Radiographic assessment in total knee arthroplasty

Sixty-five total knee arthroplasties were evaluated by the Knee Society Radiological Evaluation System which was developed to encourage uniform reporting of the results of total knee arthroplasty. All patients were examined by three independent experienced radiologists 8.9 years after surgery (range, 3-16 years) to analyze the interobserver variability. For measurement of angles, high interobserver correlation was calculated for the prosthetic component angles and the femorotibial shaft angle. The comparison of the means indicated no significant differences except for the femorotibial shaft angle. For measurement of radiolucent lines, interobserver correlation was low for all components. The differences of the means were significantly different for all components. The results of interobserver variability of the patellar evaluation revealed high interobserver correlation for the patellar angle and for patellar subluxation and dislocation evaluation. For assessment of patellar mediolateral and superoinferior displacement, a low interobserver correlation was found. For radiographic assessment of total knee arthroplasty, the measurement of angles, including alpha, beta, femorotibial shaft angle, sagittal femoral and tibial component angle, patellar angle, and patellar subluxation and dislocation evaluation are recommended. The method of assessing radiolucent lines should be reconsidered.     

Anopheles gambiae pilot gene discovery project: identification of mosquito innate immunity genes from expressed sequence tags generated from immune-competent cell lines

Together with AIDS and tuberculosis, malaria is at the top of the list of devastating infectious diseases. However, molecular genetic studies of its major vector, Anopheles gambiae, are still quite limited. We have conducted a pilot gene discovery project to accelerate progress in the molecular analysis of vector biology, with emphasis on the mosquito's antimalarial immune defense. A total of 5,925 expressed sequence tags were determined from normalized cDNA libraries derived from immune-responsive hemocyte-like cell lines. The 3,242 expressed sequence tag-containing cDNA clones were grouped into 2,380 clone clusters, potentially representing unique genes. Of these, 1,118 showed similarities to known genes from other organisms, but only 27 were identical to previously known mosquito genes. We identified 38 candidate genes, based on sequence similarity, that may be implicated in immune reactions including antimalarial defense; 19 of these were shown experimentally to be inducible by bacterial challenge, lending support to their proposed involvement in mosquito immunity.     

Excretion and biotransformation of cisapride in dogs and humans after oral administration

The excretion and biotransformation of cisapride, a novel gastrokinetic drug, were studied after a single po dose of [14C]cisapride in dogs and humans. The excretion of radioactivity amounted to 97% within 4 days after a 1 mg/kg dose in dogs (72% in feces and 25% in urine). After a 10-mg dose in humans, 44% was excreted in the 0-24-hr urine and 37% in the 0-35-hr feces; excretion was complete within 4 days. Excretion of the parent drug was greater in dogs (0.4-1.3% of the dose in urine, 23% in feces) than in humans (0.2% in urine, 4-6% in feces). This was due, at least in part, to a larger proportion of amine glucuronidation and sulfation in dogs. N-Deal-kylation at the piperidine nitrogen resulting in the main urinary metabolite, norcisapride, and aromatic hydroxylation of the 4-fluorophenyl ring were major metabolic pathways in both species. Norcisapride excretion accounted for 14% of the dose in dogs and 41-45% in humans. Minor metabolic pathways were O-dealkylation at the 4-fluorophenoxy group and piperidine oxidation. Peak plasma levels and AUC values of norcisapride in humans were 8-9 times lower than those of cisapride. Apart from more amine conjugation in dogs, the biotransformation of cisapride was similar in dogs and humans.     

Pharmacokinetics of sufentanil in general surgical patients under different conditions of anaesthesia

The pharmacokinetics of sufentanil were studied in 56 surgical patients after an intravenous bolus of 2 μg kg^-1, in association with neurolept analgesia or volatile anaesthetics (halothane, enflurane and isoflurane). Plasma concentrations of sufentanil were measured by radioimmunoassay. The kinetics of sufentanil were comparable under neurolept analgesia and under anaesthesia with halothane, enflurane or isoflurane. The overall mean elimination half-life was 182 min, Vd⁸⁵ 169 1 and the plasma clearance 910 ml min^-1. Except for the isoflurane subgroup, there was no significant correlation between half-life, the volume of distribution or clearance with age (24–77 years) or body weight (45–95 kg).     

PO-2-PCO-2-pH-nomograms for rat blood at 37 degrees C (author's transl)]

In order to determine the interdependence of the parameters of the respiratory gas transport in rat blood (Sprague-Dawley) CO-2-equilibration curves in fully oxygenated and deoxygenated blood are measured. The results are presented in the form of pH-log P-CO-2-diagrams. O-2-dissociation curves of rat blood are registered at different CO-2 partial pressures. The P-02 at S-02 equals 50% ranged between 27.7 mm Hg for P-C0-2 equals 20 mm Hg. 35.1 mm Hg for P-C0-2 equals 40 mm Hg and 42.2 for P-C0-2 equals 60 mm Hg. Cartesian and alignment nomograms are constructed using CO-2 equilibration curves and O-2 dissociation curves. These nomograms give the interrelations between P-O-2, P-CO-2, pH and S-0-2 of rat blood. Separate nomograms are presented for Hb-concentrations of 10-13 g-% and 13.1-16 g-% because of great variations of Hb concentration in rat blood. If two of these values are known the nomograms permit the reading of the remaining paramters.     

Assessment of gestational age: a simplified scoring system

Because of the disadvantages of the Dubowitz score in very ill preterms, an alternative score based on 7 morphological items was designed, and the results are compared to those of the Dubowitz score in 229 newborns. This scoring system proved to be reliable and easy to perform; standard deviation was +/- 10.2 days versus 9.7 days for the Dubowitz score.     

Distinct molecular phenotype of malignant CD34(+) hematopoietic stem and progenitor cells in chronic myelogenous leukemia

Chronic myelogenous leukemia (CML) is a malignant disorder of the hematopoietic stem cell characterized by the BCR-ABL oncogene. We examined gene expression profiles of highly enriched CD34(+) hematopoietic stem and progenitor cells from patients with CML in chronic phase using cDNA arrays covering 1.185 genes. Comparing CML CD34(+) cells with normal CD34(+) cells, we found 158 genes which were significantly differentially expressed. Gene expression patterns reflected BCR-ABL-induced functional alterations such as increased cell-cycle and proteasome activity. Detoxification enzymes and DNA repair proteins were downregulated in CML CD34(+) cells, which might contribute to genetic instability. Decreased expression of junction plakoglobulin and CXC chemokine receptor 4 (CXCR-4) might facilitate the release of immature precursors from bone marrow in CML. GATA-2 was upregulated in CML CD34(+) cells, suggesting an increased self-renewal in comparison with normal CD34(+) cells. Moreover, we found upregulation of the proto-oncogene SKI and of receptors for neuromediators such as opioid mu1 receptor, GABA B receptor, adenosine A1 receptor, orexin 1 and 2 receptors and corticotropine-releasing hormone receptor. Treatment of CML progenitor cells with the selective adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) resulted in a dose-dependent significant inhibition of clonogenic growth by 40% at a concentration of 10(-5) M, which could be reversed by the equimolar addition of the receptor agonist 2-chloro-N6-cyclopentyladenosine (P<0.05). The incubation of normal progenitor cells with DPCPX resulted in an inhibition of clonogenic growth to a significantly lesser extent in comparison with CML cells (P<0.05), suggesting that the adenosine A1 receptor is of functional relevance in CML hematopoietic progenitor cells.     

Phase II trial of gemcitabine/irinotecan in refractory or relapsed small-cell lung cancer

BACKGROUND: Gemcitabine and irinotecan have shown a broad range of activity in solid tumors, including small-cell lung cancer (SCLC), with a synergistic effect on SCLC cell lines. The objective of this phase II trial was to evaluate the activity of gemcitabine/irinotecan in patients with relapsed SCLC. PATIENTS AND METHODS: Thirty-five patients (15 with refractory disease and 20 with sensitive disease) who had experienced treatment failure with 1 previous chemotherapy regimen were recruited. Treatment consisted of gemcitabine 1,000 mg/m(2) and irinotecan 100 mg/m(2) on days 1 and 8 of a 21-day cycle for a maximum of 6 cycles. Eligibility criteria included an Eastern Cooperative Oncology Group performance status of 0-2, adequate organ function, and signed informed consent. RESULTS: All 35 patients were assessable for response, survival, and toxicity. Best objective responses exhibited were as follows: complete response in 2 patients (6%), partial response in 4 (11%; 95% confidence interval [CI], 21%-61%), stable disease in 7 (20%; 95% CI, 9%-45%), and progressive disease in 22 (63%; 95% CI, 17%-57%). Median time to disease progression was 3.4 months and median survival was 5.8 months. The 1-year survival rate was 34%. Toxicity was mainly hematologic. Grade 3/4 nausea and vomiting occurred in 9% of patients, neuropathy occurred in 2.8%, and diarrhea occurred in 14.3%. Survival was not significantly different for patients with refractory versus sensitive disease. CONCLUSION: The combination of gemcitabine/irinotecan was shown to be active as second-line chemotherapy, especially in patients with refractory disease.     

Pseudo cluster randomization: a treatment allocation method to minimize contamination and selection bias

In some clinical trials, treatment allocation on a patient level is not feasible, and whole groups or clusters of patients are allocated to the same treatment. If, for example, a clinical trial is investigating the efficacy of various patient coaching methods and randomization is done on a patient level, then patients who are receiving different methods may come into contact with each other and influence each other. This would create contamination of the treatment effects. Such bias might be prevented by randomization on the coaches level. The patients of a coach constitute a cluster and all the subjects in that cluster receive the same treatment. Disadvantages of this approach may be reduced statistical efficiency and recruitment bias, as the treatment that a subject will receive is known in advance. Pseudo cluster randomization avoids this, because in pseudo cluster randomization, not everybody in a certain cluster receives the same treatment, just the majority. There are two groups of clusters: in one group the majority of subjects receive treatment A, while a limited number receive treatment B. In the other group of clusters the proportions are reversed. The statistical properties of this method are described. When contamination is present, the method appears to be more efficient than randomization on a patient level or on a cluster level.     

Temporal trends in early clinical manifestations of perinatal HIV infection in a population-based cohort

Context  The effect of early antiretroviral therapy (ART) on the early progression of perinatal human immunodeficiency virus (HIV) infection is not well defined. Objective  To examine early disease progression and survival in a population-based cohort with perinatal HIV infection in relation to year of birth and use of ART. Design, Setting, and Patients  Retrospective study of temporal trends in early progression of perinatal HIV infection among 205 HIV-infected children in Northern California born between January 1, 1988, and December 31, 2001, and followed up through age 3 years. Main Outcome Measures  Prevalence of and age at progression to a first US Centers for Disease Control and Prevention category C diagnosis relative to year of birth, type of ART, and age at initiation of therapy. Results  Of 205 children, 134 (65%) received ART and/or Pneumocystis jiroveci pneumonia prophylaxis. By age 3 years, 81 (40%) progressed to a category C diagnosis, 41 (51%) of whom died. Untreated children were significantly more likely to progress to a category C diagnosis (62% [44/71] untreated vs 28% [37/134] treated children, P<.001); none of 23 infants who received triple ART progressed to category C. However, even without triple ART, very early mono/dual ART (by age 2 months vs 3-4 months) was associated with delayed and decreased progression to category C (P = .02). Of 33 children born between January 1, 1996, and December 31, 2001, only 7 (21%) progressed to category C (P = .02 compared with 1988-1995), 6 of 7 of whom received no therapy. More recent year of birth and more advanced therapy were associated with improved survival. Conclusions  This population-based cohort demonstrated decreased early HIV progression and improved survival at age 3 years, associated with more advanced therapy. Although limited by small sample size, the findings suggest that very early treatment, even without triple ART, was associated with improved outcome.