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J McCombs

Publications and source records attributed to J McCombs.

11 recordsLinked to original sources
PubMed2000

An evidence-based cost-effectiveness model on methods of prevention of posttraumatic venous thromboembolism.

BACKGROUND: Venous thromboembolism (VT) after injury is a major health problem. Literature data on methods of VT prophylaxis are not consistent with regard to safety and efficacy, and a recent evidence-based report could not conclude that any method was superior to any other or to no prophylaxis. Because no study exists on the cost-effectiveness (C-E) of the different methods of prophylaxis, data from the evidence-based report were used to design a C-E analysis. This analysis will assist in the design of future randomized trials with adequate power to show significant outcome differences. METHODS: A decision-tree model was designed on the basis of outcomes from the evidence-based report or relevant literature. We then calculated the cost of prevention of VT by one of the most commonly used methods-low-dose heparin (LDH), low-molecular-weight heparin (LMWH), or sequential compression devices (SCDs)-using different probabilities of incidence of VT. Finally, we adjusted the cost for expected years of life after the episode of VT to calculate the cost per life-year saved by preventing VT. RESULTS: We produced two tables that can be used to calculate the cost per life-year saved for any patient according to his or her age and the method of prophylaxis used. VT prophylaxis becomes less cost-effective as age progresses, because of decreased life-expectancy. With a widely accepted cost limit of $50,000 per life-year saved to indicate cost-effective treatment, LDH is more cost-effective than LMWH or SCDs. CONCLUSION: Our C-E model can help future investigators plan VT-related research with appropriate sample sizes to evaluate cost-effective methods of prophylaxis. LMWH and SCDs must demonstrate substantial improvements in measured outcomes to be more cost-effective than LDH. C-E must be incorporated as a primary outcome in future studies comparing different methods of VT prophylaxis.

Anticoagulants↗
PubMed1998

Low-dose theophylline increases urine output in diuretic-dependent critically ill children.

OBJECTIVE: Determine the effect of low-dose theophylline on urine output and the urinary adenosine: cAMP (cyclic adenosine monophosphate) excretion ratio (a measure of phosphodiesterase inhibition) in diuretic-dependent critically ill children. DESIGN: Observational clinical case series and animal laboratory experiment. SETTING: A university pediatric intensive care unit and a pharmacology research laboratory. PATIENTS: 10 consecutive oliguric patients treated with theophylline for diuresis. INTERVENTIONS: Urine output, fluid intake, diuretic dosages, and number of pressors (including dopamine) were monitored over the 24-h period prior to and the 24-h period immediately after theophylline was started. Hourly collections of urine were obtained at baseline and 1 and 3 h after theophylline was started and urinary excretion rates of adenosine and cAMP were measured and calculated. MEASUREMENTS AND RESULTS: Mean theophylline level in the children was 5.0 microg/ml. Urine output increased from 1.58 +/- 0.46 to 3.75 +/- 0.77 ml/kg per h (p = 0.008, paired t-test) after theophylline administration. There was no significant change in fluid intake, vasoactive agents, or dosages of other diuretics during the study periods. Intrarenal infusion of the IC50 concentration of isobutylmethylxanthine for phosphodiesterase activity resulted in a reduction of the adenosine: cAMP urinary excretion ratio in rats (p < 0.05). Low-dose theophylline had no effect on the adenosine: cAMP urinary excretion ratio in children. Concurrent therapy with dopamine was associated with an enhanced diuretic effect of theophylline (with dopamine, 1.30 +/- 0.30 to 5.07 +/- 0.77 ml/kg per h vs without dopamine, 1.77 +/- 0.76 to 2.86 +/- 1.08 ml/kg per h; p = 0.03, two-way ANOVA). There was no interaction between dopamine and low-dose theophylline on the urinary adenosine: cAMP excretion ratio (p = 0.56, two-way ANOVA). CONCLUSIONS: Theophylline increased urine output in diuretic-dependent critically ill children and the diuretic effect may have been potentiated by concurrent use of dopamine. Adenosine receptor antagonism may be a more likely mechanism for the diuretic effect of theophylline than phosphodiesterase inhibition.

Adenosine↗
PubMed1995

Update on tocolytic therapy.

OBJECTIVE: To review medications currently being used or investigated for the treatment of preterm labor. Adverse effects, pharmacoeconomic issues, and therapeutic controversies are included. DATA SOURCES: A MEDLINE search, limited to English-language articles and publication years of 1989-1994, was used to identify pertinent literature. Additional references were identified from articles retrieved in the search. STUDY SELECTION: Studies were chosen on drugs that are available or whose approval is anticipated in the US: ritodrine, terbutaline, hexoprenaline, and magnesium sulfate. Several studies comparing indomethacin and nifedipine with currently used medications are also included. Oxytocin antagonists, now in Phase II clinical trials, are discussed. Studies focusing on adverse reactions were included because of serious concerns that these reactions raise. DATA EXTRACTION: Part of the controversy surrounding tocolytic agents involves the difficulty in comparing data from different trials, particularly because the criteria for diagnosis of preterm labor vary significantly. Therefore, no attempt was made to directly compare data from different sources; individual study data are presented. DATA SYNTHESIS: Most studies reviewed using the beta-agonists showed each to be comparable in effectiveness when given parenterally during early preterm labor. These drugs usually delay delivery for 24-48 hours. There is less evidence that they are consistently effective in the long-term treatment of preterm labor. The adverse effects vary somewhat, but all beta-agonists have been reported to cause pulmonary edema, which is the most serious adverse effect associated with the use of these medications to inhibit labor. Indomethacin and nifedipine may be alternative choices for tocolytic therapy, but each has different adverse reactions that also make them less than ideal agents. Oxytocin antagonists may provide more specific therapy and are currently being investigated. CONCLUSIONS: The beta-agonists are effective in delaying delivery for 24-48 hours in most patients; however, there are potential risks involved. Magnesium sulfate, prostaglandin synthetase inhibitors, calcium-channel blockers, and oxytocin antagonists may provide alternative choices for the treatment of preterm labor associated with neonatal morbidity and mortality. Each of the medications has advantages and disadvantages at different stages of gestation.

Adrenergic beta-Agonists↗
PubMed1994

Use of chromosome microdissection, the polymerase chain reaction, and dot blot hybridization to analyze double minute chromosomes.

The potential usefulness of chromosome microdissection, the polymerase chain reaction (PCR), and dot blot hybridization as a quick screening method for determining the genetic composition of double minute chromosomes (DMs) was evaluated. DMs or abnormally banding regions (ABRs) were microdissected from multidrug-resistant hamster cell lines and amplified with PCR using primers specific for the hamster multidrug-resistance (MDR) gene, pgp 1. The microdissected-PCR-amplified products were shown to (a) hybridize to a 32P-labeled pCHP1 probe for the hamster MDR gene by using dot blot or Southern blot analysis and also (b) hybridize back to the chromosome region from which they were originally dissected by using fluorescent in situ hybridization. Microdissected/PCR-amplified DMs were also shown to hybridize to ABRs. When microdissected DMs and ABRs were amplified using hamster specific Alu primers, the resulting material was shown to hybridize with probes for hamster MDR and Alu. These results suggest that the DMs contained in these MDR hamster cell lines contain Alu-like sequences and the chromosome microdissection-PCR-hybridization approach might be used as a quick screening method for identifying genes amplified in DMs and ABRs in cell lines and human tumor samples.

Animals↗
PubMed1993

Clonal chromosomal abnormalities in Fanconi's anaemia: what do they really mean?

Patients with Fanconi's anaemia (FA) have aplastic anaemia, leukaemia, myelodysplasia and tumours. Since leukaemia has a very poor prognosis, it is desirable to identify high-risk patients. To determine the significance of clonal marrow chromosomal abnormalities we began a prospective study in 17 patients: five were normal, eight aplastic, and four myelodysplastic. Three of 11 with adequate cytogenetics had transient abnormal clones. None had leukaemia at 3-24 months. Changing cytogenetic patterns may not be related to leukaemic evolution in patients with a DNA repair defect.

Chromosome Aberrations↗
PubMed1993

Rapid detection of poliovirus by reverse transcription and polymerase chain amplification: application for differentiation between poliovirus and nonpoliovirus enteroviruses.

This report describes a rapid method of detection of poliovirus from viral isolates of clinical specimens using a single set of primers selected from the conserved 5' noncoding region of the poliovirus genome. Of the 144 clinical viral isolates examined, 81 were positive for polioviruses and 50 were positive for nonpoliovirus enteroviruses by tissue culture neutralization and infectivity. All 81 (100%) of the viral isolates identified as poliovirus by tissue culture infectivity were also positive by polymerase chain reaction. Of 50 nonpoliovirus enterovirus isolates found to be negative for poliovirus by tissue culture neutralization and infectivity, 48 were also negative by polymerase chain reaction. The high sensitivity (100%) and specificity (96%) of the primer set indicate that this assay has potential clinical applicability in the diagnosis of nonpoliovirus enterovirus infection.

Base Sequence↗
PubMed1992

Treatment of preeclampsia and eclampsia.

The characteristics and treatment of preeclampsia and eclampsia are reviewed. Risk factors for preeclampsia include (1) nulliparity, (2) a mother or sister(s) with a history of the disorder, (3) essential hypertension or renal disease, or (4) a twin or molar pregnancy. Preeclampsia is diagnosed when the systolic blood pressure (BP) increases by 30 mm Hg or the diastolic BP increases by 15 mm Hg after the 20th week of gestation and the BP rise is accompanied by edema, proteinuria, or both. Severe preeclampsia is diagnosed when the BP reaches or exceeds 160 mm Hg systolic or 110 mm Hg diastolic after bed rest. Eclampsia is the occurrence of seizures (in the preeclamptic patient) that cannot be attributed to other causes; it occurs in about 0.2% of preeclamptic patients. Magnesium sulfate (in the injectable, hydrated form) is the agent used most often for seizure prophylaxis in the preeclamptic patient in the United States. It is also used widely to control seizures once they develop. In the United States, diazepam is used to supplement magnesium sulfate if necessary to control seizures, but its use is not routine. Among antihypertensive agents, i.v. hydralazine is preferred in this country to control blood pressure in the severely preeclamptic or eclamptic patient. Several studies provide promising evidence that low-dose aspirin (60-150 mg daily beginning at 28-30 weeks of gestation) prevents preeclampsia in women who are at risk for its development. Until additional comparative studies are completed, magnesium sulfate and hydralazine will remain the standard of care for the treatment of preeclampsia in the United States.

Antihypertensive Agents↗
PubMed1984

Reproduction in XYY males: two new cases and implications for genetic counseling.

We present two children--one, 47,XY, + mar, and the other, 47,XY, + 21. Both fathers were found to have a 47,XYY chromosome constitution. The initial assumption was that the fathers' aneuploid conditions contributed to those of the offspring. However, the derivation of the marker chromosome could be paternal, maternal, or postzygotic, and examination of polymorphic structures of the number 21 chromosomes of the child with Down syndrome and his parents suggested maternal derivation of the supernumerary 21. To explore further the reproductive risks of an individual with the XYY constitution, previous reports of reproductive performance and testicular histology are examined as are two theories which suggest XYY males may be at an increased risk of producing aneuploid progeny. Based on these reports, recommendations are made for testing XYY males prior to genetic counseling.

Aneuploidy↗
PubMed1983

Characterization of human colon carcinoma cell lines isolated from a single primary tumour.

The initiation of a cultured human colon carcinoma line on a feeder layer of confluent fibroblasts is described. Attempts to initiate cultures without fibroblast feeder layers were not successful. Two sub-lines (designated HCT C and HCT C Col) were isolated and weaned from cells growing on the surface of the feeder layer. The sub-lines had different morphologies, secreted different levels of carcinoembryonic antigen (CEA) into the medium of confluent cultures and had slightly different karyotypes. Both sub-lines grew in semi-solid medium and formed xenografts when injected s.c. into athymic nude mice. Analysis of radioiodinated cell membrane components indicated small, but significant differences between the sub-lines.

Animals↗