Occult malignant breast lesions in 114 patients: relationship to age and the presence of microcalcifications

This study evaluates the mammographic findings in 352 patients, aged 30-85 years, who underwent spot localization and biopsy for evaluation of nonpalpable breast abnormalities. Malignancy was found at biopsy in 114 cases. The mammographic appearance (specifically, whether grouped microcalcifications, mass, or both were present) was correlated with patient age and histologic findings (specifically, whether the pathologic changes were infiltrating or noninfiltrating in nature). The prevalence of malignant conditions increased directly with age. The presence of grouped microcalcifications as the sole indicator of malignancy was seen in 100% (seven of seven) of the patients in the 30-39-year age group, 64% (18 of 28) in the 40-49-year age group, 37% (11 of 30) in the 50-59-year age group, 30% (seven of 23) in the 60-69-year age group, and 23% (six of 26) in the 70-85-year age group. Of the 49 tumors that were manifested solely as microcalcifications, 34 (69%) were noninfiltrating. The finding of grouped microcalcifications should be aggressively investigated, since it may indicate noninfiltrating carcinoma in an early stage, when the potential for cure is greatest.     

Implementation of intermittent preventive treatment with sulphadoxine-pyrimethamine for control of malaria in pregnancy in Kisumu, western Kenya

OBJECTIVE: In 1998, the Kenyan Ministry of Health introduced intermittent preventive treatment (IPT) with sulphadoxine-pyrimethamine (SP), one treatment dose in the second trimester (16-27 weeks) and one treatment dose between 28 and 34 weeks of gestational age, for the control of malaria in pregnancy. We evaluated the coverage and determinants of receipt of IPT after its introduction in the Provincial Hospital in Kisumu, western Kenya. METHODS: Information on the use of IPT in pregnancy was collected from women who attended the antenatal clinic (ANC) and delivered in the same hospital. In exit interviews, we assessed patterns of IPT use in the ANC. RESULTS: Of 1498 women who delivered between June 1999 and June 2000, 23.7%, 43.4% and 32.9% received > or =2, 1 or no dose of SP, respectively. Late first ANC attendance was the most important factor contributing to incomplete IPT; 45% of the women started attending ANC in the third trimester. More women received at least one tetanus toxoid immunization than at least one dose of IPT (94%vs. 67%, P < 0.05). In exit interviews, 74% correctly associated IPT with treatment of malaria; however, knowledge on the need for the second dose was poor. Three per cent of the administrations were given despite contraindications. The agreement between gestational age by date of last menstrual period and by palpation was low (kappa = 0.1). CONCLUSIONS: Education of pregnant women and ANC staff to increase earlier attendance for ANC has the potential to substantially increase the proportion of women receiving two doses of IPT with SP.     

Pharmacokinetics of sulfadoxine-pyrimethamine in HIV-infected and uninfected pregnant women in Western Kenya

BACKGROUND: Sulfadoxine-pyrimethamine (SP) is among the most commonly used antimalarial drugs during pregnancy, yet the pharmacokinetics of SP are unknown in pregnant women. HIV-infected (HIV(+)) women require more frequent doses of intermittent preventive therapy with SP than do HIV-uninfected (HIV(-)) women. We investigated whether this reflects their impaired immunity or an HIV-associated alteration in the disposition of SP. METHODS: Seventeen pregnant HIV(-) women and 16 pregnant HIV(+) women received a dose of 1500 mg of sulfadoxine and 75 mg of pyrimethamine. Five HIV(-) and 6 HIV(+) postpartum women returned 2-3 months after delivery for another dose. The pharmacokinetics of sulfadoxine and pyrimethamine were compared between these groups. RESULTS: HIV status did not affect the area under the curve (AUC(0-->infinity)) or the half-lives of sulfadoxine or pyrimethamine in prepartum or postpartum women, although partum status did have a significant affect on sulfadoxine pharmacokinetics. Among prepartum women, the median half-life for sulfadoxine was significantly shorter than that observed in postpartum women (148 vs 256 h; P<.001), and the median AUC(0-->infinity) was ~40% lower (22,816 vs 40,106 microg/mL/h, P<.001). HIV status and partum status did not show any significant influence on pyrimethamine pharmacokinetics. CONCLUSION: Pregnancy significantly modifies the disposition of SP, whereas HIV status has little influence on pharmacokinetic parameters in pregnant women.     

The fate of the open canalicular system in surface and suspension- activated platelets

We have examined the movement of fibrinogen-gold (fgn-Au) complexes in platelets activated in suspension and by surface contact. Fgn-Au probes did not react with resting cells but were bound to the external membrane of platelets in suspension 5 seconds after addition of 1 U/mL of thrombin. At intervals over a period of 5 to 20 minutes, fgn-Au probes moved from the cell surface to peripheral and then deep channels of the open canalicular system (OCS). When platelets were surface activated by exposure to carbon-stabilized, formvar-coated grids for 5 to 20 minutes and then exposed to fgn-Au complexes for 5 minutes, probes were also observed in the OCS. At 5 minutes, over 40% of the platelets had concentrated fgn-Au in their OCS. Results after 10 minutes revealed 25% with gold-filled channels, 16% after 15 minutes, and 5% after 20 minutes. The decrease in frequency of OCS staining correlated with the increasing frequency of spread platelets, suggesting that tension produced by spreading may cause collapse of the OCS or that the OCS may evaginate onto the platelet during spreading. To evaluate the latter hypothesis, platelets were initially exposed to grids for 5 minutes and then incubated with fgn-Au for intervals of 5 to 20 minutes. The frequency of platelets with fgn-Au concentrated in the OCS was greatest at 5 minutes (44%) and decreased at the same rate as the frequency of spread platelets increased. Only 14.7% of the cells contained fgn-Au in the OCS after 20 minutes. These were primarily dendritic in form, while fully spread platelets rarely contained an OCS filled with the probe. The study indicates that fgn-Au particles are cleared to channels of the OCS independent of the mechanism of platelet activation. Fgn-Au that has been concentrated in the OCS at early stages of surface activation can be externalized during platelet spreading but remain internalized in suspension-activated cells. The OCS represents a membrane reservoir that can be evaginated onto the platelet surface during interaction with surfaces.