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PubMed2006

Penile tuberculosis associated with monoclonal gammopathy of undetermined significance.

Mycobacterium tuberculosis (TB) infection of the penis is a rare but serious problem. We report a case of penile TB in a 75-year-old man who presented with fever and dyspnea. No active lung lesions except pleural and pericardial effusion were found on chest X-ray. Monoclonal gammopathy of undetermined significance was diagnosed after serum and urine electrophoresis studies, and repeated bone marrow studies. Genital examination showed diffuse papulonecrotic skin ulcers involving the whole penile shaft, extending ventrally to the median raphe of the scrotum. Pus smear showed positive acid-fast stain, and culture yielded M. tuberculosis. Culture of pleural and pericardial effusion was also positive for M. tuberculosis. Anti-TB treatment was given with isoniazid, ethambutol, rifampin and pyrazinamide, and the cutaneous lesion was noted to be healed at follow-up 6 months later. Although rare, the possibility of TB as a cause of genital ulcer should be kept in mind.

Aged↗
PubMed1991

Drug-induced gout.

A number of pharmacological agents can induce hyperuricaemia, and sometimes gout, usually by interfering with the renal tubular excretion of urate but also in some instances by increasing the formation of uric acid. Alcohol is well known to have this property and in recent years diuretic-induced hyperuricaemia has become a global phenomenon. Other drugs which can cause hyperuricaemia are salicylates, pyrazinamide, ethambutol, nicotinic acid, cyclosporin, 2-ethylamino-1,3,4-thiadiazole, fructose and cytotoxic agents. A special type of 'drug-induced gout' can follow the rapid lowering of serum uric acid by allopurinol or uricosuric drugs.

Cyclosporins↗
PubMed1993

Six months versus nine months chemotherapy for tuberculosis of lymph nodes: final results.

Of 199 patients treated for peripheral lymph node tuberculosis, 157 completed treatment as planned. Fifty received E2H9R9, 56 Z2 H9R9 and 51 Z2H6R6 regimens (E = Ethambutol; H = Isoniazid; R = Rifampicin; Z = pyrazinamide: numbers denote duration of therapy in months). In follow-up from 9 to 30 months, there were no significant differences between the regimens in enlargement of existing nodes, development of new glands or sinuses, in the need for new operative procedures, or in the percentage with measurable nodes at 30 months. Nine patients were felt to have had a clinical relapse (4 E2H9R9; 2 Z2H9R9; 3 Z2H6R6) although this was not confirmed bacteriologically in the five cases where material was sent for culture. These differences were not statistically different. The 6 month Z2H6R6 regimen performs just as well as the 9 month regimens Z2H9R9 and E2H9R9 in patients with fully sensitive organisms, and has the additional benefits of convenience and reduced cost.

Adolescent↗
PubMed1991

Short course chemotherapy for pulmonary tuberculosis.

A retrospective survey of the treatment of culture positive pulmonary tuberculosis with a standard 6-month course of unsupervised therapy, comprising rifampicin and isoniazid daily for 6 months with pyrazinamide for the first 8 weeks is reported. Of the 164 patients who commenced this regimen, 110 completed therapy as planned. There were five relapses, three of whom admitted significant non-compliance, giving a relapse rate of 4.59% (95% confidence interval, 1.49-10.7). The regimen gives satisfactory results in routine unsupervised treatment.

Adolescent↗
PubMed1998

The management of pulmonary tuberculosis in adults notified in Scotland in 1993.

The management of pulmonary tuberculosis (TB) in Scotland in 1993 was studied by asking the physicians responsible for all 321 adult cases of the disease notified that year to complete a standardized questionnaire relating to drug treatment and bacteriology. The response rate to the questionnaire was 100%. Isoniazid and rifampicin were used together in initial therapy in 98.4% of cases, while pyrazinamide was prescribed in 90.3% of cases, broadly in keeping with existing treatment guidelines. However, considerable variability was observed both in the drug regimens employed, and in the duration of initial and continuation phases of chemotherapy. Treatment regimens were therefore frequently at variance with published recommendations. Among patients prescribed drug regimens other than those recommended satisfactory completion of therapy was less common. Microbiological confirmation was provided for 84% of cases in which clinical samples were submitted. However, in approximately 11% of cases, no clinical samples were submitted. Closer adherence to existing treatment guidelines and more rigorous pursuit of microbiological confirmation should further improve the overall management of pulmonary TB in Scotland.

Adolescent↗
PubMed1996

Short-course therapy of pulmonary tuberculosis: doctor's compliance.

OBJECTIVE: The present study, conducted from 1986 to 1991, investigated the accuracy of treatment monitoring performed by practitioners in the out-patient treatment of pulmonary tuberculosis. DESIGN: All patients with smear or culture positive pulmonary tuberculosis, receiving 6-month short-course chemotherapy with Isoniazid (H), Rifampicin (R) and Pyrazinamide (Z), were included. Treatment had been initiated either in our unit, or shortly before, with discharge after an average time of 8 weeks. Practitioners were sent a flow sheet advising how to perform standardized ambulatory controls. RESULTS: Forty-three patients were included in the study, four of whom did not visit their practitioner after discharge. It must be assumed that they did not complete treatment. The average follow-up time of the remaining 39 patients was 159 weeks. In 13 cases the treatment was prolonged without obvious reason. For four patients who had not converted to a negative sputum culture at discharge, negativity was never been proven thereafter. Objective means of assessing patient compliance by H-urine strip testing were undertaken only in three cases. X-ray controls were performed adequately in 44.4% of the cases. By contrast monthly checks of liver enzymes had been done only in 23.1% of the patients. CONCLUSION: We conclude that even a highly standardized protocol of short-course tuberculosis treatment requires a certain level of experience and compliance on the part of the practitioner. We accordingly recommend that every case of pulmonary tuberculosis should be reviewed at least twice by a chest physician.

Adult↗
PubMed2000

Surface-enhanced raman spectra of some anti-tubercle bacillus drugs.

Surface-enhance Raman (SER) spectra of pyrazinamide (PZA), isoniazid (INAZ), and isonicotiamide (INCT) in silver sols have been studied over a range of solution concentration and pH. A linear calibration curve has been obtained for each of the sample molecules, and the lower limits of detection are estimated to be 5 ng for PZA and INAZ, and 10 ng for INCA. The variation of SER intensity with the sample solution pH is explained in terms of the charge of the sample species and the stability of the sols. The normal Raman and infrared spectra for the pure drug samples have also been collected, from which some vibration assignments for the molecules are given. The absorption behaviors of the molecules on the silver particle surfaces are also suggested.

Antitubercular Agents↗
PubMed2002

Long-term follow up of childhood tuberculous meningitis.

The purpose of the present study was to determine the long-term outcome of 76 children (40 females and 36 males) diagnosed and treated with modern antituberculosis drugs. The median age of the children on admission was 29.5 months and on follow-up 9 years. Antituberculosis therapy consisted of daily isoniazid (20 mg/kg), rifampicin (20 mg/kg), ethionamide (20 mg/kg), and pyrazinamide (40 mg/kg) for 6 months. Twenty-three children received daily prednisone (2-4 mg/kg) for the first month of treatment. Raised intracranial pressure was actively monitored and treated. Patients with non-communicating hydrocephalus received ventriculo-peritoneal shunts shortly after admission while communicating hydrocephalus was treated with oral acetazolamide (100 mg/kg/day) and furosemide (1 mg/kg/day) in 3-4 divided doses. Communicating hydrocephalus that did not respond to this regimen within the first month of treatment also underwent ventriculo-peritoneal shunting. Only 20% of children were functionally completely normal at follow-up. Main areas of functional deficit were cognitive impairment (80%), poor scholastic progress (43%), and emotional disturbance (40%). Twenty-five per cent of children had evidence of motor impairment, but all could walk and only 5 of 76 children (6% of total) were unable to run. One child was blind but no child had sensori-neural deafness. It was concluded that these disabilities in children from mainly deprived socioeconomic backgrounds have serious implications for their future social, academic, and career prospects. A high index of suspicion of TBM in high tuberculosis incidence communities will help prevent the morbidity documented in this study.

Acetazolamide↗
PubMed1982

Subdivision of Mycobacterium tuberculosis into five variants for epidemiological purposes: methods and nomenclature.

Virulent strains of Mycobacterium tuberculosis isolated from humans are divisible into five variants by using four tests: oxygen requirement (aerobic or microaerophilic), nitrate reductase activity, susceptibility to pyrazinamide (60 micrograms/ml) and susceptibility to thiophene-2-carboxylic acid hydrazide (5 micrograms/ml). The five variants are referred to as Classical human, Asian human, bovine, African I and African II. The relation of these variants to previously described types is discussed. This simple division has been shown to be useful in epidemiological studies.

Humans↗
PubMed2000

Molecular characterization of pncA gene mutations in Mycobacterium tuberculosis clinical isolates from China.

A sample of 35 pyrazinamide (PZA)-resistant and 30 PZA-susceptible clinical isolates recovered from Beijing and Taiyuan City, China were characterized by SSCP and sequence analysis for mutations in the pncA gene that encodes the Mycobacterium tuberculosis PZase. The purpose of this study was to understand the molecular basis and the characteristics of pncA gene mutations and its relation to PZA resistance in M. tuberculosis strains from China. Several mutations with base changes leading to amino acid substitutions were found in the PZA-resistant isolates. No mutations were seen in the 243 PZA-susceptible isolates. Among the 35 PZA-resistant isolates, 32 isolates (91.4%) had nucleotide substitutions, insertions and deletions that resulted in amino-acid substitution; or frameshifts in some strains. Other previously uncharacterized mutations were found as follows: Asn118->Thr, CG insertion at position 501; CC insertion at nucleotide position 403; a 8 base-pair deletion at start codon; Pro54->Thr; AG insertion at 368; Tyr41->His, Ser88->stop, and A insertion at nucleotide position 301. IS6110 subtyping revealed that each strain was unique; indicative of the epidemiologic independence of the isolates.

Adolescent↗
PubMed1996

Drug diffusion through cystic fibrotic mucus: steady-state permeation, rheologic properties, and glycoprotein morphology.

One manifestation of cystic fibrosis (CF) is the presence of a viscid mucus secretion in the lungs. The clearance of this mucus is significantly slower than in "normals" due to uncoordinated beating of the cilia and the increased viscosity of the mucus. In these studies, the permeabilities of p-aminosalicylic acid, isoniazid, and pyrazinamide through unpurified CF respiratory mucus and through purified pig gastric mucus solutions were compared in order to evaluate the relative barrier properties of these mucus solutions. These model compounds, while not often used clinically in CF, are used in other pulmonary diseases and have the potential to be administered by inhalation delivery systems. Permeability studies were carried out in Side-Bi-Side diffusion cells fitted with a custom membrane holder capable of retaining the mucus solutions. Permeabilities through CF mucus solution and its fractions were compared to those measured through buffer and reconstituted purified pig gastric mucus. There were 28--75% decreases in drug permeability when pig gastric mucus was replaced by different CF mucus solutions. This indicates that optimal drug delivery directly to the lungs must take into account the decreased drug transport rate across diseased mucus in addition to drug loss due to binding to the glycoproteins or inefficient delivery via aerosolization. Transmission electron microscopy revealed minor differences in the glycoprotein strand structure between reconstituted pig gastric mucus and CF mucus primarily with regard to glycoprotein chain length and extent of branching. Similar viscoelastic behaviors between the CF gel fraction and synthetic CF mucus were observed. This model CF mucus system can simulate diseased mucus and can be utilized for in vitro studies to optimize drug permeability.

Aminosalicylic Acid↗
PubMed1992

Single kidney function: early and late changes in urate transport after nephrectomy.

Renal urate transport was studied by means of pyrazinamide (PZA) and probenecid (PB): (a) before and at 2, 6, 24 weeks (24 patients), (b) 1 to 30 years after uninephrectomy in 27 and 12 patients with Ccr greater than 80 and 30 to 70 ml/min, respectively. Uninephrectomy was followed by important tubular urate transport modifications during at least two weeks, which lead to a marked uricosuria as indicated by significant increase in FEur (mean value +/- SD, 0.228 +/- 0.059 vs. 0.097 +/- 0.014 and 0.099 +/- 0.019 in normals and chronically diseased solitary kidneys). Reduced response to PZA and PB suggests a diminished reabsorptive capacity for urate mainly at the presecretory site which persisted after FENa normalization. Tubular compensations were presumably complete at six weeks, since pattern of urate transport returned to normal with an almost complete reabsorption of filtered urate load (99%) and a percentage of postsecretory reabsorption (80%) very close to those seen in normal subjects with a pair of kidneys. The adjustment in urate excretion in solitary kidneys was achieved by a significant increase of secreted urate as compared with 50% of pre-uninephrectomy values. Thus, increased urate secretion by the remaining intact organ is sufficient to maintain urate balance with a normal serum level.

Adult↗
PubMed1976

Effect of vasopressin on uric acid excretion: evidence for distal nephron reabsorption of urate in man.

1. When changes in urine flow rate were induced by vasopressin administration in eight subjects, urate excretion decreased by a mean of 14% and was positively correlated with urine flow rate (r = 0.88, P less than 0.01). The effect of vasopressin on urate excretion was not influenced by prior changes in extracellular fluid volume. 2. Mannitol administration in a dose sufficient to prevent vasopressin-induced alterations in urine flow rate blocked the effect of vasopressin on urate excretion. 3. Alterations in urate excretion produced by changes in extracellular fluid volume could be distinguished from the urate-retaining effect of vasopressin-mediated decrease in urine flow. Urate retention after vasopressin was entirely attributed to a decrease in pyrazinamide-suppressible urate excretion, consistent with either decreased secretion or enhanced post-secretory reabsorption of urate. 4. Since diminished urine flow rate in the distal part of the nephron is more likely to lead to enhanced reabsorption of urate, these results provide additional evidence for urate reabsorption in the distal part of the nephron.

Adult↗
PubMed2002

Erythema nodosum associated with reactivation tuberculous lymphadenitis (scrofula).

A 73-year-old African American female presented to our clinic with painful lower extremity lesions of 2 weeks duration. She was in her usual state of health until 3 months prior to presentation when she reported symptoms of fatigue and weakness. She also noticed an enlarging mass on the left side of her neck. She denied fevers, chills, night sweats or cough. Her symptoms were unresponsive to a course of oral dicloxacillin. The neck mass enlarged over 8 weeks and she was referred to our institution for evaluation. CT scan of the neck showed an enlarged lymph node. Ten days prior to her presentation in dermatology, a fine needle aspirate of the enlarging lymph node revealed necrotizing granulomas. Tissue was sent for routine mycobacterial and fungal cultures. Routine blood work, chest radiograph, and a tuberculin skin test were also performed. At the time of her dermatology visit she described the development of multiple new painful, non-pruritic lesions, bilaterally on the lower extremities. She also reported a red crusted area that appeared at the site of her tuberculin test that was placed subsequent to the development of her lower extremity lesions. Her past medical history was significant for Parkinson's disease, hypothyroidism and hypertension. Her current medications included l-thyroxine, estrogen and diltiazem. Her travel history was only remarkable for a trip to Jamaica the previous spring. She was born and raised in Haiti. She reported a history of a positive tuberculin skin test 20 years ago, but received no therapy. Physical examination revealed a 2 x 3 centimeter firm, nontender left lateral neck mass (Fig. 1). Her right forearm revealed an erythematous, ulcerated, indurated plaque 1.5 cm in diameter (Fig. 2.). Her lower extremities revealed tender 0.5 to 1 cm erythematous nodules below the knees bilaterally (Fig. 3). A punch biopsy of a lower extremity nodule revealed a mild pervisacular dermal infiltrate. Within the subcutaneous tissue there was septal widening. There was also a lymphohistiocytic infiltrate with a slight admixture of neutrophils within the septa of the fat lobules. There was no evidence of necrotizing vasculitis or collagen necrosis. An acid-fast stain was not performed. The histologic findings were consistent with a diagnosis of erythema nodosum. Her laboratory evaluation including CBC, electrolytes, thyroid studies, angiotensin converting enzyme level and chest radiograph were normal. Approximately 1 week after her dermatological evaluation, the fine-needle aspirate culture grew Mycobacterium tuberculosis. A diagnosis of tuberculous lymphadenitis associated with erythema nodosum was confirmed. The patient was started on quadruple therapy of isoniazid, rifampin, ethambutol and pyrazinamide. Her lower limb skins lesions rapidly resolved over the subsequent month and her neck mass also diminished in size. She completed 6 months of antituberculous therapy with complete resolution of her lymphadenopathy.

Aged↗
PubMedDate not supplied

Nodular tuberculid: a report of four patients.

The tuberculids are hypersensitivity reactions to Mycobacterium tuberculosis (MTB) and include papulonecrotic tuberculid (PNT), lichen scrofulosorum, erythema induratum of Bazin (EIB), and phlebitic tuberculid. Papulonecrotic tuberculid displays papulonecrotic lesions mostly on the extensor surfaces of the limbs. Histopathology shows necrosis, granulomatous inflammation (GI), and occasionally vasculitis, usually in the superficial dermis. Erythema induratum of Bazin shows nodulo-ulcerative lesions on the posterior aspect of the legs. Histopathology reveals a septolobular panniculitis, necrosis, GI, and vasculitis. The Mantoux test is strongly positive and associated tuberculosis (TB) may be present in both conditions. MTB cannot be demonstrated with a Ziehl-Neelsen (ZN) stain or cultured. The polymerase chain reaction has demonstrated MTB DNA in PNT (50%) and EIB (25%). The tuberculids respond to full anti-TB treatment. We document four patients with nodules on the legs in whom the pathologic changes were situated in the deep dermis and adjacent subcutaneous fat. Nodular tuberculid (NT) is regarded as a suitable term for these lesions. All patients were female. Their ages were 19 months, 12 years, 17 years, and 5 years. All patients presented with nodules on the limbs. These nodules were approximately 1 cm in diameter, dull red or bluish-red, and nontender. Ulceration was not present. The number of nodules varied from a few to many. The Mantoux test was strongly positive in all the patients. Associated pulmonary TB was present in two patients. Histopathology showed GI (n = 4), vasculitis (n = 2), and coagulative necrosis (n = 2). A ZN stain was negative in each case. All patients received anti-TB treatment for 6 months [rifampicin (n = 4), isoniazid (n = 4), pyrazinamide (n = 4), and ethambutol (n = 2)]. At 12 months follow-up, skin and pulmonary lesions had resolved in all. Nodular tuberculid should be distinguished from arthropod bites and papular urticaria, dermal erythema multiforme, evolving vasculitis, evolving folliculitis, and erythema nodosum. Histopathologically NT should be distinguished from other causes of granulomatous vasculitis and GI with or without necrosis. In children with nodules on the limbs unresponsive to routine treatment, skin biopsy should be done to exclude NT. Nodular tuberculid represents a hybrid between PNT and EIB with characteristic clinicopathologic features and should be included in the classification of cutaneous TB.

Adolescent↗
PubMed1998

Molecular genetic basis of antimicrobial agent resistance in Mycobacterium tuberculosis: 1998 update.

Knowledge of the molecular genetic basis of resistance to antituberculous agents has advanced rapidly since we reviewed this topic 3 years ago. Virtually all isolates resistant to rifampin and related rifamycins have a mutation that alters the sequence of a 27-amino-acid region of the beta subunit of ribonucleic acid (RNA) polymerase. Resistance to isoniazid (INH) is more complex. Many resistant organisms have mutations in the katG gene encoding catalase-peroxidase that result in altered enzyme structure. These structural changes apparently result in decreased conversion of INH to a biologically active form. Some INH-resistant organisms also have mutations in the inhA locus or a recently characterized gene (kasA) encoding a beta-ketoacyl-acyl carrier protein synthase. Streptomycin resistance is due mainly to mutations in the 16S rRNA gene or the rpsL gene encoding ribosomal protein S12. Resistance to pyrazinamide in the great majority of organisms is caused by mutations in the gene (pncA) encoding pyrazinamidase that result in diminished enzyme activity. Ethambutol resistance in approximately 60% of organisms is due to amino acid replacements at position 306 of an arabinosyltransferase encoded by the embB gene. Amino acid changes in the A subunit of deoxyribonucleic acid gyrase cause fluoroquinolone resistance in most organisms. Kanamycin resistance is due to nucleotide substitutions in the rrs gene encoding 16S rRNA. Multidrug resistant strains arise by sequential accumulation of resistance mutations for individual drugs. Limited evidence exists indicating that some drug resistant strains with mutations that severely alter catalase-peroxidase activity are less virulent in animal models. A diverse array of strategies is available to assist in rapid detection of drug resistance-associated gene mutations. Although remarkable advances have been made, much remains to be learned about the molecular genetic basis of drug resistance in Mycobacterium tuberculosis. It is reasonable to believe that development of new therapeutics based on knowledge obtained from the study of the molecular mechanisms of resistance will occur.

Anti-Bacterial Agents↗
PubMed2005

[Procedure in case of suspected mycobacterial infection of lymph nodes of the neck. 2. Therapy].

In the treatment of tuberculosis the patients normally receive a two month daily treatment with Isoniazid, Rifampicin, Pyrazinamid and Ethambutol, followed by a daily treatment with Isoniazid and Rifampicin for four month. The atypical mycobacterial infections can be addressed as a local infection and are amendable to surgical therapy, eventually followed by a daily treatment with antibiotics for four to twelve weeks. In Germany it is obligatory to inform the local public health department about typical mycobacterial infections. Hygiene procedures following German law are discussed in this review.

Adult↗
PubMed1994

[Esophagomediastinal fistulae as a rare complication of tuberculosis in an HIV-infected patient].

A 57-year-old man with an HIV infection, diagnosed a year ago, complained of fever and cough. The haemoglobin level was 7.5 g/dl, white cell count 3800/microliters, T-helper cell count 60/microliters and the CD4-CD8 ratio 0.1. Erythrocyte sedimentation rate was raised to 21/39 mm. Bacteriological tests were at first negative. The chest radiograph showed slight widening of the upper mediastinum which further increased over the next 10 days, at which time it also revealed a shadow in the right upper lobe. Computed tomography suggested necrotizing mediastinal lymph-nodes. Treatment was begun with rifampicin (600 mg daily) ethambutol (1.2 g daily), pyrazinamide (1.5 g daily) and ciprofloxacin (500 mg twice daily). Oesophagoduodenoscopy, performed after 3 weeks, revealed several fistulae which, after ingestion of contrast medium, were demonstrated to communicate with the mediastinum, presumably as a result of lymph-node liquefaction. Mycobacterium tuberculosis was demonstrated in gastric juice, sputum and stool only after tuberculostatic drugs had been started.

AIDS-Related Opportunistic Infections↗