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PubMed1988

Hyperthermia in combination with definitive radiation therapy: results of a Phase I/II RTOG Study.

Between August 1981 and April 1986, 133 patients with superficial malignant tumors not previously treated with radiotherapy were entered on a Phase I/II RTOG study evaluating hyperthermia plus definitive radiotherapy. Eligible patients included those with superficial epithelial or mesenchymal tumors less than 4 cm in depth. Protocol radiotherapy specified a tumor dose of 60 Gy delivered in 1.8-2.0 Gy fractions 5 times/week with a boost of 5-10 Gy through reduced portals to residual tumor. Protocol hyperthermia, delivered twice weekly, was to start within 15 minutes following irradiation and to consist of 60 minutes of heat to a tumor temperature of 43 degrees C. Sixteen patients were excluded. Of the 117 eligible patients, the treated lesions had site/histologies which were 35% head & neck/squamous, 46% breast/adenocarcinoma, and 19% other site/histologies. Lesions were 3 cm or larger for 77% of patients. Of the 41 patients with head & neck/squamous lesions, skin or subcutaneous necrosis occurred within 6 months for 2% of the patients; 12% experienced thermal blisters. Fourteen patients were followed for 6 months or more following start of treatment; none of these experienced late toxicities more severe than telangiectasis. Complete responses were observed in 51% of these patients. Of the 54 patients with breast/adenocarcinoma lesions, skin or subcutaneous necrosis occurred within 6 months for 13% of the patients; 17% experienced thermal blisters. Thirty-seven patients were followed for 6 months or more following start of treatment; complications observed during this period included 13% with ulceration and one case of skin necrosis. Complete responses were observed in 85% of these patients. Local control was maintained at nearly this level for at least 2 years. Logistic regression analyses showed site/histology, greatest tumor diameter and average tumor temperature to be significantly related to response. Based on these promising findings, the RTOG has instituted a randomized Phase III study evaluating radiation therapy with or without hyperthermia in this patient population.

Adenocarcinoma↗
PubMed1991

Unrelated donor bone marrow transplantation for correction of lethal congenital immunodeficiencies.

The majority of children with lethal congenital immunodeficiencies lack histocompatible related bone marrow donors. T-cell depleted haploidentical parental bone marrow transplantation has been used successfully in selected patients with severe combined immunodeficiency (SCID), but it has not benefited most patients with other immunodeficiencies when it has been tried. For these reasons, we undertook a pilot study using closely matched unrelated donors for bone marrow transplantation of children with life-threatening primary immunodeficiencies. Unrelated donor searches were performed for 24 patients and one or more suitable donors were identified for 21 patients. Unrelated donor bone marrow transplantation (URD BMT) has been performed in 18 patients with various diagnoses: SCID (8), Wiskott-Aldrich syndrome (WAS) (2), Chediak-Higashi syndrome (CHS) (2), combined immunodeficiencies (3), Ataxia Telangiectasis (AT) (2), and one patient with combined immunodeficiency and large granular lymphocytosis (1). The overall actuarial survival rate is 59% with excellent results observed for infants with SCID and children with WAS and CHS.

Adolescent↗
PubMed2005

Water-borne diclofenac affects kidney and gill integrity and selected immune parameters in brown trout (Salmo trutta f. fario).

The detection of residues of various pharmaceuticals in surface waters during the last two decades has prompted concerns about possible adverse effects of this kind of pollution on aquatic organisms. The objective of the present study was to investigate effects of the non-steroidal anti-inflammatory drug diclofenac, one of the pharmaceuticals most prevalent in surface waters, on brown trout (Salmo trutta f. fario), a salmonid species native to German rivers. Brown trout were exposed to 0.5, 5 and 50 microg/L diclofenac for 7, 14 and 21 days, whereby the lowest exposure concentration is comparable with concentrations commonly found in the aquatic environment. Fish exposed to diclofenac displayed significantly reduced haematocrit levels after 7 and 14 days of exposure. After 21 days, trout were examined for histopathological alterations, whereby diclofenac exposure resulted in increased monocyte infiltration in the liver, telangiectasis in gills, and the occurrence of interstitial hyaline droplets, interstitial proteinaceous fluid and mild tubular necrosis in trunk kidney. Concurrent immunohistological analysis revealed an increase of granulocyte numbers in primary gill filaments, as well as granulocyte accumulation and increased major histocompatibility complex (MHC) II expression in kidney, suggestive of an inflammatory process in these organs. Moreover, the ability of diclofenac to hinder the stimulation of prostaglandin E2 synthesis was shown in head kidney macrophages of brown trout in vitro. These findings support the hypothesis that environmental exposure of fish to diclofenac provokes the same mechanism of action in these non-target organisms as previously described for mammalian species and can thus lead to similar (possibly adverse) effects. In general, the present study suggests that exposure of brown trout to diclofenac in concentration ranges commonly found in the environment can result in adverse effects in various organs and possibly compromise the health of affected fish populations.

Animals↗
PubMed2004

Subacute toxicity evaluation of a new camptothecin anticancer agent CKD-602 administered by intravenous injection to rats.

The subacute toxicity of a new camptothecin anticancer agent, CKD-602, was investigated after 4-week repeated intravenous administration of the chemical in Sprague-Dawley rats. The test chemical was administered intravenously to rats at dose levels of 0, 0.003, 0.013, or 0.067 mg/kg/day for males and 0, 0.004, 0.018, or 0.089 mg/kg/day for females. At the end of the treatment period, 10 rats/sex/group were sacrificed. The remaining 5 rats/sex in the vehicle control and high dose groups continued the study without treatment for 2 weeks (recovery period). During the test period, clinical signs, mortality, body weights, food and water consumption, ophthalmoscopy, urinalysis, hematology, serum biochemistry, gross findings, organ weights, and histopathology were examined. In both sexes of the high dose group, an increase in the incidence of abnormal clinical signs and paleness of the eyes, a reduction in the body weight gain, food consumption and urine protein, and an increase in the water consumption were observed. Hematological investigations revealed a decrease in the red blood cells, hemoglobin and hematocrit and an increase in the mean corpuscular volume, mean corpuscular hemoglobin, platelets, and reticulocytes in a dose-dependent manner. Serum total cholesterol and total protein values were lower in females than those of controls, but not in males. An increase in the heart and liver weights and a decrease in the thymus weight were also found. Histopathological alterations included an increase in the incidence of atrophy of the sternal marrow, atrophy, fibrosis and mast cell hyperplasia of the femoral marrow, atrophy of the white pulp and extramedullary hematopoiesis of the spleen, atrophy of the thymus, auricular hypertrophy of the heart, extramedullary hematopoiesis and centriacinar telangiectasis of the liver, follicular degeneration of the ovary, and inflammation of the tail. The major treatment-related effects were not recovered at the end of 2-week recovery period. There were no adverse effects in the low and middle dose groups of both genders. In the present experimental conditions, the target organs were determined to be bone marrow, blood cells, spleen, liver, thymus, and heart. The no-observed-adverse-effect level was considered to be 0.013 mg/kg/day for males and 0.018 mg/kg/day for females.

Animals↗
PubMed2002

Atypical choroidal neovascularization in radiation retinopathy.

PURPOSE: To report atypical choroidal neovascularization associated with radiation retinopathy. DESIGN: Case report. METHODS: The patient was examined with ophthalmoscopy, fluorescein angiography, and indocyanine green angiography. RESULTS: A 32-year-old woman presented with an accelerated course of radiation retinopathy with macular edema, capillary telangiectasis, subretinal fluid, and lipid during and after pregnancy. Indocyanine green, but not fluorescein angiography, demonstrated an unusual area of choroidal neovascularization with prominent saccular dilations adjacent to a large zone of poor choroidal perfusion. Laser photocoagulation of the choroidal neovascularization resulted in an angiographic closure with absorption of the subretinal fluid and improvement of visual acuity. CONCLUSIONS: Choroidal neovascularization may be associated with radiation retinopathy and, when present, may require indocyanine green angiography for its diagnosis.

Adult↗
PubMed1981

Results of local excision and radical radiotherapy in early breast cancer.

Twenty-seven patients with a T1 or T2 N0M0 breast carcinoma were treated by local excision of the lump followed by radical radiotherapy, using orthovoltage X-rays. The crude survival rate was 100% at three years, 92% at five years, 95% at 10 years. The local recurrence rate was 8% at three years, 12% at five years, 10.5% at 10 years. The radiation dose needed to be tumour lethal is discussed. Our results and those of papers quoted indicate that 4500--5000 cGy (rad) in five weeks, given in five fractions per week, is optimal, provided the primary tumour has ben removed. A further 1000--2000 cGy to the lumpectomy site reduces the incidence of local recurrence. The cosmetic results of our treatment are illustrated. Some telangiectasis was seen but the general appearance and texture of the treated breasts was satisfactory.

Adult↗
PubMed1982

Control of severe vesical haemorrhage by therapeutic embolisation.

Therapeutic embolisation is now recognised as having a role in the management of bladder haemorrhage and is particularly valuable in severe cases where the patient's life is at risk. This paper describes the procedures which were used to manage two patients with massive haematuria, from a tumour in one case and from an arterial malformation in the other. Previous reports indicate that haemorrhage from a bladder tumour can usually be controlled by embolisation which is limited to the tumour itself but haemorrhage due to post-radiation telangiectasis requires more extensive arterial occlusion and this was taken into account in planning the embolisation procedure in the first case. Neither patient developed gluteal pain after embolisation which was probably due to the fact that the superior gluteal arteries were not completely occluded. The left axillary approach was used as a catheter passing down the aorta can usually be manipulated into the internal iliac arteries and their smaller branches on both sides without difficulty.

Adult↗
PubMed1980

The diagnosis and management of epithelial tumors of the lacrimal sac.

Five primary epithelial lesions of the lacrimal sac representing a range of epithelial tumors are presented. The benign lesions initially presented without pain or significant mass but with epiphora and a bloody discharge. The malignant lesions presented insidiously, were large, firm masses and displayed overlying skin telangiectasis rather than the diffuse erythema of dacryocystography revealed a sac partially obstructed by a subtotal space-occupying mass in benign tumors and completely obstructed with malignant lesions.

Adenoma↗
PubMed1996

Vitrectomy in eyes with peripheral retinal angioma associated with traction macular detachment.

PURPOSE: Peripheral angiomas have been associated with epiretinal membranes and traction retinal detachment. The authors investigated the timing, results, and complications of vitreous surgery to remove the retinal traction and treat the peripheral vascular tumor. METHODS: The authors reviewed the results of ten eyes that had undergone vitrectomy for macular pucker and/or traction retinal detachment. These eyes had either preoperative or intraoperative treatment of the peripheral tumor. RESULTS: Patients were followed 4 to 95 months. Six eyes had nonfamilial peripheral acquired retinal hemangioma, three had von Hippel angiomas, and one had multiple large peripheral retinal angiomas associated with extensive retinal telangiectasis. Four eyes received cryotherapy and/or laser photocoagulation 2 to 3 months before surgery. In the remaining six eyes, initial treatment to the peripheral angioma was performed at the time of vitreous surgery. At final follow-up, all eyes were attached without retinal traction. Vision improved in all eyes; six (60%) achieved 20/50 or better visual acuity. Complications included recurrent epiretinal membrane (n=3); nonregressed angiomas (n=3); increased nuclear sclerosis (n=2); and retinal detachment (n=1). CONCLUSION: Vitreous surgery, when applied to epiretinal membranes or traction retinal detachments associated with peripheral vascular tumors, has a good chance of improving vision. Treatment of the hemangioma, before or during vitrectomy, usually results in tumor regression.

Adult↗
PubMed1983

Neonatal lupus syndrome in successive pregnancies.

Two female siblings, born 15 months apart, developed neonatal lupus syndrome. Both had cutaneous lupus erythematosus (LE) lesions resolving with telangiectasis. Their cutaneous lesions were temporally related to transplacental passage of anti-SS-A (Ro) autoantibodies from their asymptomatic mother. Infants with this transient collagen vascular syndrome may have LE skin lesions, congenital heart block, and liver or hematologic abnormalities, and are possibly at risk for developing systemic lupus erythematosus (SLE) later in life. It is important to recognize that this syndrome may occur in successive pregnancies.

Female↗
PubMed1997

[Anaphylactic shock caused by fibrin glue].

We observed a case of anaphylactic shock in a 68-year-old woman after a nasal intramucosal injection of fibrin glue for telangiectasies therapy. The tests showed an allergy to aprotinin contained in the glue. In the previous years, glue and aprotinin had been administered to the patient several times for nasal bleeding.

Administration, Intranasal↗
PubMed1999

Re-irradiation of head and neck tumors. Benefits and toxicities.

Most patients with head and neck cancer that recurs after irradiation should be treated with curative surgery. In patients whose tumors are nonresectable, or if surgery would cause unacceptable morbidity, a trial of curative re-irradiation may be considered. Taking into account the overall poor prognosis of these patients and the high rate of late tissue toxicity, especially soft tissue necrosis, fistula formation, and potential nerve damage, patients should be carefully selected. Several sites, notably the larynx and nasopharynx, can be re-irradiated with a relatively high rate of locoregional tumor control. In other sites, several criteria may be used to select patients for curative re-irradiation: limited tumor size, a relatively long period since previous irradiation (a suitable, though arbitrary, minimal time period may be 1 year), good performance status, and lack of evidence of skin or soft tissue damage (skin fibrosis, atrophy or telangiectasis) by the previous irradiation course. Even when these selection criteria are used, the prognosis is poor, and long-term survival rates are low even if locoregional tumor control is achieved. Innovative strategies and techniques, including aggressive combined chemoradiation, hyperfractionation, and limiting the extent of irradiated tissues by using conformal irradiation, may improve locoregional control rates. It should be emphasized, however, that the only chance for achieving locoregional control and cure is through the delivery of a full dose of radiation, similar to the dose required for primary tumors. The delivery of a low radiation dose, commonly practiced to avoid complications, is expected to achieve palliation only.

Brachytherapy↗
PubMed2002

[Ovarian genes].

The number of ovarian follicles decreases during genital life by apoptosis, which accelerates from 40 until the menopause. Several findings plead in favour of a genetic control of these events. Ovarian insufficiency can occur by three mechanisms: reduction in the primary follicles reserve (ataxia-telangiectasy), follicular maturation blocking (modification of the genes GDF-9 and GDF-9B, null mutation of FSH receptor gene, auto-immune polyglandular disease, PBE syndrome), or apoptosis acceleration (chemotherapy, smoking, galactosemia, Turner's syndrome). However, the aetiology of premature ovarian insufficiencies in woman remains unknown in more than 90% of the cases. Genetic studies on the family cases should make it possible to identify new genes involved in ovarian control.

Animals↗
PubMed2003

Leber's hereditary opric neuropathy: a case report.

Leber's hereditary optic neuropathy (LHON) is a maternally inherited mitochondrial disease that primarily affects the optic nerve, causing bilateral vision loss in juveniles and young adults. A 12-year-old boy had complained of blurred vision in both eyes for more than 1 year. His best-corrected visual acuity was 0.08 in the right eye and 0.1 in the left. Ophthalmologic examination showed bilateral optic disc hyperemia and margin blurring, peripapillary telangiectasis, and a relative afferent pupil defect in his right eye. Fluorescein angiography showed no stain or leakage around the optic disc in the late phase. Visual field analysis showed central scotoma in the left eye and a near-total defect in the right. Upon examination of the patient's mitochondrial DNA, a point mutation at nucleotide position 11778 was found, and the diagnosis of LHON was confirmed. Coenzyme Q10 was used to treat the patient.

Child↗
PubMed2004

The biological "scrabble" of pulmonary arteriovenous malformations: considerations in the setting of cavopulmonary surgery.

Pulmonary arteriovenous fistulas are vascular malformations, which, by virtue of producing abnormal vascular connections proximal to the units of gas exchange, result in intrapulmonary right-to-left shunting. These malformations or fistulas reflect at least in part disordered angiogenesis, and less commonly recruitment and dilation of pre-existing vascular channels. Pulmonary arteriovenous fistulas occur in a number of diverse clinical settings. Such fistulas are a well-established feature of the Weber-Osler-Rendu complex, or hereditary haemorrhagic telangiectasia, an autosomal dominant vascular dysplasia characterized by mucocutaneous telangiectasis, epistaxis, gastrointestinal haemorrhage, and arteriovenous malformations in the lung, brain, liver and elsewhere. They are also seen in the patient with acute or chronic liver disease, disease that is usually but not invariably severe, or those with non-cirrhotic portal hypertension. They may occur as congenital malformations, single or diffuse, large or small in isolation, and when large or extensive enough may result in hypoxaemia, clinical cyanosis, and heart failure. Cerebral vascular accidents are also a well-known complication of this disorder. An extensive literature has accumulated with regard to the pulmonary arteriovenous fistulas seen in the setting of the Weber-Osler-Rendu complex, and there is considerable information on the genetics, basic biology, clinical findings, complications and therapeutic interventions of these malformations in the setting of this syndrome. These issues, however, are not the primary considerations of this review, although some aspects of this fascinating disorder will be discussed later. Rather the focus will be on pulmonary arteriovenous malformations that develop in the setting of cavopulmonary surgery, and their relationship to the pulmonary arteriovenous fistulas occurring in the hepatopulmonary syndrome. The complex tapestry of these overlapping and intersecting clinical observations will be unfolded in the light of their chronology.

Angiography↗
PubMed2001

Experimental mycotoxic nephropathy in pigs provoked by a diet containing ochratoxin A and penicillic acid.

Mycotoxic nephropathy was induced in 18 young pigs by diets contaminated with strains of Aspergillus ochraceus containing ochratoxin A (OTA) and penicillic acid (PA) at levels corresponding to those naturally encountered in animal feeds in Bulgaria. Haematological and biochemical parameters, as well as the morphological and ultrastructural changes in various internal organs, and especially in the kidneys, were examined at different stages of development of the disease. A mottled surface of the kidneys was only seen in pigs exposed to a mouldy diet containing 180 ppb OTA for 3 months, but microscopic lesions, as well as changes in various haematological and biochemical parameters, were observed in all groups exposed to the same mouldy diet containing only 90 or 180 ppb OTA. Histological examination showed two types of change: degenerative changes affecting the epithelial cells of the proximal tubules, which predominated at the initial stage, and proliferative changes in the interstitium, which predominated at the later stage of the disease. Telangiectasis and lymph stasis were also seen, as well as degenerative changes in the capillary endothelium. The characteristic renal lesions were similar to those observed in spontaneous cases of mycotoxic porcine nephropathy in Bulgaria, but they were a little different from the classic Danish porcine nephropathy. The enhanced toxicity of OTA in our study may be due to a synergistic effect between OTA and PA or to some other unknown metabolites produced by the same ochratoxinogenic strains of A. ochraceus.

Animal Feed↗
PubMed2001

The differential diagnosis of crystals in the retina.

Crystalline deposits in the retina may be associated with a wide variety of systemic disorders such as oxalosis, cystinosis, hyperornithinaemia and Sjögren-Larsson syndrome. Refractile crystalline deposits may also be a manifestation of drug toxicity like the antineoplastic agent tamoxifen, the anesthetic methoxyflurane and the oral tanning agent canthaxanthine. Crystals may also occur in drug abusers who inject multiple crushed tablets of methadone or meperidine intravenously (talc retinopathy). The differential diagnosis of retinal crystals also includes primary ocular diseases like Bietti's crystalline retinopathy, calcified macular drusen, idiopathic parafoveal telangiectasis and longstanding retinal detachment. This article will review the most common causes of crystalline retinopathies, their etiologies, pathologies and clinical characteristics.

Crystallization↗