Indocyanine green angiography of choroidal tumors

Background: Fluorescein angiography (FA) has been widely used in the diagnostic evaluation of cboroidal tumors. Indocyanine green angiography (ICG-A), which permits better visualization of choroidal vasculature than FA, has been recently introduced into clinical practice. Only few reports exist on the ICG-A characteristics of choroidal tumors. Methods: The fluorescein and indocyanine green angiograms of 61 patients were assessed. These included 14 patients with choroidal nevi, 30 with malignant melanomas, 7 with suspected melanomas or atypical nevi, 5 with hemangiomas and 5 with metastases. Results: The outline of pigmented tumors was more accurate on ICG-A than on FA. Characteristic patterns were seen in all intra-ocular tumors with ICG-A, so it was possible to distinguish hemangiomas from malignant lesions. Characteristic features of malignant melanomas include abnormal vascular pattern and marginal late dye leakage. None of the benign lesions showed these features. In suspected melanomas, the presence of abnormal choroidal vascular patterns and/or late dye leakage on ICG-A may indicate malignancy. Conclusion: The study suggests that ICG-A can yield additional information that is useful in differentiating amongst choroidal tumors. Better delineation of pigmented lesions with ICG-A allows more accurate treatment planning and follow-up.     

Comparison of survival among patients with breast cancer treated at First Teaching Hospital,Changchun, China,and Saint-Sacrement hospital,Quebec, Canada

The aim of this study was to compare the survival of 116 patients with breast cancer initially treated at the First Teaching Hospital (FTH) of Norman Bethune University of Medical Sciences located in Changchun, China, from 1986 to 1991 with the survival of 886 patients seen in the “Hipital du Saint-Sacrement” (HSS) located in Quebec City, Canada, from 1987 to 1992. The clinical data were collected from the hospital records at FTH. The vital status for Chinese patients was obtained from letters of follow-up or the records of local police offices. The list of patients treated at HSS and the data for each woman were extracted from computerized data banks. The major variables studied included age at diagnosis, tumor size at pathology (cm), number of lymph nodes involved, breast surgery and adjuvant treatments of breast cancer (chemotherapy, radiotherapy, immuno-therapy). Age at diagnosis was substantially lower among patients with breast cancer seen at FTH compared to those treated at HSS (x) ₁ ² =60.95,P<0.0001). The average age at diagnosis for Chinese women was about 10 years less than that for Canadian women. Patients in the two hospitals differed with respect to tumor size at pathology (x ₂ ² =6.67,P=0.036). The proportion of patients with tumor size larger than 2.0 cm was larger at FTH (48.3%) than at HSS (41.1%). The mean tumor size at pathology was 3.0 cm (standard deviation =2.1 cm) for patients treated at FTH, but 2.6 cm (standard deviation=1.8 cm) for women treated at HSS (P=0.07). The proportion of women with lymph node involvement was greater at FTH (61.1 % than that at HSS (37.3%) (x ₁ ² =16.51,P<0.0001). Surgical treatment of breast cancer varied considerably. In Changchun, radical mastectomy was frequent for any stage of breast cancer patients, but partial mastectomy was never performed. The situation was reversed in Quebec. The five year observed survival was 74.2% (standard error, 0.05) among breast cancer patients seen at FTH compared to 76.0% (standard error, 0.02) among women treated at HSS. After adjustments of confounding factors, there were no significant difference in five year observed survival between the patients treated at the two hospitals (P=0.42).     

Obesity and subcutaneous fat patterning in relation to survival of postmenopausal breast cancer patients participating in the DOM-project

Summary The effect of obesity and fat distribution on survival of breast cancer patients was studied prospectively in 241 women with a natural menopause who participated in a breast cancer screening project, the DOM-project in Utrecht, The Netherlands. Mean follow-up time was 9.1 years and endpoint of interest was death from breast cancer. Fat distribution was assessed by contrasting groups of subscapular and triceps skinfold thickness.No significant differences in survival time between more obese (Quetelet's index 26 kg/m²) and leaner (Quetelet's index < 26 kg/m²) patients or between patients with central fat distribution and patients with peripheral fat distribution were observed. Analyses were stratified by axillary node status, estrogen receptor status, and way of detection (by first screening or afterwards). Results of the stratified analyses were suggestive of a modifying effect of these factors.The absence of an association between obesity and survival time might be explained by two counteracting mechanisms. On the one hand obesity might be related to impaired survival, due to a tumor growth promoting effect of extra-ovarian estrogens. On the other hand obesity might be related to improved survival in a screened population, because obese patients profit more from screening by earlier detection of tumors than leaner counterparts.     

Interventional Radiology for Treating Soft Tissue Sarcomas

The role of interventional radiology for soft tissue sarcomas is only occasionally addressed in the literature. However, different techniques such as embolization, selective chemotherapy, chemoembolization, and acrylic cement osteoplasty can be helpful with the primary tumor, recurrences, and metastases. This article discusses these techniques and their complications in treatment of soft tissue sarcomas.     

Examination of resistance of the lens capsule against the waterjet

BACKGROUND: Although cataract surgery is highly developed today, there are still problems such as secondary cataract. In polishing the posterior capsule lens, epithelial cells often remain, causing secondary cataracts. Additionally, there are the problems of tissue heating and endothelial cell loss during phacoemulsification by ultrasound. This could be another field for improvement of cataract surgery by using the waterjet. METHODS: After removing the cornea of freshly enucleated porcine bulbs, we used the water jet from 4 to 12 bar. The hit angel on the capsule varied between 45 degrees and 90 degrees. RESULTS: Rupture of the posterior capsule occurred at a mean of 8.5 bar using the jet at 45 degrees and a mean of 8.6 bar using the jet at 90 degrees. CONCLUSION: The waterjet pressure should not be over 4 bar during polishing of the posterior capsule.     

Inducible nitric oxide synthase activity of cloned murine microglial cells

Nitric oxide (NO) is a short-lived diffusable molecule now believed to participate in multiple physiologic functions in the CNS including neurotransmission and the maintenance of vascular tone. Previously, we reported that cell lines obtained by retroviral immortalization of tissue macrophages (M?;) could be induced to synthesize nitrite (NO), a stable end product of the NO synthetic pathway. We have further characterized the induction and activity of this pathway in a panel of seven microglial clones derived from primary embryonic mouse brain cultures. Like M?;, these clones were found to release high levels of NO_-² in response to recombinant interferon-γ (rIFN-γ) as a priming signal together with either bacterial lipopolysaccharide (LPS) or exogenous recombinant tumor necrosis factor-α (rTNF-α). As previously demonstrated for M?;, phagocytosis of zymosan particles during induction of enzyme activity enhanced subsequent NO production, which is of interest in light of the postulated phagocytic role of microglia within the CNS. Biochemical characterization of enzyme activity in intact microglial clones and in isolated cytosolic fractions indicates that the microglial NO synthase present in these murine cell clones represents the M?;-like isotype. These findings suggest that microglial cells could represent a major source of NO within the CNS.     

Jacques Lisfranc 1790–1847

Jacques Lisfranc was born in Saint-Paul-Jarrest (Loire), France, April 2nd, 1790, the son of a physician. Early in his youth he demonstrated a particular interest and aptitude for the field of medicine as he observed and commented upon his father's ministrations to his patients. He accomplished his preliminary studies at the Lyceum in Lyons and then went to Paris to continue his medical training at the Hôtel-Dieu. It was there that he came under the tutelage of Dupuytren. It was soon said that Lisfranc was at least as worthy as his superior. Later the two men developed a certain animosity toward each other which became manifest rather severely in the medical political arenas of the time. Lisfranc received his doctorate of medicine in 1812 at a time that France was involved in the Napoleonic wars. He was commissioned as a surgeon and distinguished himself in campaigns in Saxony and in France. Following the war he established his practice in Paris. Fortuitously, one day Lisfranc rescued a magistrate who fell from his horse. By this serendipitous meeting Lisfranc was invited to join the faculty of medicine at the Hospital of Pity. He rose rapidly to chief of surgery and developed the reputation of being extremely competent, truly a master surgeon. For over 20 years he was affiliated with that institution and wrote numerous articles on such diverse subjects as shoulder disarticulation, the application of the stethoscope in the diagnosis of fractures, and on diseases of the uterus. In addition, he wrote two books which were well received—one onSurgery at the Hospital of Pity and the other onOperative Medicine. ThisClassics presentation has been selected because it has been generally attributed that Lisfranc was the first person to remove a cancerous tumor from the rectum. The technique involves essentially a transanal approach. As was the custom of the day, the report appears as narrated presumably by one of his assistants. Among the many distinctions Lisfranc achieved, he was founding member and ultimately President of the French Academy of Medicine and Chevalier of the Legion of Honor. Lisfranc developed an enormous clinical practice, and in spite of many physical infirmities he persisted in his surgery until the day of his death, May 12, 1847, at the age of 57.     

Tunicamycin Dissociates Depolarization-induced Calcium Entry From Transmitter Release. Involvement of Glycosylated Protein(s) in the Process of Neurosecretion in PC-12 Cells

The process of regulated secretion in PC-12 cells is tightly coupled to calcium entry, which is absolutely dependent on extracellular Ca2+([Ca2+]ex). Tunicamycin treatment of the cells dissociated depolarization-triggered Ca2+ influx from depolarization (high K+)-induced transmitter release into two distinct and independent phases. Deplarization-evoked Ca2+ influx was not affected by tunicamycin treatment (1 microg/ml, 72 h), whereas depolarization-evoked transmitter release was strongly inhibited (> 60%), suggesting at least a two-step process, and the participation of glycosylated protein(s) in the actual fusion/secretion step. Similarly, bradykinin-mediated transmitter release was linearly related to and absolutely dependent on Ca2+ entry, and was inhibited by tunicamycin treatment (> 80%), whereas bradykinin-evoked Ca2+ entry was not impaired, indicating that glycosylated protein(s) are essential for bradykinin-evoked release at a step subsequent to Ca2+ influx. The heavily glycosylated alpha2 subunit of the dihydropyridine-sensitive channel, which was used to monitor tunicamycin inhibition of glycosylation, was not expressed in the tunicamycin-treated cells, as shown by Western blot analysis. This observation allowed us to conclude that the alpha1 subunit of the heteromeric dihydropyridine voltage-sensitive Ca2+ channel, which is responsible for Ca2+ entry, is also fully functional when not assembled with its corresponding alpha2 subunit. The molecular properties of the alpha2 subunit, whose role in the complex structure of the channel is not yet understood, are shown for the first time for the L-type Ca2+ channel of PC-12 cells. Similar to cardiac and skeletal muscle cells, the alpha2 subunit appears to be a glycosylated polypeptide of molecular weight 170 kD and to display a characteristic mobility shift to 140 kD under reducing conditions.     

Endothelins Inhibit Junctional Permeability in Cultured Mouse Astrocytes

Endothelins, a family of potent vasoconstrictor peptides initially characterized in peripheral tissues, have also been reported to be synthesized in the brain. In this structure several cell types, including astrocytes, endothelial cells and certain neurons, are potential targets for these peptides. In astrocytes, endothelins induce changes in the concentration of several second messengers (calcium, diacylglycerol, arachidonic acid, cAMP) known to be involved in the regulation of gap junction channels. Using the scrape loading/dye transfer technique we have observed that two isoforms of endothelin, endothelin-1 and endothelin-3, strongly inhibit the extent of dye-coupling between confluent astrocytes, suggesting that gap junction permeability was reduced. This inhibitory effect on dye coupling was reproduced by the snake venom sarafotoxin. When used at 10⁻⁷ M, these three compounds had inhibitory effects on gap junction channels which were comparable to those induced by the well known uncoupling agents octanol and halothane. In the absence of extracellular calcium, the effects of endothelins were largely prevented, suggesting that second messengers linked to the activation of phospholipases C and/or A₂, which both are dependent on external calcium, could be involved in the uncoupling mechanism.     

Synergistic Regulation of Cytosolic Ca2+ Concentration by Adenosine and alpha1-Adrenergic Agonists in Mouse Striatal Astrocytes

Adenosine has a broad array of actions on neurons but astrocytes also possess adenosine receptors. We have previously shown that adenosine, by acting on astrocytes in the striatum, can modulate neuronal responses mediated by receptors coupled to phospholipase C through an astrocyto - neuronal interaction. In addition, adenosine was found to potentiate the alpha1-adrenergic production of inositol phosphates in astrocytes. The mechanism involved in this potentiation was further investigated by examining the effects of adenosine and alpha1-adrenergic receptor agonists on cytosolic Ca2+ in cultured striatal astrocytes from the embryonic mouse in primary culture. When used alone, methoxamine, a selective agonist of alpha-adrenergic receptors or 2-chloroadenosine, a stable analogue of adenosine, induced a transitory increase in cytosolic Ca2+, but their combined addition led to a sustained increase in cytosolic Ca2+, which seems to be due to a Ca2+ influx, because it was not observed in the absence of external Ca2+. Voltage independent Ca2+ channels contribute to this process and different blockers of voltage-operated calcium channels, such as dihydropyridines, phenylalkylamines, La3+ or Co2+ were ineffective in suppressing the sustained cytosolic Ca2+ elevation. Three observations suggest the implication of arachidonic acid in the observed potentiation: (i) arachidonic acid induced a sustained elevation of cytosolic Ca2+ similar to that evoked by the coapplication of methoxamine and 2-chloroadenosine; (ii) the addition of arachidonic acid during the calcic plateau produced by the combined application of the agonists did not increase further cytosolic Ca2+ levels; (iii) in the presence of methoxamine, 2-chloroadenosine induced a release of arachidonic acid. The stimulation of phospholipase C and the resulting activation of protein kinase C induced by methoxamine seem to be required for the potentiating effect of 2-chloroadenosine on cytosolic Ca2+. In fact, the direct activation of protein kinase C by an exogenous diacylglycerol analogue mimicked the effect of methoxamine because, in this condition, 2-chloroadenosine alone evoked a sustained elevation of cytosolic Ca2+. Therefore, methoxamine, through the successive activation of phospholipase C and protein kinase C, could allow a lipase, probably phospholipase A2, to be stimulated by 2-chloroadenosine. Arachidonic acid has already been shown to trigger the opening of K+ channels and the formation of inositol phosphates in other cell types. Therefore, in striatal astrocytes, 2-chloroadenosine, through an arachidonic acid-mediated hyperpolarization, could increase the Ca2+ driving force and thus improve Ca2+ influx through inositol phosphate-gated channels. This hypothesis is further supported by the suppressing effect of a 50 mM KCI-induced depolarization on the long lasting elevation of cytosolic Ca2+ seen in the combined presence of 2-chloroadenosine and methoxamine.