Positive captopril renography in a transplanted kidney with arteriovenous fistula.
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Biomedical subjects
Publications and source records attributed to A Hassan.
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The flow pattern in the splenic vein has been previously reported in patients with portal hypertension, but with no reference to the flow within the intrasplenic venous radicles. Using Doppler ultrasound, this study describes the intrasplenic venous flow direction in 176 adult patients with intrahepatic portal hypertension. In our series, a normal flow pattern was maintained in all except four patients (2.3%) who had either reversed or dual venous drainage patterns resulting in trans-splenic portosystemic shunts. These abnormal patterns are Doppler signs of portal hypertension which might be associated with a higher risk of oesophageal variceal bleeding. It is recommended that the intrasplenic venous flow pattern should be assessed before surgical intervention involving the spleen in patients with portal hypertension.
Reactive oxygen species play a role in the formation of gastric lesions induced by nonsteroidal antiinflammatory drugs. The present study was undertaken to determine whether endogenous antioxidants in gastric mucosa can protect it against the damaging effects of oxygen free radicals. This study examine oxygen free radical production (superoxide anions and hydrogen peroxide), gastric mucosa antioxidant defense mechanisms (glutathione, catalase, superoxide dismutase), the lesion-inducing effects of the generated oxygen free radicals (vascular permeability, lipid peroxidation) and gastric ulceration in rats treated orally with indomethacin at 10 mg/kg at 2 and 6 h after drug administration. Two hours after administration of the antiinflammatory drug, there was a sharp increase in production of oxygen free radicals in the gastric mucosa with no alteration in other parameters examined. Six hours after indomethacin administration the production of oxygen free radicals returned to basal levels, but there was a high degree of gastric ulceration and a significant increase in lipid peroxidation and vascular permeability together with decreases of 45% in glutathione concentration and 30% in catalase relative to the control group. These results suggest that like plasma, the gastric mucosa has an antioxidant capacity and only when this capacity is exhausted are the lesive effects of the oxygen free radicals manifested.
OBJECTIVE: To determine the prevalence of tearing and canalicular fibrosis in patients receiving systemic 5-fluorouracil (5-FU) therapy and the reversibility of the symptoms when treatment is stopped. DESIGN: Prospective study. SETTING: University-affiliated tertiary care hospital in Toronto. PATIENTS: Thirty patients (17 men and 13 women aged 38 to 81 years) with advanced gastrointestinal carcinoma receiving intravenous 5-FU therapy as palliative (weekly) treatment (20 patients) or adjunctive (cycle) treatment (10 patients). OUTCOME MEASURES: Tearing, eyelid changes and canalicular fibrosis during and after treatment. Patients who experienced tearing were advised to massage and wipe the lower eyelids in an upward direction. RESULTS: Tearing and canalicular fibrosis developed in 10 patients (50%) and 3 patients (15%) respectively in the palliative treatment group; no patient in the adjunctive treatment group experienced these side effects. In the palliative treatment group, the patients who experienced tearing received double the dose of 5-FU (p = 0.03) and received treatment for twice as long (p = 0.042) as those who did not experience tearing. Of the patients with tearing, those in whom canalicular fibrosis developed received treatment for three times as long as those without fibrosis and received 2.6 times the total dose (p < 0.000). Of the seven patients with tearing in whom canalicular fibrosis did not develop, four stopped 5-FU treatment, and 2 to 4 weeks later the epiphora disappeared. CONCLUSIONS: Our findings suggest that the prevalence of tearing and canalicular fibrosis in patients receiving systemic 5-FU therapy as palliative treatment is related to the total dose and duration of treatment. Such side effects are less likely in those receiving adjunctive therapy. The epiphora is often reversible on stopping therapy if canalicular fibrosis has not yet developed.
The authors describe a rare case of surgical treatment of a paresis of the brachial plexus in a 63-year-old woman. The paresis improved significantly after extirpation of a tumour of the upper mediastinum which originated in the left subclavian artery and was classified as a leiomyosarcoma.
Only 30% of children have a matched family donor (MFD). Alternative donors can be found from volunteer unrelated donor (UD) panels, and almost every child has a haploidentical parental donor (Haplo). The outcome of alternative donor BMT has previously been inferior due to increased graft rejection and GVHD. The recent outcome of 121 consecutive children undergoing MFD, UD, and Haplo BMT between 1994 and 1997 was analysed. [table in text] Preparative regimens for MFD/UD/Haplo BMT respectively included TBI in 30%/36%/11%, chemotherapy only in 59%/64%/89%, Campath 1G or none n 14%/ 0%/0%. The balance of GVHD and rejection was addressed by T-cell depletion (Campath 1M) in 2/71 MFD BMTs, T-cell depletion with addback of 5 x 10(4) T cells/kg on day zero in 33/41 UD BMTs, and T cell depletion of purified mobilised peripheral blood CD34+ cells and bone marrow in 9/9 Haplo BMTs. Stable engraftment was achieved in 68/71, and 35/41 (one patient after 2nd BMT) and 7/9 MFD, UD, and Haplo BMTs respectively. Median follow up, survival, disease free survival and, death rates for MFD/UD/Haplo BMT were 12/12/12 months, 74%/77%/78%, 69%/67%/67%, and 27%/23%/23% respectively. Within a wide range of paediatric diseases the outcome of alternative donor BMT now parallels that of MFD BMT.
We investigated T3 effects on cell proliferation and apoptosis in the optic lobe of the chick embryo between embryonic days (E) 6 and 11. Injection of T3 into the yolk increased [3H]thymidine incorporation between E7 and E9. This increased mitosis was followed by altered timing and degree of apoptosis during E9-11. In T3-treated embryos a marked increase in apoptosis occurred on E10, coincident with increased levels of mRNA encoding Bax, a pro-apoptotic protein. By E11, the overall morphology and total number of cells in each layer of the optic lobe were not different in control and treated embryos. Thus, although T3 transiently increases cell number, a homeostatic mechanism enters into play re-adjusting the balance between cellular proliferation and cell death.
Flow-mediated vasodilation (FMD) of systemic arteries, a non-invasive parameter of endothelial function, is correlated with cardiovascular risk factors. The relationship between FMD and morphologically and clinically evident coronary artery disease has not been described. This study was performed to test the hypothesis that an impairment of FMD in the brachial artery is related to the presence and/or extent and severity of coronary artery disease (CAD). We examined 74 patients with angina pectoris and 14 control subjects (age 17 36 years). Angiography revealed coronary artery disease (> or = 30% diameter stenosis) in 44 patients (CAD, age 32 67 years) and smooth coronary arteries in 30 patients (non-CAD, age 22-73 years). Vasodilation following reactive hyperemia and after sublingual nitroglycerin (NTG) was assessed in the brachial artery using B-mode high resolution ultrasound. CAD patients showed markedly impaired FMD compared to the non-CAD group (5.7 +/- 4.8 versus 12.6 +/- 6.7%, P < 0.0001) and to controls (5.7 +/- 4.8 versus 15.7 +/- 3.9%, P < 0.00001). NTG induced similar degrees of vasodilation in the CAD and non-CAD groups but less vasodilation in the CAD patients compared to controls (12.2 +/- 6.3 versus 20.4 +/- 6.9%, P < 0.01). On univariate analysis, impaired FMD in CAD patients and non-CAD patients was related to the extent of coronary disease (1-, 2- or 3-vessel disease; r = -0.67, P < 0.0001), to the maximum percent diameter stenosis in one of the major coronary vessels (r = -0.52, P < 0.0001), brachial artery diameter (r = -0.46, P < 0.0001) and plasma cholesterol level (r = -0.34, P < 0.001). On multiple stepwise regression analysis the extent of coronary disease (r = -0.51, P < 0.0001) and the baseline brachial artery diameter (r = -0.37, P < 0.0001) were independently associated with FMD in CAD and non-CAD patients. The present findings suggest that the impairment of FMD in the brachial artery, a marker of systemic endothelial function, is closely related to the angiographic extent of CAD.
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Poliomyelitis eradication activities in Egypt were reviewed to identify the critical factors for the progress seen by 1995 and to highlight problems that could be avoided in other countries in which poliomyelitis is endemic. National immunization and surveillance data demonstrate that the combination of high routine immunization coverage (>85%) with oral polio vaccine combined with two properly conducted rounds of national immunization days (NIDs) resulted in a 75% reduction in reported polio cases between 1992 and 1993. Available data suggest that earlier control strategies, such as single-round NIDs in 1990 and 1991, the administration of inactivated poliovirus vaccine (IPV) at 2 months of age in 1992-1993, and the use of "mop-up" campaigns while wild poliovirus was still widespread, did not contribute substantially to the recent decline in cases. Proper implementation of the World Health Organization's recommended strategies can eliminate wild poliovirus circulation in the large, densely populated tropical countries in which poliomyelitis remains endemic.
Apoptosis is a fundamental mechanism implicated in normal development. One of the most spectacular developmental events involving apoptosis is tail regression during amphibian metamorphosis. We analyzed how thyroid hormone (3, 5, 3'-triiodothyronine, T3), the orchestrator of metamorphosis, affects expression and function of the proapoptotic gene Bax in the tail muscle of free-living Xenopus tadpoles. During natural metamorphosis Bax mRNA was expressed in tail muscles and was spatially correlated with apoptosis. Precocious treatment of tadpoles with T3 induced Bax expression and apoptosis. To verify that Bax expression was causally related to apoptosis we used a naked DNA gene transfer method to express Bax in the dorsal tail muscle. This induced apoptosis, and the process was exacerbated by T3 treatment. To determine whether T3 effects on Bax expression involved transcriptional regulation, we injected a Bax promoter sequence into dorsal and caudal tail muscles. In the dorsal muscle, T3 treatment did not affect transcription from the Bax promoter. However, in the caudal muscle, T3 treatment significantly increased Bax transcription. We conclude that T3-induced apoptosis in Xenopus tadpole tail muscles involves Bax-activating and Bax-synergis tic mechanisms. These programs are induced in spatially and temporally distinct manners.
We studied the effects of the timing of tourniquet release in 88 patients randomly allocated for release after wound closure and bandaging (group A), or before the quadriceps layer had been closed allowing control of bleeding before suture (group B). The groups were similar in mean age, weight, gender, preoperative knee score, radiographic grading, and prosthesis implanted. Patients in group B had less postoperative pain, achieved earlier straight-leg raising, and had fewer wound complications. Five patients in group A had to return to theatre, three for manipulation under anaesthesia, one for secondary closure of wound dehiscence, and one for drainage of a haematoma. The last patient later developed a deep infection, which was treated by a two-stage revision. There were no significant differences between the two groups in operating time, or the decrease in haemoglobin concentration at 48 hours postoperatively. Some of the adverse effects of the use of a tourniquet for knee surgery can be significantly reduced by early tourniquet release, with haemostasis before the quadriceps mechanism and the wound are closed.
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The preference of the linker histones to bind to superhelical DNA in comparison with linear or relaxed molecules suggests that these proteins might, in turn, change the twist and/or writhe of DNA molecules upon binding. In order to explore such a possibility, we looked for changes in the linking number of plasmid pBR322 caused by H1 binding, using assays that involve nicking and resealing of DNA strands. Two types of enzymes were used, eukaryotic topoisomerase I and prokaryotic DNA ligase. The results revealed that H1 binding causes unwinding of the DNA, with the unwinding angle being approximately 10 degrees . The globular domain of histone H1 is also capable of unwinding DNA, but to a lesser degree.
Nonviral gene transfer into the central nervous system (CNS) offers the prospect of providing safe therapies for neurological disorders and manipulating gene expression for studying neuronal function. However, results reported so far have been disappointing. We show that the cationic polymer polyethylenimine (PEI) provides unprecedentedly high levels of transgene expression in the mature mouse brain. Three different preparations of PEI (25-, 50-, and 800-kD) were compared for their transfection efficiencies in the brains of adult mice. The highest levels of transfection were obtained with the 25-kD polymer. With this preparation, DNA/PEI complexes bearing mean ionic charge ratios closest to neutrality gave the best results. Under such conditions, and using a cytomegalovirus (CMV)-luciferase construction, we obtained up to 0.4 10(6) RLU/microgram DNA (equivalent to 0.4 ng of luciferase), which is close to the values obtained using PEI to transfect neuronal cultures and the more easily transfected newborn mouse brain (10(6) RLU/microgram DNA). Widespread expression (over 6 mm3) of marker (luciferase) or functional genes (bcl2) was obtained in neurons and glia after injection into the cerebral cortex, hippocampus, and hypothalamus. Transgene expression was found more than 3 months post-injection in cortical neurons. No morbidity was observed with any of the preparations used. Thus, PEI, a low-toxicity vector, appears to have potential for fundamental research and genetic therapy of the brain.
The effect of histone H1 binding on the cleavage of superhelical plasmids by single-strand-specific nucleases was investigated. Mapping of P1 cleavage sites in pBR322, achieved by EcoRI digestion after the original P1 attack, showed an intriguing phenomenon: preexisting susceptible sites became "protected," whereas some new sites appeared at high levels of H1. Similar results were obtained with another single-strand-specific nuclease, S1. Disappearance of cutting at preexisting sites and appearance of new sites was also observed in a derivative plasmid that contains a 36-bp stretch of alternating d(AT) sequence that is known to adopt an altered P1-sensitive conformation. On the other hand, H1 titration of a dimerized version of the d(AT)18-containing plasmid led to protection of all preexisting sites except the d(AT)18 inserts, which were still cut even at high H1 levels; in this plasmid no new sites appeared. The protection of preexisting sites is best explained by long-range effects of histone H1 binding on the superhelical torsion of the plasmid. The appearance of new sites, on the other hand, probably also involves a local effect of stabilization of specific sequences in Pl-sensitive conformation, due to direct H1 binding to such sequences. That such binding involves linker histone N- and/or C-terminal tails is indicated by the fact that titration with the globular domain of H5, while causing disappearance of preexisting sites, does not lead to the appearance of any new sites.
Photosensitizer is known to spread with vasogenic edema fluid arising from a cerebral lesion (Neurosurg 33:1075-1082, 1993), which may be essential for sensitizing malignant cells outside the main tumor mass. The present experiments seek to elucidate whether resultant necrosis of perifocal brain tissue after laser irradiation follows a corresponding time pattern and whether damage depends on the photosensitizer dose. Male Wistar rats were anaesthetized with chloralhydrate for venous cannulation, craniotomy and focal cold lesion in order to induce vasogenic edema. Simultaneously, Photofrin II (PF II) was administered at a dose of 5 mg kg-1. The animals were re-anaesthetized after either 4, 12 or 24 h for the irradiation of lesion and perifocal tissue with 200 J cm-2 of laser light (630 nm). The brains of other animals were irradiated 4 h after cold lesion with 200 J cm-2 after receiving either 0, 2.5 or 5 mg kg-1 PF II (all groups: n = 6). Resultant necrosis was assessed planimetrically in serial coronal cryosections of brains perfusion fixed 24 h after irradiation. Necrosis was significantly enhanced with irradiation 4 h after cold lesion and photosensitizer (avg. area +/- SD: 4.3 +/- 0.7 mm2) compared with lesion only (0.84 +/- 0.2 mm2). Maximal necrosis (6.3 +/- 1.6 mm2) occurred with irradiation 12 h after lesion, whereas necrosis was only slightly increased with irradiation at 24 h (2.8 +/- 0.4 mm2). Furthermore, the area of necrosis was dependent on the sensitizer dose (0 mg kg-1: 0.7 +/- 0.3 mm2, 2.5 mg kg-1: 2.09 +/- 0.2 mm2, 5 mg kg-1: 4.3 +/- 0.7 mm2; all differences p < 0.05). Therefore, to prevent unwanted side-effects such as necrosis of edematous but otherwise healthy, peritumoral tissue in the treatment of malignant cerebral tumors by PDT, tribute should be paid to the possibility of time and dose dependent sensitization of the perifocal tissue after i.v. administration of photosensitizer.
It was possible for the patients to avoid surgical intervention in a number of complicated periapical endodontic situations by means of Nd:YAG laser-assisted sterilization. A WSR has only very good primary results and the long-term successes are very limited. Once a lesions has healed in the manner explained in this study, in other words, with regeneration of the periapical anatomy, there is a very good long-term prognosis. Laser technology is an instrument whose overall effects represent a decisive improvement in the efficiency of conservative endodontic treatment in fields that were previously outside our sphere of influence.