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Biomedical subjects

K J Simpson

Publications and source records attributed to K J Simpson.

At least 19 recordsLinked to original sources
PubMed1998

Clinical significance of intrahepatic hepatitis C virus levels in patients with chronic HCV infection.

BACKGROUND: The clinical significance of a single assessment of circulating hepatitis C virus (HCV) RNA and its relation to the level of intrahepatic HCV RNA remains unclear. AIMS: To investigate the relation between intrahepatic HCV levels and clinicopathological characteristics of chronic HCV infection. PATIENTS: Ninety eight consecutive patients with chronic HCV infection were studied; none had received alpha interferon therapy. Of these, 12 patients were repeatedly negative for HCV RNA in serum by reverse transcriptase polymerase chain reaction (RT-PCR). METHODS: After diagnostic laparoscopy and liver biopsy, semiquantitative analysis of intrahepatic HCV RNA levels was carried out by limiting dilution of HCV cDNA. HCV genotypes were assessed in 96 patients by restriction fragment length polymorphism analysis of HCV cDNA. RESULTS: Ten out of 12 patients who were RT-PCR negative for HCV RNA in serum were RT-PCR positive in liver; however, this group had a significantly lower intrahepatic HCV level and serum aminotransferase level than the remaining 86 patients. Histological severity (cirrhosis: n = 10); histological activity index; HCV genotype (genotype 1: n = 41; genotype 2: n = 12; genotype 3: n = 36; genotype 4: n = 7); mode of infection (intravenous drug abuse: n = 58; post-transfusion: n = 10; haemophiliac: n = 4; sporadic: n = 26) and alcohol abuse did not affect the intrahepatic virus level. There was no correlation between patient age, duration of infection, and intrahepatic HCV level. CONCLUSIONS: Intrahepatic virus levels were not determined by host factors (age of patient, mode or duration of infection) or by virus factors (HCV genotype). Repeatedly negative RT-PCR for HCV RNA in serum does not indicate absence of HCV from the liver.

Adult↗
PubMed1998

Molecular characterisation and hormone-dependent expression of the porcine whey acidic protein gene.

A 17.5 kDa protein was isolated from porcine whey by reverse phase HPLC and identified as a putative whey acidic protein (WAP) homologue by sequencing 35 and 40 amino acid residues of the amino- and carboxy-terminus respectively. Degenerate oligonucleotides to both of these amino acid sequences were designed and used in reverse transcriptase PCR with RNA from lactating porcine mammary gland as a template. A 162 bp PCR fragment was detected and sequenced. Compilation of the deduced and determined amino acid sequence revealed a protein of 111 amino acids, which had approximately 75, 50, 40 and 35% similarity at amino acid level to camel, rabbit, rat and mouse WAP respectively. It also included the four-disulphide core characteristic of all WAP proteins and most Kunitz-type protease inhibitors. This provides the first unequivocal evidence for WAP secretion in the pig. SDS PAGE analysis of the whey fraction showed that WAP is secreted as a major protein in sow's milk from farrowing to weaning. The molecular mass of WAP in SDS PAGE was significantly greater than the 11.7 kDa determined from amino acid sequence, indicating that porcine WAP is possibly glycosylated. Northern analysis detected a single mRNA transcript of approximately 600 bp in porcine RNA from the mammary gland of lactating sows. To examine the hormone-regulated expression of the WAP gene the mammary glands of sows at day 90 of pregnancy were biopsied and explants cultured for 3 days in the presence of various combinations of porcine insulin (I), cortisol (F) and porcine prolactin (P). Northern analysis of RNA extracted from the tissue indicated that WAP gene expression was barely detectable in the mammary gland prior to culture and there was no increment in explants cultured in the presence of I and F. However, a significant increase in the accumulation of WAP mRNA was observed in explants cultured in I, F and P. A similar result was observed for beta-casein and alpha-lactalbumin gene expression.

Amino Acid Sequence↗
PubMed1997

The clinical significance of the detection of hepatitis GBV-C RNA in the serum of patients with fulminant, presumed viral, hepatitis.

In a significant number of cases of fulminant (presumed viral) hepatitis worldwide, no aetiological agent has been identified. Recently, it has been suggested that a newly described flavivirus, GBV-C, is responsible for some of these cases. This study aimed to assess the clinical significance of GBV-C RNA, demonstrated by reverse transcriptase-polymerase chain reaction (RT-PCR), in the serum of patients with fulminant non-A to E hepatitis. Twenty-three consecutive cases of non-A to E fulminant hepatitis were included in the study. GBV-C RNA was reverse transcribed and amplified using two RT-PCR based detection methods. Medical records were examined to assess clinical history, duration and mode of infection, transfusion history, liver histology and clinical outcome. Five (three female, two male; mean age 21.2 years) of 23 patients had GBV-C RNA detected in their serum by RT-PCR: all five patients were RT-PCR positive following amplification by primers specific for the 5' non-coding region (NCR), whilst four were positive by primers for the NS3 region. Prior to the onset of illness, two patients had risk factors for transmission of an infectious agent; however, all five patients had been transfused during their illness, prior to testing for GBV-C. Of these, two (of two in whom serum was available) were negative for GBV-C after the onset of fulminant hepatitis but before their first transfusion. This study does not support the hypothesis that the detection of hepatitis G virus (HGV)/GBV-C RNA in the serum of patients with fulminant hepatitis indicates a causal association. However, it does demonstrate that a careful transfusion history and screening of blood products is vital before the importance of GBV-C in the aetiology of fulminant hepatitis can be established.

Adolescent↗
PubMed1997

Jump distance of dance landings influencing internal joint forces: I. Axial forces.

Knowledge of the magnitude and rate of applying axial forces (AF) during actual dance movements is necessary for understanding the etiology of chronic injuries and osteoarthritis. The purpose of this study was to investigate the effect of jumping distance on component ankle and knee joint AFs generated during the landing phase of traveling jumps. Six female dancers performed 10 jumps each at 30, 60, and 90% maximum jump distance (JD) and 15 jumps ranging from 35 to 100% JD. A sagittal view of the right leg landing onto a force platform was filmed. Greater ground reaction force maxima, knee flexion, knee and ankle flexion velocity, tibial landing angle, net ankle and knee joint moment maxima, ankle and knee joint reaction AFs, and quadriceps AFs (QuadAF) peak magnitudes and rates of AF application (dFmax/dt) were observed (P < 0.05) at increased JD. The QuadAF was a more important determinant of knee AF than joint reaction AF. Increased quadriceps force was useful for accommodating impact forces but served to increase its contribution to Knee AF, particularly during the later portion of the impact phase. High impact situations create significant magnitudes (e.g., 14 BW) and dFmax/dt of muscle AFs which could contribute to excessive joint wear.

Adult↗
PubMed1997

Jump distance of dance landings influencing internal joint forces: II. Shear forces.

Little is known about shear loading patterns during dance movements. The purpose of the study was to investigate the effect of jumping distance (JD) on contributors of ankle and knee shear forces (SF) generated during the landing phase of traveling jumps. Six female dancers performed 10 trials each at 30, 60, and 90% maximum jump distance (JD) and 15 jumps ranging from 35 to 100% JD. A sagittal view of the right leg landing onto a force platform was filmed using a high-speed cine camera. Greater ankle and knee joint reaction shear forces (JRSF) and quadriceps SF (QuadSF) were observed (P < 0.05) at increased JD. Although the triceps surae SF (TriSurSF) also increased at greater JD for all but one participant, the effect on minimizing the increase in the ankle SF was minor. The peak QuadSF magnitude and rate of loading were always greater than the corresponding knee JRSF variables. However, the increased QuadSF that occurred at longer jumps led to increased knee SF for only half of the participants.

Ankle Injuries↗
PubMed1996

Hypoxemia during diagnostic laparoscopy: a prospective study.

BACKGROUND: Laparoscopic liver biopsy can be safely performed using local anesthesia and intravenous sedation, but the frequency of hypoxemia is unknown. METHODS: We prospectively studied 68 patients undergoing diagnostic laparoscopy and liver biopsy managed by a standard protocol. RESULTS: The mean duration of laparoscopy was 27 +/- 5.53 minutes; the mean dose of diamorphine administered was 6.9 +/- 2.7 mg; diazepam, 7.05 +/- 3.52 mg. The baseline arterial oxygen saturation was 95.6% +/- 2.5% and trough was 85% +/- 5.1%. A fall of greater than 4% saturation from the baseline occurred in 64 out of 68 patients (94%). The mean decrease in saturation was 10.1% +/- 5.4%. An arterial oxygen saturation of less than 85% was seen in 32 patients (47%). There was no correlation between the fall in oxygen saturation and the dose of diamorphine or diazepam, the duration of procedure, body mass index, hemoglobin, or volume of pneumoperitoneum induced. One-way analysis of the variance failed to show a significant relationship between the degree of oxygen saturation and Child's class, etiology of liver disease, or smoking habit. CONCLUSIONS: In this study, we demonstrated that significant desaturation is common in diagnostic laparoscopy with liver biopsy and is likely due to a combination of different pharmacologic and physiologic effects. We recommend continuous monitoring of both arterial oxygen saturation and supplemental oxygen for all patients throughout laparoscopy.

Analysis of Variance↗
PubMed1995

Clinical evaluation of liver disease.

The clinical history and examination is essential in the evaluation of patients with liver disease. This chapter details important points in the clinical history and examination allowing the physician to identify likely causes of liver damage and their investigation. The evaluation should allow the physician to differentiate acute and chronic liver diseases, and in the latter case separate those with obstructive or chronic parenchymal liver disease. It should also allow identification of important complications such as encephalopathy, ascites and portal hypertension. Identification of these main features or complications of liver disease by the clinical evaluation leads to a logical plan of investigation and prompt diagnosis and management of the liver disease.

Diagnosis, Differential↗
PubMed1995

Portal and systemic haemodynamic response to acute and chronic administration of low and high dose isosorbide-5-mononitrate in patients with cirrhosis.

Oral isosorbide-5-mononitrate (Is-5-Mn) was given in doses of 10 and 40 mg acutely and chronically (twice daily for four weeks), allowing a nitrate free interval to 25 patients with cirrhosis. Both 10 mg and 40 mg Is-5-Mn reduced the hepatic venous pressure gradient acutely and chronically, without evidence of tolerance. This was achieved by a reduction in the wedged hepatic venous pressure. The effect on mean azygos blood flow was variable with no significant mean change seen acutely or after chronic use with either dose. The variability was dependent not on the dose used but on the initial azygos flow; the flow in patients with initially low values increased and those with high azygos flows decreased after nitrate challenge. The development of the porto-collateral flow seems an important parameter in predicting haemodynamic response to Is-5-Mn.

Adult↗
PubMed1995

A comparative study of emergency transjugular intrahepatic portosystemic stent-shunt and esophageal transection in the management of uncontrolled variceal hemorrhage.

OBJECTIVES: Transjugular intrahepatic portosystemic stent-shunts (TIPSS) have been shown to reduce portal hypertension consistently and have recently been reported to arrest active variceal hemorrhage. This retrospective and nonrandomized study compares the results of TIPSS with esophageal transection (ET) and devascularization in patients with uncontrolled variceal hemorrhage admitted to a single center with an interest in variceal bleeding. PATIENTS AND METHODS: Two hundred and sixty cirrhotic patients have been referred with variceal bleeding over the past 7 yr. In 41 patients (15.8%), hemorrhage was uncontrolled despite two treatments with sclerotherapy. Thirty-eight patients were eligible for analysis. Nineteen were considered for ET and 19 for TIPSS. Patients in the two groups were well matched for age, sex, etiology of liver disease, and its severity and complications. They have been followed for 13 patient years (TIPSS-7, longest 20 months; ET-6, longest 23 months). Data for survival and rebleeding were analyzed by the Kaplan-Meier method on an intention-to-treat basis. RESULTS: Seven of the 19 were considered unfit for surgery, and 12 underwent esophageal transection and devascularization. TIPSS was undertaken successfully in 17 patients, the Palmaz stent being used in 4 and the Wallstent in 13. Successful TIPSS reduced the mean portal pressure gradient from 22.2 (SE 1.2) to 9.7 (SE 0.7) mm Hg (p < 0.001). Mortality within 30 days of the initial bleed was 42% in the TIPSS group compared with 79% in the ET group (p < 0.05). Rebleeding occurred in 15.6% patients with TIPSS, compared with 26.2% in the ET group. Encephalopathy in the two groups of patients was not significantly different (TIPSS 25% and ET 22%). TIPSS was followed by active infection in 20% compared with 36% after ET. CONCLUSIONS: This study shows that the overall mortality in this group of patients is high whatever the type of treatment used. TIPSS can be performed successfully on these patients who are often not suitable for surgery. Mortality rates were significantly lower in patients treated by TIPSS. Compared with ET, TIPSS should be regarded as the preferred mode of treatment for uncontrolled variceal hemorrhage in patients with cirrhosis.

Case-Control Studies↗
PubMed1995

Soluble adhesion molecules and interleukin-2 receptor concentrations in patients with autoimmune chronic hepatitis.

OBJECTIVE: To test the hypothesis that elevated serum levels of intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), (s)E-selectin, (s)P-selectin and soluble interleukin-2 receptor (sIL-2R) occur in patients with biochemically inactive autoimmune hepatitis (AICH) compared with controls. Such a finding would suggest continued immune activation, which in the long-term would contribute to the development of cirrhosis in such patients. METHODS: sICAM-1, sVCAM-1, sE-selectin, sP-selectin and sIL-2R were measured in serum from 50 patients with AICH, divided into two groups according to whether their serum alanine aminotransferase (ALT) levels were normal (below 40 IU/l) or increased (above 40 IU/l). Fourteen healthy subjects served as controls. Eight patients were followed after the induction of remission with increased immunosuppressive therapy. RESULTS: Elevated levels of sICAM-1, sVCAM-1 and sE-selectin were found in patients with AICH compared with controls, independent of their ALT concentration. Only sICAM-1 was significantly elevated in the patients with active disease compared with patients with inactive disease. sIL-2R concentrations were significantly higher in patients with active disease (ALT above 40 IU/l) compared with controls. sP-selectin concentrations were similar in controls and patients with AICH. In patients with clinical and biochemical relapse, increased steroid therapy was followed by a significant reduction in sICAM-1, sVCAM-1 and sIL-2R. The response of sE-selectin was more variable. sICAM-1 remained elevated in five of the eight patients treated with increased steroid therapy despite normalization of their transaminase levels, sIL-2R, sE-selectin and sVCAM-1 levels. In 52% of patients with biochemically inactive AICH (ALT below 40 IU/l), sICAM-1 was above the control range. CONCLUSIONS: These data suggest that patients with AICH have ongoing immune activation despite biochemically inactive disease. This may result in low grade hepatic inflammation and may explain the progression to cirrhosis in patients with AICH despite immunosuppressive therapy.

Adult↗
PubMed1995

Activity and subcellular distribution of phosphatidate phosphohydrolase (EC 3.1.3.4) in alcoholic liver disease.

A micromethod was developed to assay the hepatic activity and subcellular distribution of phosphatidate phosphohydrolase (PAH, EC 3.1.3.4), an important regulatory enzyme in triacylglycerol synthesis, in human needle biopsy specimens. In normal liver PAH is predominantly cytosolic in distribution, but on treatment with oleic acid it shifts to the membranous compartments of the cell, its physiologically active site. The hepatic specific activity of PAH was similar in controls and patients with fatty liver but significantly more of the enzyme was associated with the membranous compartments in patients with severe alcoholic fatty liver. These observations may explain the enhanced rates of triacylglycerol synthesis observed in these patients and may be implicated in the pathogenesis of alcoholic fatty liver.

Adult↗