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K Miller

Publications and source records attributed to K Miller.

At least 217 records · Page 12Linked to original sources
PubMed1998

Matrix metalloproteinases MMP-9 and MMP-7 are expressed in experimental autoimmune neuritis and the Guillain-Barré syndrome.

Matrix metalloproteinases (MMPs) are a family of enzymes that may be implicated in the pathogenesis of inflammatory demyelinating disorders such as multiple sclerosis. The present study investigated the expression of 92-kd gelatinase (MMP-9) and five other MMPs in sciatic nerve from Lewis rats with autoimmune experimental neuritis (EAN), an experimental model of the Guillain-Barré syndrome (GBS). Quantitative polymerase chain reaction analysis revealed an up-regulation of MMP-9 mRNA with peak levels concurrent with maximal disease severity. Increased mRNA expression was associated with enhanced enzyme activity, as detected by gelatin zymography. Immunohistochemically, MMP-9 could be localized primarily around blood vessels within the epineurium and endoneurium in diseased but not normal sciatic nerve. Among all other MMPs investigated, mRNA levels of matrilysin (MMP-7) were found to be up-regulated at the peak of the disorder, remaining at high levels throughout the clinical recovery phase of the disease. To apply these findings to human disease, sural nerve biopsies from GBS patients were examined. By using immunohistochemistry, positive immunoreactivity against MMP-9 and MMP-7 was noted and corroborated by demonstrating augmented mRNA expression in comparison with noninflammatory neuropathies. Furthermore, increased MMP-9 activity was detected by zymography. These findings indicate that 92-kd gelatinase and matrilysin are selectively up-regulated during EAN and expressed in nerves of GBS patients and thus may contribute to the pathogenesis of inflammatory demyelination of the peripheral nervous system.

Animals↗
PubMed1998

Pelvic floor electrical stimulation for genuine stress incontinence: who will benefit and when?

This study sought to determine the characteristics of women in whom pelvic floor electrical stimulation will reduce stress urinary incontinence. It also evaluates how long electrical stimulation should be used before significant improvements are seen in clinical outcomes. Subjects with genuine stress incontinence were enrolled into a multicenter non-randomized trial. They used electrical stimulation for 15 minutes twice daily or every other day for 20 weeks. At the end of 20 weeks, those with a 50% reduction in leakage episodes on voiding diary ('responders') were compared with those who did not show a 50% reduction ('non-responders'). Thirty-one subjects were enrolled and 28 completed the study. After the treatment period, 19 subjects were defined as responders and 9 as non-responders. There were no significant differences between the two groups in baseline demographics (e.g. age, parity, largest birth weight etc.) other than body mass index (greater in nonresponders). Significant subjective and objective improvements were noted among responders by 10 and 14 weeks, respectively. Compliance was higher in responders during weeks 12-15 of the study (P=0.05). It was concluded that a minimum of 14 weeks of pelvic floor stimulation was necessary before significant objective improvements were seen. Body mass index and patient compliance may affect success.

Electric Stimulation Therapy↗
PubMed1998

Testicular microlithiasis and concomitant testicular intraepithelial neoplasia.

We report a case of testicular microlithiasis developing during cancer follow-up in a previously normal testicle. Biopsy revealed testicular intraepithelial neoplasia which was treated with radiotherapy. We believe that especially in cancer follow-up newly developing microlithiasis must lead to biopsy to rule out otherwise undetectable germ cell neoplasia precursor.

Adult↗
PubMed1998

Agonist activity of LSD and lisuride at cloned 5HT2A and 5HT2C receptors.

Evidence from studies with phenylisopropylamine hallucinogens indicates that the 5HT2A receptor is the likely target for the initiation of events leading to hallucinogenic activity associated with LSD and related drugs. Recently, lisuride (a purported non-hallucinogenic congener of LSD) was reported to be a potent antagonist at the 5HT2C receptor and an agonist at the 5HT2A receptor. LSD exhibited agonist activity at both receptors. These data were interpreted as indicating that the 5HT2C receptor might be the initiating site of action for hallucinogens. To test this hypothesis, recombinant cells expressing 5HT2A and 5HT2C receptors were used to determine the actions of LSD and lisuride. LSD and lisuride were potent partial agonists at 5HT2A receptors with EC50 values of 7.2 nM and 17 nM, respectively. Also, LSD and lisuride were partial agonists at 5HT2C receptors with EC50 values of 27 nM and 94 nM, respectively. We conclude that lisuride and LSD have similar actions at 5HT2A and 5HT2C receptors in recombinant cells. As agonist activity at brain 5HT2A receptors has been associated with hallucinogenic activity, these results indicate that lisuride may possess hallucinogenic activity, although the psychopharmacological effects of lisuride appear to be different from the hallucinogenic effects of LSD.

3T3 Cells↗
PubMed1998

Subxiphoidal videomediastinoscopy for diagnostic access to the anterior mediastinum.

Access to the anterior mediastinum from the epigastric region through the retrosternal space, performed with a videomediastinoscope, is described. The method can be used to release the lower lobes of the thymus in transcervical thymectomy as well as for the diagnosis of retrosternal masses of uncertain origin on either side of the anterior mediastinum.

Endoscopy↗
PubMed1998

Pediatric hepatic trauma: does clinical course support intensive care unit stay?

PURPOSE: The objective of this study is to determine if grade of liver injury predicts outcome after blunt hepatic trauma in children and to initiate analysis of current management practices to optimize resource utilization without compromising patient care. METHODS: A retrospective review of 36 children who had blunt hepatic trauma treated at a pediatric trauma center from 1989 to present was performed. Hepatic injuries graded (AAST Organ Injury Scaling) ranged from grade I to IV. Injury Severity Score (ISS), Glasgow Coma Score (GCS), transfusion requirements, liver transaminase levels, associated injuries, intensive care unit (ICU) length of stay, and survival were analyzed. RESULTS: Mean (+/-SEM) age was 6.6+/-0.8 years, mean grade of hepatic injury was 2.4+/-0.2, mean ISS was 17+/-2.6, mean GCS was 13+/-1, and mean transfusion was 15.4 mL/kg of packed red blood cells (PRBC). There were three deaths with a mean ISS of 59+/-9 and a mean GCS of 3+/-0. Death was not associated with a high-grade liver injury, survivors versus nonsurvivors, 2.3+/-0.2 versus 2.7+/-0.3, but was associated with ISS, 13+/-1.4 versus 59+/-9 (P = .005) and GCS, 14+/-1 versus 3+/-0 (P = .005). Only one patient (grade III, ISS = 43) underwent surgery. There were no differences in mean ISS or GCS between grades I to IV patients. The hepatic injury grades of patients requiring transfusion versus no transfusion were significantly different, 3.4+/-0.2 versus 2.2+/-0.2 (P = 0.04). Abused patients had high-grade hepatic injuries and significant laboratory and clinical findings. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were significantly higher in grade III and IV injuries than in grades I and II, 1,157+/-320 versus 333+/-61 (P= .02) and 1,176+/-299 versus 516+/-86 (P= .04), respectively. No children with grade I or II injury had a transfusion requirement or surgical intervention. There were no liver-related complications. CONCLUSIONS: Mortality and morbidity rates in pediatric liver injuries, grades I to IV, correlate with associated injuries not the degree of hepatic damage. ALT, AST, and transfusion requirements are significantly related to degree of liver injury. Low-grade and isolated high-grade liver injuries seldom require transfusion. Blunt liver trauma rarely requires surgical intervention. In retrospect, the need for expensive ICU observation for low-grade and isolated high-grade hepatic injuries is questionably warranted.

Child↗
PubMed1998

Implantable venous access devices in children with hemophilia: a report of low infection rates.

OBJECTIVE: The objective of this study was to define the efficacy and complications of implantable venous access devices (IVADs) in children with hemophilia. STUDY DESIGN: Records were reviewed on all patients with congenital blood coagulation disorders monitored at two children's hospitals in whom one or more central venous catheters had been placed. RESULTS: Since 1989 external and implantable central venous catheters have been inserted to enhance venous access for regular factor concentrate infusion in 45 patients with hemophilia ranging in age from 8 months to 19.5 years (median 7.4 years); 37 patients had factor VIII deficiency and 8 factor IX deficiency. Hemorrhagic complications of catheter placement were infrequent and minor. In the 41 patients having one or more IVADs in place for a median of 31 months, only six episodes of bacteremia occurred in 5 patients during 44,070 days of follow-up. The overall rate of bacteremia complicating IVADs in these patients was 0.14 episodes per 1000 catheter days. Other catheter-related complications were uncommon. Catheters are still in place in 33 patients for a median of 32 months. CONCLUSION: The low risk of infection and other complications associated with the use of IVADs makes the use of these devices attractive in the treatment of patients with hemophilia who require frequent venous access for factor concentrate infusions.

Anti-Bacterial Agents↗
PubMed1998

Laparoscopic nephrectomy: the experience of the laparoscopy working group of the German Urologic Association.

PURPOSE: The centers of the laparoscopy working group of the German Urologic Association collected data to prove the efficacy, safety and reproducibility of laparoscopic nephrectomy. MATERIALS AND METHODS: At 14 centers 482 laparoscopic nephrectomies have been performed until December 1996 via a transperitoneal approach in 344 (71%) and a retroperitoneal approach in 138 (29%). All 482 laparoscopic nephrectomies were performed by a total of 20 surgeons with an average of 24 procedures per surgeon (range 4 to 105). The indications for nephrectomy were benign renal pathology in 444 patients (92%), including renovascular disease in 28%, hydronephrosis in 20%, reflux nephropathy in 15%, chronic pyelonephritis in 12%, end stage nephrolithiasis in 11%, renal dysplasia in 4% and renal tuberculosis in 1%. Of the remaining 38 patients (8%) laparoscopic radical nephrectomy was performed for renal cell carcinoma in 5% and for upper tract transitional cell carcinoma in 3%. RESULTS: Operating time depended mainly on the pathology of the kidney (that is small dysplastic organ versus large hydronephrosis) and the learning curve of the surgeon. However, the average operating time did not vary significantly among the different centers (maximum 277.6 and minimum 81.9 minutes). Intraoperative or perioperative complications were noted in 29 patients (6.0%), including bleeding in 22 (4.6%), bowel injury in 3, hypercarbia in 2 and pleura lesion in 1 and pulmonary embolism in 1. The conversion rate was 10.3% (bleeding, bowel injury, difficult dissection), including 4 patients with renal tuberculosis, 2 with xanthogranulomatous nephritis, and 1 each following renal trauma and embolization. The re-intervention rate was 3.4% due to bleeding in 6 cases, abscess formation in 3, intestinal stenosis in 2 and a pancreatic fistula and port hernia in 1. Mean hospital stay was 5.4 days. CONCLUSIONS: Laparoscopic nephrectomy has become a well established procedure in those urology departments focusing on laparoscopy. The indications and results are reproducible at these centers. However, for patients with severe perinephritis (that is renal tuberculosis, xanthogranulomatous nephritis, posttraumatic atrophy) a higher likelihood of open conversion must be considered.

Adolescent↗
PubMed1998

Urodynamic effects of oral oxybutynin chloride in children with myelomeningocele and detrusor hyperreflexia.

OBJECTIVES: To investigate the effects of oral oxybutynin chloride (OC) on standard urodynamic measures in children with myelomeningocele (MMC) and detrusor hyperreflexia. METHODS: Forty-one MMC children with detrusor hyperreflexia (19 boys and 22 girls, aged 2 months to 15 years; mean 4.9 years) were evaluated urodynamically before and within 3 months after initiation of oral OC therapy (0.2 to 0.3 mg/kg/day). Therapy with oral OC was always combined with clean intermittent catheterization (CIC). RESULTS: Oral OC treatment caused an increase in bladder capacity from 141 +/- 96 to 197 +/- 99 mL (+ 40%; P < 0.01), a decrease in detrusor pressure at maximal capacity from 45 +/- 32 to 28 +/- 23 cm H2O (-38%; P < 0.01), and an increase in detrusor compliance from 6.5 +/- 5.6 to 16.8 +/- 13.7 mL/cm H2O (+ 158%; P < 0.01). Improvement in urodynamic measures and continence were correlated. After a follow-up of at least 2 years, effective protection of renal function was achieved in 38 of the 41 children (93%) with conservative therapy alone. Adverse effects resulted in discontinuation of oral OC treatment in only 2 cases. CONCLUSIONS: Treatment with oral OC and CIC is effective and safe in children with MMC and detrusor hyperreflexia and should be initiated early when indicated by urodynamic findings.

Administration, Oral↗
PubMed1998

The evolution of professional identity: the case of osteopathic medicine.

The osteopathic medical profession was founded in the late 19th century and has become an accepted part of the medical establishment in the United States. Throughout its history, the osteopathic medical profession has attempted to define itself in a way that differentiates osteopathy from other alternative therapies and situates the profession as responsive to the changing health care needs of the American public. This article examines identity within the osteopathic profession by examining the ways in which the profession has created, maintained, and changed its identity in its over century-long existence. The case analysis presented here involves the examination of identity statements culled from several osteopathic data sources. The identity statements represent four specific time periods within the osteopathic profession: the founding statements of A. T. Still, statements from 1915 through 1935 when the scope of osteopathic identity was expanding, statements from 1954 through 1974 in which the osteopathic profession dealt with internal and external threats in developing a "separate but equal" identity, and recent statements from a osteopathic student web site that illustrate current and future views of osteopathic identity. The results of this case analysis highlight the role of the social environment in establishing and changing professional identity, the importance of an occupational founder in shaping the articulation of identity, and the tension between identity and practice within the osteopathic medical profession.

History, 19th Century↗
PubMed1998

Serum concentrations of soluble adhesion molecules in patients with colorectal cancer.

The concentrations of the soluble adhesion molecules E-cadherin, E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were investigated in 48 patients with colorectal cancer before treatment, and their relation to clinical, histological and routine laboratory parameters was examined. Data were collected on tumour stage at presentation, presence and sites of metastatic disease, tumour pathology and results of routine laboratory tests. Serum concentrations of ICAM-1 and VCAM-1 were significantly elevated in the patients with colorectal cancer in comparison with a group of healthy subjects (P < 0.00001). Levels of circulating ICAM-1 and VCAM-1 were increased both in patients with local and those with metastatic disease. Although elevated in some patients soluble E-cadherin and E-selectin concentrations were not significantly elevated compared with the control group (P = 0.71 and P = 0.052 respectively). The levels of circulating ICAM-1 were significantly correlated with those of VCAM-1 and E-selectin. A correlation was also found between the serum concentrations of E-selectin and ICAM-1 and alkaline phosphatase, total white cell count and platelet count. VCAM-1 was positively correlated with age and negatively with degree of tumour differentiation and haemoglobin concentration. The biological implications and possible clinical relevance of these findings are discussed.

Adult↗
PubMed1998

The population pharmacokinetics of long-term methotrexate in rheumatoid arthritis.

AIMS: Methotrexate is considered by many practitioners to be the agent of choice in the treatment of rheumatoid arthritis. The pharmacokinetics of methotrexate have been reported to exhibit significant intersubject variability. Therefore, this study was undertaken to evaluate the population pharmacokinetics of methotrexate during long-term administration in adults with rheumatoid arthritis. METHODS: Methotrexate pharmacokinetics were evaluated in a 36 month study of 62 adults with rheumatoid arthritis. Patients received oral or intramuscular doses of methotrexate weekly with pharmacokinetic studies performed every 6 months. Data were analyzed with nonlinear mixed effects modeling. RESULTS: Three thousand two hundred and sixty post oral or intramuscular dose serum methotrexate concentrations comprising 425 individual concentration vs time profiles were modeled using NONMEM. Covariates that significantly (P < 0.005) influenced the disposition of methotrexate were age (AGE, years), body weight (BW, kg), creatinine clearance (CL(CR), 1 h(-1)), gender (GEN; 0 = male, 1 = female), dose (DOSE, micromol), and fed vs fasted state (FED; 0 = fasted, 1 = fed). The final model describing the biexponential disposition of methotrexate was clearance(CL, 1 h(-1)) = (0.0810*BW + 0.257*CL(CR))*(1-(0.167*GEN); central volume (Vc, 1) = 0.311*BW; peripheral volume (Vp, 1) = 0.469*BW-0.169*AGE; intercompartmental clearance (Q, 1 h(-1)) = 4.27*(1-0.355*GEN); oral absorption rate constant (ka(p.o.), h(-1)) = 4.70-0.0439*DOSE*(1-0.507*FED); intramuscular absorption rate constant (ka(i.m.), h(-1)) = 0.122*DOSE; relative bioavailability (F) = 93.4%; and oral absorption lag time (LAG(p.o.), min) = 13.5. Pharmacokinetic parameters (%CV) for a typical fasted male subject in this study were CL, 7.341 h(-1) (27%); Vc, 23.51 (28%); Vp, 25.31 (31%); Q, 4.25 1 h(-1) (41%); ka(p.o.), 3.67 h(-1) (77%); and ka(i.m.), 3.09 h(-1) (44%). CONCLUSIONS: The population pharmacokinetics of methotrexate in adults with rheumatoid arthritis were well described by this investigation. Substantial interpatient variability was explained by incorporating patient specific data into regression equations predicting pharmacokinetic parameters.

Adult↗
PubMed1998

Pneumatic lithotripsy applied through deflected working channel of miniureteroscope: results in 143 patients.

Although extracorporeal shockwave lithotripsy (SWL) is a successful treatment for ureteral calculi, introduction of miniureteroscopes has advanced endoscopic management. We combined the use of a semirigid ureteroscope with a pneumatic lithotripter (Swiss Lithoclast) for the treatment of ureteral calculi. From January 1992 to August 1994, 143 patients (87 male, 56 female; mean age 48.7 years; age range 22-74 years) with urolithiasis underwent endoscopic lithotripsy with the Swiss Lithoclast under general anesthesia. The 0.8 = mm probe was inserted through the deflected working channel (3.4F) of the Micro-6L ureteroscope (tip diameter 6.9F). The calculi were in the distal (N = 96; 67.1%), mid (N = 34; 23.8%), and proximal part (N = 13; 9.1%) of the ureter. The mean stone size was 6.8 mm (range 5-26 mm). Of the 137 patients whose stones we could access adequately, 70 (51.1%) were stone free immediately after the procedure, and another 31 (22.6%) had residual fragments <3 mm that passed spontaneously. The remaining 36 patients underwent another 50 procedures; 30 SWL sessions in 26 patients (19%), 17 further endoscopic lithotripsies in 14 (10.2%), and open surgery in 3. Application of the Swiss Lithoclast through semirigid miniureteroscopes is highly effective for endoscopic lithotripsy, regardless of stone composition. Deflection of the probe up to 30 degrees did not impair the disintegration rate. Because of the high migration rate of mid and proximal ureteral stones, the Swiss Lithoclast is not recommended in these cases as a primary procedure. Low capital cost and simple and safe handling are the device's major advantages over laser lithotripsy.

Adolescent↗
PubMed1998

Determinants of increased energy expenditure in HIV-infected women.

BACKGROUND: Little is known about sex-specific effects of HIV infection on energy expenditure. OBJECTIVE: We investigated the determinants of energy expenditure in HIV-infected women. DESIGN: Resting energy expenditure (REE), body composition, and hormonal and nutritional indexes were compared in 33 ambulatory, premenopausal HIV-infected women and 26 weight-matched, healthy premenopausal control subjects. REE was determined by indirect calorimetry and body composition by dual-energy X-ray absorptiometry (DXA), bioelectrical impedance analysis, and skinfold-thickness analysis. Hormonal indexes included leptin, testosterone, estradiol, and insulin-like growth factor I. RESULTS: HIV-infected subjects had a higher REE than control subjects [6794 +/- 1374 compared with 6011 +/- 607 kJ/d (1624 +/- 329 compared with 1437 +/- 145 kcal/d), P = 0.0096]. On average, REE was 119 +/- 23% of Harris-Benedict predictions in HIV-infected subjects compared with 102 +/- 9% for control subjects (P = 0.0007). In HIV-infected subjects, REE was highly correlated with fat-free mass (FFM) by DXA (R = 0.641, P < 0.001), but not with weight or disease status. The slope of the regression equation for REE and FFM was significantly greater (P = 0.027, analysis of covariance) for HIV-infected subjects [REE (kJ/d) = 203.5 (kg FFM) - 1237] than for control subjects [REE (kJ/d) = 77.4 (kg FFM) + 2923]. In a stepwise regression analysis, FFM was the most significant variable (P = 0.005), followed by free testosterone (P = 0.029), which together explained 49% of the variation in REE. The final equation was REE (kJ/d) = 230.8 (kg FFM) + 395.9 (free testosterone, pmol/L) - 3304. CONCLUSIONS: Energy expenditure was higher in HIV-infected women than in control women. FFM is the primary determinant of REE in HIV-infected women, but energy expenditure is greater per kg FFM in HIV-infected subjects than in control subjects, which may contribute to the wasting syndrome.

Absorptiometry, Photon↗
PubMed1998

Matrix metalloproteinase-9 and -7 are regulated in experimental autoimmune encephalomyelitis.

Matrix metalloproteinases (MMPs) comprise a group of proteolytic enzymes that are implicated in the pathogenesis of inflammatory diseases of the nervous system such as multiple sclerosis. However, the exact function and expression pattern of MMPs in the inflamed nervous system are not known. In the present study we investigated the expression of 92-kDa gelatinase (MMP-9) in spinal cord from animals with adoptive transfer experimental autoimmune encephalomyelitis (AT-EAE), using a semiquantitative competitive reverse transcriptase-polymerase chain reaction assay. Increased levels of MMP-9 mRNA were found with peak values at times of maximum disease severity. Increased mRNA expression was associated with enhanced proteolytic activity of this enzyme, as demonstrated by gelatin zymography. Immunohistochemistry revealed immunoreactivity along the meninges, around blood vessels and within the parenchyma, in diseased but not in normal spinal cord. Furthermore, the expression pattern of five other MMPs was investigated. Matrilysin (MMP-7) was also found to be upregulated with maximum mRNA levels at the peak of the disease. In contrast, mRNAs for collagenase-3, 72-kDa gelatinase, and stromelysin-1 and -3 were not changed. Our findings indicate that 92-kDa gelatinase and matrilysin are selectively upregulated during AT-EAE and thus may contribute to the pathogenesis of inflammatory diseases of the CNS.

Animals↗
PubMed1998

Effect of montelukast on single-dose theophylline pharmacokinetics.

The effect of montelukast (MK-0476), a cysteinyl leukotriene receptor antagonist in development for treatment of asthma, on single-dose theophylline plasma concentrations was studied in three separate clinical trials. Montelukast was evaluated at 10 mg once daily (the clinical dosage), 200 mg once daily, and 600 mg (200 mg three times daily). At the clinical dosage, montelukast did not change single-dose theophylline plasma concentration in a clinically important manner. The geometric mean ratios for theophylline area under the plasma concentration versus time curve (AUC0-->infinity ) (0.92) and maximal plasma concentration (Cmax ) (1.04) were well within the predefined and generally accepted bioequivalence range of 0.80 and 1.25. Montelukast decreased theophylline Cmax by 12% and 10%, AUC0-->infinity by 43% and 44%, and elimination half-time by 44% and 39% at 200 mg/d (oral and intravenous, respectively), and at 600 mg/d, montelukast decreased theophylline Cmax by 25%, AUC0-->infinity by 66%, and elimination half-time by 63%. These results show that montelukast at the clinical dosage did not change theophylline pharmacokinetics in a clinically important manner, but at 20- to 60-fold higher dosages, montelukast significantly reduced the theophylline pharmacokinetics parameters; an apparent dosage dependence is suggested.

Acetates↗