Dietary patterns in infancy are associated with child diet and weight outcomes at 6 years.

OBJECTIVE: To assess whether patterns of dietary exposures at 9 months are associated with child diet and weight at 6 years. METHODS: Data for this study were from the Infant Feeding Practices Study II and Year 6 Follow-Up Studies. All data were self-reported monthly. Results of a previous latent class analysis revealed five dietary patterns varying in milk and solid food intake. These five infant dietary patterns were used in the current study to predict child diet and weight outcomes at 6 years, while controlling for confounding variables. RESULTS: Infants with dietary patterns higher in fruit and vegetable intake at 9 months had higher fruit and vegetable intake at 6 years. Similarly, infants with the dietary pattern characterized by foods high in energy density (that is, French Fries and sweet desserts) continued to have higher consumption of these foods at 6 years, and had a higher prevalence of overweight at 6 years (43%) compared with the other classes. Formula-fed infants had higher sugar-sweetened beverage intake and fewer met the dietary guidelines for fruit and vegetable intake at 6 years than breastfed infants, controlling for factors such as income. CONCLUSIONS: Early decisions about milk-feeding, and the types of solid foods offered in infancy can foreshadow dietary patterns and obesity risk later in childhood. Infants who were offered energy-dense foods had higher intake of these foods at 6 years of age.

Accumulation of catalytically active proteases in lacrimal gland acinar cell endosomes during chronic ex vivo muscarinic receptor stimulation.

Chronic muscarinic stimulation induces functional quiescence (Scand J Immunol 2003;58:550-65) and alters the traffic of immature cathepsin B (Exp Eye Res 2004;79:665-75) in lacrimal acinar cells. To test whether active proteases aberrantly accumulate in the endosomes, cell samples were cultured 20 h with and without 10-microm carbachol (CCh), incubated with [125I]-bovine serum albumin and then lysed and analysed by subcellular fractionation. CCh decreased total cysteine protease and cathepsin S activities in the isolated lysosome, redistributing them to early endocytic and biosynthetic compartments. CCh decreased [125I] accumulation in all compartments of cells loaded in the absence of protease inhibitors; the cysteine protease inhibitor, leupeptin, prevented the endosomal decrease but not the lysosomal decrease. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis and autoradiography demonstrated [125I]-labelled proteolytic products in endomembrane compartments of both control and CCh-stimulated cells, even in the presence of leupeptin, but analysis indicated that CCh increased the amount in endosomes. Two-dimensional fractionation analyses suggest that the CCh-induced redistributions result from blocks in traffic to the late endosome from both the early endosome and the trans-Golgi network. Therefore, we conjecture that chronic muscarinic acetylcholine receptor stimulation leads to aberrant proteolytic processing of autoantigens in endosomes, from whence previously cryptic epitopes may be secreted to the underlying interstitial space.

Biochemical changes contributing to functional quiescence in lacrimal gland acinar cells after chronic ex vivo exposure to a muscarinic agonist.

Profound secretory dysfunction can be associated with relatively modest lymphocytic infiltration of the lacrimal and salivary glands of Sjögren's syndrome (SjS) patients. SjS patients' sera contain autoantibodies to M3 muscarinic acetylcholine receptors (MAChR) that have variously been reported to have agonistic and antagonistic effects. We sought to identify consequences of chronic agonist stimulation by maintaining acinar cells from rabbit lacrimal glands for 20 h in the presence or absence of 10 microM carbachol (CCh). Exposure to CCh diminished the cells' ability to elevate cytosolic Ca2+ and secrete beta-hexosaminidase in response to acute stimulation with 100 microM CCh, but it enhanced their secretory responses to phenylephrine and ionomycin. Secretory vesicles appeared normal by electron microscopy, but confocal fluorescence microscopy revealed depletion of the secretory vesicle membrane marker, rab3D, and decreased ability to recruit secretory transport vesicles in response to acute 100 microM CCh. Additionally, the apical cortical actin cytoskeleton was disrupted and diminished compared to the basal-lateral cortical network. Subcellular fractionation analyses revealed that total membrane phase protein content was increased. The contents of beta-hexosaminidase and MAChR relative to total protein were not significantly altered, and MAChR abundance in the plasma membrane fraction was increased as the result of redistribution from endomembrane pools. However, relative cellular contents of the heterotrimeric guanosine triphosphate (GTP)-binding proteins, Gq and G11, were decreased. Additional biochemical changes included decreased contents of 47 kDa Gs and Gi3, protein kinase Calpha and rab3D and polymeric immunoglobulin (Ig) receptors; internalization of Na,K-ATPase from the plasma membranes to endomembrane compartments and decreased content of beta-hexosaminidase in the lysosomes. The observations demonstrate that chronic exposure to a MAChR agonist induces refractoriness to optimal stimulation, without causing receptor downregulation, by downregulating postreceptor-signalling mediators and effectors. The cells' secretory mechanisms for IgA and electrolytes also appear to be impaired, as does their ability to properly sort proteins to the lysosomes.

The final report of the expert panel for the radiation oncology bone metastasis work group of the American College of Radiology.

BACKGROUND: In the United States, at least half of the patients who are irradiated are done so with palliative intent. The most common presentation is the patient with bone metastasis. However, because current scientific outcome and technology techniques are insufficient for the creation of guidelines, the American College of Radiology created a work group of experts to formulate appropriateness criteria for the irradiation of bone metastasis. METHOD: A MEDLINE search to help review the community practices was initiated. Twenty-five clinical vignettes were reviewed by a panel of experts. Recommendations for each vignette were prioritized and selected based on choices proposed by panel members. RESULT: Doses in the range of 20 Gy in 5 fractions, 30 Gy in 10 fractions, or 35 Gy in 14 fractions are acceptable in most circumstances. Daily doses > 4.0 Gy were not commonly suggested. CIRCUMSTANCES: To determine optimal dose fractionation schemes, more emphasis needs to be put on the life expectancy of the patients. Rapid schedules are acceptable in patients with short life expectancy (i.e., < 3 months), but this hypothesis needs to be tested. Further research to better define the clinical indications of hemibody irradiation and strontium-89 is recommended.

Manpower needs for radiation oncology: a preliminary report of the ASTRO Human Resources Committee. American Society for Therapeutic Radiology and Oncology.

In summary, the ASTRO Committee on Human Resources believes that there is ample evidence for the existence of an oversupply of radiation oncologists in the United States at the present time. It believes that this oversupply has already affected the specialty in a variety of ways that are difficult to measure, for example, increased competition, conflicts between radiation oncology groups, conflicts between the private sector and academics, and increased costs, and that it is beginning to have a significant effect on the job market. This oversupply came about because of the rapid expansion in medical school enrollment in the 1970s. This led to an increased number of graduates available for enrollment into specialty residencies, one of which was radiation oncology. The actual number of radiation oncology residency positions offered has not changed significantly since 1972. However, only about half of the residency positions were filled in the early years. Since 1986, virtually all radiation oncology training positions in the United States have been filled, and this has led to a significantly greater number of radiation oncologists entering the field than have left the field through death or retirement. Preliminary data suggest that a shift to a managed care system would result in decreased demand for radiation oncology services, and that would increase the manpower problem for our specialty.

Posttreatment follow-up of radiation oncology patients in a managed care environment.

PURPOSE: Health care delivery in the United States is in the midst of a structural revolution called managed care. Demands for cost control within the managed care environment force radiation oncologists to defend the need and obligation to follow their patients. METHODS AND MATERIALS: We have analyzed this follow-up requirement from six potential justifications: patient care, medical-legal, quality assurance, outcome measurement, cost, and improvement of care. RESULTS: Practical recommendations for discussing the need for follow-up with the medical directors and primary care physicians of managed care entities are given. Follow-up without valid documentation of benefit is hard to justify in this era of managed care. CONCLUSIONS: Collaborative follow-up between the referring physician, the treating radiation oncologist, and the other oncologic specialists will allow for outcome measurement and improvement in practice without driving up cost or exposing the patient to undue risk.

Effect of rotary electric toothbrush versus manual toothbrush on decalcification during orthodontic treatment.

The purpose of this study was to determine whether daily use of a rotary electric toothbrush (Rota-dent, Prodentec Corp., Batesville, Ark.) and a 0.05% sodium fluoride (NaF) rinse would significantly reduce decalcification when compared with manual toothbrushing only (control group) or manual toothbrushing and daily use of a NaF rinse (rinse group). All three groups used a standard fluoride toothpaste. Ninety consecutive adolescent patients who were to receive orthodontic treatment were placed into one of three groups according to age and sex criteria. Decalcification was evaluated single blind by two calibrated examiners on the facial surfaces of all permanent teeth before appliances were placed (baseline) and 3 months after appliances were removed (posttreatment). Data were analyzed by analysis of covariance with the dependent variable derived by subtracting the baseline decalcification scores from the posttreatment scores and using the baseline scores as the covariate. The results showed that although there were no significant differences between the three groups at baseline, the Rota-dent group showed significantly (p < 0.05) less posttreatment decalcification than either the control or rinse groups. In a separate analysis of first molars, the Rota-dent group again showed the least decalcification and the control group showed the most. These data suggest that twice daily use of the Rota-dent electric toothbrush with a standard fluoride toothpaste and once daily use of a 0.05% NaF rinse is more effective for preventing decalcification in adolescents during orthodontic treatment with fixed appliances than either conventional toothbrushing with a fluoride toothpaste, or similar toothbrushing and toothpaste with a once daily NaF rinse.

Effect of Fluosol-DA on the response of intracranial 9L tumors to X rays and BCNU.

Treatment with a perfluorochemical emulsion combined with breathing a 95% or 100% oxygen atmosphere has been shown to be an effective adjuvant to radiation therapy in several animal tumor systems. Similarly, the addition of treatment with a perfluorochemical emulsion combined with breathing a high oxygen atmosphere has been shown to improve the response of several animal tumor systems to treatment with BCNU. We now report results of the use of the perfluorochemical emulsion, Fluosol-DA, and carbogen breathing with single dose radiation treatment, BCNU and combined drug and radiation treatment in intracranially implanted 9L gliosarcoma. The median enhancement in life span produced by Fluosol-DA and carbogen breathing in addition to radiation was 2 days at 10 Gy and 6 days at 20 Gy compared to radiation treatment alone. In the group receiving 20 Gy with Fluosol-DA and carbogen breathing, 2 of 20 lived 120 days. Treatment with a single intraperitoneal injection of BCNU (10 mg/kg) on day 7 post tumor cell implantation produced an increase in life span of 2 days compared to untreated control animals. The combination of drug treatment with Fluosol-DA and carbogen breathing produced an increase in life span of 26 days, which was significantly different from BCNU treatment with air breathing (p less than 0.001). Finally, when BCNU and Fluosol-DA and carbogen were combined with radiation treatment (20 Gy), an increase in life span of nearly 85 days compared to untreated controls was produced, with 47% (9 or 19) surviving 120 days. These results suggest that this combination might be effective in the treatment of malignant brain tumors.

Effect of various oxygenation conditions and fluosol-DA on cancer chemotherapeutic agents.

Adding Fluosol-DA and carbogen breathing to treatment with various anticancer drugs can result in a significant enhancement of tumor growth delay compared to the drug and air breathing. The optimal conditions for tumor response depend upon the drug, oxygenation level and duration, and perfluorochemical emulsion dosage. In this study, representative chemotherapeutic agents from several classes were tested in a tumor growth delay assay in combination with various doses of Fluosol-DA under conditions of normal aeration, carbogen breathing either for 1-2 hours or 6 hours, or with hyperbaric 100% oxygen (3 atmospheres) breathing for 1 hour to determine whether the antitumor activity of these drugs would be improved.

Synovial fluid and plasma kinetics of repeat dose sustained action tiaprofenic acid in patients with rheumatoid arthritis.

Tiaprofenic acid is a potent non-steroidal anti-inflammatory drug which, in conventional tablet form, has been shown to be rapidly absorbed and eliminated from the plasma, while synovial fluid concentrations remain constant for at least 8 hours. Recently, a sustained action formulation of tiaprofenic acid has been developed to provide the patient with the convenience of a once daily dosage. The purpose of this study was to measure plasma and synovial fluid concentrations over a 24-hour period following repeated administration of the sustained action formulation, and thus determine the pharmacokinetic profile. Eight patients suffering from rheumatoid arthritis were included in this open study (of whom 3 were subsequently excluded from the analysis). All were hospital outpatients requiring aspiration of the knee joint. The patients received sustained action tiaprofenic acid in a dosage of 600 mg once daily for a period of 7 days. Plasma and synovial fluid samples were taken on the final treatment day at 0, 4, 8, 12, and 18 hours following administration of the last treatment dose. Areas under the concentration-time curves, maximum plasma and synovial fluid concentrations, times to maximum concentration, and apparent elimination half-lives are presented and the findings compared and discussed. The drug was found to be retained in both the plasma and synovial fluid over a 24-hour period. Synovial fluid concentrations exceeded plasma concentrations at 24 hours in 4 of the 5 patients who were analysed, while in the fifth patient the levels were very similar.