Prostatic evaluation by transrectal endosonography: detection of carcinoma

Transrectal endosonography is one of the most sensitive techniques to evaluate prostatic disease and is far more accurate than conventional sonography. A retrospective review of sonographic characteristics of the prostate was made in an attempt to define the ability of the technique to distinguish benign from malignant disease. Analysis included evaluation of the capsule (smoothness, regularity, and/or invasion), abnormal foci (echogenicity, margination, brightness, thickness, and symmetry), and presence of acoustic shadowing and/or enhancement from the abnormal foci. Evaluation of 443 pathologically proved cases (the majority being large lesions) showed that differentiation between benign and large and/or invasive malignant disease may be suggested by results of transrectal endosonography. However, there is still great overlap of the sonographic appearances.     

Intraoperative arteriography: comparison of conventional screen-film with photostimulable imaging plate radiographs

This prospective study compared images obtained with a photostimulable imaging plate with matched images obtained with a conventional screen-film combination in 26 patients undergoing intraoperative arteriography. Diagnostic accuracy of the two techniques was assessed objectively, and image quality was assessed subjectively. In 16 patients (62%), the radiation exposure was reduced by 50% for the imaging plate technique by decreasing the mAs level generally used for the screen-film combination. Because of the dynamic range of the imaging plate system, no repeat examinations were necessary, while 12% of the screen-film studies had to be repeated because of over- or under-penetration. Imaging plate studies required 6% more time for processing than screen-film studies. Receiver-operating-characteristic analysis indicated no difference in diagnostic accuracy between the two imaging techniques. Subjective evaluation also revealed no difference in observer preference for imaging plate or screen-film studies. The imaging plate technique is an excellent alternative to screen-film studies in the operating room.     

alpha-Naphthoflavone metabolized by 2,3,7,8-tetrachlorodibenzo(p)dioxin-induced rat liver microsomes: a potent clastogen in Chinese hamster ovary cells

alpha-Naphthoflavone (ANF) is a widely used inhibitor of P-450-mediated metabolism. Previously, we have demonstrated that in vitro addition of ANF to human lymphocytes produced significantly greater numbers of sister chromatid exchanges (SCEs) in samples from smokers compared to nonsmokers. In order to study the mechanism of this differential induction, we investigated the clastogenic activity of ANF as a consequence of metabolism by induced and uninduced rat liver microsomes. Exponentially growing Chinese hamster ovary cells were treated with ANF for 2 h in the presence or absence of microsomes, followed by incubation for 12 (chromosome aberrations) or 24 h (SCEs). ANF induced concentration (4 to 40 microM)-dependent increases in SCEs and chromosome aberrations when coincubated with 2,3,7,8-tetrachlorodibenzo(p)dioxin-induced microsomes. At the lower concentrations of ANF, chromatid damage was most predominant, whereas at the higher concentrations, a high percentage of cells was killed. The surviving cells exhibited shattered chromosomes and multiple damage in the form of chromatid exchanges and breaks. ANF was not clastogenic nor did it induce SCEs in Chinese hamster ovary cells when incubated with microsomes from control rats or phenobarbital-treated rats. Moreover, NADPH was required for the clastogenic actions of ANF in the presence of 2,3,7,8-tetrachlorodibenzo(p)dioxin-induced microsomes. Analysis of the ANF metabolites by high-pressure liquid chromatography revealed that 2,3,7,8-tetrachlorodibenzo(p)dioxin-induced microsomes metabolized ANF to a much greater extent than control or phenobarbital-induced microsomes. Our results suggest that the clastogenic activity of ANF in Chinese hamster ovary cells is mediated by the cytochrome P-450 monooxygenase system.     

Genetic association of an alpha2-macroglobulin (Val1000lle) polymorphism and Alzheimer's disease

alpha2-Macroglobulin (A2M) is a proteinase inhibitor found in association with senile plaques (SP) in Alzheimer's disease (AD). A2M has been implicated biochemically in binding and degradation of the amyloid beta (Abeta) protein which accumulates in SP. We studied the relationship between Alzheimer's disease and a common A2M polymorphism, Val1000 (GTC)/Ile1000 (ATC), which occurs near the thiolester active site of the molecule. In an initial exploratory data set (90 controls and 171 Alzheimer's disease) we noted an increased frequency of the G/G genotype from 0.07 to 0.12. We therefore tested the hypothesis that the G/G genotype is over-represented in Alzheimer's disease in an additional independent data set: a group of 359 controls and 566 Alzheimer's disease patients. In the hypothesis testing cohort, the G/G genotype increased from 0.07 in controls to 0.12 in Alzheimer's disease (P < 0.05, Fisher's exact test). The odds ratio for Alzheimer's disease associated with the G/G genotype was 1.77 (1.16-2.70, P < 0.01) and in combination with APOE4 was 9.68 (95% CI 3.91-24.0, P < 0.001). The presence of the G allele was associated with an increase in Abeta burden in a small series. The A2M receptor, A2M-r/LRP, is a multifunctional receptor whose ligands include apolipoprotein E and the amyloid precursor protein. These four proteins have each been genetically linked to Alzheimer's disease, suggesting that they may participate in a common disease pathway.      

Pseudophakic phacoanaphylactic endophthalmitis

Two cases of pseudophakic phacoanaphylactic endophthalmitis are reported. Both responded favorably to a total posterior capsulectomy performed in addition to removal of the intraocular lens and remaining cortical material. Current theories on phacoanaphylactic endophthalmitis are discussed. Excision of the entire posterior capsule with anterior capsular flaps and entrapped cortex is emphasized as an integral part of the treatment of this condition.     

Autonomic response to auditory stimulation

Autonomic and behavioral response to fear stimulation (sudden noise 80 dB) was studied in 12 sleeping infants at ages 8–50 weeks. The aim of the present study was to identify a possible passive defense response in infants. The response, which is widespread in birds and mammals, is characterized by apnea and bradycardia with circulatory changes as seen during the forced diving response. Upon stimulation, two respiratory responses were elicited: apnea preceded by irregular respiration or simple irregular respiration. Apnea was elicited in 58% of stimulations at ages 8–16 weeks compared to 14% at 28–50 weeks. The mean duration of apnea decreased from 7.8 s(± 1.8 s) at 8–13 weeks to 4.7s (± 1.1s) at 17–20 weeks. The preceding irregular respiration increased from 5.3 s (± 4.4 s) to 10.6 s (± 5.4 s) at the same ages. The heart rate response was biphasic and were interpreted as the orienting response. The mean deceleration in relation to apnea was 16% at 8–16 weeks and was reduced to 8% at 28–50 weeks. Infants of smoking mothers were more prone to respond with apnea than infants of nonsmoking mothers (73% versus 38%). REM sleep and long postprandial sleep time increased the probability of apnea response (62% versus 38% and 66% versus 35%). The responses seen may be interpreted as expressions of the passive defense response.     

A phase I trial of recombinant human interleukin-11 (neumega rhIL-11 growth factor) in women with breast cancer receiving chemotherapy

We performed a phase I trial of recombinant human interleukin-11 (rhIL- 11) in women with breast cancer. Cohorts of three to five women were accrued to five dosage levels of rhIL-11 (10, 25, 50, 75, and 100 micrograms/kg/d). rhIL-11 alone was administered by a daily subcutaneous injection for 14 days during a 28-day prechemotherapy "cycle 0." Patients (pts) subsequently received up to four 28-day cycles of cyclophosphamide (1,500 mg/m2) and doxorubicin (60 mg/m2) chemotherapy followed by rhIL-11 at their assigned dose (days 3 through 14). Sixteen pts (13 stage IV, 3 stage IIIB) were accrued to this study. Median age was 53 years and median Eastern Cooperative Oncology Group Performance Status was 0. A grade 3 neurologic event was seen in 1 pt at 100 micrograms/kg. Because of the degree of grade 2 constitutional symptoms (myalgias/arthralgias and fatigue) at 75 micrograms/kg, dose escalation was stopped and 75 micrograms/kg was the maximally tolerated dose. No other grade 3 or 4 adverse events related to rhIL-11 were seen. The administration of rhIL-11 was not associated with fever. Reversible grade 2 fatigue and myalgias/arthralgias were seen in all pts at 75 micrograms/kg. Weight gain of 3% to 5% associated with edema was seen at doses > 10 micrograms/kg but a capillary leak syndrome was not seen. rhIL-11 alone was associated with a mean 76%, 93%, 108%, and 185% increase in platelet counts at doses of 10, 25, 50, and 75 micrograms/kg, respectively. No significant changes in leukocytes were seen. A mean 19% decrease in hematocrit was observed. Acute-phase proteins increased with treatment at all doses. Compared with patients at the 10 micrograms/kg dose, patients receiving doses > or = 25 micrograms/kg experienced less thrombocytopenia in the first two cycles of chemotherapy. We conclude that rhIL-11 has thrombopoietic activity at all doses studied, is well tolerated at doses of 10, 25, and 50 micrograms/kg, and at doses > or = 25 micrograms/kg has the potential to reduce chemotherapy-induced thrombocytopenia in this model.