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Regional lymphadenitis following antileprosy vaccine BCG with killed Mycobacterium leprae.

Phase-II and extended Phase-II studies were conducted in three different sets of the population in Thiruthani Taluk, Chengalpattu District, South India, involving BCG and killed Mycobacterium leprae (KML) combination vaccines to ascertain the acceptability of the vaccines. In the Phase-II study, 997 healthy volunteers were vaccinated on individual randomization with one of the vaccines arms: BCG 0.1 mg + 6 x 10(8) KML, BCG 0.1 mg + 5 x 10(7) KML, BCG 0.1 mg + 5 x 10(6) KML, BCG, 0.1 mg or normal saline. Blood samples were taken and the serum was tested for antibody levels against phenolic glycolipid-I (PGL-I) and the 35-kDa protein of M. leprae. In this study, we observed regional suppurative adenitis in 6% (6 out of 100), 3% (3 out of 100), and 3% (3 out of 100) of the vaccinees in the BCG 0.1 mg + 6 x 10(8) KML, BCG 0.1 mg + 5 x 10(7) KML, and BCG 0.1 mg + 5 x 10(6) KML vaccine arms, respectively, in the 13-70 year age group. Earlier BCG scar status, skin-test reactions to lepromin-A, Rees' MLSA, and serum antibody levels against PGL-I and the 35-kDa protein did not help to identify the group at risk of developing suppurative adenitis. Suppurative adenitis appears to have a different relationship between the age of the subject and the dose of the vaccine. In order to overcome the problem of regional suppurative adenitis and to know the mechanism involved, an extended Phase-II study was conducted in similar groups of the population by reducing the BCG and KML doses, i.e., with BCG 0.05 mg + 6 x 10(8) KML, BCG 0.05 mg + 5 x 10(7) KML, and BCG 0.01 mg + 5 x 10(7) KML. Biopsy specimens were collected from lymph nodes of the suppurative adenitis cases and were subjected for culture and histopathological examination. The observations showed that regional suppurative adenitis could be reduced to 1% in the BCG 0.05 + 6 x 10(8) KML group, 0.5% in the BCG 0.05 + 5 x 10(7) KML group, and 0.5% in the BCG 0.01 + 5 x 10(7) KML group. This phenomenon of suppurative adenitis appears to be related to the total dose of mycobacterial antigens. Suppurative adenitis was seen by weeks 18 and 20 post-vaccination in the latter two lower doses; whereas it was seen by week 8 in the higher dose of the combination vaccines. No case of suppurative adenitis was observed in the BCG 0.1 mg group. Culture and histopathology ruled out the possibilities of progressive BCG infection and superadded infection. Considering the above results, BCG 0.05 mg + 6 x 10(8) KML was acceptable for a large-scale vaccine trial in South India.

Adolescent↗

Acute disseminated epidermal necrosis types 1, 2, and 3: study of sixty cases.

Sixty patients with acute disseminated epidermal necrosis (ADEN) were hospitalized and carefully studied. They included thirty-nine patients with drug-associated Stevens-Johnson syndrome, five patients with drug-associated Lyell's syndrome, and sixteen patients with transitional ADEN. On the basis of growing evidence of an association between erythema multiforme major and drugs and between Lyell's syndrome and drugs, and because of the existence of transitional cases, a unitary hypothesis for this group of cases is proposed. Considering the lack of precise definitions and the confusing current terminology, we define and propose the following terms: ADEN type 1 for drug-associated Stevens-Johnson syndrome, ADEN type 2 for drug-associated transitional cases, and ADEN type 3 for drug-associated toxic epidermal necrolysis, or Lyell's syndrome. The most frequent underlying diseases in our patients were seizures, and the most frequently suspected cause of ADEN was the use of anticonvulsants. All our patients were treated with supportive therapy; none received corticosteroids. The general mortality rate was 15%. The recognition of ADEN type 2 (transitional) has important prognostic and therapeutic implications.

Adolescent↗

Mycobacterial lymphadenitis in childhood.

A total of 42 cases of childhood mycobacterial adenitis have been studied to define the optimal steps that lead to the correct diagnosis of this disease. Antigens from the atypical mycobacteria are not currently available, so the usefulness of tuberculin skin testing as a diagnostic tool was examined. Skin testing differentiates mycobacterial adenitis from infection caused by pyogenic bacteria. In addition, repetitive skin testing with tuberculin over a three- to six-month period is also useful in differentiating adenitis caused by atypical mycobacteria from that due to Mycobacterium tuberculosis. Children with atypical mycobacterial adenitis have a decreasing tuberculin response to repeated testing, while children with tuberculous adenitis have a stable response. Other factors that assist in the differentiation of adenitides include a history of recent exposure to tuberculosis and evidence of extralymphatic tuberculosis. Needle aspiration or partial excision in mycobacterial adenitis may lead to drainage and sinus tract information. A PPD skin test should be done prior to surgical manipulation of enlarged nodes. Children with reactive skin tests should undergo complete excision.

Adolescent↗

Using high-fidelity patient simulation and an advanced distance education network to teach pharmacology to second-year medical students.

The feasibility and acceptance of an Advanced Distance Education Network (ADEN) in bringing the simulated operating room (OR) to second-year medical students learning the pharmacology of anesthetic drugs is reviewed. A MedSim-Eagle (Binghamton, NY) full-scale mannequin simulator was used. Using an ADEN, students were linked in real time to a simulated OR where the anesthesiologist instructor was using a MedSim-Eagle patient simulator to present for discussion the physiologic effects of volatile anesthetics on cardiac output (CO), heart rate (HR), mean arterial pressure (MAP), and systemic vascular resistance (SVR). The use of simulation to present basic science principles of isoflurane and halothane's effect on CO, HR, MAP, and SVR in a clinical setting via an ADEN is feasible. Student acceptance of this method of education is high, as measured by a post-exercise survey. Ninety-five percent of students felt this exercise was a valuable use of their time; 93% felt the ADEN-delivered clinical simulation presentation contributed to their understanding of the pharmacology of anesthesia. Eighty-three percent of students preferred this integrated clinically oriented review to a didactic review of the material, and 92% of students who had experienced previous small group hands-on session simulation felt the ADEN-delivered session was the same or better.

Anesthesiology↗

Incidence of cutaneous tuberculosis in patients with organ tuberculosis.

BACKGROUND: Tuberculosis continues to be a health problem in some countries. The development of resistance to antituberculitic drugs and the increase in diseases and conditions associated with immunodeficiency such as AIDS and chemotherapy have caused tuberculosis to increase recently. As a result, the incidence of cutaneous tuberculosis has been increasing as well. AIM: To detect cutaneous tuberculosis in patients with organ tuberculosis and to establish some characteristics of the relation between organ and cutaneous TB. MATERIAL AND METHODS: A total of 370 patients (145 females and 225 males), aged 2-76 years (mean age 27.5), enrolled for this screening study. These patients were hospitalized patients who already had pulmonary or extrapulmonary tuberculosis diagnosed before admission. All patients underwent a general skin examination, and, if needed, cutaneous biopsies were taken from involved skin areas. RESULTS: Three hundred and forty-seven (93.78%) out of 370 patients had pulmonary tuberculosis only or in association with one of other organ tuberculoses. Twenty-three patients had extrapulmonary TB: nine were TB adenitis, six were TB peritonitis, three were bone tuberculosis, and five were TB meningitides. Of 370 patients, only 13 (3.51%) had cutaneous TB: seven scrofuloderma (SCD; 2.16%), four lupus vulgaris (LV; 1.35%), one LV and SCD, and one Bacille Calmette-Guerin (BCG) adenitis (0.027%). Cutaneous tuberculosis was observed in seven out of 260 patients with parenchymal tuberculosis (2.96%). Four out of nine patients with TB adenitis (44.4%), one out of 12 pulmopleuretic (8.3%), and one out of 67 pleuresic patients (1.40%) had cutaneous TB as well. Mean age of the 13 patients was 32.46 years: mean age of SCD and LV was 24.8 and 48 years, respectively. The one patient with BCG adenitis was 7 months old. Five (62.5%) out of eight patients with SCD, and only one (20%) out of five patients with LV were new cases. Four patients with SCD had a positive family history, while LV patients did not. CONCLUSIONS: Organ tuberculosis is rarely associated with cutaneous tuberculosis. Scrofuloderma and LV are the most frequent forms of skin TB associated with organ TB in this population. Tuberculosis adenitis is the organ TB that causes cutaneous TB most often among other organ tuberculoses. More than one form of cutaneous TB affected only one patient with pulmonary TB; therefore, it is very rare. Tuberculids were not observed in any of the patients.

Adolescent↗

Nontuberculous mycobacteria in children: a changing pattern.

UNLABELLED: Nontuberculous mycobacteria (NTM) infections seem to be increasing in numbers and in severity in developed countries worldwide. OBJECTIVE: To document the severity and to assess whether an increase in cases has occurred over the years, we described the epidemiology, clinical presentation, investigations, and treatment of NTM adenitis seen at the Montreal Children's Hospital. METHODS: Cases were identified through revision of the microbiology laboratory database for positive NTM culture from any site and through retrieval by the medical records of charts of patients with a diagnosis of adenitis and a node biopsy or excision or a diagnostic code of NTM disease, between 1990 and 2004. These charts were reviewed retrospectively. RESULTS: Over the 15-year period, we identified 36 patients with a median age of 2.8 years with NTM adenitis. Of these cases, 22 (61%) occurred in the past 5 years. Only 3 children were born outside Canada. The majority (92%) presented with a cervicofacial mass, and 25% had constitutional symptoms or fever. There were 3 cases of mediastinal adenitis and 2 cases of cervical disease extending to the deep neck vessels, all of which occurred in the past 5 years. The purified protein derivative (PPD) test for tuberculosis was positive (> or = 10 mm) in 11 of 15 patients tested (73%), none of whom had ever had contact with tuberculosis. Thirty-three patients had surgery. Of the 26 patients who had excisional biopsy or functional neck dissection, 15% required a second surgery for persistence or recurrence compared with 100% of those who had incision and drainage or curettage. Cultures were positive in 72% of the 32 specimens sent, mainly for Mycobacterium avium complex. Very few complications were noted. CONCLUSION: The number of cases of NTM disease has almost doubled between 2000-2004 compared with between 1990-1999, with more invasive cases seen in the past 4 years. The significance of this important rise in numbers is still unclear. Resolution of NTM adenitis is higher with complete surgical excision of affected lymph nodes. Moreover, given the proportion of PPD > or = 10mm among those tested, a pan-Canadian study assessing the incidence of NTM disease compared with tuberculosis is required to determine if a change in the recommendations for PPD positivity is needed.

Child↗

CT and ultrasound imaging of retropharyngeal abscesses in children.

PURPOSE: To show the role of ultrasound (US) in distinguishing retropharyngeal abscess from adenitis in children. METHODS: Eleven infants and children had clinical symptoms suggestive of retropharyngeal infection. Radiographic evaluation included, lateral neck radiography (11/11), contrast-enhanced neck CT (10/11), contrast-enhanced neck MR (1/11), and real time US (11/11) patients. US was used to characterize masses as solid (adenitis) or complex (abscess) and for guiding intraoperative aspiration and drainage. RESULTS: Contrast CT and MR showed findings suspicious for abscess in all 11 cases. Only three children had surgically drainable abscesses. CT numbers within inflammatory masses did not distinguish adenitis from abscess. US was able to correctly diagnose abscess or adenitis in each case. CONCLUSION: Lateral neck radiography and contrast CT identify and localize retropharyngeal inflammatory masses in children. US, but not CT, distinguishes between adenitis and abscess and aids in intraoperative aspiration and drainage.

Abscess↗

Pediatrics: cervical adenopathy in children.

Cervical adenopathies are common in children. The four categories, based on clinical findings are acute unilateral adenitis, acute bilateral adenitis, subacute (chronic) adenitis, and cervical node cancers. Most cases of acute pyogenic adenitis-both unilateral and bilateral-respond well to early antibiotic treatment. Penicillin is the drug of choice unless Staphylococcus aureus is thought to be the infecting organism. S aureus is trated with dicloxacillin or erythromycin. Subacute adenitis due to cat scratch fever usually resolves spontaneously. Nodes due to infection with atypical mycobacteria require excision. Because cervical node cancer is usually asymptomatic, excision and pathologic study should be done for any cervical node persistently enlarged without apparent reason.

Acute Disease↗

Chronic lymphadenopathy due to mycobacterial infection. Clinical features, diagnosis, histopathology, and management.

This report provides clinical information, diagnostic criteria, management, and outcome of 153 cases of mycobacterial lymphadenitis; 22 patients (14%) had Mycobacterium tuberculosis (TB) and 131 patients (86%) had nontuberculous mycobacterial (NTM) disease. Correct diagnosis of TB v NTM disease is essential, since antituberculous chemotherapy was effective for TB adenitis, while excisional biopsy was the treatment of choice for NTM adenopathy. Dual (PPD-NTM, PPD-T) Mantoux tests discriminated between TB and NTM adenitis in 151 (99%) of 153 patients, while dual (PPD-Battey [B], PPD-T) tests differentiated between NTM and TB adenitis in 135 (88%) of 153 cases. A PPD-T reaction of 1 to 14 mm suggested either an NTM or TB infection, whereas a PPD-T of 15 mm or greater was strongly associated with TB disease. We recommend the use of PPD-B and PPD-T antigens as reliable diagnostic discriminators between TB and NTM adenitis.

Antitubercular Agents↗

HgCl2-induced glandular pathosis in the brown Norway rat.

Low doses of HgCl2 induce a genetically restricted autoimmune syndrome in Brown Norway (BN) rats (BN(Hg)). Part of the syndrome includes spontaneously developing mononuclear cell foci in salivary and lacrimal glands, morphologically similar to focal sialoadenitis in Sjögren's syndrome in man. In this study, we have shown that Hg-induced focal adenitis in BN rat is not female predominant and not solely dependent on Hg uptake in the glands. In BN(Hg), focal adenitis was found to develop in several different glands (parotid, submandibular, lacrimal, thyroid) as a specific manifestation of immunopathosis induced by Hg in the RT1n-haplotype-carrying BN. Such manifestations were absent in another strain, the Hg-resistant Lewis (RT1l). Also a potent contact sensitizer, DNFB, induced focal adenitis in isolated glands, provided that strong sensitization had occurred. Immunohistochemical characterization of focal adenitis in BN(Hg) with monoclonal antibodies showed that T cells and dendritic cells dominate the early infiltrates, whereas B cells were absent.

Animals↗

Guanine-adenine DNA cross-linking by 1,2,3,4-diepoxybutane: potential basis for biological activity.

1,2,3,4-Diepoxybutane (DEB) is a prominent carcinogenic metabolite of 1,3-butadiene (1,3-BD), an important industrial chemical and an environmental pollutant found in cigarette smoke and automobile exhaust. DEB is capable of inducing a variety of genotoxic effects, including point mutations, large deletions, and chromosomal aberrations. The mutagenicity and carcinogenicity of DEB are thought to result from its ability to form bifunctional DNA-DNA adducts by sequentially alkylating two nucleobases within the DNA double helix. We recently reported that DEB-induced DNA-DNA cross-linking leads to the formation of 1,4-bis-(guan-7-yl)-2,3-butanediol (bis-N7G-BD) adducts [Park, S., and Tretyakova, N. (2004) Structural characterization of the major DNA-DNA cross-link of 1,2,3,4-diepoxybutane. Chem. Res. Toxicol. 17 (2), 129-136]. However, guanine-guanine cross-linking by DEB cannot explain the development of A:T base pair mutations following exposure to DEB and 1,3-BD. In the present work, four asymmetrical DNA-DNA cross-links involving both adenine and guanine nucleobases were identified in double-stranded DNA treated with racemic DEB. These novel lesions were assigned the structures of 1-(aden-1-yl)-4-(guan-7-yl)-2,3-butanediol (N1A-N7G-BD), 1-(aden-3-yl)-4-(guan-7-yl)-2,3-butanediol (N3A-N7G-BD), 1-(aden-7-yl)-4-(guan-7-yl)-2,3-butanediol (N7A-N7G-BD), and 1-(aden-N6-yl)-4-(guan-7-yl)-2,3-butanediol (N6A-N7G-BD), based on the comparison of their MS/MS spectra, HPLC retention times, and UV spectra with those of the corresponding authentic standards prepared independently. Although guanine-adenine lesions are approximately 10 times less abundant in DEB-treated double-stranded DNA than the corresponding bis-N7G cross-links, N1A-N7G-BD and N6A-N7G-BD are more hydrolytically stable and, if formed in vivo, may accumulate in target tissues. HPLC-ESI-MS/MS analysis of guanine-adenine DEB cross-links induced in synthetic DNA duplexes 5'-(GGT)5, 5'-(GT)7G, and 5'-(GAA)5 (+-strand) demonstrate that G-A cross-linking by DEB produces primarily 1,3-interstrand N1A-N7G lesions. The formation of bifunctional guanine-adenine adducts is likely to contribute to AT base pair substitutions and deletion mutations following DEB exposure.

Adenine↗

A3 adenosine and CB1 receptors activate a PKC-sensitive Cl- current in human nonpigmented ciliary epithelial cells via a G beta gamma-coupled MAPK signaling pathway.

(1) We examined A3 adenosine and CB1 cannabinoid receptor-coupled signaling pathways regulating Cl(-) current in a human nonpigmented ciliary epithelial (NPCE) cell line. (2) Whole-cell patch-clamp recordings demonstrated that the A3 receptor agonist, IB-MECA, activates an outwardly rectifying Cl(-)current (I(Cl,Aden)) in NPCE cells, which was inhibited by the adenosine receptor antagonist, CGS-15943 or by the protein kinase C (PKC) activator, phorbol 12,13 dibutyrate (PDBu). (3) Treatment of NPCE cells with pertussis-toxin (PTX), or transfection with the COOH-terminus of beta-adrenergic receptor kinase (ct-betaARK), inhibited I(Cl,Aden). The phosphatidyl inositol 3-kinase (PI3K) inhibitor, wortmannin, had no effect on I(Cl,Aden); however, the mitogen-activated protein kinase kinase (MEK) inhibitor, PD98059, inhibited I(Cl,Aden). (4) Reverse transcription-polymerase chain reaction experiments and immunocytochemistry confirmed mRNA and protein expression for the CB1 receptor in NPCE cells, and the CB1 receptor agonist, Win 55,212-2, activated a PDBu-sensitive Cl(-) current (I(Cl,Win)). (5) Transfection of NPCE cells with the human CB1 (hCB1) receptor, increased I(Cl,Win), consistent with increased receptor expression, and I(Cl,Win) in hCB1 receptor-transfected cells was decreased after application of a CB1 receptor inverse agonist, SR 141716. (6) Constitutive activity for CB1 receptors was not significant in NPCE cells as transfection with hCB1 receptors did not increase basal Cl(-) current, nor was basal current inhibited by SR 141716. (7) I(Cl,Win) was inhibited by PTX preincubation, by transfection with ct-betaARK and by the MEK inhibitor, PD98059, but unaffected by the PI3K inhibitor, wortmannin. (8) We conclude that both A3 and CB1 receptors activate a PKC-sensitive Cl(-) current in human NPCE cells via a G(i/o)/Gbetagamma signaling pathway, in a manner independent of PI3K but involving MAPK.

Cell Line, Transformed↗

The incidence of focal chronic inflammatory changes in human submandibular salivary glands.

Focal chronic inflammatory changes have been investigated in a series of otherwise non-diseased submandibular salivary glands obtained at necropsy from 96 subjects evenly divided by sex and decades of adult age. Two types of change were recorded: focal aggregates consisting predominantly of lymphocytes; and limited intralobular areas of parenchymal change similar to those present in obstructive sialadenitis. These were termed focal lymphocytic adenitis and focal obstructive adenitis respectively. For each gland the numbers of foci of each type were separately expressed per unit area of section examined. Focal lymphocytic adenitis, which was almost universally present throughout the series, in most cases was not associated with destructive changes in the parenchyma. It showed no simple pattern of incidence in relation to age and sex. Focal obstructive adenitis, also frequently present, showed a gradually increasing prevalence with age. Persistent foci of this type tended to form fibrous scars. These were more frequent in older decades. The increasing incidence of obstructive foci throughout adult life, plus in older age groups their persistence as focal scars, both contribute to the gradual reduction in parenchyma which is a feature of aging in the human submandibular gland.

Adolescent↗

[Diagnosis of streptococcal tonsillitis in the pediatric department with the help of antigen detection test].

INTRODUCTION: The aim was to examine the validity in the paediatric hospital department of an antigen detection test (ADT) for the diagnosis of streptococcal tonsillitis. MATERIAL AND METHODS: A prospective multicenter study including three Danish paediatric hospital departments was performed from May 1, 1998 to April 30, 1999. In 353 children aged 0-14 years the result of the ADT, Clearview Strep A, was compared with the result obtained with cultivation in an aerobic culture and the clinical parameters: hyperaemia, swelling, coating, adenitis and a temperature > or = 38.5 degrees C. In 126 patients the results of the ADT were also compared with white blood cell count (WBC), neutrofil count (NC) and C-reactive protein (CRP). RESULTS: The prevalence of Group A Streptococci (GAS) from culture was 15%. Sensitivity, specificity, positive and negative predictive value of ADT were 67%, 95%, 72% and 94%, respectively. The positive predictive value of the ADT was significantly lower in patients aged 0-4 years than in patients aged > or = 5 years (p = 0.02). The prevalence of positive ADT was significantly higher in patients with heavy growth of GAS than in patients with moderate or sparse growth (p = 0.01). The prevalence of adenitis (p = 0.003) and coating (p = 0.003) was significantly raised in ADT-positive patients. In patients with growth of Group A Streptococci in cultivation in an aerobic culture the prevalence of adenitis (p = 0.006) and elevated CRP (p = 0.03) was significantly raised. DISCUSSION: The sensitivity of 67% for the ADT is not satisfactory. However, in our opinion, this is not a sufficient argument against using ADT. It was a problem that the result of the ADT was sometimes difficult to read. Adjustment of the test procedure and the use of easy readable and high-sensitive optical immunoassay tests would probably improve the results significantly. Until the results of such studies exist, we suggest that the method of cultivation in an aerobic culture is used in the case of negative ADT, at least in patients with pronounced symptoms and/or clinical signs of streptococcal tonsilitis (adenitis and coating).

Antigens, Bacterial↗

[Diagnostic evaluation of cervical adenopathies in childhood].

Between 1985 and 1990, 45 children were studied in an inpatient basis hospital because of cervical lymphadenopathy. This was the most important clinical sign in these patients. Forty-three had true adenitis. In the others, one was submaxillitis and one a sarcoma. The age range was from 2.1 to 13.3 years. Seven children (16%) had neoplastic adenitis (2 papillary carcinoma of the thyroid, 4 Hodgkin's lymphoma and one non-Hodgkin's lymphoma). Thirty-six patients had benign disorders (18 mononucleosis infections, 7 nonspecific adenitis, 5 infections of mycobacteria, 2 of toxoplasma and 2 of rickettsia, one cervical Whipple and one desmopathic adenitis). We did no find any differences related to age or morphological characteristics of the lymph nodes. The evolution time in patients with malignant tumors was 16.4 weeks and 9.6 weeks in the benign group. All of the cases with supraclavicular location had a lymphoma. The mean LDH in patients with malignant tumors was 214 U/L and 614 U/L in those with non-malignant tumors (p < 0.01).

Anti-Inflammatory Agents↗