Effects of priming duration on retention over the first 1 1/2 years of life

Exposing individuals to an isolated component (a prime) of a prior event alleviates its forgetting. Two experiments with 120 human infants between 3 and 18 months of age determined the minimum duration of a prime that can reactivate a forgotten memory and how long the reactivated memory persists. Infants learned an operant task, forgot it, were exposed to the prime, and later were tested for renewed retention. In Experiment 1, the minimum duration of an effective prime decreased logarithmically with age, but was always longer than the duration of a mere glance. In Experiment 2, the reactivated memory was forgotten twice as fast after a minimum-duration prime as after a full-length one, irrespective of priming delay and infant age. These data reveal that the minimum effective prime duration psychophysically equates the accessibility of forgotten memories. We conclude that priming is perceptually based with effects that are organized on a ratio (log) scale.     

Therapeutic effects of leuprorelin microspheres in prostate cancer

Leuprorelin has demonstrated effectiveness comparable to orchiectomy and oral diethylstilboestrol for the palliation of advanced prostate cancer. Unlike orchiectomy, leuprorelin's effects are reversible; also leuprorelin is not associated with the cardiovascular or thromboembolic adverse effects of oestrogens. For these reasons, leuprorelin has been widely used as an alternative to surgical castration or to oestrogens in the treatment of metastatic prostate cancer. Sustained-release leuprorelin microsphere formulations have been developed which exhibit zero order release of active drug from the injection site, such that in the United States the 7.5 mg dosage strength is recommended to be administered once a month and the 22.5 mg dosage strength once every three months. Although most patients will have suppressed release of pituitary luteinizing hormone by the third or fourth week after the first dose of depot leuprorelin, 4-5% of treated patients have been reported to have delayed responses, taking many more weeks or months to respond. A transient biochemical hormone escape has also been reported, although worsening of clinical symptoms has not accompanied the elevation of serum testosterone levels during treatment. Usually, leuprorelin is initiated as monotherapy when patients with advanced prostate cancer become symptomatic. However, newer studies of combination therapy of luteinizing hormone releasing hormone analogs with antiandrogens suggest that early initiation of therapy, at the time of diagnosis of advanced disease, may be beneficial, particularly in a subgroup of patients with small volume disease and good performance status. Leuprorelin is also undergoing evaluation as neoadjuvant therapy prior to radical prostatectomy for localized prostate cancer. Preliminary studies suggest that neoadjuvant leuprorelin in combination with an antiandrogen may be effective in downstaging prostate tumours. Leuprorelin commonly produces several adverse effects: hot flashes, decreased libido and impotence, and tumour flare.     

Anterior segment findings in AIDS patients with cytomegalovirus retinitis

Background: Anterior segment findings in AIDS patients presenting with cytomegalovirus (CMV) retinitis have not been specifically addressed in the American literature. Methods: Our study evaluated 21 AIDS patients with CMV retinitis. Results: Nineteen (90%) of these patients exhibited corneal endothelial deposits concurrent with CMV retinitis. The endothelial deposits were microscopic, opaque, linear flecks arranged in a reticular-like fashion. Of 42 eyes evaluated, 32 (76%) demonstrated active CMV retinitis. Corneal endothelial deposits were noted in 26 (81%) of the 32 eyes with retinitis. These corneal endothelial deposits were absent in the eyes which did not have CMV retinitis. Conclusion: Meticulous examination of the retina of an HIV-positive or AIDS patient who presents with reticularly arranged, linear, flecked corneal endothelial deposits should be performed to ensure that the diagnosis of CMV retinitis can be ruled out.     

Physician Response to Prenatal Substance Exposure

Objectives: To examine physician responses to suspected prenatal substance exposure and the reasons underlying these responses. Methods: National mail survey of practicing obstetricians and pediatricians who see neonates. Response rate: 63%. Results: More than 70% of physicians reported having ever suspected prenatal substance exposure. Response rates did not vary by specialty. Twenty-seven percent reported that they had never suspected prenatal substance exposure. The most common lifetime pattern (60%) was some response whenever prenatal substance exposure was suspected; next most common was no suspicion (27%). Just over 10% had a discretionary response: acting in some cases of suspected prenatal substance exposure but ignoring others. Two percent consistently ignored their suspicions. Getting help for the patient and protecting the fetus were the most common reasons to act. Among those who had ignored their suspicions, lack of sufficient evidence of substance use was the most often cited reason. There were some important specialty differences in reasons for response and non-response and in specific responses likely to be taken. Obstetricians are far more likely to provide the patient with information and get a substance use history; pediatricians are more inclined to involve outsiders. Conclusions: Obstetricians and pediatricians seem quite willing to act on their suspicions of prenatal substance exposure, and generally respond by taking positive actions. Specialty differences are few and reflect practice differences.     

Isolation and characterization of the mouse homolog of the preprodynorphin (Pdyn) gene

We have isolated and sequenced the mouse preprodynorphin gene (Pdyn). The Pdyn gene can encode for six biologically active dynorphin peptides. The predicted mouse preprodynorphin has 90%, 67%, and 66% identity with the predicted rat, porcine, and human preprodynorphins, respectively. Using an RT-PCR technique, we show that the Pdyn gene starts being expressed at embryonic day 12.5, with a steep increase of expression by embryonic day 14.5; in the adult mouse it is expressed in the brain, but not in liver, heart, spleen, or kidney.     

Nodular lymphoid lesion of the liver: an immune-mediated disorder mimicking low-grade malignant lymphoma

Three cases of unusual lymphoid infiltrate forming nodular macroscopic masses in the liver were studied in the authors' surgical pathology laboratory. These lesions posed difficulty in diagnosis, and their differentiation from low-grade lymphoma was not possible on histopathologic evaluation alone. The liver masses were analyzed histologically and immunohistochemically as well as for clonal immunoglobulin heavy chain (IgH) and T-cell receptor gamma (TCR-gamma) gene rearrangements. The lesions were seen as solitary grossly distinct firm nodules in all three patients, measuring 0.4, 0.7, and 1.5 cm, respectively, in their greatest dimensions. Two were found in livers removed because of end-stage primary biliary cirrhosis at the time of orthotopic liver transplantation, and the third was an incidental finding during laparotomy. Microscopically, these were nodules composed of small lymphocytes, plasma cells, and immunoblasts, with varying degrees of admixed acute inflammatory cells and scattered lymphoid follicles. By immunohistochemistry and molecular studies, these were found to be reactive lymphoid proliferations. All patients are alive and well at 2, 4, and 13 years, respectively. It is concluded that these cases represent a unique type of nodular lymphoid lesion, which is probably an immune-mediated benign reactive hyperplasia. It constitutes an entity by itself and must be distinguished from low-grade lymphoma. For a definitive diagnosis, immunohistochemistry and molecular studies are required.     

Primary Bladder Neck Obstruction: Urodynamic Findings and Treatment Results in 36 Men

Purpose

We reviewed the urodynamic findings and treatment outcomes of a large series of men with primary bladder neck obstruction.

Materials and Methods

A retrospective review was done of the presenting symptoms and urodynamic findings of 36 men with primary bladder neck obstruction. Outcomes after treatment with alpha-blockers, transurethral incision of the bladder neck and prostate, or no long-term therapy were determined by chart review and patient survey in the majority of cases.

Results

Mean age of the men was 41 years. Patients had significant lower urinary tract symptoms, decreased peak urinary flow rates, elevated post-void residual, markedly elevated peak voiding pressures and poor funneling of the bladder neck during voiding. Although most patients initially chose alpha-blocker therapy, only 30 percent of those beginning alpha-blockers continued them long term, usually due to inadequate symptomatic improvement. A total of 18 men underwent transurethral incision, which resulted in significant improvements in symptom scores, peak urinary flow rates, post-void residual and peak voiding pressures. Patients reported a mean 87 percent overall improvement in symptoms after transurethral incision.

Conclusions

Video urodynamics facilitate diagnosis of primary bladder neck obstruction. Transurethral incision is the most effective therapy for primary bladder neck obstruction.     

A new chemically modified chimeric TNT-3 monoclonal antibody directed against DNA for the radioimmunotherapy of solid tumors

In the last several years, our laboratory has developed a new approach to the radioimmunotherapy of solid tumors, designated Tumor Necrosis Treatment (TNT), that exploits the presence of degenerating and necrotic cells within tumors by utilizing MAbs directed against universal, intracellular antigens. The first TNT MAb developed by our laboratory, designated TNT-1, was directed against nucleosomal determinants consisting of histone H1 and DNA. Since absolute tumor accretion of MAb is a critical determinant of antitumor efficacy in radioimmunotherapy, we sought to identify new antinuclear antibodies that displayed high tumor localization properties. In the present study, we describe a murine antinuclear antibody, TNT-3, which demonstrates 3-fold higher tumor uptake than TNT-1. Because of this characteristic, a chimeric derivative designated chTNT-3 was developed and evaluated for antigen binding and tumor targeting. ELISA studies using a series of nuclear antigens confirmed that TNT-3 is directed against single-stranded DNA and does not cross react with TNT-1. Immunohistology reveals predominantly nuclear staining reactivity in human tissues and tumors. Since it was shown by our laboratory that charge modification can significantly improve the pharmacokinetic performance of monoclonal antibodies, chTNT-3 was chemically modified with biotin to generate an improved therapeutic reagent designated chTNT-3/B. Comparative studies with unmodified MAb demonstrated that biotinylation significantly shortened its clearance time in mice and produced lower normal tissue levels, while maintaining an equal amount of uptake in tumor xenografts for up to 10 days. These in vivo characteristics suggest that chTNT-3/B is an improved TNT reagent for the radioimmunotherapy of solid tumors.     

A rejoinder to Professor Bruening

Point and Counterpoint

A rejoinder to Professor Bruening