Protective effects of Vitamin E on CCl4-induced testicular toxicity in male rats.

The increased generation of free radicals plays an important role in testicular damage. The present study aimed to investigate the adverse effects of carbon tetrachloride (CCl4) on the reproductive system of male rats as well as to examine whether Vitamin E (VE) is able to ameliorate these effects. The rats were equally divided into three groups: control, CCl4-treated, and CCl4 + VE-treated groups. After 4 weeks of treatment, the decrease in body and testes weights, sperm parameters, and the decrease in serum levels of testosterone, luteinizing hormone, and follicle-stimulating hormone of CCl4-treated rats were ameliorated by VE treatment. The co-administration of VE with CCl4 significantly decreased the level of lipid peroxidation production (malondialdehyde) and increased the activity of anti-oxidant enzymes (superoxide dismutase and catalase) when compared with the CCl4 group. Moreover, VE prevented CCl4-induced severe testicular histopathological lesions and deformities in spermatogenesis. The results demonstrate that VE augments the anti-oxidants' defense mechanism against CCl4-induced reproductive toxicity suggesting a therapeutic role in free radical-mediated infertility.

Familial essential thrombocythemia with spontaneous megakaryocyte colony formation and acquired JAK2 mutations.

Essential thrombocythemia (ET) is a chronic myeloproliferative disorder, characterized by increased proliferation of megakaryocytes and elevated platelet count that usually occurs sporadically. We report a family with seven affected individuals in three generations, including one individual with a phenotype resembling polycythemia vera, a related disorder. Megakaryocyte (CFU-MK) colony formation occurred in the absence of added cytokines in cultures of peripheral blood from affected family members. Some reports of familial ET have identified mutations in THPO and MPL, the genes for a cytokine (thrombopoietin, TPO) that regulates platelet production and its receptor (c-MPL), respectively. In this family, the MPL gene was excluded by linkage analysis. Although TPO levels were elevated in most affected family members and evidence for linkage was found between the disease and THPO (theta=0.0, Z(max)=3.0), a THPO mutation was not identified by DNA sequencing. The JAK2 V617F mutation that has been associated with 50% of sporadic cases of ET was identified as a somatic mutation, an acquired defect, in peripheral blood of the two most severely affected family members. These patients also had elevated TPO levels. Further study of familial myeloproliferative diseases will help elucidate the initiating genetic events underlying ET.

Prolonged complete remission of myelodysplastic syndrome treated with danazol, retinoic acid and low-dose prednisone.

Myelodysplastic syndrome (MDS) is a diverse group of clonal hematologic neoplasms. Different medications have been tried in MDS; however, no effective treatment has been yet established. We report a patient with MDS who achieved a complete remission in response to combination therapy of danazol, retinoic acid, and prednisone. A 53-year-old female presented with pancytopenia, macrocytosis, and hypercellular bone marrow with erythroid hyperplasia and dysplasia and 10% ringed sideroblasts. Cytogenetic studies revealed the presence of two abnormal clones. She was diagnosed as having MDS-refractory anemia and was given blood transfusions to maintain blood cell counts at acceptable levels. At the same time, she was started on a combination of danazol (600 mg/day), retinoic acid (100 mg/day), and prednisone (10 mg every other day). Fourteen months later, the patient was in complete hematologic remission; she had normal peripheral blood count, and the blood smear showed normal morphology. Bone marrow studies revealed normal trilineage hematopoiesis. She was continued on the same combination treatment for 86 months, and she remained in complete clinical remission. Eighty-eight months from diagnosis, she relapsed with acute myeloid leukemia. This is the first reported case of MDS-RA that sustained a complete hematologic remission for a prolonged period in response to this combination treatment. This report indicates that restoration of normal hematopoiesis, prolongation of disease-free survival, and delay in the transformation to acute leukemia may be achieved by this combination of treatment in a subset of patients with MDS, especially refractory anemia with severe thrombocytopenia.

Diagnosis of lymphoproliferative disorders: experience of a single institution in the long-term follow-up of discordant cases.

OBJECTIVE: To evaluate the usefulness of morphologic diagnosis, immunophenotyping and immunoglobulin (Ig) and T-cell receptor (TcR) gene rearrangement studies in the diagnosis of lymphoproliferative disorder. DESIGN: A retrospective cohort study with clinical follow-up of controversial cases. SETTING: Single institution, tertiary care centre. PATIENTS: All 273 patients whose lymphoid tissue samples were sent for molecular analysis by Southern blotting over a 4-year period. INTERVENTIONS: Patient reports were retrieved from the laboratory data system. Repeat assessment and clinical follow-up was done for discordant cases. OUTCOME MEASURES: Correlation between morphologic features and the results of immunophenotype and gene rearrangement studies of the samples. Value of the different tests in discordant cases. RESULTS: The 273 samples included 130 of non-Hodgkin's lymphoma (NHL), 23 of Hodgkin's disease, 80 of benign lymphoid hyperplasia, 16 of atypical lymphoid hyperplasia and other diagnoses. Of the 130 NHL cases diagnosed by morphologic study, 22 (17%) did not show gene rearrangement. Of the 80 morphologically benign samples, 4 (5%) showed gene rearrangement, and malignant disease developed later in those patients. Five (31%) of the 16 cases of atypical lymphoid hyperplasia showed gene rearrangement. Six of the remaining 11 cases had no detectable gene rearrangement, but hematologic malignant disease developed. No gene rearrangement was detected in Hodgkin's disease samples. One carcinoma showed gene rearrangement. Of the NHL group, 86% of the B cells and 50% of the T cells showed gene rearrangement. Seven samples showed both Ig and TcR gene rearrangement. CONCLUSIONS: Gene rearrangement analyses correlate highly with conventional morphologic diagnosis and phenotyping. The detection of gene rearrangement in lymphoid tissue has a high specificity (99%) and a reasonable sensitivity (83%) to the development of a lymphoproliferative disorder.

Induction of leukaemia in chloramphenicol-treated toads.

Chloramphenicol has been associated with the development of aplastic anaemia. As it is still widely used in Egypt, we studied its effect on 100 Egyptian toads (Bufo regularis) given a dose of chloramphenicol of 5 mg/40 g body weight for 12 weeks. We found it induced numerous, severe ultrastructural changes in almost all types of leukocytes. These changes were similar to those induced by the chemical carcinogen 7,12-dimethylbenz(a)anthracene in 100 toads used as the carcinogen control group, and similar to those in leukocytes reported in humans with leukaemia. We recommend regulations be applied on the use of this antibiotic in countries where it is still widely used.

Long-term administration of vitamin A and the process of spermatogenesis.

The effect of retinoids on spermatogenesis in adult male gerbils (Gerbillus cheesemani) was studied using light and electron microscopy. Treatment with either 13-cis-retinoic acid or retinol acetate was given for 6 weeks and their effects were compared with controls. It was found that 13-cis-retinoic acid induced almost complete cessation of spermatogenesis and produced alterations in the cytoplasm of Leydig cells. No differences were seen in the testis of animals treated with retinol acetate compared with controls using light microscopy but it appeared to produce noticeable ultrastructural changes in Leydig cells. The changes observed were reversed 12 weeks after stopping treatment. Caution should be exercised regarding the use of dietary retinoids in the prevention of cancer.

Long-term administration of vitamin A and the process of spermatogenesis

The effect of retinoids on spermatogenesis in adult male gerbils [Gerbillus cheesemani] was studied using light and electron microscopy. Treatment with either 13-cis-retinoic acid or retinol acetate was given for 6 weeks and their effects were compared with controls. It was found that 13-cis-retinoic acid induced almost complete cessation of spermatogenesis and produced alterations in the cytoplasm of Leydig cells. No differences were seen in the testis of animals treated with retinol acetate compared with controls using light microscopy but it appeared to produce noticeable ultrastructural changes in Leydig cells. The changes observed were reversed 12 weeks after stopping treatment. Caution should be exercised regarding the use of dietary retinoids in the prevention of cancer

Implications of fructose in liver tumours of the Egyptian toad

Environmental factors play an important role in the etiology of several types of cancer; this discovery has led to a great deal of interest in the role of diet in cancer etiology. It is well known that some factories which produce jams and juices use fructose rather than glucose or sucrose to sweeten their products. This study demonstrates that fructose insignificantly enhances the incidence of liver tumours in Egyptian toads previously injected with 7,12-dimethylbenz [a]-anthracene

Survey of hormonal levels in meat and poultry sold in Alexandria, Egypt

An analysis of residues from anabolic agents found in commercially available meat and poultry was undertaken in Alexandria, Egypt. This study shows that beef meat samples purchased from government cooperative supermarkets exhibit higher levels of the synthetic growth promoter, trenbolone acetate, than meat from private butchers; however, estrogen levels were much higher in chicken obtained from private growers. A comparison of different cooking methods was conducted on the chicken samples; boiling without skin is recommended to reduce the consumer's intake of hormonal residues

Normal CD5+ B lymphocytes are poor stimulators in the autologous mixed lymphocyte reaction (AMLR).

The AMLR is decreased in chronic lymphocytic leukaemia (CLL), which is characterized by a monoclonal expansion of CD5+ B lymphocytes. Since B cells are used to stimulate the AMLR, we investigated the capacity of normal CD5+ B cells to function as stimulators in the AMLR. We isolated B cells from the peripheral blood of normal individuals and fractionated them into subpopulations enriched for CD5+ and CD5- cells, which were used as stimulators in the AMLR. We found that the CD5- B cells were excellent stimulators, whereas stimulation of AMLR by B cells enriched for CD5+ cells resulted in significantly reduced proliferative responses (P < 0.005). This suggests that the reduced AMLR in CLL is due to the predominance of CD5+ B lymphocytes in the stimulating cell population.

Ultrastructural criteria that prove the similarities between amphibian and human tumors.

Toads fed with 0.5 mg 7,12-dimethylbenz(a)anthracene twice a week for 12 weeks displayed liver tumors in 27 out of 100 cases. Electron micrographs of liver tumors showed some criteria of malignancy, such as the presence of nuclear pockets, pseudoinclusions, dilatation of the cisternae of rough endoplasmic reticulum and loss of cell junctions. These features are closely similar to those of true malignancy described in humans and other mammals.

The use of toads (Bufo regularis) in a new biological assay for screening chemicals or drugs which induce leukaemia in man.

Injection of Egyptian toads Bufo regularis, with adriamycin subcutaneously in the dorsal lymph sac at a dose level of 0.1 mg/toad, once every 3 weeks for 3 months induced pronounced alterations in the blood cells. These alterations were more or less similar to the criteria reported in human leukaemia. These changes were all comparable to those observed after the treatment of the experimental animals with the chemical carcinogen 7,12-dimethylbenz(a)anthracene. It is speculated that toads (Bufo regularis) can be used as biological test animals for screening chemicals or drugs which induce leukaemia in man.

Initiation and post-initiation chemopreventive effects of beta-carotene in toad liver carcinogenesis.

Hepatocellular carcinoma were recognized in the toad, Bufo viridis, in 14 cases out of 50 by injection of 1 mg 7,12 dimethylbenz(a)anthracene (DMBA)/toad twice/week for 12 weeks. In contrast, toads treated with DMB at the same dose level and beta-carotene (betaC), 0.05 mg (3 hr prior to the carcinogen)/toad, twice/week for 12 weeks showed no tumor incidence. However, betaC at the same dose level was less effective when administered 3 hr. after the carcinogen (DMBA). In 8 cases out of 50 cases neither tumor growth nor neoplastic changes were observed in toads treated with betaC alone or olive oil. It is concluded that betaC completely blocked hepatocarcinogenesis in toads when given 3 hr. before initiation.

Adverse drug reactions and drug substitution in an arrhythmia clinic.

OBJECTIVE: To assess the impact of adverse drug reactions on antiarrhythmic drug substitution in ambulatory patients. SETTING: Tertiary care dysrhythmia clinic. PATIENTS AND METHODS: A total of 671 medical records were reviewed. Sex of the study population was equally distributed, with an average age of 53 years. Follow-up averaged 26 months for patients seen more than once. Suspected adverse drug reactions and substitution of antiarrhythmic agent were used to ascertain events in patients' charts. Patients were exposed to 1253 treatment courses. The number of successive antiarrhythmic agents per patient averaged 1.8 and varied from one to seven. RESULTS: One hundred and thirty-nine (20%) patients experienced a total of 194 adverse events (15.5% of drug courses), of which only eight (4%) were serious. Ninety-four per cent of the mostly benign adverse drug reactions were followed by a therapeutic modification: discontinuation or replacement in 87% and dosage reduction in 7%. The influence of successive drug changes was evident: the risk of a reaction was 7% in patients exposed to one agent compared with 100% in patients exposed to a seventh agent. CONCLUSIONS: First, therapeutic substitution in response to adverse drug reactions appears to be determined more by the combined expected benefit, the product of arrhythmia severity and drug efficacy, than by the severity alone of the adverse reaction; and second, the probability of an adverse drug reaction is proportional to the number of agents tried consecutively, possibly as a result of patient selection, drug selection and increased patient and doctor awareness.

Chemopreventive effects of cabbage on 7,12-dimethylbenz(a)-anthracene-induced hepatocarcinogenesis in toads (Bufo viridis).

Hepatocellular carcinoma was induced in the toad, Bufo viridis, in 29 out of 100 cases by the administration of 0.5 mg of 7,12-dimethylbenz(a)anthracene (DMBA)/toad, 3 times/week for 12 weeks. In contrast, toads treated with DMBA and cabbage diet 1 or 2 ml (3 h prior to the carcinogen)/toad, every day for 12 weeks showed a lower incidence of liver tumors: 15 and 12 cases out of 100. However, cabbage diet (2 ml/toad, every day for 12 weeks) was ineffective when administered 3 h after the carcinogen (DMBA) in 27 out of 100 cases. Neither tumor growth nor neoplastic changes were observed in toads treated with olive oil alone or with cabbage diet. It is concluded that a cabbage diet during initiation has an inhibitory effect on hepatocarcinogenesis in toads.

Effect of dietary fat on toad liver tumor induced by DMBA: ultrastructural studies.

Toads injected with 2 mg 7,12-dimethyl-benza(a)anthracene (DMBA)/toad, 3 times/week for 12 weeks induced liver tumors in 12 out of 50 cases. The electron micrograph of toad liver tumor showed disorganization of the rough endoplasmic reticulum which encircles or partially surrounds the mitochondria. Cristae mitochondrialis are rare in comparison with control. Enhancement of liver tumor incidences (29 out of 50 cases) by DMBA at the same dose level plus 2cc corn oil/toad, 3 times/week for 12 weeks was detected. Electronicrograph of this group showed the same criteria of malignancy as in the first group. No tumor incidences were detected in toads fed corn oil only. The electronmicrograph of liver cells showed a high increase in glycogen and lipid droplets.

Amiodarone-induced epididymitis: report of a new case and literature review of 12 cases.

OBJECTIVE: To report a new case and review the literature of amiodarone-related epididymitis to improve knowledge of the clinical characteristics of this reaction. DESIGN: Cohort study. SETTING: Tertiary out-patient arrhythmia clinic. PATIENTS: Males currently treated for arrhythmias with amiodarone for at least two months. Thirty-two patients were identified and all were contacted. OUTCOME MEASURES: Swelling and or/pain in the scrotum with confirmation of noninfectious epididymitis by a urologist. DATA SOURCES: Bibliography (Medline and Embase) and databases (Manufacturer, Health Protection Branch, World Health Organisation). STUDY SELECTION: Four articles with case reports. Databases searched for these key words: amiodarone and epididymitis. RESULTS: A new case is reported. Twelve cases have been presented individually and six more described collectively. Times to onset range from four to 71 months, daily doses range from 200 to 800 mg. The reaction is self-limited, with or without amiodarone reduction, and does not require antimicrobial drugs, but a noninvasive urological examination may be warranted. CONCLUSION: Awareness by cardiologists will prevent unnecessary invasive urological investigations or antibiotic therapy.

Short-term studies of the effect of acrylamide on the testes of the Egyptian toad.

The treatment of male Egyptian toads (Bufo regularis) with acrylamide (1 mg/toad twice a week for four weeks) was followed by atrophy of the testes, inhibition of spermatogenesis and necrosis of the seminiferous tubules with signs of vacuolation. Ultrastructurally, the Leydig cells of treated toads displayed varying degrees of vacuolation of the mitochondria, with a decrease in the number of ribosomes. The mechanism of the action of acrylamide in inhibiting spermatogenesis may be due to a decrease in the testosterone level, as borne out by vacuolation of the mitochondria and the decrease in the ribosomes in the Leydig cells of treated animals.

Alpha-ecdysone, a new bracken fern factor responsible for neoplasm induction in the Egyptian toad (Bufo regularis).

Neoplastic lesions were induced in 10 out of 58 experimental toads (Bufo regularis) force-fed with alpha-ecdysone, which naturally occurs in the leaves of bracken fern (Pteris aquilina). The results of this study prove that alpha-ecdysone may be one of the factors responsible for the carcinogenicity of bracken fern plant fed to cattle and other experimental animals.