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Biomedical subjects

L Jackson

Publications and source records attributed to L Jackson.

At least 73 records · Page 4Linked to original sources

Diagnosis of a complex chromosomal rearrangement using fluorescent in situ hybridisation.

We report the use of fluorescent in situ hybridisation (FISH) to clarify a complex chromosomal rearrangement (CCR) carried by a woman presenting with recurrent miscarriages. CCRs are rare cytogenetic rearrangements involving three or more chromosomes, which can be difficult to interpret using routine cytogenetic studies with GTG banding. FISH was used to establish a correct interpretation of the maternal karyotype before amniocentesis in a present pregnancy.

Abortion, Habitual↗

A randomized, placebo-controlled trial of combined insulin-like growth factor I and low dose growth hormone therapy for wasting associated with human immunodeficiency virus infection.

Loss of body mass, or wasting, is a major cause of morbidity and a contributor to mortality in human immunodeficiency virus-1 (HIV-1) infection. Dietary supplements and appetite adjuvants have had limited effectiveness in treating this condition. GH and insulin-like growth factor I (IGF-I) have been shown to be anabolic in many catabolic conditions, and limited data suggest similar efficacy in HIV wasting. In addition, it appears that GH and IGF-I may have complementary anabolic effects with opposing glucoregulatory effects. We report results from a 12-week randomized, placebo-controlled trial of combination recombinant human GH (rhGH; Nutropin; 0.34 mg, sc, twice daily) and rhIGF-I (5.0 mg, sc, twice daily) in individuals with HIV wasting and without active opportunistic infection, cancer, or gastrointestinal disease. A total of 142 subjects (140 males and 2 females) were randomized using a 2:1, double blind treatment scheme and assigned to receive either active treatment or placebo injections. Eighty subjects completed the 12-week protocol. Nutritional intake and demographic and clinical characteristics did not differ between the groups at any study time point. At 3 weeks, the treatment group had a significantly larger weight increase (P = 0.0003), but this difference was not observed at any later time point. Similarly, fat-free mass, calculated from skinfold measurements, increased transiently in the treatment group at 6 weeks (P = 0.002). No significant differences in isokinetic muscle strength or endurance testing or in quality of life were observed between the groups. Resting heart rate was significantly higher in the treatment group at each time point post-baseline. GH and IGF-binding protein-3 levels did not change; however, IGF-I levels were higher in the treatment group at 6 and 12 weeks. There were no significant between-group differences in any of the measured biochemical or immunological parameters. rhGH plus rhIGF-I treatment was associated with an increased incidence of peripheral edema and other side-effects, possibly related to fluid retention. We conclude that the combination of rhIGF-I and low dose rhGH used in this study had no significant anabolic effect in HIV wasting.

Acquired Immunodeficiency Syndrome↗

Family therapy skills for general practitioners.

General practitioners are often the first health professionals that families turn to for help at times of stress. Figures from around the world suggest that up to 80% of general practice consultations have psychological or stress based issues as a significant aspect of the presenting problems. In this paper the place of patients in a wider context is emphasised and skills with which the GP can respond to the patient and his or her family are discussed. The value of listening to patients for both the content and the feelings without necessarily trying to solve the presenting problems is emphasised.

Adult↗

Structurally defined synthetic cancer vaccines: analysis of structure, glycosylation and recognition of cancer associated mucin, MUC-1 derived peptides.

Translation of an immune response into therapy is probably the toughest task in designing vaccines for cancer due to the heterogeneity of the cell surface antigens which display tremendous variations in glycoforms. Consequently, a small segment (antigen) of cancer-associated mucin, in spite of generating antigen-specific immune responses, may be limited in therapeutic value. It is important that the synthetic segment resembles the native cancer-associated mucin in both structure and conformation. Synthetic cancer associated mucin derived 16 amino acid peptide GVTSAPDTRPAPGSTA and its partially glycosylated forms have demonstrated specific binding to two monoclonal antibodies, B27.29 and BCP8, raised against the native cancer associated mucin, MUC-1 and a MUC-1 derived synthetic peptide, respectively. In spite of the structural similarities at the core peptide level of both glycosylated and unglycosylated peptides, it appears that partial glycosylation does not inhibit and even slightly enhances binding to the MAb B27.29 indicating that the glycosylated synthetic peptide more closely resembles the native mucin epitope recognized by MAb B27.29. From molecular dynamic simulations using NMR derived distance constraints, both glycosylated and unglycosylated peptides have shown a type 1 beta turn involving the same amino acids in both glycosylated and unglycosylated peptides. The alpha GalNAc attached to the threonine (T3) and serine (S4) in the 16 amino acid sequence has not imposed any conformational changes to the peptide backbone nor has offered severe steric resistance to the binding of either antibody to the glycopeptides as indicated by hapten inhibition studies. Nevertheless, all peptides have displayed glycosylation dependent specificities in binding to these antibodies, i.e. the glycosylated peptides demonstrated relative higher affinities to the native mucin antibody B27.29 while the unglycosylated peptide is more specific to the MAb BCP8. Immune responses generated by these synthetic glycopeptides are highly specific in recognizing the native cancer associated mucin.

Acetylgalactosamine↗

Effect of maternal rotavirus immunization on milk and serum antibody titers.

This prospective study evaluated human milk and serum antirotavirus antibody concentrations following maternal rotavirus immunization. Postpartum women (33) were randomized into 3 groups and received a single oral dose of rhesus rotavirus monovalent reassortant vaccine (10(4) pfu), tetravalent vaccine (10(4) pfu), or placebo. Milk (secretory [s] IgA) and serum (IgA and IgG) specimens were tested for antirotavirus isotype-specific antibody. Sera also were tested for G1- to G4-specific antibody. Prevaccine milk and serum isotype-specific antibody concentrations were not significantly different in the 3 groups. Postvaccine sIgA log titers were significantly greater in the 2 vaccine groups than the placebo group (P = .002). Mean log10 titers at 1 week were 2.1 (95% confidence interval [CI], 2.0-2.3) in the 2 vaccine groups and 1.7 (95% CI, 1.5-1.9) in the placebo group. Milk titers did not differ between vaccine groups. There was no difference in reactogenicity between groups. The significantly higher milk concentrations of antibody to rotavirus in postpartum women who received rotavirus immunization persisted for 4 months.

Adolescent↗

Strike-through contamination in saturated sterile dressings: a clinical analysis.

This multisite study examined the risk of strike-through contamination of 4" x 4" gauze sponges using a shortcut method of saturating sterile sponges directly on their wrappers. Sterile gauze sponges were saturated directly on their wrappers on hospital over-bed tables of postoperative general surgical patients. Cultures were taken at 0.5, 1, 3, and 5 minutes after saturation to ascertain whether strike-through contamination occurred. Saturated sponges showed significant microorganism growth when compared to expected zero microorganisms at all sampling times following saturation. Although microorganisms identified in strike-through contamination were not microbiologically or pathogenically threatening, the basic principle of asepsis was violated. There was no significant difference in strike-through contamination between sponges saturated on coated wrappers and sponges saturated on uncoated wrappers. Clinicians should be aware that coated wrappers do not provide a moisture-proof barrier against strike-through contamination. The findings suggest the shortcut method should not be used for saturating sponges.

Asepsis↗

Protecting the gut and the liver in the critically ill: effects of dopexamine.

OBJECTIVE: To measure the clinical effects of dopexamine on systemic and splanchnic perfusion in critically ill patients. DESIGN: Prospective study. SETTING: General intensive care unit. PATIENTS: Ten patients with sepsis syndrome, acute respiratory failure, and at least one other organ system in failure. The median age of the patients was 62.5 yrs (range 29 to 78), and the median admission Acute Physiology and Chronic Health Evaluation (APACHE) II score was 24 points (range 14 to 38). INTERVENTIONS: Timed infusion of dopexamine to a maximum dose of 6 micrograms/kg/min. MEASUREMENTS AND MAIN RESULTS: Systemic hemodynamics and oxygen transport variables were obtained from measurements after arterial and pulmonary artery catheterization. Gastric intramucosal pH and hepatic blood flow/function measurements were made by tonometry and indocyanine green clearance, respectively. All measurements were made before dopexamine infusion, after 1 hr of dopexamine infusion, and again 1 hr after the infusion ended. Cardiac index increased with dopexamine from a baseline median of 4.0 L/min/m2 (range 1.2 to 5.5) to 4.8 L/min/m2 (range 1.5 to 8.03) (p < .01), and returned to its previous level 1 hr after the infusion ended (median 4.0 L/min/m2 [range 1.4 to 5.8], p < .01). During dopexamine infusion, gastric intramucosal pH improved significantly from a median baseline level of 7.21 (range 7.04 to 7.50) to 7.28 (range 7.13 to 7.46, p < .05). This improvement in gastric intramucosal pH was maintained (median 7.36 [range 7.13 to 7.46]) after the infusion ended. Indocyanine green half-life decreased but not significantly with dopexamine (medians before and during the infusion were 6.6 and 6.3 mins, respectively). Indocyanine green half-life increased significantly 1 hr after the infusion ended (median 7.4 mins [range 4.4 to 14.8], p < .05), and changes in cardiac index correlated with changes in indocyanine green half-life (Rs2 = 0.60, p < .001). Changes in gastric intramucosal pH were unrelated to all other measurements. CONCLUSIONS: Dopexamine improves gastric intramucosal pH, and thus, splanchnic oxygenation. This improvement in gastric intramucosal pH appears to be independent of dopexamine's systemic effects.

Acute Disease↗

Terbutaline via pressurised metered dose inhaled (P-MDI) and Turbuhaler in highly reactive asthmatic patients.

There is some concern over the environmental consequences of chlorofluorocarbons (CFCs) used in pressurized metered-dose inhalers (p-MDIs). Turbuhaler was designed to deliver a drug as a dry powder without administering additives directly to the airways. The aim of this study was to evaluate the comparative irritant and bronchodilating effects of the same dose of terbutaline delivered by a p-MDI and via Turbuhaler. Ten symptomatic, asthmatic patients, with highly reactive airways (provocative concentration of methacholine producing a 20% fall in forced expiratory volume in one second (PC20) < 0.2 mg.ml-1), inhaled, on separate days, 0.25 mg terbutaline via p-MDI or Turbuhaler. Changes in airway calibre were followed as specific airways conductance (sGaw). On a third day, patients inhaled from a placebo p-MDI containing all constituents except terbutaline. The study was conducted in a single-blind fashion and in random order. There were no significant differences in baseline sGaw on any of the study days. Inhalation of terbutaline from the p-MDI produced a transient percentage fall in sGaw at 1 min, reaching a mean maximum +/- SD of 17 +/- 8% at 10 s and then returning to baseline value after 20 s, followed by a progressive increase in sGaw to a maximum of 39 +/- 45% above baseline at 45 min. In contrast, inhalation of terbutaline via Turbuhaler caused no significant bronchoconstriction (fall in sGaw, 3 +/- 16%) at 10 s and achieved a greater increase in sGaw, reaching 63 +/- 51% at 45 min, although just failing to reach statistical significance compared to terbutaline p-MDI inhalation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

de Lange syndrome: a clinical review of 310 individuals.

Three hundred ten individuals with a clinical diagnosis of de Lange syndrome were seen and examined in conjunction with the parent support group. One hundred thirty-four males and 176 females whose ages ranged from birth to 37 years made up the study group. Examination findings were recorded for those features described by de Lange in her original report of the syndrome to determine the frequency and significance of each. In addition, questionnaires were completed by 128 of these families and medical, growth and developmental records were collected. The clinical diagnosis seems best supported by the facial features of the syndrome including the long eyelashes and confluent eyebrows (synophrys), although additional characteristics are needed. Only 27% had the upper limb deficiencies commonly associated with the syndrome. Growth was retarded in nearly all individuals, often of prenatal onset. Medical problems occurred frequently and most often involved the eye and ear, as well as the cardiac and gastrointestinal systems. Of 14 deaths, almost half were secondary to cardiac or gastrointestinal complications. The recurrence risk in 377 sibs of the patients was calculated to be less than 1%. Although development lagged significantly in speech, most individuals developed good self-help skills. The study demonstrated a higher proportion of patients affected mildly with the syndrome than is commonly appreciated. This underscores the importance of early recognition and appropriate medical and developmental support.

Adolescent↗

Quantitative analysis of the metabolism of 9,10-dihydrobenzo[a]pyrene by induced rat liver microsomes.

The ability of reduced polycyclic aromatic hydrocarbons to be converted to their fully aromatic forms by the microsomal cytochrome P-450 mixed-function oxidases may assist in the explanation of the mutagenic and tumorigenic activities of these agents. The metabolic conversion of 9,10-dihydrobenzo[a]pyrene (9,10-DHB[a]P) to benzo[a]pyrene (B[a]P) and 9- and/or 10-hydroxy-9,10-DHB[a]P (OH-9,10-DHB[a]P) was quantitatively measured. In beta-naphthoflavone-induced rat liver microsomes, 9,10-DHB[a]P was metabolized to B[a]P with a specific activity of 1.51 nmol B[a]P formed/min/mg microsomal protein. The formation of B[a]P was directly related to incubation time and microsomal protein concentration. Similarly, 9,10-DHB[a]P was converted to OH-9,10-DHB[a]P with a specific activity of 4.48 nmol OH-9,10-DHB[a]P formed/min/mg microsomal protein. Its formation was directly related to incubation time and microsomal protein concentration. The possibility of OH-9,10-DHB[a]P as a metabolic intermediate to B[a]P is discussed.

Animals↗

Continuous chemotherapy in responsive metastatic breast cancer: a role for tumour markers?

A biochemical response index comprising ESR, CEA and CA 15.3 was evaluated in 67 patients with systemic breast cancer treated by chemotherapy; 55 were assessable by UICC criteria and the response index (96% of all UICC assessable patients). Marker changes at 2 and 4 months showed a highly significant correlation with the UICC assessed response at 3 and 6 months (P < 0.001); sensitivity 100%, specificity 87%; positive predictive value 85%; negative predictive value 100%. This index was then used to select out truly responsive patients and to prospectively direct their chemotherapy. Twenty-six responding (biochemical/clinical) patients were randomised to discontinue cytotoxics after 6 months and move to maintenance hormones (n = 13) or continue chemotherapy whilst the biochemical markers kept falling or remained within the normal range. Biochemical progression prompted a change of chemotherapy. Continuous chemotherapy in biochemically defined responders was associated with a significant lengthening of remission duration and an improved quality of life and survival. We are now using the index to routinely direct chemotherapy and select out true responders for maintenance chemotherapy.

Adult↗