Characterization of the role of IL-6 in the progression of prostate cancer

BACKGROUND: We recently identified IL-6, a pleiotropic cytokine implicated in the neoplastic process of a variety of neoplasms, as a mediator of prostate cancer morbidity. In the present study, we investigated the expression of members of the IL-6 supergene family and related cytokines and the potential role of IL-6 in prostate cancer growth regulation. METHODS: Five established human prostate cancer cell lines were screened by ELISA for production of granulocyte colony-stimulating factor (G-CSF), leukemia inhibitory factor (LIF), ciliary neurotrophic factor (CNTF), oncostatin M (OSM), tumor necrosis factor (TNF), interleukin-1 (IL-1), and granulocyte macrophage colony-stimulating factor (GM-CSF). Expression of the ligand-binding component of the IL-6 receptor, IL-6Rp80, was evaluated by ELISA and RT-PCR. Sequential immunoprecipitation and immunoblotting were performed to assay for expression of the signal-transducing component of the IL-6 receptor, gp130. The effects of IL-6 on cell growth were assessed by MTT assays. RESULTS: The three hormone-refractory cell lines, DU-145, TSU, and PC-3, secreted distinct combinations of cytokines (DU-145: IL-6, GM-CSF; TSU: IL-6, LIF; PC-3: IL-6, G-CSF, LIF, IL-1, GM-CSF), each uniformly expressing IL-6. In contrast, neither of the two hormone-dependent cell lines, LNCaP-ATCC and LNCaP-GW, secreted significant quantities of any of the cytokines analyzed. None of the cell lines secreted detectable quantities of OSM, CNTF, or TNF. All cell lines, irrespective of hormone status, expressed both Il-6Rp80 and gp130. Addition of IL-6 in vitro inhibited growth of hormone-dependent cells, but had no effect on hormone-refractory lines. Anti-IL-6 neutralizing antibody inhibited growth of hormone-refractory cells. CONCLUSIONS: IL-6 appears to undergo a functional transition from paracrine growth inhibitor to autocrine growth stimulator during progression of prostate cancer to the hormone-refractory phenotype.     

Surgical management of ocular motor cranial nerve palsies

This article reviews the various surgical treatment approaches currently used in the management of ocular motor cranial nerve palsies. Regardless of the approach, the final goal is improved alignment, especially in the primary and reading positions.     

Endophthalmitis from Mycobacterium bovis-bacille Calmette-Guérin after intravesicular bacille Calmette-Guérin injections for bladder carcinoma

PURPOSE: To present clinical and histologic findings of intraocular infection with Mycobacterium bovis-bacille Calmette-Guérin after intravesicular bacille Calmette-Guérin injections for treatment of bladder carcinoma. METHODS: A 77-year-old man was initially seen with visual acuity of 20/200, focal retinitis, vasculitis, and progressive vitreous opacity in the right eye and visual acuity of light perception, intraocular inflammation, and a dense cataract in the left eye 14 months after intravesicular injection of live bacille Calmette-Guérin organisms. RESULTS: Vitreous cultures in the right eye demonstrated growth of bacille Calmette-Guérin organisms. Bilateral loss of light perception occurred despite systemic antimy-cobacterial therapy. Histopathologic examination demonstrated nongranulomatous inflammation and acid-fast bacilli in both eyes. CONCLUSION: Delayed endogenous endophthalmitis may develop after intravesicular bacille Calmette-Guérin injection that may not respond to systemic agents. Intravitreal therapy may be indicated.     

Adverse drug events in hospitalized patients A comparison of doctors, nurses and patients as sources of reports

Objective: This study investigated the relative value of adverse drug events reported by doctors, nurses and patients. Methods: The study was conducted on a total of four wards: the paediatric and internal medicine wards (including geriatric patients) of two peripheral hospitals in the Netherlands. Adverse drug events were collected by spontaneous reporting (doctor and nurse reports) and by daily ward visits, during which the patients were interviewed by a hospital pharmacist (patient reports). Criteria for relative value of the reported adverse drug events were the number of potentially serious reactions, the number of reactions not mentioned in the patient information leaflet and the number of reactions reported to new drugs (5 years or less on the Dutch market). No formal causality assessment was applied. Results: Over a period of 2 months in 1996 (Hospital I) and 2 months in 1997 (Hospital II) a total of 620 patients were included in the study and adverse drug events were reported in 179 (29%) of these cases. Doctors reported a statistically significant larger number of serious (26% of all doctor reports; odds ratio (OR) 3.2; confidence interval (CI) 1.2–8.7) and unknown (39%; OR 2.5; CI 1.0–6.0) adverse drug events than patients themselves during the daily ward visit. Doctors also reported more serious and unknown adverse drug events than nurses. Adverse reactions to new drugs were reported during the daily ward visit only (8% of all daily ward visit reports). Conclusion: This study reconfirms that doctors are the main source for reports of serious and unknown adverse drug events in hospitalized patients. However, patients themselves seem to report more adverse reactions to new drugs (during the daily ward visit). By focusing on patients using new drugs, the daily ward visit might become cost-effective. This needs to be explored in future studies. Received: 10 September 1998 / Accepted in revised form: 30 November 1998     

Commissioning new buildings: equipment

Any new building will, with occasional exceptions, require new furnishings and equipment. In principle the organisation of this is straightforward. In practice it is a complicated exercise, full of snags. Phillip Simons discusses some of the problems.     

Early tertiary elephant-shrews from Egypt and the origin of the Macroscelidea

Recent expeditions to the Fayum Depression, Egypt, have made possible the discovery of mandibles and a maxilla of a new genus and species of late Eocene elephant-shrew as well as initial evidence of the upper dentition of the early Oligocene taxon Metoldobotes. These fossils demonstrate that macroscelideans underwent a significant radiation in the Early Tertiary of Africa. Two new subfamilies are recognized and described. These Tertiary macroscelideans are the most primitive elephant-shrews known and indicate that previous hypotheses of a close phylogenetic relationship between macroscelideans and either lagomorphs, erinaceotans, or tree-shrews are unlikely. Rather, the dental anatomy of the Fayum macroscelideans provides evidence for a derivation of the order from within the Condylarthra.     

Experimental measurement of impulse response and noise for an emission computed tomography system

Experimental studies have been made of the impulse response and noise characteristics of a tomographic system using a gamma camera. Fourier transform, deconvolution and iterative methods have been used with a CDC 6600 computer to reconstruct images from data obtained for various experimental arrangements of sources in a cylindrical phantom. It is shown that with an appropriate attenuation correction the impulse response in the reconstruction is substantially constant, independent of the position of the source in the phantom and that the reconstruction technique used is of secondary importance.The resolution obtained for the impulse response and the relative noise level throughout the non image part of the reconstructions is shown for different experimental situations.The measured variance in the reconstruction of an extended uniform activity source was found to be somewhat below the theoretical value except at high count densities (above 1,000 counts per image element) where the limit of accuracy of the reconstruction is shown to be imposed by the variation in the camera sensitivity over the field of view.     

The neuro-ophthalmology of systemic lupus erythematosus

Conclusion Experience with many patients with SLE and a review of the literature indicate that neuro-ophthalmic abnormalities are frequently found in patients with SLE.The optic disc may become swollen in patients with SLE either as a result of local retinal lesions or secondary to increased intracranial pressure. Some of the cases with increased intracranial pressure resemble the entity of pseudotumor cerebri.Patients with SLE may develop an optic neuropathy. The pathogenesis appears either to be demyelinative or secondary to parenchymal microinfarcts. Some of the patients develop a clinical syndrome identical to Devic's desease. The response to corticosteroids is unpredictable. Acute anterior ischemic optic neuropathy is rare in patients with SLE.Homonymous hemianopias may occur in isolation or in association with hemiplegia, aphasia or hemisensory defects. Both formed and unformed visual hallucinations are commonly encountered, and patients may have transient amaurosis or geniculocalcarine (cortical) blindness. Visual hallucinations identical to those seen in migraine, and vascular headaches appear to be more common in patients with SLE than among controls.Diplopia occurs in patients with SLE most often as a transient phenomenon associated with vertigo. Transient ptosis may also occur. These findings, like the transient bilateral amaurosis, suggest the picture of insufficiency in the vertebrobasilar system. Diplopia may also occur from fixed lesions in the brain stem and several instances of internuclear ophthalmoplegia have been recognized. If ophthalmoplegia or ptosis develop in a patient with SLE it should suggest the possibility that the patient has myasthenia gravis which occurs with unusually high frequency among patients with SLE.     

Prolongation of the ejaculation latency in the male rat by thioridazine and chlorimipramine

Thioridazine (3 mg/kg) and chlorimipramine (1.5–6.0 mg/kg) prolonged the ejaculation latency and increased the number of mounts but did not change the number of intromissions preceding ejaculation. Blockade of peripheral and central noradrenaline receptors by phentolamine and phenoxybenzamine respectively resulted in a suppression of all aspects of the sexual behavior with increasing doses. dl-5-HTP (25–100 mg/kg) in combination with an inhibitor of peripheral 5-HTP decarboxylase (benserazide, 25 mg/kg) produced, like chlorimipramine and thioridazine, a prolongation of ejaculation latency and an increase in the number of mounts preceding ejaculation. Selective inhibition of 5-HT reuptake however, by zimelidine (0–20 mg/kg) or alaproclate (0–20 mg/kg) did not affect the mating behavior. At higher doses of these drugs some animals failed to initiate sexual activities. There was an increase in the postejaculatory interval but no change in the ejaculatory latency.It is concluded that the prolonged ejaculation latencies observed following treatment with thioridazine or chlorimipramine is not due to a blockade of central or peripheral adrenergic -receptors.