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Biomedical subjects

D Morgan

Publications and source records attributed to D Morgan.

At least 37 records · Page 2Linked to original sources
PubMed1994

Local recurrence after simple mastectomy.

A retrospective study was carried out to determine the clinical significance of local recurrence after simple mastectomy and node biopsy for primary operable breast cancer, without postoperative irradiation or systemic adjuvant therapy. Local recurrence was defined as a histologically proven lesion in or deep to the mastectomy skin flaps. A total of 966 patients with a median follow-up of 7 years were reviewed. Of these, 223 (23 per cent) developed local recurrence but half the tumours were small single lesions; 70 women had multiple discrete lesions and 21 diffuse carcinomatous dermal infiltration. Local recurrence showed significant associations with tumour grade, nodal status and the presence of lymphovascular invasion in the primary tumour. A predictive index containing these three variables was constructed. Adjuvant irradiation of the flaps is recommended for patients with high scores; such women would otherwise have a 39 per cent chance of developing local recurrence by 5 years. Different types of local recurrence have different chances of responding to local therapy: 13 per cent of single local recurrences, 32 per cent of multiple spot recurrences and 70 per cent of the diffuse type failed to respond to local therapy. Local recurrence predicts reduced patient survival.

Aged↗
PubMed1994

An outbreak of Campylobacter infection associated with the consumption of unpasteurised milk at a large festival in England.

Seventy-two laboratory confirmed cases of Campylobacter infection were identified in people who attended a large festival in England. A case-control study was undertaken to identify the vehicle of infection. Potential risk factors included the water supply to the site, and food, bottled spring water and unpasteurised milk sold at the event. Only the consumption of unpasteurised milk showed a statistical association with having a Campylobacter infection, strongly suggesting that this was the vehicle of infection.

Adolescent↗
PubMed1994

The role of home-made ice cream as a vehicle of Salmonella enteritidis phage type 4 infection from fresh shell eggs.

A family outbreak of Salmonella enteritidis PT4 infection is described in which home-made ice cream was identified as the vehicle of infection. The ice cream contained approximately 10(5) S. enteritidis PT4 organisms per gm and was probably contaminated by an infected shell egg containing between 10(5)-10(8) organisms. The continued relevance of the Chief Medical Officer's warning on the use of raw shell eggs is highlighted. Home-made ice cream using the same recipe as ice cream that had been incriminated as the cause of the family outbreak of S. enteritidis PT4 infection was used to study the growth of the organism that might have occurred in the 3-4 h it took to prepare the product. When the inoculum was in the stationary phase, as it would be from shell or other cross contamination, there was a lag phase of 3 h before growth occurred at room temperature. Even when actively multiplying organisms were introduced, as may be found in an infected egg, there was less than 3 log(10) increase in the salmonella count in 4 h at room temperature. It was, therefore, given the high S. enteritidis count, unlikely that the ice cream was cross-contaminated. By contrast, raspberry sorbet at pH 3.73 proved to be lethal to a large inoculum of S. enteritidis and may be a relatively safe raw egg containing product.

Animals↗
PubMed1994

Daily variation in step length of trained male runners.

The purpose of this study was to quantify daily intra-individual variability in mean step length, a basic descriptor for the running pattern. Following 60 minutes of treadmill accommodation, nine trained male subjects (X age = 34.2 yrs +/- 7.2, X VO2max = 57.0 +/- 4.8 ml.kg-1.min-1) performed daily (Mon-Fri) 6-minute treadmill runs at three submaximal speeds (2.68, 3.13 and 3.58 m.s-1) over a 4-week period. To minimize extraneous influences, subjects refrained from road racing and completed the 20 running sessions (5 d.wk-1.4 weeks for each speed) at the same time of day and in the same footwear. Treadmill velocity was calibrated for each 6-minute running bout and step length was determined during the last 2 minutes of each run. Results indicated that mean step length and coefficient of variation values were 0.984 m and 2.50% at 2.68 m.s-1, 1.124 m and 2.22% at 3.13 m.s-1, and 1.254 m and 2.26% at 3.58 m.s-1. Reliability analyses indicated that the percentage of variation accounted for in step length across all speeds was high and improved very little as test number increased (range = 96% for two days vs 99% for five days). Taken together, these findings suggest that when testing conditions are controlled, within-subject variability in step length measures obtained at multiple submaximal running speeds is small in trained subjects and that criterion step length values can be obtained by averaging duplicate measurements.

Adult↗
PubMed1994

Effect of step length optimization on the aerobic demand of running.

To assess whether distance runners displaying uneconomical freely chosen step lengths (FCSL) could be trained to shift FCSL toward a more optimal setting, six males and three females who exhibited uneconomical FCSL [mean optimal step length (OSL) = -9.81% of leg length from FCSL; mean change in oxygen uptake (VO2) (FCSL - OSL) = 1.46 ml.kg-1.min-1] comprised an experimental group that completed 15 treadmill sessions (30 min/day, 5 days/wk, 3 wk) of OSL training at individually determined running velocities (2.87-3.74 m/s). Training sessions featured alternating 5-min periods of combined audio and visual feedback matching OSL and no feedback. A control group of three subjects with uneconomical FCSL (2 males, 1 female) performed 3 wk of treadmill running without feedback. The extent of step length optimization was evaluated by comparing pre- and posttraining differences between FCSL and OSL and between pre- and posttraining VO2. Compared with the control group, the experimental group demonstrated a significantly (P < or = 0.05) greater relative shift in FCSL toward OSL and a marked reduction in FCSL VO2. Taken together, these results suggest that short-term audiovisual feedback training can be effective in optimizing step length and producing a decrease in aerobic demand among distance runners exhibiting uneconomical FCSL.

Adult↗
PubMed1994

Up-regulation of the connexin43+ gap junction network in haemopoietic tissue before the growth of stem cells.

The early developmental stages of haemopoiesis are thought to be regulated by paracrine growth factors and by the haemopoietic environment. Are gap junctions involved here? Gap junctions are structures in cell membranes allowing the direct transfer of ions and small molecules between adjacent cells and are known to be involved in development. We have found that although connexin43 gap junctions are rare (0.00016 +/- 0.0002/microns2 tissue) in normal adult mouse marrow their expression is 80-fold higher (0.0292 +/- 0.0147/microns2) in neonatal marrow. One difference between neonatal and adult haemopoietic tissue is that in the latter more haemopoietic cells are dividing. To test if more gap junctions were due to increased division we altered adult blood-formation by mobilizing or destroying end cells--granulocytes and red cells--or by forcing stem cells to divide by making them regenerate an ablated blood-forming system. Mobilizing end cells had no effect on the number or distribution of gap junctions in marrow but forced stem cell division caused a 100-fold increase in gap junction expression and did so before any recognizable haemopoietic cells formed. There were greater than normal numbers of gap junctions in radio-protected adult mouse marrow. The cells coupled by gap junctions are TE-7+ mesodermally derived fibroblasts, STRO-1+ stromal cells, and CD45+ and CD34+ haemopoietic cells. We propose that there is a latent network of Cx43+ gap junctions in normal quiescent marrow. In response to events that call for active division of stem cells this network is amplified and coupled to haemopoietic stem cells, perhaps enabling them to divide.

Animals↗
PubMed1994

Restoration of differentiation and suppression of tumorigenicity in somatic cell hybrids of human squamous carcinoma cells and keratinocytes.

Somatic cell hybrid cell lines derived from the fusion of human squamous carcinoma cells (FaDu-Hyg) with human keratinocytes were used to examine the relationships between cell differentiation and tumorigenicity. Treatment of the parental keratinocytes or the two hybrid cell lines with the combination of calcium and fetal bovine serum increased the expression of the envelope precursor, involucrin, 4- to 8-fold, whereas it remained unchanged in FaDu-Hyg cells. Similarly, calcium- and serum-treated keratinocytes and the two hybrid cell lines displayed a 7- to 13-fold increase of the activity of membrane-associated type I transglutaminase, whereas transglutaminase activity in FaDu-Hyg cells did not change appreciably. FaDu-Hyg cells were tumorigenic in vivo, but tumorigenicity was suppressed in both hybrid cell lines. Analysis of additional tumor cell lines indicated that the expression of transglutaminase I and involucrin are under separate genetic control and that loss of transglutaminase activity can result either from a lack of protein or from a defect in the activation step. Thus, keratinization of squamous epithelial cells appears to be controlled by several different recessive genes, which cosegregate with but are probably only partly identical with the genes that suppress tumor formation in vivo.

Animals↗
PubMed1994

Hematopoietic placental protein 14. An immunosuppressive factor in cells of the megakaryocytic lineage.

Placental protein 14 (PP14), an immunosuppressive molecule previously known to be expressed in the female and male reproductive tracts only, was shown to be expressed by hematopoietic cells of the megakaryocytic lineage. Northern blot analysis confirmed the induction specificity of PP14 mRNA in phorbol ester-treated K562 cells. Potent immunosuppressive activity in conditioned medium from phorbol ester-treated K562 cells was attributed to hematopoietic PP14 by anti-PP14 antibody blocking. Immunoprecipitation with anti-PP14 antibodies from conditioned medium revealed two distinct PP14 protein isoforms, designated PP14.1 and PP14.2. Polymerase chain reaction cloning and analysis demonstrated the presence of distinct mRNA counterparts to PP14.1 and PP14.2 that had not been resolved by Northern blot analyses. Hematopoietic PP14.1 mRNA corresponds in size to endometrial PP14 mRNA, whereas the smaller hematopoietic PP14.2 mRNA displays an internal in-frame 66-nucleotide deletion that can be explained by alternative splicing and predicts a 22-amino-acid deletion in the encoded gene product. Both PP14 mRNA isoforms were additionally detected by reverse transcriptase polymerase chain reaction analyses in two human megakaryocytic cell lines and in normal human megakaryocytes and platelets. PP14 mRNA was not detected by reverse transcriptase polymerase chain reaction in a panel of nonhematopoietic, nonendometrial tissues examined. The finding of hematopoietic PP14 within the megakaryocytic lineage provides an additional regulatory link between the coagulation and immune systems in normal and pathological settings.

Base Sequence↗
PubMed1993

Ear-nose-throat abnormalities in the CHARGE association.

A comprehensive evaluation of the otolaryngological abnormalities in 50 patients with colobomata, heart defect, atresia of the choanae, retarded growth or development, genital hypoplasia, and ear anomalies or deafness (CHARGE) was performed. All the patients had ear abnormalities; 96% (48/50) had malformed pinnae, and 54% (27/50) had facial nerve palsies. Only 8% (4/50) had normal hearing, the commonest hearing defect being severe conductive or mixed loss. Eighty-four percent (42/50) of computed tomographic scans of the temporal bone were abnormal, the characteristic abnormality being the combination of a hypoplastic incus and absent semicircular canals. Eighty-six percent (43/50) of patients had upper airway abnormalities. Posterior choanal abnormalities occurred in 56% (28/50), and 42% (21/50) had retrognathia leading to intubation difficulties. Laryngotracheal abnormalities occurred in 38% (19/50), and 14% (7/50) required tracheostomies. Careful upper airway assessment is essential to avoid potentially lethal complications such as aspiration.

Abnormalities, Multiple↗
PubMed1993

Verotoxin producing Escherichia coli O 157 infections associated with the consumption of yoghurt.

Sixteen cases of verotoxin producing Escherichia coli (VTEC) O 157:H7 Phage Type 49 infection were identified in the North West of England from 1 September to 1 November 1991, eight of whom lived in or around the same large town. Eleven of the cases were aged 10 years or less, and five of the affected children developed haemolytic uraemic syndrome. A case control study demonstrated a strong association between VTEC O 157:H7 PT 49 infection and the consumption of a locally produced live yoghurt. This is the first time that an outbreak of VTEC O 157 infection has been linked to the consumption of yoghurt and this vehicle of infection should be considered when investigating such outbreaks in future.

Adolescent↗
PubMed1993

In vivo regulation of murine hair growth: insights from grafting defined cell populations onto nude mice.

The nude mouse graft model for testing the hair-forming ability of selected cell populations has considerable potential for providing insights into factors that are important for hair follicle development and proper hair formation. We have developed a minimal component system consisting of immature hair follicle buds from newborn pigmented C57BL/6 mice and adenovirus E1A-immortalized rat vibrissa dermal papilla cells. Hair follicle buds contribute to formation of hairless skin when grafted alone or with Swiss 3T3 cells, but produce densely haired skin when grafted with a fresh dermal cell preparation. The fresh dermal cell preparation represents the single cell fraction after hair follicles have been removed from a collagenase digest of newborn mouse dermis. It provides dermal papilla cells, fibroblasts, and possibly other important growth factor-producing cell types. Rat vibrissa dermal papilla cells supported dense hair growth at early passage in culture but progressively lost this potential during repeated passage in culture. Of 19 E1A-immortalized, clonally derived rat vibrissa dermal papilla cell lines, the four most positive clones supported hair growth to the extent of approximately 200 to 300 hairs per 1-2 cm2 graft area. The remaining clones were moderately positive (five clones), weakly positive (three clones), or negative (seven clones). Swiss 3T3 cells prevented contraction of the graft area but did not appear to affect the number of hairs in the graft site produced by dermal papilla cells plus hair follicle buds alone. The relatively low hair density (estimated 1-5% of normal) resulting from grafts of hair follicle buds with the most positive of the immortalized dermal papilla cell clones compared to fresh dermal cells suggests that optimal reconstitution of hair growth requires some function of dermal papilla cells partially lost during the immortalization process and possibly the contribution of other cell types present in the fresh dermal cell preparation, which is not supplied by the Swiss 3T3 cells. The current graft system, comprising hair follicle buds and immortalized dermal papilla cell clones, provides an assay for positive or negative influences on hair growth exerted by added selected cell types, growth factors, or other substances. Characterization of the phenotype of the dermal papilla cell lines, which differ in their ability to support hair growth when grafted with hair follicle buds, may provide insight into specific dermal papilla cell properties important for their function in this system.

Animals↗
PubMed1993

Frailty and injuries in later life: the FICSIT trials.

Physical frailty and fall-related injuries present two of the biggest threats to older people's functioning and quality of life. The Frailty and Injuries: Cooperative Studies of Intervention Techniques (FICSIT) trials represent a set of eight different clinical trials concerning physical frailty and injuries in later life. This report documents the history and organization of the trials and provides an overview of the measures being collected at multiple sites and the analytic strategies to be used for multi-site investigations.

Accidental Falls↗
PubMed1993

Visual loss in an onchocerciasis endemic community in Sierra Leone.

The visual acuities of 1625 individuals recruited to a community-based clinical trial of ivermectin in southern Sierra Leone were measured, and the prevalence of visual loss in this rural population where onchocerciasis is hyperendemic was determined. Ocular examination was performed before treatment to establish the cause of visual loss. Using WHO definitions, 1.3% were blind (less than 3/60 in both eyes), 4.3% were visually impaired (between 6/24 and 3/60 in the better eye), and a further 3.4% were uniocularly blind (less than 3/60 in one eye and better than 6/24 in the other). Cataract and onchocerciasis were the major causes of visual loss in this population. More than half of the ocular morbidity was preventable or treatable by public health measures or basic curative medicine. These findings are discussed in the light of the available health and eye care services.

Blindness↗
PubMed1993

Ibutilide: enhanced defibrillation via plateau sodium current activation.

Reductions in current and energy requirements for defibrillation have previously been ascribed to type III antiarrhythmic agents that block outward potassium conductance. This study investigated the effect on defibrillation of ibutilide, a type III antiarrhythmic agent that prolongs action potential duration by activating the sodium component of the plateau inward current. Pentobarbital-anesthetized dogs were subjected to serial episodes of ventricular fibrillation lasting 10 s. In protocol I, current and energy defibrillation requirements were determined via an interactive approach after bolus injections of saline placebo and ibutilide (0.1 mg/kg i.v.). In protocol II, a current dose-response method was utilized in which four shocks each at current doses of 0.7, 0.8, 0.9, and 1.0 x an estimated defibrillation threshold were administered before and after ibutilide (0.075 mg/kg bolus; 0.00125 mg.kg-1 x min-1 i.v.). In protocol I, current and energy values associated with defibrillation measured 10.9 +/- 4.5 A and 16.0 +/- 11.9 J for ibutilide compared with 14.1 +/- 5.6 A and 27.7 +/- 17.7 J for placebo, respectively (n = 9, P < 0.005). In protocol II, ibutilide significantly shifted the current doses associated with 50% successful defibrillation from 14.8 +/- 3.7 to 8.9 +/- 2.0 A (n = 6, P < 0.05). Eight of 15 animals given ibutilide exhibited one or more episodes of spontaneous defibrillation. Ibutilide significantly (P < 0.05) increased ventricular effective refractory period (+23.4%), and both preventricular fibrillation and postdefibrillation monophasic action potential duration at 90% repolarization (+21.7% and +23.3%, n = 9, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1993

Agonist and antagonist effects of mixed action opioids in the pigeon drug discrimination procedure: influence of training dose, intrinsic efficacy and interanimal differences.

The stimulus effects of selective, high efficacy mu opioids and mixed action opioids with varying degrees of intrinsic efficacy at the mu receptor were examined in pigeons trained to discriminate between saline and either 0.056 (low) or 0.18 (high) mg/kg of fentanyl. The stimulus profiles produced by the various opioids could be separated into three groups: 1) opioids that substituted completely for both training doses of fentanyl, with steep slopes and little interanimal differences in the lowest dose (lowest discriminable dose) that produced complete substitution (fentanyl, morphine and l-alpha-acetylmethadol); 2) opioids that substituted completely for the low training dose and produced high levels of substitution for the high training dose, with relatively shallow slopes and interanimal differences in the lowest discriminable dose (butorphanol, buprenorphine, ethylketocyclazocine, ketocyclazocine, proxorphan, (-)-pentazocine and (-)-metazocine); and 3) opioids that substituted completely for the low training dose, with relatively shallow slopes and large interanimal differences in the lowest discriminable dose. Each of these opioids also antagonized the high-dose fentanyl stimulus with large interanimal differences in the lowest antagonist dose (nalbuphine, nalorphine, (-)-cyclorphan, (-)-cyclazocine, (-)-n-ally-normetazocine and levallorphan). These patterns of substitution and antagonism most likely reflect differences in the intrinsic efficacy of these drugs at the mu receptor, with low intrinsic efficacy associated with shallow dose-effect functions, large interanimal differences in the drug's lowest discriminable dose and low levels of substitution for the high-dose fentanyl stimulus. During antagonism tests with naloxone, two patterns were observed: 1) opioids against which naloxone had apparent pA2 values of approximately 7.0, with little interanimal differences and with the slopes of the Schild plots approximating -1.0 (fentanyl and morphine) and 2) opioids against which naloxone had apparent pA2 values an order of magnitude higher, with large interanimal differences and with the slopes of Schild plots being relatively shallow (butorphanol, nalbuphine, nalorphine and levallorphan). The present findings emphasize the importance of training dose, intrinsic efficacy and interanimal differences when analyzing drug discrimination data.

Animals↗
PubMed1992

Tumorigenic suppression of a human cutaneous squamous cell carcinoma cell line in the nude mouse skin graft assay.

The development of human squamous cell carcinomas has been associated with a number of genetic alterations involving chromosome 11, including cytogenetic and allelic deletions as well as amplification of genes in the 11q13 region. To determine the relevance of chromosome 11 in the formation of tumors of stratified squamous epithelial origin, we have introduced, via microcell fusion, a normal human chromosome 11 into the cutaneous squamous cell carcinoma cell line A3886TGc2. The ability of chromosome 11 to modulate the tumorigenicity of A3886TGc2 was evaluated first by inoculating cells s.c. in nude mice. All hybrids remained tumorigenic but exhibited longer tumor latencies than the parent, a result previously observed by other laboratories. We then tested our epidermally derived hybrids in the more physiologically relevant environment of the nude mouse skin graft system. The tumorigenic phenotype of three of four chromosome 11 hybrids placed into nude mouse skin grafts was completely suppressed. Polymerase chain reaction amplification of DNA from normal skin present at the suppressed graft sites failed to detect the introduced human cells. This information indicates that the normal skin is of mouse origin and suggests that the chromosome 11 microcell hybrids did not differentiate in vivo, but most likely failed to survive. We propose that external environmental factors present at the site of inoculation modulate the tumorigenic potential of these cells.

Animals↗