Out of extrapulmonary tuberculosis patients admitted to the 36 national sanatoria during the past 5 years (1978-1982), 307 cases (41.4%) were diagnosed as having bone and joint tuberculosis (187 cases of tuberculous spondylitis and 120 cases of bone and joint tuberculosis).
Dividing by sex 151 were male, and 156 were female. The average age on admission was 49.5 years (2-84 years old). The average age at the outbreak of the disease, however, was 44.5 years thus there was a 5 year delay in average from the onset of the disease to the admission.
The most frequent site of spinal tuberculous lesion was the lumbar region (52%). Complications attributed to Pott's paraplegia were seen in 20% of the spinal cases as a whole, being particularly high in the thoracolumbar region (57%).
The number of affected vertebrae was 2 in 67% of cases, and 6 or more vertebrae were affected in 8% of cases. The site of the lesion in bone and joint tuberculosis was the hip joint in 29% of cases, the knee joint in 20%, and the thoracic cage (rib) in 13%. It should be noted that these results were limited to cbservations made in the national sanatoria alone.
A considerable delay between the onset of the disease and the start of chemotherapy was observed. For example, only 43% of cases of spinal tuberculosis, and 59% of bone and joint tuberculosis started chemotherapy within 6 months from the onset of the disease.
RFP has been used from the start of chemotherapy, and the regimens administerd were mostly the combination of RFP, INH, and EB (37%), and RFP, SM, and INH (35%).
The duration of hospitalization was similar both in cases of spinal, and bone and joint tuberculosis. In total, 29% of cases were admitted up to 5 months, 18% for 6-7 months and 25% for 8-12 months, thus 71% were dischaged with in one year. Admission for more than 3 years was recorded in 5.6% of cases.
Surgery was done in 45% of cases of spinal tuberculosis, and in 72% of bone and joint tuberculosis.
The duration of chemotherapy instituted prior to surgery varied. The duration was less than one month in only 21% of cases of spinal, and in 26% of bone and joint tuberculosis.
In 62% of cases, chemotherapy was completed at the time of the survey. Overall, 3.6% of patients had 6 months chemotherapy, 4.8% had 7-9 months, and 25% had 10-12 months, making a total of 34% for a period of one year. Following surgery, chemotherapy was suspended for 9 months or shorter in less than 10% of cases, for one year in 50% of cases, and for one and a half years in 75% of cases. These figures excluded cases in which complications of tuberculosis in other organs occured, cases in which more than 2 regions were affected, or cases in which further operations were needed. However, there were no cases required chemotherapy for 3 years and longer in the surgery group.
Side effects of anti-tuberculous drugs occurred in 19% of cases; liver dysfunction (3.3%) due to RFP, peripheral neuritis (1%) due to INH, visual disturbance (2.9%) due to EB, and tinnitus or hearing disturbance due to SM (1.5%) and KM (13.3%).
Main complications were active lung tuberculosis (35%), fistulae (19%) and kidney tuberculosis (6%). In addition, nontuberculous complications, such as hypertension (6%), diabetes mellitus (3%), and rheumatoid arthritis (3%) were seen particularly in elderly patients. Fourteen patients died, but only 4 patients died of tuberculosis.
Complications due to surgery were seen in 10% of cases, including serum hepatitis (4%) and fusion failure (4%). There were no deaths associated directly with surgery.

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Impaired cell-mediated immune responses have been reported in diabetes mellitus. The present study was aimed to clarify the influence of the complicated diabetes mellitus on the optimal length of chemotherapy for pulmonary tuberculosis. We studied inpatients in our hospital during the six years period from 1977 to 1983 including 203 cases of newly diagnosed tuberculosis complicated with diabetes mellitus and 185 cases without diabetes mellitus. Forty-five retreated cases of tuberculosis complicated with diabetes mellitus and 91 cases without diabetes mellitus were also included in the study.
In newly diagnosed tuberculosis in which bacilli were sensitive to drugs, ordinary chemotherapy with INH and RFP gave an excellent result on the disease whether complicated with diabetes mellitus or not; in nearly all cases studied, acid-fast bacilli in sputa were converted to negative within 4 months after the initiation of chemotherapy. Five year follow-up study revealed only 3 cases of relapse out of 146 cases (2.1%) of diabetes mellitus-complicated tuberculosis which received the ordinary chemotherapy of less than 12 months, at most 18 months. This relapse rate of 2.1% is comparable to that in non complicated tuberculosis (2 in 133 cases, 1.5%) during the 3 year follow-up period.
In retreatment study of tuberculosis, the effect of chemotherapy was dependent on the susceptibility of drugs to bacilli at the initiation of retreatment. The result of 9-12months-chemotherapy was favorable in cases of tuberculosis which were sensitive to INH and RFP regardless of complication with diabetes mellitus or not. In cases of tuberculosis which were resistant to these drugs, no clinical as well as bacteriological improvement was achieved even after prolonged chemotherapy.
The above data indicate that coexisting diabetes mellitus in pulmonary tuberculosis gives little unfavorable effect on the treatment of tuberculosis. We conclude that the success in treatment of pulmonary tuberculosis depends on whether the bacilli are sensitive to the drugs or not and not on whether complicated with diabetes mellitus or not. In drug-sensitive cases, one year chemotherapy is enough for the treatment of diabetes mellitus complicated tuberculosis whether it has been treated before or not.

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A high performance liquid chromatography (HPLC) technique permits the determination of rifampicin (RFP) and 2.5-desacetyl RFP (DES-RFP) in human serum. It can be used to determine the serum concentration of RFP in patients. The purpose of this study is to determine the relationship between the clinical efficacy of RFP and its level of serum concentration. We measured the serum concentration of RFP in 41 tuberculous patients admitted to 6 National Sanatoria. All of them were previously untreated, and culturepositive. These cases were bacteriologically and radiologically followed up for at least 6 months from the beginning of treatment. RFP was administered at a single dose of 0.45g orally in the fasting state. Blood samples were taken at 0, 2, 4, and 6 hours after the initial administration. As it was well established that repeated daily administration of RFP results in a decrease of serum concentration, we measured the serum concentration of RFP at 1, 2, 3, and 6 months after the initial administration during the treatment. We used HPLC for the quanititative analysis of RFP and DES-RFP, on the method of assay was as follows:
Instruments: a Model ALC/GPC 204 high performance liquid chromatograph (Waters Assoc.)
Column: a stainless-steel tube (30×4mm i. d.) filled with u-Bondapack C₁₈ (Waters Assoc.)
Mobile phase: 38%CH₃ CN/0.01M CH₃ COONa (ajusted to pH7.0 with CH₃COOH)
Flow rate: 1.0ml/min
Detection: a Model 440 fixed-wavelength (340nm) UV absorbance detector (Waters Assoc.)
Assay procedure: To 50μl of plasma in 1-ml tube, 200μ; of methanol containing 500pg/μ1 p-nitrophenol, internal standard, is added. The tube is stoppered and mechanically shaken, then centrifuged for 5 min. at 3, 000 rpm. A 100-μl portion of supernatant is injected into the chromatographic column. The concentration of RFP and DES-RFP are calculated by measuring the peak heights of chromatogram.
Calibration: Calibration samples are prepared by measuring 50μl of standard RFP (150, 100, 80, 50, 30, 10ng) and DES-RFP (50, 40, 30, 20, 10, 5ng) methanol solutions into 1-ml t ubes. Methanol is evaporated under nitrogen, and the compounds are redissolved in 200μ of methanol containing 500pg/μl p-nitrophenol, internal standard and 50μl of plasma is added. The assay is done as described.
The following results were obtained
1) The mean peak serum concentration of RFP and DES-RFP on the first administration was 5.5±3.20μg/ml at 2 hours after the administration and 0.97±0.71μg/ml at 4 hours, respectively.
2) The serum peak value of RFP and DES-RFP decreased after 1 month starting administrAtion and there after it kart the same level during treatment.
3) We could neither find any relationship between the clinical prognosis and RFP serum levels nor the relation between the side effect and the serum levels of DES-RFP.

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Cases of pulmonary diseases caused from the sequel of pulmonary tuberculosis are often observed inthe recent years. Past history of pulmonary tuberculosis and pulmonary disease were in vestigated on cases admitted to Fuji City Central Hospital during 4 years from 1982 till 1985.
(1) Pulmonary diseases caused from the sequel of past pulmonary tuberculosis occnpied 48.7% of all cases of pulmonary disease, whill cases of past tuberculosis occnpied 20.6% of all cases of pulmonary diseases.
(2) Chronic pulmonary diseases including chronic obstructive pulmonary diseases and chronic pulmonary infections, or chronic respiratory failure were often observed as a post tuberculosis complication. In addition, 29.3% of pulmonary tuberculosis were relapsed cases.
(3) Time interval from past tuberculousis till present admission was in general long about 20-30 years. The most cases were in the age group 60-70. Pulmonary damages caused by past tuberculosis were compensated when partients were young lest led to chronic pulmonary diseases when they became old.

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