Search PubMed⌕ Search

Biomedical subjects

D Morgan

Publications and source records attributed to D Morgan.

At least 199 records · Page 11Linked to original sources
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↗
PubMed1992

Development of an in vitro model to study carcinogen-induced neoplastic progression of initiated mouse epidermal cells.

Initiation and promotion in mouse skin carcinogenesis produce multiple benign tumors, squamous papillomas, but only a few squamous cell carcinomas. The spontaneous conversion from the benign to the malignant phenotype occurs over many months and in stages, but induced malignant conversion can be accomplished more rapidly by exposure of papilloma-bearing mice to mutagens or by transfection of papilloma cell lines with specific oncogenes. The analysis of genetic targets responsible for carcinogen-induced neoplastic progression would be facilitated by the development of in vitro models where the process is rapid, focal, and quantitative. To this end, primary newborn mouse keratinocytes were initiated in vitro by the introduction of the v-rasHa oncogene via a defective retrovirus. Recipient cells produce squamous papillomas and have a high proliferation rate in culture medium with 0.05 mM Ca2+, but fail to grow in medium with 0.5 mM Ca2+ which is permissive for growth of malignant keratinocytes. When v-rasHa-keratinocytes were exposed to mutagens in vitro, proliferative foci emerged after culture in 0.5 mM Ca2+ for 4 weeks. These foci stained intensely red with rhodamine stain, could be easily quantitated, and readily incorporated bromodeoxyuridine. Dose-response studies with several mutagens indicated that the number of foci increased with concentration to the point where excessive cytotoxicity developed. Mutagens varied in potency for producing foci in the following order: cis-diamminedichloroplatinum greater than or equal to benzo(a)pyrene diolexpoxide I greater than N-methyl-N'-nitro-N-nitrosoguanidine greater than or equal to 4-nitroquinoline-N-oxide greater than N-acetoxy-acetyl- aminofluorene. The tumor promoter 12-O-tetradecanoylphorbol-13-acetate was inactive in the assay. A subset of cell lines derived from foci produced malignant tumors in vivo, while others were not tumorigenic. Analysis of DNA from cell lines and tumors revealed that most tumorigenic cell lines maintained the v-rasHa genome, whereas the viral sequences were deleted in nontumorigenic cell lines. Immunohistochemical analysis indicated that proliferative foci and quiescent v-rasHa keratinocytes expressed keratin 8, a marker of v-rasHa expression in cultured keratinocytes. Cells in foci, but not v-rasHa control cells, expressed keratin 13, a marker which is strongly associated with the malignant progression of skin tumors in vivo. This in vitro assay provides a quantitative model to study chemically induced focal neoplastic progression at the cellular level and to identify agents which may be selective for enhancing malignant conversion.

Animals↗
PubMed1992

Multilocus DNA fingerprint analysis of cell banks: stability studies and culture identification in human B-lymphoblastoid and mammalian cell lines.

The technique of multilocus DNA fingerprinting has great potential for the authentication of animal cell cultures and in identification of cross-contamination. The Alec Jeffreys probes 33.6 and 33.15 were used as multilocus probes to demonstrate the consistent DNA fingerprint profiles in human peripheral blood and its derivative Epstein-Barr virus (EBV) transformed B-lymphoblastoid cultures maintained by repeated subculture for six months. However, fingerprint analysis of EBV transformed cultures generated from small numbers of cells showed that the majority (seven of eight cultures) had anomalous profiles. Some of these altered profiles shared common features not seen in the peripheral blood pattern. Analysis of seven murine hybridoma clones from a single fusion experiment revealed only two clones which could not be distinguished using probe 33.15. Further studies of master and distribution cell banks for eleven cell lines demonstrated consistent fingerprint profiles in all cases except one (U937). However, this cell line showed only minor differences in the master and distribution bank profiles. These data indicate that, while changes in fingerprint profile may be identified in exceptional instances, the multilocus fingerprinting method using probes 33.6 and 33.15 is a powerful and reliable tool in the quality control of animal cell cultures.

Animals↗
PubMed1992

Coagulation abnormalities and ivermectin.

Prothrombin ratios were measured 13-16 days after treatment in 148 subjects from Sierra Leone taking part in a double-blind placebo-controlled trial of ivermectin. Prolonged prothrombin ratios were observed more frequently in the ivermectin group, although this difference was not significant and no patients suffered bleeding complications. Further investigation of these patients failed to reveal any abnormality of liver function, although factor VII and II levels were reduced in most affected individuals, suggesting interference with vitamin K metabolism. Ivermectin has a minimal effect on coagulation and concern about mass treatment for this reason appears to be unjustified.

Adolescent↗
PubMed1992

Syringobulbia: a surgical appraisal.

Syringobulbia is a term which has been clinically applied to brain stem symptoms or signs in patients with syringomyelia. Syringobulbia clefts are found on investigation or at necropsy caused by cutting outwards of the CSF under pressure from the fourth ventricle into the medulla. These should be differentiated from the ascending syringobulbia which may occur from upward impulsive fluid movements in a previously established syringomyelia. Clinical analysis of 54 patients suggests that bulbar features are most often found with neither of the above mechanisms but are due to the effects of pressure differences acting downward upon the hind-brain with consequent distortion of the cerebellum and brainstem, traction on cranial nerves or indentation of the brain-stem by vascular loops. The commonest symptoms in the 54 patients were headache (35), vertigo (27), dysphonia or dysarthria (21), trigeminal paraesthesiae (27), dysphagia (24), diplopia (16), tinnitus (11), palatal palsy (11) and hypoglossal involvement (11). Careful attention to hydrocephalus is advisable before craniovertebral surgery, but the decompression of the hindbrain and the correction of craniospinal pressure dissociation remains the mainstay of surgical treatment. The results of careful surgery are good, 45 of the 54 cases reported improvement. Most of the reported deterioration occurred in a few patients who did conspicuously badly.

Adolescent↗
PubMed1992

Generalized effects of a peer-delivered first aid program for students with moderate intellectual disabilities.

Peers with mild intellectual disabilities taught first aid skills to 4 students with moderate intellectual disabilities. A multiple probe design across participants was used to examine the effects of the peer teaching program during an acquisition and a partial sequential withdrawal phase. Generalization assessments were conducted in the participants' homes using novel, randomized simulated injuries. Results suggested that the peer teaching program resulted in acquisition of first aid skills, and the participants' skills generalized to the home, to novel simulated-injury locations, and to new trainers. Additionally, a more detailed analysis of the generalized responding suggested that when given a choice among first aid materials, participants treated burns using large adhesive bandages rather than the materials used in training. Participants also successfully treated injuries when novel instructional cues were used. The findings are discussed with respect to training issues, generalization and maintenance of the acquired skills, and the use of peer tutors with disabilities.

Child↗
PubMed1992

Macrophage activation and immunomodulation by myeloperoxidase.

Myeloperoxidase (MyPo) is an enzyme found in neutrophils and monocytes that plays an important role in the microbicidal and cytocidal activities of these cells. The present studies show that this enzyme can also affect both capacities and functions of macrophages. When resident peritoneal macrophages from C57BL/6 mice were exposed to preparations of either human or canine enzyme in vitro, tumor necrosis factor (TNF) was released. The amount of TNF produced was dose dependent and could be neutralized with polyclonal anti-TNF. Low levels of interferon were also produced by these cells. In addition, exposure of murine macrophages in vitro to this enzyme resulted in increased ability to destroy 3T12 target cells. Intravenous injection of mice with myeloperoxidase induced the production of both TNF and interferon, which could be detected in the sera. Possible mechanisms of TNF induction include radical production by myeloperoxidase or ligand-receptor interaction by the binding of this enzyme to the mannosyl-fucosyl receptor. These results, when taken in their entirety, suggest that this enzyme can modulate the immune response through effects on macrophage function.

Analysis of Variance↗
PubMed1992

Immunological studies on onchocerciasis in Sierra Leone. 2. Cell-mediated immune responses after repeated treatment with ivermectin.

Cell mediated responses of peripheral blood lymphocytes were tested by incorporation of I-125 dideoxyuridine in a standard proliferation assay. The cells were collected from age and sex-matched patients selected on the basis of their clinical and parasitological status. These patients were treated with either ivermectin or placebo at 6-monthly intervals for two years. For the purpose of comparison, the patients were divided into three groups: children aged 5-9 years; 10-19 year olds; and, those older than 20 years. Repeated drug treatment over the two year period had no effect on either mitogenic or non-parasite antigen (PPD) responses in a majority of individuals. However, in younger children (5-9 years) repeated treatment with ivermectin resulted in some enhancement of Onchocerca-specific responses measured 6 months after administration of the drug. This effect was more pronounced in children presenting with positive skin-snips. An age related decline in mitogenic responses was observed.

Adolescent↗
PubMed1992

Commentary on Canadian proposals.

An expert on United Kingdom fertilisation and embryology law comments here on recent Canadian proposals, a summary of which appears on pp 8-11.

Advisory Committees↗
PubMed1991

Effects of repeated doses of ivermectin on ocular onchocerciasis: community-based trial in Sierra Leone.

Ivermectin seems to be a safe and effective treatment for onchocerciasis when given in a single dose, but less is known about the effects of repeated doses. Also, there seem to be differences in its effectiveness in anterior and posterior segment ocular disease. The ocular effects of ivermectin were studied in 586 villagers who were taking part in a double-blind, placebo-controlled, randomised trial in Sierra Leone. Only those who had received four doses, with 6-month intervals, of ivermectin or placebo were eligible. The 296 ivermectin-treated subjects and the 272 who received placebo were comparable with respect to age, sex, Onchocerca infection, blindness, and visual impairment before treatment. After treatment, the ivermectin group had less anterior segment disease than the placebo group, with significantly lower prevalences of microfilariae in the anterior chamber and cornea, and punctate keratitis (all p less than 0.001), and iritis (p less than 0.05). There was no significant difference in the prevalence of sclerosing keratitis, optic atrophy, or chorioretinitis between the groups. Visual acuities tended to be better in the ivermectin group, but the difference was not significant. There was a small but significant (p less than 0.01) excess of vascular sheathing in the ivermectin group. These differences persisted when subjects who were blind or visually impaired at baseline were excluded from analysis. The long-term effects of ivermectin, particularly on posterior segment disease, need further evaluation. In the mean time, the mass distribution of ivermectin should be promoted for all communities with hyperendemic onchocerciasis at risk of anterior segment disease.

Adolescent↗
PubMed1991

Endoscopic repair of supraglottic laryngeal clefts.

We describe the technique of endoscopic diagnosis and endoscopic surgical repair used in the management of supraglottic interarytenoid laryngeal clefts in 11 children seen between 1981 and 1988 at the Hospital for Sick Children, London, England. Six of the children had primary type I clefts that required endoscopic repair. The symptoms included inspiratory stridor, choking during eating, and aspiration. Five of the children had previous transcervical repair of type II clefts that had partial breakdown in the interarytenoid area causing symptoms of aspiration, which required secondary repair endoscopically. All the patients had successful microlaryngoscopic closure; in two children, however, the breakdown of the repair necessitated repeated endoscopic correction. The only complication occurred in a case of postoperative supraglottitis, which was successfully managed with intubation and antibiotics. We conclude that endoscopic repair is a useful and reliable technique and an elegant alternative to the open transcervical approach for the closure of supraglottic laryngeal clefts.

Adolescent↗