Biomedical subjects

D F Moore

Publications and source records attributed to D F Moore.

At least 37 records · Page 2Linked to original sources

PubMed2001

Selective arterial distribution of cerebral hyperperfusion in Fabry disease.

Fabry disease is an X-linked recessive deficiency of lysosomal alpha-galactosidase A associated with an increased risk of early onset cerebrovascular disease. The disorder is reported to affect the posterior circulation predominantly. This hypothesis was investigated directly by the measurement of regional cerebral blood flow with positron emission tomography (PET). Resting regional cerebral blood flow (rCBF) in 26 hemizygous patients with Fabry disease and 10 control participants was examined using H(2)15O and PET. Statistical parametric mapping (SPM(t), SPM99) and PET images of patients and controls were produced. Significantly increased SPM(t) clusters were then color coded and blended with a coregistered T1 magnetic resonance imaging (MRI) template. Cerebral arterial territory maps were digitized and rescaled. Custom OpenGL and ImageVision Library C++ code was written to allow a first-order affine transformation of the blended SPM(t) and MRI template onto the arterial territory map. The affine transformation was constrained by choosing corresponding cerebral landmark "tie points" between the SPM(t) [symbol: see text] MRI template images and the cerebral arterial territory maps. The data demonstrated that the posterior circulation is the predominant arterial territory with a significantly increased rCBF in Fabry disease. No arterial distribution had a decreased rCBF.

Adult↗

PubMed2001

Enhanced endothelium-dependent vasodilation in Fabry disease.

BACKGROUND AND PURPOSE: Fabry disease is an X-linked lysosomal storage disease secondary to deficiency of alpha-galactosidase A with resulting glycolipid accumulation, particularly globotriaosylceramide in arterial smooth muscle and endothelial cells. A systemic vasculopathy, including early-onset stroke, is prevalent without a clear pathogenesis. METHODS: Seventeen normotensive and normocholesterolemic hemizygous Fabry patients (aged 21 to 49 years) and 13 control subjects (aged 21 to 48 years) were investigated by venous plethysmography, allowing assessment of forearm blood flow. Plethysmographic measurements were obtained at baseline and during intra-arterial infusion of acetylcholine and sodium nitroprusside both with and without N(G)-monomethyl-L-arginine (L-NMMA). RESULTS: Forearm blood flow was significantly higher in patients than in control subjects at all 3 acetylcholine doses (P=0.014). Patients had a greater response to acetylcholine even after the addition of L-NMMA (P=0.036). CONCLUSIONS: These results demonstrate an increased endothelium-mediated vascular reactivity in Fabry disease. The increased vessel response to acetylcholine with and without L-NMMA suggests altered functionality of non-NO endothelium-dependent vasodilatory pathways.

Acetylcholine↗

PubMed2000

Comparative efficacy of dose regimens in enzyme replacement therapy of type I Gaucher disease.

Gaucher disease is caused by a deficiency of beta-glucocerebrosidase activity. The optimum dose and frequency of enzyme replacement therapy for Gaucher patients have not been determined. We set to compare the therapeutic effects of initiating treatment with macrophage-targeted glucocerebrosidase at a high dose followed by progressive dose reductions with that produced by initial treatment at a low dose in patients with type I Gaucher disease. The study included two parts: (i) Twelve patients received every 2 weeks enzyme replacement therapy at 60 IU/kg body wt for 24 months followed by sequential dose reduction every 6 months to 30 and then to 15 IU/kg body wt. (ii) Thirty-two patients received enzyme replacement therapy at 10 IU/kg every 2 weeks for 12 months. Hematologic parameters and liver and spleen volume were monitored in all patients. All patients had intact spleens. In patients who were started on high-dose enzyme replacement therapy, hemoglobin, acid phosphatase, and organ volume improved or remained unchanged at the end of each dose reduction. Platelet count decreased significantly when the dose of enzyme was reduced from 30 to 15 IU/kg body wt. Initiation of therapy at a low dose led to a significant improvement in all measured parameters at the end of 1 year. We conclude that the minimal effective dose for the nonskeletal manifestations of Gaucher disease can be achieved either by initiating enzyme replacement therapy with a high dose followed by a stepwise dose reduction or by starting treatment at the minimal dose. High dose provides a faster clinical response and should be considered for patients with more aggressive disease. The therapeutic threshold for macrophage-targeted glucocerebrosidase appears to be 10-15 IU/kg body wt every 2 weeks.

Adolescent↗

PubMed2000

A phase I study of induction chemotherapy for older patients with newly diagnosed acute myeloid leukemia (AML) using mitoxantrone, etoposide, and the MDR modulator PSC 833: a southwest oncology group study 9617.

Older patients with acute myelogenous leukemia (AML) have overexpression of P-glycoprotein (Pgp+), and this has been shown to correlate quantitatively with therapeutic outcome. Since Pgp-mediated efflux of cytotoxic drugs can be inhibited by the cyclosporine analogue, PSC 833, we investigated the use of this agent with a 5-day mitoxantrone/etoposide regimen in patients over age 55 with newly diagnosed AML. Previous studies suggested a 33% incidence of grade IV/V non-hematologic toxicity with the use of mitoxantrone 10 mg/M(2) and etoposide 100 mg/M(2), each for 5 days, in this patient population. Since PSC 833 alters the pharmacokinetic excretion of MDR-related cytotoxins, this phase I dose-finding study was performed to identify doses of mitoxantrone/etoposide associated with a similar 33% incidence of grade IV/V non-hematologic toxicity, when given with PSC 833. Mitoxantrone/etoposide (M/E) doses were escalated in fixed ratio from a starting dose of M: 4 mg/M(2) and E: 40 mg/M(2), to M: 7 mg/M(2) and E: 70 mg/M(2), in successive cohorts of eight patients each. PSC 833 was well tolerated and the MTD of this M/E regimen with PSC 833 in this population was M: 6 mg/M(2) and E: 60 mg/M(2). The complete response (CR) rate for all patients was 50% (15/30) and was considerably higher for de novo than for secondary AML. These data suggest that the addition of PSC 833 to an M/E regimen for older patients with untreated AML is well tolerated but requires a reduction in M/E dosing to avoid increased toxicity.

Acute Disease↗

PubMed2000

A phase II trial of etoposide, leucovorin, 5-FU, and interferon alpha 2b (ELFI) + G-CSF for patients with pancreatic adenocarcinoma: a Southwest Oncology Group study (SWOG 9413).

BACKGROUND: Chemotherapeutic treatments using combinations of etoposide, leucovorin and 5-FU (ELF) have shown activity in the treatment of gastrointestinal malignancies. Interferon alpha 2b is known to have antiproliferative effects on several cell lines and has well documented in vitro evidence of synergism with 5-FU. It was postulated that the combination of ELF and interferon alpha 2b would improve response rates and survival in patients with pancreas cancer. METHODS: Fifty-five eligible patients with locally-advanced or metastatic pancreatic adenocarcinoma received a regimen consisting of: i.v. leucovorin at 300 mg/m2/day on Days 1-3 (of 28-day cycle), i.v. etoposide at 80 mg/m2/day on Days 1-3, i.v. 5-FU at 500 mg/m2/day on Days 1-3, subcutaneous interferon alpha 2b at 3 million units TIW, and subcutaneous G-CSF at 5 microg/kg/day on Days 4-14 (or until WBC exceeds 10,000/microl). Patients with no evidence of disease progression continued on treatment for a total of 6 cycles. RESULTS: Complete response was demonstrated in 1 patient, partial response in 5 patients (11% confirmed response rate). The median survival was 5 months, and the six-month survival rate was 40%. Ten patients completed all 6 cycles of treatment. Toxicity-related dose delays and reductions were necessary for most patients. CONCLUSIONS: Although the combination of ELF and interferon alpha 2b (ELFI) has modest activity in pancreatic cancer, it is a toxic and complex regimen that is not superior to other currently available approaches for the chemotherapeutic management of pancreatic cancer. ELFI cannot be recommended as a standard therapy.

Adenocarcinoma↗

PubMed2000

Phase II evaluation of interleukin-4 in patients with non-Hodgkin's lymphoma: a Southwest Oncology Group trial.

We performed a phase II, Southwest Oncology Group (SWOG) clinical trial of recombinant human interleukin-4 (rhuIL-4) in patients with previously treated non-Hodgkin's lymphoma (NHL). We studied 18 eligible patients with low-grade and 21 patients with intermediate- or high-grade NHL. All patients had received prior chemotherapy. A protocol amendment after the first four patients reduced the frequency of s.c. rhuIL-4 administration from daily to 3 times per week at 3 microg/kg and limited the number of prior chemotherapy regimens allowed. We documented no complete or partial responses in the low-grade NHL group [0%; 95% confidence interval (CI) 0-19%]. One patient in the intermediate/high-grade NHL group developed a partial response lasting longer than 15 months (5%; 95% CI 0-24%). Median survivals for the low- and intermediate/high-grade NHL groups were 15 and 13 months, respectively. Common toxicities included: arhralgia/myalgia, fatigue/malaise/lethargy, fever, headache, nausea and rigors/chills. Cardiac toxicity, gastrointestinal ulceration and nasal congestion due to rhuIL-4 were not prominent toxicities in our patients. Our previously treated NHL patients tolerated s.c. rhuIL-4 at a dose of 3 microg/kg given 3 times per week, but objective response rarely occurred. Further evaluation of rhuIL-4 in these patient populations does not appear warranted.

Adult↗

PubMed1999

Phase II trial of oral etoposide in recurrent or refractory endometrial adenocarcinoma: a southwest oncology group study.

Oral etoposide has activity in a wide variety of tumors and is well tolerated. Therefore, the efficacy of oral etoposide was assessed as a treatment of metastatic endometrial cancer. To be eligible for this group-wide Southwest Oncology Group trial, patients had to have histologically proven metastatic or recurrent endometrial carcinoma; no previous cytotoxic therapy; and adequate renal, hepatic, and hematologic function, and they had to have given informed consent. Therapy consisted of oral etoposide, 50 mg daily on days 1-21 on a 28-day schedule. Therapy was continued in the absence of toxicity or disease progression. Forty-four eligible women, with a median age of 68 years (range 38-84 years) were treated. Radiotherapy had been delivered to 33 and hormomal therapy to 21. The median duration of therapy was 69 days (range 7-510 days). The treatment was well tolerated. Only one patient had grade 4 neutropenia, and a second had grade 4 anemia. Three patients had grade 3 nausea. One complete and five partial responses (14%) were observed. An additional four patients had unconfirmed responses. Tumor regressions were noted in nodes, bone, and visceral organs. While oral etoposide has only a modest level of activity when used in chemonaive patients, the minimal toxicity of this drug makes it a candidate for use in combination chemotherapy.

Adenocarcinoma↗

PubMed1999

Phase II trial of menogaril in non-Hodgkin's lymphomas: a Southwest Oncology Group trial.

PURPOSE: To assess the efficacy and toxicity of menogaril against non-Hodgkin's lymphoma (NHL) in a group of previously treated patients. PATIENTS AND METHODS: Sixty-two eligible patients with a histologic diagnosis of NHL were enrolled, 35 of who had intermediate or high-grade histologies and 27 of who had low-grade lymphomas. Patients with intermediate or high-grade lymphomas had received only 1 prior chemotherapy regimen, while patients with low-grade histologies had received 1 or 2 prior chemotherapy regimens. Menogaril was administered at 160 mg/m2 intravenously over 1 hour, once every 28 days. RESULTS: Among the 35 patients with intermediate or high-grade lymphomas who were evaluable for response, 6 of 35 patients achieved a partial response (PR) for a response rate of 17% (95% confidence interval: 7%-34%). Median survival in this group of patients was 13 months. For those patients with low-grade lymphoma, 5 of 26 patients achieved a PR for a response rate of 19% (95% confidence interval: 6%-38%). No complete responses were observed in either patient group. The incidence of serious (grade 3 or 4) toxicity for those with intermediate/high-grade and low-grade lymphomas was 43% and 44%, respectively. Most of these toxic effects consisted of reversible myelosuppression. Menogaril was discontinued in 2 patients due to prolonged neutropenia. Cardiotoxicity was observed in 4 patients, requiring discontinuation of the drug in 1 patient. No treatment-related deaths occurred and the overall toxicity was felt to be acceptable. CONCLUSION: The observed antitumor activity of single agent menogaril against both intermediate/high-grade and low-grade lymphomas was modest. Further exploration of this agent in patients with non-Hodgkin's lymphomas does not seem warranted.

Aged↗

PubMed1998

Modeling postradiation prostate specific antigen level kinetics: predictors of rising postnadir slope suggest cure in men who remain biochemically free of prostate carcinoma.

BACKGROUND: The goals of this study are twofold: 1) to describe the postradiation kinetics of nonrecurring prostate carcinoma based on prostate specific antigen (PSA) levels in men who remain biochemically free of disease; and 2) to determine predictors of all three components of the resulting piecewise exponential model based on pretreatment and treatment characteristics. METHODS: Between March 1988 and May 1994, 153 patients with T1-T3 nonmetastatic prostate carcinoma were treated definitively with radiation therapy and at last follow-up had not failed biochemically (PSA rising on 2 consecutive occasions to a level > 1.0 ng/mL or 3 consecutive elevations). All patients were required to have at least 6 posttreatment PSA determinations and a minimum follow-up of 36 months. The median follow-up was 53 months (range, 36-94 months). A piecewise exponential model was used to describe the mean PSA levels because 1) the kinetics of postradiation PSA levels appear to follow first-order rate processes, and 2) there is evidence that PSA levels may rise slightly several years after treatment. Nonlinear mixed effects modeling was used in this situation because of the aforementioned nonlinearity and because variability between patients and within patients (PSA variation) must be taken into account. In addition, this methodology allows for modeling parameters as a function of patient and treatment characteristics. RESULTS: The random effects model based on the entire patient population demonstrated that PSA levels do not continue to drop 3 years after treatment, and that in fact the levels begin to rise slowly between 2-3 years after treatment. Pretreatment PSA was the only independent predictor of baseline PSA at time zero (end of radiation therapy). Gleason score was the only independent predictor of the rate of PSA decline after treatment, in which tumors with Gleason scores 7-10 drop at a slower rate than do tumors with Gleason scores 2-6. Finally, pretreatment prostate volume was the only independent predictor of the postnadir rise in PSA level, in which larger volumes translate to a steeper slope. CONCLUSIONS: The fact that pretreatment PSA level is the only independent predictor of the baseline PSA at time zero is not surprising. The observation that patients with tumors with higher Gleason scores have a slower rate of decline is in agreement with previous reports that these tumors contribute less PSA per unit volume than do tumors with moderate to well differentiation. Finally, the fact that no tumor-related characteristic (only pretreatment prostate volume) was predictive independently of the observed postnadir rise in PSA level suggests that these patients were cured.

Aged↗

PubMed1998

13-cis-retinoic acid or all-trans-retinoic acid plus interferon-alpha in recurrent cervical cancer: a Southwest Oncology Group phase II randomized trial.

PURPOSE: Preclinical and clinical data support the study of retinoids and interferon-alpha (IFN-alpha) in advanced squamous cell carcinoma of the uterine cervix (SCC). This phase II randomized trial of the Southwest Oncology Group sought to estimate the response rate for IFN-alpha plus either 13-cis-retinoic acid (13cRA) or all-trans-retinoic acid (ATRA) in women with recurrent cervical SCC. PATIENTS AND METHODS: Eligibility for this trial required bidimensionally measurable locally recurrent or metastatic squamous or adenosquamous carcinoma of the uterine cervix; SWOG performance status of </=2; no prior interferon, retinoids, or chemotherapy (except as radiation sensitization). All but two patients were previously treated with surgery, radiation therapy, or both. After randomization, patients received IFN-alpha-2A (subcutaneous injection; 3 x 10(6) units/m2/day) plus either 13cRA (1 mg/kg/day orally) or ATRA (150 mg/m2/day orally) in two equally divided doses. RESULTS: Total enrollment was 63 patients, 21 in the ATRA arm, 42 in the 13cRA arm. Three patients were ineligible, 1 in the ATRA arm, 2 in the 13cRA arm. Each arm had 1 patient who received no assigned treatment and was not evaluated for response or toxicity. The ATRA/IFN-alpha response rate was 5% (1/19; 95% confidence interval = 0.1-26%), consisting of 1 partial response lasting 4 weeks. The 13cRA/IFN-alpha response rate was 8% (3/39; 95% confidence interval = 2-21%), consisting of 3 partial responses lasting 17, 22, and 24 weeks, respectively. All confirmed responses were partial. One additional unconfirmed partial response occurred in the 13cRA arm. Both regimens were generally well-tolerated and produced toxicities (principally malaise and fatigue) associated with each constituent agent's known single-agent side effects. CONCLUSION: Based upon the results of this study, neither regimen can be recommended for further study in patients previously treated with radiation therapy.

Adult↗

PubMed1998

Detection and identification of Mycobacterium tuberculosis directly from sputum sediments by ligase chain reaction.

Sputum specimens received for the diagnosis of tuberculosis or other mycobacterial infections were tested by a ligase chain reaction (LCR)-based assay and acid-fast stain and culture techniques. Results from the LCR assay (Abbott LCx Mycobacterium tuberculosis [MTB] Assay) were compared to results from standard culture techniques held for 6 weeks. Four hundred ninety-three specimens from 205 patients suspected of pulmonary tuberculosis were included in the prospective study. Thirty-four (6.9%) of the specimens were culture positive for M. tuberculosis, and 13 (38%) of these were also fluorochrome stain positive. LCR sensitivities and specificities compared to culture were 74 and 98%, respectively. LCR sensitivity was 100% for fluorochrome stain-positive specimens and 57% for fluorochrome stain-negative specimens. Nine LCR-negative, culture-positive specimens were the result of low concentrations of M. tuberculosis. No inhibitors were detected in any of these specimens. Of the eight LCR-positive, culture-negative specimens, five were from patients with active tuberculosis. With these considered culture misses, final LCR sensitivity, specificity, positive predictive value, and negative predictive value were 77, 99, 91, and 98%, respectively. The same performance values for the fluorochrome acid-fast bacillus smear were 33, 98, 62, and 94%, respectively. After normal laboratory sputum processing, the Abbott LCx MTB Assay can be completed in 6 h. Thus, it is possible to have results available within 8 h of specimen submission.

DNA Ligases↗

PubMed1998

Phase II study of mitoguazone, cyclophosphamide, doxorubicin, vincristine and prednisone for patients with diffuse histologic subtypes of non-Hodgkin's lymphoma: an Eastern Cooperative Oncology Group Study (PE481).

Mitoguazone, an investigational agent with significant activity in advanced lymphoma, was added to a modified CHOP regimen (COPA) in an effort to improve the activity of standard therapy in 66 previously untreated patients with stages II-IV lymphoma and diffuse histology of intermediate or high grade other than lymphoblastic in this phase II pilot study. The regimen was well tolerated and the complete response rate in diffuse large cell lymphoma was 55%. Sixty-five percent of all complete responders were in complete response for at least one year. Despite these excellent results. it is unlikely that the addition of mitoguazone improved results compared with those obtained with standard therapy alone, since similar results have been frequently reported with the latter.

Adult↗

PubMed1998

Overview of prognostic factors in non-Hodgkin's lymphoma.

The non-Hodgkin's lymphomas are a biologically heterogeneous group of diseases with varying clinical presentations and outcomes. A number of studies have identified variables that carried independent prognostic significance. Although several staging systems had evolved that incorporated these prognostic variables, they were still unable to predict outcome. Ideally, the object of a staging system is to predict the likelihood of treatment response, time to progression or disease-free survival, and overall survival, and to provide a way to compare the outcome of similar groups of patients among various clinical trials. The need for such a system led to the creation of prognostic models such as the M.D. Anderson Tumor Score and, more recently, the International Prognostic Index. These prognostic models may identify those patients at highest risk for treatment failure, thereby identifying those patients who may require different therapeutic approaches.

Biomarkers, Tumor↗

PubMed1997

Alpha-1-acid (AAG, orosomucoid) glycoprotein: interaction with bacterial lipopolysaccharide and protection from sepsis.

In the acute phase response to a variety of insults a rise in the levels of the acute phase proteins, including elevations of serum alpha 1 acid glycoprotein (AAG) occurs. The physiological role of AAG is unknown, however, the time course of AAG production in the acute phase response together with its strong affinity for basic compounds suggests that AAG may function as an immune modulator to bind both exogenous and endogenous inflammatory mediators. Using E. coli lipopolysaccharide (LPS), an initiator of the acute inflammatory response associated with septic shock, we demonstrate that AAG-LPS complexes can activate mouse macrophages in vitro. In a mouse animal model of sepsis, AAG was shown to protect against meningococcal endotoxin. To pursue the mechanism of AAG action we demonstrated that AAG interacts directly with LPS using dynamic light scattering particle sizing and particle mobility. We also determined the enthalpy of interaction of AAG and LPS and showed that AAG leads to agglutination of LPS impregnated rabbit red blood cells. These studies suggest that AAG may function as an immune-modulator in the acute phase response, possibly by counter-regulating the activity of macrophage pro-inflammatory cytokines.

Animals↗

PubMed1997

Management of lymphoma recurrence after allogeneic transplantation: the relevance of graft-versus-lymphoma effect.

Donor lymphocyte infusions, by virtue of a graft-versus-tumor effect, have been shown to induce remissions in leukemia that recurs after allogeneic bone marrow transplantation. Similar effects have been postulated to contribute to the decreased recurrence rate observed after allogeneic transplantation in non-Hodgkin's lymphoma. This lower recurrence rate may be due to a variety of other mechanisms. We aimed to evaluate the role of graft-versus-lymphoma effects in patients in whom lymphomas recur after allogeneic transplantation. At the time of recurrence, immunosuppressive therapy was withheld. Patients with non-responding disease received an infusion of donor lymphocytes. Patients were observed for response and graft-versus-host disease. Disease in four of nine patients responded to withdrawal of immunosuppressive therapy. A minor response was observed in one of three recipients of donor lymphocyte infusions. Responses were observed among two patients with follicular lymphoma, one with large cell lymphoma and one with lymphoblastic lymphoma. A minor response was observed in a patient with prolymphocytic leukemia/lymphoma. We conclude that withdrawal of immunosuppressive therapy and donor lymphocyte infusion can induce durable remissions in patients with recurrent lymphoma after allogeneic transplantation.

Adult↗

PubMed1997

Recombinant interleukin-2 in combination with recombinant interferon-gamma in patients with advanced malignancy: a phase 1 study.

Because interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) act synergistically in vitro in the generation of lymphokine-activated killer (LAK) cells. we initiated a clinical trial of these lymphokines in combination. Twenty patients with advanced malignancy were treated at fixed dose levels of recombinant IFN-gamma given by intramuscular (i.m.) injections once a day and recombinant IL-2 given by an intravenous (i.v.) bolus injection 3 times a day for 7 days after a 3-day treatment with fixed doses (250 micrograms/m2/day) of IFN-gamma alone. A minimum of four patients were treated at each of the four dose levels studied. The side effects of the combination therapy were similar to those seen with individual lymphokines and included fever and chills, myalgia, headache, fatigue, nausea. vomiting, peripheral edema, skin rash, and hypotension. The maximum tolerated dose for the combination after a fixed dose of IFN-gamma was 2 x 10(5) U/M2/day (10 micrograms/m2/day) of IFN-gamma and 3 x 10(6) U/M2/day of IL-2, with fluid retention as the dose-limiting toxicity. Whereas natural killer (NK) or LAK activity or both were significantly increased in four of eight patients studied, only one patient with renal cell cancer had a minor response for four treatment cycles. We conclude that combination therapy with cytokines IL-2 and IFN-gamma given in this schedule had manageable toxicity and exhibited immunomodulatory effects in some patients but had no significant antitumor activity in this patient population.

Adult↗

PubMed1996

Evaluation of a deoxyribonucleic acid probe for the detection of Trichomonas vaginalis in vaginal secretions.

OBJECTIVE: Our purpose was to compare Affirm VP, a new deoxyribonucleic acid probe test, with standard "wet preparation" microscopic examinations and culture for the identification of Trichomonas vaginalis organisms in vaginal secretions. STUDY DESIGN: We examined vaginal samples from 615 women with symptoms or signs of vaginitis for T. vaginalis using the deoxyribonucleic acid probe test, microscopic examination of wet preparations of vaginal secretions, and culture in modified Diamond's medium. RESULTS: T. vaginalis was identified in specimens from 95 (15.4%) of the 615 patients. Cultures in Diamond's medium identified 93 (98%) of the 95 infected patients. Vaginal wet preparation identified 76 (80%) of the infected women. The deoxyribonucleic acid probe test detected 86 (90.5%) of the 95 infected patients. There was one false-positive deoxyribonucleic acid probe test (specificity 519/520: 99.8%). CONCLUSION: The Affirm VP deoxyribonucleic acid probe test had a sensitivity of 90% and a specificity of 99.8% for the identification of T. vaginalis organisms in women with symptoms with a high prevalence of trichomoniasis. Such a nonculture test may be of considerable benefit in diagnosing T. vaginalis infections, especially in settings where microscopy, culture, or both are unavailable, inconvenient, or unreliably performed.

Animals↗

PubMed1996

Amplification of rRNA for assessment of treatment response of pulmonary tuberculosis patients during antimicrobial therapy.

The time course of persistence of Mycobacterium tuberculosis as measured by detection of rRNA, acid-fast bacillus (AFB) smear, and culture was determined for pulmonary tuberculosis patients during antimicrobial therapy. Twenty-three patients who were initially AFB smear positive and who subsequently completed a course of antimicrobial therapy were selected for the study. Sequential specimens were tested by AFB smear, culture, and rRNA amplification (Gen-Probe Amplified Mycobacterium Tuberculosis Direct Test [MTD]). The initial diagnostic specimens of all patients were positive by culture; those of 22 patients (96%) also were positive by MTD. Overall, MTD results remained positive longer than both smear and culture results. The median times to the last positive test result were 9 days for AFB smear, 26 days for culture, and 30 days for MTD. The last positive test result was the AFB smear result in 4% of cases, the culture result in 22%, and the MTD result in 52%. Fifty-six percent of patients had a period of shedding of noncultivable M. tuberculosis which was detected by MTD after culture results had converted to negative. This noncultivable period lasted 7 to 245 days. All three tests became reproducibly negative before the end of therapy and remained negative during follow-up for up to 1 year. These results indicate that during successful antimicrobial therapy, M. tuberculosis is eliminated in sputum samples as measured by amplification of rRNA, as well as by AFB smear and culture. No long-term rRNA carrier state was detected. While the time course of clearance of M. tuberculosis measured by rRNA overall was longer than with the two traditional tests, the rRNA test results allow sensitive and precise measurement of the clearance of noncultivable M. tuberculosis from respiratory specimens. This attribute may allow rRNA testing to be useful in clarifying patient response to antimicrobial therapy.

Adult↗