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Increased survival in cystic fibrosis (CF) is associated with bone thinning and fat-free mass (FFM) loss. We hypothesized that the severity of lung disease would be associated with increased protein catabolism and systemic inflammatory status in clinically stable patients. Forty adults with CF and 22 age-matched healthy subjects were studied. Body composition was determined by dual-energy X-ray absorptiometry. Urinary pseudouridine (PSU), a marker of protein breakdown, and cross-linked N-telopeptides of type I collagen (NTx), a marker of bone connective tissue breakdown, serum tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and their soluble receptors were measured. A 3-d food intake diary revealed 21 patients had a low energy intake. Excretion of PSU (p = 0.019) and NTx (p < 0.01) was increased in patients and was inversely related to FEV(1); PSU (r = - 0.53, p = 0.001) and NTx (r = - 0.43, p < 0.01). Increased excretion of PSU and NTx (p < 0.05 for both) was also related to a low FFM. All inflammatory mediators were greater in patients and were related to PSU and NTx. Clinically stable adults were catabolic with both cellular and connective tissue protein breakdown, which was related to lung disease severity, systemic inflammation, and body composition.

Recent research suggests that oestrogen may play an important role in cognition. Epidemiological and experimental studies of hormone replacement therapy in post-menopausal women suggest that oestrogen may be important to verbal memory in particular, as well as other cognitive functions such as attention and processing speed. Some studies have also suggested that HRT may have a beneficial effect for Alzheimer's disease, both in the prevention or delay of onset and that it is also of therapeutic benefit to patients in whom the disease is established. The use of selective oestrogen receptor modulators (SERMs) and other hormonal therapies for the treatment of breast cancer is common, yet few studies have examined the possible cognitive effects of this form of treatment. Several studies have shown cognitive decline in women receiving treatment for breast cancer, but the focus has been on the effects of chemotherapy. Further confusion has resulted from the diverse methodologies used in the existing literature. A pilot study to develop a suitable cognitive battery of tests for the evaluation of cognitive function in women receiving hormonal therapy for the treatment or prevention of breast cancer is introduced.

Weight loss in chronic obstructive airways disease (COPD) is associated with an increased energy cost of breathing. To determine an association between body composition and the inflammatory response we studied 80 clinically stable patients. Body composition was determined anthropometrically and skeletal muscle mass was determined as the creatinine-height index (CHI). Forty patients had their nitrogen balance determined. Circulating concentrations of interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-alpha), and their soluble receptors were determined for 68 patients. Body mass index (BMI) was normal (> 20 kg/m(2)) in 55 patients, of whom 17 (31%) had a low CHI (< 80% predicted). A reduced CHI was associated with increased circulating levels of IL-6 (p = 0.001), TNF-alpha (p = 0.032) and their soluble receptors IL-6sr (p = 0.002), TNF-alpha sr1 (p = 0.03), and TNF-alpha sr2 (p = 0.001). Patients with a normal BMI and low CHI had inflammatory mediator levels similar to patients with a low BMI and CHI; both were significantly greater than in those with a normal BMI and CHI. Nitrogen balance was similar between normal and low CHI groups, although nitrogen excretion was significantly increased in the low CHI group. Skeletal muscle loss in COPD is probably multifactorial in origin, but our data suggest a link with systemic inflammation, even when weight loss is inapparent.

Aim: To conduct a commissioned survey of multidisciplinary breast team members' expectations of their own and each other's roles in providing different kinds of information to women with breast cancer., Design: Questionnaire based survey., Setting and Participants: Health professionals from five multidisciplinary breast care centres within a Sussex health authority., Main Outcome Measures: Interdisciplinary awareness of informational roles played by different team members., Results and Conclusions: The results of the team survey suggest that, in most cases, health professionals fulfilled the roles expected of them by the team, with two or three individuals identified as the main providers of information for each topic. However, many more professionals were involved in major discussions without the team's knowledge. The professional consistently playing a major "unseen" role was the breast nurse specialist.

We report results from an intervention study to improve communication during consultations about randomised clinical trials of cancer therapy. Patients, eligible for a trial, completed questionnaires about information preferences and attitudes to trials prior to seeing their doctors, who were either shown these questionnaires (intervention) or not (control). Fifteen doctors participated and invited 265 patients to join one of 40 different randomised clinical trials. Most patients (77.4%) agreed to trial entry and this was predicted by the Patient's Attitudes to Trials questionnaire with an 80.4% accuracy. Accrual, length of consultation, doctor and patient satisfaction were not associated with the intervention. Further research to explore the potential use of written interventions to facilitate communication and accrual to randomised clinical trials is recommended.

Low body weight and loss of bone mass are major problems in adults with cystic fibrosis (CF) and chronic pulmonary infection. Although these complications probably have a multifactorial origin, we hypothesized that the continuous acute-phase inflammatory and catabolic state may contribute. We determined body composition, bone turnover, physical activity, and circulating interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and their soluble receptors in 22 adults with CF and 22 age- and sex-matched healthy subjects. Comparisons were also made within patients before and after treatment of an exacerbation of respiratory symptoms. The patients had a lower mean (95% confidence interval [CI]) fat-free mass (FFM) 39.9 (36.3, 43.6) kg than healthy subjects, 49.4 (45.1, 53.7) kg, p < 0.05. The patients were in negative nitrogen balance and 20 had bone mineral density (BMD) Z scores

As part of a larger study designed to improve doctor-patient communication in randomised clinical trials (RCT), we audiotaped the discussions between doctor and patient in which consent was being obtained for a RCT. This paper reports on 82 discussions conducted by 5 clinical oncologists in both District General and University Hospital outpatient departments. When introducing the subject of trials, uncertainty about treatment decisions was expressed by the doctors in the majority of cases (79, 96.3%). This was most often stated in a general sense (78, 95.1%), but some mentioned personal uncertainty (12, 14.6%), an approach which helps to maintain a trusting doctor-patient relationship. The word randomization was mentioned in 51 (62.2%) consultations, although the process itself was usually described implicitly (78, 95.1%), e.g. by telling the patient that they would be allocated either one or other treatment. Analogies were used in 28 (34.1%) cases to describe the randomisation process. In addition, although treatments and side-effects were described frequently, (68, 82.9%) and (72, 87.8%) respectively, information leaflets about the trials were not given to 23 (28%) patients. The study shows that U.K. clinicians adopt individual methods when providing information and eliciting consent to trials.

This paper describes an experiment which examined how levels of processing (LOP) affected word fragment completion in a group of Wernicke-Korsakoff patients, a group of patients with closed head injury, and matched controls. The data showed that both the memory-impaired groups and the controls showed a LOP effect but that the effect was larger in controls. Data from other studies are reviewed and, in conjunction with the present findings, it is concluded that LOP effects obtained when memory-impaired individuals are tested using implicit memory tasks arise mainly from the contribution of lexical processing of targets and from contamination by explicit recollection.

Detection of hemophilia carriers is an important issue and should be addressed with great care. The allelic frequencies of three intragenic probes (Bcl I for probe p114.12, Xba I for probe p482.6, and Bgl I for probe C) and one linked probe (Bgl II for probe DX 13) are reported, together with their diagnostic yield singly and in combination. In this series, 725 individuals (405 females) in 156 families were analyzed for restriction fragment-length polymorphisms. A total of 255 females (63%) were found to be informative for their carrier state with one or more probes. The most informative intragenic probe was p482.6 (useful in 49% of informative females). The most informative probe was DX 13 (useful in 59% of informative females), but this is a linked probe that carries a 5% risk of cross-over. By the use of probes p114.12, p482.6, and DX 13, almost 98% of all the informative females could be detected. In about 71% of families with a family history and a known carrier, prenatal diagnosis was feasible.

Diflubenzuron (DFB) and Clanfenur (CFN) belong to a group of compounds called Benzoylphenyl Ureas (BPUs). Several BPUs regulate cell growth in insects and/or inhibit growth of B-16 murine melanomas. In view of potential clinical use for these compounds, DFB and CFN were selected as examples of BPUs and tested for effects on hematopoiesis in C57Bl/6 mice housed in a conventional environment. DFB and CFN exhibit anti-tumor activity in mice, cause little or no morbidity and mortality and rather than causing bone marrow suppression, which is usual for anti-cancer drugs, these agents stimulate hematopoiesis in vivo and in vitro. Stimulation in vivo was evidenced by increased (up to 112%) peripheral blood granulocytes 6 days after a single injection and enhanced granulopoiesis (approximately 25%) in bone marrow up to 18 days after treatment. That effects of DFB and CFN were on hematopoietic stem cells were indicated by 47% and 48%, respectively, increases in numbers of CFUs and 97% and 95%, respectively, increases in CFUgm. Further, bone marrow cells treated in vitro contained about twice the number of CFUs and CFUgm as control bone marrow cells. Almost all of the increase in number of spleen colonies, whether derived from donors treated in vivo or bone marrow cells treated in vitro, was accounted for by a corresponding increase in number of undifferentiated colonies. These data indicate that DFB and CFN treatment enhance numbers of pluripotential stem cells both in vivo and in vitro. The mechanism of enhancement, direct or indirect, remains to be determined.

Permanent cell lines and clones established from an untreated patient (AGS cells) with gastric carcinoma, and from a similar patient who had been treated with Adriamycin, 5FU and cytoxan (SII cells) were used in a study that compared their drug and radiation survival sensitivities to their glutathidine (GSH) values. The SII parental cell line was more resistant than the AGS cells in vitro to chlorambucil, ACT D, Adria, Bleo, and X-rays. This greater resistance was positively correlated with GSH values that were 1.77 times higher than in the AGS parental cell line. By contrast the SII parental cells were more sensitive than the AGS cells to MeCCNU and Melphalan. The drug and radiation sensitivities expressed among the clones of the two cell lines were heterogeneous and did not correlate with their GSH values.

The mean number of lymphocytes, response to phytohemagglutinin (PHA), and response to concanavalin A (Con A) in whole-blood cultures for 106 patients with head and neck cancer were 83%, 73%, and 64%, respectively, of values for healthy control individuals. During radiotherapy, lymphocyte counts declined to 44% and PHA and Con A responses declined to about one third of control values. Lymphocyte counts slowly increased after treatment to 77% of control values after two years, but responses to mitogens remained at about 40%. Responses to PHA and Con A for 38 patients who lived beyond 18 months were significantly greater before and after treatment than responses for 39 patients who died within 18 months. In general, a poor pretreatment response to PHA and Con A correlated with a poor clinical course, whereas responses near the control level indicated a good clinical course.

Several schedules of benzene exposure were evaluated for their effects on peripheral white blood cell counts, bone marrow cellularity and transplantable colony forming units (CFU-S) in male C57 Bl/6 mice. Intermittent exposure to 4000 ppm benzene in air produced leukopenia without altering the bone marrow cellularity. This same treatment, however, decreased the number of CFU-S to 30% of control values. Uninterrupted exposure to lower levels of benzene decreased peripheral cell counts within 24 h, and later decreased marrow cellularity. Exposure of a non-dividing population of stem cells (CFU-S) to benzene for up to 24 h produced no detectable effect on the subsequent development of spleen colonies, suggesting that the effect of benzene on CFU-S occurs only after peripheral cells are depleted. These findings indicate that benzene has affects on both differentiated cells and undifferentiated stem cells. An effect on the pluripotential stem cell is an important aspect of benzene toxicity, but not its exclusive or initial site of action.

Bone marrow cell responses to therapeutic doses of cis-diamminedichloroplatinum (II) (Cis-Pt) were evaluated in female C57B1/6 mice by determining bone marrow cellularity and content of transplantable colony forming units (CFUS) after treatment. Although limitation on the dosage of Cis-Pt is generally considered to be determined by renal toxicity, methods to increase the effective use of the drug such as hydration and diuresis, alteration of time-dose schedules and combination of Cis-Pt with other drugs and radiation, warrant studies on effects of the drug on other normal tissues such as bone marrow. Cis-Pt given on a time-dose schedule that is therapeutic for mice and, in general, is equivalent to regimens recommended for clinical use, was found to be myelosuppressive. The myelosuppression was dose related in that a total dose of 16 mg/kg (2 doses at weekly interval) reduced the number of CFUS/femur to 16% of the control value, 24 mg/kg (4 doses at weekly intervals) reduced the CFUS fraction to 10-14% of the value for controls and 32 mg/kg (4 doses at weekly intervals) reduced the fraction of CFUs to 6-7% of the control value. A quantitative extrapolation of these effects to man cannot be made, however, the data indicate that myelosuppression could become a significant factor as increased doses of Cis-Pt are used clinically.

Ffty-three patients with head and neck cancer tested before radiation treatment to determine numbers of blood lymphocytes and immunologic responses to mitogens of lymphocytes in whole-blood cultures had mean values that were 19% to 26% less than values for healthy individuals. Thirty patients whose disease was in stages III or IV had values similar to those in 23 patients whose disease was in stages I or II. Values for 45 patients tested at end of radiotherapy decreased to about 50% of pretreatment values; however, patients with advanced lesions experienced greater decreases (to 24% to 50%) than patients with localized lesions (to 71% to 84%). Patients with advanced lesions usually received radiation to larger areas than patients with localized lesions; therefore, the extent of decline in laboratory values was most likely dependent on volume of tissue treated.

In today's arena of competition, cost-containment, quality assurance, and high technology, the dietitian is challenged to develop and implement strategies that will assure an increase in productivity. Within a government system, such strategies must address the political climate as well as administrative and management issues. Prior to modifying any system or part of a system, it is critical to develop evaluation criteria. Each of the eight strategies discussed in this article is effective in promoting an increase in productivity.

We have shown in earlier studies that repeated weekly exposures of a human astrocytoma clone (AST 3-4) to MeCCNU (10 micrograms/ml for 1 h per week) produced a linear decrease in survival over the first 3 weekly treatments. But, after that time these cells became progressively more resistant to the 10 micrograms/ml concentration of the agent. In the studies reported here we show that these previously treated cells were also less responsive to other doses ranging from 1 to 30 micrograms MeCCNU/ml. This change in sensitivity to MeCCNU was accompanied by collateral changes in response to other agents: resistance to BCNU and Galactitol, increased sensitivity to Adriamycin, and no change to ionizing radiation. These experiments suggest that once repeated treatments with a single agent cause a tumor cell population to become more resistant, sensitivity to other agents may also change unpredictably.

The insect growth regulator diflubenzuron (DFB), which may also inhibit growth of imaginal epidermal cells in insects, was studied for antitumor activity in two mouse tumor models of epidermal origin. DFB inhibits chitin deposition, but the mechanisms by which DFB controls chitin deposition or regulates growth of insect epidermal cells are unknown. A single injection of 20 mg (800 mg/kg) of DFB into C57BL/6 mice with B16 malignant melanomas or AKR mice with skin tumors (CA 1025) induced a rapid (24 h) decrease in tumor volume in 78% and 66% of the tumors, respectively. In contrast, 85% of the melanomas and 91% of skin tumors in control mice increased in volume during the same 24-h period. Tumor volume decreased by as much as 55% for about 1% of the tumors, but the median decrease was 20% for both types of tumors. Since control tumors concommitantly increased, DFB-treated tumors decreased, relatively, to 60% of the volume of matched control tumors. After the initial volume decrease, both types of tumors resumed exponential growth resulting in an average growth curve delay, calculated for 12-14 days, of about 2.0 days. Subsequent treatment of melanomas with DFB 24 h after the initial treatment resulted in a further decrease in relative tumor volume to 40-50% of control tumor volume and a growth curve delay of 2.6 days. The most effective regimen used was 5 daily, 20-mg doses of DFB. Melanomas decreased to 40% of control tumor volume after the third injection and the mean growth curve delay was extended to 4.3 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Investigations of the effect of high dose folic acid treatment of fragile X syndrome in males has produced mixed results. However, no study had examined the possible drug effects of folic acid on non-fragile X control males. Therefore, we examined the effect of folic acid on fragile X males using non-fragile X control males. Subjects were assigned randomly to an ABA or BAB design. Duration of either folic acid or placebo condition was 4 months. Folic acid or placebo was given in a double-blind fashion. At the end of each condition, the subjects' behavior was assessed. At the end of the study, parents were asked to complete a questionnaire. Using parents' responses, we examined 22 items on the Autistic Descriptors Checklist and two subscales from the Vineland Adaptive Behavior Scale which corresponded to areas of behavior parents' noted to have shown improvement. We did not find significant differences between fragile X males and control males, within subjects, nor across folic acid and placebo conditions. Thus, our follow-up study confirms and extends our original findings, as well as those of other researchers: namely, that no dramatic changes in behavior result from high dose folic acid. Moreover, subtle improvements observed in earlier investigations were not confirmed.

In two studies, attitudes reported toward testing by behaviorally disordered students and their regular classroom counterparts were compared. In Study 1, 12 behaviorally disordered and 25 average fifth and sixth graders were given a survey regarding their attitude toward tests and the test-taking experience. Students classified behaviorally disordered reported less positive attitudes toward tests than their more average peers; these attitude differences were more pronounced on items which reflected subjective attitudes toward the test-taking situation and aspirations about performance and less pronounced on evaluation of the value of tests. In Study 2, which employed a sample of 25 behaviorally disordered and 25 regular classroom students matched on age and sex and used a longer attitude measure, differences were not found. Taken together, these studies suggest that attitudes toward tests are inconsistent in the two populations and that some behaviorally disordered students may not differ so much in this regard as supposed.

Investigations of lymphatic dysfunction in animals infected with filarial parasites has been hampered by a paucity of techniques to measure efficiency of lymphatic drainage. In this study a 99mTc-sulfur colloid technique was used to assess the efficiency of lymphatic drainage in Patas monkeys infected with filarial nematodes. In all 15 uninfected hind limbs there was rapid and consistent appearance of labeled colloid in the primary lymph node (popliteal) and subsequently in the secondary nodes (abdomino-pelvic) in 11 of 15 limbs. In contrast, in all eight limbs tested 1-9 months after infection there was reduced rate of migration of the colloid and initial appearance in the abdomino-pelvic region: subsequent accumulation was seen in the popliteal region in only four of the limbs. This data indicated that lymphatic vessels were blocked and that collateral vessels channeled the colloid to the secondary lymph nodes. The lymph flow patterns demonstrated by the isotope technique were supported at autopsy.

Four treatment regimens for patients with specified combinations of low back pain and sciatica were evaluated. The largest group studied had low back pain with limited straight-leg raising (SLR) and in them the beneficial effect of manipulation in hastening pain relief was highly significant. In similar patients without limitation of SLR, the effect was of borderline significance. In all the other groups, treated patients also recovered more quickly than their controls. Traction, for patients with low back pain and sciatica, and epidural injections when a root palsy was present also produced some significant pain relief. The effect of sclerosants for back pain was less clear.

We conducted an experimental trial of high-dose folic acid given to five males, ages 8 to 26 years, with the fra(X) syndrome. In this double blind study, each subject received 250 mg per day of folic acid for 3 months, followed by placebo for 3 months, and folic acid again for an additional three months. Based on IQ tests, behavior ratings, the Autistic Descriptors Checklist, and parental ratings, there was little evidence to suggest any positive effects seen during the administration of high-dose folic acid. Therefore, this study has provided little support for a hypothesis of benefit of high-dose folic acid in the treatment of the fra(X) syndrome.

The insect growth regulator diflubenzuron (DFB), which also inhibits growth of experimental tumors in mice, was studied to determine the influence of in vivo microsomal metabolism on its antitumor activity. DFB inhibits chitin synthesis and growth of imaginal epidermis in insects and suppresses melanogenesis and uptake of nucleosides in mouse melanoma cells, but the means of cell growth regulation and the role of metabolism of DFB in such regulation have not been established. Five daily injections of DFB (total of 4000 mg/kg) into C57BL/6 mice with B16 melanomas induced an acute 11-20% decrease in tumor volume and a 2-3 day increase in the initial tumor volume doubling time (Td), but at mid-treatment tumors regained maximum (control-like) rate of volume increase. Tumors in mice conditioned with a mixed function oxidase inhibitor (CoCl2) and treated with DFB did not decrease in mean volume, but their rate of volume increase was reduced by about 75% and the Td was increased by 4.2 days. In contrast, induction of mixed function oxidase with 3-methylcholanthrene (3-MC) or beta-napthaflavone (B-NF) enhanced the effects of DFB by a factor of 1.5 to 2.0. Therefore, aromatic hydroxylation of DFB may be required for tumor growth regulation. Three metabolites of DFB--two hydroxylated forms and a scission product, 4-chlorophenylurea (CPU), were also tested for tumor growth regulation. CPU was ineffective; a form oxidized at the 3 carbon of the phenyl ring (3-OH-DFB) was only marginally effective; but the 2-carbon form (2-OH-DFB) induced a 24% decrease in mean tumor volume and a 2.4 day increase in Td. Pretreatment with 3-MC and treatment with 2-OH-DFB also resulted in a 24% decrease in tumor volume and a 2.2 day increase in Td, but also reduced tumor volume increase to 20% between the 5th and 10th days after the initial 2-OH-DFB injection, compared to a 125% increase without 3-MC. Further, 3-MC pretreatment caused the otherwise marginally effective 3-OH-DFB to become almost as effective as 2-OH-DFB. These data support our previous report that DFB alters tumor growth and show that mixed function oxidase enhances effects of DFB, 2-OH-DFB and 3-OH-DFB.

An in vitro model has been devised so that mixtures of human tumor cells can be grown together for studies related to drug-induced or -selected changes in sensitivity. In the studies reported here, two human astrocytoma clones, one sensitive and one resistant to 1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea (MeCCNU), were carefully matched for doubling times, cell cycle phase distributions, and colony-forming efficiencies. The clones were mixed and grown together, and after only three weekly treatments with MeCCNU (10 micrograms/ml for 1 h each week) the sensitive cells in the mixture were killed, leaving behind a population that was almost 100% resistant to further exposures to MeCCNU. The loss of the sensitive cells from the mixture each week was easily detected by visual observation of flow microfluorometry histograms since the clones had different DNA indices. Repeated weekly exposures of the unmixed resistant clone (AST 1-1) to MeCCNU caused very little accumulated cell kill. Similar exposures of the unmixed sensitive clone (AST 3-4) produced a linear decrease in survival over the first three weekly treatments with 10 micrograms MeCCNU/ml, but after that time these cells became progressively more resistant to MeCCNU. It is unlikely that the change to resistance in the AST 3-4 clone occurred because of contamination with the resistant AST 1-1 cells, because their DNA index remained stable. These data show that repeated treatments with a single agent can cause a tumor cell population to become more resistant. It remains to be tested whether this resistance was the result of cellular interactions, drug-induced changes in sensitivity, or selection for resistant cells already present in the populations. This mixture model may be useful in studies on how cellular interactions influence growth and drug sensitivity in tumor and normal cell populations.

This article focuses on the development of compatibility or goodness-of-fit within adoptive families and on the possible contribution of such problems to emotional disturbance of adolescents. Subjects included 50 adopted adolescents in residential treatment (mean age = 14.96) and their families, and 50 nonadopted adolescents in treatment (mean age = 14.90) and their families. The child, both parents, and the child's caseworker were interviewed. Three distinctive interactional patterns presenting adaptational challenges are discussed: the family's adaptation to the child's hyperactivity, the family's adaptation to the child's avoidance of contact and cuddling from early infancy, and perceived incompatibility between the child's personality and the parents' style. Results are discussed in terms of behavioral and attributional contributions of both the child and parents to the development of compatibility. Implications for clinicians are discussed.