Insulin resistance has been associated with kidney disease even in the absence of diabetes; howev... more Insulin resistance has been associated with kidney disease even in the absence of diabetes; however, pathways linking insulin resistance to kidney disease are unclear. The purpose of this study was to determine if transforming growth factor (TGF)-β1, a key cytokine associated with kidney disease, responds to circulating levels of glucose and/or insulin. Urinary TGF-β1 levels were measured in 249 young
American journal of kidney diseases : the official journal of the National Kidney Foundation, 1994
Orthoclone OKT3 (Ortho Biotech Inc, Raritan, NJ) is a potent immunosuppressive agent effective in... more Orthoclone OKT3 (Ortho Biotech Inc, Raritan, NJ) is a potent immunosuppressive agent effective in the therapy of acute renal allograft rejection. Following the first one or two doses, patients often exhibit a "flu-like" illness ascribed to OKT3-induced release of cytokines. Systemic reactions resulting from the cytokines include pyrexia, pulmonary edema, bronchospasm, photophobia, headache, hypotension, rigors, hypertension, gastrointestinal disturbances, and arthralgias/myalgias. The cyclooxygenase inhibitor indomethacin has been shown to ameliorate the pyrexia associated with OKT3 administration. We conducted a retrospective analysis with the purposes of (1) confirming that indomethacin reduces pyrexia and (2) determining the effect of indomethacin on the other aforementioned adverse side effects. Group 1 patients (n = 28) received indomethacin during the initial 48 hours of OKT3 antirejection therapy. Group 2 patients (n = 28) received OKT3 without indomethacin. The inc...
The present study was to test the hypothesis that, selected bacteria instilled into the gastroint... more The present study was to test the hypothesis that, selected bacteria instilled into the gastrointestinal tract could help in converting nitrogenous wastes accumulated due to renal insufficiency into non-toxic compounds; thereby, ameliorating the biochemical imbalance. Herein we describe a prospective, blinded, placebo controlled pilot-study, using 5/6th nephrectomized Sprague Dawley rat, as a chronic renal failure model. The study group consisted of 36 nephrectomized and 7 non-nephrectomized (control) rats. After two-week nephrectomy stabilization, cohorts of six nephrectomized rats were fed casein-based diet plus one of the following regimens: (A) Control, (B) Placebo (casein-based diet without probiotics), (C) Bacillus pasteurii, (D) Sporolac(R), (E) Kibow cocktail, (F) CHR Hansen Cocktail, and (G) ECONORM. Subsequently, blood (retro-orbital) and urine (collected for measurements of blood urea-nitrogen and creatinine respectively), body weight and bacterial counts (feces) were obt...
We retrospectively compared the antiviral effect of tenofovir disoproxil fumarate (TDF) with that... more We retrospectively compared the antiviral effect of tenofovir disoproxil fumarate (TDF) with that of adefovir dipivoxil (ADV) for patients with chronic hepatitis B (CHB) who developed resistance to lamivudine (LAM). One hundred nine patients (86 males), all Asian-American except 1 Caucasian male, with LAM resistance received TDF or ADV. HBV DNA levels were measured every 3 months. The HBeAg loss and ALT normalization were assessed at 12 months on therapy. Forty-four patients (37 males) received TDF (12 with LAM) and 65 (49 males) received ADV (18 with LAM). Median ages (years) for TDF and ADV were 49 (32-68) and 45 (22-68), respectively. Median duration of therapy was 13 months (6-38) and 17 months (6-34) for the TDF and ADV groups. Baseline HBV DNA levels (log(10) copies/ml) were 6.2 +/- 1.7 for the TDF and 6.5 +/- 1.6 for ADV groups. Baseline ALT (IU/l) levels were 77.0 +/- 86.0 and 100 +/- 195 for the TDF and ADV (P = 0.46) groups, respectively. At 12 months, mean levels of log(1...
The ultimate goal of antiviral therapy for chronic hepatitis B (CHB) is prevention of hepatocellu... more The ultimate goal of antiviral therapy for chronic hepatitis B (CHB) is prevention of hepatocellular carcinoma (HCC). Earlier we reported favorable effects of antiviral therapy on survival of HCC patients following curative tumor ablation (Int J Cancer online 14 April 2010; doi: 10.1002/ijc.25382). It was the first observation made in the United States. We now report 12 year follow-up of this patient group. CHB patients with no prior antiviral therapy with a single HCC (≤ 7 cm) were studied. All patients underwent local tumor ablation as their first option. Patients diagnosed before 1999 received no antiviral treatment while those diagnosed after 1999 received antiviral treatment. Survival between the treated and untreated groups was compared. Among 555 HCC patients seen at our clinic between 1991 and 2013, 25 subjects were eligible. Nine subjects (all male patients, median age 53 years [46-66]) did not receive antiviral therapy while 16 (14 male patients, median age 56 years [20-73...
JNCI Journal of the National Cancer Institute, 1990
We measured levels of N-nitrosodimethylamine (NDMA) in peripheral blood from 13 fasting male pati... more We measured levels of N-nitrosodimethylamine (NDMA) in peripheral blood from 13 fasting male patients, 30-74 years old, who had chronic renal failure, and in five healthy control subjects (four males and one female) 31-50 years old. In the patients, we found significant (P less than .01) levels of NDMA (mean +/- SD; 201 +/- 111 ng/kg of blood), which is known to be carcinogenic in animals. Five minutes after oral administration of ethanol (0.4 g/kg of body weight), all patients exhibited a significant (P less than .01) rise in blood NDMA levels (338 +/- 125 ng/kg), suggesting continuous endogenous formation of NDMA that was unmasked by ethanol's ability to inhibit first-pass hepatic metabolism of NDMA. In five of six patients, pretreatment with oral ascorbic acid resulted in a blunting, but not statistically significant, effect on maximum blood NDMA levels after consumption of ethanol. Mean levels were 340 +/- 100 ng/kg before treatment with ascorbic acid and 237 +/- 127 ng/kg during treatment. Ethanol administration unmasks increased gastrointestinal formation of NDMA in patients with chronic renal failure. Further studies are required to confirm a possible link between endogenous NDMA formation and the increased incidence of cancer in these patients.
Earlier clinical studies have reported an ALT flare greater than 10 times the upper limit of norm... more Earlier clinical studies have reported an ALT flare greater than 10 times the upper limit of normal in some patients with chronic hepatitis B when their lamivudine (LAM) treatment was switched to adefovir (ADV) therapy. The current study compared the safety of switching directly to ADV versus overlapping LAM and ADV for 3 months followed by ADV monotherapy. Patients with chronic hepatitis B receiving LAM therapy for > or = 6 months were eligible for the study regardless of the presence of LAM resistance, HBeAg status or serum ALT levels. Eighteen patients (13 males) were randomized to direct switch to ADV and 17 patients (10 males) to overlap. HBV-DNA, ALT, albumin, and total bilirubin were assayed at baseline, 3, 6, 9, and 12 months. Study drugs were discontinued at the end of 12 months with the follow up at 3 and 6 months. The decision to continue antiviral therapy was made at the discretion of the investigator. Baseline ALT levels were similar between the direct switch and overlap group: median ALT (U/L) was 44.0 (16-266) and 33.0 (19-367) for direct switch for overlap group, respectively (P = 0.42). No ALT flare was noted at 3 months in either group: median ALT decreased from 44.0 to 34.5 U/L in the direct switch group, and from 33.0 to 23.0 in the overlap group. Furthermore, no patient in either group exhibited ALT flare throughout the 12 months. This study did not show an ALT flare during switch to ADV at 3 months or at any time later.
Chronic kidney disease may progress to end-stage renal disease, which requires dialysis or kidney... more Chronic kidney disease may progress to end-stage renal disease, which requires dialysis or kidney transplantation. No generally applicable therapies to slow progression of renal disease are available. Bacteriotherapy affords a promising approach to mitigate uremic intoxication by ingestion of live microbes able to catabolize uremic solutes in the gut. The present study evaluates the nonpathogenic soil-borne alkalophilic urease-positive bacterium Sporosarcina pasteurii (Sp) as a potential urea-targeted component for such "enteric dialysis" formulation. Data presented herein suggest that Sp survives through exposure to gastric juice retaining the ability to hydrolyze urea. In vitro, 10 cfu (colony forming units) of Sp removed from 21 +/- 4.7 mg to 228 +/- 6.7 mg urea per hour, depending on pH, urea concentration, and nutrient availability. Beneficial effects of Sp on fermentation parameters in the intestine were demonstrated in vitro in the Simulator of the Human Intestinal Microbial Ecosystem (SHIME) inoculated with fecal microbiota. Enumeration of marker organisms suggested that presence of Sp does not disturb microbial community of the SHIME. Additionally, a pilot study in 5/6th nephrectomized rats fed 10 cfu of live Sp daily throughout the study demonstrated that the tested regimen reduced blood urea-nitrogen levels and significantly prolonged the lifespan of uremic animals.
Insulin resistance has been associated with kidney disease even in the absence of diabetes; howev... more Insulin resistance has been associated with kidney disease even in the absence of diabetes; however, pathways linking insulin resistance to kidney disease are unclear. The purpose of this study was to determine if transforming growth factor (TGF)-β1, a key cytokine associated with kidney disease, responds to circulating levels of glucose and/or insulin. Urinary TGF-β1 levels were measured in 249 young
American journal of kidney diseases : the official journal of the National Kidney Foundation, 1994
Orthoclone OKT3 (Ortho Biotech Inc, Raritan, NJ) is a potent immunosuppressive agent effective in... more Orthoclone OKT3 (Ortho Biotech Inc, Raritan, NJ) is a potent immunosuppressive agent effective in the therapy of acute renal allograft rejection. Following the first one or two doses, patients often exhibit a "flu-like" illness ascribed to OKT3-induced release of cytokines. Systemic reactions resulting from the cytokines include pyrexia, pulmonary edema, bronchospasm, photophobia, headache, hypotension, rigors, hypertension, gastrointestinal disturbances, and arthralgias/myalgias. The cyclooxygenase inhibitor indomethacin has been shown to ameliorate the pyrexia associated with OKT3 administration. We conducted a retrospective analysis with the purposes of (1) confirming that indomethacin reduces pyrexia and (2) determining the effect of indomethacin on the other aforementioned adverse side effects. Group 1 patients (n = 28) received indomethacin during the initial 48 hours of OKT3 antirejection therapy. Group 2 patients (n = 28) received OKT3 without indomethacin. The inc...
The present study was to test the hypothesis that, selected bacteria instilled into the gastroint... more The present study was to test the hypothesis that, selected bacteria instilled into the gastrointestinal tract could help in converting nitrogenous wastes accumulated due to renal insufficiency into non-toxic compounds; thereby, ameliorating the biochemical imbalance. Herein we describe a prospective, blinded, placebo controlled pilot-study, using 5/6th nephrectomized Sprague Dawley rat, as a chronic renal failure model. The study group consisted of 36 nephrectomized and 7 non-nephrectomized (control) rats. After two-week nephrectomy stabilization, cohorts of six nephrectomized rats were fed casein-based diet plus one of the following regimens: (A) Control, (B) Placebo (casein-based diet without probiotics), (C) Bacillus pasteurii, (D) Sporolac(R), (E) Kibow cocktail, (F) CHR Hansen Cocktail, and (G) ECONORM. Subsequently, blood (retro-orbital) and urine (collected for measurements of blood urea-nitrogen and creatinine respectively), body weight and bacterial counts (feces) were obt...
We retrospectively compared the antiviral effect of tenofovir disoproxil fumarate (TDF) with that... more We retrospectively compared the antiviral effect of tenofovir disoproxil fumarate (TDF) with that of adefovir dipivoxil (ADV) for patients with chronic hepatitis B (CHB) who developed resistance to lamivudine (LAM). One hundred nine patients (86 males), all Asian-American except 1 Caucasian male, with LAM resistance received TDF or ADV. HBV DNA levels were measured every 3 months. The HBeAg loss and ALT normalization were assessed at 12 months on therapy. Forty-four patients (37 males) received TDF (12 with LAM) and 65 (49 males) received ADV (18 with LAM). Median ages (years) for TDF and ADV were 49 (32-68) and 45 (22-68), respectively. Median duration of therapy was 13 months (6-38) and 17 months (6-34) for the TDF and ADV groups. Baseline HBV DNA levels (log(10) copies/ml) were 6.2 +/- 1.7 for the TDF and 6.5 +/- 1.6 for ADV groups. Baseline ALT (IU/l) levels were 77.0 +/- 86.0 and 100 +/- 195 for the TDF and ADV (P = 0.46) groups, respectively. At 12 months, mean levels of log(1...
The ultimate goal of antiviral therapy for chronic hepatitis B (CHB) is prevention of hepatocellu... more The ultimate goal of antiviral therapy for chronic hepatitis B (CHB) is prevention of hepatocellular carcinoma (HCC). Earlier we reported favorable effects of antiviral therapy on survival of HCC patients following curative tumor ablation (Int J Cancer online 14 April 2010; doi: 10.1002/ijc.25382). It was the first observation made in the United States. We now report 12 year follow-up of this patient group. CHB patients with no prior antiviral therapy with a single HCC (≤ 7 cm) were studied. All patients underwent local tumor ablation as their first option. Patients diagnosed before 1999 received no antiviral treatment while those diagnosed after 1999 received antiviral treatment. Survival between the treated and untreated groups was compared. Among 555 HCC patients seen at our clinic between 1991 and 2013, 25 subjects were eligible. Nine subjects (all male patients, median age 53 years [46-66]) did not receive antiviral therapy while 16 (14 male patients, median age 56 years [20-73...
JNCI Journal of the National Cancer Institute, 1990
We measured levels of N-nitrosodimethylamine (NDMA) in peripheral blood from 13 fasting male pati... more We measured levels of N-nitrosodimethylamine (NDMA) in peripheral blood from 13 fasting male patients, 30-74 years old, who had chronic renal failure, and in five healthy control subjects (four males and one female) 31-50 years old. In the patients, we found significant (P less than .01) levels of NDMA (mean +/- SD; 201 +/- 111 ng/kg of blood), which is known to be carcinogenic in animals. Five minutes after oral administration of ethanol (0.4 g/kg of body weight), all patients exhibited a significant (P less than .01) rise in blood NDMA levels (338 +/- 125 ng/kg), suggesting continuous endogenous formation of NDMA that was unmasked by ethanol's ability to inhibit first-pass hepatic metabolism of NDMA. In five of six patients, pretreatment with oral ascorbic acid resulted in a blunting, but not statistically significant, effect on maximum blood NDMA levels after consumption of ethanol. Mean levels were 340 +/- 100 ng/kg before treatment with ascorbic acid and 237 +/- 127 ng/kg during treatment. Ethanol administration unmasks increased gastrointestinal formation of NDMA in patients with chronic renal failure. Further studies are required to confirm a possible link between endogenous NDMA formation and the increased incidence of cancer in these patients.
Earlier clinical studies have reported an ALT flare greater than 10 times the upper limit of norm... more Earlier clinical studies have reported an ALT flare greater than 10 times the upper limit of normal in some patients with chronic hepatitis B when their lamivudine (LAM) treatment was switched to adefovir (ADV) therapy. The current study compared the safety of switching directly to ADV versus overlapping LAM and ADV for 3 months followed by ADV monotherapy. Patients with chronic hepatitis B receiving LAM therapy for > or = 6 months were eligible for the study regardless of the presence of LAM resistance, HBeAg status or serum ALT levels. Eighteen patients (13 males) were randomized to direct switch to ADV and 17 patients (10 males) to overlap. HBV-DNA, ALT, albumin, and total bilirubin were assayed at baseline, 3, 6, 9, and 12 months. Study drugs were discontinued at the end of 12 months with the follow up at 3 and 6 months. The decision to continue antiviral therapy was made at the discretion of the investigator. Baseline ALT levels were similar between the direct switch and overlap group: median ALT (U/L) was 44.0 (16-266) and 33.0 (19-367) for direct switch for overlap group, respectively (P = 0.42). No ALT flare was noted at 3 months in either group: median ALT decreased from 44.0 to 34.5 U/L in the direct switch group, and from 33.0 to 23.0 in the overlap group. Furthermore, no patient in either group exhibited ALT flare throughout the 12 months. This study did not show an ALT flare during switch to ADV at 3 months or at any time later.
Chronic kidney disease may progress to end-stage renal disease, which requires dialysis or kidney... more Chronic kidney disease may progress to end-stage renal disease, which requires dialysis or kidney transplantation. No generally applicable therapies to slow progression of renal disease are available. Bacteriotherapy affords a promising approach to mitigate uremic intoxication by ingestion of live microbes able to catabolize uremic solutes in the gut. The present study evaluates the nonpathogenic soil-borne alkalophilic urease-positive bacterium Sporosarcina pasteurii (Sp) as a potential urea-targeted component for such "enteric dialysis" formulation. Data presented herein suggest that Sp survives through exposure to gastric juice retaining the ability to hydrolyze urea. In vitro, 10 cfu (colony forming units) of Sp removed from 21 +/- 4.7 mg to 228 +/- 6.7 mg urea per hour, depending on pH, urea concentration, and nutrient availability. Beneficial effects of Sp on fermentation parameters in the intestine were demonstrated in vitro in the Simulator of the Human Intestinal Microbial Ecosystem (SHIME) inoculated with fecal microbiota. Enumeration of marker organisms suggested that presence of Sp does not disturb microbial community of the SHIME. Additionally, a pilot study in 5/6th nephrectomized rats fed 10 cfu of live Sp daily throughout the study demonstrated that the tested regimen reduced blood urea-nitrogen levels and significantly prolonged the lifespan of uremic animals.
Uploads
Papers by Steve Dunn