Reactions in rabbit Fallopian tube after plastic reconstruction. I. Gross pathology, tubal patency, and pregnancy

Rabbit tubal repair surgery was aseptic with Nembutal and ether anesthesia. Both tubes were cut at the uterotubal junction, a .61 mm thick polyethylene splint was inserted, sutured to the myometrium, and the junction sutured. At 2, 6, 10, 16, and 24 weeks the splint was removed through an incision. After a dye test for patency, 1 tube was removed and the rabbit was mated 1 week later. Results were 30% distorted placement of tube, 30% fibrose tubes (especially after 16 weeks), 47% adhesion (particularly after 6 weeks), some infection, and 55% positive dye flow test. 3 out of 7 rabbits delivered, all in those of the 2-week group that had no adhesions. 2 of the pregnancies occurred in rabbits with no dye passage.     

Transplantation of neonatal porcine islets and sertoli cells into nonimmunosuppressed nonhuman primates

A Mexican group reported transplantation of cocultured neonatal porcine islets and Sertoli cells resulting in insulin independence in nonimmunosuppressed type 1 diabetes patients. We have transplanted similar islets alone (naked islets) or cocultured islets with sertoli cells (islet/sertoli cells) into an omental site and other locations of seven nondiabetic, nonimmunosuppressed, nonhuman primates. Porcine endogenous retrovirus was not detected in recipient blood 8 weeks after porcine islet grafts, and porcine C-peptide was detected at a very low level in all animals. Histology examination failed to demonstrate obviously recognizable islets, but in the animals transplanted with islet/Sertoli cells at the omentum site, there were some surviving glucagons, pan-cytokeratin, and inhibin stained cells at 8 weeks.     

Guidelines for the performance of fusion procedures for degenerative disease of the lumbar spine. Part 16: bone graft extenders and substitutes

Despite the large volume of animal data regarding the use of synthetic bone graft substitutes or extenders, there are very few data regarding the use of these substances for fusion in lumbar degenerative disease. The best available data indicate that rhBMP-2 is a viable alternative to autograft bone for interbody fusion procedures. This same substance may also be a viable alternative to autograft for PLF; however, definitive medical evidence is not yet available. There is little, if any, medical evidence to support the use of other biological agents at the present time. As promising new compounds are brought to market, well-designed cohort studies and randomized trials will be required to determine the actual usefulness of these compounds in clinical practice. It is important not to generalize the results obtained with one preparation or application to different preparations or applications. The use of synthetic calcium phosphate ceramics as graft extenders appears to be reasonable in certain situations. The medical evidence available regarding their use is limited and of poor quality. Further study will be required to establish their utility for use in spinal fusion.     

Guidelines for the performance of fusion procedures for degenerative disease of the lumbar spine. Part 6: magnetic resonance imaging and discography for patient selection for lumbar fusion

Discography is an exquisitely sensitive but not specific diagnostic test for the diagnosis of discogenic low-back pain. The restriction of the definition of a positive discographic study to one that elicits concordant pain from a morphologically abnormal disc improves the definition's accuracy. Fusion surgery based on discography alone, however, is not reliably associated with clinical success. Therefore, discography is not recommended as a standalone test for treatment decisions in patients with low-back pain. Magnetic resonance imaging is a sensitive and noninvasive test for the presence of degenerative disc disease. Discography should not be attempted in patients with normal lumbar MR images. Discography appears to have a role in the evaluation of patients with low-back pain, but it is best limited to the evaluation of abnormal interspaces identified on MR imaging, the investigation of adjacent-level disc disease, and as a means to rule out cases of nonorganic pain from surgical consideration.     

In vitro synergy and enhanced murine brain penetration of saquinavir coadministered with mefloquine

Highly active antiretroviral therapy has substantially improved prognosis in human immunodeficiency virus (HIV). However, the integration of proviral DNA, development of viral resistance, and lack of permeability of drugs into sanctuary sites (e.g., brain and lymphocyte) are major limitations to current regimens. Previous studies have indicated that the antimalarial drug chloroquine (CQ) has antiviral efficacy and a synergism with HIV protease inhibitors. We have screened a panel of antimalarial compounds for activity against HIV-1 in vitro. A limited efficacy was observed for CQ, mefloquine (MQ), and mepacrine (MC). However, marked synergy was observed between MQ and saquinavir (SQV), but not CQ in U937 cells. Furthermore, enhancement of the antiviral activity of SQV and four other protease inhibitors (PIs) by MQ was observed in MT4 cells, indicating a class specific rather than a drug-specific phenomenon. We demonstrate that these observations are a result of inhibition of multiple drug efflux proteins by MQ and that MQ also displaces SQV from orosomucoid in vitro. Finally, coadministration of MQ and SQV in CD-1 mice dramatically altered the tissue distribution of SQV, resulting in a >3-fold and >2-fold increase in the tissue/blood ratio for brain and testis, respectively. This pharmacological enhancement of in vitro antiviral activity of PIs by MQ now warrants further examination in vivo.