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Biomedical subjects

S Martino

Publications and source records attributed to S Martino.

At least 19 recordsLinked to original sources
PubMed1992

Trends in the diagnosis of in situ breast cancer in the Detroit metropolitan area, 1973 to 1987.

The recent increase in incidence in situ breast cancer has been marked by a higher detection rate among white women. Although the increase in incidence may reflect the concomitant uptrend in mammographic screening, the lower proportion of cases among black women is of major public health concern. Time trends in the diagnosis of in situ breast cancer were evaluated in a population-based analysis of data accrued from the Metropolitan Detroit Cancer Surveillance System. The proportions of in situ cases detected among all women with breast cancer were measured annually between 1973 and 1987, and the average interval percentage changes were calculated for eight subgroups of women stratified by race and age at diagnosis. Although the proportions of in situ cancers were generally higher among white than black women, the greatest increase in average interval percentage change was observed in the oldest age category of black women. The disparity seen in younger black and white women suggests possible implications for breast cancer screening. From 1973 through 1987, the largest increase in diagnosis of in situ breast cancer occurred in black women older than 70.

Adult↗
PubMed1992

Racial differences in cancer of the male breast--15 year experience in the Detroit metropolitan area.

Characteristics of cancer of the male breast were evaluated in a population based review of 244 cases identified retrospectively through the Metropolitan Detroit Cancer Surveillance System (MDCSS) between 1973 and 1987. The mean age at diagnosis was 65 years and median survival time, 44 months. There were no apparent time trends in incidence for either white or black men from 1973 through 1987. Modified radical mastectomy was the most common surgical procedure, while simple and radical mastectomy declined in popularity over time. Cox's proportional hazards regression model was used to test the simultaneous effects of age, race, stage, and treatment on survival. Men older than 65 at diagnosis had a greater risk of dying than men under 65 (RR 1.52, 95% confidence interval, 1.01-2.28). Survival was significantly worse for men who presented at a more advanced stage; regional versus localized (RR 2.19, 95% confidence interval, 1.39-3.45) and remote versus localized (RR 4.31, 95% confidence interval 2.26-8.23). Race had no significant effect on survival in men with breast cancer in the Detroit Metropolitan Area.

Adult↗
PubMed1992

Effect of calcium replacement on the hemodynamic changes associated with high dose interleukin-2 therapy.

Administration of high-dose IL-2 results in hemodynamic changes that are similar to those seen in septic shock. These include a decrease in systemic vascular resistance (SVR) with a resultant drop in mean arterial pressure (MAP). Hypocalcemia is seen in septic shock and with IL-2 administration. Calcium replacement in septic shock has been reported to result in hemodynamic improvement; we therefore administered calcium to patients receiving high dose IL-2 to correct ionized hypocalcemia. Five consecutive patients underwent invasive hemodynamic monitoring before and during IL-2 administration. Calcium chloride was administered to correct ionized hypocalcemia, and hemodynamic parameters were monitored before and after calcium administration. Ionized hypocalcemia was associated with an elevation in parathyroid hormone levels. There was no toxicity related to the administration of calcium. An improvement in the MAP and SVR was seen early and late (after a dose of IL-2 was held) in the IL-2 treatment cycle; there were minimal effects at other points. Because of the potential hemodynamic benefit of calcium replacement, we recommend that ionized hypocalcemia be corrected in patients receiving high-dose IL-2.

Adult↗
PubMed1992

Phase I trial of recombinant macrophage colony-stimulating factor by rapid intravenous infusion in patients with cancer.

Fourteen patients were entered into a phase I dose-escalation trial of macrophage colony-stimulating factor (M-CSF). M-CSF was administered to inpatients by rapid 15 min i.v. infusion every 8 h x 5 days, repeated after a 9-day rest. Dose levels evaluated were 20, 40, 80, 330, and 1,100 micrograms/m2. Monitoring of patients every 4 h included vital signs, daily complete blood count (CBC), and serum chemistries (SGOT, creatinine, and bilirubin) while receiving M-CSF. No clinical or laboratory evidence of toxicity was seen. The average serum t1/2 varied with dose level. At 330 and 1,100 micrograms/m2, the serum t1/2 was 25 and 84 min, respectively, implying a saturable mechanism of clearance. After 5 days of treatment, the t1/2 decreased by twofold, consistent with enhancement of the saturable mechanism. Monocyte cytotoxicity against the A375 melanoma cell line was evaluated pretreatment and day 5 of each cycle. No consistent enhancement of monocyte cytotoxicity was seen. No effect on peripheral blood monocyte number was seen until the 1,100 micrograms/m2 dose level. At this dose level, the mean monocyte number on day 5 was increased compared to baseline (1,300 mm3 vs. 300/mm3). Clinical activity was seen in two patients with previously progressive leiomyosarcoma metastatic to the liver. A partial response (PR) lasting 7 months occurred at the 330 micrograms/m2 dose level while a patient treated at 1,100 micrograms/m2 has had stable disease for 20+ months. The maximum tolerated dose (MTD) of M-CSF was not determined. Based on clinical responses, a phase II trial is warranted in patients with metastatic soft tissue sarcoma.

Antineoplastic Agents↗
PubMed1992

[Captopril versus placebo in the prevention of hemicrania without aura. A randomized double-blind study].

Endogenous opioids are known to be involved in the pathophysiology of idiopathic headache. In fact, decreased levels of enkephalin (E) or endorphin (BE) during headache attacks might be a marker of an altered pain-inhibiting system of central neurotransmission or could be secondary to alterations of brain circulation that often occur during the headache crisis. Recently, captopril (C) has been shown to be apt to restore the availability of endogenous opioids, to improve cerebral blood flow via the inhibition of both the cerebral and systemic renin-angiotensin system or of catecholamine release. It has also been reported to be able to restore the nociceptive-antinociceptive balance through an increase of serum kinin (K) or prostaglandin (Pr) levels. In the present study, the efficacy of C in reducing the frequency (F), duration (D), or severity (S) of headache paroxysm were investigated in a double blind trial vs. placebo (P). Twenty-six subjects (5 males and 21 females; mean age 37 +/- 11 years) suffering from idiopathic headache at least for one year have been allocated to treatment with C (25 mg three times/day) or P according to a double-blind randomized protocol for 4 months. The effects of C or P have been evaluated with Migraine Index Correct, related to changes in F, D or S of headache attacks. Our results indicate that C is effective in reducing F, D or S in subjects with idiopathic headache.

Adult↗
PubMed1991

5-Fluorouracil, etoposide, and cisplatin in the management of metastatic non-small cell lung cancer.

Encouraging response rates have been reported in Stage III non-small cell lung cancer when 5-fluorouracil (5-FU), etoposide (VP-16), and cisplatin (FED) have been combined with radiation therapy (RT) or RT and surgery. The current study evaluated the effectiveness of FED chemotherapy in 32 patients with metastatic non-small cell lung cancer. Treatment consisted of 5-FU (800 mg/m2/d) on days 1 to 4 by continuous infusion, intravenous (IV) VP-16 (60 mg/m2) over 1 hour on days 1 to 4, and IV cisplatin (60 mg/m2) over 1 hour on day 1. Treatment cycles were repeated every 28 days as toxicity permitted. Partial responses occurred in 7 of 32 patients (22%; 95% confidence limit [CL] 0.09, 0.40), including 6 of 19 patients (32%) with performance status of 0 or 1, and 1 of 13 patients (8%) with performance status of 2 or 3. The median response duration was 5.0 months. Although toxicity was modest and consisted of primarily hematologic and gastrointestinal side effects, this combination does not appear to provide an advantage over other cisplatin combinations in Stage IV non-small cell lung cancer.

Adult↗
PubMed1991

Randomized trial of doxorubicin, bisantrene, and mitoxantrone in advanced breast cancer: a Southwest Oncology Group study.

Four hundred eleven women with metastatic breast cancer were randomly assigned to receive either 60 mg/m2 doxorubicin (130 patients), 320 mg/m2 bisantrene (146 patients), or 14 mg/m2 mitoxantrone (135 patients). The doses were given intravenously every 3 weeks with a cross-over design to determine their relative efficacy and toxicity. To be eligible, patients must have had one previous chemotherapy regimen, and patients who were estrogen receptor positive must have failed endocrine therapy. There were 365 patients assessable for response and 399 assessable for toxic effects. The median age was 57 years; 18% were premenopausal or perimenopausal. Visceral dominant disease was present in 66% of the patients. Ninety-seven percent of the patients had a disease-free interval from diagnosis to first recurrence of less than 1 year. The response rate was 28% with doxorubicin, 13% with bisantrene, and 14% with mitoxantrone (P = .004). Median time to treatment failure was 133 days with doxorubicin, 66 days with bisantrene, and 68 days with mitoxantrone (logrank P = .06). The median survival was 315 days for doxorubicin, 290 days for bisantrene, and 177 days for mitoxantrone (logrank P = .04), although survival at 2 years was similar for all three agents. There were five responses in the 66 patients crossed over to doxorubicin and one response each for patients crossed over to bisantrene (39 patients) or mitoxantrone (63 patients). Toxicity leading to discontinuance of therapy was more common with doxorubicin, and discontinuance of therapy was due primarily to patient's request or cardiotoxicity. The major dose-limiting toxic effect for all three agents was leukopenia. Nausea and vomiting, mucositis, and alopecia were more severe with doxorubicin. Congestive heart failure developed in nine patients treated with doxorubicin, zero patients treated with bisantrene, and two patients treated with mitoxantrone. A decrease in the left ventricular ejection fraction, as defined by moderate to severe Alexander grade changes, was more common in patients treated with doxorubicin (doxorubicin-treated patients = 20%, bisantrene-treated patients = 5%, and mitoxantrone-treated patients = 10%). This study demonstrates that bisantrene and mitoxantrone have only modest activity in metastatic breast carcinoma. The activity of doxorubicin is greater than that of the other two agents, but at a cost of increased toxicity.

Adenocarcinoma↗
PubMed1991

Effects of a low-fat diet on levels of oxidative damage to DNA to human peripheral nucleated blood cells.

Fat in the diet has been associated with increased breast cancer risk. In this study, blood samples were obtained from 21 women at high risk for breast cancer who had been randomly assigned to either a nonintervention diet or a low-fat diet. Oxidative damage was examined in the DNA from nucleated peripheral blood cells. The levels of oxidized thymine, specifically 5-hydroxymethyluracil, were threefold higher in the nonintervention diet group than in the low-fat diet group. Without regard to diet arm, there also was a significant linear relationship between daily total fat intake and 5-hydroxymethyluracil level. These results suggest that oxidative damage to DNA may be a marker of dietary fat intake. In addition, oxidative DNA damage may be a mechanistic link between fat in the diet and cancer risk, since such damage is associated with the process of tumor promotion.

Adolescent↗
PubMed1991

Isolated adrenocorticotropic hormone deficiency associated with common variable immunodeficiency.

A 14-year-old girl has been suffering from an isolated adrenocorticotropin hormone (ACTH) deficiency with secondary glucocorticoid deficiency and common variable immunodeficiency since the age of 6.6 years. Human corticotropin releasing hormone administration did not increase ACTH and cortisol levels, strongly suggesting a pituitary deficiency. Despite the profound humoral defect, severe infections have never developed and the antibody response to herpes viruses was intact. We speculate that the association between two rare disorders, simultaneously diagnosed 2 months after measles, is not coincidental but caused by close interactions between neuro-endocrine and immune systems.

Adolescent↗
PubMed1991

Effect of heroin and morphine on cardiac performance in isolated and perfused rabbit heart: evaluation of cardiac haemodynamics, myocardial enzyme activity and ultrastructure features.

In the present study the effects of heroin and morphine administration on cardiac function, myocardial enzyme activity and cardiac ultrastructure features have been evaluated in isolated and perfused rabbit hearts. In 24 male rabbits the hearts were excised and immediately perfused in a retrograde non recirculating Langendorff apparatus. Successively, heroin 1 x 10(-5) or 1 x 10(-4) M or morphine at 1 x 10(-4) M were individually administered in 18 rabbits for 45 min. In 6 rabbits, used as controls, the isolated hearts were perfused with perfusion fluid for the same time. At the end of perfusion period the hearts were removed and histology was studied. During the perfusion period, creatine phosphokinase (CPK), lactic dehydrogenase (LDH) activity, heart rate (HR), derivative of intraventricular pressure time ratio (dP/dt) and changes in systolic ventricular pressure (SVP), diastolic ventricular pressure (DVP) and in coronary blood flow (CBF) were also evaluated. At the end of perfusion period no significant changes in CPK, LDH, HR, dP/dt ratio, SVP, DVP and CBF in comparison with basal values were observed in all groups. Histological specimen were characterized by slight derangements in atrial and ventricular structure both after heroin and after morphine administration. In conclusion our data suggest that alterations following opioids administration might rather be related to a systemic action involving only indirectly the heart.

Animals↗
PubMed1990

A phase I-II study of dacarbazine in combination with outpatient interleukin-2 in metastatic malignant melanoma.

Because of encouraging response rates published with recombinant interleukin-2 (rIL-2) alone in metastatic malignant melanoma (MMM), dacarbazine (DTIC) and rIL-2 were sequentially combined to evaluate efficacy, toxicity, pharmacokinetics, and immunologic interaction. Thirty-two patients aged 18 to 67 years have received 127 courses of treatment. The dose of DTIC was 1.0 g/m2 as a 24-hour infusion every 28 days on day 1. Recombinant interleukin-2 (2.0, 3.0, 4.0, or 5.0 x 10(6) Cetus units/m2) was administered as a 30-minute infusion on days 15 through 19 and 22 through 26 of each 28-day cycle. Seven of 32 patients (22%) who received therapy had a remission, one complete and six partial. The complete response was in a lung mass. Partial responses were seen in lymph nodes, liver, and lung. The median duration of response was 4.7 months. One patient is in persistent partial remission of the liver for greater than 2 years. One patient had residual mediastinal disease resected after partial response and remains without evidence of disease for 18+ months. This regimen was generally well tolerated, did not create overlapping toxicity, and produced encouraging responses in visceral sites. This provides a framework for future combinations of chemotherapy with rIL-2 alone or in combination with other biologic response modifiers in an outpatient setting.

Adolescent↗
PubMed1990

Phase II study of deoxydoxorubicin in previously untreated metastatic breast cancer.

With the objective of identifying new chemotherapeutic agents active against breast cancer, we administered the phase II agent deoxydoxorubicin (DxDx) to 25 patients who had received no prior chemotherapy for their metastatic breast cancer. A dose of 30-35 mg/M2 given at 3 week intervals resulted in a response rate of 12%. The patients were subsequently treated with a combination of 5-fluorouracil, methotrexate, vincristine, cyclophosphamide, and prednisone. A response rate of 38% was achieved with this combination as second line therapy. Toxicity of DxDx was predominantly hematopoietic. One patient developed congestive heart failure. Median survival from onset of treatment with DxDx was 39 weeks. DxDx appears to be minimally active against metastatic breast cancer. Whether the administration of phase II agents as first line therapy offers an advantage in the overall management of metastatic cancer, needs further evaluation.

Adult↗
PubMed1990

A phase I trial of recombinant interleukin-2 combined with recombinant interferon-gamma in patients with cancer.

Twenty-six patients with metastatic cancer were entered into a phase I trial of concurrent recombinant interleukin-2 (IL-2) and recombinant interferon-gamma (IFN-gamma). IL-2 was administered as a continuous intravenous infusion for 5 days. IFN-gamma was administered by a daily intramuscular (IM) injection during the 5 days of IL-2 administration. Treatment was repeated twice after 9-day rest periods. After a 2-week rest, patients without evidence of tumor progression were retreated. Natural killer (NK)- and lymphokine-activated killer (LAK)-cell activity were assayed in each patient before treatment, on day 1, and on day 5 of each cycle. Constitutional symptoms occurred in most patients but were not dose-limiting. Other toxicities included hypotension responsive to fluids, transient elevations in liver function tests, erythema/pruritus, eosinophilia, and transient leukopenia/thrombocytopenia. The maximum-tolerated dose (MTD) of the combination was 1 x 10(6) U/m2/d of IL-2 combined with 0.50 mg/m2/d of IFN-gamma. The dose-limiting toxicity was pulmonary manifesting as rales and shortness of breath. The dose of the combination that resulted in the optimal generation of in vivo LAK-cell activity was a dose of at least 0.25 mg/m2/d of IFN-gamma combined with 1 x 10(6) U/m2/d of IL-2. Objective clinical responses were seen in five of 26 patients. These included a partial response of 2 months duration in a patient with non-Hodgkin's lymphoma (NHL), mixed responses in a patient with NHL and two patients with renal cell carcinoma (RCC), and an ongoing assessable response in a patient with bone metastases from RCC. The recommended dose for phase II trials of this combination is 0.50 mg/m2 of IFN-gamma and 1 x 10(6) U of IL-2.

Adolescent↗
PubMed1989

Serum interleukin 2 (IL-2) levels and prolactin bioactive/radioimmunoassay ratios of women at risk for breast cancer.

In a cohort of women at high risk for developing breast cancer we have observed that 74% of the women with prolactin BA/RIA ratios over 1.4 had detectable levels of IL-2 in their serum (990 +/- 400 mU/ml) and the IL-2 levels were correlated with the prolactin BA/RIA ratio (R = 0.79; P greater than 0.004). Women with BA/RIA ratios were either approximately 1.0 or less than 0.55 had lower levels of serum IL-2 (177 +/- 70 and 130 +/- 40 mU/ml, respectively). Detectable levels of serum IL-2 were found in 58% of those women with BA/RIA ratios of 1.0 and 55% of those with BA/RIA ratios less than 0.55.

Adolescent↗
PubMed1988

Treatment of metastatic breast cancer with AZQ: a phase II trial.

Seventeen patients with metastatic breast cancer who had failed prior chemotherapy were treated with intravenous AZQ at a dose of 15-20 mg/m2 weekly for four consecutive weeks followed by a two-week rest period. No responses were observed. Myelosuppression was the dose-limiting toxicity. One patient experienced massive liver infarction possibly related to AZQ. Our data suggest that this agent at the schedule and dosage used is of no benefit in pretreated breast cancer patients.

Antineoplastic Agents↗