Bartonella henselae infection in immunocompetent patients: cat scratch disease

BACKGROUND: Cat scratch disease, whose etiologic agent is Bartonella henselae, is a benign disease in immunocompetent subjects, characterized by lymphadenopathy of prolonged course and occasional involvement of other organs such as liver, spleen, central nervous system, eye and lung. In immunocompromised patients, the infection is bacteremic and disseminated. AIM: To report Chilean cases of cat scratch disease. PATIENTS AND METHODS: Ten children (seven male, aged between 6 and 13 years old) with histologically or serologically confirmed cat scratch disease are reported. RESULTS: Lymphadenopathy location was pre auricular in four cases, axillary in two, inguinal in two and epitrochlear in two. Three children had fever over 39 degrees C and two had a parinaud syndrome. Nine children had a history of cat scratch and one of a cat byte. Six had an erythrocyte sedimentation rate over 40. Lymph node ultrasound examination was a useful diagnostic tool. Two patients had splenic granulomas. Lymph node biopsies were obtained in four cases, showing a suppurative granulomatous lymphadenitis in all and a positive Warthin-Starry stain in two. Serology, done in patients without histological confirmation was positive with titles ranging from 1:64 to 1:8192. All patients had a satisfactory outcome with regression of lymphadenopathy. CONCLUSIONS: Infections by Bartonella hemselae occur in the Chilean population and must be considered in the differential diagnosis of regional lymph node enlargement.     

Bronchiolitis obliterans-organizing pneumonia (BOOP)-like variant of Wegener's granulomatosis. A clinicopathologic study of 16 cases

The classic histologic features of Wegener's granulomatosis (WG) in lung include necrotizing granulomatous inflammation and necrotizing vasculitis. Recently, several histologic variants have been recognized, including cases characterized by bronchocentric inflammation, a marked eosinophil infiltrate, alveolar hemorrhage, and capillaritis or interstitial fibrosis. We report 16 cases of another variant in which bronchiolitis obliterans-organizing pneumonia (BOOP)-like fibrosis represents the main histologic finding. The extensive geographic necrosis characteristic of Wegener's granulomatosis was absent in all cases, although small suppurative granulomas, minute foci of bland necrosis, and microabscesses were common. All cases showed the typical necrotizing vasculitis of Wegener's granulomatosis. Other frequent findings included darkly staining multinucleated giant cells, prominent acute inflammation, aggregates of epithelioid histiocytes, hemosiderin-filled macrophages, and areas of nonspecific parenchymal fibrosis. The clinical and radiographic features of this variant of Wegener's granulomatosis appear to be indistinguishable from the classic type. Pathologists need to be aware that Wegener's granulomatosis can occasionally manifest histologic changes suggestive of BOOP. The diagnosis will not be overlooked if additional features, especially vasculitis, suppurative granulomas, tiny necrotic zones, microabscesses, and multinucleated giant cells, are appreciated.     

Factors influencing outcome and length of stay in a stroke rehabilitation unit. Part 2. Comparison of 318 screened and 248 unscreened patients

Amyloidosis associated with Crohn's disease was found in 7 patients among 85 subjected to intestinal resection for granulomatous enterocolitis. Most of the patients had symptoms of inflammatory bowel disease of relatively short duration before the diagnosis of amyloidosis was made and were without suppurative complications. Systemic involvement was seen in 6 of the patients. One died postoperatively from renal failure, and in 2 other patients kidney transplantation was performed because of deterioration of a pre-existent renal insufficiency. Six patients were alive 6 months to 10 years after amyloidosis was diagnosed. There is great risk of rapid deterioration of kidney function postoperatively in these patients. However, our experience suggests that in some cases the progression of amyloidosis may be delayed or even brought to a halt after surgical treatment of Crohn's disease.     

Impairment of mycobacterial immunity in human interleukin-12 receptor deficiency

In humans, interferon gamma (IFN-gamma) receptor deficiency leads to a predisposition to mycobacterial infections and impairs the formation of mature granulomas. Interleukin-12 (IL-12) receptor deficiency was found in otherwise healthy individuals with mycobacterial infections. Mature granulomas were seen, surrounded by T cells and centered with epithelioid and multinucleated giant cells, yet reduced IFN-gamma concentrations were found to be secreted by activated natural killer and T cells. Thus, IL-12-dependent IFN-gamma secretion in humans seems essential in the control of mycobacterial infections, despite the formation of mature granulomas due to IL-12-independent IFN-gamma secretion.     

Striate cortical contribution to the transcorneal electrically evoked response of the visual system

Analyses of current-source-density (CSD) and multiple unit activity (MUA) in area 17 of the cat were performed to determine the sources of the cortical transcorneal electrically evoked response. Cortical field potential, CSD and MUA profiles were obtained with multi-electrodes. CSD findings include: current sinks (inward cell membrane current) within 20 ms latency, in layers 4 and 6 of the striate cortex; current sinks corresponding to N3 (negative component of the EER; latency, 35 ms) in layer 4 and lower layer 3 with current sources (outward cell membrane current) for N3 in the supragranular layers; current sinks with latency over 40 ms in the supragranular layers. In the layers 4 and 6, simultaneous MUA was seen. When the stimulus frequency was increased or with dual stimulation, the N3 current sinks were decreased. This indicates that N1 (latency, 9 ms) and N2 (latency, 20 ms) reflect near-field potentials in layers 4 and 6, generated by geniculocortical afferents, and that N3 is a post- and polysynaptic component. It is also suggested that dipoles composed of cell bodies and the apical dendrites of pyramidal cells of layer 3, generated by satellite cells in layer 4, play a major role in generating N3.     

Rapid polymerase chain reaction-based detection of the causative agent of cat scratch disease (Bartonella henselae) in formalin-fixed, paraffin-embedded samples

Bartonella (formerly Rochalimaea) henselae (Bh) plays a central role in cat scratch disease. A polymerase chain reaction (PCR)-based assay that can detect Bh DNA in formalin-fixed, paraffin-embedded (FF-PE) samples would have utility in the evaluation of processed lymph nodes suggestive of this disorder. Fresh or FF-PE cultures of Bh and related species were analyzed. Thirteen lymph nodes (12 FF-PE and one fresh cell suspension) with necrotizing suppurative granulomatous inflammation and seven FF-PE negative control lymph nodes were also evaluated. PCR was performed using a novel, hemi-nested protocol. Amplified products were analyzed by gel electrophoresis. The fresh and FF-PE Bh cultures showed a specific PCR product with an analytical sensitivity of 0.5 pg bacterial DNA. Seven (54%) of 13 clinical lymph node samples with morphological features suggestive of cat scratch disease also had detectable Bh DNA, whereas none of the seven negative control lymph nodes yielded positive results. We have designed a rapid and sensitive PCR test that can reliably detect Bh DNA in fresh and FF-PE samples. Our findings indicate that this assay has clinical utility in the diagnosis of cat scratch disease.     

Centroblastic and centroblastic-centrocytic lymphomas associated with prominent epithelioid granulomatous response without plasma cell differentiation: a clinicopathologic study of 12 cases

To clarify the clinicopathologic features of B-cell lymphoma associated with prominent epithelioid granulomatous responses other than immunocytomas, 12 patients were studied. There were six men and six women. The lymphoma generally affected elderly patients (median age, 58.5 years) and was mostly nodal in origin. Seven of the 12 patients had a localized lesion (stage I or II), and five had an advanced lesion (stage III or IV). Histologically, four patients showed a follicular growth pattern and eight a diffuse growth pattern. Based on the updated Kiel classification, nine patients showed centroblastic lymphomas, and three showed centroblastic-centrocytic lymphomas. The epithelioid cells were accumulated in large, poorly demarcated masses. Trabecular fibrosis compartmentalized in the lymph nodes, producing a vague nodular pattern in low-power fields. Immunohistochemical studies of the tumor cells revealed positive membrane staining with L26 in all 12 patients and with LN-1 antibody in 9 of 10 patients. Expression of the bcl-2 protein was present in all seven patients tested. Genotypic investigation exhibited germline configuration of the immunoglobulin heavy chain gene, the T-cell receptor beta-chain gene and the bcl-2 gene in all three patients investigated. By in situ hybridization, Epstein-Barr virus genomes were detected in only a few tumor cells in three of the patients tested. This study indicated that most, if not all, of the B-cell lymphomas with prominent epithelioid granulomatous responses other than immunocytoma were of follicular center cell origin.     

Influence of ultraviolet-B irradiation on engraftment, graft-versus-host disease and graft-versus-leukemia effect in a rat model for allogeneic bone marrow transplantation

Serum anti-Bartonella henselae IgG and IgM antibody titers for the diagnosis of cat scratch disease (CSD) were determined by indirect fluorescence antibody (IFA) tests. B. henselae as antigen were harvested either by cocultivating with Vero cells (cocultivated B. henselae) or by cultivating without them (non-cocultivated B. henselae). Based on the results on 110 healthy adults, cut off values were set at 1:32 for IgG, and < 1:20 for IgM antibodies. According to these criteria, IgG antibody was positive in 2.7% of the 110 adults, while nobody was positive for IgM antibody. The titers did not change depending on the types of antigen used. On the other hand, IgG antibody titers against cocultivated B. henselae tended to be higher than those against non-cocultivated B. henselae in 33 CSD suspected patients; 75.8% of the patients were anti-B. henselae IgG positive when tested with cocultivated B. henselae as antigen, while only 48.5% of the same patients gave positive results with non-cocultivated B. henselae. Anti-B. henselae IgM antibody was positive in 24.2% of the 33 CSD suspected patients against both types antigen. Vero cells themselves seemed to nonspecifically bind some IgM (but not IgG). We recommended cocultivated B. henselae as antigen for IgG IFA, and non-cocultivated B. henselae for IgM IFA in the serological tests of CSD.     

Granulomatous Pneumocystis carinii in AIDS patients

Seven cases of Pneumocystis carinii pneumonia with granulomatous reaction in patients infected with the human immunodeficiency virus are described. The patients were all adult men between the ages of 32 and 45 years, with different high-risk factors. Clinically, all the patients presented with a history of non-productive cough and shortness of breath. Two of the patients had a past history of pulmonary pneumocystosis. Radiologically, six patients had diffuse pulmonary infiltrates and one nodular pulmonary infiltrate. Transbronchial lung biopsies were obtained in four patients and open lung biopsies in three. All presented a predominant granulomatous reaction composed of epithelioid and multinucleated giant cells. Several other special stains to detect the presence of other microorganisms to account for the granulomatous reaction were negative.     

Risk factors for type 1 reactions in leprosy

Kaposiform hemangioendothelioma (KHE) is a rare vascular neoplasm that previously has been described only in children. We report three cases occurring in adults. The patients, two men and one woman, were aged 64, 55, and 48 years, respectively. Lesions arose on the chest wall, the lateral aspect of the neck, and in the groin and buttock, and each was situated in superficial soft tissue. Tumor size ranged from 0.9 to 7 cm. Histologically, in all cases a lobular or nodular growth pattern of densely packed spindle-shaped tumor cells closely associated with small slitlike and sievelike blood vessels was seen. Within one lesion, small nodules of plumper, epithelioid tumor cells were identified. Well-formed capillaries frequently containing fibrin thrombi were observed mainly in the periphery of tumor nodules. Areas of hemorrhage and hemosiderin deposits were observed in two cases. Associated lymphangiomatosis composed of diffusely infiltrating lymphatic spaces of the dermis and subcutis was present in one case. Nuclear atypia was minimal in all cases, and mitotic figures were rare in two cases; in one case up to 6 mitoses in 10 high-power fields were noted focally. Immunohistochemically, well-formed capillaries stained positively for all the vascular markers used; however, endothelial cells lining the small slitlike and sievelike vascular spaces did not stain for von Willebrand factor. At least focally, actin-positive pericytes were seen. Neoplastic spindled cells stained only focally for CD34 and CD31. Two lesions were excised with clear margins; in one case only repeated biopsies were done. Follow-up information between 14 and 28 months revealed no sign of recurrence or metastasis. In adults, the differential diagnosis of KHE comprises especially Kaposi's sarcoma and spindle cell hemangioendothelioma; further differential diagnoses include tufted hemangioma and cellular capillary hemangioma, which occur rarely in adults.     

"Proximal-type" epithelioid sarcoma, a distinctive aggressive neoplasm showing rhabdoid features. Clinicopathologic, immunohistochemical, and ultrastructural study of a series

Eighteen examples of an unusual malignant soft-tissue neoplasm, the morphology of which ranged from that of "atypical" epithelioid sarcoma to that of a rhabdoid tumor or undifferentiated carcinoma (with transitional forms) are described. Patients included 11 males and seven females; their median age was 35.5 years with most patients aged 20 to 40 years. Development of a mass was the main presenting symptom. Six tumors developed in the pelvis and perineal region, four in the pubic region and vulva, three in the buttocks, one in the deep soft tissues of the left hip, one on the penis, one in left forearm, one in left axilla, and one on the occiput. Tumor size ranged from 1 to 20 cm (median, 4 cm). On microscopic examination, the tumor cells invaded the subcutaneous or deep soft tissues, had prominent epithelioid or rhabdoid features, had marked cytologic atypia, and grew in a multinodular pattern in half of the cases. Areas of necrosis were often seen. A granuloma-like pattern reminiscent of that observed in classic epithelioid sarcoma was observed in only two cases. Immunohistochemically, positivity for cytokeratin, epithelial membrane antigen, and vimentin was seen in all but one of the cases. Of 16 cases, 10 and eight tumors reacted with desmin and CD34, respectively; five of 15 reacted at least focally with smooth-muscle actin, whereas three of 13 and one of 10 reacted for HMB-45 and carcinoembryonic antigen, respectively. S-100 protein and CD31 yielded negative results. Seven tumors were investigated at the ultrastructural level, four of which showed prominent intracytoplasmic intermediate filament aggregates, often accumulating into paranuclear whorls, which is in keeping with the rhabdoid phenotype. Five tumors showed features of epithelial differentiation (i.e., tonofilament-like structures or desmosomes or both), whereas one tumor displayed features of myofibroblastic differentiation. Differential diagnoses include mainly conventional epithelioid sarcoma, extrarenal malignant rhabdoid tumor, epithelioid malignant peripheral nerve sheath tumor, melanoma, rhabdomyosarcoma, and undifferentiated carcinoma. Follow-up information on 14 patients (range, 4 months to 8 years; median, 19 months) revealed local recurrence in one case and metastatic dissemination in six patients, leading to death in five. In our opinion, the above-described neoplasms represent a usually "proximal-type" of epithelioid sarcoma. In contrast to the conventional, "distal-type" epithelioid sarcoma, the proximal variant is characterized by a predominantly large-cell, epithelioid cytomorphology, marked cytologic atypia, frequent occurrence of rhabdoid features, and lack of a granuloma-like pattern in most cases. It appears to be somewhat more aggressive (or at least metastasizes earlier) than usual epithelioid sarcoma.     

Pathogenesis of pulmonary Cryptococcus neoformans infection in the rat

The pathogenesis of Cryptococcus neoformans pulmonary infection in the rat was studied after intratracheal inoculation. Lungs were examined at various times following infection for histopathology in conjunction with macrophage markers, proliferating cell nuclear antigen (PCNA), and capsular glucuronoxylomannan (GXM) antigen. Serum GXM, immunoglobulin M (IgM) and IgG titers and organ fungal burden were compared with pathological findings. C. neoformans organisms were in the lung parenchyma 2 h postinoculation, and GXM antigen was present in surrounding tissues shortly thereafter. Extrapulmonary dissemination occurred early in infection. Two phases of host cellular inflammatory response were discernible: early local macrophage recruitment at 2 to 4 days followed by granulomatous inflammation, which reached maximum intensity 14 days after infection. The granulomatous phase was preceded by lymphocyte influx with macrophage proliferation and maturation into epithelioid histiocytes; this was paralleled by a shift of yeasts from extracellular to intracellular spaces. Tissue IgG deposits, serum IgG to GXM, and localization of tissue GXM immunoreactivity to epithelioid cells were noted at 2 to 4 weeks. A 10-fold decrease in lung fungal burden occurred 25 days postinfection and was associated with resolving granulomas, fewer proliferating cells, and decreased tissue GXM. The present study demonstrates that (i) C. neoformans penetrates the lung parenchyma shortly after infection; (ii) immunocompetent rats control pulmonary cryptococcosis efficiently, with minimal extrapulmonary dissemination and low levels of serum GXM; and (iii) macrophage activation is likely to play a crucial role in limiting C. neoformans infection in the rat lung.     

A 1H NMR NOE study on Co(II) stellacyanin: some clues about the structure of the metal site

The granulomatous response is a phylogenetically primitive specialized immunological reaction of the body to wall off an irritant, ingest and remove it, characterised by a localized collection of epithelioid cells, macrophages and lymphocytes. The cells forming the granuloma, its mechanism of formation and types of granuloma have been discussed. A classification of granulomatous diseases of the oral cavity based on etiology has been suggested.     

Cat-scratch disease and bacillary angiomatosis

Cat-scratch disease (CSD) was first described by Debré in 1950, yet the causative bacterial agent of CSD remained obscure until 1992, when Bartonella (formerly Rochalimaea) henselae was implicated in CSD by serological and microbiological studies. B. henselae had initially been linked to bacillary angiomatosis (BA), a vascular proliferative disease most commonly associated with long-standing human immunodeficiency virus (HIV) infection or other significant immunosuppression. B. henselae has also been associated with bacillary peliosis, relapsing bacteraemia and endocarditis in humans. Cats are healthy carriers of B. henselae, and can be bacteraemic for months or years. It has recently been demonstrated that B. henselae can be transmitted from cat to cat by the cat flea, but not by direct contact between animals. The author discusses the present state of knowledge on the aetiology, clinical features and epidemiological characteristics of cat-scratch disease and bacillary angiomatosis.     

Relationship between cardioventilatory coupling and respiratory sinus arrhythmia

The clinical data, microbiological results and antibiotic treatment of 65 children who have required incision and drainage of suppurative head and neck abscesses was retrospectively investigated with the aim of developing a more effective clinical protocol of treatment, improving speed of resolution and rationalizing the need for surgical intervention. A positive culture grew in 78% of children and of these 45% were Staphylococcus aureus, 9% Streptococcus pyogenes, and 8% atypical mycobacteria. Only 3% of the samples grew anaerobes. All isolates of S. aureus were sensitive to Flucloxacillin and all isolates of S. pyogenes were sensitive to penicillin. All anaerobes were Metronidazole sensitive. In 40% of the children there were no localizing symptoms which could guide the treatment, therefore we recommend Flucloxacillin and Metronidazole as the antibiotic regimen of choice in acute suppurative lymphadenitis. The increasing incidence of atypical mycobacterial lymphadenitis is noteworthy.     

Molecular diagnosis of cat scratch disease: a two-step approach

Amplification of Bartonella henselae DNA has been proposed as a diagnostic test for cat scratch disease (CSD). The sensitivities of the following three PCR assays were compared. PCR/rRNA with universal primers amplifies part of the 16S rRNA gene, followed by hybridization with a specific B. henselae probe; PCR/CS and PCR/HSP amplify portions of the gltA and the htrA genes, respectively, each followed by restriction fragment length polymorphism analysis. The threshold of detection of B. henselae DNA in pus was 10(-4), 10(-3), and 10(-2) ng for PCR/rRNA, PCR/CS, and PCR/HSP, respectively. By these three assays, B. henselae DNA was detected in 100, 94, and 69% of 32 pus and lymph node specimens from CSD patients, respectively. The similar sensitivities of the PCR/rRNA and the PCR/CS assays for detecting B. henselae DNA in clinical specimens are in contrast to the 10-fold difference in sensitivities in favor of PCR/rRNA demonstrated with purified B. henselae DNA in sterile pus, suggesting that in the majority of cases, the bacterial load in clinical specimens is large enough to be identified by the PCR/CS assay. A two-step approach is suggested to achieve maximal sensitivity for detecting B. henselae in clinical specimens: initial testing by PCR/CS (which does not require hybridization), followed by PCR/rRNA with PCR/CS-negative specimens when CSD is strongly suspected.     

Tuberculous lymphadenitis

Tuberculous lymphadenitis is a common extrapulmonary tuberculosis. Its incidence is about 28%. Pulmonary hilar lymphadenitis and mediastinal lymphadenitis are often visible in the routine chest X-ray films during pulmonary tuberculosis. But abdominal lymphadenitis are difficult to detect on this method. Computed tomography is a useful tool to detect the tuberculous lymphadenitis both mediastinal and abdominal. The active tuberculous lymphadenitis shows characteristic findings with contrast enhanced CT, central low attenuation and peripheral rim enhancement were seen. On the contrary homogeneous without low attenuation area and with calcification were inactive tuberculosis. Bacterial diagnosis is difficult and PCR method is effective for detect the tuberculosis. Usual anti-tuberculous chemotherapy were performed for the tuberculous lymphadenitis and effective but on the fistula formation surgical procedure are also performed.     

Spirocerca lupi (Rudolphi, 1809) nodule in the rectum of a dog from Connecticut

A small nodule causing repeated rectal prolapse was surgically removed from a four year old Dachshund residing for her entire life in Connecticut. Histologic examination of the biopsy specimen revealed sections of Spirocerca lupi (Rudolphi 1809) surrounded by a granulomatous reaction and fibrous wall.