Why we should treat chronic viral hepatitis.
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Antiviral Agents↗
Biomedical subjects
P D King
Publications and source records attributed to P D King.
Efficacy and safety of combined meperidine and midazolam for EGD sedation compared with midazolam alone.
BACKGROUND/AIMS: Safety concerns have been raised about the use of the combination of an opioid and benzodiazepine for esophagogastroduodenoscopy (EGD) sedation, a common practice of American gastroenterologists. If we could show that patients in American practice settings satisfactorily tolerate EGD with midazolam alone, as is commonly done in Europe, it would provide impetus for American gastroenterologists to change practice habits. METHODS: We performed a randomized, double-blind trial to determine whether meperidine, used in addition to midazolam, improved patient tolerance to EGD compared with the use of midazolam alone in our academic practice setting. Safety parameters were also examined. One hundred twenty adult patients undergoing diagnostic EGD were randomized to receive either 50 mg of meperidine (group I) or 1 mg of midazolam (group II). Patients were then given additional midazolam in incremental doses at the discretion of the attending gastroenterologist to induce a state of conscious sedation. RESULTS: Including the study drug, patients in group I received an average of 1.8 mg less of midazolam compared with group II (mean total midazolam dose, 3.8 mg vs 5.6 mg; p = 0.037). Patients in group I showed improved tolerance for EGD compared with those in group II in terms of a physician rating of "poor" for the overall adequacy of sedation (7 vs 20%, p = 0.033), the need for supplemental narcotics or droperidol during the procedure (7 vs 20%, p = 0.033), the need for additional medication during intubation of the esophagus (12 vs 25%, p = 0.06), the need for a faculty member to accomplish esophageal intubation (7 vs 20%, p = 0.051), the presence of retching, which interfered with the procedure (21 vs 39%, p = 0.046), and premature termination of the exam (0 vs 7%, p = 0.055). No difference was seen in the degree of amnesia, in the willingness of patients to undergo another EGD in the future, or in cardiorespiratory parameters. CONCLUSIONS: In our academic practice setting, 50 mg of meperidine given i.v. at the start of the procedure improved the ability of our patients to tolerate EGD from the endoscopists' standpoint. We found no difference in cardiorespiratory parameters between the groups.
Adolescent↗
Acute hepatitis associated with the use of a Chinese herbal product, ma-huang.
Herbal medicines are widely perceived by the public as being healthful and innocuous. A number of herbal medicines have now been linked with hepatotoxicity. We report a case of acute hepatitis associated with the use of ma-huang, a herbal product derived from plants of the Ephedra species, which is advertised as being useful for causing weight loss and enhancing energy levels. Given the lack of reports in the literature of hepatotoxicity with ma-huang and ephedrine, we speculate that the ma-huang product our patient took contained some other ingredient or contaminant or was misidentified. Our report and others in the literature, which we review, indicate that the clinician should consider herbal medicines as a possible cause of unexplained liver injury.
Acute Disease↗
Esophageal dilation with polyvinyl (American) dilators over a marked guidewire: practice and safety at one center over a 5-yr period.
OBJECTIVE: Improvements in dilator technology over the past decade have revolutionized esophageal dilation. There remains, however, a number of controversies relating to several technical aspects of wire-guided dilation, including whether or not fluoroscopy is necessary. We describe our experience with wire-guided esophageal bougienage. METHODS: We retrospectively reviewed our experience with esophageal dilation using polyvinyl (American) dilators and marked guidewires over the period 1990-1994 to assess the practice habits of our endoscopists and the safety of the technique. We did 606 wire-guided dilations on 354 adult patients. Dilations were done by six different endoscopists. RESULTS: Fluoroscopy was used in only 32/606 dilations (5.3%) and then only to pass a guidewire when the scope could not be passed through the stricture. Fluoroscopy was not used to monitor dilator passage. Peptic strictures were dilated to their maximal target size (determined by the individual endoscopist) in one session in 195 of 253 instances (77.1%). Practice differences were seen between the individual endoscopists relating to how rapidly dilation was accomplished, the number of dilators passed per session, and the maximal dilator size passed. No perforations or other serious complications occurred in our series. CONCLUSIONS: Wire-guided esophageal bougienage is a very safe procedure when careful attention to technique is observed. No perforations were seen in our series of over 600 dilations. Fluoroscopy is needed only in those cases in which a scope cannot be passed through a stricture to assist with guidewire passage. In a majority of cases, peptic strictures can be dilated to a 45-to 51-Fr size in a single session.
Dilatation↗
Novel isoforms of murine intercellular adhesion molecule-1 generated by alternative RNA splicing.
Intercellular adhesion molecule-1 (ICAM-1)-deficient mice, produced by homologous recombination and previously recognized to be devoid of the common form of ICAM-1, are shown to express residual amounts of ICAM-1 Ag in thymus and lung. We demonstrate that this expression of ICAM-1 is possible because the mutated exon 5 in these animals has been skipped by alternative splicing of RNA. Three different alternative isoforms of ICAM-1 are expressed in mutant mice. Moreover, two of these isoforms are expressed in wild-type mice together with two additional alternative isoforms that cannot be produced in mutant mice. All alternatively spliced isoforms of ICAM-1 detected are missing complete extracellular Ig domains. In both mutant and wild-type mice, expression of alternatively spliced isoforms is up-regulated following stimulation of animals with LPS. Furthermore, all alternative isoforms of ICAM-1, except one, retain the ability to bind to the well-recognized ICAM-1 counter-receptor LFA-1. These findings, along with the restricted tissue distribution in mutant mice, indicate that alternative isoforms of ICAM-1 are significant physiologic adhesion structures which could play a distinct role in the functioning of the immune system of intact animals.
Alternative Splicing↗
Polymyositis, pulmonary fibrosis, and hepatitis C.
Polymyositis has been associated with several viral infections, and a spectrum of immune-related diseases may occur with hepatitis C virus (HCV) infection. Both polymyositis and HCV infection may be accompanied by interstitial lung disease; however, no association between polymyositis and HCV infection has been reported previously. We report a new association in a patient with HCV infection: anti-Jo-1 positive polymyositis and interstitial lung disease.
Antibodies, Antinuclear↗
Prospective, randomized trial comparing a new sodium phosphate-bisacodyl regimen with conventional PEG-ES lavage for outpatient colonoscopy preparation.
BACKGROUND: Several recent trials have shown that colonoscopy preparation with sodium phosphate solution is as effective and at least as well tolerated as conventional PEG-ES lavage. These trials utilized two 1.5-fluid oz doses, one given on the evening before colonoscopy and the other early the next morning. METHODS: We devised a new sodium phosphate regimen in which the entire dose was given on the evening before examination (1.5 fl oz at 4 PM, 1.5-fl oz at 7 PM and 10 mg of bisacodyl at 10 PM) and performed a prospective, randomized trial that compared it with conventional PEG-ES lavage in terms of quality of colon cleansing, patient tolerance, and safety in an outpatient colonoscopy population with normal renal function. Seventy-two patients received sodium phosphate-bisacodyl and 75 PEG-ES lavage. RESULTS: The overall quality of colon cleansing and frequency of unsatisfactory preparations were similar with both methods. Patients found preparation with sodium phosphate-bisacodyl to be easier than PEG-ES lavage (p = 0.005). No clinically important adverse effects were seen with either method of preparation. The average cost of sodium phosphate-bisacodyl was $4.32 per patient compared with $18.15 for PEG-ES lavage preparation. CONCLUSION: Preparation with sodium phosphate-bisacodyl, given on the evening before colonoscopy, is a well-tolerated, efficacious, and cost-effective alternative to conventional PEG-ES lavage.
Adolescent↗
The effect of droperidol on objective markers of patient cooperation and vital signs during esophagogastroduodenoscopy: a randomized, double-blind, placebo-controlled, prospective investigation.
We investigated the effect of droperidol on objective markers of cooperation and vital signs in 140 patients undergoing elective diagnostic esophagogastroduodenoscopy. Procedure duration and the total doses of midazolam and meperidine required during the procedure were evaluated as objective markers of patient cooperation. The droperidol group comprised 66 patients and the placebo group 74 patients. Patient and procedure characteristics were similar for both groups. Droperidol produced a 10% reduction in procedure duration. Linear multiple regression modeling revealed droperidol to be a significant predictor of procedure duration (p = .036). Droperidol significantly reduced midazolam and meperidine requirements (p < .01). Nonetheless, four patients in the droperidol group received naloxone to reverse prolonged, excessive drowsiness. Droperidol produced a significant reduction in procedure-associated increase in pulse rate but did not exacerbate procedure-associated reduction in mean arterial pressure. Droperidol favorably influences markers of patient cooperation during elective, diagnostic esophagogastroduodenoscopy. However, the clinical significance of these changes is unclear.
Adjuvants, Anesthesia↗
Safety of early feeding after percutaneous endoscopic gastrostomy.
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Aged↗
Failure of isradipine to reduce infarct size in mouse, gerbil, and rat models of cerebral ischemia.
BACKGROUND AND PURPOSE: The dihydropyridine L-type calcium channel blocker isradipine has been reported to exhibit neuroprotective properties in some, but not all, studies performed in the rat middle cerebral artery occlusion (MCAO) model. In the present study, we examined isradipine in several other models of focal and global ischemia: rat rose bengal, mouse MCAO, and gerbil bilateral carotid artery occlusion (BCAO). For comparison, a novel calcium channel blocker, SB201823A, that we have previously shown to be neuroprotective in rat and gerbil models was also examined in the mouse. METHODS: In the gerbil BCAO model, isradipine was administered at 2.5 mg/kg i.p. as a single dose 60 minutes after ischemia (n = 10). Corresponding controls received vehicle (n = 10), and sham-operated animals received no treatment (n = 6). Locomotor activity and histological assessments were made at 4 days after ischemia. In the rat photothrombotic occlusion model, isradipine was administered at 2.5 mg/kg i.p. as a single dose 60 minutes after ischemia (n = 10), and corresponding controls (n = 10) received vehicle. Histological assessment was made at 7 days after ischemia. In the mouse MCAO model, isradipine was also administered at 2.5 mg/kg i.p. as a single dose 60 minutes after ischemia. Histological assessments were made at 1 (n = 13), 2 (n = 9), and 4 (n = 9) days after ischemia. Vehicle numbers were n = 10, n = 6, and n = 8, respectively. Isradipine and SB201823A were also examined using a combined preischemia and postischemia regimen. Isradipine was administered at 2.5 mg/kg i.p. before occlusion, 1.25 mg/kg i.p. 1 hour after occlusion, 1.25 mg/kg i.p. 2 hours after occlusion, and 2.5 mg/kg twice a day for 3 days after occlusion (n = 16). Corresponding controls received vehicle at the same time points (n = 14). SB201823A was administered 30 minutes before occlusion, 30 minutes after occlusion, and twice daily for 3 days (n = 12). Corresponding controls received vehicle (n = 9). Histological assessment was performed at 4 days after ischemia. RESULTS: When given after ischemia, isradipine failed to affect lesion volume in both the rat and mouse models. In the gerbil, locomotor hyperactivity and hippocampal cell loss were unaffected. Given before and after ischemia in the mouse, isradipine was also ineffective, whereas SB201823A produced a significant reduction in lesion volume. CONCLUSIONS: The L-type calcium channel blocker isradipine was devoid of neuroprotective activity in focal and global models of cerebral ischemia in three species of normotensive animals. These results were compared with data for the novel calcium channel blocker SB201823A, which exhibited a significant effect after pre- and postocclusion administration in the mouse model of permanent focal ischemia.
Animals↗
Hepatic transport of rose bengal by perfused rabbit liver: the effect of albumin binding on the unidirectional rate constants.
The effect of albumin on the unidirectional rate constants for the hepatic transport of rose bengal was studied using perfused rabbit livers. Rabbit livers were perfused in a recirculating system with albumin concentrations between 10 and 600 microM and the disappearance of I-125 rose bengal following a bolus injection was recorded. A distributed model of hepatic transport was used to estimate the rate constants for influx into cells, efflux from cells to plasma and biliary excretion. When the rate constants were corrected for albumin binding, the influx, but not the efflux or excretion constant, was a steeply rising function of the perfusate albumin concentration. The result that the influx but not efflux constant is albumin dependent suggests that the phenomenon is not due to slow diffusion across an unstirred fluid layer or to nonequilibrium binding within such a layer. The possibility that the albumin-dependent influx is due to a direct exchange of rose bengal between albumin and a membrane carrier protein is also considered. The independence of the efflux constant and the albumin concentration makes this hypothesis less tenable. However, these data are consistent with the facilitation of albumin-ligand dissociation by liver cells. This analysis represents the first reduction to practice of distributed modeling of disappearance curves. The fact that the excretion constant is independent of the perfusate albumin concentration serves to validate the model that has previously only been considered on theoretical grounds.
Animals↗
Lymphoma in the setting of dermatitis herpetiformis: another case.
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Celiac Disease↗
Hepatotoxicity of chemotherapeutic and oncologic agents.
Problems arise in cancer chemotherapy when liver function tests are not normal, when drugs that possess known hepatic toxicity are to be given, and when abnormalities arise after drug administration. Most hepatotoxic drug reactions are idiosyncratic, occuring because of either hypersensitivity mechanisms or host metabolic idiosyncrasy. The clinician must always consider that liver injury is due to an idiosyncratic drug reaction, especially in a setting where patients typically receive many drugs, such as an oncology service. Chemotherapeutic agents often possess predictable, dose-dependent ("direct") hepatotoxicity, however. This article addresses the spectrum of hepatotoxic effects of chemotherapeutic agents. The hepatotoxic potential of single-agent as well as combination chemotherapy is discussed and recommendations for dose modifications in patients with impaired hepatic function are provided.
Antineoplastic Agents↗
A positively selecting thymic epithelial cell line lacks costimulatory activity.
The participation of costimulatory molecule interactions in positive selection of T lymphocytes was addressed by assessing the ability of a positively selecting thymic epithelial cell (TEC) line, 427.1, to stimulate allospecific CTL responses. Stimulation of H-2s spleen cells with the H-2b expressing 427.1 line does not result in the generation of cells capable of lysing H-2b target cell lines. The level of expression of MHC class I molecules by 427.1 is lower than that found in other stimulatory TEC lines. However, this finding does not account for the nonstimulatory phenotype. Up-regulation of MHC class I did not result in stimulation, and fusion of 427.1 cells with stimulatory TEC resulted in a line with low MHC class I molecule expression and stimulatory phenotype. The TEC line 427.1 does not express the costimulatory molecule B7/BB1, and transfection of the B7/BB1-encoding DNA results in expression of the molecule and conversion into a stimulatory phenotype, demonstrating directly that the non-stimulatory phenotype is a result of lack of costimulation. However, B7/BB1 expression does not improve the ability of 427.1 TECs to induce positive selection. Intrathymic injection of the B7/BB1 transfected, compared with mock transfected 427.1 cells, rescued fewer CD8+ mature thymocytes in beta 2-microglobulin negative mice. Therefore, unlike the peripheral T cell responses to Ag, positive selection of T cells in the thymus may not depend on the costimulation provided by the presenting cell.
Animals↗
Reactive hemophagocytic syndrome simulating acute hepatitis. A case due to hepatic peripheral T-cell lymphoma.
The reactive hemophagocytic syndrome may mimic acute hepatitis, as we report here. It should be considered when hepatitis is accompanied by high fever, progressive cytopenias, and weight loss, with or without adenopathy and striking lactate dehydrogenase elevation. Bone marrow, lymph node, or liver biopsy are necessary to confirm the diagnosis. Recognition is important, because the syndrome has multiple potential causes amenable to therapy. Preliminary reports suggest that high-dose corticosteroid therapy is useful in suppressing cytokine-stimulated fever and hemophagocytosis, whatever the underlying cause.
Acute Disease↗
Sjögren's syndrome without mixed cryoglobulinemia is not associated with hepatitis C virus infection.
OBJECTIVES: Hepatitis C virus infection has been associated with the formation of autoantibodies. Furthermore, several autoimmune and immune-complex mediated disorders have been proposed to be associated with hepatitis C virus infection. The best documented of these associations is between hepatitis C virus infection and essential mixed cryoglobulinemia. Essential mixed cryoglobulinemia is itself frequently associated with Sjögren's syndrome, and hepatitis C virus infection has been reported to be accompanied by lymphocytic sialadenitis and by xerophthalmia. We therefore searched for hepatitis C virus RNA and antibodies in 48 patients with SS-A/SS-B autoantibodies. METHODS: Patients with both SS-A and SS-B autoantibodies were included if stored serum samples and medical records were available. No patients had clinically apparent chronic liver disease, and no patients had cryoglobulinemia. Six patients (group 1) had abnormally high aminotransferase values on one or more occasion, a history of acute hepatitis, or blood product exposure through transfusion or intravenous drug use. In 18 cases (group 2) no liver disease could be established, but there was insufficient information to exclude it. The 24 remaining patients (group 3) had no risk factors for liver disease, no known history of acute or chronic liver disease, a normal physical examination for signs of chronic hepatitis, and repeatedly normal aminotransferase values. Antibody to hepatitis C virus was determined by RIBA-2 (Chiron Corp, Emeryville, CA). The samples were tested for hepatitis C virus RNA after polymerase chain reaction amplification. RESULTS: No patient had detectable antibody to hepatitis C virus; 47 were negative, and one sample from group 1 was indeterminate. No patients were positive for hepatitis C virus RNA. CONCLUSIONS: We conclude that our patients with Sjögren's syndrome, without cryoglobulinemia and with detectable SS-A/SS-B autoantibodies, do not have clinically apparent liver disease, hepatitis C viremia by polymerase chain reaction, or antibodies to hepatitis C virus by second-generation testing using RIBA-2.
Adult↗
A case of Whipple's disease in Missouri.
Whipple's disease is a rare disorder which has fascinated physicians since its description in 1907. The onset is usually indolent, the symptoms are protean and multisystemic, and disease has often been present for years before a diagnosis is made. Although rare, its identification is important since therapy is simple and effective. We report a case of Whipple's disease in a lifelong resident of Missouri and review the important features of the disease.
Female↗