Quantitative determination of characteristic components from compound of Lysionotus pauciflorus Maxim. by LC-MS/MS and its application to a pharmacokinetic study.

Tuberculosis of cervical lymph nodes is called scrofula in Traditional Chinese Medicine (TCM). Clinical manifestation is that unilateral or bilateral neck can have multiple enlarged lymph nodes of different sizes. Current therapeutic drugs include Lysionotus pauciflorus Maxim. tablets and compound of Lysionotus pauciflorus Maxim., which have a significant effect on tuberculosis of cervical lymph nodes. This compound is composed of three herbs, Lysionotus pauciflorus Maxim., Prunella vulgaris L. and Artemisia argyi Levl.et Vant. A selective and sensitive LC-MS/MS method was established and validated in rat plasma for the first time. Chromatographic separation was achieved on a Wonda Cract ODS-2 C18 Column (150 mm × 4.6 mm, 5 µm). The mobile phase contained 0.1% formic acid aqueous solution and acetonitrile with a flow rate of 0.8 mL/min. The detection was performed in negative electrospray ionization mode and the precursor/product ion transitions of six components and internal standard (IS) sulfamethoxazole were quantified in multiple reaction monitoring (MRM) using QTRAP-3200 MS/MS. The method fulfilled US Food and Drug Administration guidelines for selectivity, sensitivity, accuracy, precision, matrix effect, extraction recovery, dilution integrity, and stability. This proposed method was then successfully applied to a pharmacokinetic study after oral administration of 10 mL/kg compound extracts in rats. The pharmacokinetic parameters and plasma concentration-time profiles would prove valuable in pre-clinical and clinical investigations on the disposition of compound medicine.

Treatment outcome of extrapulmonary tuberculosis under Revised National Tuberculosis Control Programme.

BACKGROUND: Extrapulmonary tuberculosis (EPTB) constitutes 15-20% of tuberculosis cases in India. Earlier studies have evaluated treatment outcomes of EPTB with little information on outcomes of individual site of EPTB. AIMS: The objective was to study the outcome of Directly Observed Treatment Short course (DOTS) treatment of EPTB in different organ systems under Revised National Tuberculosis Control Programme. METHODS: Multi-centric retrospectives record review was carried out in three states in India. Data were collected from TB registers and analysed. RESULTS: Of the total 2219 patients studied, there were more males in age group 15-45. The commonest sites of EPTB were lymph node (34.4%) and pleural effusion (25.2%) followed by abdominal (12.8%) and central nervous system (CNS) (9.4%). Lymph node involvement was more common in females (58%) and pleural effusion in males (70%). Overall treatment completion rate was 84% in EPTB patients. Treatment completion was 86% in HIV negative EPTB patients compared to 66% in HIV positive patients. Individually, treatment completion rate observed as follows: lymph node 90.9%, genitourinary 92.6%, bone and joint 86%, pleural effusion 84.7%, abdominal 76% and CNS (tuberculoma and meningitis) 63.7%. The site of EPTB was not recorded in 173 (7.8%) patients. CONCLUSION: Treatment outcome of EPTB was poor in HIV infected patients and those with CNS tuberculosis. More efforts are needed to improve the treatment completion rates in these groups of patients.

Paradoxical reaction associated with cervical lymph node tuberculosis: predictive factors and therapeutic management.

OBJECTIVES: The aims of this study were to determine predictive factors of paradoxical reaction in patients with cervical lymph node tuberculosis (TB) and to discuss the therapeutic management of this condition. MATERIALS AND METHODS: A retrospective study was performed of 501 patients managed for cervical lymph node TB over a period of 12 years (from January 2000 to December 2011). Statistical data were analyzed using IBM SPSS Statistics version 20.0. RESULTS: Paradoxical reaction occurred in 67 patients (13.4%), with a median delay to onset after starting TB treatment of 7 months. Lymph node size ≥3cm and associated extra-lymph node TB were independently associated with paradoxical reaction. Treatment consisted of surgical excision (71.6%), restarting quadruple therapy (10.4%), reintroduction of ethambutol (23.8%), and addition of ciprofloxacin (20.8%); steroids were given in two cases . All patients recovered after an average treatment duration of 14.91±7.03 months. CONCLUSION: The occurrence of paradoxical reaction in cervical lymph node TB seems to be predicted by associated extra-lymph node TB and a swelling size ≥3cm. The treatment of paradoxical reaction remains unclear and more randomized trials are necessary to improve its management.

Homeopathy in the treatment of tubercular lymphadenitis (TBLN)--an Indian experience.

Tuberculosis (TB) has been known since antiquity. In spite of effective antibiotic treatment, it is still a major worldwide public health problem. Endogenous factors are important in the development of active disease. Homeopathic medicines have the potential for immune-modulation and hence to influence endogenous factors in disease. In India, patients with tubercular lymphadenitis (TBLN) often consult homeopaths but such cases are seldom documented. The objective of the present study is to document such experience. A retrospective exploratory study of 25 positively diagnosed cases of TBLN has lead to the development of a homeopathic regime consisting of a patient specific constitutional medicine, one disease specific biotherapy (Tuberculinum) and Silicea 6x as supportive medicine. Homeopathy can be used as a complement to conventional anti tubercular treatment (ATT) with beneficial results. Further validation in controlled trials with immunological markers is required.

Knowledge of cervical tuberculosis lymphadenitis and its treatment in pastoral communities of the Afar region, Ethiopia.

BACKGROUND: Infection with Mycobacterium bovis (Mb) predominantly causes cervical TB lymphadenitis (TBL). Raw milk is considered the main source of Mb infection and raw milk is a major food source for Afar pastoralists. The aim of this study was to assess Afar pastoralists' knowledge concerning cervical TBL and its treatment. METHODS: A community-based cross-sectional survey involving 818 interviewees was conducted in two districts of the Afar Region, Ethiopia. In addition, two focus group discussions (FGDs) were conducted in each of the study areas, one with men and the other with women. RESULTS: Of the 818 interviewees [357 (43.6%) females and 461 (56.4%) males], 742 (90.7%) reported that they had knowledge of cervical TBL, mentioning that swelling(s) on the neck resulting in a lesion and scar are common symptoms. However, only 11 (1.5%) individuals mentioned that bacteria or germs are the causative agents of TBL. Three interviewees and a male discussant mentioned drinking raw milk as the cause of TBL. A considerable proportion (34.2%) of the interviewees and almost all the discussants suggested herbal medicine as an effective treatment. Male study participants were 1.82 times more likely to have overall knowledge of TBL than female study participants (adjusted OR, 1.82; 95% CI, 1.32 to 2.51, p < 0.001). CONCLUSION: The pastoral community members in the study areas had little biomedical knowledge of the cause, the source of infection and the transmission route of cervical TBL. Furthermore, most community members believed that herbal medicines are the most effective treatment for TBL. Therefore, TB control programs in the Afar Region require the incorporation of public health education introducing current biomedical knowledge of the disease. In addition, further studies are important to elucidate which medicinal plants are used by Afar pastoralists to treat TBL.

Randomized, double-blind study on role of low level nitrogen laser therapy in treatment failure tubercular lymphadenopathy, sinuses and cold abscess.

BACKGROUND: Effectiveness of low level nitrogen laser therapy along with antitubercular treatment (ATT) in cases of treatment failure and drug resistant tubercular lymphadenopathy, sinuses and cold abscess. METHODS: In a double-blind randomized controlled trial of LLLT, 104 patients assigned to either the low level nitrogen laser therapy along with ATT (LLLT group) (n = 54) or ATT only (Chemotherapy group) (n = 50). Both groups were treated two times per week for five weeks. Those in the treatment group received pulse nitrogen laser with a pulse duration of seven nanosecond, wave length 337 nanometer and average power output of 5 mW whereas those in the control group were treated with sham laser. The primary outcome measure was bacteriological conversion and the secondary outcome measures were decrease in size of lesion and the clinical improvement. RESULTS: Acid Fast Bacilli (AFB) smear, AFB culture and Polymerase Chain Reaction (PCR) conversion rate at five weeks (after 10 sittings of laser) were 49.15%( Fishers P exact test-p = 0.015), 60%, 44.44% (Fishers P exact test-p = 0.048) in LLLT group as compared to 11.86%, 20%,17.77% in chemotherapy group. Average percentage reduction in the size of gland at 5 weeks was 70.67% (p value 0.01) as compared to 54.81 in chemotherapy group. Average time taken for closure of sinuses was 11.03 weeks in LLLT group as compared to 26 weeks in chemotherapy group. The follow up was conducted for two years. CONCLUSION: Low level nitrogen laser therapy can be used as an adjunctive therapy along with antitubercular drugs in cases not responding and drug resistant tubercular lymphadenopathy, sinuses and cold abscess.

A clinical dilemma: abdominal tuberculosis.

AIM: To evaluate the clinical, radiological and microbiological properties of abdominal tuberculosis (TB) and to discuss methods needed to get the diagnosis. METHODS: Thirty-one patients diagnosed as abdominal TB between March 1998 and December 2001 at the Gastroenterology Department of Kartal State Hospital, Istanbul, Turkey were evaluated prospectively. Complete physical examination, medical and family history, blood count erythrocyte sedimentation rate, routine biochemical tests, Mantoux skin test, chest X-ray and abdominal ultrasonography (USG) were performed in all cases, whereas microbiological examination of ascites, upper gastrointestinal endoscopy, colonoscopy or barium enema, abdominal tomography, mediastinoscopy, laparoscopy or laparotomy were done when needed. RESULTS: The median age of patients (14 females,17 males) was 34.2 years (range 15-65 years). The most frequent symptoms were abdominal pain and weight loss. Eleven patients had active pulmonary TB. The most common abdominal USG findings were ascites and hepatomegaly. Ascitic fluid analysis performed in 13 patients was found to be exudative and acid resistant bacilli were present in smear and cultured only in one patient with BacTec (3.2 %). Upper gastrointestinal endoscopy yielded nonspecific findings in 16 patients. Colonoscopy performed in 20 patients showed ulcers in 9 (45 %), nodules in 2 (10 %) and, stricture, polypoid lesions, granulomatous findings in terminal ileum and rectal fistula each in one patient (5 %). Laparoscopy on 4 patients showed dilated bowel loops, thickening in the mesentery, multiple ulcers and tubercles on the peritoneum. Patients with abdominal TB were divided into three groups according to the type of involvement. Fifteen patients (48 %) had intestinal TB, 11 patients (35.2 %) had tuberculous peritonitis and 5 (16.8 %) tuberculous lymphadenitis. The diagnosis of abdominal TB was confirmed microbiologically in 5 (16 %) and histo-pathologically in 19 patients (60.8 %). The remaining nine patients (28.8 %) had been diagnosed by a positive response to antituberculous treatment. CONCLUSION: Neither clinical signs, laboratory, radiological and endoscopic methods nor bacteriological and histopathological findings provide a gold standard by themselves in the diagnosis of abdominal TB. However, an algorithm of these diagnostic methods leads to considerably higher precision in the diagnosis of this insidious disease which primarily necessitate a clinical awareness of this serious health problem.

Surgical treatment of bacillus Calmette Guérin lymphadenitis.

Although its protective effect is contested and the risk of contracting tuberculosis is rather low nowadays, BCG vaccination is frequently performed. Changes of strain repeatedly led to an increased complication rate. In Austria between 1990 and 1991, of 3386 newborn babies (Strain Pasteur) 116 developed lymphadenitis 3 to 28 weeks after vaccination. The affected children received four types of treatment: nothing specific, isoniazid, or surgery with and without isoniazid. Surgical treatment was found to be necessary in 96 cases. Bacilli were successfully grown in culture in 46% of cases up to week 20 after vaccination; but later than 20 weeks no culture became positive. All cultured bacteria were isoniazid-sensitive. From our data we drew the following conclusions: isoniazid therapy did not prove successful when inflamed lymph nodes exceeded a certain size. Suppurative lymphadenitis in lymph nodes exceeding 1.0 to 1.5 cm usually led to infiltration or even perforation of the skin. Surgery prevents these complications and significantly reduces healing time. Adjuvant isoniazid therapy cannot be recommended, except for generalized BCG tuberculosis.

[Study on TCM treatment of 210 scrofulous sinus patients].

210 cases of scrofulous sinus has been reported. Baluodan (BLD) has removed necrotic tissue and promote the granulation. It had potent inhibition on TB with no side effect in animal experiments and clinical trials. The total effective rate was 98.57%. The average of treatment course was 39.0 +/- 13.7 days. Follow-up for 2-4 years showed 3 cases had recurrence (1.4%). Its advantages were high effective rate, short curative course, low recurrence rate, with convenient in administration, and easy to spread.

Hepatotoxicity associated with acetaminophen usage in patients receiving multiple drug therapy for tuberculosis.

We report three patients who experienced hepatotoxic reactions in association with acetaminophen ingestion while undergoing treatment for active tuberculosis with isoniazid, rifampin, and other agents. All were young adult women. One patient intentionally took a large amount of acetaminophen and had typical signs and symptoms of acetaminophen overdosage; another took acetaminophen in combination form for a minor upper respiratory illness. She experienced no symptoms. The remaining patient took acetaminophen to ameliorate the symptoms of fever and malaise that were subsequently attributed to tuberculosis. She had the rapid onset of signs and symptoms of isoniazid hepatotoxicity. The patterns of liver function abnormalities were similar: each patient experienced pronounced serum elevations of hepatocellular enzymes with at most only modest rises in those of bilirubin. All antituberculous drugs were withheld until symptoms resolved and laboratory values became normal; then treatment for tuberculosis was resumed without isoniazid and was successfully completed in all three patients. These cases plus similar reports in the literature suggest that isoniazid or rifampin, or both, may potentiate the hepatotoxicity of acetaminophen, perhaps by induction of cytochrome P450 isozymes that oxidize acetaminophen to its toxic metabolites.