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Biomedical subjects

J R Starke

Publications and source records attributed to J R Starke.

At least 19 recordsLinked to original sources
PubMed2004

Pharmacokinetics of ethambutol in children and adults with tuberculosis.

SETTING: Five hospitals in the United States. OBJECTIVE: To describe ethambutol pharmacokinetics in children and adults with active tuberculosis (TB). DESIGN: Prospective, open-labeled study in 56 adults and 14 children with active tuberculosis who received ethambutol as part of their multidrug TB regimens. RESULTS: Most serum samples were collected up to 10 h post dose and assayed using a validated gas chromatography assay with mass selective detection (GC/MS). Concentration data were analyzed using non-compartmental and population pharmacokinetic methods. Drug exposure increased with dose, but less than proportionally at doses >3000 mg. Lower than expected maximum serum concentrations (Cmax <2 microg/ml) were common in adults. Very low Cmax (<1 microg/ml) were common in children, as was delayed absorption (time to Cmax >3 h). Many Cmax were at or below typical TB minimal inhibitory concentrations. Cmax values for HIV-positive patients were 20% lower than HIV-negative patients with daily doses, but were similar with larger twice-weekly doses. CONCLUSIONS: Adult TB patients often had lower than expected ethambutol serum concentrations, and most pediatric TB patients had very low ethambutol serum concentrations. Higher doses and therapeutic drug monitoring may be indicated for many of these patients.

Absorption↗
PubMed2002

Population pharmacokinetics of ethionamide in patients with tuberculosis.

SETTING: Three US referral hospitals. OBJECTIVE: Determine the population pharmacokinetic (PK) parameters of ethionamide (ETA) following multiple oral doses. DESIGN: Fifty-five patients with tuberculosis (TB) participated. Patients received multiple oral doses of ETA as part of their treatment. They also received other anti-tuberculosis medications based upon in vitro susceptibility data. Serum samples were collected over 12 h post-dose, and concentrations were determined using a validated high-performance liquid chromatography (HPLC) assay. Concentration-time data were analyzed using population methods. RESULTS: ETA areas under the concentration-versus-time curve (AUCs) increased linearly with increasing oral doses from 250 to 1000 mg. Compared to the population pattern, delayed absorption was seen at least once in 15% of patients. ETA PK parameter estimates were independent of age, weight, height, gender, and creatinine clearance. TB patients appeared to have larger volumes of distribution (3.22 l/kg) and clearance values (1.88 l/h/kg) compared to previously studied healthy volunteers. This resulted in lower AUC values (3.95 mcg h/ml) in the TB patients. ETA displayed a short elimination half-life (1.94 h). The effect of different dosing strategies on calculated pharmacodynamic parameters was explored. Simulated doses of 250 mg BID to TID failed to achieve serum concentrations above the MIC. CONCLUSION: ETA PK parameters differed between TB patients and healthy volunteers, possibly due to differences in the completeness of absorption. Doses of at least 500 mg appear to be required to achieve serum concentrations above the typical ETA MIC. Additional research is needed to determine the optimal dosing of ETA.

Administration, Oral↗
PubMed2002

A critical review of diagnostic approaches used in the diagnosis of childhood tuberculosis.

SETTING: The diagnosis of tuberculosis (TB) in children is seldom confirmed, and is based mainly on clinical signs, symptoms and special investigations. Various attempts in the form of diagnostic approaches have been made to rationalise this diagnostic process. AIMS: To review and describe published diagnostic approaches aimed at diagnosing mainly intrathoracic tuberculosis in children in developing countries; to compare diagnostic approaches with each other and with bacteriologically confirmed TB; and to describe modifications to the diagnosis of TB in HIV-infected or malnourished children. METHODS: Literature review classified into 1) diagnostic approaches, 2) characteristics used in diagnostic approaches, and 3) studies done to validate diagnostic approaches. RESULTS: Sixteen systems were analysed. Comparison of systems is difficult because characteristic definitions and the ranking of characteristics are not standardised, few studies have been performed to validate these diagnostic approaches, and the gold standard of diagnosis is not practicable in most settings. The minority of systems are adapted for HIV-infected and malnourished patients. RECOMMENDATIONS: Characteristic definitions and ranking of characteristics should be standardised. Any new diagnostic approaches developed should be relevant to developing countries with limited resources, a high burden of tuberculosis, malnutrition and HIV/AIDS and a young population. Studies done to validate diagnostic approaches should be conducted scientifically.

Age Factors↗
PubMed2001

Childhood tuberculosis: treatment strategies and recent advances.

Over the past 20 years, several major studies have shown that 6-month therapy, initially using isoniazid, rifampin and pyrazinamide, is highly effective and extremely safe for the treatment of most forms of childhood tuberculosis. The various drug schedules and frequency of administration will be reviewed. Directly observed therapy is an essential component of a paediatric tuberculosis treatment plan, though using it does not solve all problems with adherence to treatment. As the rates of drug-resistant tuberculosis increase around the world, special aspects of paediatric tuberculosis will have to be considered when designing treatment regimens for children. Finally, the next frontier of antituberculosis therapy may be the manipulation of the host immune system.

AIDS-Related Opportunistic Infections↗
PubMed2001

Congenital tuberculosis presenting as sepsis syndrome: case report and review of the literature.

We report an infant with congenital tuberculosis who presented with fulminant septic shock, disseminated intravascular coagulation and respiratory failure. Aggressive resuscitation and supportive care and prompt initiation of antituberculosis medications led to resolution of the shock state. We reviewed six other cases with a similar presentation. Congenital tuberculosis should be in the differential of the infant presenting acutely with sepsis syndrome.

Diagnosis, Differential↗
PubMed1999

Tuberculosis of the central nervous system in children.

Tuberculosis remains one of the most common and important infectious diseases in the world. Between 1% and 2% of children with untreated tuberculosis infection will develop tuberculous meningitis. In 1997, 186 cases of tuberculous meningitis were reported in the United States. The initial clinical manifestations of tuberculous meningitis are protean, making early disease difficult to recognize. The clinical and radiographic manifestations of tuberculous meningitis result from the combination of basilar meningitis, infarction, and vasculitis. Early diagnosis can be problematic as Mycobacterium tuberculosis is difficult to detect by rapid tests. Although the response to antituberculosis chemotherapy is generally favorable, complications commonly occur, particularly if the diagnosis is delayed. With appropriate public health management of known tuberculosis cases, cases of CNS tuberculosis in children can be prevented.

Antitubercular Agents↗
PubMed1999

Directly observed therapy for tuberculosis in children.

DOT is an important part of the treatment strategies for tuberculosis in children. It is highly effective, relatively inexpensive, and is the only way to ensure that the child is adequately treated. Although the public health ramifications of inadequate treatment of tuberculosis in children are not as severe as those for inadequate treatment in adults, the personal health consequences of nonadherence in children can be disastrous. In countries with adequate resources, DOT should be considered the standard of care for children with tuberculosis disease. The goal for the world should be to treat every child with tuberculosis with DOT.

Child↗
PubMed1997

Tuberculosis. An old disease but a new threat to the mother, fetus, and neonate.

Tuberculosis is the leading infectious disease in the world. In developing countries and certain areas of industrialized countries, rates of tuberculosis are highest among women and men of childbearing age. True congenital tuberculosis is rare; the greatest threat to the neonate is the acquisition of tuberculosis infection shortly after birth, which tends to progress rapidly to serious tuberculosis disease in a large proportion of untreated infants. Effective methods for prevention and treatment of the disease are available and inexpensive but still are not used appropriately in most parts of the developing world. The clinician caring for pregnant women should be aware of the risk factors for tuberculosis infection and disease and should test women and families according to risk.

Algorithms↗
PubMed1996

Tuberculosis in children.

During the past decade, a resurgence in adult tuberculosis and immigration has expanded the pool of children and adolescents infected with Mycobacterium tuberculosis. The evaluation and treatment of children depend on the stage of tuberculosis: exposure, infection, or disease. The major roles of the primary care physician in the control of tuberculosis are evaluating risk of infection, skin-testing patients with risk factors for tuberculosis disease, treating the infection, and initially evaluating children with possible tuberculosis disease. The cornerstone of the new tuberculosis control strategy is to identify risk factors with a good medical history and perform the best possible testing when risk factors are present.

Adolescent↗
PubMed1996

Detection of Mycobacterium tuberculosis in clinical specimens from children using a polymerase chain reaction.

OBJECTIVE: We evaluated the usefulness of the polymerase chain reaction (PCR) using the insertion sequence IS6110 as the target for DNA to detect Mycobacterium tuberculosis in clinical specimens from children. STUDY DESIGN: This was a prospective, controlled, blinded study comparing PCR on clinical specimens, mycobacterial culture, and clinical diagnosis. PATIENTS: Sixty-five hospitalized children were evaluated, 35 with tuberculosis disease and 30 controls. Cases were defined by culture and/or specific clinical criteria. Controls included patients with tuberculosis infection but no detectable disease as well as patients free of tuberculosis infection and disease. RESULTS: Polymerase chain reaction had a sensitivity of 40% and a specificity of 80% compared with clinical diagnosis. Mycobacterial culture had a sensitivity of 37%. The combination of culture and PCR identified 19 of 35 children (54%) with clinically diagnosed tuberculosis. There were six children with false-positive PCR results: One had tuberculosis infection without disease, two had Mycobacterium avium lymphadenitis, and three had diagnoses unrelated to tuberculosis. CONCLUSIONS: The sensitivity of PCR is comparable to that of culture for detecting M tuberculosis in children, and may strengthen and hasten the clinical diagnosis in culture-negative patients. However, because of the limitations in specificity, the results of PCR alone are insufficient to diagnose tuberculosis in children. Although ongoing refinements in PCR techniques should improve the specificity of this test, epidemiologic and clinical information continue to be the most important consideration in the diagnosis of tuberculosis in culture-negative children.

Adolescent↗