Phase I-II study of gamma interferon and 5-fluorouracil for patients with metastatic renal cell carcinoma

We have completed a phase I/II trial to evaluate the toxicity and efficacy of the combination of gamma interferon and 5-fluorouracil in metastatic renal cell carcinoma. Gamma interferon was administered at a weekly dose of 100 micrograms. 5-fluorouracil was given as a 5 day continuous infusion days 1-5 of each 21 day cycle. In the phase I portion of the trial, the gamma interferon dose was held constant, while the 5-fluorouracil was escalated from 500 to 800 mg/m2/day. Serum neopterin and beta 2 microglobulin were measured prior to and 48 hours after each dose of gamma interferon for the first six weeks of treatment. Dose limiting toxicity was not encountered in the phase I part of the trial; therefore the phase II study was initiated at the 800 mg/m2/day dose of 5-fluorouracil. No responses were seen among 34 patients treated on the phase II trial. Forty-six percent of patients experienced disease stabilization and the remainder progressed through treatment. In the phase I trial, increments in neopterin and beta 2 microglobulin levels differed significantly between patients treated with lower and higher doses of 5-fluorouracil. We conclude that the addition of 5-fluorouracil to gamma interferon does not appear to enhance the cytokines clinical activity. Incremental increases in macrophage activation markers with escalating 5-fluorouracil doses suggests a role for 5-fluorouracil beyond its usual proposed cytotoxic activity and warrants further investigation into potential immunologic effects of this drug.     

Motility Disorders after Roux-en-Y Gastrojejunostomy

About 30% of patients who have a Roux-en-Y gastrojejunostomy after gastrectomy suffer from abdominal pain, nausea, vomiting of food and bloating made worse by eating. This syndrome, called the Roux stasis syndrome, is caused, in part, by a motility disorder of the Roux limb. Transection of the jejunum during the construction of the limb separates the limb from the natural small intestinal pacemaker located in the duodenum. Ectopic pacemakers then appear in the limb and trigger retrograde contractions in its proximal portion. These contractions slow transit through the limb and result in Roux stasis. Current nonsurgical treatment of the syndrome includes the use of prokinetic agents and intestinal pacing, neither of which has demonstrated long-term benefits. A near-total gastrectomy may speed upper gastrointestinal transit somewhat, but stasis in the Roux limb often persists. Our current approach aims at preventing the syndrome by the use of an ‘uncut’ Roux limb, an operation which preserves myoneural continuity between the duodenal pacemaker and the Roux limb and so prevents the appearance of ectopic pacemakers and stasis in the limb.     

Development and regulation of substance P expression in neurons of the tadpole optic tectum.

Activity-dependent synaptic plasticity is characteristic of developing visual systems. Using the frog retinotectal system, we investigated the extent to which afferent input affects neurotransmitter expression in a target structure. We have concentrated on a particular subpopulation of tectal cells that is immunoreactive to substance P (SP). Early in development, SP expression in tectal neurons was restricted to the anterior lateral region of the tectum. As tadpoles developed, this expression expanded into progressively more posterior and medial regions in a manner that closely followed the gradient of tectal maturation. At all times, however, anterior and lateral tectal regions had a greater percent of SP-like immunoreactive (SP-ir) cells than posterior and medial ones. Horseradish peroxidase (HRP) labeling of the retinal ganglion cell projection in conjunction with SP immunocytochemistry demonstrated that innervation by retinal ganglion cell terminals preceded the expression of SP by tectal cells. This suggested that the optic nerve may influence SP differentiation and/or expression. In support of this idea, transection of the optic nerve resulted in a decrease in SP expression in the deafferented tectal lobe of tadpoles. This result, opposite to that seen previously in the adult, also indicates that optic nerve-dependent regulation of SP expression in the developing and mature systems occurs through different pathways.     

Effects of pesticide seed treatments onRhizobium japonicum and its symbiotic relationship with soybean

Summary SeventeenRhizobium japonicum cultures isolated from soybean nodules induced formation of nodules on taproots of soybean plants. All isolates reduced acetylene to ethylene to different extentsin vitro. Paper disc assay indicated that two insecticides, lindane (-1,2,3,4,5,6-hexachlorocyclohexane), chlorpyrifos (O,O-diethyl O-3,5,6-trichloro-2-pyridyl phosphorothioate), and a fungicide, thiram (tetramethylthiuratn disulphide) individually or in combination caused significant inhibition of the growth ofR. japonicum No. 16.The effects of insecticide-fungicide seed treatments on the nitrogenase activity of soybean plants in nitrogen-fixing capacity, weights of leaves, stems, and nodules were determined. Thiram, singly or in combination with lindane and/or chlorpyrifos, significantly delayed growth of the plants and affected the activity of nitrogenase in the fixation of nitrogen 3 weeks after treatments. No drastic effect of any of the pesticide treatments on soybean plant growth was observed after 8 weeks.Contribution No., Research Institute, Agriculture Canada, London, Ontario.     

Sex differences and similarities in the management and outcome of stroke patients

BACKGROUND AND PURPOSE: Previous studies have documented sex differences in the management and outcome of patients with cardiovascular disease. However, little data exist on whether similar sex differences exist in stroke patients. We conducted a study to determine whether sex differences exist in patients with acute stroke admitted to Ontario hospitals. METHODS: Using linked administrative databases, we performed a population-based cohort study. The databases contained information on all 44 832 patients discharged from acute-care hospitals in Ontario between April 1993 and March 1996 with a most responsible diagnosis of acute stroke. The main outcomes measured consisted of sex differences in comorbidities, the use of rehabilitative services, the use of antiplatelet therapy and anticoagulants (in elderly stroke survivors aged > or =65 years only), discharge destination, and mortality. RESULTS: Male stroke patients were more likely than female stroke patients to have a history of ischemic heart disease (18.1% versus 15.3%, respectively; P<0.001) and diabetes mellitus (20.1% versus 18. 7%, respectively; P<0.001), whereas female patients were more likely than male patients to have hypertension (33.8% versus 30.0%, respectively; P<0.001) and atrial fibrillation (12.9% versus 10.2%, respectively; P<0.001). There were no sex differences in the usage of in-hospital rehabilitative services. The overall 90-day postdischarge use of aspirin and ticlopidine was similar in stroke survivors aged 65 to 84 years. However, among stroke survivors aged > or =85 years, men were more likely than women to receive aspirin (36. 0% versus 30.7%, respectively; P<0.001) and ticlopidine (9.2% versus 6.8%, respectively; P=0.007). Use of warfarin was similar for the two sexes. Men were more likely than women to be discharged home (50. 6% versus 40.9%, respectively; P<0.001) and less likely to be discharged to chronic care facilities (16.8% versus 25.2%, respectively; P<0.001). The risk of death 1 year after stroke was somewhat lower in women than men (adjusted odds ratio 0.939, 95% CI 0.899 to 0.980; P=0.004). The mortality differences were greatest among elderly stroke patients. CONCLUSIONS: Elderly men are more likely than elderly women to receive aspirin and ticlopidine and equally like to receive warfarin after a stroke. Despite these differences, elderly women have a better 1-year survival after a stroke.     

Rate of stroke recurrence in patients with primary intracerebral hemorrhage

BACKGROUND AND PURPOSE: Primary intracerebral hemorrhage (PICH) is a devastating illness with high early mortality. Hypertension is a major risk factor both for ischemic cerebrovascular disease and for intracranial hemorrhage. Survivors of PICH are at risk for both recurrent hemorrhage and ischemic cerebrovascular disease. We sought to determine the rate of recurrence of ICH or cerebral ischemia in a cohort of PICH patients at the Toronto Hospital, Toronto, Canada. METHODS: A retrospective search of computerized hospital records from 1986 to 1996 for patients with a discharge diagnosis of intracerebral hemorrhage (International Classification of Diseases, Ninth Revision-Clinical Modification [ICD-9-CM] code 431) was conducted to identify the index cases. Charts were abstracted for demographic and clinical characteristics. CT scans, MR scans, or radiologist reports were reviewed. To determine recurrence, the database was linked to the Ontario Provincial Government Vital Statistics Registry and to the Canadian Institute for Health Information database of hospital discharge abstracts. Logistic regression analysis was used to identify predictive factors for mortality after PICH. A Cox proportional hazards model was fitted to identify predictive factors for recurrent ICH or stroke. RESULTS: A total of 746 charts were identified by computer search. After abstraction, 423 index patients with PICH were identified. Of these, 27.4% died in the first 30 days of their admission. Predictors of death were age, intraventricular rupture of hemorrhage, and trilobar hemorrhage. The recurrence rate for PICH was 2.4% (95% CI 1.4% to 3. 9%) per year, whereas the recurrence rate for ischemic cerebrovascular disease was 3.0% (95% CI 1.8% to 4.7%) per year. The only significant predictor of readmission for ICH was lobar location of the index hemorrhage, with a hazard ratio of 3.8 (95% CI 1.2 to 12.0). CONCLUSIONS: PICH has a high 30-day mortality rate. Survival from the initial insult portends a moderate risk of recurrence of 2. 4% per year for PICH and 3.0% per year for ischemic cerebrovascular disease. Patients with PICH are at risk for both ischemic stroke or TIA and recurrent hemorrhage; thus, PICH may be a marker for ischemic stroke. Patients with lobar hemorrhage have a 3.8-fold increased risk of recurrent ICH.     

Transarterial embolisation of complex cavernous sinus dural arteriovenous fistulae with low-concentration cyanoacrylate

We report the effectiveness of low-concentration n-butyl-2-cyanoacrylate (NBCA)-Lipiodol-tungsten mixture (10–15 %) in the management of patients with aggressive or recurrent complex cavernous dural arteriovenous fistulae (CSDAVF). We treated five patients with complex CSDAVF with a low concentration of an NBCA-Lipiodol-tungsten mixture after catheterisation of the feeding arteries arising from the external carotid artery. Three had a recurrent CSDAVF after transarterial particulate embolisation. Three refused transvenous treatment or could not be treated in this way; two patients had also feeding dural branches of the internal carotid artery. All patients had complete resolution of symptoms and signs within a month of the procedure. No definite neurological complication was found during follow-up ranging from 12 to 36 months. Transarterial embolisation with low-concentration cyanoacrylate appears to be an effective alternative management of aggressive or recurrent CSDAVF. Received: 8 November 1999/Accepted: 2 March 2000     

胸骨后甲状腺肿物的手术处理

为探讨胸骨后甲状腺肿物手术切除的进路方式，回顾性分析３０年来外科治疗的结果。１９６５年至１９９４年间全部患者共８７例，其中结节性甲状腺肿６４例，占７３．６％；甲状腺腺瘤１３例，占１４．９％；甲状腺恶性肿瘤１０例，占１１．５％。通过颈部入路手术切除的占７０％（６１／８７），胸骨正中劈开切除的占１６％（１４／８７），前切口开胸切除的占１４％（１２／８７）。随着经验的积累，除误诊为纵隔其它来源的肿物外，１９８０年以后已不再行前切口开胸手术切除，１９８５年以后的４３例中，只有１例胸骨后结节性甲状腺肿的患者行胸骨劈开手术，其余均从颈部入路手术。由于颈部入路相对并发症少、损伤小、安全可靠，建议对良性的胸骨后甲状腺肿物和部分恶性肿物行颈部衣领式切口手术。     

Effects of nitric oxide donors on the afferent resting activity in the cephalopod statocyst

The effects of bath applications of the nitric oxide (NO) donors sodium nitroprusside (SNP), diethylamine sodium (DEA), 3-morpholinosydnonimine (SIN-1), and S-nitroso-N-acetyl-penicillamine (SNAP) on the resting activity (RA) of afferent crista fibers were studied in isolated statocysts of the cuttlefish Sepia officinalis. The NO donors had three different effects: inhibition, excitation, and excitation followed by an inhibition. The SNAP analog N-acetyl-DL-penicillamine (xSNAP; with no NO moiety) had no effect. When the preparation was pre-treated with the NO synthase inhibitor N(G)-nitric-L-arginine methyl ester HCl (L-NAME), the NO donors were still effective. When the preparation was pre-treated with the guanylate cyclase inhibitors methylene blue (M-BLU) or cystamine (CYS), NO donors had only excitatory effects, whereas their effects were inhibitory only when pre-treatment was with the adenylate cyclase inhibitors nicotinic acid (NIC-A), 2',3'-dideoxyadenosine (DDA), or MDL-12330A. When pre-treatment was with a guanylate and an adenylate cyclase inhibitor combined, NO donors had no effect; in that situation, the RA of the afferent fibers remained and the preparation still responded to bath applications of GABA. Selective experiments with statocysts from the squid Sepioteuthis lessoniana and the octopod Octopus vulgaris gave comparable results. These data indicate that in cephalopod statocysts an inhibitory NO-cGMP and an excitatory NO-cAMP signal transduction pathway exist, that these two pathways are the key pathways for the action of NO, and that they have only modulatory effects on, and are not essential for the generation of, the RA.