Polymorphonuclear leukocyte function in the preterm neonate: effect of chronologic age

In this study, effect of chronologic age on polymorphonuclear leukocyte (PMN) chemiluminescence and random and chemotactic motility was evaluated in 38 stable preterm neonates of less than 32 weeks' gestation during the first month of life. Chemiluminescence and random and chemotactic motility of PMNs from preterm neonates were first evaluated at mean postnatal age of 9.8 days and then weekly for an ensuing 21-day period. For comparison, one blood sample was obtained for PMN functions from 14 healthy term neonates younger than 72 hours of age and seven normal adults. On day 1 PMN chemiluminescence and random and chemotactic motility values in preterm neonates were significantly lower (P less than .001) compared with those in term neonates and PMN function values of term neonates were significantly lower (P less than .001) than those of adults. Although initial PMN chemiluminescence and random and chemotactic motility values in preterm neonates were depressed, subsequent values on days 7, 14, and 21 increased significantly (P less than .002). On day 21 (mean postnatal age of 30.8 days) no differences existed in chemiluminescent activity and random motility between preterm and term neonates; chemotactic motility in preterm neonates, however, remained impaired. Mean cumulative age (gestational age at birth plus postnatal age) of preterm neonates on day 21 of study was 32.5 weeks, suggesting that chronologic age has more effect on maturational changes in PMN functions than gestational age.     

Simultaneously presenting head and neck and lung cancer: a diagnostic and treatment dilemma.

OBJECTIVES/HYPOTHESIS: Synchronous tumors are defined as malignancies presenting within 6 months of the index tumors. A significant subset of patients present at initial evaluation with malignant tumors of both the head and neck (head and neck squamous cell carcinoma) and the lung, which are termed simultaneous primaries. The management and treatment outcomes in this cohort of patients have not been clearly defined and are the subject of the present review. STUDY DESIGN: Retrospective chart review of previously untreated patients. METHODS: From January 1974 to December 1997, a total of 2964 patients were treated for mucosal squamous cell carcinoma of the head and neck. Forty-two patients fulfilled the criteria for synchronous head and neck and lung malignancy. Of these, 27 patients had simultaneous tumors of the head and neck and the lung. This cohort of patients (n = 27) was stratified into three treatment groups. Patients in group A (n = 10) had resectable head and neck and lung primaries treated with curative intent. Group B (n = 8) was composed of patients who could have been treated with curative intent but declined and were given only palliative therapy. Patients in group C (n = 9) were candidates for only palliative treatment. RESULTS: The estimated 5-year disease-specific survival in group A was 47%, whereas patients in group B had a 5-year disease-specific survival of only 13% (P =.05). There were no survivors beyond 1 year in group C. The presence of mediastinal adenopathy in patients in group A portended poor clinical outcome. There was an estimated 5-year disease-specific survival of 51% in patients with no preoperative evidence of mediastinal adenopathy (n = 7), whereas 67% of patients with radiological evidence of mediastinal adenopathy died (two of three patients). CONCLUSION: The presence of simultaneous head and neck squamous cell carcinoma and pulmonary malignancies should not be a deterrent to aggressive surgical therapy because a potentially satisfactory outcome can be expected in these patients.     

In vivo MRI measurements of tumor growth induced by dichloroacetate: implications for mode of action

Dichloroacetate (DCA) is an important by-product of the chlorination of drinking water that produces liver cancer in rodents. Assessment of the risk that results from concentrations that occur in drinking water will be dependent upon the mode of action held responsible for these tumors. A study by Stauber and Bull [Stauber, A.J. and Bull, R. J (1997) Differences in phenotype and cell replicative behavior of hepatic tumors inducted by dichloroacetate (DCA) and trichloroacetate (TCA). Toxicol. Appl. Pharmacol. 144, 235-246] in mice treated with DCA demonstrated a lesion distribution that was skewed towards many small, altered foci of cells that are assumed to be precursor lesions [EPA, (1996). U.S. Environmental Protection Agency: Proposed Guidelines for carcinogen risk assessment; notice. Fed. Reg. 61, pp. 17960-10811]. The present study was designed to determine the extent to which the tumorigenic effects of DCA could be explained by its effect on tumor growth rates (i.e. tumor promoting activity). In vivo magnetic resonance imaging (MRI) allowed accurate determination of growth rates of individual lesions in mice that had been treated with DCA in drinking water at 2 g/l. Out of thirty treated mice, ten were found to have hepatic tumors detectable by MRI at 48 weeks of treatment. These tumor-bearing animals were assigned to two groups matched on the size of lesions observed by in vivo MR1. Treatment with DCA continued in one group of five mice and was stopped in the other. For both groups, tumor growth rates were determined by measuring changes in size of all lesions greater than 1 mm(3) in volume during a 14-day period. Removal of DCA treatment resulted in growth rates that could not be distinguished from zero across all lesion sizes represented in the sample. These data are in agreement with previous observations of DCAs effects on replication rates within tumors (Stauber and Bull, (1997)). Tumor growth rates observed in animals maintained on treatment decreased with lesion volume in a manner that is consistent with a stochastic Gompertz birth-death process proposed by Tan [Tan, W.Y. (1986) A stochastic Gompertz birth-death process. Stat. Prob. Lett. 4, 25-28]. Parameters of this model obtained by fitting measured growth rates were used to predict the lesion-size distribution expected after one year of DCA treatment. The shape of the predicted lesion-size distribution was similar to that observed by Stauber and Bull (Stauber and Bull, (1997)) in mice sacrificed after 40 weeks of DCA treatment. We conclude that the effects of DCA on the division and/or death rates of spontaneously initiated cells can account for the predominance of small lesions in DCA-treated animals.     

Post-initiation effects of chlorophyllin and indole-3-carbinol in rats given 1,2-dimethylhydrazine or 2-amino-3-methyl- imidazo

Chlorophyllin (CHL) is a water-soluble derivative of chlorophyll, the ubiquitous pigment in green and leafy vegetables, whereas indole-3-carbinol (I3C) is present in cruciferous vegetables such as cabbage, broccoli and cauliflower. In rats initiated with 1,2-dimethylhydrazine (DMH), CHL and I3C reportedly promoted or enhanced the incidence of colon tumors when they were administered after, or during and after the carcinogen exposure, respectively. The same compounds given post-initiation inhibited the formation of colonic aberrant crypts induced by heterocyclic amines, such as 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), but tumor suppression was not examined in the latter studies. In the present investigation, male F344 rats were treated with IQ or DMH during the first 5 weeks of a 1 year study; IQ was given in the diet (0.03%), whereas DMH was administered once a week by s.c. injection (20 mg/kg body wt). Beginning 1 week after the last dose of IQ or DMH until sacrifice, rats received 0.001, 0.01 or 0.1% (w/v) CHL in the drinking water or 0.001, 0.01 or 0.1% I3C in the diet. Compared with controls given carcinogen alone, 0.1% I3C treatment suppressed the multiplicity of IQ-induced colon tumors, and CHL inhibited in a dose-related manner the incidence of IQ-induced liver tumors. However, 0.001% CHL increased significantly the multiplicity of DMH-induced colon tumors while having no effect on the colon tumors induced by IQ. These results indicate that both the choice of carcinogen as well as the dose of the tumor modulator can be important determinants of the events that occur during post-initiation exposure to CHL or I3C. Based on the present findings and data in the literature, it is possible for CHL and I3C to act as tumor promoters or anticarcinogens, depending upon the test species, initiating agent and exposure protocol.     

The role of supraomohyoid neck dissection in patients with positive nodes

BACKGROUND: Supraomohyoid neck dissection (SOHND) is currently used as a staging procedure for patients with clinically negative nodes in the neck who are at increased risk (>20%) for metastatic disease. OBJECTIVE: To assess the potential role of SOHND in patients with clinically positive nodes at levels I, II, or III. We evaluated, in particular, whether selective neck dissection in patients with clinically positive nodes results in decreased regional control and/or diminished survival. PATIENTS AND METHODS: We retrospectively reviewed the charts of all patients who underwent SOHND from January 1, 1971, to December 31, 1997. The oral cavity and oropharynx represented the primary sites in the majority of the patients. Two-year follow-up information was available on all patients. RESULTS: During the study period, 69 patients underwent 84 SOHNDs. Of the 69 patients, there were 30 patients with clinically negative nodes and 39 patients with clinically positive nodes in the neck. The overall regional control rates were 88% vs 71% for pathologically negative vs positive nodes, respectively, with or without adjuvant radiation therapy. Adjuvant radiation therapy significantly improved regional control in patients with pathologically positive nodes but not in patients with NO disease (P = .005). Similar results were noted in patients with both clinically and pathologically positive nodes. CONCLUSIONS: Supraomohyoid neck dissection in patients with pathologically positive nodes in the neck is inadequate therapy for regional control without postoperative radiation therapy. However, in patients with pathologically positive nodes in the neck, SOHND with postoperative radiation therapy can achieve regional control comparable to that of comprehensive neck dissection and postoperative radiation therapy.     

Basophil releasability in the newborn: factors limiting immunoglobulin E-mediated histamine release

Cord basophil preparations from 53 term neonates were studied for various factors affecting immediate hypersensitivity reactions including: basophil IgE receptor density and histamine releasability following incubation with calcium ionophore A23187, zymosan-activated serum (C5a), and anti-IgE. Basophil histamine content (geometric mean, 0.4 pg/basophil, with content in 14/28 cord blood samples below 0.2 pg/cell) is considerably below that of atopic and nonatopic individuals (geometric mean, 2.3 pg/basophil). Histamine release is normal with both A23187 (range 33% to 88%) and C5a (range 11% to 58%). Normal release with anti-IgE was shown in five of nine cord blood samples (range 13% of 52%), but four of five cell preparations required IgE preincubation. Indirect evidence indicates that basophils from newborns contain less than 30,000 total IgE receptors/cell. IgE-mediated histamine release in basophils from newborns is minimized by suboptimal IgE binding. Optimal IgE binding is not favored in basophils from neonates because of low serum IgE and low IgE receptor density. Serum IgE and IgE receptors increase to a variable degree as the child grows older and may determine the clinical onset of allergic disease.     

Understanding Uncontrolled Hypertension: Is It the Patient or the Provider?

The relative contributions of adherence and treatment intensity to blood pressure (BP) control are not well understood. The authors studied patients with uncontrolled hypertension (N=410) from 3 primary care clinics in the Veterans Affairs (VA) medical system. A questionnaire was used to assess patient adherence to therapy, and VA system pharmacy fills were used to assess the intensity of the antihypertensive regimen. At baseline, an inadequate antihypertensive regimen was implicated as the most probable reason for uncontrolled BP in a majority of patients (72%), while nonadherence could only be implicated in 13%. In multivariate longitudinal analyses, patients who had an increase in their medical treatment during the study had lower final diastolic BP levels compared with the patients who did not (-3.70 mm Hg; P<.05). While patient adherence to therapy plays a role, vigorous clinical management by the clinician is a more important contributor to BP control.