Background : The p53 gene codes for a DNA-binding nuclear phosphoprotein that appears to inhibit the progression of cells from the G1 to the S phase of the cell cycle. Mutations of the p53 gene are common in a wide variety of human cancers, including lung cancer. In lung cancers, point mutations of the p53 gene have been found in all histological types including approximately 45% of resected NSCLC and even more frequently in SCLC specimens. Mutant forms of the p53 protein have transforming activity and interfere with the cell-cycle regulatory function of the wild-type protein. The majority of p53 gene mutations produce proteins with altered conformation and prolonged half life; these mutant proteins accumulate in the cell nucleus and can be detected by immunohistochemical staining. But protein overexpression has been reported in the absence of mutation. p53 protein overexpression or gene mutation is reported poor prognostic factor in breast cancer, but in lung cancer, its prognostic significance is controversial. Method : We investigated the p53 abnormalities by nucleotide sequencing, polymerase chain reaction-single strand conformation polymorphism(PCR-SSCP), and immunohistochemical staining. We correlated these results with each other and survival in 75 patients with NSCLC resected with curative intent. Overexpression of the p53 protein was studied immunohistochemically in archival paraffin- embedded tumor samples using the D07(Novocastra, U.K.) antibody. Overexpression of p53 protein was defined by the nuclear staining of greater than 25% immunopositive cells in tumors. Detection of p53 gene mutation was done by PCR-SSCP and nucleotide sequencing from the exon 5-9 of p53 gene. Result: 1) Of the 75 patients, 36%(27/75) showed p53 overexpression by immunohistochemical stain. There was no survival difference between positive and negative p53 immunostaining(overall median survival of 26 months, disease free median survival of 13 months in both groups). 2) By PCR-SSCP, 27.6%(16/58) of the patients showed mobility shift. There was no significant difference in survival according to mobility shift(overall median survival of 27 in patients without mobility shift vs 20 months in patients with mobility shift, disease free median survival of 8 months vs 10 months respectively). 3) Nucleotide sequence was analysed from 29 patients, and 34.5%(10/29) had mutant p53 sequence. Patients with the presence of gene mutations showed tendency to shortened survival compared with the patients with no mutation(overall median survival of 22 vs 27 months, disease free median survival of 10 vs 20 months), but there was no statistical significance. 4) The sensitivity and specificity of immunostain based on PCR-SSCP was 67.0%, 74.0%, and that of the PCR-SSCP based on the nucleotide sequencing was 91.8%, 96.2% respectively. The concordance rate between the immunostain and PCR-SSCP was 62.5%, and the rate between the PCR-SSCP and nucleotide sequencing was 95.3%. Conclusion : In terms of detection of p53 gene mutation, PCR-SSCP was superior to immunostaining. p53 gene abnormalities either overexpression or mutation were not a significant prognostic factor in NSCLC patients resected with curative intent. However, patients with the mutated p53 gene showed the trends of early relapse.
Much has teed changed in the field of hospital administration in the It wake of the rapid development of sciences, techniques ana systematic hospital management. However, we still have a long way to go in organization, in the quality of hospital employees and hospital equipment and facilities, and in financial support in order to achieve proper hospital management. The above factors greatly effect the ability of hospitals to fulfill their obligation in patient care and nursing services. The purpose of this study is to determine the optimal methods of standardization and quality nursing so as to improve present nursing services through investigations and analyses of various problems concerning nursing administration. This study has been undertaken during the six month period from October 1971 to March 1972. The 41 comprehensive hospitals have been selected iron amongst the 139 in the whole country. These have been categorized according-to the specific purposes of their establishment, such as 7 university hospitals, 18 national or public hospitals, 12 religious hospitals and 4 enterprise ones. The following conclusions have been acquired thus far from information obtained through interviews with nursing directors who are in charge of the nursing administration in each hospital, and further investigations concerning the purposes of establishment, the organization, personnel arrangements, working conditions, practices of service, and budgets of the nursing service department. 1. The nursing administration along with its activities in this country has been uncritical1y adopted from that of the developed countries. It is necessary for us to re-establish a new medical and nursing system which is adequate for our social environments through continuous study and research. 2. The survey shows that the 7 university hospitals were chiefly concerned with education, medical care and research; the 18 national or public hospitals with medical care, public health and charity work; the 2 religious hospitals with medical care, charity and missionary works; and the 4 enterprise hospitals with public health, medical care and charity works. In general, the main purposes of the hospitals were those of charity organizations in the pursuit of medical care, education and public benefits. 3. The survey shows that in general hospital facilities rate 64 per cent and medical care 60 per-cent against a 100 per cent optimum basis in accordance with the medical treatment law and approved criteria for training hospitals. In these respects, university hospitals have achieved the highest standards, followed by religious ones, enterprise ones, and national or public ones in that order. 4. The ages of nursing directors range from 30 to 50. The level of education achieved by most of the directors is that of graduation from a nursing technical high school and a three year nursing junior college; a very few have graduated from college or have taken graduate courses. 5. As for the career tenure of nurses in the hospitals: one-third of the nurses, or 38 per cent, have worked less than one year; those in the category of one year to two represent 24 pet cent. This means that a total of 62 per cent of the career nurses have been practicing their profession for less than two years. Career nurses with over 5 years experience number only 16 per cent: therefore the efficiency of nursing services has been rated very low. 6. As for the standard of education of the nurses: 62 per cent of them have taken a three year course of nursing in junior colleges, and 22 per cent in nursing technical high schools. College graduate nurses come up to only 15 per cent; and those with graduate course only 0.4 per cent. This indicates that most of the nurses are front nursing technical high schools and three year nursing junior colleges. Accordingly, it is advisable that nursing services be divided according to their functions, such as professional, technical nurses and nurse's aides. 7. The survey also shows that the purpose of nursing service administration in the hospitals has been regulated in writing in 74 per cent of the hospitals and not regulated in writing in 26 per cent of the hospitals. The general purposes of nursing are as follows: patient care, assistance in medical care and education. The main purpose of these nursing services is to establish proper operational and personnel management which focus on in-service education. 8. The nursing service departments belong to the medical departments in almost 60 per cent of the hospitals. Even though the nursing service department is formally separated, about 24 per cent of the hospitals regard it as a functional unit in the medical department. Only 5 per cent of the hospitals keep the department as a separate one. To the contrary, approximately 12 per cent of the hospitals have not established a nursing service department at all but surbodinate it to the other department. In this respect, it is required that a new hospital organization be made to acknowledge the independent function of the nursing department. In 76 per cent of the hospitals they have advisory committees under the nursing department, such as a dormitory self·regulating committee, an in-service education committee and a nursing procedure and policy committee. 9. Personnel arrangement and working conditions of nurses 1) The ratio of nurses to patients is as follows: In university hospitals, 1 to 2.9 for hospitalized patients and 1 to 4.0 for out-patients; in religious hospitals, 1 to 2.3 for hospitalized patients and 1 to 5.4 for out-patients. Grouped together this indicates that one nurse covers 2.2 hospitalized patients and 4.3 out-patients on a daily basis. The current medical treatment law stipulates that one nurse should care for 2.5 hospitalized patients or 30.0 out-patients. Therefore the statistics indicate that nursing services are being peformed with an insufficient number of nurses to cover out-patients. The current law concerns the minimum number of nurses and disregards the required number of nurses for operation rooms, recovery rooms, delivery rooms, new-born baby rooms, central supply rooms and emergency rooms. Accordingly, tile medical treatment law has been requested to be amended. 2) The ratio of doctors to nurses: In university hospitals, the ratio is 1 to 1.1; in national of public hospitals, 1 to 0.8; in religious hospitals 1 to 0.5; and in private hospitals 1 to 0.7. The average ratio is 1 to 0.8; generally the ideal ratio is 3 to 1. Since the number of doctors working in hospitals has been recently increasing, the nursing services have consequently teen overloaded, sacrificing the services to the patients. 3) The ratio of nurses to clerical staff is 1 to 0.4. However, the ideal ratio is 5 to 1, that is, 1 to 0.2. This means that clerical personnel far outnumber the nursing staff. 4) The ratio of nurses to nurse's-aides; The average 2.5 to 1 indicates that most of the nursing service are delegated to nurse's-aides owing to the shortage of registered nurses. This is the main cause of the deterioration in the quality of nursing services. It is a real problem in the guest for better nursing services that certain hospitals employ a disproportionate number of nurse's-aides in order to meet financial requirements. 5) As for the working conditions, most of hospitals employ a three-shift day with 8 hours of duty each. However, certain hospitals still use two shifts a day. 6) As for the working environment, most of the hospitals lack welfare and hygienic facilities. 7) The salary basis is the highest in the private university hospitals, with enterprise hospitals next and religious hospitals and national or public ones lowest. 8) Method of employment is made through paper screening, and further that the appointment of nurses is conditional upon the favorable opinion of the nursing directors. 9) The unemployment ratio for one year in 1971 averaged 29 per cent. The reasons for unemployment indicate that the highest is because of marriage up to 40 per cent, and next is because of overseas employment. This high unemployment ratio further causes the deterioration of efficiency in nursing services and supplementary activities. The hospital authorities concerned should take this matter into a jeep consideration in order to reduce unemployment. 10) The importance of in-service education is well recognized and established. 1% has been noted that on the-job nurses. training has been most active, with nursing directors taking charge of the orientation programs of newly employed nurses. However, it is most necessary that a comprehensive study be made of instructors, contents and methods of education with a separate section for in-service education. 10. Nursing services'activities 1) Division of services and job descriptions are urgently required. 81 per rent of the hospitals keep written regulations of services in accordance with nursing service manuals. 19 per cent of the hospitals do not keep written regulations. Most of hospitals delegate to the nursing directors or certain supervisors the power of stipulating service regulations. In 21 per cent of the total hospitals they have policy committees, standardization committees and advisory committees to proceed with the stipulation of regulations. 2) Approximately 81 per cent of the hospitals have service channels in which directors, supervisors, head nurses and staff nurses perform their appropriate services according to the service plans and make up the service reports. In approximately 19 per cent of the hospitals the staff perform their nursing services without utilizing the above channels. 3) In the performance of nursing services, a ward manual is considered the most important one to be utilized in about 32 percent of hospitals. 25 per cent of hospitals indicate they use a kardex; 17 per cent use ward-rounding, and others take advantage of work sheets or coordination with other departments through conferences. 4) In about 78 per cent of hospitals they have records which indicate the status of personnel, and in 22 per cent they have not. 5) It has been advised that morale among nurses may be increased, ensuring more efficient services, by their being able to exchange opinions and views with each other. 6) The satisfactory performance of nursing services rely on the following factors to the degree indicated: approximately 32 per cent to the systematic nursing activities and services; 27 per cent to the head nurses ability for nursing diagnosis; 22 per cent to an effective supervisory system; 16 per cent to the hospital facilities and proper supply, and 3 per cent to effective in·service education. This means that nurses, supervisors, head nurses and directors play the most important roles in the performance of nursing services. 11. About 87 per cent of the hospitals do not have separate budgets for their nursing departments, and only 13 per cent of the hospitals have separate budgets. It is recommended that the planning and execution of the nursing administration be delegated to the pertinent administrators in order to bring about improved proved performances and activities in nursing services.