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Biomedical subjects

B A Solomon

Publications and source records attributed to B A Solomon.

At least 37 records · Page 2Linked to original sources
PubMed1995

Neurotoxic reaction to lindane in an HIV-seropositive patient. An old medication's new problem.

Scabies is a common infestation for patients of all ages throughout the world. One of the standard therapies for scabies is 1% lindane lotion. Lindane has been associated with neurotoxic reactions, specifically seizures. We describe a case of a middle-aged adult man with human immunodeficiency virus (HIV) infection who was found to have typical scabies and was treated with a single topical application of lindane. Two hours after the application, the patient experienced a new-onset generalized seizure. We believe that the triad of HIV infection, medications that reduce seizure thresholds, and percutaneous absorption factors, in the aggregate, induced the seizure. We believe that lindane should not be prescribed for patients with HIV infection.

Administration, Topical↗
PubMed1995

In vivo evaluation of a hollow fiber liver assist device.

Orthotopic liver transplantation is the only effective form of therapy currently available for patients with fulminant hepatic failure (FHF). The use of an extracorporeal (EC) liver assist device (LAD) may result in improved presurgical clinical management. Alternatively, patients treated with LADs could avoid the transplantation procedure if they are able to regenerate a critical mass of hepatocytes that will sustain functional viability. In this study, the efficacy of a prototype hollow fiber LAD seeded with rabbit hepatocytes was assessed in vivo by the use of two different animal models: (1) normal rabbits injected with diazepam or lidocaine, and (2) a galactosamine (Gal)-intoxicated rabbit model of FHF. The EC LAD clearly decreased the blood levels of the two drugs and significantly generated diazepam and lidocaine metabolites indicating the maintenance of active P450 forms in the cellular component of the devices. A 6-hour EC treatment significantly increased the survival time and delayed the onset of hepatic encephalopathy (HE) in the Gal-intoxicated rabbits. Histological evaluations of postmortem livers showed greater hepatocyte regenerative activity in the animals treated with hepatocyte-seeded LADs than in the two control groups, e.g., rabbits not treated or treated with unseeded devices. These findings support the concept that a microporous hollow fiber LAD seeded with rabbit hepatocytes is able to sustain drug detoxification in vivo as well as to modify the course of FHF in a well-characterized animal model.

Animals↗
PubMed1993

Treatment of severe diabetes mellitus for more than one year using a vascularized hybrid artificial pancreas.

We report the successful application of a hybrid artificial pancreas device for the treatment of severe diabetes mellitus induced by total pancreatectomy in two dogs. Control of the blood sugar was achieved for more than 1 year in these two animals without any immunosuppressive therapy. Although exogenous insulin was required therapy. Although exogenous insulin was required during the latter part of the study period, removal of the devices resulted in a rapid increase in the fasting blood sugar levels and the exogenous insulin requirements (P < 0.001 versus weeks 1-52 in both dogs). Metabolic studies, postexplant in vitro studies, and histologic analyses confirmed islet cell survival and insulin production by the devices. This hybrid artificial pancreas has a clear clinical potential for islet cell transplantation without immunosuppression.

Animals↗
PubMed1993

Modification of neutrophil functions by naftifine.

Naftifine (NF), a topical antimycotic agent, is highly active in vitro and in vivo against a wide range of pathogenic fungi. NF inhibits human polymorphonuclear leucocyte (PMN) chemotaxis. Following stimulation with zymosan-activated serum, 85-97% of the PMNs exhibited detectable membrane ruffling and polarity. In contrast, NF-treated PMNs did not exhibit such chemotactic factor-induced shape changes. We also analysed the effect of NF on PMN superoxide anion (O2-) and chemiluminescence (CL) production, as a measure of respiratory burst activity. Stimulation of PMNs pre-incubated with NF (37 degrees C for 30 min at 1-150 micrograms/ml) by FMLP, PMA and zymosan resulted in a dose-dependent inhibition in PMN CL. Doses of NF which depressed chemotaxis, inhibited CL and diminished O2- production in a statistically significant manner (P < 0.05-0.001). In conclusion, NF alters membrane-related responses in PMNs, and this alteration may be associated with a change in PMN morphology. Binding of NF to PMN membrane sterol, with a subsequent alteration in membrane configuration, is the most likely cause of the inhibition of PMN function. The data collectively document biochemical and morphological differences between control and NF-treated PMNs as determined by stimulus-specific CL and O2- generation and membrane shape change. Such differences may account, in part, for its efficacy in inflammatory fungal skin diseases.

Allylamine↗
PubMed1992

Transplantation of encapsulated canine islets into spontaneously diabetic BB/Wor rats without immunosuppression.

Extended survival of canine islet xenografts implanted in spontaneously diabetic BB/Wor rats has been achieved by islet encapsulation inside cylindrical chambers fabricated from permselective acrylic membranes. Intraperitoneal implantation of the encapsulated islets reversed the diabetic state of the 10 recipients within 24 h. Plasma glucose levels declined from a preimplantation level of 459 +/- 30 to 102 +/- 14 mg/dl during the first 10 days. All of the animals sustained these levels for at least 1 month, and 2 animals for at least 2 and 8 months, respectively. To confirm that glucose homeostasis resulted from the encapsulated islet grafts, the implants were removed from 2 rats 1 month postimplantation, whereas a third was removed at 2 months. Hyperglycemia was observed immediately in all 3 animals, with glucose levels rising from 100 +/- 3 to 510 +/- 43 mg/dl within 1 day. In contrast, diabetic control rats (n = 4) receiving nonencapsulated islets became hyperglycemic in less than 1 week. The iv glucose tolerance test K value (decline in glucose levels, percent per min) at 10 days was 2.3 +/- 0.4 compared with 0.6 +/- 0.1 (P less than 0.005) and 3.1 +/- 0.1 (P less than 0.02) for untreated diabetic (n = 4) and normal control (n = 4) groups. Histological analyses and electron microscopy of long term functioning grafts revealed well preserved islets, with hormone-producing alpha-, beta-, and delta-cells; the membranes were generally free of fibrosis and host cell adherence. These results demonstrate that permselective artificial membranes can protect discordant islet xenografts from both graft rejection and autoimmune destruction for more than 1 month in an animal model that is similar in several respects to human type I diabetes.

Animals↗
PubMed1992

Treatment of severely diabetic pancreatectomized dogs using a diffusion-based hybrid pancreas.

Long-term survival of dog islet allografts implanted in diabetic pancreatectomized dogs was achieved by islet encapsulation inside cylindrical chambers fabricated from permselective acrylic membranes (nominal M(r) exclusion of 50,000-80,000). Dog islets were isolated from the pancreases of outbred mongrel dogs by collagenase digestion. Chambers containing mean +/- SE 316 +/- 63K islet equivalents (mean islet volume, 558 +/- 111 mm3, purity 90-95%) were peritoneally implanted into six totally pancreatectomized dogs. The dogs were monitored for glycemic control by fasting and postprandial blood glucose determinations, and responses to both intravenous glucose (intravenous glucose tolerance test 0.5 g/kg) and oral glucose (oral glucose tolerance test 1 g/kg). All of the dogs required appreciably lower dosages of exogenous insulin therapy for control of fasting blood glucose levels, with the mean daily insulin dose dropping from 38 +/- 7 to 5 +/- 1 U/day during the 1st wk. Three recipients required no insulin for greater than 82, greater than 68, and 51 days. Intravenous glucose tolerance test K values (decline in glucose levels, %/min) at 1 and 2 mo postimplantation were 2.7 +/- 0.4 and 2.0 +/- 0.5, respectively compared with 3.5 +/- 0.5 before pancreatectomy. The glucose values during oral glucose tolerance tests at 2 wk, although returning to less than 125 mg/dl (less than 7.0 mM) by 2 h, exceeded the normal range, with peak values of 174 to 202 mg/dl (9.7 to 11.3 mM). These preliminary results are encouraging, and represent an important step in determining the feasibility of using this type of diffusion-based hybrid artificial pancreas as treatment for diabetes mellitus in humans.

Animals↗
PubMed1991

Xenotransplantation of canine, bovine, and porcine islets in diabetic rats without immunosuppression.

Permselective acrylic membranes were employed to prevent immune rejection of discordant islet xenografts isolated from various large animals. Canine, porcine, and bovine islets were seeded into tubular diffusion chambers and transplanted into the peritoneum of 27 nonimmunosuppressed streptozotocin-induced diabetic Lewis rats. Six recipients received islet grafts from bovine calves, 7 received grafts from pigs, and 14 received grafts from dogs. Four of the latter were removed at 1 month. In the control group of 10 diabetic rats, 4 received nonencapsulated canine islets, 3 received nonencapsulated bovine islets, and 3 received nonencapsulated porcine islets. Recipients of encapsulated islets promptly dropped from a pretransplantation plasma glucose level of 487 +/- 36 (mean +/- SEM) to 84 +/- 2 (canine), 81 +/- 4 (bovine), and 81 +/- 3 mg/dl (porcine) during the first week. All of the animals sustained these levels for at least 1 month. One rat spontaneously reverted to diabetes at 54 days posttransplantation; 4 other rats became hyperglycemic (glucose, greater than 600 mg/dl) after membrane removal on day 30. The remaining 22 rats maintained fasting euglycemia for greater than 10 weeks. In contrast, rats that received nonencapsulated islets became hyperglycemic in less than 7 days. Intravenous glucose tolerance test K values (decline in glucose levels, %/min) at 1 month for the canine and bovine encapsulated islet transplant group were 3.5 +/- 0.3 and 3.3 +/- 0.1 compared with 3.3 +/- 0.1 (P = 0.63) and 0.91 +/- 0.1 (P less than 0.0001) for normal (n = 4) and diabetic (n = 4) control groups. Morphologic studies of long-term functioning grafts (30-130 days) revealed well-preserved alpha, beta, and delta cells, with varying degrees of granulation. These results demonstrate that immune isolation of islet tissue using permselective artificial membranes can protect discordant islet xenografts from immune rejection in the absence of any immunosuppressive drugs.

Analysis of Variance↗
PubMed1991

Biohybrid artificial pancreas: long-term implantation studies in diabetic, pancreatectomized dogs.

Diabetic complications such as neuropathy, retinopathy, and renal and cardiovascular disease continue to pose major health risks for diabetic patients. Consequently, much effort has focused on approaches that could replace conventional insulin therapy and provide more precise regulation of blood glucose levels. The biohybrid perfused artificial pancreas was designed to incorporate islet tissue and a selectively permeable membrane that isolates this tissue from the immune system of the recipient. Biohybrid pancreas devices containing canine islet allografts were implanted in ten pancreatectomized dogs requiring 18 to 32 units of injected insulin daily. These implants resulted in good control of fasting glucose levels in six of these animals without further exogenous insulin for periods of up to 5 months.

Animals↗
PubMed1991

Successful treatment of diabetes with the biohybrid artificial pancreas in dogs.

We have investigated a new hybrid artificial pancreas device to transplant islet allografts without immunosuppression. The device consists of a chamber through which passes a copolymer membrane connected to standard vascular grafts. Islets are placed inside the chamber but are outside of the blood stream. Nominal molecular porosity of 80,000 daltons permits free diffusion of nutrients and insulin across the membrane but inhibits the entry of immunoglobulins and immunocytes from the blood stream into the chamber. Initial studies focused on the technical feasibility of implanting the unseeded (no islets) devices. In 12 normal mongrel dogs, the arterial limb of the device was anastomosed end-to-end to the common iliac artery and the venous limb end-to-side to the common iliac vein. Vascular patency was monitored by an audible bruit over the device. Two devices currently remain patent at 388 and 421 days. The remaining experiments failed due to thrombosis and membrane rupture, with 2 failing as late as 170 and 279 days. In a second series, both arterial and venous anastomoses were done end-to-side and dogs were placed on low-dose aspirin therapy. All 8 dogs are currently maintaining patent unseeded devices (96-226 days postimplantation). Subsequent studies determined the function of devices seeded with isolated canine pancreatic islet allografts in totally pancreatectomized, severely diabetic dogs. Diabetes was controlled by once-a-day insulin injection. After 2-3 weeks of diabetic control, a seeded device was implanted. Diabetic control was monitored by fasting blood levels and postprandial and intravenous glucose tolerance tests, and vascular patency by the loudness of the bruit. In the first series of 6 dogs given seeded devices without aspirin, no significant function was discernible, with failure attributable to thrombosis, poor islet viability, and surgical complications. In the second series of 13 dogs given aspirin, 8 dogs have required an appreciably lower dose of injected insulin to maintain fasting blood glucose at acceptable levels. Of note are 4 dogs that required virtually no exogenous insulin for at least 3 weeks. One dog lost function on day 74 and another still requires no insulin at 267 days postimplantation. However, despite normal fasting glucose levels, the glucose tolerance tests showed delayed return to normal levels. Weight lost following pancreatectomy was rapidly regained in the presence of a functioning seeded device. Histologic examination of the removed devices revealed no signs of rejection.

Animals↗
PubMed1990

A new microporous membrane for diagnostic immunoassays.

A family of new microporous composite membranes that do not require post-immobilization blocking or quenching steps has been developed for diagnostic immunoassay applications. These membranes, Autobloc membranes, are shown to have low nonspecific binding of proteins. Immobilization of antibody or antigen to the membrane can be achieved either by covalent binding or by adsorption. The correlation between the initial immobilization capacity for IgG and the effective immobilization capacity of microporous membranes is discussed. The performance of Autobloc membranes is demonstrated by dot-enzyme-linked immunoassays in the flow-through mode with several commonly used enzyme-substrate systems and compared to the performance of other membranes. The advantages of using Autobloc membranes are suggested.

Enzyme-Linked Immunosorbent Assay↗
PubMed1989

Monoclonal antibody production in hollow fiber bioreactors using serum-free medium.

Murine hybridoma cells that produce monoclonal antibody directed against human fibronectin have been cultured in VITAFIBER II and VITAFIBER V hollow fiber bioreactors using defined, serum-free WRC 935 medium. During a two-week growth period, following inoculation of the bioreactors, the cells proliferated to an extent where the bioreactor was filled with cultured cells. Using a 5 sq. ft. VITAFIBER V bioreactor, over 15 grams of antibody were produced during the 40 days of the experiment. This antibody was greater than 95% IgG. During the production period, this packed mass of cells produced 579 +/- 15 mg IgG per day. Because the medium is formulated for air equilibration and high cell densities, WRC 935 medium is especially useful for production of gram quantities of monoclonal antibodies using continuous feed hollow fiber bioreactor cell culture systems.

Animals↗