Biomedical subjects
Publications and source records attributed to I A el Hag.
Two cases of intraspinal mycetoma caused by Madurella mycetomatis and Streptomyces somaliensis presenting with paraplegia are reported. In these cases, there was neither skin or bone involvement by the disease. The route of entry of the organisms is not known; however, hematogenous blood vessel invasion by S. somaliensis was identified in the second case.
AIM: To study the morphology and function of the liver in visceral leishmaniasis (Kala-azar). METHODS: Percutaneous liver biopsy specimens from 18 patients with confirmed visceral leishmaniasis were examined under light and electron microscopy before and after treatment with pentovalent antimony. The tissue was also examined for hepatitis B surface and core antigens using immunoperoxidase staining. Liver function was investigated in nine patients before and after treatment. RESULTS: Specimens before treatment showed Kupffer cells and macrophages colonised by leishmania parasites in 40% of cases. A chronic mononuclear cell infiltrate had affected the portal tracts and lobules. Ballooning degeneration of the hepatocytes, fibrosis of the terminal hepatic venules, and pericellular fibrosis were common findings. The fibrosis was related to Ito cells transforming to fibroblast-like cells. None of the patients had hepatitis B infection. All patients had biochemical evidence of liver dysfunction before treatment. Liver function improved after treatment. CONCLUSION: Visceral leishmaniasis causes morphological and functional disturbance in the liver. Focal fibrosis rather than cirrhosis occurs. The exact aetiology of hepatic damage is unclear but may have an immunological basis.
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A therapeutic dose of labelled 5-fluorouracil (5-FU) was infused via the hepatic artery during 30 min with or without ligation of the left portal venous branch in Wistar rats with a secondary liver cancer in the left lateral lobe. After another 60 min, the incorporation of 5-FU into the acid soluble fraction (ASF), ribonucleic acid (RNA) and deoxyribonucleic acid (DNA), was determined in tumor, ligated and unligated liver lobes, small intestine, kidney, and bone marrow. The liver nucleotide profile was examined with isotachophoresis. Portal venous branch ligation (PVBL) caused the following changes, compared with the unligated control group: in the tumor, the incorporation of 5-FU into RNA and DNA decreased and the ratio RNA/acid-soluble fraction labelling decreased. The incorporation increased in intestinal and bone marrow RNA. It was unchanged in liver and kidney. The ratio of tumor to peripheral normal-tissue (small intestine, bone marrow, and kidney) labelling of RNA and DNA decreased. Liver nucleotides (F)UTP, (F)UDP-glucuronic acid, (F)UDP-N-acetylhexosamine, and NAD were lower in the ligated than in the unligated liver lobe. ATP and energy charge did not decrease significantly. In conclusion, PVBL in conjunction with hepatic arterial administration of 5-FU increased systemic drug exposure and possibly decreased hepatic tumor anabolism. It has not been examined how this interferes with the therapeutic effect.
Liver and intestinal nucleotides and energy charge levels were examined in rats at portal vein clamping for 1, 5 or 30 min and after reflow for 1 or 6 h following 30 min clamping. In both tissues, clamping resulted in a loss of ATP, energy charge, UTP, GTP, UDP-glucuronic acid and UDP-N-acetylhexosamine levels, which all, except ATP and total adenosine phosphates, essentially recovered at 1 h reflow. At 6 h reflow, liver UDP-glucuronic acid and liver glutathione decreased in both clamped and sham operated rats.
A therapeutic dose of labelled 5-fluorouracil (5-FU) was infused via the hepatic artery during 30 min with or without a simultaneous temporary clamping of the portal vein in a model of secondary liver cancer in Wistar rats. After another 60 min, the incorporation of 5-FU into the acid soluble fraction, RNA and DNA was determined in tumor, liver, small intestine, kidney, and bone marrow. The liver and intestinal nucleotide profiles were examined with isotachophoresis. Temporary portal vein clamping caused the following changes, as compared with the control group with intraarterial infusion only: in the liver, the incorporation of 5-FU into the acid soluble fraction increased without a concomitant increase into the RNA or of the level of (F)UTP. Liver ATP decreased. In the tumor, the ratio of RNA to acid soluble fraction labelling decreased. There was a generally decreased ratio of tumor to peripheral normal tissue (small intestine and kidney) labelling. In conclusion, portal vein clamping in conjunction with hepatic arterial administration of 5-FU led to a decreased anabolism of 5-FU in the liver and tumor, and increased systemic drug exposure. It is not known how this interferes with the therapeutic effect.
Adriamycin (Adr) and degradable starch microspheres (DSM) were infused either combined or each separately into the hepatic artery in rats. Liver ATP, GTP, UDP-glucuronic acid, UDP-N-acetyl-hexosamine and energy charge and glutathione were decreased 20 min later with combined treatment but not by Adr or DSM when infused alone. the nucleotide levels were normalized 60 min after the combined treatment. After one week, the Adr rats showed a less weight gain than controls. The Adr + DSM rats lost weight. Only minor changes were found in the livers at microscopical examination at this time.
Rats with solitary liver tumors were treated with adriamycin administered via the hepatic artery with and without degradable starch microspheres. Tumor growth inhibition was significantly greater, and tumors were decreased in size 7 days after, following treatment with adriamycin + microspheres. The bone marrow seemed to be protected. However, the addition of microspheres to adriamycin gave a body weight loss and evidence of increased liver damage. Possible interrelations between liver damage, antitumor effect and body weight loss are indicated.
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Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
The blood supply to the mycetoma lesion and its vasculature were studied in patients with various types of mycetoma using histological, ultrastructural, angiographic and sonographic techniques. The mycetoma lesion proved to be well vascularized. However, certain vascular abnormalities were demonstrated. In histological sections, the small arteries and arterioles showed medial muscular hypertrophy in 83%, intimal fibrosis in 33%, arteritis in 7% and endarteritis obliterans with narrowed lumen in 7% of the patients. No vascular occlusion, ischaemic changes or arteriovenous shunts were observed. These changes were confirmed ultrastructurally. Angiography of the lesion showed a brisk pathological circulation which was more evident in eumycetoma. The vascular Doppler study showed normal blood flow pattern in the affected limb. Regional intra-arterial chemotherapy for mycetoma is suggested as a possible treatment modality.
Rats were fed a 0% casein diet for 1 week, with or without enteral or parenteral administration of essential amino acids, or a 25% casein diet, in one group supplemented with 5-fluorouracil treatment. Ninety minutes before sacrifice the rats were given a tracer of [3H]orotic acid. Incorporation into the acid soluble fraction, RNA, and DNA was determined in liver, small intestine, bone marrow, and kidney. Nucleotide profile was examined in liver and intestine. Protein deficiency caused inter alia a decrease in body weight; a decrease in RNA/DNA ratio and an increase in the specific RNA labeling in liver and kidney; an altered nucleotide profile in the liver; an increase in the nucleotide/DNA and RNA/DNA ratios and a decrease in the specific labeling of the acid soluble fraction, RNA, and DNA in the bone marrow. These changes were prevented to the same extent by giving essential amino acids, either orally or intravenously. The minor changes in intestinal nucleotide profile in protein deprivation were prevented to a slightly larger extent by amino acids orally than parenterally. 5-Fluorouracil treatment gave a decrease in the RNA/DNA ratio in the liver and kidney but an increase in the nucleotide/DNA and RNA/DNA ratios in the bone marrow. Nucleotide profiles were unaltered. The amount of DNA per gram of tissue decreased in bone marrow and increased in kidney. Parenteral administration per se resulted in almost no changes.
The effect of intravenously injected tauromustine (TCNU) on tumor growth and body weight was studied in rats with subcutaneously implanted experimental carcinomas. With a colonic tumor, a single dose or that dose split on 4 consecutive days gave the same tumor growth delay but the body weight loss was less at the split dose. Injection of the single dose for 1 min, 30 min or 2 h each had the same effect. Rats of another strain were implanted with a hepatoma. 9 out of 10 rats were cured. A late effect was body weight loss due to disturbed growth of the teeth.
The effect of the cytostatic nitrosourea drugs TCNU and BCNU on tumor growth was studied in rats with a transplantable colon adenocarcinoma implanted into the liver. The drugs were given as a single dose into the hepatic artery alone or together with degradable starch microspheres (DSM). The effect of the treatment on tumor growth was measured 7 days later. Compared to control animals, TCNU decreased tumor growth. BCNU alone did not significantly decrease tumor growth. The antitumor effect of both drugs was significantly improved by DSM. The addition of DSM to the drugs caused liver damage in a few rats. There were no differences between different treatment groups regarding body weight changes. DSM may protect bone marrow against BCNU toxicity. Injection of DSM alone had no effect either on tumor growth or on survival.
Rats with an adenocarcinoma of the colon implanted into the liver were treated by a bolus injection of adriamycin by the hepatic artery. In addition, vascular occlusions were performed in the following three ways. 1. The hepatic artery was ligated (HAL) immediately after adriamycin injection. 2. The portal venous branch nourishing the tumor was ligated immediately after adriamycin injection. 3. The Pringle maneuvre (clamping of the hepatic artery, the portal vein and the common bile duct) was performed during 5 min before and 10 min after injection. Tumor size was measured at operation and 6 and 12 days later in the first experiment, 7 days later in the other two experiments. The combination of adriamycin and HAL retarded tumor growth at day 6 as compared to controls, adriamycin alone and HAL alone. The differences were not significant at day 12. The other vascular occlusions did not improve the antitumor effect of adriamycin.
Rats were inoculated subcutaneously into both flanks with a transplantable adenocarcinoma of the colon. They were treated intravenously with either 5-FUrd (5-fluorouridine) or 5-FdUrd (5-fluoro-2'-deoxyuridine) with or without addition of dipyridamole 20 and 30 min later, respectively, for 3 consecutive days. Dipyridamole improved the antitumor activity of 5-FUrd but decreased that of 5-FdUrd.