Cell death and disposal in retinoblastoma: an electron microscopic study

Background: Tumor necrosis and cell death are common features of retinoblastoma. In non-malignant retinal cells after ischemia, as well as in many nonretinal tumors, cell death occurs in at least two ways. We investigated whether similar patterns of cell death could be demonstrated in retinoblastoma cells. Methods: Nine globes with retinoblastoma from eight patients were studied. Paraffin sections stained with HE or the Feulgen method were examined by light microscopy. Several samples from each tumor were selected for electron microscopic study. Results: Ultrastructurally, two main types of cell death were identified. Type I was characterized by progressive lysis of the cytoplasm and karyoplasm. Nuclear chromatin either dissolved or was transformed into compact clumps becoming extracellular dense bodies. Phagocytosis of cell remnants by neighboring tumor cells, or occasional macrophages, was common. Type II was characterized by progressive condensation and shrinkage of the cytoplasm and nucleus. Type II was subdivided in two forms distinguished mainly by characteristic patchy vs crescentic chromatin condensation. Small parts of condensed cytoplasm were engulfed by neighboring tumor cells. Compact cell remnants then underwent either phagocytosis by neighboring retinoblastoma cells or progressive intercellular disaggregation. Conclusion: Retinoblastoma cells may undergo at least two types of cell death. Type I fits the definition of necrosis, while both forms of type II exhibited several features consistent with apoptosis. The types of cell death observed in retinoblastoma exhibited similarities to patterns observed in ischemic retina, as well as in other malignant tumors. Type II cell death (apoptosis) may play a role in limiting tumor growth.Presented in part at the 1993 ARVO Meeting in Sarasota, Fla., USA     

Intraperitoneal Versus Interpleural Morphine or Bupivacaine for Pain after Laparoscopic Cholecystectomy

Background: Opioids can produce peripheral analgesic effects by activation of opioid receptors on sensory nerves. This study was designed (1) to examine a novel route of opioid administration, the intraperitoneal injection; (2) to compare this to interpleural application, and (3) to compare opioid with local anesthetic effects under both conditions.

Methods: At the end of laparoscopic cholecystectomy, 110 patients received the following injections in a double-blind, randomized manner: Group 1 (n = 18) was given intraperitoneal morphine (1 mg in 20 ml saline) and 20 ml intravenous saline. Group 2 (n = 17) received intraperitoneal saline and 1 mg intravenous morphine. Group 3 (n = 15) received 20 ml 0.25% intraperitoneal bupivacaine and intravenous saline. Group 4 (n = 20) received interpleural morphine (1.5 mg in 30 ml saline) and 30 ml intravenous saline. Group 5 (n = 20) received interpleural saline and 1.5 mg intravenous morphine. Group 6 (n = 20) received 30 ml 0.25% interpleural bupivacaine and intravenous saline. Postoperative pain was assessed using a visual analog scale, a numeric rating scale, and the McGill pain questionnaire. Pain localization, supplemental analgesic consumption, vital signs, and side effects were recorded for 24 h.

Results: Neither intraperitoneal nor interpleural morphine produced significant analgesia after laparoscopic cholecystectomy (P > 0.05, Kruskal-Wallis test), whereas interpleural bupivacaine was effective (P < 0.05, Kruskal-Wallis test, up to 6 h postoperatively) but not intraperitoneal bupivacaine (P > 0.05, Kruskal-Wallis test). Shoulder pain was not prevalent in the majority of patients during the first 6 h. By 24 h, about half of the patients complained of shoulder pain, which was rated "low" by about one-third of all patients. No significant side effects occurred.     

Traumatic complications of acupuncture. Therapists need to know human anatomy

OBJECTIVES: To review the traumatic injuries that have been associated with acupuncture and to discuss how these adverse effects may be reduced by increased awareness of normal anatomy and anatomical variations. METHODS: Literature search accompanied by postmortem anatomical studies. RESULTS: Traumatic lesions after acupuncture have been described in thoracic and abdominal viscera, in the peripheral and central nervous systems, and in blood vessels. Deaths have been recorded from pneumothorax and cardiac tamponade. The anatomical structure of the body at several acupuncture points is such that needles can reach vulnerable structures. CONCLUSION: While the frequency of adverse effects of acupuncture is unknown and they may be rare, knowledge of normal anatomy and anatomical variations is essential for safe practice and should be reviewed by regulatory bodies and those responsible for training courses.     

CARD In Situ Hybridization: Sights and Signals

During the last decade, several strategies have been developed to improve the detection sensitivity ofin situ hybridization (ISH) by amplification of either target nucleic acid sequences prior to ISH (e.g.,in situ PCR), or the detection signals after the hybridization procedures (signal amplification). Here we outline the principles of tyramide signal amplification using the catalyzed reporter deposition (CARD) technique, summarize applications as well as possible limitations of CARD ISH, and discuss some future directions ofin situ nucleic acid detection using this amplification strategy.     

Adherence to antiretroviral medications in an inner-city population

Adherence to antiretroviral medications is essential for optimal treatment of HIV infection. We investigated nonadherence to antiretroviral medications in an inner-city population by using a confidential interview and a self-administered anonymous questionnaire. We estimated adherence on the day before and the month before the interview and asked reasons for nonadherence. Of 173 people who were taking antiretroviral medications, all participated in the confidential interview and 101 also completed the anonymous questionnaire. Results of the confidential interview and the anonymous questionnaire revealed rates of 6% and 28%, respectively, for nonadherence to any drug on the preceding day and of 11% and 39%, respectively, in the preceding month. The most common reasons for nonadherence in both methods were forgetfulness, inaccessibility of medications, and perceived or actual toxicity. On 12% of the anonymous questionnaires one reason for nonadherence was perceived or actual lack of drug efficacy: this reason was not given in any of the confidential interviews. Responses about the extent of nonadherence and the reasons for it may differ depending on the method of ascertainment. Interventions to improve adherence should focus on making medication dosages easier to remember, ensuring a continued supply of medications, and circumventing toxicities.     

Progressive multifocal leukoencephalopathy and human immunodeficiency virus-associated white matter lesions in AIDS: magnetization transfer MR imaging

PURPOSE: To determine the magnetization transfer features of progressive multifocal leukoencephalopathy (PML) and human immunodeficiency virus (HIV)-associated white matter lesions (WML) (hereafter, HIV-WML) on magnetic resonance (MR) images obtained in patients with acquired immunodeficiency syndrome (AIDS). MATERIALS AND METHODS: Conventional MR imaging and magnetization transfer MR imaging were performed in 21 AIDS patients with 42 areas of white matter hyperintensity on MR images (13 patients had 25 PML lesions, eight patients had 17 WML). The magnetization transfer ratio was calculated for each lesion. RESULTS: Compared with normal-appearing white matter (magnetization transfer ratio = 47.9%), both PML and HIV-WML showed reduced magnetization transfer ratio. The magnetization transfer ratio was significantly lower in PML lesions (magnetization transfer ratio = 26.1%) than in HIV-WML (magnetization transfer ratio = 38.0%, P < .0001), and there was no overlap in the magnetization transfer ratio between PML lesions and HIV-WML. The separation in magnetization transfer ratio between the two lesion types was valid for lesion as small as 0.5 cm2. CONCLUSION: The larger reduction in magnetization transfer ratio for PML lesions is most likely due to demyelination, whereas the reduction in HIV-WML may be associated primarily with gliosis. PML lesions appear to cause strong reductions in magnetization transfer ratio early in the course of disease. Magnetization transfer MR imaging is a noninvasive tool that improves the differentiation between PML and HIV-WML in patients with AIDS.     

Three cases of dural arteriovenous fistula of the anterior condylar vein within the hypoglossal canal

Dural arteriovenous fistulas (DAVFs) of the anterior condylar vein are an uncommon but important subset of fistulas occurring at the skull base that can be confused with DAVFs of the marginal sinus on angiography. MR angiography source images can document the intraosseous extent and the relationship to the hypoglossal canal of this type of fistula, which can have significant clinical implications. We present the imaging features of angiography, CT, and MR angiography of three cases of DAVFs localized to the anterior condylar vein and within the hypoglossal canal, which were confirmed by source images from MR angiography. Transvenous coil embolization was curative in two of three cases and would seem to be the treatment of choice when venous access is available.     

Orbital surgery – perioperative problems and results

Fragestellung: Orbitotomien nehmen innerhalb der Ophthalmochirurgie auf Grund der involvierten anatomischen Strukturen und des daraus resultierenden Spektrums m?glicher perioperativer Probleme eine Sonderstellung ein. Um einen überblick über die Art und H?ufigkeit intra- und postoperativer Probleme bei Orbitotomien zu erhalten, führten wir eine retrospektive Auswertung an unserer Klinik durchgeführter Orbitotomien durch. Patienten und Methode: Es wurden 48 Orbitotomien bei 46 Patienten berücksichtigt, die zwischen 08/1995 und 02/1998 operiert wurden. Ergebnisse: Schwerwiegende intraoperative Komplikationen waren mit zwei transfusionspflichtigen Blutungen und einer Liquorfistel selten. Sie wurden interdisziplin?r behandelt. Postoperativ traten vorübergehende funktionelle St?rungen mit guter Rückbildungstendenz wie Visusminderungen (35 %), Motilit?tsst?rungen mit oder ohne Doppelbildwahrnehmung (20 %) und Lidfehlstellungen auf. Ihnen liegt v. a. die postoperative ?dem- und H?matombildung zugrunde. Persistierende Funktionseinschr?nkungen waren dagegen selten (10 %). Schlu?folgerung: Unsere Untersuchung zeigt, da? perioperativ bei Orbitotomien v. a. vorübergehende funktionelle Einschr?nkungen auftreten, die sich rasch zurückbilden. Schwere Komplikationen sind dagegen selten, treten v. a. intraoperativ auf und k?nnen eine interdisziplin?re Therapie erfordern.      

Multiple mechanisms are involved in the acute vasodilatory effect of 17beta-estradiol in the isolated perfused rat heart.

The purpose of this study was to define the dose-dependent effects of 17beta-estradiol on coronary flow and cardiac function in isolated rat hearts and to identify the mechanisms involved in its vasodilator action. Hearts from female and male Wistar rats were perfused at constant pressure (100 mm Hg). Stereoisomer specificity and the mechanism of vasodilation by 17beta-estradiol were examined in female rat hearts. Function was measured by a left ventricular (LV) balloon and coronary flow (CF) with an ultrasonic flowmeter. 17Beta-estradiol at 10(-6), 5 x 10(-6), and 10(-5) M increased CF in female hearts by 5 +/- 2, 27 +/- 4 (p < 0.05 vs. baseline), and 40 +/- 4% (p < 0.05 vs. baseline), respectively. The effect of 17beta-estradiol in hearts from male rats was similar but less pronounced compared with females [deltaCF 8 +/- 3, 19 +/- 3 (p < 0.05 vs. baseline)] and 25 +/- 7% (p < 0.05 vs. baseline; p < 0.05 vs. female 17beta-estradiol). Maximum vasodilation by the stereoisomer 17alpha-estradiol was significantly smaller [deltaCF 5 +/- 3, 4 +/- 3 (p < 0.05 vs. female 17beta-estradiol) and 14 +/- 1% (p < 0.05 vs. baseline; p < 0.05 vs. female 17beta-estradiol)] for 10(-6), 5 x 10(-6), and 10(-5) M. Pretreatment with the NO-synthesis inhibitor Nomega-methyl-L-arginine (10(-4) M) had no effect on the maximal vasodilator response to 17beta-estradiol (10(-5) M) [deltaCF 36 +/- 6% (p < 0.05 vs. baseline)]. When hearts were pretreated with the prostaglandin-synthesis inhibitor diclofenac (10(-6) M), the maximal vasodilator effect of 17beta-estradiol was partially attenuated [deltaCF 12 +/- 7% (p < 0.05 vs. female 17beta-estradiol)]. Similarly, pretreatment with the K+ATP-blocker glibenclamide (10(-6) M) partially inhibited the maximal vasodilator effect of 17beta-estradiol [deltaCF 22 +/- 6% (p < 0.05 vs. baseline; p < 0.05 vs. female 17beta-estradiol)]. Pretreatment with the Ca2+ channel antagonist nifedipine (7.2 x 10(-8) M) completely blocked the vasodilator effect. In isolated perfused rat hearts, 17beta-estradiol induced marked acute coronary vasodilation; this effect is in part gender specific, and in female hearts, largely stereoisomer specific. The dilator effect is mediated predominantly by calcium channel blockade, but prostaglandin release and K+ATP channel activation also are involved. In the isolated perfused rat heart, NO production does not contribute to the acute vasodilator effect of 17beta-estradiol.