Osteoblastic metastases from medullary carcinoma of the thyroid.
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Biomedical subjects
Publications and source records attributed to A Kedar.
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In a preliminary experiment the wet weight of the rat urinary bladder appeared to correlate with cyclophosphamide toxicity. The effect of a proposed antidote (SMES), given on various time schedules, was studied using the wet weight as a measure of toxicity. At a cose of 20 mg/kg/SMES it was found to neutralize the toxicity of 100 mg cytoxan only when given simultaneously. It is suggested that this model might be used in further studies.
A fourteen-year old female presented with a mediastinal mass and pleural effusion. A diagnosis of a poorly differentiated lymphocytic lymphoma was made from a lymph node biopsy. Fluid from a pleural tap contained numerous lymphoblasts; 91.5% of these lymphoblasts had a thymus leukemic antigen. At presentation, although morphologically normal, no adenosine deaminase (ADA) activity could be demonstrated in her peripheral blood lymphocytes. Lysates of her lymphocytes mixed with lysates of lymphocytes with known ADA activity resulted in ADA activity that was greater than expected. With disappearance of tumor following the institution of therapy, ADA activity appeared in her lymphocytes and the above phenomenon disappeared.
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A subcutaneous (S.C.) was compared with an intradermal (I.D.) inoculation route of C-1300 neuroblastoma cells in adult A/J mice. This study was prompted by a recent report of increased metastases in intradermally inoculated murine neuroblastoma. The median survival in our line was longer in the I.D. group (44 days as compared to 34.5 days). Despite this feature, liver metastases, when detecp). In this series of experiments no other metastatic sites were found. Histologically both groups showed a similar picture under light microscopy, i.e., a highly undifferentiated tumor with little matrix and an absence of neuronal elements. It appears that the C-1300 neuroblastoma cell line utilized in this study differs biologically from that used by other investigators.
A child with Niemann-Pick disease type B, diagnosed at the age of two years and followed up for three years is described. Despite extensive visceral involvement--as deduced from marked hepatosplenomegaly and pulmonary infiltration--the child is in general good health and has no apparent neurologic abnormality. Biochemical studies revealed a tenfold increase of sphingomyelin content in his liver biopsy specimen and a markedly reduced sphingomyelinase activity in peripheral blood leukocytes. His parents were found to be heterozygous carriers of the disease, showing sphingomyelinase activity values intermediate between those of patient and healthy subjects. The relevant literature, concerning patients with the non-neuronopathic type B form, is reviewed.
Four adolescents with Hodgkin's disease also developed autoimmune diseases. There were two idiopathic thrombocytopenic purpura (ITP), one polymyositis, and one scleroderma. The first two patients developed ITP in the absence of a spleen, and with their Hodgkin's disease in remission. The first patient with Hodgkin's disease has been continuously free of cancer for over five years. The second patient was a 17-year-old male whoe Hodgkin's disease recurred, but whose disease was in remission at the time the ITP occurred. The polymyositis occurred in an 18-year-old youth when he was in his initial remission for his Hodgkin's disease, but his disease subsequently recurred two years later. This youth presented with Coombs positive autoimmune hemolytic anemia. The polymyositis did not respond to therapy, and he is left with severe muscle wasting and weakness; however, the polymyositis is now quiescent. The scleroderma occurred in an 18-year-old female who had been continuously free of Hodgkin's disease for eight years. The scleroderma did not respond to drug therapy and she now has moderate skin changes, but remains in continuous remission of her Hodgkin's disease. Although there are a few reports of Hodgkin's disease and concurrent autoimmune disorders, physicians dealing with cancer in adolescents should be aware of this association.
A 12 1/2-year-old female presented with Ewing's sarcoma of the manubrium sterni which extended into the anterior mediastinum. At presentation there was no evidence of metastatic disease. Her initial treatment consisted of radiation therapy and chemotherapy. The residual tumor was subsequently resected and the sternal defect was repaired with Marlex mesh. Postoperatively, she was maintained on chemotherapy consisting of BCNU, cyclophosphamide, and adriamycin. The adriamycin was discontinued after she developed sterile fibrinous pericarditis. She remains free of her disease two years after diagnosis. Although extremely rare, Ewing's does occur in the sternum and this area is amenable to wide local resection without severe functional disability.
To evaluate the effect of prostaglandin inhibition on the renal blood flow of the ischemic kidney, we administered indomethacin to 10 anesthetized dogs with renal artery stenosis and contralateral nephrectomy. Following the operation to produce renal ischemia, there was an increase of blood pressure associated with an increase of renin and the prostaglandins F1 (PGF1), and E (PGE). The administration of indomethacin to the intact, normotensive animals caused the anticipated decrease of prostaglandin E, renin, and renal blood flow. However, in the hypertensive dogs, indomethacin caused a paradoxical 45 per cent increase in the renal blood flow, despite a 44 per cent decrease of prostaglandin E. PGF1, PGE, renin, and erythropoietin exhibited the anticipated decreased levels. The study suggests that prostaglandins may not be the sole important factor in the regulation of renal blood flow in the presence of ischemia. Other important factors likely include the renin-sensitive angiotensin, the adrenergic, and the kallikrein-kinin systems.
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The potential difference in survival due to scheduling of cyclophosphamide treatment was examined in A/J mice inoculated with neuroblastoma C1-1300 cells. Treatment was started on the third day post tumor implantation. There were four groups of animals each consisting of 30 mice: Group A, a control group, was injected with 0.3 cc of normal saline for a week. Group B was injected with cyclophosphamide 50 mg/kg/day every other day for five doses. This cycle was repeated in the same fashion starting on day 17. Group C was injected with cyclophosphamide 250 mg/kg on day 3 and this was repeated on day 17. Group D was injected with cyclophosphamide 50 mg/kg/day for five consecutive days. This cycle was repeated on day 17-21. The median survival for group B was 26.2 days (the same as the control group), for group C 47.7 days (87% increased survival) and for group D 63.2 days (143% increased survival with 30% possible cures). Twenty-three percent of the mice in group B died of pneumonia and another 23% had minor evidence of lung infection. Only three mice in this group had tumor at the time of death. The study suggests that the response of murine neuroblastoma as well as the development of pneumonia in A/J mice treated with cyclophosphamide might be schedule dependent.
A 19-year-old woman with a diagnosis of osteosarcoma was initially treated with amputation of her right leg and adjuvant adriamycin. She developed pulmonary metastases 18 months following diagnosis. She was then given cis-dichlorodiammineplatinum(II) (DDP) at a dose of 100 mg/m2 iv approximately every 4 weeks as the sole drug. Following the fifth dose of DDP, she complained of numbness and tingling in her hands and leg. A distal sensory loss extending to both elbows and her remaining knee was found on examination. Nerve conduction tests were compatible with peripheral neuropathy of the "glove and stocking" type. DDP was withheld and her sensory loss improved over the next 2 months, but became worse after another course of DDP was administered. The temporal relationship between the findings and the administration of DDP implicates this drug as the causative agent in the peripheral neuropathy.
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A 17-year-old female presented with axillary lymphoadenopathy, which, on biopsy, demonstrated an anaplastic large cell lymphoma of the lymphohistiocytic type (ALCL-LH). The tumor cells expressed the CD30 antigen and reacted with the ALK1 antibody, suggesting the presence of the nucleophosmin-anaplastic large cell lymphoma kinase (NPM/ALK) fusion protein. No other adenopathy was found. Following a wide excision of the lymph node and without postoperative treatment, the patient remains free of disease 5 years later. This case demonstrates the potential curability of patients with early stages of ALCL by local treatment.
Priapism is common in pubertal males with sickle cell disease, but the association between low-dose exogenous testosterone administration and priapism in such patients has not been well documented. Two adolescents with homozygous sickle cell disease (SCD) and delayed maturation with behavioral problems developed priapism about one week after receiving an intramuscular injection of testosterone enanthate. Neither had a previous history of priapism. We conclude that testosterone should not be administered to male patients with SCD because of the risk of inducing priapism and possible impotence.
Renal and metabolic complications of tumor lysis syndrome (TLS) were recognized frequently in the 1960s and 1970s. Strategies were designed to prevent TLS. We conducted a retrospective chart review study to identify the current TLS risk in children with acute leukemia. Children were considered to have "laboratory tumor lysis syndrome" (LTLS) if two of the following metabolic changes occurred within 4 days of the start of chemotherapy: a 25% increase in serum phosphate, potassium, uric acid, or blood urea nitrogen levels, or a 25% decline in serum calcium concentration. Clinical TLS (CTLS) was defined as LTLS plus a serum potassium level higher than 6.0 mmol/L or acute renal failure. Twenty-one of 30 children developed LTLS; one developed CTLS. Absolute blast count, pretreatment white blood cell count, pretreatment lactic dehydrogenase, and sex or tumor DNA index did not correlate with the development of LTLS. LTLS is still frequent in children undergoing chemotherapy for acute leukemia; CTLS, however, is much less common.
Renal dysfunction may occur in survivors of bone marrow transplantation (BMT). The renal function of children who have survived 5 to 10 years after BMT has not been reported. Bone marrow transplantation was performed in 55 children with acute lymphoblastic leukemia less than 18 years of age at the University of Florida between September 1983 and October 1992. All received a uniform conditioning regimen of high-dose cystosine arabinoside and fractionated total body irradiation. Twenty-three are currently surviving. The survival average period following transplantation is 79 +/- 6.6 (SD) months. The longest survival is 129 months after BMT. We retrospectively examined data evaluating kidney function prior to transplantation, within 150 days after transplantation, and at each child's most recent clinic visit (1.7 to 10 years after transplantation). We were able to collect follow-up data regarding renal function for 17 survivors. Two children (11%) have renal dysfunction in the form of hypertension, glucosuria, and hematuria. One of them had acute renal insufficiency during the first 100 days following BMT. An unexpected finding was the presence of hyperfiltration in 10 patients. In conclusion, in this homogeneous group of children, allogenic BMT did not lead to significant long-term renal dysfunction.
In two patients with sickle cell disease who presented with headache pituitary adenoma and high levels of serum prolactin were found. Treatment with bromocriptine has controlled the headache. We believe that prolactin level determination should be part of the work-up of patients with sickle cell disease who complain of headache.