Interferon alpha-2a and dacarbazine in melanoma.
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Biomedical subjects
Publications and source records attributed to A Giuliano.
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A 30-yr-old woman with malignant hypertension was found to have biochemical evidence of pheochromocytoma. Bilateral adrenal tumors were demonstrated on computerized tomographic scanning and confirmed at the time of surgery. Complete removal of one adrenal gland with partial removal of the other adrenal gland resulted in normalization of her blood pressure and biochemical parameters (norepinephrine and epinephrine) with preservation of adrenocortical function.
The effect of lithium on PTH release from human parathyroid tissue was studied using a perifusion system and an immunoradiometric assay for intact human PTH. Tissue was obtained from three patients undergoing surgery for thyroid disease, three patients with secondary hyperparathyroidism due to chronic renal insufficiency, and four patients with primary hyperparathyroidism due to a parathyroid adenoma. Addition of lithium in concentrations equivalent to the therapeutic serum levels normally attained in man (1.3 mmol/L) resulted in a significant (P less than 0.05) increase in PTH release under normocalcemic (1.15 mmol/L) conditions from normal and hyperplastic tissues. The magnitude of the lithium-induced response of PTH release ranged from a 1.4- to 5.3-fold increase above basal levels (perifusion with 1.15 mmol/L calcium alone) and was comparable to the response during a low calcium (0.42 mmol/L) perifusion. Although the response to lithium was delayed compared to that of hypocalcemia, PTH returned to basal levels immediately after removal of either stimulator. In contrast, parathyroid adenomas did not respond to either lithium or hypocalcemia in a characteristic manner, but, rather, functioned in an autonomous fashion with repeated pulsatile bursts of PTH release that were not suppressible even under hypercalcemic (1.70 mmol/L) conditions. These in vitro studies suggest that lithium therapy may elevate serum PTH levels in some patients and could, thus, be responsible for hypercalcemia in them.
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To determine the role of chemotherapy in the multidisciplinary treatment of patients with osteosarcoma, a randomized prospective trial of postoperative adjuvant chemotherapy was begun in 1981. Fifty-nine patients with nonmetastatic classic intramedullary osteosarcoma were randomized; 32 received postoperative adjuvant chemotherapy consisting of high-dose methotrexate, Adriamycin (Adria Laboratories, Columbus, OH), and BCD (bleomycin, cytoxan, actinomycin D), and 27 patients received no adjuvant chemotherapy. At a median follow-up of 2 years, there was a statistically significant improvement in both disease-free and overall survival in those who received adjuvant chemotherapy. In addition, there was no difference in the less than 20% disease-free or overall survival of patients treated in the 1970s who did not receive chemotherapy, as compared with the concurrent nontreatment controls. Therefore, with identical staging procedures, uniform surgical management, and standard pathologic evaluation, postoperative adjuvant chemotherapy definitely improves disease-free and overall survival in patients with osteosarcoma.
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Sixteen patients with necrotizing fasciitis were observed under clinical and laboratory conditions for collection, preservation, and culture that permitted optimal retrieval of anaerobes. The clinical observations of necrosis of fascia, subcutaneous fat and skin with thrombosis of the microvasculature, and absence of myonecrosis were clearly apparent in these patients. Two clear-cut groups of culture and gram stain results were found, suggesting that the clinical entity of necrotizing fasciitis can occur after infection by different infecting organisms. The cultivation of Streptococcus pyogenes (group A), either alone or in combination with staphylococcus, in three patients conforms to the culture results found by Meleney [1] in his original description.
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BACKGROUND: One- and five-year breast cancer survival rates are significantly lower among Southwest American Indian (AI) women compared with non-Hispanic whites, primarily due to late stage at diagnosis. By detecting cancers at an earlier stage, screening mammography can reduce breast cancer mortality by 30% among women ages 50-69 years. METHODS: To determine rate of and predictors of participation in breast cancer screening services among Southwest AI women, randomly selected AI women living on the Arizona Hopi reservation were interviewed. Independent predictors of breast cancer screening were determined using logistic regression analyses among respondents ages > or = 40 years (n = 314). RESULTS: Of respondents > or = 40 years, 26.4% had had a mammogram in the past 2 years, and 23.2% of women > or = 50 years had had both a mammogram and a clinical breast examination. Mammography screening in the past 2 years was independently associated with an age between 50 and 59 years, knowledge of the procedure, belief that mammography can detect breast cancer, having yearly Pap smears, and use of the Hopi-language. CONCLUSION: Self-reported breast cancer screening rates among this population of AI women are far below objectives set for the Year 2000. This study confirms the importance of breast cancer screening knowledge and participation in routine medical services to rates of breast cancer screening.
A study was performed on the structure-activity relationships of a series of phenol derivatives, CVFM analogs, derived from the two most active compounds of a first series (1A and 1B) of inhibitors of Ras farnesyl transferase (FTase) that we have recently described. We report the synthesis and the activity of a second series of compounds in which the phenylalanine residue was replaced by unconventional aromatic and non-aromatic amino acids, with varying electronic, lipophilic, steric and conformational properties. The compounds showed to be significantly less active than reference compounds against FT, with the only exception of derivative 3A (IC50 = 3 microM), which is slightly more active than 1A but not 1B. Subsequently we tested the effects of compounds 1A, 1B and 3A, 3B on the anchorage-dependent growth of two epithelial cell lines of rats, FRTL-5 and the same line v-Ha-ras transformed. Compound 3A derived from lead compound 1A, showed an appreciable selectivity against transformed cells. In contrast, compounds derived from derivative 1B had only a modest cellular activity.
BACKGROUND: Protein Fv is an endogenous protein, synthesized in liver and largely released in the digestive tract during acute and chronic viral hepatitis, that binds to immunoglobulin (Ig) from various mammalian and nonmammalian species. METHODS: Basophils obtained from normal subjects were purified by a double Percoll gradient and elutriation. The secretion of histamine induced by protein Fv was assayed by a fluorometric technique, the extracellular protein levels of IL-4 and IL-13 were measured by ELISA, and IL-4 mRNA levels were evaluated by RT-PCR. RESULTS: Protein Fv concentration-dependently induced histamine and IL-4 and IL-13 release from purified basophils. IL-4 mRNA, constitutively present in basophils, was increased after stimulation by protein Fv. Histamine and IL-4 secretion from basophils, but not histamine and IL-13 release, activated by protein Fv was significantly correlated (rs = 0.70, p<0.001). Basophils from which IgE had been dissociated by brief exposure to lactic acid no longer released IL-4 in response to protein Fv and anti-IgE. Two preparations of human VH3(+) monoclonal IgM inhibited protein Fv-induced secretion of IL-4 and histamine from basophils. In contrast, VH6(+) monoclonal IgM did not inhibit the release of mediators caused by protein Fv. CONCLUSIONS: These results indicate that protein Fv, which acts as an endogenous superallergen, interacts with the VH3 domain of IgE to induce the synthesis and release of IL-4, IL-13 and the secretion of histamine from basophils.
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Although cervical cancer is a common female cancer, little attention has been given to genetic susceptibility factors. The present case-control study was undertaken to examine MTHFR polymorphism as a potential molecular marker of cervical intraepithelial neoplasia (CIN) susceptibility and to relate the findings to smoking, HPV infection, ethnicity, parity and oral contraceptive use, which are known risk factors for cervical cancer. A base change from C to T at the nucleotide position 677 of the MTHFR gene results in substitution of valine (GTC) for alanine (GCC). The homozygous normal (Ala/Ala), homozygous mutant (Val/Val), and heterozygous mutant (Ala/Val) genotypes for the MTHFR gene were determined in cervical tissues of 64 cases of CIN lesions and 31 controls. The genotype frequencies of both Val/Val (17%) and Ala/Val (56%) were significantly higher in subjects with CIN lesions compared to controls with Val/Val (10%) and Ala/Val (39%), (trend p = 0.03). The results suggested a significantly increased CIN risk with an alanine to valine substitution at amino acid 223 of MTHFR with an odds ratio of 2.9 (95% confidence interval: 1.2-7.9, p = 0.02). Age, ethnicity, smoking and oral contraceptive use were weakly and nonsignificantly associated with CIN risk. HPV infection was associated with a statistically nonsignificant threefold increase in CIN risk. Parity and MTHFR genotype displayed a strong interaction. Neither nulliparous women with MTHFR polymorphism nor parous women without the polymorphism were at higher risk than women who did not have children and were MTHFR homozygous normal (the reference category). Women with mutant MTHFR genotype who had children, however, showed a significantly higher risk of CIN, with an odds ratio of 23 (95% confidence interval: 2.3-225) as compared to the reference category. No other factors displayed such a strong pattern of interaction. Since MTHFR polymorphism and pregnancy increases folate requirements and can impair folate status, this association could reflect an inadequate response of mutant MTHFR genotype carriers to the increased demand for folate imposed by pregnancy. Tissue folate deficiency, in turn, could increase the risk of CIN in the affected women.
Fine needle aspiration cytology (FNAC) is increasingly used for the initial diagnosis of breast carcinoma, yet few studies have investigated the prognostic importance of cytologic features seen in breast FNAC. We studied the relationship between prognosis and smear morphology in 26 patients with breast carcinoma for whom information from long-term follow-up was available. Specifically, we attempted to correlate nuclear grade and smear pattern with hormonal receptor status, lymph node status, breast recurrence and distant metastasis. In an additional five patients (on whom insufficient follow-up information was available), smear pattern and nuclear grade were correlated with hormonal status. Smears were classified into three patterns: typical (sheets and clusters), individual cell predominant and cluster predominant. The individual cell predominant pattern was associated with an increased incidence of distant metastasis when compared with the other two smear patterns (P less than .05). No statistically significant association was observed between smear pattern and the other factors studied. Nuclear grade 2 (of 3) was also associated with an increased incidence of distant metastasis. However, most grade 2 tumors (10/12) were of the individual cell predominant pattern. Smear pattern classification, along with DNA ploidy analysis and hormone receptor analysis of FNAC-derived material, may yield valuable prognostic information.
A 7 year old girl presented with persistent right upper abdominal colicky pain, fever, elevated white blood cells count, high blood sedimentation rate and mild liver enlargement. At surgical exploration 33 live ascarides (ascaris lumbricoides) were taken off from the hepatic duct. Medical treatment with mebendazole was given in full doses after surgery. She remained well for six years except for intermittent episodes of colicky right upper abdominal pain. At age 13 year ascarides were again demonstrated at the common biliary duct by abdominal echography. A second operation was necessary to eliminate parasites from the lower biliary tree, together with medical treatment for the patient and her family. One year later she was free of symptoms.