant hemolysis as measured by plasma-free hemoglobin levels. Wound infections did not occur. We conclude that the MDP ran successfully as an left ventricular assist device for 7 days in sheep has potential for long-term support, and may serve as an alternative to current technologies. Presented data were not obtained in a clinical trial; however, the results are promising enough to proceed with longer duration animal studies.