Perioperative transfusion, postoperative infection, and recurrence of head and neck cancer.

BACKGROUND: Immunologic effects of perioperative transfusion and postoperative infection have been purported to influence cancer recurrence rates. METHODS: Records of all head and neck cancer patients having surgical extirpation of the primary tumor and/or regional nodes at our institution over a 5-year period were reviewed. Time to recurrence was the outcome measure. All variables were evaluated via univariate analysis using log rank tests, with Cox proportional hazards used for multivariate analyses. RESULTS: Univariate analysis identified the following as potential prognostic factors associated with recurrence: nodal stage, total lymphocyte count, overall stage, amount transfused, occurrence of a transfusion, and the American Society of Anesthesiologists status. Various backward stepwise multivariate regression models showed that neither transfusion nor postoperative infection independently influenced recurrence. However, transfusion of 3 or more units did surface as an independent contributor to recurrence, and in certain subgroups there was a trend toward improved survival for those who had a postoperative infection. CONCLUSIONS: In this series, neither perioperative transfusion nor postoperative infection independently influenced recurrence.

Does cigarette smoking paradoxically increase survival in idiopathic dilated cardiomyopathy?. The Washington, D.C., Dilated Cardiomyopathy Study.

Recent studies have suggested that patients with idiopathic dilated cardiomyopathy (IDCM) who smoke have an improved prognosis as compared with nonsmokers. We examined this paradoxical finding using data from a population-based study in Washington, D.C. (n = 127). Current smokers were more likely to have a left-ventricular ejection fraction (LVEF) of 25% or greater as compared with IDCM patients who were past smokers or lifelong nonsmokers (p < or = 0.02). The cumulative survival among current smokers at 12 and 24 months was 88.1 and 81.4%, respectively, as compared with 77.9 and 71.6% among past smokers and 74.0 and 64.3% among patients who had never smoked. In a univariate analysis using the proportional hazards model, lifelong nonsmokers and former smokers were about twice as likely to die as compared with smokers, although the association was not significant (p > 0.10). In multivariable analysis, older age, LVEF, and ventricular arrhythmias - but not cigarette smoking-were found to be statistically significant independent predictors of survival (p < or = 0.05).

Evaluation of alternate methods of rapid assessment of endemicity of Onchocerca volvulus in communities in southern Cameroon.

Potential diagnostic indicators of onchocerciasis (subcutaneous nodules, depigmentation or leopard skin, microfilaruria, diethylcarbamazine patch test positivity, excoriations, and pruritus) were evaluated in a rain forest region of southern Cameroon for usefulness in rapid assessment of onchocerciasis endemicity in communities. Thirty-two study villages were selected, representing high, intermediate, and low prevalence levels, and 846 adult male residents of these communities 20 or more years of age were examined according to a defined protocol. Skin snips (from each iliac crest) served as the reference standard. Skin snip positivity was 75.5%; the effect of age was minimal. Leopard skin and nodules showed the strongest correlation with both the skin snip prevalence and community microfilarial load, as reflected by the adult male study population. We selected > or = 20% nodules or > or = 20% leopard skin as the most appropriate local criteria for assigning a community to high priority for control, which corresponds to a > or = 90% skin snip prevalence in adult males. While this criteria should not be applied to regions with savannah onchocerciasis, we believe the methodology can and should be used to determine appropriate diagnostic indicators for rapid assessment of Onchocerca volvulus endemicity in regions with different dynamics of transmission and clinical expression of disease.

Respiratory illness, beta-agonists, and risk of idiopathic dilated cardiomyopathy. The Washington, DC, Dilated Cardiomyopathy Study.

An epidemiologic study was carried out to examine the possible role of beta-agonists and other respiratory medications in the development of idiopathic dilated cardiomyopathy. Associations with respiratory medications, bronchial asthma, emphysema, and chronic bronchitis were examined by comparing newly diagnosed cases (n = 129) ascertained from five Washington, DC, area hospitals for the period 1990-1992 with neighborhood controls (n = 258) identified by using a random digit dialing technique. The cases and controls were matched on sex and 5-year age intervals and were compared in the analysis using conditional logistic regression methods. A statistically significant association was observed between idiopathic dilated cardiomyopathy and history of emphysema or chronic bronchitis (adjusted odds ratio (OR) = 4.4, 95% confidence interval (CI) 1.6-12.4). The association with bronchial asthma was of borderline significance (adjusted OR = 1.9, 95% CI 0.9-4.2). Associations were also observed with use of oral beta-agonists (adjusted OR = 3.4, 95% CI 1.1-11.0) and beta-agonist inhalers or nebulization (adjusted OR = 3.2, 95% CI 1.4-7.1), as well as with use of oral corticosteroids, inhaled corticosteroids or cromolyn, and theophylline medications. A total of 20.0% (23 of 115) of the cases had a reported history of beta-agonist inhaler use compared with 6.7% (17 of 254) of the controls. The strength of these associations was diminished when the temporal relation between exposure to beta-agonist inhalers or oral preparations and clinical diagnosis of idiopathic dilated cardiomyopathy was taken into account, however, and the associations with duration of beta-agonist medication use were not statistically significant (p > 0.05). The results of this study suggest, but do not prove, that use of beta-agonists has an etiologic role in idiopathic dilated cardiomyopathy.

Acral lentiginous melanoma.

Between 1958 and 1990, 82 patients with acral lentiginous melanoma were treated by the Tulane Surgical Service with regional perfusion, excision of lesion, and lymph node dissection. The patient group comprised 27 white men, 29 white women, 18 black men, and 8 black women, with an average age of 61 years. More foot lesions than hand lesions were reported, and all the lack men had foot lesions. In stage I patients, overall 5-year survival rates were 65% at 5 years and 44% at 10 years, with differences by race and gender. The black men did poorest, with a 13% 10-year survival rate. Survival rates were worse with increasing disease stage when calculated using univariate analysis. The 5-year survival rate of all patients with stage III and stage IV disease was 26%. A multivariate analysis was performed in 78 of 82 patients in whom all variables of Clark's level, age, race, stage, and sex were known. A strong relationship was observed between decreasing survival time and increasing Clark's level, with stage of marginal significance. In a multivariate analysis of patients with stage I disease, an increasing level of invasion was found to be significant, with a trend for a relationship to thickness. A trend toward decreased survival time was observed in men and blacks.

Effect of administration of diethylcarbamazine with and without fluconazole on experimental fungal infections in mice.

Other researchers have found that diethylcarbamazine (DEC) is effective treatment for filariasis despite a lack of demonstrated in vitro antifilarial activity. The results of our previous investigations using feline and murine leukemia virus models encouraged us to investigate the use of DEC with other infections. In our current experiments, DEC treatment was associated with lower brain fungal burden in fluconazole-treated mice following intravenous injection of Aspergillus fumigatus or increasing numbers of Cryptococcus neoformans organisms, and lower brain and kidney levels of Candida albicans following intravenous injection of increasing numbers of C. albicans. Further investigation of combined DEC and fluconazole treatment of fungal infections is warranted.

Albendazole in the treatment of onchocerciasis: double-blind clinical trial in Venezuela.

A double-blind clinical trial was conducted in Monagas State, Venezuela to assess the tolerance and efficacy of albendazole in the therapy of Onchocerca volvulus infection. Forty-nine patients (26 treated and 23 controls) received a 10-day course of albendazole (400 mg/day) or a placebo. Consistent with the excellent tolerance observed, albendazole did not kill microfilariae. However, analysis of changes in microfilarial densities (mf/mg of skin) over one year showed that albendazole was active against O. volvulus, presumably by interfering with embryogenesis. The nature, degree, and duration of this effect remain to be determined.

Effect of administration of diethylcarbamazine on experimental bacterial and fungal infections in mice.

Other researchers have found that diethylcarbamazine (DEC) is effective treatment for filariasis despite a lack of demonstrated in vitro antifilarial activity. The results of our previous investigations using feline and murine leukemia virus models encouraged us to investigate the use of DEC with other infections. In the current experiments, DEC treatmentS was associated with (a) increased survival and decreased brain Streptococcus pneumoniae levels following S. pneumoniae challenge in previously immunized mice; (b) increased serum antibody levels to S. pneumoniae, Escherichia coli, and Haemophilus influenzae following inoculation of live bacteria; and (c) lower brain fungal levels following intravenous injection of Aspergillus fumigatus or increasing numbers of Cryptococcus neoformans organisms, and lower brain and kidney levels of Candida albicans following intravenous injection of increasing numbers of C. albicans.

Effect of administration of diethylcarbamazine on murine leukemia virus (Cas-Br-M) infected mice.

Previous studies indicate that decreased serum viral infectivity and viral antigen levels follow oral administration of diethylcarbamazine (DEC) in feline leukemia virus infected cats, even though DEC has not been shown to exhibit in vitro antiviral activity. In this investigation, DEC was given by oral administration or (single dose) IP injection to murine leukemia virus (Cas-Br-M) inoculated mice to permit evaluation of its effect on viral-induced central nervous system disease. The survival of Cas-Br-M inoculated mice receiving DEC in water was significantly prolonged relative to similarly inoculated mice receiving distilled water. Among the Cas-Br-M inoculated mice euthanatized after the study, higher body weights and trend toward less severe brain and splenic lesions were noted in those receiving DEC in drinking water. Given these results, the possible utility of DEC in treatment of retroviral and other infections warrants further study.

Distribution and excretion of capsular antigen after immunization with Haemophilus influenzae type b polysaccharide-Neisseria meningitidis outer membrane protein conjugate vaccine.

The occurrence of Haemophilus influenzae type b capsular polysaccharide antigenemia and antigenuria following immunization was studied in 48 healthy 2-month-old infants. Each received a conjugate vaccine consisting of H. influenzae type b capsular polysaccharide covalently linked to Neisseria meningitidis serotype b outer membrane protein at 2 and 4 months of age. Infants were alternated at enrollment for collection of blood and urine after either the first or second dose. Specimens were obtained "early" (2-3 days) after immunization and "late" (7 days) after immunization and assayed for antigen. Antigen was detected in the serum of 3 (6%) of 48 infants, uniformly in the "early" specimen obtained after the first dose of vaccine. Antigenuria occurred in 37 (80%) of 46 infants; for greater than or equal to 7 days in 12 (26%). Antigenuria was frequent after administration of the vaccine but antigenemia was not. These data should be considered in the evaluation of an infant with suspected H. influenzae type b invasive disease.

A method for the evaluation of dose-toxicity relationships in clinical trials.

This paper considers a proportional hazards model that describes the relationship between time-dependent cumulative dose of drug and development of toxicity. We estimate probabilities of developing toxicity in both the presence and the absence of competing risks and provide variances for the latter case. Mitoxantrone data collected in Southwest Oncology Group studies illustrate the methods.

Hematologic effects of short-term oral diethylcarbamazine treatment given to chronically feline leukemia virus-infected cats.

Diethylcarbamazine (N,N-diethyl-4-methyl-1-piperazine carboxamide [DEC]) is widely used, especially in tropical regions, to prevent and treat filariasis. The antifilarial effect of this drug has been attributed to immunomodulation. Evidence is accumulating to indicate that DEC may mitigate the course of feline leukemia virus infection (FeLV) in cats. Previous studies have suggested that continuous oral DEC treatment given shortly after evidence of FeLV infection prevents or delays lymphopenia and prolongs survival. The present study focuses on the hematologic effects of one month oral DEC treatment given to adult chronically FeLV-infected cats and uninfected cats as compared to untreated FeLV-infected cats. Such treatment frequently resulted in abruptly lowered peripheral lymphocyte counts in chronically FeLV-infected cats. Further studies are warranted to evaluate whether administration of DEC could eliminate circulating retroviral-infected cells.

Effect of continuous oral diethylcarbamazine treatment on lymphocyte counts of feline leukemia virus-infected cats.

In previous studies, administration of diethylcarbamazine (DEC) resulted in increased serum antibody titers to feline oncornavirus-associated cell membrane antigen (FOCMA) in cats infected with feline leukemia virus (FeLV). FeLV infection of cats frequently results in immunosuppression associated with lymphopenia. The present investigation demonstrated that chronic administration of DEC prevented or delayed severe lymphopenia in two FeLV-infected offspring of an FeLV-infected queen as compared to two untreated littermates.

Charity Hospital experience with long-term survival and prognostic factors in patients with breast cancer with localized or regional disease.

Long-term survival, the prognostic effects of race, age, tumor size, number of positive nodes, and presence of grave signs (fixation, peau d'orange/edema, dimpling/retraction, satellite nodules, and ulceration) in this distribution of estrogen receptors (ERs) and progesterone receptors (PRs) were studied in 2480 patients (1815 blacks, 665 whites) diagnosed with localized or regional breast cancer at Charity Hospital of Louisiana at New Orleans (CHNO) from 1948 to 1985 and followed up in the CHNO Tumor Registry. Breast cancer-specific survival rates were 57%, 45%, 41%, 39%, 38%, and 35% at 5, 10, 15, 20, 25, and 30 years, respectively. Size of tumor, clinical status of nodes, and degree of fixation were important prognostic clinical factors, and number of nodes was an important pathologic factor with no additional value of the "grave signs." Size and fixation were related. Independent of size, clinical and pathologic status and fixation were related. ER was related to age and PR was related to number of nodes. The excess mortality from breast cancer at later intervals from diagnoses was small compared with mortality from other causes. Some, but not all, clinical findings were important prognostic indicators. ER and PR were related to some variables with unclear meaning.

Prevalence of giardiasis in patients with cystic fibrosis.

A group of 107 patients with cystic fibrosis and a control group of 64 normal members of households of patients with cystic fibrosis were surveyed for Giardia lamblia cysts and trophozoites by counterimmunoelectrophoresis of fecal samples. The patient group had a significantly higher rate of infestation than the control group (28.0% vs 6.3%, P = 0.0006), and the disparity between the two groups increased with age (P = 0.005). Aside from cystic fibrosis, all risk factors examined were without influence, except for the presence of household members less than or equal to 5 years of age. We conclude that our patients with cystic fibrosis have a previously unrecognized increased prevalence of giardiasis compared with that in a control population.

Cardiotoxicity in patients treated with mitoxantrone: Southwest Oncology Group phase II studies.

A model describing the development of cardiotoxicity as a function of cumulative dose of a drug and other covariates is presented. Methods are given for testing and illustrating a cumulative dose effect. Also, equations for estimation of the probability of developing cardiotoxicity in the presence or absence of competing risks are given. The methods are illustrated for mitoxantrone by means of data obtained from Southwest Oncology Group studies.

Factors influencing the survival of patients with regional melanoma of the extremity treated by perfusion.

Patients with regional metastases of malignant melanoma (75 with Stage IIIA soft tissue metastases, 124 with Stage IIIB nodal metastases and 75 with Stage IIIAB soft tissue and nodal metastases) treated by regional perfusion between 1957 and 1982 were retrospectively studied to identify prognostic factors relating to survival. In patients with Stage IIIB disease, the melanoma specific cumulative survival rates at five years was 72 per cent for one, 33 per cent for two to three and 20 per cent for four or more positive lymph nodes. In patients with Stage IIIAB disease, those with one node had a better survival rate at five years than those with multiple nodes (45 versus 25 per cent). In patients with Stage IIIA melanoma, two groups were identified based upon the results of prior treatment--those with and without prophylactic lymph node dissection (PLND) at the time of primary therapy. The factors associated with decreased survival rates in patients with PLND were: 1, increasing age; 2, presence of subcutaneous or both subcutaneous and dermal metastases, and 3, treatment at normothermic temperatures or earlier date of treatment. No significant factors were found in the group without PLND; however, the survival time was similar to that for patients with Stage IIIAB and one positive node (45 per cent at five years). Knowledge of these factors is important in assessing the prognosis and establishing randomization criteria for prospective studies evaluating various forms of therapy.

Long term effect of gynecologic age on somatic growth of children.

A sample of New Orleans black primiparous women under 25 years of age, participants in the national collaborative perinatal study, and their singleton children were studied to determine the relationship of maternal gestational age (GeA), gynecologic age (GyA) and size for GeA (S/GeA) on the child's growth over seven years observation. Early childbearers (less than 4 years GyA) had a somewhat higher proportion of preterm births than the late group (greater than or equal to 4 yrs GyA). A repeated measures analysis of variance after correction for maternal prepregnant weight and weight gain, demonstrated the early group remained smaller throughout the seven years in weight, length and head circumference. Preterm infants showed catch up by one year in height and weight in both Early and Late Groups, though the Early Preterm infants failed to catch up with the other groups in head circumference. In this lower socio economic group, the legacy of early childbearing appears to be smaller child body dimensions which are likely permanent.