MEASUREMENT OF HALF-VALUE LAYER IN COMPUTED TOMOGRAPHY SCANNERS USING LUMINESCENCE OF POLYETHERSULFONE RESIN BY X-RAY IRRADIATION.

In this study, a method for estimating the half-value layer (HVL) and effective energy (Eeff) by imaging the luminescence from a polyethersulfone (PES) resin with rotating irradiation of X-rays in a computed tomography scanner was developed. The luminescence of the PES resin was imaged using a charge-coupled device camera. The PES-HVL was determined from the luminance attenuation profile corresponding to the X-ray attenuation within the resin. The PES-HVLs for tube potentials of 80-135 kVp were converted into Eeff values and were compared to those of a conventional lead-covered case method. The Eeff obtained using the proposed luminescence imaging method agreed within ~3.9% of that obtained using the conventional method. Moreover, dose simulations based on the X-ray spectrum calculated from the HVLs were performed using a poly(methyl methacrylate) phantom with a diameter of 16 cm. The simulated doses based on the luminescence imaging method agreed with the in-phantom dosimetry within ~9%.

[Quality of health care for diabetic and hypertensive patients in primary care settings servicing Mexican Seguro Popular]. / Sistema de Protección Social en Salud y calidad de la atención de hipertensión arterial y diabetes mellitus en centros de salud.

OBJECTIVE: To assess health care quality provided to type-2 diabetic and hypertensive patients in primary care settings from the Mexican Ministry of Health and to evaluate whether accredited clinics providing services to the Mexican Seguro Popular performed better in terms of metabolic control of those patients compared to the non-accredited. MATERIAL AND METHODS: Cross-sectional study performed on 2008. Previous year clinical measures were obtained from 5 444 diabetic and 5 827 hypertensive patient's clinical records. Adequate metabolic control (glucose <110 mg/dl for diabetes and blood pressure <140/90 mmHg for hypertension) associated factors were assessed by multiple-multilevel logistic regression methods. RESULTS: Patients attending accredited clinics were more likely to be controlled, however, metabolic control was not constant over time of accreditation. CONCLUSIONS: Additional efforts are required to monitor accredited clinics' performance in order to maintain both metabolic control and clinical assessment of patients.

Sistema de Protección Social en Salud y calidad de la atención de hipertensión arterial y diabetes mellitus en centros de salud / Quality of health care for diabetic and hipertensive patients in primary care settings servicing Mexican Seguro Popular

OBJETIVO. Medir la calidad técnica de la atención a pacientes con diabetes mellitus tipo 2 (DM) e hipertensión arterial (HAS) en los centros de salud (CS) de los Servicios Estatales de Salud de México, al comparar su desempeño según condición de acreditación al Seguro Popular (SP). MATERIAL Y MÉTODOS. Estudio transversal realizado en 2008. Durante el año previo fue recolectado el historial de atención de 5 444 expedientes de pacientes con DM y 5 827 con HAS. Se determinaron los factores asociados al buen control metabólico de DM (glucosa<110 mg/dl) y HAS (tensión arterial <140/90 mmHg) mediante modelos de regresión logística multinivel. RESULTADOS. Fue estimado mejor control metabólico en los pacientes de los CS acreditados, sin embargo, este no fue constante de acuerdo con el tiempo de acreditación. CONCLUSIONES. Es necesario monitorear el desempeño de las unidades acreditadas para mantener constante el buen control metabólico y el tratamiento clínico de estos pacientes.

OBJECTIVE. To assess health care quality provided to type-2 diabetic and hypertensive patients in primary care settings from the Mexican Ministry of Health and to evaluate whether accredited clinics providing services to the Mexican Seguro Popular performed better in terms of metabolic control of those patients compared to the non-accredited. MATERIAL AND METHODS. Cross-sectional study performed on 2008. Previous year clinical measures were obtained from 5 444 diabetic and 5 827 hypertensive patient's clinical records. Adequate metabolic control (glucose <110 mg/dl for diabetes and blood pressure <140/90 mmHg for hypertension) associated factors were assessed by multiple-multilevel logistic regression methods. RESULTS. Patients attending accredited clinics were more likely to be controlled, however, metabolic control was not constant over time of accreditation. CONCLUSIONS. Additional efforts are required to monitor accredited clinics' performance in order to maintain both metabolic control and clinical assessment of patients.

Community assessment: a church community and the parish nurse.

In central Massachusetts a large urban parish asked the University of Massachusetts, Amherst School of Nursing to conduct a community assessment for the church and newly employed parish nurse. The aims of the assessment were: to determine the health status of parishioners, identify their perceived health needs and perceived barriers in meeting those needs, and to assist the church and parish nurse in developing a health program for their faith community. Findings of the assessment are based on questionnaire and focus group data. Four hundred and twenty-one questionnaires were completed, and six focus groups were held to validate the data. Results showed most parishioners felt they were in good health (93%), believed faith and spiritual beliefs were important in maintaining health and well-being (91%), and thought that the church should play a role in helping parishioners meet their health needs (70%). In addition, focus group discussions revealed a need for respite care for primary caretakers of the ill and elderly, and health education programs for their teen and elderly populations. In conclusion, parishioners were positive and articulated support of the parish nurse and activities designed to address the physical, emotional, and spiritual needs of their community.

Preparation, hydrolysis and intramolecular transesterification of 3'-deoxy-3'-thioinosine 3'-S-dimethylphosphorothiolate.

The hydrolytic reactions of the dimethyl ester of 3'-deoxy-3'-thioinosine 3'-S-phosphorothiolate have been followed over a wide aciditiy range by HPLC. At pH > 3, only hydroxide ion catalyzed isomerization to the 2'-dimethylphosphate takes place, whereas under more acidic conditions hydrolysis to the 2'-monomethylphosphate and 3'-S-monomethylphosphorothiolate competes. The latter is the only product accumulating in very acidic solutions (1 M hydrochloric acid). Mechanisms of the reactions are discussed.

Mouse popliteal lymph node assay for assessment of allergic and autoimmunity-inducing potentials of low-molecular-weight drugs.

In the present collaborative study, popliteal lymph node (PLN) responses to penicillin G (an allergenic chemical), D-penicillamine (an autoimmunity-inducing chemical), and barbital (a negative reference chemical) were investigated in three different mouse strains by ten pharmaceutical companies. Two inbred mouse strains (BALB/c and A/J) and one outbred strain (ICR) were subcutaneously injected with saline solutions containing penicillin G (1.25, 2.5 and 5 mg/mouse), D-penicillamine (0.5, 1 and 2 mg/mouse), or barbital (2 mg/mouse) into one hind footpad and saline only was injected into the contralateral footpad. PLN cellularity indices were determined on day 7. In the three strains tested, the penicillin G and D-penicillamine injections resulted in approximately dose-dependent responses. In contrast, barbital failed to generate a significant PLN reaction. In the typical data from one of the participating laboratories, the PLN responses of A/J, BALB/c, and ICR to penicillin G were high, intermediate and low, respectively, while their PLN responses to D-penicillamine were all high. Some variation in PLN cellularity indices was observed among the participating laboratories, but reproducibility of the popliteal lymph node assay (PLNA) evaluation was partly confirmed. Although the appropriate selection of mouse strains and drug dosage levels has to be considered, these results suggest that the PLNA may be an appropriate screening system for prediction of the allergic or autoimmunity-inducing potentials of low-molecular-weight drugs.

Detection of oligonucleotide hybridization on a single microparticle by time-resolved fluorometry: quantitation and optimization of a sandwich type assay.

Uniformly sized (50 micro m) porous glycidyl methacrylate/ethylene dimethacrylate particles (SINTEF) were used as the solid phase in a sandwich type mixed-phase hybridization assay based on time-resolved fluorescence detection on a single particle. These particles were coated with oligodeoxyribonucleotide probes by conventional phosphoramidite chain assembly. An oligodeoxyribonucleotide bearing a photoluminescent europium(III) chelate, ¿2,2',2",2"'-¿¿4'-¿4"'-[(4, 6-dichloro-1,3,5-triazin-2-yl)amino]phenyl¿-2,2':6',2"-terpyrid ine-6, 6"-diyl¿bis(methylenenitrilo)¿tetrakis(acetato)¿eur opi um(III), was hybridized to a complementary sequence of the target oligonucleotide, and the resulting duplex was further hybridized to the particle-bound probes. The latter binding was quantified by time-resolved measurement of the emission signal of a single particle. Kinetics of hybridization and the effect of the concentration of the target oligomer and the fluorescently tagged probe on the efficiency of hybridization were studied. The intensity of the emission signal was linearly related to the concentration of the target oligomer over a range of 5 orders of magnitude. The length of the complementary region between the target oligomer and the particle-bound probe was varied, and the effect of point mutations and deletions on the hybridization efficiency was determined in each case. The maximal selectivity was observed with 10-16-base pair complementary sequences, the optimal length depending on the oligonucleotide loading on the particle. Discrimination between the complete matches and point mismatches was unequivocal, a single point mutation and/or deletion decreasing the efficiency of hybridization by more than 2 orders of magnitude.

Experimental methods for immunization and challenge in antigenicity studies in guinea pigs.

Optimal experimental methods for antigenicity studies in guinea pigs were investigated on: (1) the effects of different immunizing methods using complete or incomplete Freund's adjuvants (CFA or IFA), and various injection sites, the number of immunizations, the immunizing doses, and the immunizing periods, (2) the relationship between the severity of active systemic anaphylaxis (ASA) reactions and passive cutaneous anaphylaxis (PCA) titers, (3) positive control for oral administration, and (4) the effects of incubation mixture of drug and serum protein as the challenge for the ASA assay. The following results provided useful information for designing more appropriate methods for antigenicity studies: (1) The optimal immunization method for benzylpenicillin (PcG), cephaloridine, 2,4,6-trinitrobenzene sulfonic acid and adriamycin, which were selected as positive controls for low molecular medicines in this experiment, involved subcutaneous administration of 1 ml of a test substance in CFA (1st immunization) or IFA (2nd and 3rd immunizations) at two doses, 1 and 10 mg/animal, 3 times at 2-week intervals on the back of a guinea pig. Blood collection for PCA assay was needed 2 weeks after the last immunization, and ASA assay, 1 or 2 days after the blood collection. (2) The insensitivity of ASA reactions in bovine serum albumin-immunized animals with very high PCA titers was overcome by increasing the challenge antigen dose from 1 to 10 mg/animal. (3) Most animals administered lysozyme at 0.1, 1 or 10 mg/animal by gavage for 2 weeks or more showed ASA and PCA reactions. (4) Incubation of a mixture of 20 mg/ml of PcG and 2 mg/ml of guinea pig serum albumin for 4 hr was the most effective as challenge for the induction of ASA reaction in PcG-immunized guinea pigs.

Importance of clinical staging in limited small-cell lung cancer: a valuable system to separate prognostic subgroups. The University of Toronto Lung Oncology Group.

PURPOSE: In an attempt to assess the response to treatment and survival of a group of patients treated with standard chemotherapy and radiotherapy, we undertook a retrospective review of small-cell lung cancer (SCLC) patients treated by the University of Toronto Lung Oncology Group. PATIENTS AND METHODS: We reviewed the records of 264 patients with limited SCLC who were treated from 1976 to 1985. Based on radiologic review and physical examination, patients were assigned to three prognostic groups: group 1 (very limited SCLC), negative mediastinoscopy and/or no evidence of mediastinal nodes on radiologic review; group 2, x-ray evidence of mediastinal node involvement or a positive mediastinoscopy; group 3, supraclavicular adenopathy or x-ray evidence of pneumonic consolidation, pleural effusion, or atelectasis. All patients received combination chemotherapy, radiotherapy to the primary site, and prophylactic cranial irradiation. RESULTS: Complete response was seen in 52% of patients and partial response in 29%. Response rates did not differ among the three prognostic subgroups. The median survival time for patients in group 1 was 15.7 months, compared with 12 months for group 2 and 11 months for group 3 (P = .0175). Projected 5-year survival for group 1 was 18%, compared with only 6% and 2% for groups 2 and 3, respectively. There was no difference among the prognostic subgroups with respect to either local or distant recurrence rates. CONCLUSION: Using simple clinical staging techniques, we were able to identify a subgroup of patients with very limited SCLC who had a significantly better prognosis. We recommend that randomized clinical trials stratify patients according to the presence or absence of clinically detectable mediastinal lymphadenopathy.

In vitro cytotoxicity test for estimating non-ocular irritation dose of ophthalmic solutions.

The in vitro cytotoxicity test for estimating the non-ocular irritation dose of ophthalmic solutions was investigated. In the in vitro test, normal human epidermal keratinocytes (NHEK) in a confluent monolayer were incubated for 48 hr in a medium with test compounds. The concentration of a test compound which causes a 50% reduction in NHEK viability was determined as IC50 by MTT colorimetric assay. For comparison, the in vivo rabbit ocular irritation tests were carried out by the standard Draize method. The maximum concentration, which did not show any ocular irritation, was determined as DS0. The results showed the correlation coefficient between the IC50 values and the DS0 values for 19 test compounds to be 0.82. However, the correlation coefficients for 10 compounds, which have IC50 values of less than 300 micrograms/ml, and for 7 alcohols were 0.99. The IC50-DS0 correlation curves obtained could be utilized as the critical concentrations for ocular irritation. These results suggest that our in vitro/in vivo test can estimate non-ocular irritation dose of the ophthalmic preparations in advance of the in vivo tests.

Second primary malignancies following diagnosis of small-cell lung cancer.

PURPOSE AND METHODS: The records of 800 patients with small-cell carcinoma of the lung (SCLC) treated between 1971 and 1985 at University of Toronto-affiliated hospitals were reviewed for the occurrence and relative risk of second primary malignancies (SPMs). Almost all patients who developed a SPM were treated previously with chemotherapy and radiation therapy. RESULTS: Nineteen metachronous SPMs (MSPMs) and 11 synchronous SPMs (SSPMs) were identified. SSPMs were detected between 1 and 12 months after the diagnosis of SCLC. The MSPMs were identified between 1 and 10 years after the diagnosis of SCLC. MSPMs included non-small-cell lung cancer (NSCLC) (four patients), hematologic malignancies (HM) (three patients), and 12 with other solid tumors (OST). The median survival times after the diagnosis of MSPM was 33 months, 10 months, and 1 month, respectively, for those with NSCLC, OST, and HM. Expected cancer incidence rates were used to compute a relative risk rate for developing a MSPM in a subset of 392 patients on whom accurate follow-up information was available. The calculated relative risk for all tumors was 3.73. The relative risk for the development of secondary NSCLC was 6.83. CONCLUSION: We suggest that increased predisposition to SPM may relate to secondary effects of multimodality treatment and biologic considerations.

Treatment of adults with severe aplastic anemia: primary therapy with antithymocyte globulin (ATG) and rescue of ATG failures with bone marrow transplantation.

PURPOSE: To evaluate a policy of immunosuppression with antithymocyte globulin (ATG) as primary therapy for adults with severe aplastic anemia (SAA) regardless of the availability of an HLA-identical bone marrow donor. PATIENTS AND METHODS: Thirty-one consecutive adults with SAA who satisfied the age criteria for allogeneic bone marrow transplantation (BMT) (age less than 51 years) were treated with ATG 20 mg/kg/day for 10 days along with high-dose corticosteroids. Patients with an HLA-identical donor received a transplant if they did not respond to ATG or if they developed life-threatening complications during or soon after ATG administration. Eight patients with no response to ATG were also treated with oral cyclosporine 12.5 mg/kg/day. RESULTS: Eleven patients had a complete and five a partial response to ATG; two patients improved with cyclosporine treatment, resulting in an overall response rate of 58% to immunosuppression. Nine of 14 patients with donors received a BMT: seven because they did not respond to ATG and two because of serious infections. Seven grafts were obtained from related and two from unrelated donors. There was no significant difference in survival between those with and without a related HLA-identical donor (log-rank p value = 0.969). At a median follow-up of 58 months, 26 of 31 are alive with an actuarial survival of 80% at 5 years. Two patients died of infection, two died from complications of BMT, and one remains transfusion-dependent. One patient died of refractory leukemia at 30 months; one patient relapsed with hypoplasia 95 months after initial therapy with ATG. He showed a complete response to treatment with cyclosporine. No other late hematologic events have occurred. CONCLUSIONS: This treatment approach resulted in the restoration of hematopoiesis and independence from transfusion in 80% of patients with SAA entered into the study. The efficacy of allogeneic BMT in salvaging cases in which ATG failed does not appear to be compromised. Follow-up for the development of clonal hematologic disorders remains an important part of this treatment policy.

The effect of treatment time and treatment interruption on tumour control following radical radiotherapy of laryngeal cancer.

A significant effect of overall treatment time on local control was found in a retrospective review of 1012 radically irradiated squamous cell carcinomas of the larynx. The actuarial local relapse free rate (LRFR) at 5 years for the whole group was 59%. The effect of treatment time on local control was modelled to the linear-quadratic equation. Using logistic regression analysis treatment time and dose were significant (p = 0.008 and p = 0.04, respectively). When the analysis was adjusted for the influence of stage and laryngeal subsite treatment time remained a significant prognostic factor (p = 0.02). The derived value of gamma/alpha was 0.7 Gy/day and when adjusted for stage and sub-site 0.8 Gy/day. This equates to a dose increment to maintain iso-effective local control of 0.64 Gy/day and 0.73 Gy/day respectively for daily fractions of 2.5 Gy and an assumed alpha/beta for tumour of 25 Gy. To provide an estimate of the clinical impact of treatment interruptions not compensated for by dose escalation a Cox regression was performed. Significant variables were T stage, N stage, sex, total dose and total length of treatment interruption. Using the proportional hazard model it was calculated that each day of treatment interruption resulted in an increase in the hazard of local relapse by 4.8% (p = 0.006). Based on our data it was calculated that this would result in a decrease in local control of 1.4% for each day of uncompensated treatment interruption.

Small-cell carcinoma of the lung: derivation of a prognostic staging system.

Retrospective data on 22 pretreatment attributes were evaluated in 614 patients with small-cell carcinoma of the lung (SCCL). The series included 284 patients with limited disease (LD) and 328 patients with extensive disease (ED) managed between 1974 and 1986. Prognostic factors were evaluated by univariate analysis and by the Cox multivariate regression model. Recursive partition and amalgamation algorithm (RECPAM), two clustering methods well suited for obtaining strata and adapted for censoring survival data, were developed and used in the formulation of a new prognostic staging system. In univariate analysis, prognosis was significantly influenced by extent of disease (DE), the number of metastatic sites, and the detection of mediastinal spread in LD. Poor performance status (PS), male sex, and advanced age were negatively correlated with survival, as were increased serum levels of alkaline phosphates (AP), lactate dehydrogenase (LDH), carcinoembryonic antigen (CEA), total WBC count (WBCC), and low platelet count and low serum sodium. The Cox model identified plasma LDH and mediastinal spread as the only significant factors in LD; the influence of PS, number of metastatic sites, bone metastasis, brain metastasis, and platelet count were identified as significant in ED. The RECPAM model identified four distinct risk groups defined in a classification tree by the following eight attributes: DE, PS, serum AP, serum LDH, mediastinal spread, sex, WBCC, and liver metastasis. The four groups were distinguished by median survival times of 59, 49, 35, and 24 weeks, respectively (P = .0001). Interactions among prognostic factors are emphasized in the RECPAM classification model as evidenced by reassignment of patients across conventional staging barriers into alternate prognostic groups. The advantages of using RECPAM over the more conventional Cox regression techniques for a new staging system are discussed.

Role of interleukin-1 and prostaglandin in in vitro bone resorption induced by Actinobacillus actinomycetemcomitans lipopolysaccharide.

Lipopolysaccharide (Y4 LPS) isolated from Actinobacillus actinomycetemcomitans strain Y4 induced bone resorption in BALB/c mouse calvaria organ culture. The calcium release from LPS-low responsive C3H/HeJ mouse calvaria by Y4 LPS was very low. Indomethacin almost completely inhibited prostaglandin E2 (PGE2) production by Y4 LPS-stimulated BALB/c mouse calvaria, but did not suppress interleukin-1 (IL-1) release from the calvaria, and partially suppressed the bone resorption. Dexamethasone strongly inhibited the PGE2 and IL-1 production by Y4 LPS-stimulated BALB/c mouse calvaria, as well as Y4 LPS-induced bone resorption. Dexamethasone inhibited expression of membrane IL-1 on osteoblastic cells stimulated with Y4 LPS, but indomethacin did not. Furthermore, anti-IL-1 serum partially suppressed the calcium release from Y4 LPS-stimulated BALB/c mouse calvaria. These results suggest that both PGE2 and IL-1 participate in Y4 LPS-induced bone resorption in vitro.

A management approach to incompletely excised basal cell carcinomas of skin.

There were 187 incompletely resected basal cell carcinomas (BCC) of skin referred to the Princess Margaret Hospital between 1970 and 1985. Median age at presentation was 62 years. The commonest location of these lesions was in the head and neck region (93%). One hundred twenty lesions were immediately treated: 119 were irradiated and 1 was excised. The remaining 67 lesions were managed expectantly. Follow-up time for the entire population ranged from 1 month to 17 years, with a median time of 2.7 years. The 5-year probability of remaining relapse-free in the group immediately treated was 91% versus 61% if managed expectantly (p = 0.0001). If only lateral margins were positive, the crude probability of local failure was 3/18 (17%), versus 9/27 (33%) if the deep margins were involved (p = 0.2). Once relapse occurred in the group of lesions treated expectantly, 17/20 (85%) of these relapses were salvaged by either radiation or surgery. The 10-year actuarial probability of local control for the lesions immediately treated and observed were similar: 92% and 90%, respectively (p = 0.5). An economic analysis revealed that immediate radiation treatment saved the health system only $223.00 per patient. Since there is no difference in the ultimate local control between these two approaches, and these elderly patients may be spared the morbidity of unnecessary treatments, it is suggested that a policy of observation may be adopted for basal cell carcinomas of skin which have been incompletely excised.

Structure and mineral content in weight-bearing bones following hindlimb suspension in young rats.

Responses of structure and mineral content in weight-bearing bones to 1-week hindlimb suspension were studied in growing rats. The weight, volume, and length of femur, tibia, and fibula were less in suspended rats than cage controls, although there was no significant difference in the weight/volume ratio. The diameter of mid-shaft, the thickness of cortical bone, and the ratio of cortical bone thickness to femur diameter were significantly less in the suspended rats. The width of marrow space showed no differences, suggesting that the cortical bone was mainly affected. The sum of mineral content and the mineral content per diameter in the cross section of femurs were decreased following suspension, suggesting a change in the internal structure of cortical bone. Data also indicated that the reduction of femur diameter was caused by decreased thickness which is accompanied by the decreased mineral content of the cortical bone. It was suggested that there is a close relationship between the responses of bones and muscles to hindlimb suspension of young rats, although the degree of weight loss was greater in muscles than in bones.

[Effect of lipopolysaccharide on biological properties and induction of alveolar bone resorption in rats].

A study was made on the effects of lipopolysaccharides (LPS) from Escherichia coli and Actinobacillus actinomycetemcomitans on mitogenic response and the release of calcium from mouse calvaria. LPS exhibited significant mitogenic activity on mouse spleen cells, and increased the release of calcium from mouse calvaria in vitro. The effect of LPS from E. coli on alveolar bone resorption in Wistar male rats was also studied. LPS was infused by an Alzet miniosmotic pump that was implanted subcutaneously on the backs of the rats. A catheter connected to the pump was brought up to the maxillary right second molar using a nylon ligature. In this way the rats were continuously infused for 7 days with LPS. Alveolar bone loss was measured by an image-analyser (Nexus 6411). Rats stimulated by LPS exhibited significant alveolar bone loss, but bone loss was not observed in rats stimulated by saline. Polymyxin B effectively inhibited the LPS-stimulated bone resorption.