Over-the-counter topical antipruritic agents are commonly recommended by office-based physicians: an analysis of US practice patterns.

BACKGROUND: Pruritus is one of the most common complaints among patients who visit physicians. Over-the-counter topical antipruritic medications are widely recommended by physicians and are self-administered by patients for the treatment of pruritus. However, there are few scientific controlled studies evaluating the effect of these drugs on pruritus. OBJECTIVES: To assess the role of physician-recommended over-the-counter medications for the treatment of pruritus. METHODS: Records were analyzed for office-based physician visits in which over-the-counter antipruritic topical medications were recommended in the National Ambulatory Medical Care Survey between the years 1995 and 2000. RESULTS: The largest proportion of over-the-counter antipruritic agent recommendations were during visits to dermatologists, accounting for 41% of all such recommendations. Other physicians that recommended such agents included family physicians and pediatricians, accounting respectively for 26% and 21% of the recommendations. The most commonly recommended over-the-counter medications included hydrocortisone preparations (72%) and diphenhydramine (15%). Over-the-counter medications were more frequently recommended in the pediatric age group. CONCLUSION: This study demonstrates that over-the-counter medications are frequently recommended for the treatment of pruritus.

Provider characteristics and behaviors as predictors of immunization coverage.

BACKGROUND: Most studies of immunization behaviors measure adherence to standard immunization practices, relying on surveys without linking reported behaviors to objectively measured immunization rates. This study attempts to close that gap. METHODS: In 1997, pediatric, family, and general providers in Pennsylvania serving children aged < 36 months (N = 251) completed immunization behavior surveys. We linked these responses to patient chart audits for practice-level immunization rates. RESULTS: Immunization rates for our sample fell short of national goals (average up-to-date immunization status at 12 months = 69%). They were significantly higher for pediatricians than for family/general practitioners (78% vs 58%, p < 0.001) and for practices treating > or = 100 children in the past 30 working days than for those treating < 100 children (77% vs 62%, p < 0.001). Behaviors with significant associations to higher immunization coverage were: (1) appropriately giving diphtheria, tetanus toxoids, and pertussis immunization under false contraindications versus withholding it (73% vs 66%, p < 0.05); (2) willingness to give at least four injections at one visit versus fewer injections (74% vs 65%, p < 0.01); and (3) holding immunization in-service training versus no training (71% vs 65%, p < 0.05). However, multivariate analysis showed that only provider specialty remained a significant predictor of coverage. CONCLUSIONS: Pediatricians have higher coverage rates than family/general practitioners. Although pediatricians see more children, the number of immunization-delayed children at 12 months is approximately the same for both provider groups. Therefore, efforts to improve coverage should continue to be directed toward both groups.

Predicting the 'where' and resolving the 'what' of a moving target: a dichotomy of abilities.

Anticipation timing (AT) and dynamic visual acuity (DVA) were assessed in a group of college students (n = 60) under a range of velocity and duration conditions. Subjects participated in two identical sessions 1 week apart. Consistently with previous work, DVA performance worsened as velocity increased and as target duration decreased; and there was a significant improvement from the first to the second session. In contrast, AT performance improved as velocity increased, whereas no improvement from the first to the second session was indicated; but increasing duration again benefited performance. Correlational analyses comparing DVA and AT did not reveal any systematic relationship between the two visual tasks. A follow-up study with different instructions on the AT task revealed the same pattern of AT performance, suggesting the generalizability of the obtained stimulus relationships for the AT task. The importance of the often-overlooked role of stimulus variables on the AT task is discussed.

Comparison of copper-67- and iodine-125-labeled anti-CEA monoclonal antibody biodistribution in patients with colorectal tumors.

UNLABELLED: Copper-67 has comparable beta-particle emissions to that of 131I, but it displays more favorable gamma emission characteristics for application in radioimmunotherapy (RIT). This study investigates the potential of 67Cu-labeled monoclonal antibody (MAb) 35 for RIT of colorectal carcinoma. METHODS: Biokinetics of simultaneously injected 67Cu- and 125I-labeled MAb35 were studied in six patients scheduled for surgery of primary colorectal cancer. RESULTS: Whole-body clearance (T 1/2) of 67Cu, estimated from sequential anterior and posterior whole-body scans and corrected for decay of 67Cu, was 41 hr. Serum clearance of 67Cu was faster (27.41 hr) than that of 125I (38.33 hr). Mean tumor uptake of the 67Cu-labeled compound (0.0133% ID/g) exceeded that of 125I (0.0095% ID/g), and tumor-to-blood ratios were higher for 67Cu than for 125I, with averages of 6.07 and 2.41, respectively. The average 67Cu/125I ratio was 1.9 for tumor uptake, 0.7 for blood and 2.6 for tumor-to-blood ratios. Nonspecific liver uptake of 67Cu as calculated from whole-body scans was high in four patients, up to 25% of residual whole-body activity at 48 hr, but did not increase with time. We also observed some nonspecific bowel activity, as well as moderate to high uptake in benign polyps. CONCLUSION: Copper-67-labeled MAb35 is more favorable than its radioiodine-labeled counterpart for RIT of colorectal carcinoma due to higher tumor-to-blood ratios, but the problem of nonspecific liver and bowel uptake must first be overcome. The absolute accumulation of activity in tumor remains low, however, so the probability of cure with this compound alone is questionable. The use of 67Cu as one component of a multimodality adjuvant treatment seems to remain the most appropriate application for RIT.

Timing effects of combined radioimmunotherapy and radiotherapy on a human solid tumor in nude mice.

Timing effects of radioimmunotherapy (RIT) combined with external-beam radiotherapy (RT) were assessed in human colon carcinoma xenografts. Initially, dose effects of fractionated RT and RIT were evaluated separately. Then, 30 Gy RT (10 fractions over 12 days) were combined with three weekly i.v. injections of 200 microCi of 131I-labeled anti-carcinoembryonic antigen monoclonal antibodies in four different treatment schedules. RIT was given either prior to, concurrently, immediately after, or 2 weeks after RT administration. The longest regrowth delay (RD) of 105 days was observed in mice treated by concurrent administration of RT and RIT, whereas the RDs of RT and RIT alone were 34 and 20 days, respectively. The three sequential combination treatments produced significantly shorter RDs ranging from 62 to 70 days. The tumor response represented by the minimal volume (MV) also showed that concurrent administration of RT and RIT gave the best result, with a mean MV of 4.5% as compared to MVs from 26 to 53% for the three sequential treatments. The results were confirmed in a second experiment, in which a RT of 40 Gy was combined with an identical RIT as above (three injections of 200 microCi of 131I-labeled monoclonal antibodies). At comparable toxicity levels, the maximum tolerated RT or RIT alone gave shorter RDs and less tumor shrinkage compared to simultaneous RT+ RIT. These results may be useful for designing clinical protocols of combined RIT and RT.

Radioimmunotherapy and fractionated radiotherapy of human colon cancer liver metastases in nude mice.

Radioimmunotherapy (RIT) and radiotherapy (RT) were evaluated in nude mice developing liver metastases of human colon cancer. Without treatment, 90% of preconditioned nude mice, injected with LS174T cells intrasplenically and splenectomized, died between 26 and 93 days after grafting with few to several hundred liver metastases. RIT with 500 microCi of 131I-labeled anti-carcinoembryonic antigen monoclonal antibodies, injected i.v. in 3 weekly fractions, was initiated 1 to 3 weeks after grafting. Mean survival increase was 43 days for mice treated at 2 weeks. From 13 mice treated at 1 week, 8 mice showed long-term survival, a significantly better cure rate compared to RIT at 2 weeks. Mice undergoing RIT at 3 weeks showed similar survival as untreated controls. Mice injected with 131I-labeled irrelevant IgG1 or unlabeled antibody showed no significant survival increase. Conventional fractionated external beam RT of the liver showed that 40-50 Gy treatment initiated 1 week after grafting gave long-term survival in 7 of 13 mice, significantly better compared to RT at 2 weeks. With combined RIT + RT initiated 2 weeks after grafting, 5 of 11 mice had long-term survival in the absence of major toxicities. Thus, early RIT and RT were more efficient than later treatments, and combination therapy might give further improvement.

Combined effects of interleukin-3 and interleukin-11 on hematopoiesis in irradiated mice.

The survival rate and recovery of peripheral blood cells and platelets were studied in Balb/c mice subjected to different single doses of whole-body irradiation and treated with a combination of interleukin-3 (IL-3) and interleukin-11 (IL-11). In a first group of 20 mice, 7.5 Gy irradiation, immediately followed by 2 and 5 days therapy of IL-3 and IL-11, respectively, increased the survival rate to 82% compared to 20% in untreated controls. In a second group of mice irradiated with 7 Gy, we observed significantly higher platelet, white blood cell (WBC), and red blood cell (RBC) counts after treatment with both cytokines, as compared to IL-3 or IL-11 alone or untreated controls. In addition, the survival rate of the mice with the combined therapy was also increased to 84%, compared to 48% in untreated controls. Irradiation (8.5 Gy) gave 100% mortality for the control mice, and therapy with combined IL-3 plus IL-11 had only a marginal effect. Interestingly, syngeneic bone marrow transplantation (BMT) alone, performed 16 hours after irradiation, increased the survival rate to 70%, while BMT combined with administration of IL-3 plus IL-11 increased it to 97%. Furthermore, BMT combined with cytokine administration could partially prevent the severe WBC and RBC depletion observed in mice treated with BMT alone and promoted a more rapid recovery of platelets and RBC. These data show that the combination of IL-3 and IL-11 has a radioprotective effect and can enhance recovery of platelets, WBC, and RBC in irradiated mice. Combined IL-3 plus IL-11 therapy may be clinically useful in myelodepression, especially in platelet depletion related to radiation therapy or chemotherapy, or after bone marrow transplantation.

Carcinoembryonic antigen expression, antibody localisation and immunophotodetection of human colon cancer liver metastases in nude mice: a model for radioimmunotherapy.

Colorectal cancer frequently disseminates through the portal vein into the liver. In this study, outbred Swiss nude mice were adapted to facilitate the induction of liver metastases by a pre-grafting treatment with 6 Gy total body irradiation and i.v. injection of anti-asialo GM1 antibody. One day later, cultured LS 174T human colon cancer cells were injected into the surgically exposed spleen, which was resected 3 min later. In 48 of 65 mice, a few to several hundred liver metastases were macroscopically observed at dissection 3 to 4 weeks after transplantation. Ten of 10 mice, followed-up for survival, died with multiple large confluent liver metastases. By reducing the radiation dose to 4 or 0 Gy, or omitting the anti-asialo GM1 antibody injection, only 60%, 37% or 50% of mice, respectively, had visible metastases 3 weeks after transplantation. Carcinoembryonic antigen (CEA) measured in tumour extracts was in the mean 25.6 micrograms/g in liver metastases compared with 9.2 micrograms/g in s.c. tumours. Uptake of radiolabelled anti-CEA monoclonal antibody (MAb) in the metastases 12, 24 and 48 hr after injection gave a mean value of 39% of the injected dose per gram of tissue (ID/g). In comparison, MAb uptake in s.c. and intrasplenic tumours or lung metastases gave a mean percentage ID/g of 20, 18 and 15, respectively. Laser-induced fluorescence after injection of indocyanin-MAb conjugate allowed direct visual detection of small liver metastases, including some that were not visible under normal light. Preliminary results showed that mice, pre-treated with 4 Gy irradiation and the anti-asialo GM1 injection, were tolerant to radioimmunotherapy with a total dose of 500 muCi 131I labeled anti-CEA intact MAbs given in 3 injections.

Biodistribution of anti-CEA F(ab')2 fragments after intra-arterial and intravenous injection in patients with liver metastases due to colorectal carcinoma.

The biodistribution of simultaneous intra-arterial and intravenous injections of a radiolabelled anti-CEA MAb F(ab')2 fragment was studied in three patients with liver metastases from colorectal cancer. Identical MAb fragments, labelled with either 125I or 131I, were injected over a period of 30 min into the hepatic artery and into a peripheral vein. After 1 or 2 days, biodistribution was measured in the surgically removed metastases, normal tissue samples and blood. By tissue radioactivity counting, tumour uptake in the range 6.3-9.1% of injected dose per gram was found. Superimposable metastasis-to-blood and metastasis-to-normal liver ratios were obtained for both iodine isotopes in all three patients. The results indicate that the intra-arterial injection of MAb F(ab')2 fragments gives no measurable advantage over more convenient injections into a peripheral vein.

Expression of the DF3-P epitope in human ovarian carcinomas.

Recent studies have described the generation of a mAb, designated DF3-P, which reacts with underglycosylated precursors of the DF3/MUC1 mucin-like glycoprotein. The present work demonstrates that the epitope recognized by mAb DF3-P is expressed by cell lines derived from human epithelial ovarian carcinomas and not a teratocarcinoma. Indirect immunofluorescence assays of single-cell suspensions support expression of the DF3-P epitope on the surface of ovarian carcinomas. Immunofluorescence studies on chamber slides further demonstrate that the mAb DF3-P-reactive cells are present in clusters. We also demonstrate that 125I-labeled mAb DF3-P selectively localizes to human ovarian carcinoma xenografts in athymic mice. The percentage of injected 125I dose/g tissue ranged between 10 and 17% for implanted CAOV-3 and OVCAR-3 tumors. Finally, the results of immunoperoxidase staining studies demonstrate that the DF3-P epitope is detectable in formalin-fixed sections of ovarian tumors and that mAb DF3-P exhibits little if any reactivity with normal surrounding tissues. Selective expression of the DF3-P epitope may be useful as a target for radioimaging or immunotherapeutic approaches to ovarian cancer.

Radiolabeled chimeric anti-CEA monoclonal antibody compared with the original mouse monoclonal antibody for surgically treated colorectal carcinoma.

UNLABELLED: Biodistribution and tumor uptake of a chimeric human-mouse monoclonal antibody (MAb) and the original mouse MAb have been comparatively studied. METHODS: Eighteen patients with suspected colorectal cancer scheduled for surgery underwent immunoscintigraphy with 123I-labeled chimeric anti-CEA MAb. Iodine-125 and 131I trace-labeled chimeric and original mouse MAb were simultaneously injected for biodistribution studies. RESULTS: Similar serum kinetics and a low immunogenicity were observed for both antibodies. Mean binding capacity to CEA measured in PBS after radiolabeling was identical for both MAbs and it was slightly decreased when measured in serum 1-4 hr after injection. Radiochromatograms of patients sera showed immune complex formation related to the amount of circulating CEA. Postoperative ex vivo radioactivity counting in tissue samples revealed similar antibody distributions with notably similar antibody uptakes in tumors. High tumor uptakes (between 0.02 to 0.06% injected dose per g) were observed in 3 of 13 patients operated for primary or metastatic colorectal cancer. CONCLUSION: In this dual-label technique, the radioiodinated anti-CEA IgG4 chimeric MAb and the original mouse IgG1 MAb were shown to have very similar behavior in colorectal cancer patients.

Combined radioimmunotherapy and radiotherapy of human colon carcinoma grafted in nude mice.

The effect of combined radioimmunotherapy (RIT) and fractionated external beam radiotherapy (RT) was assessed in two human colon cancer xenografts, Co112 and LS174T in nude mice. These tumors were selected for being resistant to RIT alone, as is usually the case in the clinical situation. Tumor-bearing mice were treated with a combination of five X-ray fractions over 5 days followed by RIT with two doses of 1.5 mCi 131I-labeled anticarcinoembryonic antigen monoclonal antibody F(ab')2. In Co112 and LS174T, RIT alone achieved a regrowth delay similar to that of fractionated RT with total doses of 28 and 26 Gy, respectively. In both tumor types, an additive therapeutic effect, measured as increased regrowth delay or local control, was observed when combining RT of different dose levels with RIT. Normal tissue responses were assessed by monitoring acute peak skin reactions and blood cell count. Bone marrow depression for the combination treatment was similar to that of RIT alone; relative to skin, at equitoxic levels, no mice bearing Co112 tumors were locally controlled with a 32 Gy RT dose alone, while this RT combined with RIT gave a local control of 100%. These studies show a therapeutic benefit when external beam RT is combined with RIT.

Direct comparison of a radioiodinated intact chimeric anti-CEA MAb with its F(ab')2 fragment in nude mice bearing different human colon cancer xenografts.

Tumour localisation and tumour to normal tissue ratios of a chimeric anti-carcinoembryonic antigen (CEA) monoclonal antibody (MAb), in intact form and as an F(ab')2 fragment labelled with 125I and 131I, were compared in groups of nude mice bearing four different colon cancer xenografts, T380, Co112 or LoVo, of human origin, or a rat colon cancer transfected with human CEA cDNA, called '3G7'. For each tumour, three to four mice per time point were analysed 6, 12, 24, 48 and 96 h after MAb injection. In the different tumours, maximal localisation of intact MAb was obtained at 24 to 48 h, and of F(ab')2 fragment 12 to 24 h after injection. Among the different tumours, localisation was highest with colon cancer T380, with 64% of the injected dose per gram (% ID/g) for the intact MAb and 57% for its F(ab')2 fragment, while in the three other tumours, maximal localisation ranged from 14 to 22% ID g-1 for the intact MAb and was about 11% for the F(ab')2. Tumour to normal tissue ratios of intact MAb increased rapidly until 24 h after injection and remained stable or showed only a minor increase thereafter. In contrast, for the F(ab')2 fragment, the tumour to normal tissue ratios increased steadily up to 4 days after injection reaching markedly higher values than those obtained with intact MAb. For the four different xenografts, tumour to blood ratios of F(ab')2 were about 2, 3 and 5 to 16 times higher than those of intact antibodies at 12, 24 and 96 h after injection, respectively.

Placental pathology of idiopathic intrauterine growth retardation at term.

Placental examination was carried out in 128 consecutive cases of idiopathic intrauterine growth retardation (IUGR) at term and the findings were compared with those of 179 gestational age-matched cases with normal growth. Mean pregnancy weight and mean maternal weight gain during pregnancy of IUGR cases were both significantly lower than for non-IUGR cases. There was a higher frequency of a history of previous growth-retarded infants between IUGR cases (18 of 128, or 14%) compared with non-IUGR cases (7 of 179, or 3.9%). The studied placental lesions were placental infarction, chronic villitis, hemorrhagic endovasculitis, and placental vascular thromboses. One or more of these lesions were present in 71 of 128 (55%) of IUGR cases, and 58/179 (32%) of non-IUGR cases. Thirty-eight of 72 (53%) cases with chronic villitis were IUGR (30% of all IUGR cases). Thirty-one of 49 cases (63%) with placental infarction were IUGR cases (24% of all IUGR cases). Nineteen of 32 cases (59%) with hemorrhagic endovasculitis were IUGR cases (15% of all IUGR cases). Twelve of 17 cases (71% with placental vascular thromboses were IUGR (9% of all IUGR cases). Relationships of all placental lesions to IUGR were independent of each other. IUGR infants more frequently had multiple types of lesions in their placentas. Chronic villitis and hemorrhagic endovasculitis tended to occur in the same placentas. There were no significant relationships between maternal characteristics and placental lesions, except for an association between low pregravid weight and increased incidence of placental infarction. Decreased birth length was associated only with placental infarction (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Preterm delivery: correlations of fetal growth and placental pathology.

The present study of 466 consecutive liveborn preterm singleton deliveries included 238 cases of spontaneous preterm labor and delivery, 175 cases with premature rupture of membranes, 13 cases of nonhypertensive abruption, 18 cases of preeclampsia, and 22 cases of placenta previa. Placental infarction, chronic villitis, and decidual pathologic processes showed different associations with fetal growth, depending on the clinical circumstances. Placental infarction was associated with decreased growth in all groups except placenta previa; in cases of placenta previa, placental infarction was associated with heavier infants. Chronic villitis was related to decreased growth in spontaneous rupture of membranes and preterm labor cases but was related to increased growth in cases of preeclampsia.

Placental pathologic findings in preterm birth.

Microscopic features of placentas from 539 consecutive preterm deliveries and 214 term deliveries were compared. The presence of either umbilical or chorionic vasculitis was identified in 38% of the cases at 22 to 28 weeks' gestation, in 32% of the cases at 29 to 32 weeks' gestation, in 13% of the cases at 33 to 36 weeks' gestation, and in 10% of the cases at term (p less than 0.0001). Decidual vascular abnormality was present in 70% of the cases at 22 to 28 weeks' gestation, in 35% of the cases at 29 to 32 weeks, in 29% of the cases at 33 to 36 weeks, and in 15% of the cases at term (p less than 0.0001). Chronic villitis was significantly more frequent in preterm deliveries without umbilical vasculitis than in those cases with umbilical vasculitis (17% vs 8%, p less than 0.05). Our data indicate that the placental lesions of umbilical-chorionic vasculitis, decidual vascular abnormality, and chronic villitis are related to preterm birth. Umbilical-chorionic vasculitis reflects acute ascending bacterial infection. Decidual vascular abnormality has been associated with maternal autoimmune or alloimmune disorders. Chronic villitis may indicate either congenital viral infection or maternal-fetal immunopathologic conditions. Both decidual vascular abnormality and chronic villitis may reflect the activation of inflammatory mechanisms capable of leading to preterm delivery.