Combination of phenotype assessments and CYP2C9-VKORC1 polymorphisms in the determination of warfarin dose requirements in heavily medicated patients.

The relative contribution of phenotypic measures and CYP2C9-vitamin K epoxide reductase complex subunit 1 (VKORC1) polymorphisms to warfarin dose requirements at day 14 was determined in 132 hospitalized, heavily medicated patients. Phenotypic measures were (1) the urinary losartan metabolic ratio before the first dose of warfarin, (2) the S:R-warfarin ratio at day 1, and (3) a dose-adjusted international normalized ratio (INR) at day 4. CYP2C9 and VKORC1 genotypes were determined by gene chip analysis. In multivariate analyses, the dose-adjusted INR at day 4 explained 31% of variability observed in warfarin doses at day 14, whereas genotypic measures (CYP2C9-VKORC1) contributed 6.5%. When S:R-warfarin ratio was used, genotypes contributed more significantly (23.5%). Finally, urinary losartan metabolic ratio was of low predictive value. The best models obtained explained 51% of intersubject variability in warfarin dose requirements. Thus, combination of a phenotypic measure to CYP2C9-VKORC1 genotypes represents a useful strategy to predict warfarin doses in patients receiving multiple drugs (11+/-4 drugs/day).

Evaluation of a hybrid system for three-dimensional measurement of trunk posture in motion.

Ambulatory assessment of trunk posture is important in improving our understanding of the risk of low back injury. Recently, small inertial sensors combining accelerometers, gyroscopes and magnetometers were developed and appear to be promising for measuring human movement. However, the validity of such sensors for assessing three-dimensional (3D) trunk posture in motion has not been documented. The purpose of this study was to evaluate a hybrid system (HS) composed of two inertial sensors for the 3D measurement of trunk posture. A secondary purpose was to explore the utility of adding another source of information, a potentiometer, to measure the relative rotation between both sensors in order to improve the validity of the system. The first sensor was placed over the sacrum and the second on the upper part of the thorax. Both sensors were linked by a flexible rod with a potentiometer. A complementary quaternion filter algorithm was used to estimate trunk orientation by taking advantage of the nine components of each sensor and the potentiometer. The HS's orientations were compared to those obtained from a 3D optoelectronic system. Validation of the HS was performed in three steps in which six subjects had to perform manual handling tasks in: (1) static postures; (2) dynamic motions of short duration (30s); and (3) dynamic motions of long duration (30min). The results showed that the root mean square (RMS) error of the HS was generally below 3 degrees for the flexion and lateral bending axes, and less than 6 degrees for the torsion axis, and that this error was lower for the short-duration tests compared to the long-duration one. The potentiometer proved to be an essential addition, particularly when the magnetometer signals were corrupted and only the gyroscope and accelerometer could be combined. It is concluded that the HS can be a useful tool for quantifying 3D trunk posture in motion.

Ability of a first-pass pharmacokinetic model to characterize cyclosporine blood concentrations after administrations of Sandimmune or Neoral formulations.

Most recent cyclosporine (CsA) pharmacokinetic (PK) studies have focused on noncompartmental analysis. Because CsA undergoes significant first-pass elimination after oral dosing, the most appropriate compartment model may need to take this process into account for the construction of a valid population PK model for Sandimmune (SAN) and Neoral (NEO) formulations. Twenty patients with cardiac transplants were stabilized for at least 4 weeks on a certain dose of SAN, then changed to the same daily dose of NEO. Blood samples were obtained at times 0, 1, 2, 3, 4, 6 and 12 hours after dosing at steady state. Pharmacokinetic modeling was performed using ADAPT II. Quality of fit was assessed by visual graph inspections, R2 values, and Akaike criterion test. Eight pharmacokinetic models were constructed and evaluated. These included one- and two-compartment with and without a first-pass effect and a time-lag. Neoral and SAN data were consistently best fitted using a two-compartment or the two-compartment first-pass model. However, a time-lag process was found to be necessary for SAN. The use of a two-compartment first-pass with (SAN) or without (NEO) a time-lag process appears to fit CsA concentrations at least as well as a two-compartment model. This first-pass model may be very useful for population pharmacokinetics and Bayesian control analysis.

Pitfalls and complications of cricopharyngeal myotomy.

Despite a meticulous operative technique, complications still may occur following cricopharyngeal myotomy. In our series of 205 patients, infection was seen in 11 patients (5.3%) with fistula formation for two patients (1.0%). These complications were seen more frequently in patients treated for a pharyngoesophageal diverticulum. Mortality directly related to the surgical procedure was seen in three patients (1.4%), all suffering from muscular dystrophy.

Chiropractic treatment of cervical radiculopathy caused by a herniated cervical disc.

OBJECTIVE: To present a case of cervical radiculopathy, caused by an MRI documented herniated cervical disc, which was treated with conservative care including chiropractic manipulative therapy. CLINICAL FEATURES: A 60-yr-old woman was treated by a chiropractor for symptoms including a deep, constant, burning ache in the left arm, and severe neck and left shoulder pain. A diagnosis of acute herniated cervical disc was made based on the findings of physical examination and an MRI study of the patient's cervical spine. Important orthopedic findings included exacerbation of the radicular symptomatology with the performance of Valsalva's and cervical compression tests. Neurologic findings included absent biceps and hyporeflexive triceps reflexes on the left, as well as C6 sensory deficit and C7 and C8 sensory hypesthesia. The primary finding on the MRI scan was posterior and lateral herniation on the C6-7 disc. INTERVENTION AND OUTCOME: Treatment included chiropractic manipulative therapy, longitudinal cervical traction and interferential therapy. The patient began a regular schedule of treatments, which started on a daily basis but were gradually reduced as the patient progressed. By the third week of treatment, neck and shoulder pain was completely resolved. Subjective evaluation indicated the radicular pain to be improved by 60% within 6 wk. The patient's pain, numbness and grip strength returned to normal within 5 months. CONCLUSION: Conservative treatment including chiropractic manipulative therapy seems to be a reasonable alternative to surgery, for cervical radiculopathy caused by a herniated cervical disc. Clinical trials should be performed to evaluate long term success rate, risk of permanent disability, rate of recovery and cost effectiveness of this and other forms of treatment for cervical radiculopathy caused by herniated nucleus pulposus.

Gastrointestinal tract hemorrhage. The value of a nasogastric aspirate.

A bloody nasogastric aspirate is believed to imply active upper gastrointestinal tract bleeding, while a nonbloody yellow-green nasogastric aspirate that contains duodenal secretions suggests the absence of bleeding proximal to the ligament of Treitz. To validate these beliefs, physicians were asked to predict the presence of active gastrointestinal tract bleeding and whether bile was present in a nasogastric aspirate obtained immediately before endoscopy in 73 episodes of bleeding in 62 patients. A relationship was found between the physician's assessment of the presence of active bleeding demonstrated endoscopically and the appearance of the nasogastric aspirate. However, the sensitivity and specificity were low (79% and 55%, respectively). No association between the assessment of bile in the nasogastric aspirate and the presence of bile acids was demonstrated. These data do not support the placement of a nasogastric tube to determine whether or not a patient is bleeding, the location of the bleeding, and whether endoscopy should be performed.

Disseminated Yersinia enterocolitica. Case report and review of the literature.

Yersinia enterocolitica is an uncommon cause of infectious diarrhea in the United States. Rarely, it is a cause of extraintestinal disease. Yet an association exists between Y. enterocolitica infection and axial arthropathy. We present a patient with long-standing arthritis, consistent with incomplete Reiter's syndrome, who developed Y. enterocolitica colitis with hepatic and pulmonic infection.

Alpha-interferon. Its effect upon lymphocyte subpopulations and HLA-DR expression within the liver.

Alpha-interferon (IFN-alpha) has been shown to be beneficial in the treatment of chronic active hepatitis occurring as a consequence of hepatitis B virus (HBV) infection. Therefore, it has been used to reduce the high rate of allograft infection in clinical liver transplantation of HBV-positive individuals. This study was performed to evaluate the effect of IFN-alpha on lymphocyte subsets as well as the HLA-DR antigen expression in liver tissue. The resected livers obtained from two groups of patients who received liver transplants between 1983 and 1987 at the University of Pittsburgh were examined: group A consisted of 11 patients who were not treated (controls), and group B consisted of 10 patients (experimental group) who were treated with IFN-alpha for 29.4 +/- 5.6 days prior to transplantation. No differences between the two groups existed in terms of a variety of demographic and clinical characteristics. Both groups had cirrhosis as a result of chronic HBV infection. Monoclonal antibodies to cell-surface antigens unique to different lymphocyte populations and the HLA-DR antigens were used in conjunction with the avidin-biotin-immunoperoxidase technique to identify cells in tissue sections. The number of HLA-DR-positive lymphocytes in the liver was increased (P less than 0.005) within the portal areas in rIFN-alpha-treated group as compared to that seen in the untreated group (84.4 +/- 13.6/HPF vs 33.3 +/- 4.8/HPF). Moreover, the intensity of the HLA-DR antigen expression in the portal areas (P less than 0.02) and in the hepatic lobule (P less than 0.05) was greater in the treated group than in untreated group.(ABSTRACT TRUNCATED AT 250 WORDS)

Use of midazolam for percutaneous liver biopsy.

The standard procedure for percutaneous liver biopsy (PLB) involves only the use of local anesthesia. However, at times, a PLB can be frightening and uncomfortable. Such experiences often limit the willingness of patients to undergo subsequent follow-up biopsies. To investigate the ability of midazolam, a new water-soluble benzodiazepine preparation, noted for its potency, rapid onset of action, and amnestic qualities, to enhance patient acceptability of a follow-up liver biopsy, a "sedative dose" of midazolam (2 mg) or saline was administered immediately prior to and following a percutaneous liver biopsy. The initial dose was used to sedate the subject while not impairing patient cooperation during the biopsy procedure; the second dose was used to induce amnesia for the biopsy procedure. The next morning patient recollection for the preceding biopsy procedure and their willingness to undergo a future PLB were assessed using a questionnaire. Forty-one patients (ages 18-78) were randomized to receive either midazolam (N = 21) or saline/placebo N = 20) treatment. All PLBs were obtained with a Trucut needle. All subjects were given 2-5 cc of 2% xylocaine local anesthetic at the biopsy site. The questionnaire utilized evaluated patient experience of the procedure with respect to their recall, level of anxiety during the procedure, and willingness to undergo a repeat procedure. The data obtained revealed that those receiving midazolam admitted to experiencing less discomfort during the biopsy procedure (P less than 0.04) and had less memory for the procedure (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Midazolam versus diazepam for combined esophogastroduodenoscopy and colonoscopy.

This study compares the effects of two different benzodiazepines used for conscious sedation during combined upper gastrointestinal endoscopy (EGD) and colonoscopy. Subjects were assessed for their degree of analgesia and amnesia for the procedure, prior experience with endoscopy, and willingness to undergo another similar procedure should such be necessary. The patients were randomized single blind to receive either midazolam or diazepam for their preprocedure sedation. The amount of preprocedure sedation utilized was determined by titration of the dose to achieve slurring of speech. Prior to receiving either agent, the subjects were shown a standard card containing pictures of 10 common objects, were asked to name and remember them, and were told they would be "quizzed" (at 30 min and 24 hr) after being sedated for their recollection as to the objects pictured on the card. Each subject filled out a questionnaire addressing their perceived discomfort during the endoscopic procedure and their memory of the procedure 24 hr after the procedure. Sixty-three percent of the midazolam-sedated subjects reported total amnesia for their colonoscopy vs 20% of diazepam-sedated patients (P less than 0.001). Fifty-three percent of midazolam-sedated patients reported total amnesia of their upper gastrointestinal endoscopy vs only 23% of diazepam-sedated subjects (P less than 0.05). The midazolam-sedated subjects reported experiencing less pain with both upper gastrointestinal endoscopy (P less than 0.05) and colonoscopy (P less than 0.001) than did the diazepam-sedated group. Most importantly, the midazolam group was more willing to undergo another similar endoscopic procedure should they be asked to do so by their physician (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

T-cell populations in liver and renal transplant recipients with infectious esophagitis.

Individuals undergoing hepatic and renal transplants are susceptible to infections of the gastrointestinal tract, particularly the esophagus. The most common responsible agents are Candida and herpes simplex virus (HSV) with cytomegalovirus (CMV), Aspergillus, and other agents being regarded as unusual pathogens even in this unique population. Altered T-cell populations have been associated with CMV colitis in healthy homosexuals and in individuals with the acquired immunodeficiency syndrome (AIDS). Similarly, individuals with Epstein-Barr virus infections have altered T-cell populations. Whether these infections alter T-cell populations in infected individuals or the abnormalities in T-cell subpopulations occur first and enhance the likelihood of an infection in susceptible populations is as yet unknown. In this study peripheral blood T-cell populations in individuals before (19 patients) and after (47 patients) liver transplantation and after receiving a renal allograft (21 patients) were compared. Those individual having any symptoms related to esophageal disease underwent upper gastrointestinal endoscopy combined with mucosal biopsies, brushings, and cultures and were subdivided into those with and without infectious esophagitis. CMV esophagitis was found to be associated with an arithmetically decreased T-cell helper/suppressor (H/S) ratio principally due to an increase in the suppressor cell number. Such a reduction in the TH/S ratio and in the number of circulating suppressor cells was not found in esophagitis due to either HSV or Candida and was unrelated to the serum cyclosporine level or prednisone dosage prescribed.(ABSTRACT TRUNCATED AT 250 WORDS)

Infectious esophagitis following liver and renal transplantation.

Upper gastrointestinal endoscopy was performed for the evaluation of infectious esophagitis in 19 consecutive subjects evaluated prospectively before orthotopic liver transplantation (OLTx), in a separate group of 27 subjects post-OLTx, and in 21 subjects following orthotopic renal transplantation (ORTx). None of the pre-OLTx patients had evidence of infectious esophagitis, whereas 11% of the post-OLTx and 24% of the post-ORTx patients had esophageal infections. Candida esophagitis was found only in the post-ORTx patients, whereas cytomegalovirus and herpes simplex viral esophagitis were found in both the post-ORTx and post-OLTx patients. Dysphagia was associated with evidence of herpes simplex virus infection (P less than 0.001) and epigastric pain was associated with Candida infection (P less than 0.001). No association between the administration of prednisone or the blood level of cyclosporine A and esophagitis was found. Finally, the use of standard low-dose mycostatin prophylaxis was not effective for prevention of Candida esophagitis. Nonetheless the use of higher doses of mycostatin was therapeutic.