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Biomedical subjects

K J Simpson

Publications and source records attributed to K J Simpson.

At least 37 records · Page 2Linked to original sources
PubMed1999

A comparison of the Sport Stirrup, Malleoloc, and Swede-O ankle orthoses for the foot-ankle kinematics of a rapid lateral movement.

Little information exists about the efficacy of various brace designs to restrict inversion during lateral movements. The purpose of the study was to determine whether semi-rigid stirrup (AirCast Sport Stirrup), semi-rigid modified stirrup (Malleoloc), or a soft, sleeve design (Swede-O) brace varied in their abilities to restrict inversion without hindering plantar/dorsiflexion when a lateral cutting movement is performed compared to a no-brace condition (No-Br). Nineteen volunteers who had previously sprained their right ankles performed 10 sideward cutting trials/brace condition. Based on kinematic data, captured using high-speed cameras, none of the braces restricted inversion compared to the No-Br condition. Plantar flexion was inhibited for all braces, and less dorsiflexion was exhibited for the Swede-O. For three participants, greater toe-in landings were observed for the Swede-O. Based on chi-square analyses, the participants rank of braces for stability and overall performance in decreasing order: Malleoloc, AirCast, Swede-O. It was concluded that the participants may have exhibited injury avoidance behavior during conditions perceived to be less stable, thereby reducing inversion when wearing no brace or the Swede-O brace. It also is tenable that the motion of the shoe was influenced by the presence of the braces, hence, no inversion restriction was observed.

Adult↗
PubMed1999

Novel CXCR2-dependent liver regenerative qualities of ELR-containing CXC chemokines.

Severe acute liver injury due to accidental or intentional acetaminophen overdose presents a major clinical dilemma often requiring liver transplantation. In the present study, liver regeneration after profound liver injury in mice challenged with acetaminophen was facilitated by the exogenous addition of ELR-containing CXC chemokines such as macrophage inflammatory protein-2 (MIP-2), epithelial neutrophil-activating protein-78 (ENA-78), or interleukin 8. Intravenous administration of ELR-CXC chemokines or N-acetyl-cysteine (NAC) immediately after acetaminophen challenge in mice significantly reduced histological and biochemical markers of hepatic injury. However, when the intervention was delayed until 10 h after acetaminophen challenge, only ELR-CXC chemokines significantly reduced liver injury and mouse mortality. The delayed addition of ELR-CXC chemokines to cultured hepatocytes maintained the proliferation of these cells in a CXCR2-dependent fashion after acetaminophen challenge whereas delayed NAC treatment did not. These observations demonstrate that ELR-CXC chemokines represent novel hepatic regenerative factors that exhibit prolonged therapeutic effects after acetaminophen-induced hepatotoxicity.

Acetaminophen↗
PubMed1999

Cytokines, for better or worse?

Cytokines play an important role in the pathogenesis of many diseases including liver failure. Both newly described and 'classic' pro-inflammatory cytokines, such as tumour necrosis factor-alpha, have been implicated in both hepatic injury and liver regeneration. In addition, increased circulating concentrations of these cytokines suggest they may have a hormone-like endocrine effect on tissues distant to their production, leading to the hypotension, lung injury and cerebral oedema that occur in such patients. Increased understanding of the cytokine networks involved in acute liver failure may lead to the development of novel therapies, which may reduce the requirement for liver transplantation in this condition.

Animals↗
PubMed1999

The outcome of the first 165 orthotopic liver transplants in Scotland.

The Scottish Liver Transplant Unit is now in its sixth year of existence. We present the outcome of the first 165 transplants which have at least 12 months follow up. The overall patient (n = 143) survival rates at 1, 3 and 5 years were 86.6%, 79.3% and 74.7% and the graft survival rates were 76.9%, 69.1% and 64.8%. The one year survival rate for patients with chronic liver disease (n = 113) was 89.2% compared with 76.6% for acute liver failure (Breslow = 0.05). The one year survival rate for the first 71 patients receiving their primary graft was 81.7% compared with 91.5% for the subsequent 71 patients (Breslow = 0.09). The majority of deaths (n = 29) were due to sepsis (n = 7), at operation (n = 6) or due to graft vascular insufficiency (n = 4). There were two cases of de novo haematological malignancy. The outcome of the first 165 transplants in Scotland compares very well with other countries throughout the world.

Adolescent↗
PubMed1998

Drug abusers and poisoned patients: a potential source of organs for transplantation?

One of the major constraints to transplantation of solid organs is lack of availability of grafts and any attempt to use all available donors is to be welcomed. We address the possibility of expanding the transplant donor pool by inclusion of more patients who have suffered intoxication with drugs premortem. Particularly important in this context is the exclusion of organ-specific damage, and also infective risk to the potential recipient due to viral causes in the donor.

Brain Death↗
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↗
PubMed1998

Autocrine inhibition of milk secretion in the lactating tammar wallaby (Macropus eugenii).

The lactating tammar wallaby progressively alters the rate of secretion and composition of its milk to provide appropriate nutrition for the developing offspring, whose needs are signalled by changes in the pattern and efficiency of its sucking. Tammars are also capable of asynchronous concurrent lactation, when the mother provides a dilute milk for a newborn young permanently attached to the teat (phase 2A of lactation), and a concentrated milk from an adjacent mammary gland for a young-at-heel (phase 3). The relationship between suckling behaviour and milk secretion, and the ability of adjacent glands to function independently, suggests that milk secretion is controlled locally, within each mammary gland, by a mechanism sensitive to frequency and completeness of milk removal. To determine if tammar milk contains a factor able to control milk secretion, milk fractions have been screened in tissue and cell culture bioassays. A 6-30 kDa fraction of phase 3 whey was found to inhibit milk constituent synthesis and secretion in vitro, and inhibitory activity was associated with two discrete fractions obtained by anion exchange chromatography, which contained protein bands migrating anomalously at 66 kDa and 63 kDa in SDS-PAGE. These bands were recognised in Western blotting by antiserum raised against a bovine autocrine inhibitor of milk secretion. By the same criteria, milk secreted in phase 2B of tammar lactation, when milk secretion is low and suckling intermittent but less vigorous than phase 3, also contained a feedback inhibitor of milk secretion. The results indicate that, as in dairy animals, marsupial milk secretion is under local control through feedback inhibition by a milk protein, and raise the possibility that autocrine feedback may influence the transition from phases of low milk secretion (phase 2A, 2B) to a high rate in the final third phase of lactation.

Animals↗
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↗
PubMed1996

Pathogenesis of alcoholic hepatic steatosis.

Chronic alcohol misuse is the most common cause of hepatic steatosis. The accumulation of lipid is reversible with abstinence, but some workers have suggested that the severity of hepatic steatosis predicts the progression with time to alcoholic cirrhosis. Triacylglycerol is the major accumulating lipid and subcellular fractionation and electron microscopy studies have shown accumulation of lipid droplets within the golgi fraction. This is consistent with the reports in both experimental animals and man of reduced hepatic secretion of very low density lipoprotein triacylglycerol which may be secondary to acetaldehyde-induced disruption of the cytoskeletal elements. In addition, hepatic production of triacylglycerol increases, but most studies in animal models suggest that increased triacylglycerol synthesis becomes less important as hepatic lipid accumulates.

Journal Article↗