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Biomedical subjects

R Chin

Publications and source records attributed to R Chin.

At least 19 recordsLinked to original sources
PubMed2004

The HLA-DR2 haplotype is associated with an increased proliferative response to the immunodominant CD4(+) T-cell epitope in human interferon-beta.

Human CD4(+) T-cell epitopes were identified in interferon-beta (IFN-beta)-1b. A prominent peptide epitope region was found that induced a proliferative response in 16% of all donors tested. Responses corresponded to the presence of the HLA-DR2 haplotype. Responsive donors expressing the HLA-DQ6 allele showed an increased level of proliferation to the epitope as compared to peptide-responsive HLA-DQ6 negative donors. A similar result was found for HLA-DR15-expressing donors. PBMC from donors expressing HLA-DR15 were more likely to proliferate in response to IFN-beta in a whole-protein in vitro assay than donors who did not carry this haplotype. It is striking that the common DQ6 allele HLA-DQB1(*)0602 is found in linkage disequilibrium with HLA-DRB1(*)1501, and this combination defines the HLA genotype associated with the development of multiple sclerosis. The HLA association between a response to IFN-beta and MS might explain the prevalence of neutralizing antibody development, and may underlie the etiology of the disease.

CD4-Positive T-Lymphocytes↗
PubMed2002

Malignant epithelial tumor of unknown origin of the broad ligament.

Malignant epithelial tumor of the broad ligament is rare and to our knowledge only 17 cases have been reported. We report a 54-year-old Japanese woman in whom transvaginal sonography (TVS) and magnetic resonance imaging (MRI) showed a left adnexal tumor. Serum CA125 was elevated to 10,000 U/ml. Preoperatively, we diagnosed this tumor was a left ovarian malignant tumor though, it was confirmed a the 47x57 mm tumor in the left broad ligament at laparotomy. Histologically most of the tumor showed serous papillary adenocarcinoma with changes similar to poorly differentiated carcinoma and as seen in transitional cell carcinoma on hematoxylin-eosin staining. After three courses of platinum based adjuvant chemotherapy, the patient is alive with no recurrence at 18 months postoperatively.

Broad Ligament↗
PubMed2002

Effectiveness of a croup clinical pathway in the management of children with croup presenting to an emergency department.

OBJECTIVE: The aim of this study was to evaluate the safety and effectiveness of a clinical pathway for croup in an emergency department (ED). METHODOLOGY: This before-and-after intervention study on all consecutive children aged 6 months to 10 years who presented to our ED with moderate/severe croup was conducted over a 6-month period. Children with a clinical croup score (CSS) of 2 or more and resting stridor were considered eligible for entry into the study. Children were treated with either oral dexamethasone, or a combination of oral dexamethasone suspension and nebulized adrenaline. Children were clinically assessed, observed in the emergency short-stay ward and discharged or admitted according to the clinical pathway. The following outcomes were measured: admission rates, hospital re-presentation, length of stay, and adverse clinical events. Children in the post-intervention group were followed up by telephone within 48 h of discharge. RESULTS: There were 157 patients recruited in the pre-intervention group and 110 in the post-intervention group. Significant reductions were reported in the length of stay (18.9 h compared with 5.2 h), hospital admission (52.9% compared with 18.0%) and intensive care admission (10.2% compared with 0.0%) after the introduction of the croup clinical pathway. No children in the study experienced an adverse clinical event. Follow-up interviews of parents indicated that the new treatment strategy was well received. CONCLUSION: The use of the croup clinical pathway in the ED is safe and effective in guiding consistent management, resulting in reduced admission rates, earlier discharge home, and no reported adverse events.

Anti-Inflammatory Agents↗
PubMed2001

Safety of the weight-adjusted dosing regimen of tenecteplase in the ASSENT-Trial.

The results of the ASsessment of Safety and Efficacy of a New Thrombolytic agent (ASSENT-2) trial revealed that tenecteplase (TNK) is equivalent to tissue plasminogen activator (t-PA) for treating myocardial infarction. Because careful consideration of safety is important with all agents, including the newer bolus therapies, and across a range of doses, this study evaluated the safety of TNK compared with t-PA across a range of weight and dose categories. The 5 doses of TNK ranged from 30 to 50 mg and were adjusted for estimated weight. Rates of death and intracranial hemorrhage were determined among patients receiving TNK and t-PA in ASSENT-2, stratified by categories of estimated weight corresponding to each TNK dose. Respective rates of death with TNK versus t-PA were not significantly different in any estimated weight category: <60 kg (12.54% vs 11.46%), 60 to 69 kg (8.22% vs. 8.97%), 70 to 79 kg (5.57% vs 5.48%), 80 to 89 kg (4.66% vs 5.36%), and > or =90 kg (4.91% vs. 3.96%, all p > or =0.26). Respective rates of intracranial hemorrhage were also not significantly different: <60 kg (2.20% vs. 2.29%), 60 to 69 kg (0.97% vs. 1.33%), 70 to 79 kg (1.15% vs. 1.10%), 80 to 89 kg (0.73% vs 0.49%), and > or =90 kg (0.47% vs 0.47%, all p > or =0.33). Adjustment for small baseline differences in this randomized sample did not change the results. Thus, across the range of estimated weight categories corresponding to each TNK dose, TNK is as safe and effective as t-PA.

Aged↗
PubMed2001

Chronic antigen-specific immune-system activation may potentially be involved in the loosening of cemented acetabular components.

Previous studies have attempted to determine whether aseptic loosening and osteolysis are caused by a T cell-mediated type IV hypersensitivity reaction or a nonspecific foreign body reaction involving phagocytic macrophages. The purpose of this study was to examine the role of the B7-CD28 costimulatory pathway (which is indicative of an activated immune response) in loosening and osteolysis of total joint replacements (TJRs). We harvested periprosthetic tissues from 24 loose, cemented, all polyethylene, acetabular components in patients undergoing revision total hip replacement surgery for aseptic loosening. Prostheses were classified radiographically as to whether ballooning, scalloping osteolysis was present or not. Monoclonal antibodies were used to identify macrophages, antigen presenting cells (APCs) expressing B7-1 or B7-2, total T lymphocytes, and T cells expressing CD28 or CTLA-4. The large numbers of positive cells, including macrophages, T cells, and APCs in both groups are substantially higher than previously reported. Macrophages constituted the predominant cell type, the majority of which were APCs. B7-1 was expressed by 18.3% of all cells, and B7-2 was expressed by 61.0% of cells. Despite the fact that there were no statistically significant differences in expression of proteins in the B7-CD28 pathway between the osteolytic and nonosteolytic groups, the magnitude of positive staining suggests that the process of aseptic loosening (not osteolysis) may involve proteins of the B7-CD28 pathway, particularly B7-2. One possible antigenic stimulus is protein-coated particulate wear debris from prosthetic materials.

Adult↗
PubMed2001

Baseline oxygen saturation predicts exercise desaturation below prescription threshold in patients with chronic obstructive pulmonary disease.

BACKGROUND: Recent studies of exercise-induced hypoxemia in patients with chronic obstructive pulmonary disease (COPD) have shown that oxygen supplementation during exertion increases exercise tolerance and alleviates dyspnea. Although measurements of forced expiratory volume in 1 second and diffusion capacity for carbon monoxide (DLCO) are known to predict exercise-induced desaturation in patients with COPD, baseline oxygen saturation has never been studied as a predictor of exercise-induced desaturation. METHODS: A retrospective analysis was performed of 100 consecutive patients with forced expiratory volume in 1 second-forced vital capacity ratio of 70% or less who underwent exercise testing for desaturation. Any desaturation to 88% or less with exercise was considered significant. Nineteen patients with total lung capacity of 80% or less were excluded to avoid evaluating those with combined obstructive and restrictive defects; 81 patients remained available for study. RESULTS: Nineteen (51%) of 37 patients with resting saturation of 95% or less desaturated with exercise as opposed to 7 (16%) of 44 with resting saturation of 96% or greater (P =.001). The sensitivity and the negative predictive value of baseline saturation of 95% or less as a screening test for exercise desaturation were 73% and 84%, respectively. If all patients with DLCO of 36% or less were excluded, 40 patients were left for study. Eight (40%) of 20 patients with baseline saturation of 95% or less compared with 0 of 20 with resting saturation of 96% or greater desaturated with exercise (P =.006). In this subset, the sensitivity and the negative predictive value of baseline saturation of 95% or less as a screening test for exercise desaturation both improved to 100%. CONCLUSIONS: In patients with COPD, baseline saturation of 95% or less is a good screening test for exercise desaturation, especially in patients with DLCO greater than 36%. This readily available office screening procedure merits further study in larger prospective patient cohorts.

Aged↗
PubMed2001

Effects of anticancer drugs on the metabolism of the anticancer drug 5,6-dimethylxanthenone-4-acetic (DMXAA) by human liver microsomes.

AIMS: To investigate the effects of various anticancer drugs on the major metabolic pathways (glucuronidation and 6-methylhydroxylation) of DMXAA in human liver microsomes. METHODS: The effects of various anticancer drugs at 100 and 500 microM on the formation of DMXAA acyl glucuronide (DMXAA-G) and 6-hydroxymethyl-5-methylxanthenone-4-acetic acid (6-OH-MXAA) in human liver microsomes were determined by high performance liquid chromatography (h.p.l.c.). For those anticancer drugs showing significant inhibition of DMXAA metabolism, the inhibition constants (Ki) were determined. The resulting in vitro data were extrapolated to predict in vivo changes in DMXAA pharmacokinetics. RESULTS: Vinblastine, vincristine and amsacrine at 500 microM significantly (P < 0.05) inhibited DMXAA glucuronidation (Ki = 319, 350 and 230 microM, respectively), but not 6-methylhydroxylation in human liver microsomes. Daunorubicin and N-[2-(dimethylamino)-ethyl]acridine-4-carboxamide (DACA) at 100 and 500 microM showed significant (P < 0.05) inhibition of DMXAA 6-methylhydroxylation (Ki = 131 and 0.59 microM, respectively), but not glucuronidation. Other drugs such as 5-fluoroucacil, paclitaxel, tirapazamine and methotrexate exhibited little or negligible inhibition of the metabolism of DMXAA. Pre-incubation of microsomes with the anticancer drugs (100 and 500 microM) did not enhance their inhibitory effects on DMXAA metabolism. Prediction of DMXAA-drug interactions in vivo based on these in vitro data indicated that all the anticancer drugs investigated except DACA appear unlikely to alter the pharmacokinetics of DMXAA, whereas DACA may increase the plasma AUC of DMXAA by 6%. CONCLUSIONS: These results indicate that alteration of the pharmacokinetics of DMXAA appears unlikely when used in combination with other common anticancer drugs. However, this does not rule out the possibility of pharmacokinetic interactions with other drugs used concurrently with this combination of anticancer drugs.

Antineoplastic Agents↗
PubMed2001

In vitro susceptibilities of wild-type or drug-resistant hepatitis B virus to (-)-beta-D-2,6-diaminopurine dioxolane and 2'-fluoro-5-methyl-beta-L-arabinofuranosyluracil.

Prolonged treatment of chronic hepatitis B virus (HBV) infection with lamivudine ([-]-beta-L-2',3'-dideoxy-3' thiacytidine) or famciclovir may select for viral mutants that are drug resistant due to point mutations in the polymerase gene. Determining whether such HBV mutants are sensitive to new antiviral agents is therefore important. We used a transient transfection system to compare the sensitivities of wild-type HBV and four lamivudine- and/or famciclovir-resistant HBV mutants to adefovir [9-(2-phosphonyl-methoxyethyl)-adenine; PMEA] and the nucleoside analogues (-)-beta-D-2, 6-diaminopurine dioxolane (DAPD) and 2'-fluoro-5-methyl-beta-L-arabinofuranosyluracil (L-FMAU). The drug-resistant mutants contained amino acid substitutions in the polymerase protein. We found that the M550I and M550V plus L526M substitutions, which confer lamivudine resistance, did not confer cross-resistance to adefovir or DAPD, but conferred cross-resistance to L-FMAU. The M550V substitution in isolation conferred a similar phenotype to M550I, except that it did not confer significant resistance to L-FMAU. The L526M substitution, which is associated with famciclovir resistance, conferred cross-resistance to L-FMAU but not to adefovir or DAPD. Inhibition of HBV secretion by DAPD, L-FMAU, and adefovir did not always correlate with inhibition of the generation of intracellular HBV replicative intermediates, suggesting that these analogs may preferentially inhibit specific stages of the viral replication cycle.

Adenine↗
PubMed2001

Staging by positron emission tomography predicts survival in patients with non-small cell lung cancer.

BACKGROUND: Positron emission tomography (PET) scanning is used increasingly to detect and stage lung cancer, but the test performance characteristics and relationship of PET to patient outcomes remain undefined. OBJECTIVE: To determine the test performance characteristics and relationship of PET scanning stage to patient outcomes relative to the 1997 International System for the Staging of Lung Cancer. DESIGN: Survival analysis using pathologic staging as the criterion standard for comparison of survival as predicted by staging by PET and CT. SETTING: University-based hospital. PATIENTS: All consecutive patients undergoing PET scanning for the evaluation of possible non-small cell lung cancer (NSCLC) during a 5-year period. MAIN OUTCOME MEASURES: Long-term survival of patients with NSCLC after staging by PET. RESULTS: One hundred fifty-two thoracic PET scans were obtained for the staging of possible NSCLC during a 5-year period. One hundred twenty-three patients (81%) demonstrated increased (18)F-fluorodeoxyglucose uptake. The overall sensitivity and specificity of PET for detecting malignancy were 95% and 67%, respectively, compared with 100% and 27% for chest CT. PET and CT had similar accuracy for staging the overall extent of disease (91% and 89%, respectively). PET stage correlated highly with survival using either nodal location or overall stage (p = 0.003, p = 0.002), as did pathologic staging (p = 0.0001, p = 0.0001). CT scan results did not accurately predict survival (p = 0.608, p = 0.338). CONCLUSION: PET scanning is a highly sensitive technologic advance in detecting and staging of thoracic malignancy and may more accurately predict the likelihood of long-term survival in patients with NSCLC than chest CT does.

Carcinoma, Non-Small-Cell Lung↗
PubMed2001

Hemoptysis in patients with renal insufficiency : the role of flexible bronchoscopy.

STUDY OBJECTIVES: To assess the indications, yield, and therapeutic impact of flexible bronchoscopy (FB) in patients with hemoptysis and renal insufficiency. DESIGN: Retrospective cohort analysis. SETTING: Tertiary-care university hospital. PATIENTS: Thirty-four patients over a 7.5-year period who underwent FB to evaluate hemoptysis in the setting of renal insufficiency (ie, serum creatinine level, > 1.5 mg/dL). MEASUREMENTS AND RESULTS: The etiology of hemoptysis was undetermined in 41% of cases. Defined causes of bleeding included infections (29%), pulmonary renal syndromes (15%), airway injury (9%), and pulmonary embolism (6%). No specific bleeding site was identified, but FB lateralized hemorrhaging to one lung in 24% of patients. FB results influenced therapy in 29% of patients overall and in 8% of patients without respiratory tract infection. The hospital survival rate was 47% and did not differ based on the presence or absence (presence vs absence) of the following variables: a defined etiology for hemoptysis (45% vs 50%); lateralized bleeding (38% vs 50%); or management alterations prompted by other FB findings (50% vs 46%). Factors associated with survival included the onset of bleeding prior to hospital admission (80% vs 33%; p = 0.02), the absence of respiratory failure requiring mechanical ventilation at the time of FB (90% vs 29%; p = 0.002), and lack of prohemorrhagic factors (other than uremia) such as disseminated intravascular coagulation, recent treatment with warfarin, heparin, or antiplatelet agents (78% vs 33%; p = 0.05). During the 6 months following hospital discharge, hemoptysis recurred in 14% of patients, and 5 patients died, for an overall mortality rate of 62%. CONCLUSIONS: These data suggest that FB in hospitalized patients with hemoptysis and renal insufficiency, and without radiographic findings suggesting neoplastic disease, has a low yield and limited impact. Whether FB influences outcome in selected patients in this setting requires prospective investigation.

Bronchoscopy↗
PubMed2001

Prospective randomized trial comparing oxygen administration during nasal flexible bronchoscopy : oral vs nasal delivery.

STUDY OBJECTIVES: To determine the optimal method of delivering supplemental oxygen during flexible bronchoscopy (FB). DESIGN: Prospective study. SETTING: University medical center. PATIENTS: Ninety-seven consecutive patients undergoing outpatient nasal FB during a 7-month period. INTERVENTION: During FB, delivery of oxygen was alternated weekly and administered by nasal cannula either nasally (52 patients) or orally (45 patients). Prior to the procedure, patients completed a questionnaire regarding oral or nasal breathing preferences, history of sinus disease, allergy history, and perceived degree of nasal congestion. RESULTS: Comparison of oxygen delivery groups demonstrated no significant difference in oxygen requirements (4.1 L/min nasal vs 3.8 L/min oral, p = 0.63), overall saturation nadir (90.9% nasal vs 91.4% oral, p = 0.85), or average saturation (95.8% nasal vs 95.7% oral, p = 0.57). No correlation between subjective symptoms or sinus or allergy history was found for oxygen requirements, average saturation, or saturation nadir. CONCLUSIONS: These data suggest that during nasal FB, no discernible difference exists between administration of oxygen using cannulas placed either nasally or orally.

Bronchoscopy↗
PubMed2001

Use of reperfusion therapies in elderly patients with acute myocardial infarction.

Almost one-third of patients with acute myocardial infarction (AMI) are aged >75 years, and this proportion is expected to increase as the population ages. Mortality and complication rates are particularly high in the elderly, yet reperfusion therapies, including thrombolysis and primary percutaneous transluminal coronary angioplasty (PTCA), are under-utilised among eligible patients. There is a concern, whether real or perceived, that the risks of such therapies may outweigh the potential benefits. Presently, there are no randomised clinical trials of thrombolytic therapy in the elderly that definitively assess its efficacy in patients aged >75 years. In the meta-analysis of randomised trials by the Fibrinolytic Therapy Trialists, thrombolysis was associated with a mortality reduction among patients aged >75 years, though this reduction did not meet formal statistical significance. Because the point estimates for mortality reduction were in the direction that favoured use of thrombolytic therapy, the American Heart Association/American College of Cardiology AMI guidelines recommend thrombolysis as a Class 2a therapy in this age group. Observational studies using data from the Cooperative Cardiovascular Project database and the National Registry of Myocardial Infarction have recently cast some doubt on the benefit of thrombolysis among the elderly, but definitive answers from a randomised trial are still lacking. Meanwhile, primary PTCA, which has been compared to thrombolysis in both trial and observational settings, appears to offer the mortality benefit of reperfusion with lower stroke rates. Since primary PTCA is not widely available, efforts must be made to maximise available therapies in the elderly. Early diagnosis is essential, as is prompt reperfusion among eligible patients, since delay is so strongly associated with mortality with both thrombolysis and PTCA. Finally, newer, more fibrin-specific thrombolytics may decrease the bleeding risk associated with thrombolytic therapy.

Aged↗
PubMed2000

Reductions of vascular endothelial growth factor and placental growth factor concentrations in severe preeclampsia.

OBJECTIVE: The aim of this study was to determine whether plasma concentrations of vascular endothelial growth factor and placental growth factor are altered in women with severe preeclampsia. STUDY DESIGN: We performed a case-control study to compare plasma concentrations of vascular endothelial growth factor and placental growth factor between women with severe preeclampsia and normotensive women admitted for delivery. Twenty-one women with severe preeclampsia were matched for gestational age and ethnicity with 21 normotensive women. Vascular endothelial growth factor and placental growth factor concentrations were measured with a specific antigen-capture enzyme-linked immunosorbent assay. RESULTS: Women with severe preeclampsia demonstrated significantly lower plasma concentrations of both vascular endothelial growth factor (6.36 +/- 3.96 pg/mL vs 18.65 +/- 5.98 pg/mL; P <.0001) and placental growth factor (138 +/- 119 pg/mL vs 531 +/- 340 pg/mL; P <.0001) than did women with normotensive pregnancy. Logistic regression analysis showed an independent association between plasma vascular endothelial growth factor concentration and plasma placental growth factor concentration and preeclampsia. CONCLUSION: Patients with severe preeclampsia had decreased maternal serum concentrations of both vascular endothelial growth factor and placental growth factor.

Endothelial Growth Factors↗
PubMed2000

Pulmonary cryptococcosis in the immunocompetent host. Therapy with oral fluconazole: a report of four cases and a review of the literature.

Isolated pulmonary cryptococcosis (IPC) is an infrequently diagnosed infection, the management of which is not well defined. In past years, IPC traditionally has not been treated in the immunocompetent host, given its perceived benign and self-limited course and the toxicity associated with amphotericin B. However, some patients manifest prominent and disabling symptoms, and infection occasionally may disseminate. Fluconazole is active against Cryptococcus neoformans, is easily administered, and has an excellent safety profile. We present four healthy hosts with IPC who were treated with oral fluconazole for 6 to 8 weeks. A review of the literature was conducted to identify other cases of IPC in healthy hosts who were also treated with fluconazole. Our results and the limited experience reported in the literature suggest that fluconazole may be an appropriate choice for the treatment of IPC in the immunocompetent host. Indications for treatment are not defined, but symptomatic patients, those with multiple nodules or extensive infiltrates on chest radiographs, and/or those testing positive for serum cryptococcal antigen might be potential candidates for therapy.

Administration, Oral↗
PubMed2000

Managing life-threatening hemoptysis: has anything really changed?

STUDY OBJECTIVES: To delineate current chest clinicians' approaches to the management of patients with life-threatening hemoptysis. DESIGN: Survey during a computer-assisted interactive continuing medical education presentation. SETTING: The 1998 American College of Chest Physicians (ACCP) Annual Scientific Assembly. PARTICIPANTS: Chest clinicians attending the respiratory emergency symposium. RESULTS: Most clinicians (86%) had cared for patients with life-threatening hemoptysis, and 28% had cared for patients with fatal events during the previous year. Those clinicians favored management in the ICU setting (95%) with early endotracheal intubation (85%), and they tended to use a large-bore, single-lumen endotracheal tube (57%). The majority (64%) favored the early performance of diagnostic bronchoscopy during the first 24 h. Most clinicians (79%) used the flexible instrument, a higher frequency than respondents at a similar symposium on hemoptysis at the 1988 ACCP meeting (48%; p < 0.0001). Most current clinicians (77%) had experience with endobronchial measures to control bleeding, but few (14%) found them to be consistently worthwhile. Chest CT scanning was often helpful in diagnosis (55%). In their management of bleeding, half of these clinicians favored the use of interventional angiography, even in operable patients, which is a substantial change from 1988 when 23% had favored this approach (p < 0.0001). CONCLUSIONS: During the past decade, life-threatening hemoptysis has remained an important problem. Flexible bronchoscopy and interventional angiography have become increasingly established, more widely accepted approaches to patient care.

Angiography↗
PubMed2000

The usefulness of positron emission tomography in evaluating patients for pulmonary malignancies.

STUDY OBJECTIVE: Positron emission tomography (PET) can contribute to diagnosing and staging lung cancer, but it has not been determined whether this information influences patient care. DESIGN: We reviewed the effects of thoracic PET scan results during an 11-month period. For each patient, physicians ordering these scans reported how PET specifically altered management, and graded the ease of interpretation and overall usefulness of PET on a 5-point scale. In addition, to appraise general attitudes about PET, we surveyed 488 national American Thoracic Society (ATS) members and 44 physicians at our comprehensive cancer center. RESULTS: One hundred twenty-six questionnaires regarding patients were mailed to 37 ordering physicians, and 98 responses (78%) were returned, primarily by cardiothoracic surgeons (35%) and pulmonologists (47%). Respondents reported that PET provided new information in 83 patients (85%) and altered patient management in 64 cases (65%). Major effects on management included decisions regarding biopsy (n = 16), surgery (n = 16), and palliative treatment (n = 16). Chest clinicians found PET to be more helpful (4.4 vs 3.9, p = 0.007) and easier to interpret (4.2 vs 3.7, p = 0.025) than other specialists. Among 139 ATS members (28%) responding to the general survey, 51 members (39%) had access to PET. PET was more frequently available to university-based (49%) than community-based (27%) physicians (p = 0.016). The majority of physicians without current access to PET (69%) indicated that they would like to have it available. ATS members with access to PET reported that PET results generally affect decisions regarding biopsy or surgery most often, but found the procedure less helpful than physicians at our center (2.77 vs 3. 56, p = 0.003) and ordered it less often for lung cancer staging (60% vs 96%, p = 0.002). CONCLUSION: PET scanning is useful in the management of patients with suspected thoracic malignancies, but impressions about its roles vary, with PET regarded more highly where, as at our center, it is used more often. Whether PET alters patient outcomes requires investigation.

Attitude of Health Personnel↗