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Biomedical subjects

N Young

Publications and source records attributed to N Young.

At least 19 recordsLinked to original sources

Comparison of duplex ultrasound with angiography in assessment of carotid bifurcation disease.

This is a study comparing duplex ultrasound against the "gold standard" of angiography in assessing atherosclerotic disease of the carotid bifurcation, prior to prospective endarterectomy surgery. Thirty-nine patients were studied with both sonography and angiography studies being performed within one month of each other. Plaques were described by sonography as being "smooth" or "irregular" in surface and "homogeneous" or "heterogeneous" in composition. Ultrasound showed an overall 92% sensitivity, against the standard of angiography, in its ability to assess the degree of internal carotid stenosis. There was only a 63% sensitivity with the common carotid arteries and only a 65% sensitivity with the external carotid arteries. Ultrasound did not show a high accuracy in detecting plaque ulceration when compared against angio-graphy.

Adult

Use of percutaneous transluminal balloon angioplasty to treat renovascular disease.

This is a retrospective study of the ability of percutaneous transluminal balloon angioplasty (PTA) to treat hypertension and renal impairment in patients with haemodynamically significant renal artery stenoses (those over 50%). Thirty-two patients underwent PTA procedure in a 4 year study period. Seventeen were male, 15 female, with an average age of 61 years. Thirty patients had atherosclerosis and 2 had fibromuscular hyperplasia (FMH) lesions. The procedure was technically unsuccessful in 28% of 37 arteries attempted, primarily in the > 80% stenosis group. The mean clinical follow-up period was 20 months. In those patients with technically successful PTAs, none was cured, with no change in the status of hypertension or medication required. Clinical improvement was seen in 37% (7 of 19) patients with atherosclerotic disease and who had PTA of significant unilateral lesions or of the haemodynamically significant side in cases of bilateral disease. Two patients with FMH lesions had improvement. Five patients with PTA of only one side in cases of significant bilateral disease gained no benefit. Nine patients with pre-existent renal insufficiency and technically successful PTAs had no improvement of renal function. No mortality or any significant morbidity resulted from the procedure. These results are more compatible with more recent than the earlier literature.

Adult

Multiple use of cycler set in cycler peritoneal dialysis.

STUDY OBJECTIVE: To evaluate the multiple use of cycler set with universal connector set. DESIGN: The study was designed to reuse the cycler set for two to three treatments, each of 16-24 hours using Pac-X or Pac-Xtra cycler and to continue to use the same set if the patient was disconnected for any reason. SETTING: Tertiary-referral university hospital. PATIENTS AND METHODS: 204 ESRD patients on peritoneal dialysis (PD) admitted to University Hospital from January 1989 to July 1991 were studied. The patients were disconnected and reconnected in between or during PD treatments. Five-liter dialysate bags were used. All the fluid was either set initially or added as clinically indicated. RESULTS: 2491 cycler PD treatments were performed with Pac-X and Pac-Xtra cyclers using 940 cycler tubing sets. 1624 disconnections were made in between and 336 were made for radiological investigations, special procedure, physical therapy and surgery during PD treatments. No episode of peritonitis or mechanical failure occurred. The multiple use resulted in 62% reduction in cycler sets thereby reducing the disposable supplies and a substantial saving in the nursing time. CONCLUSIONS: The multiple use of cycler set with universal connector and manifold set was safe and economical in the patients undergoing cycler PD in the hospital setting.

Humans

Positive role of Clostridium difficile infection in diarrhea in infants and children.

A retrospective review of children with Clostridium difficile infection and diarrhea identified 43 patients. Fifteen (35%) had immunoglobulins below the normal range for age, and typified those with transient hypogammaglobulinemia of infancy, because all increased their levels over the following 12 months. The age of those with hypogammaglobulinemia was significantly younger (p less than 0.01), averaging 18.8 months, than those with normal immunoglobulins who had a mean age of 4.6 yr. The number with recurrent C. difficile infection was significantly greater (p less than 0.001) in the hypogammaglobulinemic group than in those with normal immunoglobulins (46% vs 18%). Eleven children were identified who had C. difficile toxin in the stool after antibiotic therapy, but who had no diarrhea at the time of study. All had normal immunoglobulins. Control patients (20 without and 40 with diarrhea) had no evidence of C. difficile infection, and all but three had normal immunoglobulins. Three (7%) of those with diarrhea had IgA deficiency, and all had a diagnosis of milk protein allergy. These data suggest that immunoglobulin values be obtained in infants and children who have problematic C. difficile diarrhea in order to identify disorders of immunoglobulin synthesis which may be the underlying cause of repeated upper respiratory disease requiring antibiotic usage.

Adolescent

Effective planning for office and outpatient chemotherapy administration.

The trend in cancer care today is to successfully maintain the patient outside the traditional inpatient setting. This review has focused on some of the advantages and disadvantages in the administration of chemotherapy at home, the physician's office, and the ambulatory care facility. Effective planning for chemotherapy administration and the selection process for each of these settings depends on the needs of the patient and family. We can conclude that, although it is possible to use a combination of setting to maximize patient care, the ambulatory care concept provides broader choices for patients, families, and clinicians.

Ambulatory Care

Viruses and bone marrow failure.

Some generalizations can be drawn from a review of virus-associated bone marrow failure. The story of B19 parvovirus illustrates that viral infection may be an occult cause of marrow failure. Although the epidemiology of transient aplastic crisis suggested a viral aetiology, the implication of a single virus was surprising; the sporadic appearance of chronic bone marrow failure in immunosuppressed persons has had none of the features of a viral illness. The incrimination of parvovirus in these cases required development of specific immunological and molecular assays. Human and animal retrovirus studies have shown that small changes in the virus genome can have dramatic effects on the biology of the infectious agent and its pathogenicity in infected hosts. In Epstein-Barr virus infection, the host's immune response may play a more important role in mediating disease than virus cytotoxicity. Finally, the association of aplastic anaemia with hepatitis may be underestimated because of the inability to diagnose virus infection without obvious liver disease. The true spectrum of bone marrow disease due to virus infection is not known.

Acquired Immunodeficiency Syndrome

Decreased interleukin 1 production in aplastic anaemia.

Interleukin 1 (IL-1) is an important regulator of immune system function. IL 1 also affects haematopoiesis in vitro: it causes release of colony stimulating factors from fibroblasts and endothelial cells and can directly act on primitive haematopoietic stem cells. We investigated IL 1 production in vitro by stimulated peripheral blood mononuclear cells of patients with aplastic anaemia (N = 17), patients with other haematologic diseases (N = 27), and normal individuals (N = 22) using a bioassay for IL 1 activity. Ten aplastic patients showed markedly decreased IL 1 production. IL 1 production by fibronectin-affinity purified monocytes was decreased in six of seven of these patients; in three other cases, in which IL 1 mononuclear cell production was undetectable, sufficient monocytes could not be isolated. IL 1 alpha and IL 1 beta precursor molecules were also absent or much decreased when mononuclear cell lysates from these patients were analysed by immunoblot using specific polyclonal sera. Aplastic patients with low IL 1 production were distinguished by the severity of their disease and the degree of neutropenia. Patients with myelodysplasia with comparable degrees of pancytopenia had normal IL 1 production. This is the first example of deficient haematopoietic growth factor production in a bone marrow failure syndrome. Decreased IL 1 production may contribute to the pathogenesis of some cases of aplastic anaemia and to susceptibility to infection.

Adolescent

Translational regulation of B19 parvovirus capsid protein production by multiple upstream AUG triplets.

The B19 parvovirus produces two capsid proteins in strikingly different quantities (VP1 less than 4%, VP2 greater than 96%) from overlapping RNAs that are derived from the same transcription unit. Immediately upstream from the VP1 translation initiation site is an unusual sequence containing multiple ATG triplets. During RNA processing this sequence is spliced out of VP2 RNA. To test the regulatory role on translation of this sequence containing upstream AUGs, synthetic RNAs were produced in vitro by T7 RNA polymerase from various plasmid constructions. Translation of VP1 RNA was very inefficient compared to VP2 RNA in a cell-free system, indicating that capsid protein production was regulated at the level of translation. Removal of upstream AUG sequences from VP1 RNA greatly increased the efficiency of translation. Conversely, the addition of the same AUG-rich sequence upstream of the initiation site of VP2 decreased its translation. These data indicate that an upstream AUG-rich region acts as a negative regulatory element in the translational control of B19 capsid protein production.

Capsid

A comparison between the in vivo and in vitro activity of five potent and competitive NMDA antagonists.

1. Phosphonate analogues of glutamate have been tested and compared as N-methyl-D-aspartate (NMDA) antagonists in electrophysiological and binding experiments. The compounds tested were three established NMDA antagonists: D-2-amino-5-phosphonopentanoate (D-AP5), DL-2-amino-7-phosphonoheptanoate (DL-AP7), 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonate (CPP), and two novel putative NMDA antagonists: 3-(2-carboxypiperidin-4-yl)propyl-1-phosphonate (CPPP) and 3-(2-carboxy-piperidin-4-yl)methyl-1-phosphonate (CPMP). 2. When administered electrophoretically to rat spinal neurones in vivo, these compounds were found to be selective NMDA antagonists with little effect on excitations evoked by quisqualate and kainate. CPMP and CPPP were approximately equipotent with CPP and about 5 times more potent than D-AP5. 3. Following systemic administration, 2-5 mg kg-1 i.v. of CPP, CPMP and CPPP reduced NMDA-evoked excitations by 70-100% whereas 50-100 mg kg-1 of D-AP5 and DL-AP7 produced a similar effect. The onset of the effects required 20-30 min and lasted more than six hours. 4. On bath application to cortical wedges, the IC50 values (microM) for antagonism of 40 microM NMDA were: CPP, 0.64 +/- 0.06 (mean +/- s.e.mean; n greater than 4); CPMP, 1.65 +/- 0.13; CPPP 0.89 +/- 0.09; D-AP5, 3.7 +/- 0.32; DL-AP7, 11.1 +/- 2.1; and DL-AP4 and DL-AP6 were inactive at 100 microM. 5. In binding studies with [3H]-CPP, the Ki values (nM) were: CPP, 446 + 150 (mean + s.e.mean; n > 3); CPMP, 183 + 74 and CPPP, 179 +/- 13 whereas against NMDA (lO microM)-stimulated [3H]- TCP (thienylcyclohexylpiperidine) binding the ICjo values (microM) for CPMP and CPPP respectively were 5.6 + 2.7 and 4.5 + 2.2. 6. Systemic administration of CPPP and CPMP, at doses sufficient to antagonize NMDA, also reduced cardiovascular responses to 5-hydroxytryptamine (Bezold-Jarisch reflex). This illustrates a role for NMDA receptors in central cardiovascular control. 7. The results indicate the systemic doses of piperidine and piperazine analogues of D-AP5 which may be used for assessing the role ofNMDA receptors in central synaptic function.

2-Amino-5-phosphonovalerate

Functional mapping of the genome of the B19 (human) parvovirus by in vitro translation after negative hybrid selection.

We have analyzed the coding capacity of B19 parvovirus transcripts by in vitro translation using the negative hybrid selection technique. Five different antisense oligonucleotides (18-mers) corresponding to different portions of the B19 genome were hybridized to RNA samples extracted from human erythroid bone marrow cells infected with B19 parvovirus in vitro, and RNase H was added to cleave specific B19 RNA molecules at selected sites. B19-specific translation products of these RNA samples were determined by immunoprecipitation. We localized the B19 nonstructural protein to the left-side transcript and the two capsid proteins to overlapping transcripts from the right side of the genome.

Erythroblasts

The gene encoding the nonstructural protein of B19 (human) parvovirus may be lethal in transfected cells.

The B19 parvovirus is a cause of bone marrow failure in humans. B19 is toxic to erythroid progenitor cells in vitro. Viral products possibly responsible for toxicity were explored by transfection of cloned B19 genome into HeLa cells. The nonstructural (NS) protein was detected in cells 30 h after transfection. Plasmids containing the B19 genome were transfected with selectable marker genes in stable transformation assays. Plasmids that contained the left side of the B19 genome, which encodes the NS protein of the virus, inhibited antibiotic-resistant colony formation. Transformation occurred when NS protein expression was blocked by mutation. Suppression of transformation by NS protein was not tissue specific, suggesting a role for NS protein in toxicity for nonpermissive cells without parvovirus replication or virion accumulation.

Capsid

Hematologic and hematopoietic consequences of B19 parvovirus infection.

In hybridization experiments, B19 shows some reactivity with autonomous rodent parvoviruses but none with adenoassociated virus sequences; its termini are more closely related to adenoassociated virus than to autonomous parvoviruses. B19 shares with all parvoviruses regions of conserved homology in the left side of the genome. The absence of an internal promoter and its unusual pattern of transcription sets B19 apart from both dependent and autonomous parvoviruses. Although clearly an autonomous parvovirus, in its extraordinary fastidious behavior B19 resembles a dependent parvovirus, capable of replication only in the special nuclear milieu of terminally differentiating erythroid cells. Adaptations at the molecular level may have been necessary for B19 parvovirus to acquire its high degree of specificity and low level of pathogenicity and thus succeed in human populations.

Adult