Multidrug-resistant tuberculosis. 5. Human immunodeficiency virus infection and multidrug-resistant tuberculosis

Outbreaks of multidrug-resistant tuberculosis (MDR-TB) among human immunodeficiency virus (HIV)-infected persons reported in the United States were very serious and the risks were increased by the delay of diagnosis, rapid progression from infection to active disease, inadequate therapy and poor tuberculosis (TB) control. Prevalence of drug-resistant TB among HIV-infected patients in Japan was studied. The results of drug susceptibility were collected through the nationwide working group for a survey of HIV-infected TB. Data of susceptibility for 39 cases were obtained. The isolates of two cases were resistant to isoniazid and rifampicin (including clinical failure of response), although no outbreak of MDR-TB was found in Japan. Case study of a patient who developed MDR-TB revealed that drug resistance might be selected by insufficient anti-TB therapy. The rate of resistance to any of the anti-TB drugs in HIV-infected patients seemed to be high, although strictly evaluation was difficult due to no standardization for drug susceptibility testing. Of 9 cases with resistance to any of the anti-TB drugs, 8 had extrapulmonary TB including 5 cases of disseminated TB. In contrast thirteen of 30 cases without drug resistance had extrapulmonary TB. Since it has been reported that HIV infection is related to increased rates of drug resistance of TB bacilli, treatment with four-drug regimen should be started and sufficient courses of therapy are needed in HIV-infected TB patients.     

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.     

Therapeutic strategies for patients with tuberculosis

OBJECTIVES: To determine the effectiveness of strategies used to promote adherence to anti-tuberculosis treatment. SEARCH STRATEGY: MEDLINE 1966-1996 (August), Cochrane Collaboration Trials Registers (October 1996), LILACS 1982-1996 (September); reference lists in articles on adherence, contact with experts in the fields of TB and adherence research. SELECTION CRITERIA: Randomised or pseudo-randomised controlled trials of interventions to promote compliance with curative or preventive chemotherapy for TB, with at least one measure of adherence. DATA COLLECTION AND ANALYSIS: Data on study methods, participants, interventions and outcomes were collected for each study and methodological quality was assessed. Estimates of effect were assessed for categorical outcomes using the Peto odds ratio, with 95% confidence intervals. MAIN RESULTS: Strategies found to be of benefit were reminder cards sent to defaulters, assistance of patients by lay health workers, monetary incentives offered to patients, and increased supervision of TB clinic staff. It is not possible to determine from current trials whether health education by itself leads to better adherence to treatment. Even though directly-observed therapy (DOT) is widely advocated as the most cost-effective means of ensuring completion of TB treatment, no completed trials could be found which confirm or refute this view. CONCLUSIONS: RCT evidence exists that certain strategies improve adherence to anti-tuberculous therapy, and these should be adopted into clinical practice depending on their appropriateness to practice circumstances. Further innovations should be tested to find solutions that will be useful in low income countries. Randomised trials evaluating the independent effects of directly-observed therapy (DOT) are awaited.     

Clinical features and outcome in disseminated mycobacterial diseases in AIDS patients in Taiwan

OBJECTIVE: To describe and compare the clinical features and outcome of disseminated tuberculosis (TB) and Mycobacterium avium complex (MAC) disease in AIDS patients. DESIGN: Prospective cohort study. SETTING: A 1800-bed university teaching hospital, the largest centre for HIV/AIDS patients in Taiwan. METHODS: From July 1994 through June 1997, a standardized protocol was used to record the demographic and clinical features in all hospitalized HIV-infected patients, and to perform routine studies and invasive procedures for diagnosis of disseminated mycobacterial diseases. To compare the survival, control patients were selected from the HIV-infected patients hospitalized in the same hospital during the same study period, and had similar age, sex, CD4+ cell counts and antiretroviral therapy regimens. RESULTS: A total of 22 cases of disseminated TB and 15 cases of disseminated MAC were identified. Disseminated TB and MAC occurred in patients with similarly low CD4+ cell counts (median, 23 versus 5 x 10(6)/l; P = 0.08). The clinical features favouring disseminated TB included night sweats, peripheral lymphadenopathy, acid-fast bacilli in sputum smears, chest radiographic findings of hilar enlargement, and lack of prior AIDS-defining illnesses. Hepatosplenomegaly, elevated serum alkaline phosphatase (more than twice the upper limit of normal), elevated serum gamma-glutamyl transpeptidase (more than three times the upper limit of normal), and leukopenia favoured disseminated MAC. The patients with disseminated TB survived much longer than patients with disseminated MAC (mean survival, 96 versus 22 weeks, P = 0.008) but had a similar outcome to control patients (P = 0.60). CONCLUSION: Disseminated TB and MAC are distinguishable by clinical features in AIDS patients with similar immunocompromised states. Those features may facilitate diagnosis and selection of specific therapeutic regimens. Disseminated TB was not associated with a shortened survival period in AIDS patients when they completed anti-TB treatment. In contrast, disseminated DMAC was associated with shortened survival despite treatment with potent regimens. These results may emphasize the importance of prophylaxis for MAC in this population.     

Epidemiology and clinical consequences of drug-resistant tuberculosis in a Guatemalan hospital

STUDY OBJECTIVE: To determine the epidemiology and clinical consequences of drug-resistant TB in Guatemala. DESIGN: A prospective study conducted for 12 months. SETTING: A thoracic referral hospital in western Guatemala. PATIENTS: Three hundred and seventy-six patients with confirmed TB. RESULTS: Of 376 confirmed cases, 335 (89%) were culture-positive. Tests of drug sensitivities to four first-line antituberculous drugs were performed in 172 (51%) of the culture-positive cases. Fifty-one patients (30%) were resistant to at least one antimicrobial agent, and 26 (15%) were resistant to at least two drugs. In a multivariate model of clinically available patient characteristics, only cavitary disease (odds ratio=2.1; 95% confidence interval, 1.1-6.6) and a history of taking anti-TB medication for >2 weeks (OR=3.0; 95% CI, 1.5-10.3) were independent predictors of resistance to two or more anti-TB agents. Resistance to two or more anti-TB drugs was the single independent predictor of treatment failure (OR=6.4; 95% CI, 2.3-17.8). Twenty-four of 172 patients (14%) who denied having received prior anti-TB therapy were infected with resistant organisms, suggesting ongoing transmission of drug-resistant strains. Although 84% (69 of 82 cases) of patients with fully susceptible organisms and 89% (17 of 19 cases) with singly resistant organisms were cured, only 45% of patients (10 of 22 cases) infected with organisms resistant to two or more agents were successfully treated. CONCLUSIONS: At this sentinel site for complicated TB, a substantial subset of cases who are infected with drug-resistant bacteria cannot be easily identified or treated.     

Medical-resource use for suspected tuberculosis in a New York City hospital

OBJECTIVE: To compare resource use by diagnostic outcome among hospital admissions during which tuberculosis (TB) was suspected. DESIGN: Retrospective study based on chart review and microbiology laboratory data. SETTING: The department of medicine in a municipal hospital serving central Brooklyn, New York. PARTICIPANTS: We identified all adult admissions in 1993 during which TB was suspected. We assigned each admission to one of four mutually exclusive groups defined by the results of microbiological tests (acid-fast bacilli [AFB] smear and culture): culture-positive and smear-positive (C+S+); culture-positive and smear-negative (C+S-); culture-negative and smear-positive (C-S+); or culture-negative and smear-negative (C-S-). Each admission was divided into two separate periods to which the utilization of medical resources was assigned: the diagnostic and the postdiagnostic periods, which were separated by the date of receipt of the first definitive culture report. RESULTS: Data on 519 admissions (93 C+S+; 57 C+S-; 30 C-S+; and 339 C-S-) were analyzed. Although C+S+ were more likely than other groups to have an admitting diagnosis of TB, approximately one quarter of the admissions without TB (C-S+, C-S-) were admitted with the principal diagnosis of TB. For the four groups, C+S+, C+S-, C-S+, and C-S-, the respective rates of TB isolation and anti-TB treatment, and median lengths of isolation were 98%, 87%, and 34 days; 74%, 74%, and 7 days; 83%, 83%, and 15 days; and 44%, 29%, and 0 days. During the diagnostic period, the rate and length of isolation were similar in the AFB-smear-positive groups (C+S+ and C-S+). We estimated that admissions without culture-proven TB (C-S+ and C-S-) accounted for 3,174 (36%) of the 8,712 days of TB isolation expended and for 65% of the 16,671 days of anti-TB treatment. The vast majority of this resource consumption (2,737 [86%] of 3,174 days of isolation) occurred during the diagnostic period before a definitive culture result was known. CONCLUSIONS: Our results suggest that prolonged diagnostic uncertainty and misclassification of cases due to false-positive and false-negative smears are associated with substantial medical-resource consumption. New diagnostic modalities that reduce the period of diagnostic uncertainty could reduce the utilization of resources later found to be unnecessary.     

Diagnosing ascitic etiology on a biochemical basis

BACKGROUND/AIMS: The analysis of ascitic fluid has been complicated by several new tests. To simplify its assessment, we evaluated ascitic fluid pH with six other parameters prospectively and simultaneously in blood and ascitic fluid in sixty patients with ascites. METHODOLOGY: Sixty patients were selected on whom abdominal paracentesis was performed in order to determine which tests were the most reliable for the etiological diagnosis of ascites. Their ascitic fluid pH, cholesterol, albumin, and total proteins were analyzed to distinguish between malignant and cirrhotic ascites. The diagnosis of cirrhosis was based on histological findings, and/or clinical, biochemical, and endoscopic/ultrasonographic findings in whom percutaneous liver biopsy was contraindicated. RESULTS: The serum-ascites albumin gradient was higher (p<0.001) in cirrhotic as compared to tubercular, malignant or cardiac ascites. We discovered that ascitic fluid lactate dehydrogenase and cholesterol were best for diagnosing malignant ascites, ascitic fluid glucose and ascitic fluid/blood glucose ratio were perfect for diagnosing tubercular ascites, and ascitic fluid pH and lactate dehydrogenase were suitable for diagnosing spontaneous bacterial peritonitis. Correspondingly, ascitic fluid albumin, ascitic fluid/serum albumin, total proteins, and serum ascites albumin gradient were best for diagnosing sterile cirrhotic ascites. CONCLUSIONS: Diagnostic paracentesis is a useful procedure. The practice of ordering a battery of tests on every ascitic fluid specimen should be abandoned. Rather, an algorithm approach should be adopted in which the results of initial analysis guide us to further relent tests that help in arriving at the etiology of ascites.     

Acute and chronic diarrhoea and abdominal colic associated with enteroaggregative Escherichia coli in young children living in western Europe

BACKGROUND: Enteroaggregative Escherichia coli (EAggEC or EAEC) can spread and cause disease in developing countries, but it is not presently known whether it spreads disease in industrialised countries. Therefore, we did a prospective study to assess the incidence and the clinical manifestations of infections due to EAEC in children in Germany. METHODS: 798 children with diarrhoea, admitted to hospital within a defined geographical area during a 24-month period, were included in the trial. EAEC were cultured from stool specimens, screened by PCR, and identified by colony hybridisation from DNA sequences found on the virulence plasmid. The findings were confirmed by aggregative adherence to HEp-2 cells. Stool samples from 580 children admitted to hospital without diarrhoea were also studied as controls. FINDINGS: EAEC were found in the stools of 16 (2%) of 798 children with diarrhoea, but in none of 580 children without diarrhoea. Only four of the EAEC-infected children had travelled to developing countries. Most EAEC infections were acquired in the summer months. Infection with EAEC was associated with acute, watery diarrhoea in 12 children, and with chronic diarrhoea of up to 5 months' duration in four. Five children had abdominal colic that lasted for 2-4 weeks as their main symptom. The incidence of EAEC infection was 7.7 patients admitted to hospital per 100,000 children in the general population aged younger than 16 years. INTERPRETATION: EAEC infection is associated with acute, watery diarrhoea and may be acquired in industrialised countries. Chronic diarrhoea or abdominal colic of unknown aetiology in young children may also be caused by EAEC infection.     

Diagnosis and therapy of fungal keratitis--a review

The diagnosis and current therapy of keratomycosis is presented in an overview. The following characteristics are helpful in clinical diagnosis: unsharp borders of the infiltrate, elevated infiltrate with initially epithelium, satellites and pyramidal hypopyon. The microbiological and microscopic confirmation is often possible only after repeated debridements. Lactophenol Blue is very suitable for staining the material obtained. Fluconazol is recommended for the local treatment of candida keratomycosis. Alternatively, amphotericin B is a potent antimycotic. However, a debridement is necessary to enhance bioavailability of this drug. If pharmacotherapy is not efficient enough, keratoplasty should be performed as soon as possible.     

Twenty years of childhood coeliac disease in the Netherlands: more diagnoses and a changed clinical picture

OBJECTIVE: To assess the incidence of childhood coeliac disease in the Netherlands and to study the clinical features. DESIGN: Prospective. SETTING: Leiden University Medical Centre, Leiden, the Netherlands. METHOD: Cases of childhood coeliac disease in the Netherlands in 1993-1995 were identified by means of the Dutch Paediatric Surveillance Unit. Inclusion criteria were: birth in the Netherlands, diagnosis with at least one small bowel biopsy in 1993-1995 and age at diagnosis 0-14 years. The data were cross checked with the Dutch Network and National Database of Pathology and compared with data from a previous study on childhood coeliac disease, 1975-1990. RESULTS: 297 Coeliac patients were identified by means of the Surveillance Unit, another 32 through the National Database of Pathology. The mean crude incidence rate of diagnosed childhood coeliac disease was 0.51/1000 live births, which was in the range of rates found in other West European countries and significantly higher than the mean crude incidence rate of 0.18/1000 live births found in the Netherlands in 1975-1990. The clinical presentation was classic up to 1990: chronic diarrhoea, abdominal distention and growth failure. From 1993 onward, however, the number of children with chronic diarrhoea and abdominal distention decreased significantly and the number with weight loss, anaemia and abdominal pain increased. Associated disorders were present in 13.7% of the cases. CONCLUSIONS: The incidence of diagnosed childhood coeliac disease in the Netherlands showed a tendency to increase significantly during the past decade. In a period of 20 years a significant trend toward change in the clinical presentation of coeliac disease in Dutch children was observed.     

Corticosteroids in the treatment of tuberculous pleurisy. A double-blind, placebo-controlled, randomized study

Although several studies on tuberculous (TB) pleurisy suggest that the addition of corticosteroids to anti-TB therapy may have beneficial effects, these agents are not used routinely. To assess the effects of short-term oral prednisone therapy in TB pleurisy, 74 patients were randomly assigned in a double-blind fashion to treatment with either placebo or prednisone at a dose of 0.75 mg/kg/d for up to 4 weeks with gradual reduction over an additional 2 weeks. All subjects received a standard 3-drug anti-TB chemotherapy regimen for 6 months. TB pleurisy was diagnosed by histologic study and/or culture of pleural biopsy specimens obtained at thoracoscopy. Complete drainage of the effusion was performed simultaneously. Outcome measures were assessed periodically for 24 weeks, including indexes of morbidity and pleural thickening. After randomization, four patients were excluded from the final analysis. Of the 70 patients analyzed, 34 received prednisone and 36 received placebo. Demographic and clinical characteristics of the treatment groups were comparable at the time of hospital admission. Although a statistically significant improvement in symptoms occurred earlier in the prednisone group (8 weeks) than in the placebo group (12 weeks), between-group comparison showed no significant differences at any of the follow-up evaluations. The proportion of subjects in the prednisone group (53.1%) with residual pleural thickening at 6 months did not differ significantly from that of the placebo group (60%). Pleural effusions did not recur in any of the patients. Initial complete drainage of the effusion was associated with greater symptomatic improvement than any subsequent therapy. We conclude that standard anti-TB therapy and early complete drainage is adequate for the treatment of TB pleurisy. The addition of short-term oral prednisone therapy neither results in clinically relevant earlier symptom relief nor confers a beneficial effect on residual pleural thickening.     

Diagnostic value of closed percutaneous pleural biopsy vs pleuroscopy in suspected malignant pleural effusion or tuberculous pleurisy in a region with a high incidence of tuberculosis: a comparative, age-dependent study

OBJECTIVE: To compare the value of closed percutaneous pleural biopsy versus pleuroscopy for diagnosis of undiagnosed exudative pleural effusion in an age-dependent manner. DESIGN: Prospective clinical study. SETTING: University hospitals. PATIENTS: Forty-nine consecutive patients with undiagnosed exudative pleural effusion following the initial clinical and paraclinical investigations, including bronchoscopy. Cases were divided into younger and older groups according to their ages. INTERVENTION: Closed pleural biopsy immediately followed by pleuroscopy with a flexible fiberoptic bronchoscope from the same incision site. RESULTS: In the older age group, pleuroscopy was superior to closed pleural biopsy for the diagnosis of the underlying pleural disease (P = 0.0007), while they were almost equally diagnostic in the younger cases (P = 0.58). CONCLUSION: For those patients with undiagnosed exudative pleural effusion who are older than 50 years of age, pleuroscopy could be chosen as the first procedure of choice as compared to closed pleural biopsy if malignant pleural effusion is suspected.     

Chronic enteropathy of unknown etiology in patients with AIDS. An analysis of 40 cases

BACKGROUND: Data about the etiology of chronic enteropathy in AIDS patients are scarce and are very dependent upon the geographical area. The aim of this study was to detect microorganisms potentially associated with chronic enteropathy in AIDS patients with diarrhoea for more than one month, and initial negative routine stool bacterial cultures and examinations for ova and parasites. The degrees of associated intestinal malabsorption and immunodeficiency were also analysed. PATIENTS AND METHODS: Forty consecutive patients were recruited from January 1993 to December 1994. The following studies were performed: Intestinal absorption tests (d-xylose and 14C-triolein), CD4/CD8 cell counts, microbiological studies (standard stool cultures for detection of bacteria and examinations for ova and parasites including the detection of Enterocitozoon bieneusi spores by the Weber's stain), upper gastrointestinal endoscopy or colonoscopy with intestinal biopsies and blood cultures for CMV and mycobacteria. RESULTS: The median duration of diarrhoea was 4 months and the mean weight loss was 8.4 kg. Ninety percent of patients had less than 0.1 x 10(9) CD4+ cells/l, with a mean CD4+ cell count of 0.035 x 10(9)/l. Malabsorption was found in 84% of patients. An etiological diagnosis of chronic enteropathy was reached in 60% of the patients. The yield of pathological examination was 37% and the microbiological test using samples of faeces and blood were positive in 45% and 20% of cases respectively. The most frequently identified microorganisms were CMV (10 cases), E. bieneusi (9), enterobacteria (8), Cryptosporidium parvum (5), Leishmania donovani (2). Patients with enteropathy caused by E. bieneusi had lower count of CD4 cells (p = 0.005) and with higher serum levels of alkaline phosphatase (p = 0.02) than patients with CMV enteropathy. CONCLUSIONS: Stool Weber's stain and CMV and mycobacterial blood cultures should be added to the standard work-up diagnosis in patients with chronic diarrhoea and a CD4+cells count below 0.1 x 10(9) l. Upper and/or lower gastrointestinal endoscopies with intestinal biopsies should be performed only in patients with persistent diarrhea without microbiological diagnosis or a lack of response to treatment.     

Intractable diarrhoea associated with secondary amyloidosis in rheumatoid arthritis

OBJECTIVE: To examine the clinical characteristics of intractable diarrhoea associated with secondary amyloidosis in rheumatoid arthritis (RA). METHODS: Of 179 RA patients with biopsy confirmed secondary amyloidosis, 24 cases (23 women and one man) with intractable diarrhoea lasting for more than one month were retrospectively evaluated. RESULTS: The mean (SD) duration of diarrhoea was 87 (64) days. Prodromal symptoms of gastrointestinal dysfunction (n = 21) and impaired peristalsis (n = 16) were observed. Laboratory data showed hypoproteinaemia (4.7 (0.85) g/dl) caused by malabsorption or protein loss and high values of C reactive protein (17.0 (9.3) mg/dl). Recurrence of intractable diarrhoea (n = 4) and transition from intractable diarrhoea to other gastrointestinal problems of amyloidosis (ischaemic colitis (n = 2) and intestinal pseudo-obstruction (n = 4)) were observed. In 19 patients (25 episodes) the duration of intravenous hyperalimentation at remission (18 episodes) was 68 (52) days. Corticosteroid pulse therapy was administered to 10 patients (11 times) and the time elapsed from the end of corticosteroid pulse therapy to the end of diarrhoea was 18 (14) days. One and five year survival rates after the onset of intractable diarrhoea were 73.4% and 38.9%. Seven of 13 patients (54%) had died as a result of infectious diseases. CONCLUSION: Intractable diarrhoea associated with secondary amyloidosis in RA is a serious clinical entity and the prognosis is poor. Although it is assumed that intravenous hyperalimentation treatment and corticosteroid pulse therapy are favourable regimens for intractable diarrhoea, the patients should be monitored for possible infectious complications.     

Adolescents'' image of their suicide attempt

Given the suspected role of mycobacteria in the establishment of disorders with an autoimmune background and joint damage, a study was conducted to analyze whether rheumatic symptoms were likely to be present in tuberculosis (TB) patients. To this end, 330 patients with a bacteriologic confirmation of tuberculosis were investigated for the presence of arthritic complaints. The latter were recorded in five of them with rheumatic symptoms mostly involving interphalangeal and metacarpophalangeal joints, and preceding the clinical manifestations of the TB illness. Three out of these five patients remained arthritic by the time of the bacteriologic conversion and fulfilled the criteria for the diagnosis of rheumatoid arthritis. In the two remaining patients sputum negativization was accompanied by a disappearance of rheumatic manifestations. These patients were also assessed for their peripheral levels of major T cell subsets as well as for the presence of autoantibodies. Comparisons with a series of non-arthritic TB cases, rheumatoid arthritis patients, and controls revealed that presence of rheumatic manifestations was associated with a different profile of autoantibody formation and T cell subset changes. Evidence recorded in the present study indicates that joint affectation in TB is a rare event, being rather the exception than the rule.     

Spontaneous bacterial peritonitis: clinical study, microbiological findings and clinical course

One hundred and forty-four episodes of spontaneous bacterial peritonitis (SBP) treated in our service between July 1988 and September 1995 were studied retrospectively to assess the clinical presentation, microbiological findings, possible pathogens, treatment and course. Ascites, abdominal pain and fever were the most common symptoms. Only 3.5% of cases were asymptomatic. The outcome was fatal in 12 (8.33%). Among the factors analyzed, only a prothrombin time of less than 35% correlated significantly with a higher mortality rate (60% and 8.33%, respectively; p < 0.01). Ascitic fluid culture was positive in 43.05% of cases; significant differences existed between these patients and those with negative ascitic fluid culture with respect to clinical findings or course. Gram-negative microorganisms were those most frequently isolated (48.38%). Treatment was initiated within 12 hours in 77.7% of the patients, between 12 and 72 hours in 11.8% and later in 10.41%. Intravenous cefotaxime was administered in 86.1% of cases and other drugs or drug combinations in only 13.9%; the mortality rate was much lower with cefotaxime (2.4% vs 45%; p < 0.01).     

Primary gastric tuberculosis

Intestinal tuberculosis (TB) comprises 5% of all cases of TB and may be a major problem in immigrant communities, although the incidence of pulmonary TB is declining. Gastric TB is rare, constituting 0.1-2% of all cases of TB. Gastric TB usually develops secondary to other tuberculous lesions, most commonly pulmonary. On endoscopy antral infiltrative lesions are found. Primary gastric TB is very rare, only 8 cases having been reported in the English literature. We report a case of primary gastric TB in a 55-year-old woman who presented with abdominal pain and gastric outlet obstruction. The diagnosis was confirmed by endoscopic biopsies which showed granulomas, but no acid-fast bacilli. The Mantoux test was positive, acid-fast bacilli were found in the gastric juice, and a positive culture for TB was obtained on gastric lavage. There was an excellent response to antituberculous chemotherapy. With the relative rate of extra-pulmonary TB increasing, primary gastric TB should be taken into account in the differential diagnosis of infiltrative lesions of the antrum.     

Central nervous system metastasis in breast cancer

BACKGROUND AND PURPOSE: Central nervous system (CNS) metastasis occurs in at least 30% of patients with breast cancer. Standard treatment is the same as in other solid tumors, though clinical behavior, and sensitivity to radiation therapy (RT) and to chemotherapy may differ considerably. Most of these patients die within a few months, but a substantial subgroup may survive a year or more. The last decade has given rise to new diagnostic methods, new surgical and radiotherapeutic techniques, and the clinical evidence of a chemotherapy permissive blood-brain barrier in CNS metastases. The literature was reviewed to assess the clinical impact of early diagnosis, recognition of prognostic factors, and of the recently developed therapeutic approaches. MATERIAL AND METHODS: Review of the literature on CNS involvement in breast cancer focusing on clinical studies on early diagnosis, new modes of treatment, and factors influencing outcome. RESULTS: Although randomized studies are still awaited, systemic chemotherapy seems a valuable alternative for RT of brain metastases in selected cases. In meningeal carcinomatosis, long survival may be independent of intraventricular chemotherapy. Neurotoxicity of intensive intraventricular treatment is considerable. In epidural metastasis, early diagnosis with prompt start of treatment remains the crucial factor for outcome. Radiation therapy is the mainstay of treatment of epidural metastasis, but new surgical techniques and even systemic chemotherapy should be considered in selected cases. CONCLUSIONS: Recognition of prognostic factors combined with appropriate use of various recently developed therapeutic possibilities will improve the clinical outcome including better local tumor control and less treatment-induced neurotoxicity in a considerable number of patients with CNS metastasis from breast cancer.     

The role of endoscopy in the diagnosis of Sch?nlein-Henoch purpura

During a 10 years period 62 adult patients were admitted with diagnosis of Sch?nlein-Henoch purpura in our hospital. 25 female and 37 male patients ranged from 30 to 87 years (mean: 59.5 years) presenting with cutan, joint, renal and particularly abdominal involvement were investigated retrospectively. During the course of the disease, all patients developed purpuric rash (100%), 14 (22.5%) patients had joint symptoms and renal involvement occurred in 12 (19.3%) patients. In this study, we discuss 15 (24%) patients with gastrointestinal symptoms appearing in Henoch's purpura. Analysis of the gastrointestinal clinical features revealed: abdominal pain 13 (86%), massive colorectal bleeding 3 (20%), occult blood loss 10 (66%) vomiting 6 (40%) and diarrhoea in 3 (20%) patients. All the patients underwent lower and upper endoscopic examination, in 3 cases the author saw purpuric mucosal lesions in duodenum and in 8 patients were also found coin-like elevated lesions, additionally, biopsy from colonic lesions showed leukocytoclastic vasculitis. It is concluded that endoscopy can be helpful in the diagnosis and treatment of Sch?nlein-Henoch purpura, especially is those without typical skin rash.     

Clinical utility of an amplification test based on ligase chain reaction in pulmonary tuberculosis

We evaluated the sensitivity and specificity of a new semiautomated direct amplification test (DAT), the LCx-MTB, for the diagnosis of pulmonary tuberculosis (TB) and assessed its positive predictive value by focusing on patients with high clinical and radiologic suspicion of pulmonary TB. Respiratory tract specimens from 32 consecutive patients with high suspicion of active pulmonary TB (case patients) and from 204 control patients were cultured for Mycobacterium tuberculosis and tested by LCx-MTB. Sensitivity and specificity of LCx-MTB when compared with culture was, respectively, 80 and 98%. Pulmonary TB was confirmed in the 32 case patients without knowledge of the LCx results: 18 patients were smear- and culture-positive for M. tuberculosis, and all gave at least one specimen that was LCx-positive. Eight patients were smear-negative culture-positive, and seven gave at least one LCx-positive specimen. LCx-MTB was negative in all the specimens obtained from six patients with smear- and culture-negative TB. A positive LCx-MTB result in a smear negative specimen was 100% predictive that at least one of the case patients' specimens would yield M. tuberculosis. As a consequence, knowledge of the LCx-MTB results at the time of specimen collection could have hastened the start of the antituberculosis therapy in three (21%) smear-negative case patients and could have avoided unnecessary invasive diagnostic procedures in four (29%). We conclude that the sensitivity of LCx-MTB in detecting M. tuberculosis DNA in respiratory tract specimens is similar to other DATs, that LCx-MTB is a reliable test for confirmation of TB in smear-positive patients and that LCx-MTB could be beneficial as a diagnostic step in smear-negative patients with a high suspicion of pulmonary TB.