局部注药联合口服康复新液辅助治疗颈淋巴结结核疗效观察

目的:探讨局部注射药物联合口服康复新液辅助治疗颈淋巴结结核的临床疗效及安全性。方法:按照随机数字表法将2010年1月-2014年1月我院收治的140例颈淋巴结结核患者分为对照组(n=70)和观察组(n=70),对照组口服异烟肼、利福平、乙胺丁醇、吡嗪酰胺及肌注链霉素进行全身抗结核治疗,观察组在对照组的基础上局部注射异烟肼、链霉素粉联合口服康复新液治疗。比较两组患者治疗后1个月、3个月及6个月症状缓解率,淋巴结吸收率,治疗后3个月复发率及不良反应发生率。结果:观察组治疗后1个月、3个月及6个月的症状缓解率、淋巴结吸收率均高于对照组(P0.05)。治疗后3个月,观察组复发率为2.86%,显著低于对照组的11.43%(P0.05)。观察组恶心、局部反应、白细胞减少及肝功能损害发生率均低于对照组(P0.05)。结论:局部注射抗结核药物联合口服康复新液辅助治疗颈淋巴结结核可提高患者的症状缓解率和淋巴结吸收率,且安全性高,有重要的临床推广价值。     

Spectrum of cytomorphology of tuberculous lymphadenitis and changes during anti-tubercular treatment

OBJECTIVE: To analyse the morphological changes in tuberculous lymph nodes and the clinical response during short course anti tubercular chemotherapy. METHODS: Thirty-six patients with tuberculous lymphadenitis under treatment were followed up clinically and cytologically at 0, 2, 4 and 6 months. RESULTS: Twenty-six (72.2%) patients had palpable lymph nodes at the end of chemotherapy. Of the 14 patients with residual lymph nodes exceeding 1 cm in size, 92.8% (13) still had evidence of continuation of the disease. Acid-fast bacilli could be found in 38.8% patients at the end of 6 months. Intense lymphocytic infiltration of granulomata in the early phase of chemotherapy predicted a favourable outcome. CONCLUSIONS: Following completion of anti-tubercular treatment a significant percentage of patients have persistent lymphadenopathy and harbour the disease. Morphological follow up of these patients is essential as they may be at increased risk of relapse.     

Intermittent Chemotherapy for Tuberculosis in an Urban Community

A regimen designed for effective foolproof antituberculosis treatment, acceptable on a routine basis, was applied to all patients newly diagnosed at the Chest Clinic, Hammersmith Hospital, in 1963, 1964, and 1965. During the first three months of treatment patients received daily (six days a week) streptomycin 0.75 g. plus isoniazid 300 mg. plus sodium para-aminosalicylate (P.A.S.) 12 g. The P.A.S. was usually stopped when bacterial sensitivity reports made this possible. For a further 15 months streptomycin 1 g. plus isoniazid 600 mg. was given on three alternate days each week to complete a total of 18 months'' treatment.Of the total of 140 patients (66% sputum-positive) 112 (80%) completed the planned 18 months with intermittent streptomycin plus isoniazid and a further eight completed treatment on alternative regimens (a total of 85%). The equivalent figures for one year are 88% and 94%. Excellent clinical and radiological results, together with sputum conversion, were achieved in 138 of the 140 patients (99%). Only two patients were lost from surveillance, because of failure to co-operate, before quiescence was obtained.It is concluded that the total efficiency of supervised intermittent treatment is greater than that of unsupervised daily regimens. Since 100% arrest of tuberculosis is possible with co-operative patients, less should not be accepted in developed countries.     

Tuberculous Lymphadenitis

A total of 43 episodes of tuberculosis lymphadenitis were treated in 32 adult patients. In 12 instances the affected lymph node was excised without any chemotherapy; there were 10 relapses. The treatment was local excision of the affected lymph nodes together with antituberculosis chemotherapy with at least two drugs in 30 instances; there were no relapses following such therapy.Presumably patients with tuberculosis lymphadenitis are still sometimes treated with surgery alone because that was at one time the orthodox line of surgical teaching. Such a view is out of date: these patients should always be given antituberculosis therapy in addition to any surgical measures.     

Controlled Comparison of Oral Twice-weekly and Oral Daily Isoniazid plus PAS in Newly Diagnosed Pulmonary Tuberculosis

A controlled clinical trial was undertaken in 247 patients with newly diagnosed pulmonary tuberculosis to assess the relative efficacies of a fully supervised twice-weekly oral regimen of isoniazid plus PAS (para-aminosalicylic acid) and a standard self-administered daily regimen of the same drugs following an initial intensive phase of two weeks of daily streptomycin, PAS, and isoniazid. Among patients who had isoniazid-sensitive cultures initially and who attended the clinic regularly the numbers with a favourable bacteriological response at the end of the year of chemotherapy were 79 (88%) out of 90 for the twice-weekly regimen and 72 (87%) out of 83 for the daily regimen; the numbers of patients with considerable radiographic improvement were 54 (60%) and 53 (64%) respectively. Complaints of vomiting or diarrhoea that did not require a reduction of the PAS dosage were made on one or two occasions by 23(21%) out of 109 twice-weekly and 25 (23%) out of 108 daily patients, and on at least three occasions by 4 (4%) and 12 (11%) respectively. Finally, all five patients who had chemotherapy changed on account of hypersensitivity to PAS had been receiving the daily regimen, as also had one patient who died of agranulocytosis.     

Investigation of remaxol efficacy in complex therapy of experimental generalized tuberculosis on mice

Efficacy of remaxol in complex chemotherapy of generalized drug resistant tuberculosis was studied on mice. Mycobacterium tuberculosis 5419 SPBNIIF isolated from a patient with freshey diagnosticated pulmonary tuberculosis resistant to isoniazid (10 mcg/ml), rifampicin (40 mcg/ml), streptomycin (10 mcg/ml) and ethionamide (30 mcg/ml) was used in the experiments. The main polychemotherapy included 4 antituberculosis drugs in the highest therapeutic doses: isoniazid, amikacin, ethambutol and tavanic, the treatment course was 8 weeks. Remaxol was administered in a dose of 25 ml/kg intraperitoneally 5 times a week (14 injections). Significant activating effect of remaxol on the tension of the lung tissue local immunity was revealed by changes in the granuloma cell composition (from mainly epitheliod to mainly lymphoid) and by more frequent large lymphohistiocytic infiltrates. The use of remaxol also greatly increased the absorptive and digestive activity of the peritoneal macrophages phagocytosis, inhibited in the process of the experimental tuberculosis development.     

Management of extra-pulmonary tuberculosis (excluding miliary and meningeal) in south and west Wales (1976-8).

In a retrospective survey of the management of extrapulmonary tuberculosis lymph node and genitourinary tuberculosis were found more commonly than bone and joint or gynaecological disease. Only 29% of patients received 18 moths'' chemotherapy while 31% received nine to 12 months'' treatment with rifampicin and isoniazid regimens and 34% had short-course chemotherapy with other regimens. Five patients were not offered any chemotherapy after diagnosis, and in five patients the diagnosis was overlooked because of administrative errors. One patient died from tuberculosis (renal). Poor drug compliance appeared less of a problem than in pulmonary tuberculosis. Only 14% of patients had their disease managed solely by consultants who were not specialists in chest disease. Liaison with a chest consultant did not necessarily ensure chemotherapy for 18 moths.     

Multidrug chemotherapy of tuberculosis in rhesus monkeys

Occurrence of tuberculosis caused by Mycobacterium bovis in a colony of rhesus monkeys allowed evaluation of a modern multidrug therapeutic regimen. Fifteen tuberculin positive rhesus monkeys with disseminated tuberculosis were evaluated for extent of disease by radiographic techniques, physical examination and laparotomy prior to treatment. Monkeys were divided into treatment groups of 3, 6 and 12 months duration and were treated once daily with isoniazid, rifampin and ethambutol. All animals survived their treatment course, had marked clinical improvement and rapid resolution of radiographically demonstrable lesions. Lesion regression evaluated by necropsy and histopathology correlated positively with length of treatment interval. Mycobacterium bovis was not isolated from any animal following treatment. Multidrug chemotherapy of tuberculosis was considered successful and practical in rhesus monkeys at the 12 month treatment interval. Chemotherapy may provide a reasonable alternative to destruction of valuable animals infected with tuberculosis.     

Lymphadénite tuberculeuse cervicale simulant une métastase ganglionnaire d’un carcinome papillaire de la thyroïde. À propos d’un cas

Cervical lymph nodes represent one of the most frequent clinical symptoms of extrapulmonary tuberculosis. Their appearance in a neoplastic suggests lymph node metastasis. We report an atypical tuberculous lymphadenetis mimicking lymph node metastasis in a 42-year-old patient followed for papillary thyroid carcinoma operated and treated by iodine 131 therapy. Evolution was marked by the appearance of left cervical adenopathies suggesting lymph node metastatic extension on echographic criteria. A lymph node excision was undertaken and the pathologic study revealed a tuberculous lymphadenitis. The patient was put under antibacillary treatment and evolution was satisfactory. We also expose, through this work, a certain number of techniques of exploration likely to ascertain the diagnosis of a tuberculous lymphadenitis and to monitor the therapeutic strategy.     

Bacteriostatic and bactericidal activity of antituberculosis drugs against Mycobacterium tuberculosis, Mycobacterium avium-Mycobacterium intracellulare complex and Mycobacterium kansasii in different growth phases.

Bacteriostatic and bactericidal activities of rifampicin, isoniazid, streptomycin, enviomycin and ethambutol against Mycobacterium tuberculosis, Mycobacterium avium--M. intracellulare complex and Mycobacterium kansasii were studied in different growth phases. Bacteriostatic activities of the drugs were similar in different growth phases, except isoniazid. M. tuberculosis was much less susceptible to isoniazid in the lag phase than in the log and the stationary phases. In contrast, bactericidal activity was influenced by the growth phase. M. tuberculosis was killed by isoniazid, streptomycin and rifampicin. The bactericidal activity of isoniazid was strongest. The bactericidal activity of isoniazid and streptomycin was most marked in the log phase. M. avium complex and M. kansasii resisted the bactericidal activity, but some strains of M. avium complex were killed by streptomycin and enviomycin, and the activities of these two drugs were most marked in the lag phase.     

A THERAPEUTIC REGIMEN FOR TUBERCULOUS MENINGITIS

The results of treatment of tuberculous meningitis in Highland Alameda County Hospital, since the advent of streptomycin, in 34 cases were: dead, 21 patients, or 61 per cent; alive, 10 patients, or 29 per cent. Three cases were excluded from the ultimate report due to inadequate follow-up. The mean survival time of the ten survivors at the time of report was 35 months, the longest being 74 months.The composite results of treatment elsewhere, as reported in the literature, have been: dead, 892, or 59 per cent; alive, 629, or 41 per cent.The pathogenesis of the disease and the effects of chemotherapy are discussed.A therapeutic regimen for tuberculous meningitis is presented, which has been used at Highland Hospital since INH became established as the most effective component in the combined chemotherapeutic attack on the disease.     

Cryptococcal lymphadenitis in a dog.

We describe a case of canine crytococcosis, the clinical symptoms were: feverish syndrome, vomiting and diarrhoeas and bilateral lymphadenitis in superficial lymph nodes. Microbiology and histopathology study of popliteal lymph node biopsy demonstrated the presence of round yeasts of some 3 microm of diameter, which we identified as Cryptococcus neoformans. Thirty months after suspending the medication the dog returned to the surgery; the dog was very thin and it had nervous symptoms; the owners decided it upon euthanasia. After carrying out the necropsy we take samples for their microbiology and histopathology study, both techniques detect to C. neoformans in marrow, CNS tissue and lymph nodes.     

Use of streptomycin and isoniazid during a tuberculosis epizootic in a rhesus and cynomolgus breeding colony

An epizootic of tuberculosis occurred following the addition of new cynomolgus monkeys to a nonhuman primate breeding colony. A total of 5/47 cynomolgus and 51/148 rhesus became tuberculin positive (reactors). Mycobacterium tuberculosis was cultured from reactors which were euthanatized and monkeys which died spontaneously. The isolates were sensitive to the standard antitubercular agents. Rhesus reactors and their unweaned infants were quarantined and given streptomycin and isoniazid by intramuscular injection. Isoniazid was added to the drinking water quarantined and given streptomycin and isoniazid by intramuscular injection. Isoniazid was added to the drinking water of the remainder of the breeding colony to curtail the outbreak. Isoniazid toxicity was observed in both infants and adults with an overall incidence of 3%. Forty-eight rhesus reactors and their infants born before the outbreak were alive and healthy at the end of the treatment period. In addition, nine surviving infants were born during the 6 month treatment period. Tuberculin tests were still positive in many of the treated reactors following treatment. In this epizootic, the institution of quarantine and chemotherapy instead of euthanasia resulted in significant savings.     

Chromosomal aberrations in tuberculosis patients before and after treatment with short-term chemotherapy

Cytogenetic effects of 4 common anti-tubercular drugs, isoniazid (H), streptomycin (S), rifampicin (R) and pyrazinamide (Z), in 3 different combinations (2 SHRZ, 2 HRZ and 2 H2R2Z2) were evaluated in the lymphocytes of tuberculosis patients undergoing chemotherapy, in order to estimate their mutagenic potential in combination. All 3 regimens showed an increased frequency of chromosomal aberrations after treatment compared to before treatment. These findings are of significance in the treatment of tuberculosis, as the drugs in question are observed to be mutagenic/clastogenic.     

Antituberculous Therapy in Pregnancy: Risks to the Fetus

A total of 1,939 reported births to mothers who received isoniazid ethambutol, rifampin and streptomycin alone or in combination, for all or part of their pregnancies, were surveyed to determine teratogenicity of these agents. There was no significant increase in birth defects with isoniazid, ethambutol and rifampin, in contrast to the use of streptomycin which was associated with mild auditory and vestibular defects. Guidelines for the treatment of active tuberculosis in pregnancy are therefore established.     

Standardized Treatment of Active Tuberculosis in Patients with Previous Treatment and/or with Mono-resistance to Isoniazid: A Systematic Review and Meta-analysis

Background

A standardized regimen recommended by the World Health Organization for retreatment of active tuberculosis (TB) is widely used, but treatment outcomes are suspected to be poor. We conducted a systematic review of published evidence of treatment of patients with a history of previous treatment or documented isoniazid mono-resistance.

Methods and Findings

PubMed, EMBASE, and the Cochrane Central database for clinical trials were searched for randomized trials in previously treated patients and/or those with with mono-resistance to isoniazid, published in English, French, or Spanish between 1965 and June 2008. The first two sources were also searched for cohort studies evaluating specifically the current retreatment regimen. In studies selected for inclusion, rifampin-containing regimens were used to treat patients with bacteriologically confirmed pulmonary TB, in whom bacteriologically confirmed failure and/or relapse had been reported. Pooled cumulative incidences and 95% CIs of treatment outcomes were computed with random effects meta-analyses and negative binomial regression. No randomized trials of the currently recommended retreatment regimen were identified. Only six cohort studies were identified, in which failure rates were 18%–44% in those with isoniazid resistance. In nine trials, using very different regimens in previously treated patients with mono-resistance to isoniazid, the combined failure and relapse rates ranged from 0% to over 75%. From pooled analysis of 33 trials in 1,907 patients with mono-resistance to isoniazid, lower failure, relapse, and acquired drug resistance rates were associated with longer duration of rifampin, use of streptomycin, daily therapy initially, and treatment with a greater number of effective drugs.

Conclusions

There are few published studies to support use of the current standardized retreatment regimen. Randomized trials of treatment of persons with isoniazid mono-resistance and/or a history of previous TB treatment are urgently needed. Please see later in the article for the Editors'' Summary     

Lymphatic mapping and sentinel lymph node biopsy in patients with melanoma of the lower extremity

Lymphatic mapping and sentinel lymph node biopsy is a new technique used in the surgical treatment of patients with malignant melanoma. The purpose of this study was to evaluate the results of this approach for patients with melanoma of the lower extremity. Between May of 1994 and June of 1997 at the H. Lee Moffitt Cancer Center and Research Institute, 85 consecutive patients with clinical stage I and II melanoma of the lower extremity underwent lymphatic mapping and sentinel lymph node biopsy. These nodes were identified in all 85 patients by intraoperative lymphatic mapping with both radiolymphoscintigraphy and a vital blue dye injection. Eleven patients (12.9 percent) had histologically positive sentinel lymph nodes, and 10 patients underwent inguinal complete lymph node dissections. All 10 patients had no further histologically positive lymph nodes confirmed by subsequent complete dissection. Among 74 patients with histologically negative sentinel lymph nodes, only 2 patients (2.7 percent) developed inguinal nodal metastases during a mean follow-up period of 21.8 months (range, 13.5 to 58.3 months). The sensitivity of lymphatic mapping and sentinel lymph node biopsy in this series was 100 percent and the specificity was 97.3 percent. Therefore, we conclude that the use of lymphatic mapping and sentinel lymph node biopsy can accurately stage patients with melanoma of the lower extremity and provide a rational surgical approach for these patients.     

Potentially Serious Side Effects of High-dose Twice-weekly Rifampicin

Daily rifampicin in a single dose of 600 mg, combined with other drugs, usually streptomycin and isoniazid, was given to 49 patients for three months. It was planned to continue for another 15 months with twice-weekly rifampicin 1,200 mg plus isoniazid 900 mg, but the high incidence of side effects led to cessation of the intermittent regimen when only two patients had completed 18 months.Though there was no serious problem with daily treatment 11 patients (22%) were unable to continue rifampicin on the intermittent regimen. In 8 (16%) a pyrexial syndrome occurred. In one of these patients there was also temporary renal failure, and in another precipitous thrombocytopenia led to epistaxis and bleeding into the tongue and lips. Symptomless thrombocytopenia developed in two other patients, making three cases (6%) of thrombocytopenia in all.In 16 (33%) of the 49 patients antibodies to rifampicin were detected in the blood. Side effects occurred in 9 (56%) of these, including the three developing thrombocytopenia, but in only 2 (6%) of the 33 patients with no antibodies detected. This association of toxic reactions with antibodies is highly significant (P<0·001).     

初诊腋窝淋巴结阳性乳腺癌新辅助化疗后对腋窝淋巴结转阴性前哨活检的影响分析

摘要 目的：探究对初诊腋窝淋巴结阳性乳腺癌行新辅助化疗患者开展腋窝前哨淋巴结活检的临床意义。方法：选择2017年1月至2020年10月于我院接受改良根治术或保乳术治疗的100例初诊腋窝淋巴结阳性乳腺癌患者,将其中50例病理检测II B、III期行4~8个疗程新辅助化疗后实施前哨淋巴结活检患者设为研究组,将50例I、II A期直接行前哨淋巴结活检患者设为对照组,对比两组患者前哨淋巴结检出率、准确率、假阴性率和灵敏度,同时就患者病理特征与前哨淋巴结检出率的相关性开展分析。结果：（1）比较显示研究组患者与对照组患者在前哨淋巴结检出数、前哨淋巴结检出率以及前哨淋巴结假阴性率方面组间差异不大（P>0.05）;（2）病理学特征分析显示肿瘤直径以及临床N分期同新辅助化疗后患者前哨淋巴结检出阳性率密切相关（P<0.05）。结论：对初诊腋窝淋巴结阳性行新辅助化疗乳腺癌患者实施前哨淋巴结活检具有较显示的临床意义,能够较好的预测患者腋窝淋巴结状况,同时化疗前肿瘤直径、临床N分期是影响前哨淋巴结检出率的重要影响因素。     

Sentinel lymph node biopsy after neoadjuvant chemotherapy in breast cancer

The indication of neoadjuvant chemotherapy has been recently extended; it is now applied not only in locally advanced breast cancer but in primarily resecable tumours as well, in order to promote breast conservation. Based on recent clinical results, the reconsideration of traditional lymph node dissection in axillary staging is timely in patients receiving neoadjuvant chemotherapy. Precise axillary staging needs surgical removal of lymph nodes. Based on prospective randomised trials, sentinel lymph node biopsy appears to be appropriate for axillary staging even in tumours requiring neoadjuvant treatment. The extended indication of sentinel lymph node biopsy raises several questions and problems. In the present paper the authors review the results and possible limitations of sentinel lymph node biopsy in relation to neoadjuvant chemotherapy.