Cancer early-detection services in community health centers for the underserved. A randomized controlled trial

BACKGROUND: Achieving cancer early-detection goals remains a challenge, especially among low-income and minority populations. DESIGN/SETTING: A randomized trial based in 62 community health centers for the underserved in New York, New Jersey, and western Connecticut. Family physicians were on staff at most of the centers. INTERVENTION: Workshops, materials, and ongoing advice for center leaders promoted implementation of a preventive services office system to identify patients in need of services at each visit through use of medical record flow sheets, other tools, and staff involvement. EVALUATION END POINTS: The proportion of randomly selected patients by center who were up to date for indicated services at baseline (n = 2645) and follow-up (n = 2864) record review. RESULTS: Only 1 service (breast self-examination advice) increased more in intervention centers. Seven of 8 target services increased significantly for the 62 centers overall. During the study, the medical director changed in 26 centers (42%). Keeping the same medical director at intervention centers was associated with improvements in services. CONCLUSIONS: Cancer early-detection services are improving in community health centers, but the intervention had only a small impact, as determined by record review. To have an impact, the intervention required that there be no change in medical director. The relationship of changes in the practice environment to services delivered is complex and deserves more study.     

Skeletal muscle buffering capacity and endurance performance after high-intensity interval training by well-trained cyclists

Chronic nicotine administration in animal models evokes a dose-dependent increase in brain nicotinic receptor numbers. Genetically determined variability in nicotinic receptor number in different mouse strains has also been reported, which is thought to affect sensitivity to nicotine, as well as the development of tolerance. Humans self-administer nicotine principally in the form of cigarettes and other tobacco products. The present study compared [3H]nicotine binding in human postmortem brain from thalamus and hippocampus of nonsmoking subjects, subjects who had variable life-long smoking histories and subjects who had quit smoking. A significant increase was seen in [3H]nicotine binding in both hippocampus and thalamus of subjects with life-long smoking histories. In the hippocampus, this change resulted from a change in total receptor number (Bmax), with no change in receptor affinity (Kd). There was also a positive correlation between the degree of smoking, as measured by the average reported packs smoked per day, and the number of nicotine binding sites found in both the hippocampus and thalamus, showing that humans exhibit a dose-dependent increase in brain nicotinic receptor binding. Receptor levels in these brain regions after smoking cessation were at or below those found in the control population, which indicated that smoking-induced changes are reversible after cessation of nicotine treatment. These results suggest that increases in nicotinic receptor levels in the human brain may underlie nicotine tolerance and addiction in smokers.     

Preparation and imaging of nuclear spreads from cells of the zebrafish embryo. Evidence for large degradation intermediates in apoptosis

We describe a method for preparing nuclear spreads from cells of live, unfixed zebrafish embryos at the late-gastrula (approximately 8000 cell) stage of development. The method consists of a sequence of four steps: (1) a slow, gentle lysis, in low to moderate salt concentration, of cells and then nuclei, to release DNA-containing fibres; (2) spreading of the released fibres by a transverse fluid flow; (3) electrostatic, and possibly also covalent, attachment of the spread fibers to poly(L-lysine)-coated glass microscope slides; and (4) continued incubation to produce periodic cleavage of the DNA within the fibres, apparently through activation of endogenous nucleases. The nuclear spreads are imaged with epifluorescence, at a spatial resolution approaching the Rayleigh limit (approximately 230 nm for blue light). The epifluorescent signal is provided from Hoechst 33,258 bound specifically to the DNA, from a dye-coupled antibody conjugate bound specifically to histone H1 in the fibres, or from a DNA nick end-labelling assay. The spontaneous cleavage of DNA-containing fibres in step (4) of the above procedure can be blocked by the chelating agents EGTA and EDTA, by the caspase-2,3,7 inhibitor N-acetyl-Asp-Glu-Val-Asp-aldehyde, and by the caspase-1,4,5 inhibitors N-acetyl-Tyr-Val-Ala-Asp-aldehyde and N-acetyl-Tyr-Val-Ala-Asp-chloromethyl ketone. These data suggest that the spontaneous cleavage of fibres is catalysed by nucleases that become activated through a caspase-mediated mechanism. The involvement of caspase-dependent nucleases would suggest that an apoptosis pathway is activated in the spreads during their prolonged incubation. If bona fide apoptosis is induced in living zebrafish embryos by treatment with camptothecin (a topoisomerase I poison), and then nuclear spreads are prepared, we observe a similar fragmentation of the spread fibres. However, in this case the fragmentation is more rapid and complete. We hypothesize that, during the early phase of apoptosis, one or more endogenous nucleases are activated by a caspase-mediated mechanism. The nuclease(s) then specifically recognize and cleave a susceptible, periodically repeating feature of interphase chromatin.     

Aiding troubled employees: the prevalence, cost, and characteristics of employee assistance programs in the United States

Bilirubin neurotoxicity can be mediated by numerous mechanisms due to its increased permeability in neuronal membranes. The present study tests the hypothesis that a prolonged bilirubin infusion modifies the N-methyl-D-aspartate (NMDA) receptor/ ion channel complex in the cerebral cortex of newborn piglets. Studies were performed in seven control and six bilirubin-exposed piglets, 2-4 d of age. Piglets in the bilirubin group received a 35 mg/kg bolus of bilirubin followed by a 4-h infusion (25 mg/kg/h) of a buffer solution containing 0.1 N NaOH, 5% human albumin, and 0.055 Na2HPO4 with 3 mg/mL bilirubin. The final mean bilirubin concentration in the bilirubin group was 495.9 +/- 85.5 mumol/L (29.0 +/- 5.0 mg/dL). The control group received a bilirubin-free buffer solution. Sulfisoxazole was administered to animals in both groups. P2 membrane fractions were prepared from the cerebral cortex. [3H]MK-801 binding assays were performed to study NMDA receptor modification. The Bmax in the control and bilirubin groups were 1.20 +/- 0.10 (mean +/- SD) and 1.32 +/- 0.14 pmol/mg protein, respectively. The value for Kd in the control brains was 6.97 +/- 0.80 nM compared with 4.80 +/- 0.28 nM in the bilirubin-exposed brains (p < 0.001). [3H]Glutamate binding studies did not show a significant difference in the Bmax and Kd for the NMDA-specific glutamate site in the two groups. The results show that in vivo exposure to bilirubin increases the affinity of the receptor (decreased Kd) for [3H]MK-801, indicating that bilirubin modifies the function of the NMDA receptor/ion channel complex in the brain of the newborn piglet. We speculate that the affinity of bilirubin for neuronal membranes leads to bilirubin-mediated neurotoxicity, resulting in either short- or long-term disruption of neuronal function.     

Thyroid gland and thyroid status in patients with chronic liver diseases

We have conducted a prospective study aimed to analyse contraceptive use among women seeking for legal abortion in the State University Hospital "Ma?chin dom"--Sofia. Our date demonstrate that the patients were well informed about the existing contraceptive methods. On the contrary the percentage of women-using contraception and especially those, using highly effective ones is relatively low. The patients claim the possible side effects of the high effective contraception as a reason against use.     

Radiotherapy and chemotherapy for invasive thymomas: a multicentric retrospective review of 90 cases. The FNCLCC trialists. Fédération Nationale des Centres de Lutte Contre le Cancer

PURPOSE: Thymoma is a rare disease. The treatment of patients with invasive thymoma remains controversial. The prognosis of such patients is poor, even with the use of postoperative radiation therapy and chemotherapy. We retrospectively reviewed the outcome and prognostic factors in a series of 90 patients presenting with an invasive thymoma treated by partial resection or biopsy and radiation therapy. METHODS AND MATERIALS: From 1979-1990, 163 patients with the diagnosis of lymphoepithelial thymoma were treated in 10 French cancer centers. Patients were staged using the postoperative "GETT" classification derived from that of Masaoka. Ninety patients who presented with an invasive thymoma, 58 Stage III (21 IIIA: partial resection and 37 IIIB: biopsy) and 32 Stage IVA (intrathoracic thymoma spread), are the subject of this report. Treatment combined surgery and radiation therapy (+/- chemotherapy), with curative intent. Surgery consisted of partial resection in 31 patients (21 Stage III), and biopsy in 55 patients (37 Stage III). The median radiation dose to the tumor was 50 Gy (30-70 Gy). Supraclavicular radiation was performed in 59 patients (median dose 40 Gy). Chemotherapy, combined with radiation in 59 patients, consisted of multidrug regimens, mainly platinum based. RESULTS: The median follow-up is 105 months (20-165 months). The 5- and 10-year overall survival rates are 51 and 39%, respectively. There is a great impact of the extent of surgery on survival: the 5- and 10-year survival rates were 64% and 43%, respectively, after partial resection, compared to 39% and 31% after biopsy (p < 0.02). Local control at 8.5 years was obtained in 59 of 90 patients (66%): 40 Stage III, 19 Stage IVA. There is a significant relationship between the extent of surgery and the local control (16% of relapse after partial resection vs. 45% after biopsy, p < 0.05). Seven patients developed significant (grades 3-4 WHO grading system) treatment-induced side effects. Stage, histologic type, and chemotherapy were not prognostic factors. CONCLUSION: In this large multicentric retrospective study of invasive thymomas (Stage III-IVA) treated by surgery and radiation, results show the importance of loco-regional treatments, such as surgery and radiation therapy. There is also a great impact of radiation on local control. However, the rate of local recurrence (34%) justifies recommending a higher dose of radiation (> 50 Gy) than doses used in this study, for incompletely resected patients. The role of chemotherapy needs to be further assessed.     

Rhinotillexomania: psychiatric disorder or habit?

BACKGROUND: Conditions once considered bad habits are now recognized as psychiatric disorders (trichotillomania, onychopagia). We hypothesized that nose picking is another such "habit," a common benign practice in most adults but a time-consuming, socially compromising, or physically harmful condition (rhinotillexomania) in some. METHODS: We developed the Rhinotillexomania Questionnaire, mailed it to 1000 randomly selected adult residents of Dane County, Wisconsin, and requested anonymous responses. The returned questionnaires were analyzed according to age, sex, marital status, living arrangement, and educational level. Nose picking was characterized according to time involved, level of distress, location, attitudes toward self and others regarding the practice, technique, methods of disposal, reasons, complications, and associated habits and psychiatric disorders. RESULTS: Two hundred fifty-four subjects responded. Ninety-one percent were current nose pickers although only 75% felt "almost everyone does it"; 1.2% picked at least every hour. For 2 subjects (0.8%), nose picking caused moderate to marked interferences with daily functioning. Two subjects spent between 15 and 30 minutes and 1 over 2 hours a day picking their nose. For 2 others, perforation of the nasal septum was a complication. Associated "habits" included picking cuticles (25%), picking at skin (20%), biting fingernails (18%), and pulling out hair (6%). CONCLUSION: This first population survey of nose picking suggests that it is an almost universal practice in adults but one that should not be considered pathologic for most. For some, however, the condition may meet criteria for a disorder-rhinotillexomania.     

Detection of Toxoplasma gondii tachyzoites and bradyzoites in blood, urine, and brains of infected mice

Previously, a strong stimulatory response of peripheral blood mononuclear cells (PBMC) to a fermented mistletoe extract (Iscador Pini, i.p.) could be observed in normal and allergic individuals. Aim of this study was therefore to analyse the cell subtypes involved in this in vitro reactivity. PBMC from 11 non-mistletoe treated healthy and allergic individuals were therefore investigated. Flow cytometric analyses revealed that this mistletoe extract stimulated T-cells (CD3+), especially T-helper cells (CD4+), as well as monocytes at concentrations of 100 or 1,000 micrograms/ml. Furthermore, an increased proportion of T- and T-helper cells expressing the interleukin-2 (IL-2) receptor (CD25) and monocytes expressing HLA-DR molecules, respectively, could be demonstrated. There was no evidence for a major involvement of B- (CD19+), natural killer- (NK-; CD56+) and T-suppressor cells/cytotoxic T-lymphocytes (CD8+). To get more insights whether the T-cell proliferation induced by i.p. was the consequence of a primary or a secondary type of immune response, kinetic studies (n = 5) were performed hereby comparing the reactivity of the non-recall antigen keyhole limpet hemocyanin (KLH) as well as the recall antigen purified protein derivative (PPD) derived from Mycobacterium tuberculosis with that of i.p. I.p. at a concentration of 100 micrograms/ml always exhibited the kinetics of a primary immune reaction. These findings were further substantiated by additional flow cytometric studies analysing changes in the proportions of naive (CD45RA+) and memory/effector cells (CD45RO+) during the exposure to i.p. It could be shown that the proportion of naive cells decreased and that of the transition stage increased, which could indicate that there was a change towards memory/effector cells. In conclusion, these data demonstrate that i.p.-related antigens act like "non-recall"-antigens, and the in vitro immune response involves T-cells as well as monocytes.