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Biomedical subjects

M Griffin

Publications and source records attributed to M Griffin.

At least 163 records · Page 9Linked to original sources
PubMed1995

Peripheral transluminal angioplasty under ultrasound guidance: initial clinical experience and prevalence of lower limb lesions amenable to ultrasound-guided angioplasty.

PURPOSE: Currently, endovascular techniques require monitoring by radiographic imaging for accurate catheter placement. The aim of this study was first to determine the feasibility of angioplasty under ultrasound guidance using a special catheter system. Based on this outcome, the second goal was to investigate the prevalence of lesions amenable to ultrasound-guided angioplasty. METHODS: A balloon catheter system (Echomark) has been developed, which allows accurate catheter guidance by ultrasound imaging. An ultrasound-sensitive piezoelectric sensor positioned in the middle of the balloon portion of the angioplasty catheter is interfaced to an external duplex scanner via the catheter system. The exact position of the balloon relative to the transducer is calculated and reproduced on the screen of the duplex scanner to guide balloon positioning. In the feasibility assessment of the procedure, 16 patients with disabling claudication and rest pain were selected for balloon angioplasty under ultrasound guidance based on arteriographic and hemodynamic lesion criteria of > 50% stenosis with a peak systolic velocity ration > 2.5 in a lesion < 4 cm long that could be imaged by duplex ultrasonography. A fall in the peak systolic velocity ratio below 2.0 was selected for a procedural endpoint corresponding to < 30% residual stenosis on the completion angiogram. In the second part of the study, the prevalence of stenoses amenable to ultrasound-guided angioplasty was studied in 80 patients presenting with symptoms of peripheral arterial disease. RESULTS: In the feasibility study, 20 stenoses (5 common iliac, 6 external iliac, and 8 superficial femoral arteries and 1 graft) meeting the inclusion criteria were subjected to ultrasound-guided angioplasty with confirmation by completion angiography. The procedure was possible in 18 (90%) of the 20 stenoses. The two failures occurred in iliac arteries that could not be imaged by duplex scanning due to obesity, bowel gas, and/or vessel wall calcification. In one case, the peak systolic velocity ratio exceeded 2.5 despite a satisfactory control arteriogram; redilation was performed, and the ratio fell below 2.0. In the second part of the study, 21 (26.2%) of the 80 patients had 29 stenoses that were amenable to angioplasty according to angiographic criteria (> 50% stenosis and < 4 cm length). All these stenoses were evaluated with duplex scanning to determine their suitability for angioplasty under ultrasound guidance. Twenty-three (79%) of the 29 lesions selected for angioplasty were well visualized by duplex, and angioplasty would have been possible based on our initial clinical experience. CONCLUSIONS: Angioplasty under ultrasound control is a feasible technique for peripheral lesions. Ultrasound allows monitoring of both anatomical and hemodynamic parameters during angioplasty and thus provides a procedural endpoint that correlates to the control angiogram. A large proportion (79%) of stenoses deemed suitable for angioplasty can be well visualized by ultrasound, but obesity, vessel wall calcification, and bowel gas may limit the ability to obtain a satisfactory ultrasound image. Ultrasound-guided angioplasty is a potentially useful procedure that warrants further investigation.

Angioplasty, Balloon↗
PubMed1994

A case control study of infection with an epidemic strain of multiresistant Salmonella typhimurium DT104 in England and Wales.

Laboratory reports of a multiresistant strain of Salmonella typhimurium definitive type (DT) 104 rose in 1993; this led the Public Health Laboratory Service to investigate cases and identify possible risk factors for infection. Information derived from questionnaires, and details of previous isolations of S. typhimurium DT104 from food and animals, were used to design an unmatched case control study. Eighty-three cases whose isolations were of the same plasmid profile type (the 'epidemic strain') and 235 controls were included in the analysis. Illness was independently associated with the consumption of several food items and contact with animals, particularly ill farm animals. The number of isolations of this organism continues to rise, and control measures may include reducing infection in animals used for food, reducing the risk of contamination at all stages of the food chain, and raising awareness of measures to prevent food poisoning among food handlers and the general public.

Adolescent↗
PubMed1994

Urinary MHPG and clinical symptoms in patients with unipolar depression.

The relationship between levels of urinary 3-methoxy-4-hydroxyphenylglycol (MHPG) and symptom scores on the Hamilton Rating Scale for Depression was examined in 31 patients with unipolar depression. Patients with either low MHPG or high MHPG showed significant sleep disturbance in the form of early morning awakening. Patients with mid-range or high MHPG showed decreased work and activities. Endogenomorphy factor scores represented a blend of these findings.

Adult↗
PubMed1994

Bone strength and histomorphometry of the distal femur.

The ultimate bone strength of the distal femur was measured radially, by indentation testing, around the transepicondylar line in 3 mm depth steps up to 12 mm below the subchondral bone plate. Specimens from 10 cadavers were used. This orientation of specimens was chosen as a way to provide measurement in a more physiologic orientation for load bearing and to standardize the assessment. Bone hardness declined sharply over the first 6 mm below the surface, tending to plateau at deeper levels. Within the top 6 mm layer the lateral condyle was softer than both the medial condyle and the central patellofemoral area (P < .05), but at deeper levels it maintained greater hardness. Of the histomorphometric parameters, those showing the greatest consistent correlation with hardness were bone volume fraction and trabecular separation. When the tibiofemoral and patellofemoral compartments were compared it was found that for a given value of bone volume fraction, condylar bone is marginally harder than patellofemoral bone. The data are relevant to the design of implants that match their geometric and material properties to the shape and strength of the underlying bone.

Adult↗
PubMed1994

Improved fit by asymmetric tibial prosthesis for total knee arthroplasty.

The adequacy of the fit of the prosthesis to the tibia is an important variable in the outcome of total knee arthroplasty. A good fit covers the cancellous bone of both condyles, involves the denser bone of the tibial shell, but does not overhang beyond the bone at any point. In this research, an anatomically shaped tibial prosthetic base plate was developed from tibial measurements. A series of five template sizes, chosen to fit our patient database, was then evaluated for fit in the operating room by one surgeon. The assessment included bone exposure and the overhang of the prosthesis beyond the bone perimeter. The measurements of overhang or bone exposure were analysed. A commercial prosthesis was used as a control. An asymmetrical tibial plate conformed well to the anatomical shape of the resected upper tibia resulting in very little exposed bone and very few cases of overhang. The absence of such overhang provides better function in the surrounding stabilizing soft tissues, and so permits recovery of the maximum range of motion post-operatively.

Anthropometry↗
PubMed1994

Ductal carcinoma in situ presenting as a stellate lesion on mammography.

Ductal carcinoma in situ (DCIS) usually manifests as microcalcification on mammography, but several other unusual forms of presentation on mammography are also described. One such atypical appearance is the stellate mass without calcification. This may occur with DCIS alone or when DCIS is associated with a complex sclerosing lesion (CSL). We retrospectively analysed the histopathological specimens and mammograms of women who were referred for biopsy from two large breast screening programmes, and were found to have DCIS as the dominant histological lesion. Of 677 women referred for surgical biopsy, 86 (13%) showed histological evidence of DCIS as the predominant lesion, and of these, seven (8%) showed a stellate appearance on mammography without associated calcification. In three cases the mammographic appearance was due to DCIS alone, and four were due to a CSL with associated DCIS. Only one case showed microinvasion (< 1 mm), and this was not large enough to account for the stellate lesion. We advocate biopsy of all radial lesions which are not surgical scars, as malignancy associated with benign lesions such as CSLs could be missed by cytological sampling errors.

Aged↗
PubMed1994

Management of medically fragile infants and children.

Medically fragile infants and children present a host of challenges. The neonatal intensive care unit (NICU) is initially the mainstay of care for these infants, but it does not meet the critical developmental interactive needs of the child and parents to ensure positive psychosocial bonding. The care of these infants is further complicated by high daily costs (ranging from $1,000 to $2,500 per neonatal intensive care bed day) and lengthy, expensive inpatient stays (typically ranging from one week to five months or more). FHP Utah, a managed care organization, met these challenges through an innovative case management-oriented home care program called "Welcome Home." The program has produced a major impact on the quality and the cost of care for medically fragile infants. This article summarizes the first year's experience in implementing and operating the program.

Home Care Services↗
PubMed1994

Transfection of tissue transglutaminase into a highly malignant hamster fibrosarcoma leads to a reduced incidence of primary tumour growth.

Reduced expression of the tissue transglutaminase in both murine and human tumours has been consistently associated with tumour growth and progression. To investigate the functional effects of transglutaminase expression we have transfected a constitutive human tissue transglutaminase expression construct into a highly malignant hamster fibrosarcoma cell line Met B. Met B clones expressing the exogenous tissue transglutaminase exhibited a reduced incidence of primary tumour formation and an increased adherence to tissue culture plastic and fibronectin coated surfaces when compared to transfected and non transfected control cells. Transglutaminase transfected clones exhibited no significant differences in their growth rates measured in vitro, cell morphology or levels of spontaneous apoptosis measured by the determination of detergent insoluble apoptotic envelopes. The data demonstrates a suppressive effect of tissue transglutaminase on tumour growth and confirms its importance in the phenotypic changes associated with the cancer process.

Animals↗
PubMed1993

Identification of sites on the human Fc epsilon RI alpha subunit which are involved in binding human and rat IgE.

The high affinity IgE Fc receptor (Fc epsilon RI), found on mast cells and basophils, is a tetrameric receptor complex. The extracellular portion of the Fc epsilon RI alpha subunit consists of two immunoglobulin-like domains and binds IgE in the absence of the other subunits. To localize the high affinity IgE binding site within the Fc epsilon RI alpha subunit, we generated a series of chimeric receptor constructs where one of the two immunoglobulin-like domains was either deleted or substituted with those from the human Fc gamma RIIIA alpha or the rat Fc epsilon RI alpha subunit. The chimeric receptors were monitored for their capacity to bind human and rat IgE, and their reactivity with different antireceptor antibodies. Domain I substitutions maintained high affinity human IgE binding. Domain II substitutions resulted in a total loss of both human and rat IgE binding. Single-domain alpha subunits could not bind IgE, suggesting that both extracellular domains are required for proper protein folding or IgE binding. To further localize the IgE binding sites, homolog-scanning mutagenesis was performed. At least three independent regions of domain II encompassing residues 118-129, 136-150, and 148-162 were required for IgE binding. Our results suggest that domain II of the human Fc epsilon RI alpha confers most of the important contributions to the binding of the human IgE Fc molecule, whereas domain I of the rat Fc epsilon RI alpha makes important contributions to the binding of rat IgE.

Amino Acid Sequence↗
PubMed1993

The inhibition of human duodenal adenylate cyclase activity by Ca2+ and the effects of EGTA.

This study demonstrates that the inhibition of adenylate cyclase activity by Ca2+ is enhanced in the presence of increasing [EGTA] (0, 0.3, 1, 2.5 mM) by 2 orders of magnitude. It has been established that this effect is not because of poor Ca2+ buffering by low [EGTA] or high Ca2+ binding by the membrane preparation. It is present irrespective of stimulus. We suggest the enhanced sensitivity of adenylate cyclase to Ca2+ induced by EGTA is caused by the Ca-EGTA complex being a more inhibitory species than Ca2+. Thus consideration of the effects of the Ca-EGTA complex should be made when interpreting the results from experiments involving Ca2+ and EGTA.

Adenylyl Cyclase Inhibitors↗
PubMed1993

Alveolar type II cell-fibroblast interactions, synthesis and secretion of surfactant and type I collagen.

During alveolar development and alveolar repair close contacts are established between fibroblasts and lung epithelial cells through gaps in the basement membrane. Using co-culture systems we have investigated whether these close contacts influence synthesis and secretion of the principal surfactant apoprotein (SP-A) by cultured rat lung alveolar type II cells and the synthesis and secretion of type I collagen by fibroblasts. The alveolar type II cells remained cuboidal and grew in colonies on fibroblast feeder layers and on Matrigel-coated cell culture inserts but were progressively more flattened on fixed fibroblast monolayers and plastic. Alveolar type II cells cultured on plastic released almost all their SP-A into the medium by 4 days. Alveolar type II cells cultured on viable fibroblasts or Matrigel-coated inserts above fibroblasts accumulated SP-A in the medium at a constant rate for the first 4 days, and probably recycle SP-A by endocytosis. The amount of mRNA for SP-A was very low after 4 days of culture of alveolar type II cells on plastic, Matrigel-coated inserts or fixed fibroblast monolayers: relatively, the amount of mRNA for SP-A was increased 4-fold after culture of alveolar type II cells on viable fibroblasts. Co-culture of alveolar type II cells with confluent human dermal fibroblasts stimulated by 2- to 3-fold the secretion of collagen type I into the culture medium, even after the fibroblasts' growth had been arrested with mitomycin C. Collagen secretion, by fibroblasts, also was stimulated 2-fold by conditioned medium from alveolar type II cells cultured on Matrigel. The amount of mRNA for type I collagen increased only modestly when fibroblasts were cultured in this conditioned medium. This stimulation of type I collagen secretion diminished as the conditioned medium was diluted out, but at high dilutions further stimulation occurred, indicating that a factor that inhibited collagen secretion also was being diluted out. The conditioned medium contained low levels of IGF-1 and the stimulation of type I collagen secretion was abolished when the conditioned medium was pre-incubated with antibodies to insulin-like growth factor 1 (IGF-1). There are important reciprocal interactions between alveolar type II cells and fibroblasts in co-culture. Direct contacts between alveolar type II cells and fibroblasts appear to have a trophic effect on cultured alveolar type II cells, increasing the levels of mRNA for SP-A. Rat lung alveolar type II cells appear to release a factor (possibly IGF-1) that stimulates type I collagen secretion by fibroblasts.

Animals↗
PubMed1993

Characterization of the transglutaminase-mediated large molecular weight polymer from rat liver; its relationship to apoptosis.

A large molecular weight sodium dodecyl sulfate (SDS)-insoluble polymer was isolated from rat liver and shown to be a product of transglutaminase activity by virtue of its high epsilon(gamma glutamyl)lysine content. Antiserum raised against this polymer crossreacted with another product of transglutaminase activity, the apoptotic envelope isolated from cultured hamster fibrosarcoma cells. The amino acid composition of isolated apoptotic envelopes and the SDS-insoluble polymer were found to be comparable, although not identical. Using the polymer antiserum, the apoptotic index (mg polymer protein per mg DNA) of normal and tumor tissue was determined and found to correlate with the associated transglutaminase activity. Localization of proteins involved in polymer formation in neonatal rat liver cells was found immunohistochemically to be in those cells undergoing apoptosis; these cells also stained selectively for transglutaminase. Several proteins from liver homogenate were found to crossreact with the antipolymer serum, notably proteins of 120, 80, 43 and 38 kDa.

Animals↗
PubMed1993

Interleukin-2-activated human effector lymphocytes mediate cytotoxicity by inducing apoptosis in human leukaemia and solid tumour target cells.

The mode of cytotoxic action employed by cytolytic lymphocytes remains unclear, with the possibility of several mechanisms being utilized dependent upon the activation state of the effector cell. In this work, the induction of apoptosis in target cells by 'killer' lymphocytes at differing states of activation has been studied. Although the cytotoxicity of natural killer (NK) cells and recombinant human interleukin-2 (rhIL-2) or interferon-alpha (IFN-alpha)-activated effector cells, against NK-sensitive target cells, was high, their cytotoxic action appeared to be mediated via differing pathways. Effector cells activated short term (4 hr) with rhIL-2 and those mediating rhIL-2 lymphokine-activated killer (LAK) activity after long-term (4 day) activation were found to induce the formation of sodium dodecyl sulphate (SDS)-insoluble apoptotic bodies in NK-sensitive target cells, as well as increasing the level of activity of the apoptosis related enzyme tissue transglutaminase, thus suggesting the induction of the apoptotic pathway as a means of effecting target cell death. Non-activated and short-term (4 hr) IFN-alpha-activated effector cells did not appear to utilize this pathway in the target cell as their means of cytotoxicity. Effector cells showing LAK activity were also cytotoxic towards NK-insensitive cells, and this cytotoxicity again appeared to be mediated via the apoptotic pathway.

Apoptosis↗
PubMed1993

High initial nortriptyline doses in the treatment of depression.

BACKGROUND: Guidelines for doses of nortriptyline are generally somewhat vague and usually recommend a fairly wide dose range. Additionally, the safety and utility of beginning treatment at higher initial doses have not been adequately investigated. METHOD: Nortriptyline treatment was initiated with a 75- to 125-mg dose depending on weight in 26 depressed inpatients in an open-label study. RESULTS: The mean Hamilton Rating Scale for Depression score decreased by 45% within 1 week (p < .001) and remained essentially unchanged at the end of Week 2. Orthostatic hypotension was the side effect of major concern since it is virtually the only significant cardiovascular effect in young healthy individuals treated with tricyclic antidepressant medication. Only 2 patients developed orthostasis, which required additional treatment with fludrocortisone, and no patients were dropped from the study due to side effects. None of the patients evidenced significant ECG changes. Twenty-one patients (81%) reached therapeutic drug levels on the initial dose regimen by the end of Week 1. CONCLUSION: Subjects tolerated high initial doses well and appeared to reach significant benefit within the first week. However, double-blind controlled studies are needed before any definitive conclusions can be drawn.

Adult↗