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Biomedical subjects

F Lokiec

Publications and source records attributed to F Lokiec.

At least 19 recordsLinked to original sources
PubMed1996

Stress fracture of the proximal femur after screw removal.

We describe a case of stress fracture of the proximal femur occurring in a patient after removal of an internal fixation device for a comminuted subtrochanteric fracture. The presenting clinical picture resembled a late postoperative infection with a positive technetium and gallium bone scan and normal radiological findings. The stress fracture occurred after removal of the fixation device when the patient started full weight-bearing. The patient was treated initially as having osteomyelitis until a second X-radiograph some weeks later demonstrated a stress fracture through one of the previous screw holes. This case illustrates well the possible complication of a insufficiency fracture subsequent to the occurrence of stress risers through screw holes in a weakened bone when submitted to normal load. The clinical presentation may sometimes resemble late postoperative infection.

Adult↗
PubMed1995

Pharmacokinetics of irinotecan and its metabolites in human blood, bile, and urine.

Two patients were treated with CPT-11 for colorectal cancer and had a percutaneous biliary catheter for extrahepatic biliary obstruction. The first patient was treated with CPT-11 according to the 100-mg/m2 weekly therapeutic schedule, and the second patient was treated every 3 weeks, with a dose of 350 mg/m2 being given at the first course, after which it was decreased to 300 mg/m2 for the following courses. In plasma, the active identified metabolite of CPT-11, SN-38, occurred mainly in the form of a glucuronide conjugate. CPT-11 was mainly excreted in bile and urine as CPT-11. The cumulative biliary and urinary excretion of CPT-11 and its metabolites (SN-38 and SN-38 glucuronide conjugate) over a period of up to 48 h ranged from 25% (100 mg/m2 weekly) to 50% (300 mg/m2 every 3 weeks). This means that CPT-11 can be excreted under other, not yet identified metabolite forms.

Antineoplastic Agents, Phytogenic↗
PubMed1995

[Penetration of ceftriaxone (1 or 2 gr intravenous) into mediastinal and cardiac tissues in man].

Ceftriaxone penetration into heart tissues (valves, myocardium, auricles and pericardium) and mediastinal tissues (fat and sternal bone) was evaluated after two regimens of ceftriaxone administration. Ten patients were given 1,000 g intravenously of ceftriaxone 30 min. before anesthesia. Ten other patients received the same dose and then a second 1,000 mg dose at the time of initiation of cardiopulmonary bypass. Similar and very satisfactory ceftriaxone tissue penetrations were observed in both groups. However, for some patients in the two groups and mainly in the sternal bone at the time of thorax closure, ceftriaxone levels in tissues were less than the MICs for some potential pathogens (Methicillin susceptible Staphylococcus aureus and Staphylococcus epidermidis). During the different steps of the surgical procedures all patients in both groups had tissue levels greater than the MICs for Gram negative aerobic bacilli, except for Pseudomonas spp.

Adult↗
PubMed1994

Concentrations of ceftriaxone in cerebrospinal fluid of children with meningitis receiving dexamethasone therapy.

The penetration of ceftriaxone into cerebrospinal fluid (CSF) was studied with 11 children (mean age: 2 years, 4 months; range: 4 months to 8 years) with meningitis, receiving dexamethasone (0.15 mg/kg of body weight intravenously four times daily) as adjunctive therapy. Ceftriaxone was given intravenously at doses of 50 mg/kg twice daily to patients < 18 months old and 100 mg/kg once daily to patients > or = 18 months old. CSF was collected after 1 day of treatment at the expected peak concentration of ceftriaxone in CSF. Concentrations of ceftriaxone in CSF ranged from 0.7 to 9.2 mg/liter, with a mean value of 4.0 (standard deviation [SD], 2.9) mg/liter. Values were significantly higher for patients with CSF glucose levels of < 1 mmol/liter on admission to the hospital than for patients with CSF glucose levels of > or = 1 mmol/liter (mean values of 7.1 [SD, 2.2] mg/liter versus 2.2 [SD, 1.1] mg/liter; P < 0.001). After 1 day of treatment, ceftriaxone concentrations in the CSF of children receiving dexamethasone are similar to the mean values reported for children not treated with dexamethasone.

Ceftriaxone↗
PubMed1993

Human pharmacokinetics of a new Vinca alkaloid S 12363 with use of a monoclonal antibody-based radio- or enzyme immunoassay.

S 12363 is a new Vinca alkaloid derivative, characterized by the grafting of an alpha-aminophosphonate, onto the Vinca nucleus, facilitating drug penetration and increasing intracellular drug retention. As a high cytotoxic activity had been demonstrated in in vitro and in vivo models recommended by the National Cancer Institute, a phase I trial was initiated in cancer patients. In order to quantify S 12363 systemic levels in humans, two monoclonal antibody-based immunoassays, RIA (radio-) and EIA (enzyme immunoassay) were developed. The gamma-emitting probe used in the RIA, 125I-(deacetyl-O4-vinblastine)-tyramine, bound very tightly to the monoclonal antibody (dissociation constant, Kd = 2.5 x 10(-11) M), demonstrating a high affinity mainly directed toward the catharantine nucleus (vindesine, vincristine, vinblastine, 100% cross-reactivity; vinorelbine, 0.3% cross-reactivity). In the EIA, a deacetyl O4-vinblastine/ovalbumine conjugate was used as the competing antigen. Its binding to the monoclonal antibody was revealed by an anti-mouse immunoglobulin G conjugated to biotin which interacts with streptavidin labeled with alkaline phosphatase. This method permitted obtaining nearly the same sensitivity and reproducibility with EIA as with RIA, their respective minimum quantitation limits being 0.100 and 0.040 ng/ml (106 and 42 pM) of S 12363 in plasma. These assays allowed the study of S 12363 systemic pharmacokinetics in cancer patients during a phase I trial up to 72 h after dosing. As determined by RIA, the S 12363 plasma profile was triphasic with a terminal half-life; t1/2 gamma = 49 +/- 16 h, a plasma clearance, CL = 0.14 +/- 0.04 liter/h/kg, and a volume of distribution at steady state, Vdss = 5.0 +/- 2.8 liter/kg. The pharmacokinetics of S 12363 is linearly related to dose when increased from 0.08 up to 0.84 mg/m2 in humans. Its plasma profile and pharmacokinetic parameters are close to those of other Vinca alkaloids with clearance and terminal half-life being intermediate between those of vinblastine and vincristine. Therapeutic doses are 4 to 10 times lower and should be a direct consequence of the higher uptake and retention by the cells of this new aminophosphonate Vinca alkaloid derivative.

Adolescent↗
PubMed1993

Oral acyclovir and recurrent genital herpes during late pregnancy.

OBJECTIVE: To assess plasma acyclovir levels in pregnant women given oral acyclovir during late gestation and to determine the role and effect of oral acyclovir on asymptomatic shedding of virus in cases of recurrent genital herpes. METHODS: Five pregnant women with proven genital herpes isolate (herpes simplex virus [HSV] 2) after 37 weeks' gestation were studied. Oral acyclovir was administered every 8 hours at dosages of 300, 400, and 300 mg in two subjects, and 200 mg five times daily in the other three until delivery. Plasma acyclovir peak and trough levels were determined. Viral cultures were obtained from both the mothers and neonates at delivery. RESULTS: There was no difference in acyclovir plasma levels among the patients. Furthermore, acyclovir levels were comparable to those of nonpregnant adults. The drug failed to suppress asymptomatic shedding of virus and transmission of HSV 2 to the neonate in one of five of the patients. CONCLUSION: Our study suggests that asymptomatic shedding of virus is not prevented by use of oral acyclovir during late gestation in proven recurrent genital herpes even though plasma acyclovir levels were within the normal range.

Acyclovir↗
PubMed1993

Adhesions of distal tibiofibular syndesmosis. A cause of chronic ankle pain after fracture.

Ankle pain after uncomplicated ankle fractures poses a diagnostic and therapeutic challenge, especially in joints that exhibit insignificant radiographic changes. Ankle joint arthroscopy has become an important diagnostic and therapeutic tool for such cases. Adhesion of the distal tibiofibular syndesmosis, as yet an undescribed entity, was found to be the cause of chronic ankle pain in 11 of 19 patients suffering from chronic ankle pain after an uncomplicated fracture of the ankle. Symptoms resolved after arthroscopic resection of the adhesions in all 11 patients. Arthroscopy has an important role in diagnosis and management of unexplained ankle pain after a seemingly uncomplicated fracture.

Adult↗
PubMed1992

Effects of diclofenac on ceftriaxone pharmacokinetics in humans.

The effects of diclofenac, a nonsteroidal antiinflammatory drug, on the biliary and urinary excretion of ceftriaxone were evaluated in subjects with a T drain in the common bile duct. The kinetic study was carried out on the sixth postoperative day of treatment with ceftriaxone alone (2 g intravenously; group 1) or ceftriaxone combined with diclofenac (50 mg every 12 h orally from postoperative days 3 to 6; group 2). A significant increase in the elimination half-life of ceftriaxone was observed in group 2 patients. Diclofenac caused a significant rise in ceftriaxone biliary excretion. This increase was not sufficient to balance the significant deficit of urinary excretion of ceftriaxone.

Aged↗
PubMed1992

Pharmacokinetics and tissue penetration of a single dose of ceftriaxone (1,000 milligrams intravenously) for antibiotic prophylaxis in thoracic surgery.

The pharmacokinetics and tissue penetration of ceftriaxone after a single intravenous injection of 1,000 mg to 17 patients for antibiotic prophylaxis in thoracic surgery were studied. The patients were scheduled for elective noncardiac thoracic surgery. Adequate levels in serum (higher than or equal to the MIC for 90% of isolates of Staphylococcus aureus, Streptococcus spp., Escherichia coli, Haemophilus influenzae, and Klebsiella pneumoniae) were found for all patients throughout the surgical procedures. Mean maximal (5-min) and final (24-h) ceftriaxone levels in serum were 157 +/- 42 and 8.6 +/- 4.5 mg/liter, respectively. The beta-phase elimination half-life was 8.6 +/- 3 h, the plasma clearance was 18.4 +/- 6.25 ml/min, and the apparent volume of distribution at steady state was 0.21 +/- 0.07 liters/kg. At the time of the thoracotomy, the ceftriaxone concentrations were 13.5 +/- 7.8 micrograms/g in thoracic wall fat and 27 +/- 9 micrograms/g in lung tissue. At the time of closure, the ceftriaxone concentration was 15 +/- 9 micrograms/g in thoracic wall fat. During the different steps of the surgical procedures, 100% of patients had adequate levels in tissue (higher than or equal to the MIC for 90% of isolates of Streptococcus spp., E. coli, H. influenzae, and K. pneumoniae). For S. aureus, 90 to 100% of patients had adequate tissue ceftriaxone levels.

Adult↗
PubMed1992

Value of early pharmacodynamic and pharmacokinetic investigations with anticancer drugs: data from phase I tolerance studies on a new vinca alkaloid derivative.

1. A novel anticancer vinca alkaloid derivative (I) has been given as an i.v. bolus to cancer patients, using four different dosage regimens with dose levels ranging from 0.04 to 0.84 mg/m2 (equivalent to between 0.12 and 1.35 mg per dose), and the pharmacokinetics determined up to 72 h after dosing. In addition, secondary effects of leukopenia and neutropenia, were related to drug exposure using a sigmoid Emax model. 2. Plasma levels of I declined in a triphasic manner with a terminal half-life of approximately 50 h; most drug elimination (55%) being associated with the terminal phase. 3. Clearance of I was relatively low (245 +/- 160 ml/min) and remained constant with increasing doses. Initial distribution volume was low (approximately 71) but once distribution was complete, it was comparatively high (327 +/- 2121). 4. Both leukopenia and neutropenia were fitted successfully to a sigmoid Emax model showing that these effects were related to the total exposure to the drug. The Hill constant was less than 1, indicating a relatively shallow exposure/response curve and a predictable, graded increase in response with increasing I exposure, rather than a sudden quantal response. 5. Pharmacokinetically, I shows some similarities to other vinca alkaloids in its plasma level decline profile, although there are some notable differences which can be exploited clinically. In addition, the ability to model both leukopenia and neutropenia to the exposure to I, provides a valuable tool in the design of the most appropriate dosage regimen for the drug, as well as for dose adjustment taking into account inter-individual variations.

Adolescent↗
PubMed1992

The snapping biceps femoris syndrome.

Snapping of tendons is a well-described entity in the literature, occurring mostly in athletes around the hip, ankle, shoulder, and elbow, but rarely the knee. A case of snapping of the biceps femoris tendon (BFT) in a patient with a painful knee and no history of trauma is described. An abnormal anterior insertion of the BFT was found to be the cause of the pain and snapping. Surgical treatment, reinsertion of the tendon in its anatomic position, completely corrected the abnormality, whereas conservative treatment failed.

Adult↗
PubMed1992

[Prevention of fetal and neonatal transmission of the varicella-zoster virus].

Varicella occurs in 0.7 to 0.13% of pregnant women. The risk of transmission of the varicella-zoster virus to the fetus is small. The virus causes malformations (cutaneous scars and above all central nervous system anomalies). Mother-to-offspring transmission is more common during the perinatal period (20%), when mild or severe (fatal in 20% of cases) congenital varicella may occur. Prevention of transmission of the varicella-zoster virus from the mother to her fetus or neonate rests on detection of fetal varicella (antenatal ultrasonography, fetal IgM assays) and on administration of both specific anti-VZ virus immune globulins and acyclovir to the mother and neonate during the perinatal period.

Acyclovir↗