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Biomedical subjects

L J Russell

Publications and source records attributed to L J Russell.

At least 19 recordsLinked to original sources

Combined electric field and ultrasound therapy as a novel anti-tumour treatment.

The permeabilising effects of electric pulses on cell membranes and the use of ultrasound energy of various intensities, for both thermal effects and enhancement of drug and gene delivery, have led to extensive research into the potential applications of these systems in the development of novel anti-cancer treatments. In the present study we have demonstrated for the first time that the application of brief electric pulses 'sensitises' tumour cells to the effects of low intensity ultrasound. The studies were conducted in human tumours established in athymic nude mice and in many instances resulted in the reduction of tumour mass. The combined electric field and ultrasound approach (CEFUS) was applied in vivo to a murine colon adenocarcinoma (C26) and a human oesophageal adenocarcinoma (OE19). The experiments performed demonstrated the anti-tumour effects of the combined therapy. Varying the electrosensitisation parameters used (voltage, waveform, electrode type) contributed to optimise the procedure. Exponential electric pulses with a peak of 1000 V/cm were initially used, but square wave pulses (1000 V/cm, 1 ms, x2, 1 Hz) were found to be just as effective. All ultrasound application parameters were kept constant during the study. The growth rate of C26 tumours treated with CEFUS was significantly reduced with respect to untreated controls at day 7 (96% of average initial tumour volume in CEFUS group versus 615% for controls, P < 0.05). Similar reduction was observed in OE19 tumours treated with CEFUS by day 4 (82% versus 232%, P < 0.032). Our preliminary data suggest that this novel technology could potentially be of wide application in clinical practice for the treatment of solid tumours and is worth further investigation.

Adenocarcinoma↗

How accurate are pressure ulcer grades? An image-based survey of nurse performance.

We report a descriptive study using a questionnaire and twelve digital photographs classified by a consensus panel of experts using the European Pressure Ulcer Advisory Panel and Stirling plus digits classifications. The expert panel comprised 5 tissue viability specialists/clinical lecturers in tissue viability with many years of collective experience and examined 30 images over 2 1/2 hours. In general consensus on wound grading was good; in only 2 images was there insoluble disagreement. Two hundred subjects were recruited from a Tissue Viability Society (N = 50), the European Pressure Ulcer Advisory Panel (N = 50), five Community Trusts (N = 50) and five Acute Trust (N = 50) in England and Wales. The subjects were asked for demographic details (qualifications achieved, number of years qualified, employment grade and how their knowledge of classification of pressure ulcers has been obtained). The second part of the questionnaire asked them to classify twelve digital photographs of pressure ulcers using the European Pressure Ulcer Advisory Panel (EPUAP) and the Stirling plus digits systems. The study demonstrated that there is considerable lack of consensus when pressure ulcers are graded using the Stirling plus digit grading system and less disagreement when the EPUAP scale is used. The study also demonstrates that the statistical returns from different hospital and community units cannot be considered to be directly comparable. Furthermore, the study showed that the nurses most educated in pressure ulcer care (Clinical Nurse Specialists in Tissue Viability) were the most keen to receive extra education, whilst ward nurses were happy with their current knowledge and did not believe further education on pressure ulcer grading was necessary.

Health Knowledge, Attitudes, Practice↗

Determinants of the first decade of bone loss after menopause at spine, hip and radius.

This study documented bone loss at three different sites in the early postmenopausal period, and examined potential predictors. Forty-three women underwent repeated measurements of bone density at the lumbar spine, proximal femur and distal radius for up to 14 years. Individual rates of bone loss were calculated for the spine and hip; for radial trabecular bone, rates were calculated separately for two time periods, earlier and later after menopause. In the spine and radius, initially high rates of loss diminished with time after menopause. No positive correlations for bone loss were found between the three sites, suggesting that faster than average bone loss was specific to individual bones. High body mass index (BMI) was significantly protective against fast bone loss at the spine and radius; in the spine, each unit increase in BMI was associated with a approximately 5% reduction in the rate of bone loss. Of the other variables measured (maximum oxygen consumption, lean body mass, fat mass, mean psoas muscle area at the L3 level, hand grip strength as well as anthropometry) only bone densitometry was sufficiently predictive to help guidance on hormone replacement or other prophylactic therapy. The data suggest that the known relationship between excessive leanness and risk of osteoporosis and vertebral fracture after menopause might in part be due to fast post-menopausal bone loss. Because bulk of psoas muscle was associated with low spine loss rates, the data also support a role for applied muscular loading in local maintenance of bone density.

Adult↗

Churg-Strauss syndrome leading to small bowel infarction: an unusual case of abdominal pain in a young patient.

A 33-year-old man with a history of severe asthma presented to the emergency department with a week-long history of severe unrelenting abdominal pain, nausea and decreased appetite. He was admitted to hospital, and routine gastrointestinal investigations were performed, which did not elucidate the cause of his abdominal pain. Exploratory laparotomy demonstrated patchy infarction of the entire small bowel, characteristic of Churg-Strauss syndrome. The patient subsequently underwent 12 separate laparotomies to salvage surviving small bowel. The patient is maintained on total parenteral nutrition.

Abdomen, Acute↗

Cholesterol esterification is not essential for secretion of lipoprotein components by HepG2 cells.

Hepatic acyl CoA:cholesterol acyltransferase (ACAT) activity may determine storage of cholesterol and supply of cholesteryl esters for the neutral lipid core of very low density lipoprotein. Inhibition of cholesterol esterification in HepG2 cells, by the ACAT inhibitor 447C88, partially reduced the secretion of labelled total cholesterol, but the secretion of apoprotein B mass, and of radiolabelled triacylglycerol and phosphatidylcholine were unaffected. Furthermore, this compound was shown to substantially deplete the intracellular cholesteryl ester mass without affecting secretion of lipoprotein components. In contrast, the less potent ACAT inhibitor, CL277,082, significantly decreased secretion of labelled triacylglycerol, phosphatidylcholine and total cholesterol, in a manner which mirrored the decreases in secretion of apoB. This study clearly illustrates that ACAT inhibitors can exert differential effects on secretion of apoB-containing lipoproteins, which do not correlate with their efficacy in inhibiting ACAT, arguing that cholesterol esterification is not essential for lipoprotein secretion from these cells.

Anticholesteremic Agents↗

Congenital recessive ichthyosis unlinked to loci for epidermal transglutaminases.

Congenital recessive ichthyosis has a broad range of clinical presentations, which may be considered a spectrum of phenotypes with classic lamellar ichthyosis at one pole and classic congenital ichthyosiform erythroderma at the other. The identification of mutations in the transglutaminase-1 gene as a cause of lamellar ichthyosis implicates transglutaminases in other congenital recessive ichthyoses. We investigated two multiplex families with clinical manifestations between the two poles for linkage to the transglutaminase-1 locus on chromosome 14. Strongly negative lod scores prompted a search for linkage to two other epidermally expressed transglutaminases, transglutaminase-2 and transglutaminase-3, on chromosome 20. No evidence for linkage was found. These data confirm the hypothesis that the congenital recessive ichthyoses are genetically heterogeneous and in two families exclude two other transglutaminases that could be considered as candidate loci for at least some of the nonlamellar recessive ichthyoses.

Child↗

Mutations in the gene for transglutaminase 1 in autosomal recessive lamellar ichthyosis.

We recently mapped the disease locus for severe autosomal recessive lamellar ichthyosis (LI) to chromosome 14q11 and showed complete linkage with TGM1, the gene encoding transglutaminase 1. We have now identified point mutations in TGM1 in two of the multiplex LI families used in the linkage study. Each nucleotide change causes a non-conservative amino acid substitution of histidine for one of two adjacent arginine residues in exon 3 of the gene (Arg141His, Arg142His). Within the transglutaminase family, these arginines are invariant within a conserved region, distant from the catalytic site of the enzyme. We hypothesize that these mutations adversely affect formation of crosslinks essential in production of cornified cell envelopes and a normal stratum corneum layer of the skin.

Amino Acid Sequence↗

Stimulation of low-density lipoprotein uptake in HepG2 cells by epidermal growth factor via a tyrosine kinase-dependent, but protein kinase C-independent, mechanism.

Epidermal growth factor (EGF), a potent mitogenic polypeptide, stimulated the uptake and degradation of [3H]sucrose-labelled low-density lipoprotein (LDL) by HepG2 cells. The increase in LDL uptake was prevented by the presence of the tyrosine kinase inhibitor genistein. Activation of protein kinase C with phorbol 12-myristate 13-acetate (PMA) also stimulated the uptake of [3H]LDL by HepG2 cells. When EGF and PMA were added together, PMA increased the response to EGF in an additive manner. The protein kinase C inhibitor Ro-31-8220 prevented the increase in LDL uptake caused by PMA, but did not affect EGF stimulation of LDL uptake. Similarly, down-regulation of protein kinase C activity by chronic treatment with PMA also did not affect the EGF stimulation of LDL uptake. These results suggest that the EGF stimulation of LDL uptake and degradation by HepG2 cells is mediated by a tyrosine kinase-dependent, but protein kinase C-independent, mechanism.

Acetates↗

Linkage of autosomal recessive lamellar ichthyosis to chromosome 14q.

We have mapped the locus for lamellar ichthyosis (LI), an autosomal recessive skin disease characterized by abnormal cornification of the epidermis. Analysis using both inbred and outbred families manifesting severe LI showed complete linkage to several markers within a 9.3-cM region on chromosome 14q11. Affected individuals in inbred families were also found to have striking homozygosity for markers in this region. Linkage-based genetic counseling and prenatal diagnosis is now available for informative at-risk families. Several transcribed genes have been mapped to the chromosome 14 region containing the LI gene. The transglutaminase 1 gene (TGM1), which encodes one of the enzymes responsible for cross-linking epidermal proteins during formation of the stratum corneum, maps to this interval. The TGM1 locus was completely linked to LI (Z = 9.11), suggesting that TGM1 is a good candidate for further investigation of this disorder. The genes for four serine proteases also map to this region but are expressed only in hematopoietic or mast cells, making them less likely candidates.

Adolescent↗

The role of genetic counseling in visually impaired adolescents.

The presence of genetic disorders in a high percentage of adolescents with significant visual impairments emphasizes the important role that genetic counseling can play in this population. However, its intended goals have been controversial. Responses to structured interviews about genetic counseling services from three groups of former students from the Kentucky School for the Blind were compared. One group consisted of students who had received genetic counseling; another, of students who had declined it; and a third, of students who had graduated before the service was available. In all groups, genetic counseling was viewed as a valuable service which would have been pursued by the majority of those who did not have the opportunity to receive it, and by many of those who refused it initially. Although genetic counseling did little to enhance knowledge of the cause of the specific visual impairment, it appeared to be useful in providing information regarding the risk of visual impairment in future offspring. A relatively high rate of unplanned pregnancies was noted in the group who had refused genetic counseling. The significance of this observation is uncertain. One interpretation is that the group refusing genetic counseling may have consisted of individuals who had fewer concerns as adolescents about family planning issues. These observations suggest that it may be appropriate to recommend to adolescents with significant visual impairments to defer childbearing until independent life experiences are accumulated outside the school setting. Then, prior to considering childbearing, genetic counseling should be sought.

Adolescent↗

Homogeneous amperometric immunoassay for theophylline in whole blood.

A homogeneous spectrophotometric EMIT immunoassay kit for the quantitation of theophylline in serum or plasma has been modified to produce a rapid, amperometric immunoassay requiring a 50 microliters whole blood sample. The basis of the detection system for the assay is the electrochemical oxidation of NADH produced by G6PDH-labelled theophylline at a potential of +150 mV vs Ag/AgCl using platinised activated carbon (PACE) electrodes. Comparison of the amperometric whole blood method with the conventional spectrophotometric plasma assay produced a reasonable correlation: y = 0.90x - 1.01, (r = 0.98, n = 12). The advantage of the new method is that simple and robust instrumentation can rapidly determine theophylline in whole blood with no sample pre-treatment or separation steps.

Biosensing Techniques↗

Pro-oxidant effects of lipoxygenase-derived peroxides on the copper-initiated oxidation of low-density lipoprotein.

It has been proposed that lipoxygenases, specifically 15-lipoxygenase, may play an important role in promoting the oxidation of low-density lipoprotein (LDL) in the artery wall. It is well known that peroxides are unstable in the presence of transition metals, decomposing to form the alkoxy and peroxy radicals, and so initiating lipid peroxidation. To test whether lipoxygenase-derived peroxides may promote the oxidation of LDL in the presence of copper, the lipoprotein was enriched with lipid peroxides derived from the enzymic action of 5- and 15-lipoxygenases on either linoleic or arachidonic acid. All of these products were found to promote oxidation, whereas the related hydroxy fatty acids had no effect. This suggests that lipoxygenase-derived peroxides associated with the LDL particle may promote peroxidation in the presence of a suitable transition metal catalyst. This result has implications both for the mechanism of the potential pro-oxidant action of lipoxygenases in vivo and for the ex vivo assessment of the oxidizability of LDL samples isolated from different donors.

Arachidonic Acid↗

Partial duplication of the face: case report and review.

Complete or partial facial duplication is a rare congenital malformation. A spectrum of structural abnormalities varying in degrees of severity has been described in affected individuals. We present discordance for facial duplication between monozygotic twins in which maxillary and mandibular duplication was present in one. The involved twin showed the following findings: ocular hypertelorism, bifidity of the nose, duplication of the maxilla, macrostomia, cleft of the lower lip, hamartoma of the vomer, supernumerary teeth, duplication of the mandibular teeth, bifidity of the tongue, and hamartoma of the floor of the mouth. Surgical management of the facial anomalies is discussed. A review of the literature and discussion of this rare malformation are presented.

Cleft Palate↗

The pinworm, Enterobius vermicularis.

The pinworm, Enterobius vermicularis, is the most common intestinal parasite in the primary care setting, regardless of race, socioeconomic or cultural circumstances. This article discusses symptoms, diagnosis, and treatment.

Animals↗

Ivemark's "asplenia" syndrome: a single gene disorder.

Congenital heart defects as a group represent a significant proportion of congenital malformations. Most are isolated and multifactorially determined; a relatively small proportion are due to a single gene defect, and result in an increased risk of recurrence among first-degree relatives. We have reported the cases of three male siblings with Ivemark's "asplenia" syndrome to support an autosomal recessive mode of inheritance. We have stressed the importance of early recognition of mendelian disorders with associated cardiac malformations to provide meaningful counseling regarding prognosis, medical management, and risk of recurrence.

Adult↗

Gastrocolic fistula presenting as acute diarrhea.

Abdominal pain, diarrhea, weight loss, vomiting, foul eructation, feculent vomiting and melena are among the presenting symptoms of patients with a gastrocolic fistula. A routine physical examination is useful in ruling out the more common causes of the presenting complaints. Barium enema shows the gastrocolic fistula in 90 to 100 percent of cases. En bloc resection of the stomach and colon is the treatment of choice. Alternative therapies include a temporary diverting colostomy, total parenteral nutrition and antacid therapy.

Adult↗