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Biomedical subjects

M H Cohen

Publications and source records attributed to M H Cohen.

At least 73 records · Page 4Linked to original sources
PubMed1989

Thrombosis: the major Hickman catheter complication in patients with solid tumor.

Major complications of Hickman catheter placement (thrombosis and infection) were determined in 168 patients with solid tumor (lung, 79; head and neck, 56; esophagus, 24; and miscellaneous, 9). Catheter-related thrombosis was clinically detected in 22 individuals and was detected at autopsy in six (total 17 percent). The 17 percent figure underestimates the true incidence of thrombosis since only 25 percent of study patients had autopsies. Patients with adenocarcinoma of the lung constituted a high risk group. Nine of 20 (45 percent) of these patients had thrombosis compared to 25, 9, and 16 percent of patients with squamous cell cancers of lung, head and neck and esophagus, respectively (p less than 0.002). Three patients with thrombosis had pulmonary emboli and two died. Thrombosis occurred despite daily heparin catheter flushing. INfections occurred in 11 patients. One had suspected endocarditis, one had a subcutaneous tunnel infection, and nine had exit site infections. All responded to local or systemic antibiotics. Better methods to prevent thrombosis are needed.

Adenocarcinoma↗
PubMed1988

Simultaneous chemotherapy and radiotherapy for squamous cell lung cancer.

Simultaneous chemotherapy and radiotherapy was evaluated in 13 patients with inoperable, limited stage squamous cell lung cancer. The chemotherapeutic agents bleomycin, methotrexate, 5-fluorouracil, vinblastine, and cisplatin were administered on days 1 and 5 of two treatment cycles given 5 weeks apart. Radiation therapy was given in three 2-week cycles, the first two starting on the second day of each chemotherapy cycle and the third starting 3 weeks after the second course of radiation. The total dose was 5000-5500 rad (50-55 Gy) in 180 rad fractions. The objective response rate (complete response + partial response) was 85%, with 38% complete responders. Median survival was 7 months with two patients surviving 34 months, one with disease and one disease-free. Treatment toxicity was predominantly hematopoietic and renal. Two patients died with massive pulmonary hemorrhage while receiving treatment and a third patient died of acute respiratory failure 1 month after completing therapy. The severe toxicity and the failure to obtain long duration tumor control makes this regimen unsuitable for future use.

Aged↗
PubMed1988

Lung cancer, tuberculin reactivity, and isoniazid.

We determined the incidence of tuberculosis in lung cancer patients with known tuberculin status. All patients received chemotherapy with or without radiation therapy, corticosteroid therapy, or both, and none received isoniazid prophylaxis. Positive tuberculin reactivity was found in 89 of the 257 patients; among these 89, tuberculosis developed in one patient before and in one patient after chemotherapy. Among the other 168 patients, one case of tuberculosis developed after chemotherapy. For all lung cancer patients, the incidence of tuberculosis was higher than age-specific and race-specific rates in a control population. The risk of tuberculosis was judged to be significantly higher in patients with positive than with negative tuberculin reactivity; among tuberculin reactors, however, the risk of tuberculosis was estimated to be less than the potential risk of isoniazid hepatotoxicity reported in the literature for patients in a similar age group. The median survival for tuberculin-positive lung cancer patients was 9.6 months. Because of the limited survival in these patients, and because of the high risk of isoniazid hepatotoxicity for patients in this age group, we do not recommend isoniazid prophylaxis for tuberculin-positive patients receiving chemotherapy for lung cancer.

Adult↗
PubMed1988

Cystic hypersecretory duct carcinoma of the breast. Report of a case with fine-needle aspiration.

A patient with a recently described rare histologic variant of ductal carcinoma of the breast, so-called cystic hypersecretory duct carcinoma, is described. The findings on fine-needle aspiration biopsy, and to our knowledge, the first cytologic study of this entity reported in the literature, are described and differentiated from mucinous carcinoma and benign mucocelelike lesions. The histologic differential diagnosis, with an emphasis on benign lesions that may have a predominant cystic component, is also discussed.

Aged↗
PubMed1987

Long-term treatment of rheumatoid arthritis comparing nabumetone with aspirin.

This report summarizes the results of a 17-investigator multicenter six-month randomized double-blind parallel group study. The safety and efficacy of nabumetone 1,000 mg taken at bedtime was compared with that of aspirin 900 mg four times daily in the treatment of adult patients with active class II or III classical or definite rheumatoid arthritis. Two hundred sixty-four patients were entered into the study. Two hundred fifty-seven (126 nabumetone and 131 aspirin) patients were evaluable for safety. Two hundred thirty-four (113 nabumetone and 121 aspirin) patients were evaluable for efficacy. There was significant improvement in each of six clinical measurements of efficacy in both treatment groups and little difference between groups. The somewhat greater improvement in articular index and duration of morning stiffness in the nabumetone-treated group did not reach statistical significance. There was an equal percentage of patient withdrawal for lack of efficacy in each group. Overall, the rate of patient withdrawal due to adverse experiences was greater (p = 0.01) for aspirin-treated patients. These experiences were usually dispepsia, abdominal pain, and tinnitus. It was concluded that nabumetone was an effective anti-inflammatory drug in the treatment of rheumatoid arthritis with less toxicity than aspirin.

Adolescent↗
PubMed1987

Comparison of the safety and efficacy of nabumetone and aspirin in the treatment of osteoarthritis in adults.

A six-month, multicenter, double-blind study compared the efficacy and safety of two therapeutic regimens in 332 patients with osteoarthritis. The patients received either 1,000 mg of nabumetone as a single bedtime dose or 900 mg of aspirin in four divided doses. At the end of the study, patients in both treatment groups showed significant improvement from baseline for all five parameters; no statistically or clinically significant differences were observed between the groups. The safety data did reveal clinically and statistically significant differences between the groups. Aspirin-treated patients experienced a greater frequency of withdrawal from the study because of adverse experiences (34 percent versus 13 percent), a greater incidence of having at least one treatment-related adverse experience (73 percent versus 52 percent), a greater percentage of patients with at least one moderate or severe treatment-related adverse experience (47 percent versus 22 percent), and a greater percentage of patients with treatment-related adverse experiences affecting the gastrointestinal system (43 percent versus 32 percent) or the inner ear (32 percent versus 10 percent). The results of this study demonstrated that nabumetone, 1,000 mg at bedtime, is as efficacious as aspirin, 900 mg four times daily, produces fewer adverse effects, and is indicated in the treatment of osteoarthritis.

Adult↗
PubMed1987

Left ventricular systolic circular index: an echocardiographic measure of transseptal pressure ratio.

An echocardiographic index of left ventricular (LV) short axis circularity can be defined by the equation: left ventricular systolic circularity index (LVSCI) = 4 pi(LV area) X 100/(LV perimeter). This index was measured from two-dimensional echocardiograms in 98 children (ages 1 day to 19 years) with congenital heart disease, and results were compared to right ventricular/left ventricular peak systolic pressure ratios (RVP/LVP) determined at cardiac catheterization. LVSCI was also computed in 50 children without cardiovascular or pulmonary disease to define the normal range. A short axis image of the left ventricle at the level of the papillary muscles was obtained from the left parasternal position. Area and perimeter were determined by computer planimetry of the LV endocardium at end systole. LVSCI was measured from three consecutive beats and averaged. In the normal group all values of LVSCI exceeded 93% (mean 96%). In the group with congenital heart disease RVP/LVP correlated exponentially with LVSCI: RVP/LVP = e2.6-0.04 LVSCI; with r = 0.88, SEE = 0.39, and p less than 0.001. If patients with suprasystemic right ventricular pressures (RVP/LVP greater than 1.2) are excluded, there is a linear correlation between RVP/LVP and LVSCI: RVP/LVP = 2.3-0.021 LVSCI; with r = 0.80, SEE = 0.14, and p less than 0.001. LVSCI could distinguish between patients with normal, mildly elevated, moderately elevated, and severely elevated RVP/LVP. We conclude that LVSCI is a readily determined parameter that is independent of age or body size and predicts RVP/LVP in children with congenital heart disease.

Adolescent↗
PubMed1987

Clearance of continuous intravenous morphine for severe cancer pain.

Four cancer patients with intractable pain received continuous morphine infusions in doses of 15-275 mg/h for a time period ranging from 4 to 27 days. Serum morphine concentrations were determined periodically following adjustments in infusion rates. As doses were changed and continued at static hourly rates, serum morphine concentrations were relatively constant 20 hours and beyond the time of the respective change, thus suggesting morphine elimination half-lives of less than or equal to 4 hours. High doses did not influence the time required to achieve steady-state concentrations. Steady serum morphine concentrations corresponded with hourly morphine doses in a parallel manner. High interpatient variabilities in clearances and steady-state serum morphine concentrations were noted. These data suggest that at morphine infusions up to 275 mg/h elimination pathways permit handling of increasing concentrations of morphine without nonlinear blood level increases. Also, marked interpatient and intrapatient variations in patient dose requirements were noted.

Female↗
PubMed1987

Chemotherapy alone or chemotherapy with chest radiation therapy in limited stage small cell lung cancer. A prospective, randomized trial.

STUDY OBJECTIVE: To determine the effect of concurrent chest radiation therapy on response rate, recurrence, and treatment toxicity among patients with limited stage small cell lung cancer who are receiving combination chemotherapy. DESIGN: Randomized trial with a median follow-up of 57 months. SETTING: A single government institution--the National Cancer Institute. PATIENTS: Consecutive sample of 96 patients with histologically confirmed small cell lung cancer that was confined to the hemithorax of origin or mediastinal and supraclavicular nodes, and which could be encompassed within a tolerable radiation portal ("limited stage"). All patients were followed until death or the end of the study period. INTERVENTIONS: Chemotherapy: Cyclophosphamide, methotrexate, and lomustine in 6-week cycles alternating with vincristine, adriamycin, and procarbazine in 6-week cycles, for a total of 48 weeks. Radiation therapy: Chest irradiation to 40 Gy in 15 fractions over 3 weeks, given simultaneously with the first chemotherapy cycle. MEASUREMENTS AND MAIN RESULTS: The combined therapy led to a significantly higher response rate (complete responses, 81%, compared with partial responses, 43%; 95% Cl for the difference, 20% to 56%), significantly improved local control of the chest tumor (p less than 0.001), and significantly longer survival (p less than 0.035) (median, 15.0 months, compared with 11.6 for chemotherapy alone). The combined therapy produced significantly more myelosuppression, weight loss, esophagitis, and pulmonary dysfunction. There were more infections and deaths from toxicity in the combined treatment group, but the differences between groups were not statistically significant. CONCLUSION: A regimen of combined chemotherapy and chest radiation therapy given concurrently is superior to chemotherapy given alone in inducing remission and prolonging survival in patients with limited stage small cell lung cancer, and the benefit of combined therapy is reduced by its greater toxicity.

Actuarial Analysis↗
PubMed1987

Hickman catheter clots: a common occurrence despite daily heparin flushing.

Central vein thrombosis is the major Hickman catheter complication in our patient population. After noting clots attached to the disposable infusion plug of these catheters, we prospectively determined whether the presence of clots indicated a high-risk group for thrombosis. Forty-three patients (41 with solid tumor, two with acute leukemia) were studied. Catheters were flushed daily with heparin (10 units/ml), and urokinase (5000-10,000 units) was injected when blood could not be drawn. Clots within the catheter lumen were detected visually after expressing, onto a 4 X 4-inch gauze pad, the first 5-10 ml of admixed blood and flush solution or iv infusion fluid drawn from the catheter prior to blood drawing. Clots were detected in 153 of 508 specimens (30%). Forty of 43 patients had clots, varying in length from fragments to 5 cm, in at least one specimen. Inpatients and outpatients had a similar percentage of clotted specimens. Eight patients developed clinical (six) or autopsy-proven (two) thrombosis. There was no difference between patients with and without thrombosis in percent of discards positive for clots. This study indicates that clots are frequently present in the lumina of Hickman catheters. It is likely that these clots embolize to the lungs when catheters are flushed. Consequences of embolization are unknown.

Blood Specimen Collection↗
PubMed1986

Bombesin in human and guinea pig alveolar macrophages.

Bombesin found in neuroepithelial bodies and oat cell carcinoma of the lung, is thought to play an important role in normally developing and malignant lung. Monocytes-macrophages and human small cell lung carcinoma cells share several features, including macrophage-specific surface markers and the expression of functional receptors for bombesin-like neuropeptides and growth factors. Because small cell lung carcinoma cells synthesize immunoreactive bombesin, we investigated the possibility that alveolar macrophages also contain bombesin, a plausible hypothesis considering the many reports of neuropeptide production by immune cells and cells of bone marrow origin. Adherent human peripheral blood mononuclear cells as well as human and guinea pig alveolar macrophages were found to contain bombesin. The peptide was detected by radioimmunoassay, immunohistochemistry, high-pressure liquid chromatography with the use of different monospecific antibodies.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Improvement of human tumor cloning assay by suspension of fibroblasts into the bottom layer of agarose.

Twenty-nine human tumors were cultured on a soft agarose cloning assay under three conditions: (1) standard (control); (2) standard with varying numbers of mitomycin C-treated 3T3 Swiss mouse embryonic fibroblasts suspended into the bottom layer of agarose; and (3) standard with varying concentrations of conditioned medium derived from those same fibroblasts. Suspension of 1 X 10(5) fibroblasts into the bottom layer of agarose was found to significantly increase the number of colonies formed over control specimens, as did cultures with 30% conditioned medium. In addition, compared with control, both of these techniques increased the number of specimens which would allow optimal vitro chemotherapy sensitivity testing. Specifically, growth of at least 30 colonies per plate increased from 7% of specimens treated under control conditions to 36% and 52% of specimens treated with 30% conditioned medium and 1 X 10(5) fibroblast-supplemented agar, respectively. This data indicate that 3T3 Swiss mouse fibroblasts improve cloning efficiency when suspended in the bottom layer of agarose or when used to produce conditioned medium. As a consequence, these techniques may permit a better opportunity to define the role of the cloning assay for cancer chemotherapy.

Colony-Forming Units Assay↗
PubMed1986

Non-small-cell lung cancer. Major cause of late mortality in patients with small cell lung cancer.

Among 360 patients with small cell lung cancer treated in National Cancer Institute therapeutic trials from 1973 to 1982, 40 were two-year cancer-free survivors. Of these 40 patients, six had later development of non-small-cell lung cancer at 3.5 to 8.0 years (median 5.1) after the diagnosis of small cell lung cancer. Three had the second malignant tumor in the contralateral lung, one in a different lobe, and two in the same lobe as the initial small cell lung cancer. Ten patients had relapses of small cell lung cancer at 2.1 to 6.2 years (median 3.2) from diagnosis. Three recurrences were in the same site or lobe as the initial lesion, four in the same lobe and in sites outside the thorax, and three solely in sites outside the thorax. It is concluded that these non-small-cell lung cancers usually represent second primary lung tumors and that most late small cell lung cancers represent relapses occurring up to 6.2 years from diagnosis. In this study, the risk of development of non-small-cell lung cancer after two years of disease-free survival following small cell lung cancer is 4.4 percent per person-year, approximately 10 times higher than the rate of 0.5 percent previously determined in screening studies of men at high risk for lung cancer. Non-small-cell lung cancer represents more than a third of lung cancer deaths in patients with small cell lung cancer surviving beyond two years from diagnosis and more than half of lung cancer deaths beyond three years. It is recommended that all patients treated for small cell lung cancer discontinue smoking.

Adult↗
PubMed1986

Conduction abnormalities detected by electrophysiologic testing following repair of ostium primum atrioventricular septal defect.

Since 1983 we have performed electrophysiologic studies in 6 patients who had previously undergone repair of an ostium primum atrioventricular septal defect. Information obtained during electrophysiologic studies was crucial in guiding appropriate pacemaker therapy in these patients. As judged from the resting electrocardiogram, sinus or junctional bradycardia was present in 3/6, atrial flutter / fibrillation in 2/6, and paced rhythm in 2 patients who had had ventricular pacemakers implanted for complete atrioventricular block. During maximal exercise testing 4 patients had reduced heart rates; 2 had sudden drops in heart rate at 1 min postexercise; 1 patient had exercise induced ventricular bigeminy; and 1 patient with atrial flutter and 2: 1-4: 1 block at rest developed 1: 1 conduction during Stage II with an effective ventricular rate of 220/min. During electrophysiologic studies, the maximum corrected sinus node recovery time was abnormal in five of the six, ranging from 410 to 5630 msec. There was no spontaneous atrial rhythm in the other patient. Complete atrioventricular block was present in 2 patients while the atrioventricular Wenckebach phenomenon occurred abnormally at atrial pacing cycle lengths greater than 450 msec in 2 others. Supraventricular tachycardia or atrial flutter/fibrillation, was either spontaneous or induced in 2/6 patients, while ventricular tachycardia was induced in 1/3 patients who underwent programmed ventricular stimulation. Electrophysiologic studies were important in unmasking severe sinus node disease in 3 patients and atrioventricular node disease in 2. We therefore recommend that electrophysiologic studies be strongly considered as part of the evaluation of conduction abnormalities following repair of ostium primum atrioventricular septal defect.

Adolescent↗
PubMed1986

Late intensive combined modality therapy followed by autologous bone marrow infusion in extensive-stage small-cell lung cancer.

To attempt to improve the poor prognosis of extensive-stage small-cell lung cancer (SCLC) patients, we tried to administer late intensive combined modality therapy (LICMRX) to patients with good tumor regression after 12 weeks of conventional chemotherapy. Twenty-nine consecutive extensive-stage SCLC patients received 6 weeks of cyclophosphamide, methotrexate, and lomustine (CMC) induction therapy, followed by 6 weeks of vincristine, doxorubicin, and procarbazine (VAP). After restaging for assessment of tumor response, autologous bone marrow (ABM) was collected in patients in good medical condition with complete response (CR) or partial response (PR) and no tumor on marrow examination. LICMRX consisted of irradiation with 2,000 rad in five fractions for five days to sites of initial tumor involvement, followed by cyclophosphamide, 60 mg/kg for 2 days, and etoposide, 200 mg/m2 for 3 days and then by ABM infusion. Prophylactic cranial irradiation (PCI) was administered thereafter, but no further chemotherapy was used. Due to lack of tumor regression or poor medical condition, only ten of the original 29 patients were eligible for LICMRX; two refused, so only eight (28%) received therapy. Three patients who began LICMRX in CR developed recurrence of SCLC after an additional 4, 8, and 15 months. Of five patients with PR, one attained CR but relapsed at 3 months, two remained in PR and progressed at 2 and 4 months, and two died of infection without recovery from LICMRX. Mean time from ABM infusion to recovery of granulocyte count to 500/microL was 15.8 days in the six surviving patients (range, 12-22). The major non-hematologic toxicity of LICMRX was severe esophagitis. Among all 29 patients, there were six CRs (21%) and no 2-year survivors, compared with a CR rate of 36% and 10% 2-year survivors in 78 extensive-stage patients previously treated with CMC plus VAP without LICMRX. We conclude that the LICMRX given in this study can be administered to only a minority of extensive-stage SCLC patients and is very unlikely to yield substantial improvement in the fraction of 2-year survivors (95% confidence limits for 2-year survival 0% to 10%).

Adult↗
PubMed1986

Pulmonary toxicity with combined modality therapy for limited stage small-cell lung cancer.

To assess the pulmonary toxicity of radiation therapy combined with chemotherapy v chemotherapy alone, we reviewed the clinical course of 80 patients with limited stage small-cell lung cancer treated in a randomized prospective trial. Life-threatening pulmonary toxicity, defined as bilateral pulmonary infiltrates extending beyond radiation ports with symptoms requiring hospital admission, developed in 11 patients (28%) receiving combined modality therapy and in two (5%) receiving chemotherapy alone. Eight of these 13 patients died from pulmonary complications with no clinical evidence of tumor in five. Pulmonary toxicity initially presented at a median of 63 days (range, 21 to 150 days) after the start of combined modality therapy and at a median of 217 days after chemotherapy alone. Biopsies obtained in 11 patients with severe toxicity revealed only interstitial fibrosis with no evidence of an infectious agent. Review of pretreatment parameters such as age, performance status, and radiation portal area failed to reveal any significant differences between patients with or without pulmonary complications. However, initial pulmonary function tests (PFTs) revealed a significantly lower vital capacity (P = .03) and forced expiratory volume (FEV/1.0 second) (P = .04) in patients with subsequent pulmonary complications. Pulmonary toxicity was significantly more common with combined modality therapy than with chemotherapy alone (P = .017) and worse than expected with radiotherapy alone. Six- or 12-month PFTs in completely responding patients revealed improvement within the chemotherapy alone group and no clear trend within the combined modality group. For the group treated with radiation therapy and chemotherapy, there was significantly less improvement after 6 or 12 months in the forced vital capacity (P less than .005) and FEV/1.0 second (P less than .005) than observed for the group treated with chemotherapy alone. Despite the increased incidence of pulmonary toxicity, overall survival favored the combined modality arm (P = .07). Enhanced local control and disease-free survival appeared to compensate for the initial increased pulmonary morbidity and mortality in the group with combined modality therapy.

Adult↗