Effect of golimumab and pamidronate on clinical efficacy and MRI inflammation in axial spondyloarthritis: a 48-week open randomized trial.

OBJECTIVES: To compare the effect of golimumab (GLM) and pamidronate (PAM) on clinical efficacy and magnetic resonance imaging (MRI) inflammation in axial spondyloarthritis (aSpA). METHOD: Patients who fulfilled the Assessment of SpondyloArthritis Society (ASAS) criteria for aSpA and had active disease [Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score ≥ 4] were randomized in a 2:1 ratio to receive either GLM (50 mg) or PAM (60 mg) 4 weekly for 48 weeks. Clinical efficacy was assessed at intervals. Inflammation of the spine and sacroiliac joints (SIJs) on MRI was graded by the Spondyloarthritis Research Consortium of Canada (SPARCC) scoring system. RESULTS: Twenty patients were assigned to GLM and 10 to PAM (83% men; age 33.4 ± 10.9 years; disease duration 4.4 ± 3.4 years). The baseline characteristics of the two groups were similar. At week 48, the proportions of patients who achieved an ASAS20 response were not significantly different between the GLM and PAM groups (65% vs. 56%; p = 0.69). Although there were no differences in BASDAI, spinal pain, and Medical Outcomes Study 36-item Short Form Health Survey (SF-36) scores between the two groups at week 48, the Ankylosing Spondylitis Disease Activity Score (ASDAS), Bath AS Functional Index (BASFI), C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) levels were significantly lower in GLM-treated patients. The SPARCC scores of the spine and SIJs decreased significantly in GLM- but not in PAM-treated patients. The differences in SPARCC scores between the two groups at week 48 were statistically significant. The frequency of adverse events (AEs) was similar in both arms. CONCLUSIONS: In patients with aSpA, the clinical response rate and improvement in pain and quality of life (QoL) were similar between GLM and PAM groups after 48 weeks. However, significant reduction in inflammatory markers and MRI inflammation was only observed with GLM treatment.

Specific epitopes of the structural and hypothetical proteins elicit variable humoral responses in SARS patients.

BACKGROUND: Severe acute respiratory syndrome (SARS) is an infectious disease which was caused by a novel coronavirus (SARS-CoV). SARS has caused an outbreak in the world during 2003 and 2004, with 8098 individuals being infected and a death toll of 774 in 28 regions around the world. Specific humoral responses to viral infection remain unclear. OBJECTIVE: To analyse the antigenicity of the SARS-CoV genome and identify potential antigenic epitopes in the structural proteins. METHODS: Potential antigenic epitopes were identified in the structural proteins (nucleocapsid, membrane, spike, and small envelope proteins) and hypothetical proteins (SARS3a, 3b, 6, 7a, and 9b) that are specific for SARS-CoV. A peptide chip platform was created and the profiles of antibodies to these epitopes were investigated in 59 different SARS patients' sera obtained 6-103 days after the onset of the illness. Serial sera from five additional patients were also studied. RESULTS: Epitopes at the N-terminus of the membrane protein and the C-terminus of nucleocapsid protein elicited strong antibody responses. Epitopes on the spike protein were only moderately immunogenic but the effects were persistent. Antibodies were also detected for some putative proteins, noticeably the C-termini of SARS3a and SARS6. CONCLUSIONS: Important epitopes of the SARS-CoV genome that may serve as potential markers for the viral infection are identified. These specific antigenic sites may also be important for vaccine development against this new fatal infectious disease.

High Incidence of Zidovudine Induced Anaemia in HIV Infected Patients in Southern Odisha.

Zidovudine (AZT), a nucleoside reverse transcriptase inhibitor was the first breakthrough in AIDS therapy in 1990.This study was conducted with an aim to determine prevalence of AZT induced anaemia in HIV infected patients initiated on AZT containing anti retroviral therapy(ART) regimen and also to find out any risk factor for causing AZT induced anaemia. Study was carried out in ART centre, M.K.C.G, MCH, Berhampur between Jan 2009 and Dec 2011. HIV infected patients registered at ART centre were treated according to National AIDS Control Organisation (NACO) guidelines. Patients (n = 1221) with Hb >8 gm/dl were prescribed AZT based ART regimen. Patients having anaemia (<8 gm/dl) were excluded from the study. Correlation of baseline characteristics (age, sex, weight, Hb level, CD4 count, World Health Organization (WHO) clinical stage) with risk of developing anaemia was also calculated. 178 (14.6 %) patients on AZT regimen developed anaemia. Patients with low CD4 count were more prone to develop severe anaemia. Age, sex, weight, WHO clinical stage had no relation with development of anaemia. Incidence of AZT induced anaemia was very high and patients having low CD4 count were more susceptible to develop anaemia.

Lymphadenopathy of Kimura's disease.

Kimura's disease is an important category of reactive lymphadenopathy in the Oriental population. The enlarged nodes are mostly located in the head and neck region. Salient pathological changes include florid germinal centers, Warthin-Finkeldey type polykaryocytes, vascularization of germinal centers, increased postcapillary venules in the paracortex, eosinophilic infiltration, and sclerosis. The pathology of Kimura's disease is quite different from that of angiolymphoid hyperplasia with eosinophilia (epithelioid hemangioma). Immunoperoxidase studies show IgE reticular networks in germinal centers. Nondegranulated surface IgE-positive mast cells are present in the paracortex. The authors propose that Kimura's disease represents an aberrant immune reaction to an as yet unknown stimulus. Although the individual histological features are nonspecific, the constellation of features is highly characteristic of Kimura's disease. Since lymphadenopathy can herald involvement of other tissues and the prognosis is excellent, accurate diagnosis of this disease in lymph node biopsies may spare the patients unnecessary radical surgery.

Angiocentric T-cell lymphoma of the skin. An aggressive lymphoma distinct from mycosis fungoides.

Among 37 consecutive cases of malignant lymphoma in which the skin was either the only site of disease or one of the prominent sites of initial involvement, 19 cases had a distinctive histological appearance. These cases corresponded to what has been termed "angiocentric lymphoma," and all were found to exhibit a T-cell phenotype either by frozen-section immunohistochemistry or by using monoclonal antibodies reactive in paraffin sections. There were nine men and 10 women; the mean age was 48.2 years. The lesions were nodular and were either ulcerated or had intact skin. One case presented with involvement of one anatomical region of skin, five had involvement of multiple regions of skin, and 13 had concurrent extracutaneous disease. The disease pursued an aggressive course and was not uncommonly resistant to treatment. Histologically, the lymphomatous infiltrate occurred predominantly in the mid to deep dermis with involvement of the subcutaneous layer. The pattern was mainly perivascular and peri-adnexal with or without confluence; the overlying epidermis and papillary dermis were often spared. A prominent feature was invasion of small or large blood vessels by lymphoma cells. Eight cases showed extensive coagulative necrosis of the neoplastic and normal tissues, and 12 cases showed intraneural invasion. The neoplastic lymphoid cells consisted of either a monomorphous population or a variable mixture of small, medium-sized, and large cells with stippled chromatin and distinct nucleoli. Although the nuclei were often irregularly folded, few exhibited a cerebriform configuration. The cytoplasm was pale to clear. These cases exhibit a remarkable histological similarity to the T-cell lymphomas of the nasal/nasopharyngeal region; in addition, there are features that overlap with so-called lymphomatoid granulomatosis of the skin.

Epstein-Barr virus-associated gastric lymphoma in Hong Kong Chinese.

We report 11 cases of gastric lymphoma that harbor the Epstein-Barr virus (EBV) encoded small messenger RNA, EBER-1, detected by in situ hybridization. The cases represented 18% of 61 consecutive gastric lymphomas from three institutions in Hong Kong between 1988 and 1993. The mean age of patients was 62 years (range, 33 to 87). The male to female ratio was 5:6. Nine of the 11 (81.8%) EBER-1+ gastric lymphomas were diffuse large cell lymphomas of B-cell type without low grade components. Macroscopically these lymphomas appeared either as large noncleaved cell (centroblastic) or immunoblastic type. From the available follow-up data, five of the nine patients with B-cell lymphoma were alive and well 48, 40, 14, 13, and 12 months, respectively, after gastrectomy and chemotherapy. One patient died of postoperative pneumonia and one died of a second malignancy (esophageal squamous carcinoma) 40 months after gastrectomy. None of the EBER-1+ B-cell gastric lymphomas showed histological features characteristic of low grade lymphoma of the mucosa-associated lymphoid tissue (MALT) type reported to be common in some Western countries. Of the two patients with T-cell lymphoma, one had a pleomorphic T-cell lymphoma and the other had an angiocentric lymphoma. The former was lost to follow-up after the biopsy and the latter presented with gastric perforation and died 1.5 months after gastrectomy. It is concluded that a significant proportion of gastric lymphomas in Hong Kong Chinese are EBV-related and that they show histological features more akin to conventional node-based lymphomas than to MALT-type lymphomas.

Monoclonal antibodies reactive with normal and neoplastic T cells in paraffin sections.

Without fresh or frozen tissue, it previously has been impossible to confirm the T-cell nature of reactive or neoplastic lymphoid cells. The availability of antibodies reactive with T cells in paraffin sections now allows retrospective analysis of a large number of cases. Two commercially available monoclonal antibodies, MT1 and MT2, were tested for their reactivities with T cells in a wide range of formalin-fixed, paraffin-embedded tissues, including 130 cases of immunologically characterized lymphoma. In reactive lymph nodes, MT1 stained the T-cell areas, whereas MT2 stained both the T-cell areas and mantle-zone B lymphocytes. MT1 stained 38 of 55 T-cell lymphomas (69.1%; 94.7% of cases from one hospital that used a shorter fixation time, and 55.6% of cases from another hospital that used a longer fixation time). MT2 stained only 6 (10.9%) of the T-cell lymphomas. Among the 74 cases of B-cell lymphoma, 3 (4.0%) were stained by MT1 and 30 (40.5%) by MT2.MT1 was also reactive with 3 of 4 cases of granulocytic sarcoma, as expected from its reactivity with normal granulocytes. Neither MT1 nor MT2 stained Reed-Sternberg cells or their variants in HodgKin's disease. We conclude that MT1 is a valuable marker for T cells, particularly when used with a panel of antibodies reactive with B cells in paraffin sections. MT2 is of limited value because of its cross-reactivity with many B-cell lymphomas.

Gastric adenocarcinoma with ciliated tumor cells.

Ciliated metaplasia (CM) of gastric mucosa is common in Japanese individuals but rare in whites. We studied 36 consecutive gastrectomies from Chinese individuals for the presence of CM. The gastrectomies were performed for adenocarcinoma (n = 22), benign ulcer (n = 13), and malignant lymphoma (n = 1). Ciliated metaplasia was found in 16 (44.4%) of the stomachs, with equal distribution between male and female patients. Ciliated metaplasia was present in 11 cases (50%) of adenocarcinoma and in five cases (38.5%) of benign ulcer, the difference being statistically insignificant. Contrary to previous studies, there was no increased frequency of CM in gastric mucosa harboring an intestinal-type adenocarcinoma compared with those with non-intestinal-type tumors. Ciliated metaplasia always co-existed with intestinal metaplasia. Colonization by Helicobacter pylori was not associated with an increased incidence of CM. In five cases (22.7%) of adenocarcinoma ciliated tumor cells were found, and all of these cases showed CM in the gastric mucosa. In one of these cases the whole tumor was composed of glands formed by ciliated cells. In the other cases there was a morphologically different nonciliated component. The cilia in the tumor cells showed light microscopic and ultrastructural changes identical to those of the cilia seen in CM affecting the nonneoplastic gastric mucosa. This study documents for the first time the co-existence of CM and ciliated adenocarcinoma in the same stomach. It is concluded that in the Hong Kong Chinese population CM is commonly present in gastric mucosa harboring an adenocarcinoma or benign ulcer. Adenocarcinomas with ciliated cells are strongly associated with CM.

Pathologic changes of gastric mucosa colonized by Helicobacter pylori.

One hundred eighty-nine consecutive gastric biopsies showing colonization by Helicobacter pylori (HP) were studied. Epigastric pain and bleeding were the clinical presentations in 167 cases (88.4%). Major endoscopic findings were gastritis (n = 72, 38.1%) and ulceration (n = 101, 53.4%). Duodenal ulcer was associated with 32 (44.4%) and 29 (28.7%) cases of gastritis and gastric ulcer, respectively. Histologically, the HP-colonized gastric epithelium showed characteristic degenerative changes that were topographically related to the bacteria but unrelated to the inflammatory infiltrate. Disintegration and loss of apical mucus with formation of epithelial pits was seen in nearly all cases. Other changes included microerosion, conventional erosion, and frank ulceration. Only the disintegration of apical mucus, epithelial pit, and microerosion were specific for HP colonization. These conditions were absent in areas not colonized by HP and in 79 consecutive HP-negative gastric biopsies seen during the same study period. The epithelial degenerative changes in HP-colonized gastric mucosa are easy to recognize in routine hematoxylin-eosin-stained sections and they could serve as histologic guides to the localization of the bacteria. It is proposed that HP-colonized gastric mucosa is a distinct pathologic entity with a pathologic spectrum ranging from active chronic gastritis to erosion and frank ulcer. Damage to the mucin-containing portion of the gastric epithelial cells appears to be the basic cytopathologic effect of HP on the gastric mucosa. As effective specific treatment for HP infection is available, identification of HP colonization in gastric biopsies should be attempted in all cases of gastritis and gastric ulcer.

Large B-cell lymphomas with a high content of reactive T cells.

Twenty-one cases of large, B-cell lymphoma with an unusually high content of reactive T lymphocytes are described in this report. Fifteen patients presented with lymphoma in nodal sites and six patients presented with lymphoma in extranodal sites. With two exceptions, all patients were more than 50 years of age. The male to female ratio was 1:2. Histologically, isolated to small groups of large lymphoid cells were intermingled with many small lymphocytes. The large cells were neoplastic and exhibited B-lineage markers; immunoglobulin light chain restriction could be demonstrated in two thirds of the cases. There was a rich infiltrate of immunophenotypically mature T lymphocytes that comprised more than 50% of the cellular population. The T lymphocytes ranged from small cells with dark, round nuclei to slightly larger cells with elongated, irregular nuclei. There were occasional medium-sized blastic cells. There was also a variable infiltrate of histiocytes with or without epithelioid features, eosinophils and plasma cells, and increased vascularity. The peculiar morphologic features were also reproduced in other sites in the four patients for whom additional histologic materials were available for examination. We postulate that the abundance of T cells results either from a florid host reaction or from cytokine secretion by the neoplastic B cells, attracting T cells to the vicinity. The morphologic and immunologic features mimic those of a variety of benign lymphoproliferative diseases, angioimmunoblastic lymphadenopathy and lymphomas arising in angioimmunoblastic lymphadenopathy, peripheral T-cell lymphoma, secondary B-immunoblastic lymphoma, and Hodgkin's disease. Careful morphologic evaluation and immunophenotypic studies using leukocyte antibodies reactive in paraffin-embedded sections are of great assistance in determining a diagnosis.

Nodular paragranuloma can transform into high-grade malignant lymphoma of B type.

A follow-up study of 537 cases of Hodgkin's disease, lymphocyte predominance type, nodular--designated as nodular paragranuloma (NP)--found simultaneous presence of (n = 11) or subsequent transition into (n = 3) a large cell lymphoma (LCL) in 14 cases. Morphologically, the LCLs were classified in ten cases as centroblastic lymphoma (malignant lymphoma, diffuse, large cell, non-cleaved cell), in three cases as immunoblastic lymphoma (malignant lymphoma, large cell, immunoblastic), and in one case as large cell anaplastic lymphoma. Eleven of the 14 LCLs were studied immunohistologically. Five cases showed a monotypic immunoglobulin (Ig) pattern, seven were positive to the monoclonal B-cell marker Ki-B3, and three showed both monotypic Ig and Ki-B3 positivity. With anti-Ig and Ki-B3, nine of the 11 LCLs could be classified as B-cell non-Hodgkin's lymphoma. Only one case of LCL exhibited the typical phenotype of Hodgkin cells, ie, positivity to anti-CD15 (3C4) and anti-CD30 (Ber-H2). A retrospective follow-up study of these secondary LCLs of B type revealed a longer survival time than that of primary B-type LCLs and other secondary LCLs. These findings indicate that B-type LCL is the most common outcome when NP progresses into a lesion of higher malignancy and provide further evidence of a close relationship of NP to the B-cell system. They also suggest that it would be clinically relevant to distinguish between cases of B-type LCLs secondary to NP and cases of LCLs without association with NP. This implies that signs of a preexisting NP should be looked for when a B-type LCL is diagnosed.

T- and T/natural killer-cell lymphomas of the salivary gland: a clinicopathologic, immunohistochemical and molecular study of six cases.

Primary salivary gland lymphomas are almost always of B lineage, with most being represented by low grade B-cell lymphoma of mucosa-associated lymphoid tissue. This study characterizes the rare non-B-cell lymphomas of the salivary gland based on an analysis of six cases. All patients were men, with a mean age of 53.5 years. They presented with submandibular or parotid mass, which on histological examination showed extensive interstitial infiltration by small, medium-sized, or large lymphoid cells. There was prominent invasion and expansion of the ducts and acini in five cases. Angioinvasion was evident in two cases. Three cases were of T lineage and were CD56 negative; one of these cases expressed CD30. Three cases showed an immunophenotype of CD2+ CD3(f)- CD3(p)+ CD56+, consistent with T/natural killer (NK) cell lymphoma. In situ hybridization for Epstein-Barr virus (EBV)-encoded early nuclear RNA (EBER) showed positive reaction exclusively in the three CD56+ cases. Clonal T-cell populations were shown in two CD56-negative cases by polymerase chain reaction on paraffin sections using primers for the T-cell-receptor (TCR) gamma-chain gene, but not in the other four cases (the three CD56+ cases and one CD56- case). Four patients (two CD56+ and two CD56-) died within 3 years, and two were disease free at 4 and 1.5 years, respectively. This study shows that salivary gland T- or T/NK-cell lymphomas cannot be reliably distinguished from B-cell lymphomas on morphological grounds alone, because both can show prominent lymphoepithelial lesions. It appears that T/NK-cell lymphomas, which are often extranodal in localization and strongly associated with Epstein-Barr virus (EBV), show a predilection to involve the salivary glands as well.

Correlation of content of B cells and Leu7-positive cells with subtype and stage in lymphocyte predominance type Hodgkin's disease.

Cases of lymphocyte predominance type Hodgkin's disease were investigated using immunohistochemical methods and compared for morphological subtype and clinical stage. Cases of nodular paragranuloma showed a high, diffuse paragranuloma a moderate, and the mixed type a low, content of B cells. There was no significant correlation between B cell content and clinical stage. The number of Leu7+ cells was significantly increased in stage I of nodular paragranuloma. Hodgkin cells did not react with the CD15 antibody in most cases of paragranuloma but showed reactivity in the mixed type.

Enumerating T-cell subsets on blood smears. An evaluation of an indirect immunoalkaline phosphatase method.

Peripheral blood T-lymphocyte subsets in 179 Chinese subjects were enumerated by an indirect immunoalkaline staining method done on ordinary blood smears. Absolute counts (X 10(9)/L) were 1.32 +/- 0.53 (T11), 0.73 +/- 0.31 (T4), 0.45 +/- 0.22 (T8) for males (n = 135) and 1.22 +/- 0.39 (T11), 0.69 +/- 0.20 (T4), 0.44 +/- 0.19 (T8) for females (n = 44). T4:T8 ratio for males and females were 1.79 and 1.58, respectively (0.05 less than P less than 0.10). Within-film area-to-area difference was 4.2 +/- 2.1% (n = 537 films). Interobserver discrepancy was 54 per 3,000 cells counted, or 1.8%. Film-to-film difference was 5.4 +/- 2.6% (30 pairs). T-lymphocyte subsets enumeration by immunostaining blood smears is a simple and reliable alternative to the immunofluorescence method. It avoids procedures that could artifactually affect lymphocyte subsets. The lower T4:T8 ratios revealed in this study could result because of technical reasons.

Invasive squamous cell carcinoma and cervical intraepithelial neoplasia III of uterine cervix. Morphologic differences other than stromal invasion.

The authors compared 69 cases of surgically proven invasive squamous cell carcinoma (ISCC) of uterine cervix with 48 cone biopsy specimens that showed cervical intraepithelial neoplasia (CIN) grade III. Histologic features that were preferentially associated with ISCC included the following: giant bizarre cells (66.7% in ISCC, 6.26% in CIN III, P < .01); large keratinized cells (87% in ISCC, 0% in CIN III, P < .01); keratin pearls (40.6% in ISCC, 0% in CIN III, P < .01); necrosis (79.7% in ISCC, 8.3% in CIN III, P < .01); and neovascularization (56.5% in ISCC, 0% in CIN III). In 51 (74%) cases of ISCC, a CIN III component was present, of which 18 (35.3%) showed large keratinized cells or keratin pearls in the in situ components. None of the CIN III cases showed more than one of the above features. In the ISCC group, the above features occurred with similar frequency in microinvasive and frankly invasive tumors. The authors' results agree with previous Papanicolaou-smear cytologic studies, which found that ISCC can be distinguished accurately from CIN III by the morphology of the neoplasm. The authors concluded that cervical biopsy specimens that show two or more of the above features are highly suggestive of ISCC, even when stromal tissue is absent or insufficient for the assessment of invasion. Furthermore, in cervical biopsy specimens showing CIN III, the presence of large keratinized cells or keratin pearls may signify the presence of invasive lesions elsewhere in the cervical mucosa.

Progressive transformation of germinal centers with and without association to Hodgkin's disease.

Progressively transformed germinal centers occurred in about 3.5% of cases of chronic nonspecific lymphadenitis. They are larger than germinal centers and are composed of follicular mantle lymphocytes, small clusters of proliferating mainly medium-sized B- and T-cells, as well as an extensive network of follicular dendritic cells. Sixty-six patients with lymph node enlargement containing progressively transformed germinal centers and staging and sequential biopsies of 213 patients with Hodgkin's disease (mixed and nodular sclerosis type) were investigated with special reference to the relationship of this lesion to Hodgkin's disease. In most cases, progressively transformed germinal centers developed without any obvious signs of illness and seemed to have no association with Hodgkin's disease. The patients could be differentiated into two groups. The larger group, Group 1 (n = 55 of 66) consisted of patients showing progressively transformed germinal centers without association to Hodgkin's disease. The smaller group, Group 2 (n = 11 of 66) showed progressively transformed germinal centers obviously with association to nodular paragranuloma (Hodgkin's disease lymphocytic predominance type). Progressively transformed germinal centers preceding (n = 3), simultaneously (n = 4), and after development of nodular paragranuloma (n = 4) were found. With regard to subtypes of Hodgkin's disease other than paragranuloma, progressively transformed germinal centers also could be found in sequential biopsies of Hodgkin's disease of mixed and nodular sclerosis type. In one case, progressively transformed germinal centers preceded, in another case they occurred simultaneously in mixed type of Hodgkin's disease, and in two cases of nodular sclerosis type progressively transformed germinal centers developed after the onset of Hodgkin's disease. These findings suggest that progressively transformed germinal centers may be a result of different processes that may be occasionally related not only to nodular paragranuloma, but also in rare cases to nodular sclerosis and mixed type of Hodgkin's disease.

New aggressive variant of suppressor/cytotoxic T-CLL.

Three cases of CD8+ CLL are reported. The patients are young (28, 18, 27 years old). The leukemia cells are predominantly small lymphocytes with irregular nuclei bearing notches and lobations. Cytoplasmic azurophilic granules are absent. Cytochemistry shows periodic acid-Schiff granular, alpha-naphthylacetate esterase focal, and acid phosphatase focal/granular positivities. Immunophenotypically cells are CD2+, CD3+, and CD8+ and lack CD4 as well as B-cell and NK cell antigens. All patients died within 20, 16, and 9 months, respectively. The clinicopathologic features of these cases differ clearly from those of the CD8+ CLL with azurophilic granules. These three cases represent a morphologically distinctive and more aggressive variant of CD8+ CLL.

Helicobacter pylori-related gastritis and gastric ulcer. A continuum of progressive epithelial degeneration.

One hundred forty-five consecutive gastric biopsy specimens showing colonization by Helicobacter pylori (HP) were studied. Biopsy specimens were obtained from patients with the following conditions: gastric ulcer (GU; 76), active chronic gastritis (ACG; 52), GU with duodenal ulcer (DU; 10), and ACG with DU (7). The mean age of the patients in the ACG group was 8.6 years less than the patients in the GU group. Helicobacter pylori colonization and HP-induced epithelial degeneration (ED) were quantified by a grading system (grades 0 to 6) comprising both focal and global scores for bacterial density (HP grade) and severity of ED (ED grade). The ED grade was directly proportional to the HP grade in all biopsy specimens. Gastric ulcer biopsy specimens were associated with higher HP grades: HP grade more than 5 in 25 cases (32.9%) and ED grade more than 5 in 18 cases (23.6%) of GU compared with similar respective scores in 9 cases (17.9%) and 2 cases (3.8%) of ACG. The difference was due primarily to a higher global score of bacterial density and higher focal score of ED in the GU biopsy specimens. These results support the hypothesis that HP-positive ACG and HP-positive GU are lesions within a single disease spectrum. Heavy HP colonization and severe HP-induced epithelial damage are predisposing factors in ulcerogenesis. Because HP-positive ACG is probably a preulcerative state, eradication of the bacteria in HP-positive ACG might prevent subsequent GU.

Coccoid forms of Helicobacter pylori in the human stomach.

Helicobacter pylori (HP) may transform from helical bacillary forms to coccoid forms after several days' in vitro incubation. The authors examined 111 consecutive gastrectomy specimens for the presence of coccoid forms of H pylori. Tissues from 64 stomachs (57.7%) showed colonization by H pylori, including 49 cases (76.6%) of adenocarcinoma, 14 cases (21.9%) of benign peptic ulcer, and 1 case (1.6%) of malignant lymphoma. Of these, coccoid forms of H pylori were identified in 53 cases (82.8%). In hematoxylin-and-eosin-stained sections coccoid forms of H pylori appeared as solid, round, basophilic dotlike structures. Under an electron microscope, coccoid forms of H pylori appeared as U-shaped bacilli, with the ends of the two arms joined by a membranous structure. Ultrastructural findings were identical to those from cultures of H pylori. With anti-Helicobacter antibody, coccoid forms of H pylori were positively stained by immunoperoxidase. Helical bacillary forms of H pylori invariably coexisted with the coccoid forms. By semiquantitative analysis, the number of coccoid forms in adenocarcinoma was significantly (P > .01) greater than that in benign peptic ulcers. This study confirms that H pylori can exist in coccoid forms in the human stomach. Coccoid forms should be distinguished from the pathogenic or nonpathogenic bacterial cocci, fungal spores, and cryptosporidia that may colonize the human stomach.