Warthin-Finkeldey polykaryocytes demonstrate a T-cell immunophenotype.

Warthin-Finkeldey polykaryocytes have been described in various benign and malignant lymphoid conditions since their initial identification in tonsils of patients in the prodromal stage of measles. However, the nature of these multinucleated giant cells is obscure. The authors studied the immunohistochemical profile of the Warthin-Finkeldey-type giant cells in three cases of lymphoid proliferations (two reactive, one neoplastic) containing many multinucleated cells using a panel of paraffin-reactive antibodies. Warthin-Finkeldey polykaryocytes demonstrated reactivity with Leu22 (CD43), anti-CD3, and OPD4, indicating that these cells are multinucleated T lymphocytes. The significance of these results with respect to the disorders in which these cells are found and their possible role in pathogenesis of disease are discussed.     

Estimation of tumor growth fractions in archival formalin-fixed, paraffin-embedded tissues using two anti-PCNA/Cyclin monoclonal antibodies. Factors affecting reactivity.

Immunohistochemical detection of cell cycle-related markers for estimation of tumor growth fractions using paraffin-embedded tissue sections would have applications in experimental and clinical pathology as an in situ histologic alternative to flow cytometry. The monoclonal antibodies 19A2 and PC10 detect the proliferating cell nuclear antigen (PCNA/Cyclin), an auxiliary protein to DNA polymerase-delta. In a prospective group of uniformly handled, formalin-fixed malignant lymphomas we previously demonstrated 19A2 to be a reliable marker of proliferative activity similar to Ki-67 in frozen tissue. The present study examines the applicability of this technique in archival formalin-fixed material. Studies on tonsilar tissue revealed that formalin fixation beyond 30 hours adversely affected reactivity of 19A2, possibly explaining the variable results in nonuniformly fixed archival material. We found that only 27 (56%) of 48 archival cases of infiltrating ductal carcinoma showed sufficient reactivity with 19A2 to permit reliable quantification of the tumor growth fraction. Acid pretreatment with 2N HCl had no apparent effect on 19A2 reactivity. Using both antibodies on a group of 32 archival lymphomas, carcinomas, and sarcomas, significantly more biopsies stained reliably for PC10 (84%) than for 19A2 (72%; P < 0.036). Further, none of the cases that did not react with PC10 reacted with 19A2. PC10 may recognize a different epitope of PCNA/Cyclin which may be more resistant to alterations by fixation. In the 23 cases that reliably stained for both markers, largely carcinomas, there was excellent correlation between estimated growth fractions (r = 0.96). Although immunostaining provides a useful way to estimate tumor growth fractions in paraffin-embedded tissues, modifications of technique and cautious interpretation of results are advisable when using archival material.     

Post-learning ethanol effects on a water-finding task in rats

Ethanol's post-training facilitation of memory was examined using a latent learning paradigm known as the "water-finding task." Rats were assigned to one of two ethanol groups (E0.75 g/kg or E1.5 g/kg) or to a control group (saline) and individually placed in a novel open field containing a drinking tube. Following this exposure, subjects were immediately administered intraperitoneal (IP) injections of either the saline or ethanol and 48 hours later, re-introduced to the field. Initial latencies to contact the tube each time were recorded. A linear regression analysis of trial 2 latencies regressed onto trial 1 latencies indicated a statistically significant effect of ethanol on the relation between initial and subsequent latencies. Though the control rats' trial 2 latencies were completely random with respect to their previous speeds (rSAL = -0.07), the ethanol rats' trial 2 latencies were positively correlated with initial speeds (rE0.75 = 0.35, rE1.5 = 0.67). These results suggest that under conditions of post-training ethanol, trial 2 behavior is more similar to, or controlled by, trial 1 behavior and are consistent with the argument that, under certain training and testing contexts, ethanol can come to exert control over a response's recurrence.     

Time-restricted feeding schedules modify temporal variation of gentamicin experimental nephrotoxicity.

The effect of timing of gentamicin dosing relative to food access periods was evaluated in experimental animals. Female Sprague-Dawley rats were treated for 4 and 10 days with gentamicin (40 mg/kg of body weight/day) intraperitoneally at either 0700, 1300, 1900, or 0100 h according to three food presentation schedules: food was available from 0800 to 1600 h in the first group, from 1600 to 0000 h in the second group, and from 0000 to 0800 h in the last group. Animals were thus subjected to a restricted feeding period. Results indicate that time-restricted feeding schedules displace the peak and the trough of gentamicin-induced renal toxicity, as evaluated by changes in the inhibition of sphingomyelinase activity, cellular regeneration (incorporation of [3H]thymidine into DNA of renal cortex), and blood urea nitrogen and serum creatinine levels, as well as histopathological lesions observed after 10 days of treatment. In fact, the toxicity was minimal when gentamicin was injected during the feeding period, while the maximal toxicity was found when gentamicin was administered during the fasting period. It is concluded that the feeding period can modulate aminoglycoside nephrotoxicity. The time of dosing of gentamicin relative to the time of feeding seems to be a more important modulator of gentamicin nephrotoxicity than the light-dark cycle.     

Age differences in expectations and readiness regarding lifestyle modifications in individuals at high risk of diabetes

Bouchard DR, Langlois M-F, Domingue M-E, Brown C, LeBrun V, Baillargeon J-P. Age differences in expectations and readiness regarding lifestyle modifications in individuals at high risk of diabetes.ObjectiveThe main objective of this study was to determine whether expectations and readiness to modify eating habits and physical activity (PA) level are different between young and older individuals with prediabetes who agreed to participate in a lifestyle modification program.DesignCross-sectional analysis.SettingPrimary care or referral center.ParticipantsAdults between ages 27 and 78 years (N=74) were tested before starting a 12-month lifestyle intervention.InterventionsNot applicable.Main Outcome MeasuresThe visual analog scale questionnaire was used to assess expectations and readiness (ie, intentions, conviction, and self-confidence) to modify the PA level and eating habits. The PA level was assessed with a pedometer and eating habits with a questionnaire. Analyses were stratified by the age group: <60 years old versus ≥60 years old.ResultsBody mass loss expectations in terms of goal (?22.9% vs ?17.9% of the current body mass; P=.04), acceptable (?15.6% vs ?9.4%; P=.01), and failure (?7.6% vs ?3.8%; P=.05) in future body mass loss were all greater for the younger group. Despite no significant age group difference in the initial PA level and eating habits, the youngest group had a greater intention to increase the PA level (89% vs 81%; P=.004) and to eat healthier (90% vs 85%; P=.001). Finally, the PA level and the consumption of fruits and vegetables, but not body mass, were associated with intentions or self-confidence to make some lifestyle modifications within age groups.ConclusionsIn individuals at high risk for diabetes, increasing age is associated with lower expectations and reduced readiness with regard to lifestyle modifications. Thus, age should be considered when planning a lifestyle modification program.     

Use of high dose corticosteroids in patients with inoperable brain tumours.

Eleven patients with inoperable brain tumours were treated with high doses of corticosteroids (methylprednisolone 200-2000 mg/day) for up to 151 days (mean 55 days). Neurological improvement occurred in eight patients on high doses after deterioration on concentional doses (methylprednisolone 80-120 mg/day). In two patients steroids could be completely discontinued for several months. Serious adverse effects included sepsis in three patients and myopathy in tow. All three patients with sepsis also received chemotherapy. There were no deaths that could be attributed to steroids. The most likely effect of high dosage steroids is reduction of cerebral oedema. It is conceivable that in some instances high dose steroids may also result in tumour inhibition or oncolysis or both.     

Update on Surgical Treatments for Pelvic Organ Prolapse

Purpose of Review

The purpose of this review is to update readers on recent controversies and current evidence regarding surgical procedures for the treatment of female pelvic organ prolapse.

Recent Findings

Topics discussed include the role of patient selection and individualized care that involves the patient in surgical decision-making. Perioperative decisions reflect rapidly advancing technology, innovations in surgical technique, surgical training, and surgeon’s own unique preferences, all of which provide an opportunity for improved outcomes and also require deliberate attention to unanticipated patient safety concerns.

Summary

Pelvic reconstructive surgery for pelvic organ prolapse requires an appreciation for complex pelvic anatomy and advanced surgical training. In a field focused on patient-centered quality of life outcomes, it is imperative to involve the patient in the decision-making process while also balancing differences in surgeons’ skills, biases, and available technology. These topics are explored in detail and offered a thoughtful approach to surgical management.

     

Essential thrombocythemia with the Philadelphia chromosome and BCR-ABL gene rearrangement. An entity distinct from chronic myeloid leukemia and Philadelphia chromosome-negative essential thrombocythemia

A 64-year-old woman presented with a platelet count of 3,225 x 10(9)/L. Bone marrow morphology showed massive megakaryocytic hyperplasia; cytogenetic studies showed the presence of the Philadelphia chromosome (Ph). The presence of a rearrangement involving the major breakpoint cluster region (mbcr) on chromosome 22 was confirmed by Southern blotting techniques. A diagnosis of Ph positive essential thrombocythemia (ET) was made. Such cases constitute less than 5% of patients with ET and it has been proposed that they be considered examples of chronic myelogenous leukemia (CML) because of a shared propensity to progress to blast crisis. An argument is presented for retaining Ph positive ET as an entity separate from Ph negative ET and Ph positive CML.