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Biomedical subjects

A Johnson

Publications and source records attributed to A Johnson.

At least 415 records · Page 23Linked to original sources

Cellular cholesterol metabolism in mitogen-stimulated lymphocytes--requirement for de novo synthesis.

The relationship between cholesterol synthesis and uptake in proliferating lymphocytes has been examined. [14C]Acetate incorporation into lymphocytes cultured under lipoprotein-deficient conditions increased initially in response to mitogen, decreased after 24 h, and increased rapidly between 72 and 96 h. Addition of LDL (10 micrograms/ml) to the culture during the 'trough' period caused [14C]acetate incorporation to return rapidly to baseline, while at peak periods LDL suppression of cholesterol synthesis was minimal. Lymphocytes cultured in the presence of the HMG-CoA reductase inhibitor, mevinolin, exhibited a time-dependent increase in their capacity to incorporate [14C]acetate into cholesterol, evident when mevinolin was removed by washing prior to assay. PHA enhanced 125I-labelled LDL receptor-mediated binding by lymphocytes cultured in lipoprotein-deficient medium over a 4 day period and mevinolin augmented the effect. [3H]Thymidine incorporation into mitogen-stimulated lipoprotein-deficient cultures was inhibited up to 75% by mevinolin (1 mumol/l). LDL (2.5-10 micrograms/ml) substantially reversed this inhibition in 72 h cultures, but only partially overcame inhibition in cells cultured for 96 h. Results suggest that endogenous cholesterol synthesis may be obligatory for lymphocyte proliferation after the initial round of cell division.

Acetates↗

Selective reduction of multifetal pregnancies.

Selective reduction was carried out in 46 multifetal pregnancies by means of potassium chloride injection into the pericardial region of the fetus. There were three indications for the procedure: to improve perinatal outcome and to increase the likelihood that a term infant would be born in a multifetal pregnancy (34 women); to allow the birth of a healthy infant without the birth of a congenitally abnormal coexisting fetus (8 women); and to preserve a singleton pregnancy when the woman would otherwise have the whole pregnancy terminated (4 women). Of the 80 fetuses left after reduction 75 (94%) have survived. In 3 cases ultrasound scanning showed cardiac activity in the injected fetus 20-30 min after the initial injection despite 2 min of asystole immediately after the injection; repeated injection, carried out the same day, led to fetal death in all 3 cases. Selective reduction of multifetal pregnancies for the three indications described is an ethically justifiable option for the management of multifetal pregnancy, to which there are no public policy obstacles.

Congenital Abnormalities↗

Reduced serum haptoglobin values in hemophiliacs receiving monoclonally purified factor VIII concentrates.

Hemophiliacs often have mild anemia, and hemolysis has been suggested as the likely mechanism on the basis of the reduced serum haptoglobin values frequently observed in these patients. It has been suggested that hypohaptoglobinemia results from isohemagglutinins or other contaminating proteins in the infused factor concentrates. The advent and increased utilization of Factor VIII concentrates that are highly purified by use of monoclonal antibodies have provided the opportunity to study whether proteins other than Factor VIII contained in the concentrate induce hemolysis. Of 49 consecutively studied Factor VIII-deficient hemophiliacs, 19 (39%) had a reduced serum haptoglobin level (less than 27 mg/dl). In particular, 16 of 35 (46%) of patients receiving only monoclonally purified Factor VIII products (Monoclate or Hemofil-M) had a reduced serum haptoglobin value. Haptoglobin measurements were variable on repeat measurement in 8 patients. Haptoglobin levels did not correlate with type or severity of hemophilia, hemoglobin value, or alterations in liver function. Low serum haptoglobin values were also observed in children with leukemia, without apparent hemolysis, who had extensive cutaneous hemorrhage associated with thrombocytopenia. We propose that reduced serum haptoglobin values in hemophiliacs do not result from immune-mediated hemolysis due to contaminating proteins in the concentrate. Moreover, hypohaptoglobinemia may not be due to hemolysis at all but may instead result from dissolution of hematomas and other foci of internal hemorrhage.

Adolescent↗

Cellular cholesterol regulation--a defect in the type 2 (non-insulin-dependent) diabetic patient in poor metabolic control.

This study investigates the relationship between Type 2 (non-insulin-dependent) diabetes mellitus and hypercholesterolaemia with regard to delivery of cholesterol to cells and regulation of endogenous cholesterol synthesis. The ability of LDL, from hypercholesterolaemic and Type 2 diabetic patients, to suppress cellular cholesterologenesis and to enhance mitogen-stimulated lymphocyte proliferation was compared. Cholesterol synthesis was estimated by measuring [14C]-acetate incorporation into cholesterol and lymphocyte proliferation was assessed by [3H]-thymidine incorporation into mitogen-stimulated normal lymphocytes. The results indicate that LDL from both Type 2 diabetic patients in poor metabolic control and hypercholesterolaemic patients was significantly less effective (p less than 0.001) than LDL from non-diabetic normocholesterolaemic subjects in suppressing cholesterol synthesis in lymphocytes. LDL from all hypercholesterolaemic patients enhanced lymphocyte proliferation to a greater extent than LDL from normocholesterolaemic subjects and this effect was significantly increased using LDL from Type 2 diabetic, hypercholesterolaemic patients. Both suppression of [14C]-acetate incorporation and enhancement of [3H]-thymidine uptake could be related to an increased esterified/free cholesterol ratio in the LDL particle. The fact that cholesterol synthesis and cell proliferation were markedly altered by the above changes in LDL composition suggests a mechanism for cellular cholesterol accumulation in the Type 2 diabetic patient, even in the absence of elevated serum cholesterol levels.

Apolipoproteins B↗

What do psychiatric emergency patients really want and how do they feel about what they get?

Psychiatric emergency patients range along a continuum from persons who present to the service with specific requests for help, to individuals who are brought to the service in handcuffs against their will for reasons they do not understand. In addition, studies suggest that psychiatric emergency patients' wishes and expectations often fall outside the traditional framework of psychiatric assessment, are not straightforward or concrete or are not accurately perceived by the clinicians who see them. How these factors impact on patient satisfaction with the treatment they have received is not well-understood, because the manner in which specific patient variables and treatments might relate to patient satisfaction among the psychiatric emergency service population has not been systematically studied. In contrast, psychiatric inpatients and outpatients usually express positive attitudes about their mental health care, although this finding may be skewed by a lack of real anonymity. Chronic patients tend to express less satisfaction with their treatment programs than do others, and patient satisfaction in some studies has been related to patient demographics, diagnoses, treatment histories and patients' global rating of treatment outcome.

Consumer Behavior↗

An investigation of nosocomial infection with Corynebacterium jeikeium in surgical patients using a ribosomal RNA gene probe.

Twelve strains of multi-resistant Corynebacterium jeikeium isolated during a one year period in a surgical unit in Innsbruck were analyzed with regard to their plasmid content, antibiotic susceptibility, and the use of ribosomal ribonucleic acid (rRNA) to probe restriction fragment length polymorphism (RFLP). Plasmids were detected in five of the strains. Southern blotting of genomic DNA digested with HindIII or PvuII and hybridized with a biotin-labelled cDNA probe derived from total rRNA revealed characteristic banding patterns. Seven of the 12 strains showed similar RFLP profiles, consistent with them being related epidemiologically. The minor changes in RFLP profiles observed in these seven strains suggest that Corynebacterium jeikeium may be subject to genetic drift over a relatively short time span. Strains from other sources, included for comparison, differed markedly from those from Innsbruck. Patterns of antibiotic susceptibility which appeared not to be plasmid encoded, correlated broadly with RFLP profiles. This study suggests that strains of Corynebacterium jeikeium may be transferred between hospital patients.

Corynebacterium↗

Antenatal microbiologic and maternal risk factors associated with prematurity.

In a prospective study of 202 women (gestational age 24 +/- 4 weeks), we evaluated possible influences of lower genital tract infection or bacterial conditions on obstetric outcomes, including preterm labor, preterm premature rupture of membranes, and preterm birth. The presence of bacterial vaginosis (18.7%) was associated with an increased risk of preterm labor (relative risk, 2.6; 95% confidence interval, 1.08 to 6.46). For women with bacterial vaginosis who also had Mobiluncus species morphotypes identified on Gram stain, the relative risk of preterm labor was 3.8 (95% confidence interval, 1.32 to 11.5). Presence of vaginal Mycoplasma hominis (10.8% of patients) was associated with both preterm labor (relative risk, 1.8; 95% confidence interval, 0.77 to 4.4) and preterm birth (relative risk, 5.1; 95% confidence interval, 1.45 to 17.9). Recovery of Staphylococcus aureus (3.0%) was associated with preterm labor (relative risk, 3.1; 95% confidence interval 1.12 to 8.7). Identification of two or more bacterial-linked abnormalities was also associated with preterm labor (relative risk, 3.3; 95% confidence interval, 1.44 to 7.58). An increased level of vaginal wash protease (greater than or equal to 10 trypsin units) (16%) was associated with preterm labor and was noted in 50% of women with preterm premature rupture of membranes. A history of prior preterm birth was the single best historical predictor of both preterm labor (relative risk, 3.6; 95% confidence interval, 1.92 to 6.83) and preterm birth (relative risk, 6.7; 95% confidence interval, 2.2 to 20.4). History of three or more abortions, antenatal urinary tract infection, and occurrence of medical complications during pregnancy also correlated with increased risk of preterm labor. These findings affirm and refine associations of various maternal reproductive tract infections with preterm labor, premature rupture of membranes, and birth, allowing for controlled treatment trials aimed at prevention of preterm birth.

Adult↗

Acute haemodialysis during the Armenian earthquake disaster.

On the 7 December 1988 an earthquake struck a densely populated region in northern Armenia. Up to 50,000 people were killed and many thousands were seriously injured. At least 385 of these casualties developed acute renal failure secondary to crush syndrome and required dialysis. The Armenian renal unit at Yerevan, in common with units elsewhere, was already overstretched to cope with the dialysis requirements of their patients with chronic renal failure before the earthquake. Most of the patients requiring dialysis were transferred to other hospitals in the USSR but 120 patients remained in Yerevan, the majority at the regional renal unit, overwhelming the resources. We assisted by taking a team of dialysis personnel, equipped with portable haemodialysis machines, to Yerevan. We performed 57 haemodialysis sessions and treated 15 patients, 13 of whom ultimately survived. Valuable lessons were learnt about the medical management of disasters abroad.

Acute Kidney Injury↗

The effect of antibody isotype on the activation of C3 and C4 by immune complexes formed in the presence of serum: correlation with the prevention of immune precipitation.

Radioimmunoassays for C3a and C4a have been used to measure the activation of complement during the formation of immune complexes in human serum by the interaction of DNP-BSA and each of 11 mouse anti-DNP monoclonal antibodies of varied isotype and affinity. Those containing IgG2 or IgM were potent activators of C4, whilst IgG1 containing complexes were less efficient. C3 activation in normal serum was similar for complexes containing IgG1, IgG2a, IgG2b or IgM. IgA complexes did not activate C3 or C4. All complexes except those containing IgA precipitated more slowly in serum than in buffer. IgG2 antibodies were potent activators despite being very slow to precipitate in buffer. In serum containing EGTA activation of C4 was abolished and precipitation of complexes occurred at the same rate as in buffer. Nevertheless, C3 activation still occurred by the alternative pathway for all IgG and IgM complexes. Antibodies of the same isotype did not necessarily activate complement to the same extent. The ranking of the ability to activate complement was the same as that observed when performed complexes containing the same antibodies were added to serum. The levels of C4a generated were similar under both conditions but for most antibodies more C3a was generated by preformed complexes.

Antibodies, Monoclonal↗

Mitotic activity and survival in advanced non-Hodgkin's lymphoma of unfavourable histology.

The number of mitoses per high power field (mitotic index, MI) was assessed in 2 microns sections of lymph node biopsies from 58 adults with non-Hodgkin's lymphoma. All had diffuse nodal lymphomas of unfavourable histology and stage II-IV disease. The patients were treated with chemotherapy and followed for a minimum of 3 years or until death. None out of 29 patients with a MI greater than or equal to 3.0 survived for 3 years after diagnosis whereas 13 out of 29 other patients with MI less than 3.0 became long-term survivors (P = 0.00002). Differences in age, sex or clinical stage between short- and long-term survivors were negligible. The initial chemotherapy regimens were not more intense for the long-term survivors. Twenty-nine patients were given an equivalent initial treatment with CHOP or CHOP plus methotrexate. The association between MIs and survival was evident also in this subgroup. The results indicate that survival is extremely poor for patients with advanced diffuse nodal lymphomas of unfavourable histology and a high mitotic count. It seems especially important to evaluate alternative chemotherapy regimens, suggested to be more effective than current programmes, in this subset of patients.

Adult↗

Safety and efficacy of long-term tocolysis with indomethacin.

Indomethacin was utilized in 24 pregnancies (31 exposed fetuses) in preterm labor who labored despite intravenous tocolysis. The mean gestational age at the start of indomethacin therapy was 25.1 weeks (+/- 4.4), mean duration of indomethacin therapy was 43.9 days (+/- 31.4), mean gestational age at delivery 33.1 weeks (+/- 3.7). Neonatal follow-up revealed the same incidence of complications in these indomethacin-exposed infants, when they were compared with all other infants born in the same time period and exposed to intravenous tocolytics only when matched for gestational age at delivery.

Apgar Score↗

Comparison of anaesthesia ventilators using a lung model.

The ventilatory performance of six anaesthesia ventilators (Alphavent Drägerwerk; MCM 801 Ventilator Dameca; Ohmeda 7000 Ventilator and Ohmeda 7800 Ventilator Ohmeda; Servo Ventilator 900 D and Ventilator 710 Siemens-Elema) was tested in a lung model and compared with the ventilatory performance of the old Engström 300 (Gambro Engström). The lung model consisted of one tracheal tube, two bronchial tubes which could be partially occluded, and two lungs (glass jars filled with water to a suitable compliance). Dialled (set) minute volume was compared to recorded minute volume. Gas distribution between obstructed and non-obstructed lung was calculated. All ventilators had a linear relationship between dialled and measured volume. Only the Servo Ventilator 900 D produced a gas distribution which was as good as, or better than that produced by the Engström 300.

Airway Obstruction↗

A new method for studying the ventilatory response in patients.

A method for clinical studies of the ventilatory response to carbon dioxide and to hypoxaemia in patients is described. The main parameters with this method are respiratory frequency, tidal volume, minute volume, timing, and drive. The ventilation of volunteers was not affected while breathing air through the designed apparatus. The response to carbon dioxide and to hypoxaemia in volunteers was reproducible and similar to what has previously been described. Our method proved suitable to test the ventilatory responses in patients with varying degrees of impaired ventilation-perfusion ratios and thus also in patients with a low PaO2. Our method has a higher accuracy than earlier methods.

Adult↗

Is late walking a marker of morbidity? Steering Committee, Oxford Region Child Development Project.

We identified 410 infants who were not walking independently by the age of 18 months from among a geographically defined population of 4275 infants who either were born weighing less than 2000 g or had needed admission to the special care nursery in the neonatal period. The outcome of the late walkers was ascertained at the age of 3 years by health visitors using a standard questionnaire. Of the late walkers, 230 (56%) had an associated abnormality diagnosed before the age of 3 years, and in 77 of these children (33%) this was definite or suspected cerebral palsy. The high prevalence of late walking among infants born before 28 weeks' gestation (46%) was almost entirely accounted for by a high incidence of impairment. Late walking is a simple marker of morbidity in this group of infants.

Age Factors↗