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Biomedical subjects

R Andrews

Publications and source records attributed to R Andrews.

At least 73 records · Page 4Linked to original sources
PubMed1995

Secondary tumours following etoposide containing therapy for germ cell cancer.

BACKGROUND: Reports have implied etoposide as the cause of secondary leukaemia in patients treated for germ cell cancer. PATIENTS AND METHODS: Between 1979 and 1992, 679 male patients with germ cell cancer received etoposide containing chemotherapy. RESULTS: Six of 679 patients developed acute myeloid leukaemia (relative risk 150; CI: 55-326). None of these patients had a primary mediastinal germ cell tumour and only 1 patient received previous radiotherapy. The median interval between the onset of cytotoxic treatment and the development of leukaemia was 27 months. The FAB M4 morphology was seen in 4 of 6 cases. CONCLUSION: The benefit of etoposide containing protocols outweigh the risk of leukaemia in patients with intermediate or high risk disease, however in patients with good risk disease non-etoposide containing protocols should be explored.

Acute Disease↗
PubMed1995

Assessment of an inner city visual screening programme for preschool children.

AIMS: The efficiency of preschool visual screening programmes to detect amblyopia is questionable. In this study such a programme in an inner city was assessed to determine its effectiveness. METHODS: The results of screening and hospital treatment of 712 patients who were considered to require referral were entered into a database for analysis. Default rates were assessed and the efficacy of treatment determined. RESULTS: The only effective screening test for the detection of amblyopia was visual acuity. A large proportion of referred patients had refractive problems only. High default rates, particularly in geographical areas of lower socioeconomic grading, severely handicapped any attempt to reduce the incidence of amblyopia. CONCLUSION: A fresh approach to the detection and care of amblyopia in the inner city community is required, perhaps by performing screening of children in their first year of attendance at school to reduce default rates. Cycloplegic refraction of children who are found to have reduced visual acuity before their referral to hospital is also recommended.

Amblyopia↗
PubMed1995

Effects of captopril and oxygen on sleep apnoea in patients with mild to moderate congestive cardiac failure.

OBJECTIVES: To determine the effects of captopril and oxygen on sleep quality in patients with mild to moderate cardiac failure. DESIGN: An open observational study. PATIENTS: 12 patients with New York Heart Association class II-III heart failure were studied at baseline. 9 of these patients were then examined at the end of 1 month of treatment with captopril; 9 of the patients were separately assessed during a single night of supplementary oxygen. MAIN OUTCOME MEASURES: Sleep patterns by polysomnography, overnight oximetry, and subjective sleep assessment using visual analogue scores. RESULTS: Abnormal sleep was present in all baseline studies. Complete polysomnograms after treatment with captopril were obtained in 8 patients. Light sleep (stages 1 and 2) was reduced (mean (SEM) 61%(8)% to 48%(6)% actual sleep time, P < 0.05) but slow wave (stages 3 and 4) and REM (rapid eye movement) sleep increased (25%(6)% to 31%(5)%, 14%(2)% to 21%(5)% actual sleep time, P < 0.05). Apnoeic episodes (242(59) to 118(30), P < 0.05), desaturation events (171(60) to 73(37), P < 0.05), and arousals (33(5) to 18(3) P < 0.01) were reduced. Visual analogue scores of sleep quality increased 49(5) to 69(5), P < 0.01). Complete polysomnograms were obtained in 7 patients treated with oxygen. Light sleep duration was reduced (55% (7)% to 42%(5)% actual sleep time, P < 0.05) and slow wave sleep increased (30%(5)% to 38%(6)% actual sleep time, P < 0.05). REM sleep duration was not significantly different. Total arousals (33(6)% to 20(2) P < 0.05), desaturation events (140(33) to 38(10), P < 0.01), and apnoeic episodes (212(53) to 157(33), P < 0.05) were reduced. Visual analogue scores of sleep quality were unchanged. CONCLUSIONS: Captopril and oxygen may improve sleep quality and reduce nocturnal desaturation in patients with mild to moderate cardiac failure. Improved sleep quality could explain the reduction in daytime symptoms seen after treatment in patients with chronic heart failure.

Captopril↗
PubMed1995

Failure of "effective" treatment for heart failure to improve normal customary activity.

OBJECTIVES: To examine the effects of drug treatment on laboratory exercise tests in relation to measures of daily activity in patients with chronic heart failure. SETTING: University teaching hospital. SUBJECTS: 18 patients with mild to moderate chronic heart failure (New York Heart Association functional class II-III) and 10 age matched healthy controls. METHODS: Assessments were made before and after 12 weeks of vasodilator drug treatment. Exercise capacity was measured during two different types of treadmill exercise, one using a ramp protocol and the other a fixed work load. Corridor walk tests at three self selected speeds were also undertaken and measures of customary activity assessed from pedometer scores. RESULTS: Exercise times were significantly increased from baseline (P < 0.01) with both treadmill protocols after 12 weeks of drug treatment, with a positive correlation between the duration of treadmill exercise for both protocols (r = 0.69, P < 0.01). Corridor walk tests of 100 m at a self selected slow speed also improved (P < 0.02) but these did not correlate with the changes in treadmill exercise time. The pedometer scores of the patients with heart failure were greatly reduced compared with those of the controls (258 (45) x 10(2) v 619 (67) x 10(2) steps/week, P < 0.001) and after 12 weeks of treatment were unchanged (261 (42) x 10(2) steps/week). CONCLUSIONS: These data confirm the need to use different exercise protocols when assessing the benefits of drug treatment in patients with chronic heart failure. Treatments that seem effective with conventional laboratory based exercise tests may not improve daily activities. This may reflect a failure of apparently successful treatment and should be considered when interpreting clinical trials.

Activities of Daily Living↗
PubMed1995

Stereotactic volumetric radiofrequency lesioning of intracranial structures for control of intractable seizures.

Computed tomography (CT) scans provide three-dimensional information about intracranial structures, which can be used to place stereotactically guided radiofrequency (RF) lesions and destroy a targeted volume of tissue. This technique was used for lesioning of the corpus callosum (CC) or the amygdala-hippocampus complex (AHC) in 9 patients with intractable seizures. The procedures were monitored by intraoperative CT scans. Lesions were made in the AHC in 7 patients and the CC in 2 patients. In addition, multiple subpial transection (MST) was performed in 6 patients. The longest follow-up is 29 months with a median of 19 months. Five patients (56%) are free of seizures, 3 patients (33%) have greater than 90% reduction in seizure activity and 1 patient (11%) has greater than 50% but at most 90% reduction in seizure activity. There were no complications except for temporary hemiparesis following MST in 1 patient. The results suggest that stereotactic volumetric RF lesioning of the AHC and the CC may be safe and effective in controlling intractable seizures.

Adolescent↗
PubMed1995

Minimally invasive surgical approach for intractable seizure.

Minimally invasive procedures (multiple subpial transection, topectomy and amygdalahippocampotomy) were used to treat 24 patients with intractable seizures. The seizure foci were in both hemispheres in 3 patients, all 4 lobes of a hemisphere in 1 patient, 3 lobes of a hemisphere in 5 patients, 2 lobes of a hemisphere in 11 patients and the temporal lobe alone in 4 patients. The longest follow-up is 41 months, with a median of 18 months. Sixteen patients have a follow-up of more than 1 years, with excellent results in 10 (66%) and good in the remaining 6 (38%). There were no permanent complications These results are encouraging, because the majority of the patients were poor candidates for surgery.

Adolescent↗
PubMed1995

Clinical and economic factors in the treatment of congestive heart failure.

Congestive heart failure (CHF) is a disease of massive clinical and economic importance throughout the developed world. Approximately 1% of the population are affected, with incidence and prevalence of CHF increasing with age. The major aetiological factor is ischaemic heart disease and, despite advances in treatment, mortality from CHF remains appallingly high, and comparable to that of many malignancies. The majority of patients with CHF require treatment with a diuretic, though there is now clear evidence that the addition of an angiotensin converting enzyme (ACE) inhibitor will not only improve symptoms but also reduce mortality and delay the progression of the disease. The vast economic impact of CHF is now becoming fully appreciated, with the majority of expenditure on hospital admissions. The earlier and more widespread use of ACE inhibitors in the treatment of CHF would be highly cost effective, with substantial savings in hospitalisation costs, though new and effective treatments are still urgently required.

Age Distribution↗
PubMed1994

Effects of granulocyte colony-stimulating factor and stem cell factor, alone and in combination, on the mobilization of peripheral blood cells that engraft lethally irradiated dogs.

The effects of recombinant canine granulocyte colony-stimulating factor (rcG-CSF) and recombinant canine stem cell factor (rcSCF), a c-kit ligand, on the circulation of hematopoietic progenitor and stem cells were studied in a canine model. Administration of rcG-CSF (10 micrograms/kg) for 7 days led to a 5.4-fold increase in CFU-GM/mL of blood, while 7 days of rcSCF (200 micrograms/kg) led to an 8.2-fold increase. Although treatment with low-dose rcSCF (25 micrograms/kg) had no effect on the level of peripheral blood progenitors, 7-day exposure to a combination of G-CSF plus low dose SCF led to a 21.6-fold increase (P = .03). To assess the ability of these factors to increase the circulation of cells capable of rescuing animals after lethal total body irradiation (TBI), 1 x 10(8) peripheral blood mononuclear cells (PBMC)/kg were collected and cryopreserved from animals after 7 days of treatment with G-CSF, SCF or a combination of the two. One month later, animals were exposed to 9.2 Gy TBI and transplanted with the previously collected cells. Control animals transplanted with 1 x 10(8) PBMC/kg collected without pretreatment died with marrow aplasia 11 to 29 days after TBI as did animals treated with only low-dose SCF before cell collection. In contrast, all animals given PBMC collected after G-CSF, high-dose SCF, or a combination of G-CSF plus low-dose SCF recovered granulocyte function. Recovery to 500 granulocytes/microL after transplant took 17, 18.8, and 13.6 days, respectively, (P = .056 for the difference between the combination G-CSF-SCF group and the other two groups). In both the G-CSF and SCF groups, 4 of 5 animals completely recovered while 1 of 5 in each group died with prolonged thrombocytopenia. In the combination group, all 5 animals became long-term survivors. These studies demonstrate that both G-CSF and SCF dramatically increase the level of peripheral blood hematopoietic progenitor and stem cells and support the view that these factors can act synergistically.

Animals↗
PubMed1994

A genetic linkage map for the zebrafish.

To facilitate molecular genetic analysis of vertebrate development, haploid genetics was used to construct a recombination map for the zebrafish Danio (Brachydanio) rerio. The map consists of 401 random amplified polymorphic DNAs (RAPDs) and 13 simple sequence repeats spaced at an average interval of 5.8 centimorgans. Strategies that exploit the advantages of haploid genetics and RAPD markers were developed that quickly mapped lethal and visible mutations and that placed cloned genes on the map. This map is useful for the position-based cloning of mutant genes, the characterization of chromosome rearrangements, and the investigation of evolution in vertebrate genomes.

Animals↗
PubMed1994

Unruptured aneurysm of the left sinus of Valsalva presenting with atrial fibrillation.

Congenital aneurysms arising from the left sinus of Valsalva are extremely uncommon, and when unruptured often asymptomatic. Abnormalities of rhythm are more commonly associated with dilatation of the right coronary sinus although the reason for this is unclear. We report the first case of an unruptured aneurysm involving the left sinus of Valsalva presenting with paroxysmal atrial fibrillation. Two-dimensional echocardiography confirmed the diagnosis.

Adult↗
PubMed1994

Inhibition of platelet aggregation by transdermal glyceryl trinitrate.

OBJECTIVE: To determine the optimum conditions for the demonstration of an antiplatelet effect of nitric oxide and to use these conditions to elucidate the effects of a transdermal glyceryl trinitrate patch on platelet aggregation in normal volunteers. METHODS: An open prospective crossover study. The effects of nitric oxide on platelet aggregation in whole blood and platelet rich plasma as stimulated by adenosine diphosphate and U46619 was assessed in the presence and absence of iloprost and MB22948. Optimum conditions for the demonstration of an antiplatelet effect of nitric oxide were then applied to whole blood from normal volunteers in the presence and absence of a transdermal glyceryl trinitrate patch. SETTING: University hospital. SUBJECTS: Eight normal volunteers. MAIN OUTCOME MEASURES: Platelet aggregation in the presence and absence of transdermal glyceryl trinitrate. RESULTS: The optimum conditions for the demonstration of an antiplatelet effect of nitric oxide in whole blood were collecting blood into a tube containing MB22948 and citrate and stimulating platelet aggregation with adenosine diphosphate in the presence or absence of iloprost. Using this method a significant effect of transdermal glyceryl trinitrate on platelet aggregation was shown (P < 0.03) in the presence and absence of iloprost. CONCLUSIONS: These results are consistent with an inhibitory effect on platelet aggregation of nitric oxide liberated by transdermal glyceryl trinitrate. Optimum test conditions are needed to show this effect. The clinical significance of the antiplatelet effect of transdermal glyceryl trinitrate is unknown.

Adenosine Diphosphate↗
PubMed1994

Reengineering and improving the information-intensive work of patient tracking for inpatients and outpatients.

This article describes a CQI-driven effort to reengineer the tracking procedures for both inpatients and outpatients, refined to the extent that they have been identified as "best practices." The goal was to shift the work paradigm from a departmental focus to one that accepts work as a network of processes, but also to prepare for the new era of the electronic medical record, moving computer record keeping far closer to the point of care, requiring more precise recording of patient location.

Admitting Department, Hospital↗
PubMed1993

Hematopoietic precursors resistant to treatment with 4-hydroperoxycyclophosphamide: requirement for an interaction with marrow stroma in addition to hematopoietic growth factors for maximal generation of colony-forming activity.

We tested the ability of CD34+lin- precursor cells isolated from marrow after treatment with 4-hydroperoxycyclophosphamide (4HC) to generate colony-forming cells (CFC). In liquid cultures, recombinant human stem cell factor (SCF), in combination with interleukin-1 (IL-1), IL-3, IL-6, granulocyte-macrophage colony-stimulating factor, or granulocyte colony-stimulating factor caused untreated, but not 4HC-treated, CD34+lin- cells to form CFC. However, generation of CFC from CD34+lin- cells treated with 60 micrograms/mL of 4HC was possible in the presence of an irradiated allogeneic stromal cell layer. This generation was increased when combinations of hematopoietic growth factors including SCF and IL-3 were added. Maximal generation of CFC was seen after 11 to 21 days of culture. At that time, generation of CFC from CD34+lin- 4HC-treated cells equalled that from untreated cells. The phenotype of these 4HC-resistant CD34+lin- precursors was also further defined as CD38-. These studies show that the generation of CFC from the 4HC-resistant, highly immature population of CD34+lin- cells requires an as yet undefined interaction with marrow stroma in addition to known hematopoietic growth factors.

ADP-ribosyl Cyclase↗
PubMed1993

Nonamer binding protein induces a bend in the immunoglobulin gene recombinational signal sequence.

DNA bending has been shown to play a critical role in conservative site-specific DNA recombination reactions such as lambda integration. V(D)J recombination, the only mammalian site directed recombination system, is directed by recombinational signal sequences composed of heptamer, nonamer and spacer elements. The nonamer element, GGTTTTTGT, is similar to the consensus sequence for bent DNA. Using the circular permutation electrophoretic mobility assay, we show that the nonamer sequence has a detectable intrinsic bend. The nonamer sequence has been shown to be the binding site for nonamer binding protein (NBP). Binding of NBP to the nonamer site increases the apparent angle of the bend from 32 degrees to 66 degrees. The identification of a protein induced DNA bend near the site of V(D)J recombination may have implications for our understanding of the mechanism of V(D)J recombination.

Animals↗
PubMed1993

Ureaplasma urealyticum in a neonatal intensive care population.

The incidence of Ureaplasma colonization at birth and its effect on the development of chronic lung disease (CLD) and on mortality was studied in a neonatal intensive care population. Ureaplasma colonization was associated with a birthweight < 1000 g (odds ratio [OR] 3.45 confidence intervals [CI] 2.13-5.60) and a gestational age < 30 weeks (OR 2.54 CI 1.71-3.79). In a case-controlled study of 112 infants, significant associations with Ureaplasma colonization were maternal pyrexia in labour (n = 38 vs 21; P = 0.015), the requirement for antibiotics in labour (n = 39 vs 16; P = 0.0005) and vaginal delivery (n = 78 vs 58; P = 0.009). Risk factors associated with the development of CLD were birthweight < 1000 g (OR 3.77 CI 2.53-5.62) and delivery by Caesarean section (OR 1.65 CI 1.11-2.43). Within the group delivered by Caesarean section. Ureaplasma colonization was also associated with an increased risk of CLD (OR 1.97 CI 1.08-3.62). Ureaplasma colonization of infants at birth is associated with factors suggestive of maternal chorioamnionitis as well as preterm birth and low birthweight. In infants delivered by Caesarean section, Ureaplasma colonization is associated with an increased risk of chronic lung disease.

Adult↗
PubMed1993

Pulmonary artery dissection in a patient with idiopathic dilatation of the pulmonary artery: a rare cause of sudden cardiac death.

A 31 year old man presented with a left hilar mass. Thoracic tomography showed this mass to be the pulmonary artery, and subsequently idiopathic dilatation of the pulmonary artery was diagnosed. He remained well until 11 years later when he died suddenly. Postmortem examination confirmed idiopathic dilatation of the pulmonary artery with death due to pulmonary artery dissection and cardiac tamponade. It seems likely that idiopathic dilatation of the pulmonary artery predisposed to fatal pulmonary artery dissection.

Adult↗
PubMed1993

Phosphodiesterase inhibitors. Do the risks outweight the benefits?

Despite the justifiable concern about the use of oral cyclic adenosine monophosphate phosphodiesterase (cAMP PDE) inhibitors, the intravenous preparations are clearly effective in the treatment of acute heart failure, whether it occurs de novo or complicating chronic congestive heart failure (CHF), and in low output states following cardiac surgery. There are no grounds to curtail their use in these areas, though any advantages over conventional agents such as dobutamine need further investigation with regard to end-points other than haemodynamic parameters. The long term use of oral cAMP PDE inhibitors in the treatment of chronic CHF should remain restricted by the increase in mortality now confirmed in severe CHF. However, in view of the distressing nature of the condition there remain subgroups of patients in whom the benefits may outweight the risks.

3',5'-Cyclic-AMP Phosphodiesterases↗