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In the development of triage and bypass protocols, many different scoring systems and triage criteria are being used. Our purpose was to evaluate the Revised Trauma Index (RTI) as a triage tool for both its severity prediction ability and triage accuracy. A total of 2,340 trauma admissions were evaluated using the RTI and the Injury Severity Score (ISS). The data were submitted to standardized statistical analysis and compared to other published data for under and overtriage. Our results show a linear correlation between the RTI and the ISS with a correlation coefficient of .62. There is 5% death rate at an RTI level of 15, which yields a 5% undertriage rate for death and a 37.3% overtriage rate for predicting an ISS greater than 15. This compares to under and overtriage rates for the Trauma Score, CRAMS, Pre-Hospital Index, and Mechanism of Injury scales varying from 19% to 56% undertriage and 7% to 82% overtriage. We reached the following conclusions. a) The RTI is a simple, fast triage tool for predicting major trauma. b) The RTI is related to the ultimate ISS. c) Use of an RTI greater than or equal to 15 results in an acceptable undertriage rate, with a better rate for overtriage than existing scores. d) Therefore, we recommend the RTI for use in emergency medical direction and bypass protocols.

Human pancreas contains receptors for estrogens and androgens as well as aromatase activity. FAM chemotherapy was administered to 14 patients with pancreatic cancer (seven at Stage IV). The median survival of these patients was 24.4 +/- 4.8 weeks. FAM chemotherapy plus aminoglutethimide/hydrocortisone (AG/HC) (250 mg bid AG + 20 mg bid HC) was administered to 14 patients (seven at stage IV). The median survival of this group was 17.3 +/- 2.9 weeks (P = 0.74 vs FAM alone). We conclude that addition of AG/HC does not add to the survival of patients with carcinoma of the pancreas treated with chemotherapy.

Concentrations of triglycerides are increased and concentrations of high-density lipoprotein (HDL) cholesterol are low in women with hyperandrogenism. These alterations could be related to excessive androgen or estrogen, to hyperinsulinism, or to a combination of these abnormalities. We examined their independent influences on lipids in 21 women with hyperandrogenism, subgrouped according to apparent source of androgen excess. Results for lipid, androgen, and insulin did not differ among subgroups, so these data were pooled. Free plus albumin-bound testosterone (uT) was correlated with triglycerides (r = 0.69, P less than 0.01) and HDL cholesterol (r = -0.56, P less than 0.01). Both triglycerides (r = 0.66, P less than 0.01) and HDL cholesterol (r = -0.48, P less than 0.05) were also correlated with insulin measured during fasting. Partial correlation revealed that, after adjusting for insulin, lipids were associated with uT. This suggests that androgen excess is independently related to lipid excess. Insulin also was correlated with lipids when adjusted for uT. Free plus albumin-bound estradiol was not associated with any of the lipids. We conclude that altered lipids in women with hyperandrogenism result from the independent effects of androgen and insulin.

A monoclonal antibody (mAb) exhibiting a high degree of species specificity for the yeast phase of the dimorphic fungus Histoplasma capsulatum was produced by a modification of the standard mAb production protocol. The technique for generating mAbs involved the use of the immunosuppressive drug cyclophosphamide to diminish the response in mice to immunodominant cross-reactive epitopes. This mAb exhibited clear specificity and did not react by ELISA with the closely related genera Blastomyces, Paracoccidioides and Sporothrix. In Western blots it recognized a linear determinant on a 70-75 kDa molecule in H. capsulatum antigen, with an extremely faint reactivity to antigens of identical molecular mass derived from Sporothrix and Paracoccidioides, and no reactivity against Blastomyces antigen.

Polyamines may be involved in hormone-dependent breast cancer cell proliferation. The antiestrogen 4-hydroxy-tamoxifen and the polyamine synthesis inhibitor alpha-difluoromethylornithine (DFMO) inhibited MCF-7 growth, and this effect was additive. Transforming growth factor beta (TGF-beta) levels were increased by both compounds; again the effect was additive. Exogenous putrescine antagonized DFMO but not the antiestrogen. However, exogenous TGF-beta did not inhibit cell growth. Secretion of insulin-like growth factor 1 (IGF-1) was not affected by DFMO-induced polyamine depletion but 4-hydroxytamoxifen increased IGF-1, which suggests an estradiol-like effect. Thus polyamines are involved in basal TGF-beta secretion but do not mediate antiestrogen-induced TGF-beta secretion. IGF-1 secretion by MCF-7 cells is not under polyamine control. The antiproliferative effects of 4-hydroxytamoxifen and DFMO cannot be accounted for by either suppression of IGF-1 secretion (a growth stimulatory factor) or stimulation of TGF-beta production (a growth inhibitory polypeptide).

A panel of monoclonal antibodies (Mabs) was raised against histoplasmin, the antigen derived from the mycelial phase of Histoplasma capsulatum var. capsulatum which contains the diagnostically useful H and M antigens. A number of Mabs were obtained which recognized a 70-75 kD component of an antigenic preparation of H. capsulatum var. capsulatum by Western blotting. When reacted with histoplasmin by Western blotting the Mabs recognized a similar 70-75 kD band, together with a series of higher molecular mass bands at approximately 130, 190 and 230 kD, a pattern which correlates strongly with both the published relative molecular mass (Mr) of the M antigen and the known subunit structure of the enzyme catalase. These Mabs were also shown to recognize a commercial preparation of Aspergillus niger catalase by ELISA. Other dimorphic fungi were also reactive with these Mabs by Western blotting, indicating the presence of common epitopes on the catalase molecules of these species.

We have provided evidence for a critical role of polyamines in the growth of the hormone-responsive N-nitrosomethyl-urea (NMU)-induced rat mammary tumor in vitro. The present experiments were designed to test whether polyamines are involved in the growth of this experimental tumor in vivo. To test this hypothesis, groups of rats bearing NMU-induced mammary cancers were randomly allocated to receive no treatment or escalating doses of the polyamine biosynthesis inhibitor alpha-difluoromethyl-ornithine (DFMO) (0.5%, 1%, 2%, 3% in drinking water). DFMO inhibited tumor growth in a dose-dependent fashion and consistently reduced tumor putrescine level. To evaluate the time dependency of this effect, additional groups of rats received either no treatment or 2% DFMO for 3, 7, 14, and 21 days. At all times DFMO suppressed tumor putrescine level as well as spermidine to spermine ratio. Finally, exogenous administration of putrescine (200 mg/kg/i.p./day x 21 days) given concomitantly with DFMO restored tumor growth, partially repleted tumor putrescine level, and raised the spermidine to spermine ratio to control levels. Putrescine, given alone, had no significant effect on either tumor polyamine levels or tumor growth. Except for modest weight loss, no major toxicity was encountered. These results indicate that polyamines play an important role in the growth of the NMU rat mammary tumor in vivo. The interaction between polyamines and hormones in supporting NMU mammary tumor growth in vivo remains to be elucidated.

We assessed the bronchodilator response to cumulative doses of nebulised fenoterol in 16 patients with severe asthma to determine (1) the magnitude of the bronchodilator response, (2) the factors determining this response, and (3) the dose producing maximum bronchodilation. To reflect the degree to which ventilatory function returned to normal, individual bronchodilator responses were assessed as the change in FEV1 (post-fenoterol FEV1 - initial FEV1) and expressed as a percentage of the predicted maximum response (predicted FEV1 - initial FEV1). The bronchodilator response was extremely varied (about 55% of predicted maximum in six patients, 40% in three patients, and 20% in seven patients), as was the dose producing maximal bronchodilation (1 mg in three patients, 2 mg in six patients, and 2.5 or 3 mg in seven patients). In individual patients the maximum response could be predicted by the response to the initial dose of fenoterol and by the duration of the episode of severe asthma. The maximum response was not predicted by the initial severity of obstruction or the patient's usual treatment.

Analyses were undertaken to determine the causes of cerebral palsy in a prospective study of 43,437 full-term children. Presumed causes were found for about 71% of the 34 quadriplegic and 40% of the 116 nonquadriplegic patients with cerebral palsy. Risk estimates based on predictive models, adjusted for multiple factors, suggest that 53% of the quadriplegic patients with cerebral palsy could be attributed to congenital disorders, 14% to birth asphyxia, and 8% to other identified disorders. Thirty-five percent of the nonquadriplegic patients with cerebral palsy could be attributed to congenital disorders and 6% to other disorders. In the victims of cerebral palsy, characteristic consequences of birth asphyxia were more often the result of nonasphyxial disorders. These included meconium in the amniotic fluid, low 10-minute Apgar scores, neonatal apnea spells, seizures, persisting neurologic abnormalities, and slow head growth after birth.

In this pilot clinical trial conducted in 10 postmenopausal women with advanced breast cancer, we evaluated the endocrine effects and toxicity of combined somatostatin analog and dopaminergic therapy in the attempt to suppress both growth hormone (GH) and prolactin (PRL) secretion. The patients' mean age was 63 years (range: 54-77) and the average number of previous treatments was 4.8 +/- 2 (SD). All patients were treated with the somatostatin analog SMS 201-995 (100-200 micrograms s.c. in a.m. and h.s.) and bromocriptine (2.5 mg orally twice a day). During treatment, GH levels following provocative testing (either L-DOPA or insulin-induced hypoglycemia) were suppressed in 7/9 patients. Basal somatomedin-S (Sm-C) levels declined in 6/9 women. Both GH and Sm-C levels decreased in 4 patients, while in the remaining 5 only one of the two parameters was lowered on treatment. PRL secretion (during provocative TRH testing) was almost totally abolished in 8/9 patients. The treatment did not affect circulating levels of FSH, LH, E1, E2, E1-S, T4, T3RU, or cortisol. Seven patients experienced no side effects. Nausea occurred in 3, but was severe enough in only one to require discontinuation of therapy. One patient experienced disease stabilization consisting of less than 50% regression of skin nodules and pleural effusion, a decline in CEA titer, and an improved performance status lasting 7 months. We conclude that combined SMS 201-995 and bromocriptine therapy is safe and frequently suppresses GH and PRL secretion. Its role in the treatment of metastatic breast cancer should be tested in patients with less advanced disease.

Lipoprotein lipid and androgen profiles were compared after a 12-hour fast that involved 13 women with polycystic ovary syndrome and 13 who did not have the syndrome. All women were matched for percent ideal body weight. As expected, patients with polycystic ovary syndrome had significantly higher luteinizing hormone--to--follicle-stimulating hormone ratios, higher testosterone levels, higher free testosterone levels, higher dehydroepiandrosterone sulfate levels, and lower testosterone-estradiol-binding globulin binding capacity than the other women. Patients with polycystic ovary syndrome had significantly higher mean serum triglyceride levels, very-low-density lipoprotein cholesterol levels, and lower high-density lipoprotein cholesterol levels. Differences in body weight do not explain the male pattern of lipoprotein lipid concentrations in women with polycystic ovary syndrome. The association of hyperandrogenism with lipoprotein lipid abnormalities should be evaluated in regard to the influence of endogenous sex steroids on differences between the sexes in incidence of cardiovascular disease.

Recent reports have suggested that the sensitivity to chemotherapy of endocrine-dependent breast cancer may be enhanced by transient exposure to hormonal stimulation. To test this concept, 39 postmenopausal women with proven metastatic breast carcinoma and measurable disease were entered into this prospective, double-blind trial; 35 are currently evaluable. All patients were continuously treated with aminoglutethimide and hydrocortisone to lower estrogen production, plus cyclic chemotherapy. Patients in the "stimulation" arm received in addition, Estrace 2 mg b.i.d. sublingually for 3 days before and on the day of chemotherapy. Estrace administration appeared to accelerate tumor growth as demonstrated by increased bone pain, hypercalcemia, and growth of skin lesions. Response rates, response duration, and survival were similar in the stimulation and control groups.

The study was designed to ascertain the relationship between visual loss in the central 30 degrees of vision and the density of the relative afferent pupillary defect (APD). The APD of 26 patients was quantified using a neutral log density filter. The mean threshold light sensitivity on Humphrey automated perimetry (Program 30-1) of one eye was substracted from the fellow eye total to yield the interocular visual field difference (VFD). A direct correlation was noted such that the log density of the APD increased linearly with an increase in VFD (r = 0.69, P = 0.0001). In the absence of ptosis or ocular media opacification, a VFD greater than 8.7 that is not associated with an APD is suggestive of functional visual loss. Four patients had an APD despite normal static automated perimetry, indicating that an APD may be one of the earliest signs of retinal ganglion cell or axonal dysfunction.

Twenty patients have undergone pelvic exenteration at the University Hospital of the Pennsylvania State University from 1979 to 1985. The majority of operations were performed for cancers of the cervix or vagina that recurred following radiotherapy. Operative mortality was 5.0%. Of those surviving the procedure, 16 patients (84%) were rehospitalized for complications that occurred more than 30 days after exenteration. The majority of these involved the gastrointestinal or urinary tracts. Fifty-eight percent of the complications requiring surgical intervention occurred more than 1 year after surgery while 74% of the complications managed conservatively occurred within 1 year of surgery. The 2-year survival for all patients was 70%; survival decreased to 58% at 5 years. The most important risk factor for reduced survival was the extension of tumor laterally into the surgical margins.

To determine the relationship of gonadotropin excretion to spermarche, 26 boys ranging in age from 10.3 to 17.5 years each provided ten overnight urine samples. Microscopic observation of sperm was found in 33 (13%) of the 260 samples, with 50% of the boys exhibiting sperm in at least one specimen. No further cumulative gain in detecting spermaturia occurred after the seventh urine collection. The median age of spermarche was computed by logistic regression analysis to be 14 years. Three urine collections from each boy were assessed for gonadotropin levels. At age 14 years mean follicule-stimulating hormone and luteinizing hormone excretion were, respectively, 857 and 503 mIU/h, into the reported adult daytime range. Spermarche is a midpubertal event associated with age-appropriate gonadotropin production.

Five hypogonadal men were treated with transdermal testosterone therapy, using a testosterone patch applied to the scrotal skin. Daily application of the patch, which contained 10 mg testosterone, produced an increase in serum testosterone concentrations from a pretreatment value of 45 +/- 12 (+/- SE; 1.5 +/- 0.4) to 436 +/- 80 ng/dL (15.1 +/- 2.8 nmol/L; P less than 0.001) after 4 weeks of treatment. Normal serum testosterone concentrations were achieved in all men after 6-8 weeks of therapy and were maintained during continued long term therapy for 9-12 months with a patch containing 15 mg testosterone. All men reported a subjective increase in libido and sexual function during therapy, and three men preferred it to testosterone injections. The serum testosterone and estradiol levels did not rise above the normal adult male range at any time during therapy. However, elevated serum dihydrotestosterone (DHT) concentrations occurred during treatment; the pretreatment DHT concentration was 95 +/- 3 ng/dL (3.3 +/- 0.1 nmol/L), and it increased to 228 +/- 40 ng/dL (7.8 +/- 1.4 nmol/L) after 4 weeks of treatment and remained elevated thereafter. The individual mean DHT to testosterone ratio increased from a pretreatment value of 0.2 (range, 0.1-0.3) to 0.6 (range, 0.4-0.7) after 2 weeks of therapy and remained high thereafter. Comparison of the serum DHT levels in patients during therapy with those in normal men who had similar testosterone concentrations [531 +/- 62 vs. 566 +/- 72 ng/dL (18.4 +/- 2.1 vs. 19.6 +/- 2.5 nmol/L); P greater than 0.05] revealed that the mean serum DHT concentration was significantly higher in the patients [315 +/- 69 vs. 87 +/- 6 ng/dL (10.8 +/- 2.4 vs. 2.9 +/- 0.2 nmol/L); P less than 0.001], as was the mean DHT to testosterone ratio [0.6 (range, 0.25- 1.1) vs. 0.16 (range, 0.09- 0.24); P less than 0.001]. The high serum DHT levels presumably were due to increased metabolism of testosterone to DHT by the 5 alpha-reductase in the scrotal skin. Serum 3 alpha-androstanediol glucuronide levels were not elevated in the patients. We conclude that transdermal testosterone therapy is an effective long term treatment for hypogonadism in men. It is, however, associated with high serum DHT levels, whose potential long term effects on the prostate and other tissues need to be investigated.

To determine which groups of patients are at highest risk for operative or late mortality, 259 consecutive patients who underwent operation between 1978 and 1984 were studied; 170 underwent aortic valve replacement and 89 underwent aortic valve replacement combined with coronary artery bypass grafting. Multivariate analysis of risk factors selected emergency operation and patient age older than 70 years as the strongest predictors for operative death. Although patients having aortic valve replacement and coronary artery bypass grafting had a higher operative mortality rate (13.5 versus 3.5%), the combined operation had no independent predictive effect on early or late results. At a mean follow-up time of 48 months after surgery, 72% of the survivors of operation were living, 10% were lost to follow-up and 18% were dead. Seventy-seven percent of long-term survivors were in New York Heart Association functional class I or II. The incidence of thromboembolism, paravalvular leak, bacterial endocarditis and hemorrhage each occurred at a rate of less than 1% per patient-year. The factors associated with late death were preoperative age, male sex, left ventricular end-diastolic pressure, cardiac index and functional class. Despite an increase in operative mortality, patients undergoing emergency operation were not at higher risk of late death. Operative mortality is concentrated among several high risk groups. For patients undergoing elective operation, operative mortality is low, especially if the patient is less than 70 years old. Late results are good for all groups of patients undergoing operation, including those who are at greater risk of dying at operation.

The authors examined physicians' reasons for ordering an exercise tolerance test and the influence of the test results on management decisions. Subjects of this study included 265 family physicians in Pennsylvania who completed a questionnaire on the management of a patient with typical chronic stable angina. Eighty-one percent of the respondents reported they would order a noninvasive stress test as a first step in the management of the patient. Of these physicians, 40% would refer the patient to a cardiologist only if the exercise tolerance test were strongly positive, 8% would refer only if it were negative, and 53% would not change their referral decisions on the basis of test results. No more than 57% of the physicians rated as very important any given reason for ordering a noninvasive diagnostic test. The results suggest that a test may be ordered routinely but without a consensus as to why it is ordered and without an effect on clinical management decisions.

Recent evidence indicates that the antiestrogen tamoxifen (TAM) may inhibit breast cancer cell proliferation, at least in part, through suppression of the polyamine (PA) pathway. To directly test this hypothesis, we evaluated the effect of TAM administration on ornithine decarboxylase (ODC) activity, the rate-limiting enzyme in PA synthesis, as well as cellular PA levels in the hormone-responsive MCF-7 breast cancer cell line in culture. In detailed time course studies, we observed that TAM significantly inhibited the rise in ODC activity observed in control cells following a medium change. Chronic treatment with escalating amounts of TAM caused a dose-related decrease in tumor pools of putrescine and spermidine, while spermine levels were unaffected. The TAM effects on ODC activity and PA pools were reversible with exogenous estradiol administration. However, addition of putrescine to TAM-treated cells did not result in a reversal of the antiproliferative effect of TAM, despite repletion of cellular PA pools. Administration of TAM to the hormone-independent MDA-MB-231 breast cancer cell line did not suppress ODC activity or cellular PA levels despite induction, at high concentrations, of an estradiol-irreversible inhibition of proliferation. We conclude that, in the hormone-responsive MCF-7 breast cancer cell line, TAM causes a significant suppression of the PA pathway, the relation of which, if any, to its antiproliferative action remains obscure. This effect seems to be mediated through the estrogen receptor and does not appear to be a nonspecific consequence of inhibition of cell proliferation.

We present a method to display the results of linear regression when the independent variables are highly correlated. In this method the sum of squares of regression (SSR) for pairs of variables are partitioned into orthogonal and shared components. A shared component is the reduction in the SSR of one of the variables when the other variable is added to the regression equation. This method shows how the SSR for one variable depends on the other variables present in the regression equation and explains apparent inconsistencies between forward and backward stepwise regression. To demonstrate the potential usefulness of this method we reanalyzed previously reported data on the relationship between coronary heart disease (CHD) and diet. The analysis suggested that carbohydrate and alcohol intake are negatively associated with CHD because they are associated with greater caloric intake. Protein and fat intake are also associated with greater caloric intake, but in addition they are associated with factors that increase the risk of CHD.

These experiments were designed to test whether autocrine/paracrine mechanisms are involved in the growth-promoting action of progesterone (Pg) in the N-nitrosomethylurea-induced rat mammary tumor cultured in vitro in soft agar clonogenic assay. In support of our hypothesis, we observed that conditioned media obtained from Pg-treated tumors (Pg-CM), consistently stimulated colony formation in our system to the same degree as Pg itself (approximately 140% of control). Treatment with heat, trypsin, and concanavalin A abolished the colony-stimulating effect of Pg-CM, thus suggesting the possible glycoprotein nature of the Pg-inducible growth factor(s). The growth-promoting action of Pg-CM was rather specific since CMs obtained from tumors exposed to a variety of other steroid hormones rarely stimulated colony formation and usually only to a modest degree. Administration of the polyamine biosynthetic inhibitor, alpha-difluoromethylornithine, abolished the colony-stimulating effect of Pg-CM. The inhibitory effect of alpha-difluoromethylornithine was reversed in a dose-dependent fashion by exogenous administration of spermidine, which entirely restored the growth-promoting action of Pg-CM. Addition of increasing amounts of spermidine, however, did not potentiate Pg-CM action under our experimental conditions. Our results indicate that autocrine/paracrine mechanisms may mediate, at least in part, the colony-stimulating effect of Pg in our system. The polyamine pathway plays an essential role in the expression of such control of tumor growth by Pg.

Beta-blockade therapy to improve survival in idiopathic dilated cardiomyopathy (IDC) has been both advocated and criticized. However, randomized studies have not been performed. Thus, 50 patients with IDC were randomized in pairs to standard therapy (C) alone or with beta blockade (BB). Beta-blockade therapy with metoprolol was titrated from 12.5 to 50 mg twice daily as tolerated (final average dose, 61 mg/day). Groups were comparable in age (C, 50 +/- 15 years; BB, 51 +/- 13 years), gender (C, 76% male; BB, 56% male), entry functional class (C, 2.8 +/- 0.8; BB, 2.7 +/- 0.7), and left ventricular ejection fraction (C, 27 +/- 12%; BB, 29 +/- 10%). Follow-up averaged 19 months (range 1 to 38). One subject in each group was lost to follow-up. There were 3 early BB dropouts (within 2 days) due to low-output syndrome (2 patients) or fatigue (1 patient). Eleven patients died. By intention to treat, 5 BB and 6 C patients died (difference not significant). By actual treatment, 3 BB patients died, including 2 late dropouts (at 0.2, 10 and 17 months), and 8 C patients died (at 2, 9, 9, 15, 18, 24, 29 and 32 months, p = 0.12). In additional, functional evaluation on follow-up (functional class, San Diego questionnaire and exercise time) all tended to favor those receiving BB. Low-dose BB is tolerated in 80% of IDC patients on a long-term basis. Those continuing to take BB have a good prognosis. Mortality in C patients, however, is less than in some retrospective studies.(ABSTRACT TRUNCATED AT 250 WORDS)

One hundred and one patients with oat (small) cell lung cancer have been treated with CAVE [Cytoxan, Adriamycin, Vincristine, and etoposide (VP-16)] chemotherapy +/- RA233 (a platelet-inhibiting agent). There was no difference in disease-free interval, pattern of relapse, or survival between groups.

This study tested the hypothesis that counseling of newly diagnosed cancer patients by former cancer patients will increase the use of coping strategies and reduce psychological stress beyond what can be accomplished by just counseling from professional staff. Thirty-two newly diagnosed patients in a gynecologic oncology service were subjects in this study. All subjects received supportive services from professionals assigned to the service. Control group patients received just the professional support program, while the experimental group patients received professional support plus additional counseling by former cancer patients that emphasized four coping strategies characteristic of patients who have adapted well to cancer. Results 6 and 12 weeks after entering the study showed no statistically significant differences in emotional status between experimental and control groups and only one significant difference in coping behaviors that was opposite to what was predicted. The findings do not support the hypothesis.

Differentiation is a term that indicates the degree to which a tumor resembles histologically the tissue or cell of origin. A system to quantitate the proportion of breast cancer cells participating in glandular differentiation or remaining within ducts was employed. The degree of tumor differentiation of 58 primary breast cancers was correlated with estrogen (ER) and progesterone receptors (PR) and tumor aromatase activity. There was a significant association between tumor differentiation (greater than or equal to 2% cancer cells exhibiting glandular differentiation) and the presence of ER or PR in tumors. Conversely, there was no correlation between tumor differentiation and measurable tumor aromatase activity.

Immunogold electron microscopy using LR Gold as a resin was undertaken to determine the distribution of actin and tubulin within the hyphae of Histoplasma capsulatum capsulatum and H. capsulatum duboisii. Both of these proteins were found throughout the cytoplasm when probed with the appropriate monoclonal antibodies.

Sixty-four patients were randomized prior to pelvic radiotherapy into one of three dietary groups: the control group maintained a regular diet except that they drank at least 480 cc of milk daily; the lactose-restricted group was placed on a lactose-restricted diet; and the lactase group drank at least 480 cc of milk with lactase enzyme added to hydrolyze 90% of the lactose. The patients kept records of their stool frequency and the number of diphenoxylate tablets required to control their diarrhea during a 5 week course of standard whole pelvis irradiation. The data does not support the concept that one of the mechanisms of radiation-induced diarrhea associated with pelvic irradiation is a reduction the ability of the intestine to hydrolyze ingested lactose due to the effect of the radiation on the small intestine. There was not a significant difference in stool frequency or diphenoxylate usage among the dietary groups.

Problem reporting rates of 180 persons with cancer (PWC) were compared with those of their closest in age same sex cancer-free siblings living outside their households for the same time periods. PWC had significantly higher reporting rates for physical, activities of daily living, nutrition, and emotional problems and a significantly lower rate for family problems. Sibling problem reporting rates, which indicate the likelihood that PWC would have experienced similar problems without a diagnosis of cancer, were highest for physical, emotional, employment, and family problems suggesting that noncancer factors are especially likely to play a role in those types of problems. Regression analyses showed that female and younger PWCs tended to report more problems than their siblings suggesting that they were more affected by cancer and its treatments than were other types of PWC.

Recent evidence indicates that hormone-responsive but not -resistant human breast cancer cells in culture are sensitive to the antiproliferative effect of the polyamine (PA) biosynthetic inhibitor alpha-difluoromethylornithine (DFMO). The present experiments were designed to investigate the potential differential involvement of the PA pathway in the growth of these different biological subtypes of human breast cancer. Thus, we evaluated the effect of DFMO on proliferation, ornithine decarboxylase (ODC) activity, and PA levels of the hormone-dependent MCF-7 and -independent MDA-MB-231 breast cancer cell lines. When tested at comparable cell density, the two cell lines had similar levels of ODC activity and PA. Administration of DFMO (0.01, 0.1, 1, 4 mM) for 6 days caused a similar dose-dependent inhibition of proliferation (up to approximately 15% of control) associated with suppression of ODC activity to undetectable levels at the highest dose. In both cell lines, putrescine and spermidine levels were maximally suppressed by doses of DFMO greater than 0.1 mM. Higher doses of DFMO (1 and 4 mM) also suppressed spermine levels to approximately 60% of control. In detailed time-course studies, DFMO administration (0.1 mM) similarly suppressed by 80% the rise in ODC observed in both cell lines following a medium change. At all time points, putrescine and spermidine levels were likewise suppressed to a similar extent. Addition of putrescine (0.1-2.5 mM) to DFMO-treated cells repleted cellular PA levels and restored growth to approximately 80% of control in both cell lines. We conclude that, under these experimental conditions, PA are similarly involved in the growth of the hormone-responsive MCF-7 and -resistant MDA-MB-231 human breast cancer cell lines.

Despite considerable evidence suggesting a critical role of polyamines in the hormonal control of breast cancer growth in vitro, their role in in vivo tumor growth is not established. In these experiments, we evaluated the individual and combined effects of the polyamine biosynthesis inhibitor alpha-difluoromethylornithine (DFMO) and ovariectomy on the growth and cellular levels of ornithine decarboxylase (ODC) and polyamines of N-nitrosomethylurea-induced rat mammary tumors. Despite a similar suppressive effect on ODC activity, the two treatments had a different effect on polyamine levels. As expected, DFMO selectively suppressed putrescine, whereas spermidine and spermine levels were minimally or not affected at all. Since quantitatively putrescine contributes the least to overall polyamine pools, the DFMO effect on this latter parameter was modest. In contrast, ovariectomy, by suppressing the more abundant spermidine and spermine, produced a more profound suppression of total polyamine pools. This finding is in agreement with the notion that hormones not only control ODC activity, but also other enzymes involved in the synthesis of the distal polyamines. Ovariectomy was also more potent than DFMO administration in inhibiting N-nitrosomethylurea-induced mammary tumor growth. No major additive/synergistic effects were observed between DFMO and ovariectomy on tumor growth and cellular levels of ODC activity and polyamines. DFMO administration lowered the tumor level of progesterone receptors and appeared to potentiate the suppressive effect of ovariectomy. In contrast, neither treatment, alone or in combination, altered tumor levels of estrogen receptors. DFMO administration did not affect circulating levels of estradiol and prolactin or uterine and ovarian weights, thus suggesting that its effects were not indirectly mediated through alterations of the endocrine milieu of the host.

Thirty-nine patients with a variety of advanced malignancies were treated with recombinant IFN-gamma 4A (AMGen, specific activity 1 to 5 x 10(7) U/mg protein). IFN-gamma 4A was administered at a dose of 10-2,000 micrograms/m2/d. Following a 2-week rest, a maintenance phase was continued with injections 3 d/wk. Immunologic monitoring studies were performed on patients' peripheral blood cells before administration of IFN-gamma 4A, then on Days 15 and 90. Flow cytometric analysis was used to determine the absolute number of CD 3+, CD 4+, CD 8+, CD 19+, and CD 16+ cells using a panel of monoclonal antibodies. Natural killer (NK) cell function was assayed by monitoring lysis of the K562 cell line in the Cr51 release assay. Changes from baseline were observed on Days 15 and 90 in all parameters studied, although the ratio of helper to suppressor cells seemed to remain within the normal range. Whereas there were no substantial changes in CD 3+ and CD 4+ cells on Day 15, IFN-gamma 4A had an enhancing effect on CD 8+, CD 19+, and CD 16+ cells. This trend continued at Day 90 only for CD 19+ and CD 16+ cells at the higher dose levels. An increase in functional NK cell activity at Day 15 was less noted on Day 90. Comparison of intravenous (IV) to intramuscular-subcutaneous (IM-SC) administration showed differences in the effect on lymphocyte subpopulations at 450 and 1,000 micrograms. The effect of IFN-gamma 4A on the equilibrium among lymphocyte subpopulations and the possibility of its role in combination therapy with other biologic response modifiers are discussed.

Hypofibrinogenemia and disseminated intravascular coagulation are common events in patients with metastatic prostate carcinoma. This study tests the hypothesis that prostate tumor growth and metastasis is associated with sustained activation of fibrinolysis secondary to increased release of plasminogen activator. We implanted an androgen-insensitive prostate tumor into an inbred strain of rats and serially measured plasminogen, plasminogen activator, plasmin and fibrinogen. Control groups included animals without tumor and a group implanted with transitional cell bladder carcinoma, a locally infiltrating tumor not usually associated with hemostatic complications. Our results showed a significant and steady rise in plasma plasminogen activator, plasmin and fibrinogen levels in animals implanted with prostate cancer. This, however, is not specific for prostate tumor. Similar, perhaps more profound changes were noted in animals implanted with the transitional cell carcinoma.