Stimulation of megakaryocyte and platelet production by a single dose of recombinant human thrombopoietin in patients with cancer.

BACKGROUND: Thrombocytopenia is frequently encountered in patients with cancer. It is associated with an increased risk for clinically important bleeding episodes, which increases the demand for platelet transfusion. OBJECTIVE: To assess hematopoietic response to and clinical tolerance of recombinant human thrombopoietin, a recently cloned novel cytokine. DESIGN: Phase I and II clinical cohort study. SETTING: The University of Texas M.D. Anderson Cancer Center, Houston, Texas. PATIENTS: 12 patients with sarcoma who had high risk for severe chemotherapy-induced thrombocytopenia. INTERVENTION: A single intravenous dose of thrombopoietin (0.3 to 2.4 micrograms/kg of body weight) 3 weeks before chemotherapy. MEASUREMENTS: Peripheral blood and bone marrow evaluation before and after thrombopoietin administration. RESULTS: A single dose of thrombopoietin was associated with an increase in platelet counts (mean increase from baseline, 61% to 213%; P = 0.002) in a dose-related manner. This increase began by day 4 in most patients and peaked on a median of day 12. This sustained response was associated with a prolonged serum thrombopoietin half life (20 to 30 hours). The platelets appeared morphologically normal and showed normal aggregation in response to various agonists. Platelet response was accompanied by a dose-related increase in bone marrow megakaryocytes (as much as 4-fold); the expansion of the bone marrow progenitors of myeloid, erythroid, multipotential, and megakaryocytic lineages; and the marked mobilization of progenitors (maximum, 5.7-fold to 10-fold) of multiple cell lineages in the peripheral blood. Treatment was well tolerated, and no serious adverse events occurred. CONCLUSIONS: Thrombopoietin, administered as a single dose, is a potent stimulus for prolonged platelet production in humans. It merits further evaluation for the prevention and treatment of thrombocytopenia.

Single-dose ampicillin/sulbactam versus ceftriaxone as treatment for uncomplicated gonorrhoea in a Ugandan STD clinic population with a high prevalence of PPNG infection.

During the period November 1989 to March 1991 a total of 330 patients (269 males and 61 females) with signs and symptoms of uncomplicated lower genital tract infections with Neisseria gonorrhoeae were treated at a sexually transmitted disease clinic in Kampala, Uganda. Patients were randomized for treatment with either intramuscular ampicillin/sulbactam (1 g ampicillin/0.5 g sulbactam), plus 1 g probenecid orally, or ceftriaxone (250 mg). In those cases where N. gonorrhoeae was isolated and the patients returned for a follow-up visit, 70/74 (95%) of the patients treated with ampicillin/sulbactam and 71/72 (99%) of those treated with ceftriaxone had favourable clinical outcomes. All 24 patients with penicillinase-producing N. gonorrhoeae (PPNG) treated with ampicillin/sulbactam had a favourable clinical outcome compared with 95% (20/21) of those with PPNG treated with ceftriaxone. The infecting pathogen was eradicated in 65/71 (92%) of the evaluable patients treated with ampicillin/sulbactam and in 60/63 (95%) of the ceftriaxone group. Both drug regimens were well tolerated and there were no reports of adverse drug effects. In summary, in a predominantly male group of clinic patients in Kampala, Uganda, ampicillin/sulbactam was as safe and effective as ceftriaxone in treating uncomplicated gonococcal infections of the lower genital tract caused by either PPNG or non-PPNG strains.

The value of a clinical definition for epidemic KS in predicting HIV seropositivity in Africa.

Kaposi's sarcoma (KS) in African adults can present in endemic (non-HIV-related) and epidemic (HIV-related) forms. We evaluated the usefulness of a clinical case definition for epidemic KS in predicting HIV seropositivity. A total of 235 patients with KS presenting to the Uganda Cancer Institute from January 1, 1988 to March 31, 1990 were evaluated with history and physical examination. Symptomatic patients underwent chest radiography and upper gastrointestinal endoscopy. One hundred seventy-four patients (80%) underwent HIV ELISA testing with Western blot confirmation. The clinical case definition had a 91% sensitivity and a 95% specificity in predicting HIV seropositivity. Oral KS was the most sensitive specific site of involvement in predicting HIV seropositivity. The clinical case definition is useful in assessing patients to determine prognosis and likelihood of responding to aggressive therapy.

The value of a clinical definition for epidemic KS in predicting HIV seropositivity in Africa

Kaposi's sarcoma (KS) in African adults can present in endemic (non-HIV-related) and epidemic (HIV-related) forms. We evaluated the usefulness of a clinical case definition for epidemic KS in predicting HIV seropositivity. A total of 235 patients with KS presenting to the Uganda Cancer Institute from January 1; 1988 to March 31; 1990 were evaluated with history and physical examination. Symptomatic patients underwent chest radiography and upper gastrointestinal endoscopy. One hundred seventy-four patients (80pc) underwent HIV ELISA testing with Western blot confirmation. The clinical case definition had a 91pc sensitivity and a 95pc specificity in predicting HIV seropositivity. Oral KS was the most sensitive specific site of involvement in predicting HIV seropositivity. The clinical case definition is useful in assessing patients to determine prognosis and likelihood of responding to aggressive therapy