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Biomedical subjects

M Stek

Publications and source records attributed to M Stek.

At least 19 recordsLinked to original sources
PubMed2005

Indinavir/ritonavir 800/100 mg bid and efavirenz 600 mg qd in patients failing treatment with combination nucleoside reverse transcriptase inhibitors: 96-week outcomes of HIV-NAT 009.

OBJECTIVE: Nucleoside reverse transcriptase (NRTI) sparing is a favourable option for patients with NRTI failure or toxicity. METHODS: Patients judged to be failing NRTI therapy were enrolled in a single-arm, open-label study of indinavir/ritonavir (IDV/r) 800/100 mg twice a day (bid)+efavirenz (EFV) 600 mg once a day (qd). The primary endpoint was the change in time-weighted average HIV RNA from baseline. The initial 48-week protocol was extended to 96 weeks by a single amendment. Analysis was by intention to treat. RESULTS: Sixty-one patients (23 female) were enrolled in the study. Baseline median inter-quartile range (IQR) NRTI exposure was 4.4 (3.9-4.7) years; baseline median viral load was 4.09 log(10) HIV-1 RNA copies/mL (range 3.75-4.61 log(10) copies/mL); baseline median CD4 count was 169 cells/microL (range 60-277 cells/microL). The mean (SD) change in time-weighted average HIV RNA from baseline at 48 and 96 weeks was -2.1 (0.7) and -2.1 (0.8) log(10) copies/mL respectively, resulting in 87% and 69% of patients with HIV RNA <50 copies/mL. Sixteen per cent of patients permanently ceased therapy and 26% underwent temporary drug interruptions because of study drug-related adverse events. Fasted-lipid values rose significantly over the 96 weeks of study, as did median blood glucose and median serum creatinine levels. Twelve (20%) patients underwent IDV dose reduction, mainly because of nephrotoxicity (nine of 12 patients). Blood pressure values deteriorated following switch, but markers of nucleoside toxicity improved. CONCLUSIONS: IDV/r 800/100 mg bid+EFV 600 mg qd gave a potent, durable response in these NRTI failures and was reasonably well tolerated. However, we observed adverse effects on renal, metabolic and blood pressure parameters. Lower doses of boosted IDV might improve toxicity while maintaining efficacy, and this possibility warrants further investigation.

Adult↗
PubMed2005

Pharmacokinetic interaction study of indinavir/ritonavir and the enteric-coated capsule formulation of didanosine in healthy volunteers.

Didanosine enteric-coated should be taken on an empty stomach, but the once-daily combination of indinavir/ritonavir can be taken with food. Because these drugs are frequently included in 1 regimen, the food effects on the pharmacokinetics were evaluated. This was a randomized, 4-way crossover study of single doses of didanosine enteric-coated 400 mg and indinavir/ritonavir 1200/400 mg in 8 healthy subjects. The following regimens were given: didanosine enteric-coated 2 hours after breakfast (reference regimen A), indinavir/ritonavir with breakfast (reference regimen B), didanosine enteric-coated + indinavir/ritonavir 2 hours after breakfast (test regimen C), and didanosine enteric-coated + indinavir/ritonavir with breakfast (test regimen D). Breakfast was 550 kcal, 28% fat. Blood samples were drawn before and up to 24 hours after ingestion. Statistical comparisons of test regimens C and D with reference regimens A and B were made using the equivalence approach for indinavir and didanosine area under the curve and C(max) (0.80-1.25). Eight subjects (5 men, 3 women) were enrolled and completed the study. Indinavir area under the curves were bioequivalent in test regimens C and D compared to reference regimen B. A 14% increased C(max) was observed in test regimen C. Didanosine area under the curve in test regimen D was 4% lower and suggestive of bioequivalence compared to reference regimen A. However, test regimen C didanosine area under the curve was 23% lower and bioinequivalent compared to reference regimen A. Didanosine C(max) decreased 42% and 46% in test regimens C and D, respectively, in comparison to reference regimen A. In this study, dosing didanosine enteric-coated 400 mg once daily + indinavir/ritonavir 1200/400 mg once daily with breakfast indicated no decrease in the amount of absorption for either didanosine and indinavir and that this regimen could be administered with food.

Administration, Oral↗
PubMed2000

Dose-finding study of a once-daily indinavir/ritonavir regimen.

In antiretroviral therapy, to improve compliance the need is increasing to develop regimens that combine potency and safety with convenient dosing. The objective of our study was to find a once-daily dosing regimen of a HIV-protease inhibitor, indinavir (IDV), by combining it with ritonavir (RTV). In the study, 12 healthy volunteers took a single IDV dose of 800 mg on day 1. Plasma and urine sampling was done for 12 hours. From day 2 to day 21, participants took RTV liquid 200 mg (group A) or 400 mg (group B) once daily. Repeated pharmacokinetic sampling was performed over the course of 24 hours, after single doses of indinavir 400 mg (day 15), 800 mg (day 18), and 1200 mg (day 21). The best dosage regimen in this pharmacokinetic study was selected based on efficacy and tolerability criteria. The study comprised 10 male and 2 female healthy volunteers, mean age, 25 years (range, 18-50 years), mean weight, 70 kg (range, 52-83 kg). One male participant discontinued on day 8 due to influenza. All other participants completed the study without the occurrence of serious adverse events. RTV inhibited indinavir plasma clearance by 51% to 70%, leading to increased and prolonged IDV exposure. Renal clearance was influenced by the addition of RTV and dosage increments of IDV. The efficacy criterion was best fulfilled by 1200 mg IDV/400 mg RTV, whereas this combination performed most poorly on tolerability criteria. Based on the single dose data, a once-daily regimen of IDV with a low dose of RTV is possible. The best dosage regimen to start with among those studied here appears to be 1200 mg IDV/400 mg RTV, which could be decreased at steady state to 800 IDV/400 RTV or 1200 IDV/200 RTV if toxicity occurs. Steady-state pharmacokinetic data of once-daily IDV/RTV regimens in HIV-infected patients are warranted.

Adolescent↗
PubMed2000

Experience of healthcare workers taking postexposure prophylaxis after occupational HIV exposures: findings of the HIV Postexposure Prophylaxis Registry.

OBJECTIVE: To collect information about the safety of taking antiretroviral drugs for human immunodeficiency virus (HIV) postexposure prophylaxis (PEP). DESIGN: A voluntary, confidential registry. SETTING: Hospital occupational health clinics, emergency departments, private physician offices, and health departments in the United States. RESULTS: 492 healthcare workers (HCWs) who had occupational exposures to HIV, were prescribed HIV PEP, and agreed to be enrolled in the registry by their healthcare providers were prospectively enrolled in the registry. Three hundred eight (63%) of 492 of the PEP regimens prescribed for these HCWs consisted of at least three antiretroviral agents. Of the 449 HCWs for whom 6-week follow-up was available, 195 (43%) completed the PEP regimen as initially prescribed. Forty-four percent (n=197) of HCWs discontinued all PEP drugs and did not complete a PEP regimen. Thirteen percent (n=57) discontinued > or =1 drug or modified drug dosage or added a drug but did complete a course of PEP Among the 254 HCWs who modified or discontinued the PEP regimen, the two most common reasons for doing so were because of adverse effects attributed to PEP (54%) and because the source-patient turned out to be HIV-negative (38%). Overall, 340 (76%) HCWs with 6-week follow-up reported some symptoms while on PEP: nausea (57%), fatigue or malaise (38%), headache (18%), vomiting (16%), diarrhea (14%), and myalgias or arthralgias (6%). The median time from start of PEP to onset of each of the five most frequently reported symptoms was 3 to 4 days. Only 37 (8%) HCWs with 6-week follow-up were reported to have laboratory abnormalities; review of the reported abnormalities revealed that most were unremarkable. Serious adverse events were reported to the registry for 6 HCWs; all but one event resolved by the 6-month follow-up visit. Fewer side effects were reported by HCWs taking two-drug PEP regimens than by HCWs taking three-drug PEP regimens. CONCLUSIONS: Side effects from HIV PEP were very common but were rarely severe or serious. The nature and frequency of HIV PEP toxicity were consistent with information already available on the use of these antiretroviral agents. Clinicians prescribing HIV PEP need to counsel HCWs about PEP side effects and should know how to manage PEP toxicity when it arises.

Adolescent↗
PubMed1997

Precision and discriminatory ability of calcaneal bone assessment technologies.

To determine if measuring skeletal status at the calcaneus is a potentially valuable technique for diagnosing osteoporosis, we examined five calcaneal assessment techniques in 53 young normal women and 108 postmenopausal women with osteoporosis and compared these measurements to dual-energy X-ray absorptiometry (DEXA) at the calcaneus, hip, and spine. The five instruments, including single-energy X-ray absorptiometry (SEXA) and four quantitative ultrasound (QUS) instruments, were evaluated for precision, ability to discriminate osteoporotic from young normal subjects, and correlation to the other instruments. The coefficient of variation (%CV) for instrument, positioning, interobserver, and short-term precision of the five calcaneal instruments ranged from 1.34-7.76%, 1.63-7.00%, 1.84-9.44%, and 1.99-7.04%, respectively. The %CVs for positioning, interobserver, and short-term precision were similar for calcaneal DEXA, calcaneal SEXA, and stiffness (as measured by Achilles). The %CVs for instruments precision were similar between calcaneal DEXA and SEXA. The ability of the five calcaneal instruments to discriminate osteoporotic from young normal subjects was similar based on the analysis of area under the receiver operating characteristic curves (range 0.88-0.93) and equivalent to DEXA of the calcaneus and hip (0.88-0.93). The correlations between the measurements of five calcaneal instruments were strong (0.80 < or = r < or = 0.91, p < 0.001). These data suggest that although the precision is variable, the calcaneal QUS and SEXA instruments can discriminate between osteoporotic patients and young normal controls and appear to be a useful technique for assessment of osteoporosis.

Absorptiometry, Photon↗
PubMed1995

The American Urological Association symptom index: does mode of administration affect its psychometric properties?

PURPOSE: We determine whether self-administration and interviewer administration of the American Urological Association (AUA) symptom index are equivalent. MATERIALS AND METHODS: The AUA symptom index was administered twice to 41 visually impaired or illiterate men. Men who were able were randomized to self-administration first and then interviewer administration (43) or the reverse (40). RESULTS: The scores in each group were reliable. However, because we could not reject a differential carryover effect, the nonsignificant test of mode effect in the crossover design may have been invalid. At time 1 there was no significant difference between group mean scores for randomized patients (p = 0.13). CONCLUSIONS: Although the AUA symptom index should be self-administered when possible, interviewer administration appears to be acceptable.

Aged↗
PubMed1987

Early diagnosis of Schistosoma mansoni in mice using assays directed against cercarial antigens isolated by hydrophobic chromatography.

Two diagnostic assays are described for the early diagnosis of acute schistosomiasis, using a defined cercarial antigen preparation obtained by hydrophobic chromatography. Circulating IgM antibodies against this antigen fraction could be detected by ELISA as early as 1 wk after exposure in experimentally infected mice; IgM levels against other antigens and IgG levels against all the preparations examined were not significantly elevated until approximately 4-5 wk postinfection. Circulating antigen was detected as early as 3 days after exposure by a competitive inhibition ELISA using rabbit serum prepared against the cercarial antigen; antigen levels in the serum of mice with a 100-worm infection were found to exceed 100 ng/ml. Studies using sera from infected humans indicate that the assay can also recognize chronic S. mansoni, S. haematobium or S. japonicum infections. In a very limited field study, the specificity of the circulating antigen assay with regard to other helminthic infections was found to be 85%; sensitivity 100%. Preliminary characterization of the relevant antigen indicates that it is a relatively hydrophobic polypeptide with a molecular weight of approximately 41,000 daltons. The implications of these findings with regard to the treatment of travelers or the conduct of seroepidemiological studies in endemic areas are discussed.

Animals↗
PubMed1986

Development of circulating antigen assay for rapid detection of acute schistosomiasis.

A circulating antigen assay to detect acute schistosomiasis mansoni in experimentally infected mice has been developed. The competitive-inhibition enzyme-linked immunosorbent assay uses rabbit serum prepared against purified cercarial antigen. The assay detects a 100-worm infection as early as 1 week after exposure; circulating antigen levels in mouse serum exceeded 0.1 microgram/ml. Preliminary characterisation of the cercarial antigen shows that it is a hydrophobic polypeptide of approximate molecular weight 41,000. A rapid and accurate diagnosis of acute schistosomiasis in travellers would facilitate appropriate chemotherapy before the onset of pathology. A circulating antigen assay would also be valuable for seroepidemiological studies in areas where the disease is endemic.

Acute Disease↗
PubMed1985

Praziquantel for treatment of schistosomiasis in patients with advanced hepatosplenomegaly.

We evaluated praziquantel for therapy of active Schistosoma mansoni infection in 15 rural Egyptian males with hepatosplenic schistosomiasis. Criteria for inclusion in this study were two pre-treatment S. mansoni egg counts with a mean of greater than 100 eggs g-1 faeces and an enlarged spleen. Fourteen of 15 patients had hepatomegaly, five had ascites, and six had serum albumin below 3 g dl-1. Schistosoma haematobium infection (less than 10 eggs ml-1 urine) was present in three patients. Praziquantel was administered in a single oral dose of 30 mg kg-1 body weight. Eight of the 15 patients (53%) had mild and transient reactions in the form of fever (usually one day), gastrointestinal symptoms, headache and skin rash. Criteria for parasitological cure were the absence of live eggs in two stool samples and a negative rectal snip biopsy three months after therapy. Ten patients ceased to pass live eggs (cure rate 67%). For the five who were still passing live eggs there was a mean egg reduction of 95%. The three patients with S. haematobium demonstrated parasitological cures. We conclude that praziquantel is an effective and well tolerated drug for treatment of S. mansoni infection in patients with advanced hepatosplenic schistosomiasis, and it is the drug of choice for patients with coexisting S. haematobium infection.

Adolescent↗
PubMed1985

Comparison of an enzyme-linked immunosorbent assay using crude S. haematobium soluble egg antigen with a radioimmunoassay using purified S. mansoni egg antigen for the serodiagnosis of schistosomiasis haematobium.

An enzyme-linked immunosorbent assay (ELISA) using crude Schistosoma haematobium soluble egg antigen (ShSEA) was compared with a radioimmunoassay (RIA) employing purified heterologous species S. mansoni egg antigen (MSA1) for the serodiagnosis of schistosomiasis haematobium in a group of 45 Nigerian school children living in an area endemic for S. haematobium. Both assay systems appeared applicable. The ELISA proved to be more sensitive detecting 100% of the 27 parasitologically positive individuals while the RIA defined 89% of this group. Neither test had false-positive results for the 10 non-endemic area parasitologically negative controls, although the ELISA demonstrated that 56% of the 18 endemic area parasitologically negative controls had anti-ShSEA antibodies. The RIA indicated that 44% of this group had anti-MSA1 antibodies. These latter findings were interpreted as related to the hyperendemicity of schistosomiasis haematobium for the study area.

Adolescent↗
PubMed1984

Murine immunization by cesium-137 irradiation attenuated Schistosoma mansoni cercariae.

Cesium-137, becoming a more readily available ionizing gamma radiation source for laboratory use, was shown to effectively attenuate Schistosoma mansoni cercariae for vaccine production. In parallel comparison studies with the murine model, cesium-137 attenuated cercariae consistently afforded better (P greater than 0.05) protection than did the cobalt-60 prepared vaccine. Dose-response data indicated that the optimal total irradiation with cesium-137 was between 45 and 50 Krad.

Animals↗