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.

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.

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.

Sputum cytology of patients with severe acute respiratory syndrome (SARS).

BACKGROUND: Severe acute respiratory syndrome (SARS) is a newly described form of atypical pneumonia linked to a novel coronavirus. AIMS: To review the sputum cytology of 15 patients who fulfilled the World Health Organisation clinical criteria for SARS in an attempt to evaluate whether early diagnosis is feasible with routine sputum examination. METHODS: All sputum samples from patients with SARS from the four major hospitals in Hong Kong were reviewed; abnormalities were sought in the cellular component, including abnormal numbers and morphology of the component cells compared with those from age matched controls taken over the same period one year ago. RESULTS: Fifteen sputum samples from patients were compared with 25 control samples. In the patients with SARS, loose aggregates of macrophages were seen more frequently in the sputum. These macrophages frequently showed morphological changes, such as cytoplasmic foaminess, vacuole formation, and nuclear changes (including multinucleation and a ground glass appearance) when compared with the control samples. CONCLUSIONS: The cytological features of SARS are non-specific, but the observation of any of the described features should prompt further investigations, especially in patients with suspicious clinical features.

Intestinal obstruction and gastrointestinal bleeding due to systemic amyloidosis in a woman with occult plasma cell dyscrasia.

A 60-year-old woman presented to our hospital with repeated vomiting. Upper gastrointestinal endoscopy revealed a 1 cm diameter ulcer with clean base on the roof of the gastric antrum. Histological examination of gastric biopsies revealed abundant amorphous eosinophilic deposits in the submucosa. Congo red stain for amyloid was positive. A barium follow-through study revealed a mass in the jejunum causing incomplete obstruction. Urine for Bence Jones protein was negative. Serum protein electrophoresis did not reveal any abnormal band and serum immunoelectrophoresis did not detect any monoclonal immunoglobulin. Bone marrow examination, however, revealed an increased proportion of plasma cells. Subsequent immunohistochemical staining demonstrated monoclonal lambda light chains in the marrow plasma cells, thereby confirming a plasma cell dyscrasia. Amyloidosis involving the gastrointestinal tract can produce a wide variety of non-specific symptoms and signs. A high index of suspicion is necessary to arrive at an early diagnosis. Management consists of supportive therapy for the gastrointestinal tract as well as treatment of the underlying condition.

Gastric polypoid lesions--illustrative cases and literature review.

Currently, upper gastrointestinal endoscopies are frequently performed for patients with various gastrointestinal symptoms. From time to time, lumps and bumps in the stomach are encountered on endoscopy. Four cases of gastric polypoid lesions are presented. The classification, differentiation, and management approach to these lesions are discussed. Although there is consensus that all gastric adenomatous polyps should be removed, as should gastric hyperplastic polyps that are symptomatic and/or bear dysplastic foci on forceps biopsy, controversy still exists over the management of asymptomatic gastric hyperplastic polyps that do not bear any dysplastic focus on forceps biopsies. Endoscopic ultrasonography (EUS) has a promising role in the evaluation of gastric submucosal polypoid lesions.

The accuracy of intraoperative frozen section in the diagnosis of ovarian tumors.

A retrospective study of 316 ovarian neoplasms which had frozen section evaluation between January 1, 1990 to December 31, 1995 was conducted to determine the accuracy of frozen section diagnosis of ovarian neoplasms. The frozen section results were compared with final diagnoses from paraffin sections. The frozen section diagnosis was accurate in 95.2% of all cases and inaccurate in 4.8%. The positive predictive value of a positive (or malignant) frozen section was 100%, the negative predictive value of a negative (or benign) frozen section was 98.2%. The sensitivity for malignant tumors as 87%. For tumors of borderline malignancy, the sensitivity and specificity were 60% and 98.6% respectively. Of the false negative frozen section diagnoses, 73% (8 cases) occurred in tumors of borderline malignancy. We concluded that with the exception of the sensitivity for the diagnosis of tumors of borderline malignancy, the sensitivity and specificity of frozen section diagnosis for benign and overtly malignant ovarian neoplasms are high.

Splenic lymphoma with villous lymphocytes showing del(7) and inv(10).

A 49-year-old woman presented with splenic lymphoma with villous lymphocytes (SLVL) that showed a clonal abnormality of del(7)(q22q32) in addition to inv(10)(p13q23), the latter being a previously undescribed abnormality in chronic lymphoproliferative disorders. A review of the literature on cytogenetic abnormalities of SLVL indicates that del(7q) is strongly associated with SLVL and may be important in the pathogenesis of this disorder.

A case of colonic tuberculosis mimicking Crohn's disease.

A 26-year-old Thai woman who has lived in Hong Kong for the past 3 years presented with a 2-month history of feverishness, intermittent epigastric discomfort, anorexia, and weight loss. She had had per rectal bleeding for 10 days. Colonoscopy on two separate occasions revealed multiple ulcerations involving the entire colon, with rectal sparing. Histological examination of the two sets of colonic biopsies that were obtained during colonoscopy suggested Crohn's disease. There was no response to mesalazine and metronidazole, but the patient responded promptly to a therapeutic trial of antituberculous drugs. Cultures from the first set of colonic biopsies were negative for acid-fast bacilli, but 8 weeks after the second colonoscopy, cultures from the second set of biopsies yielded Mycobacterium tuberculosis. This case illustrates that the diagnosis of colonic tuberculosis requires a high index of suspicion. In cases where the information available does not reveal a definite differentiation between colonic tuberculosis and Crohn's disease, corticosteroids should be withheld. The administration of corticosteroids to a patient with colonic tuberculosis may have disastrous results, and a therapeutic trial of antituberculous drugs should be considered instead.

Hairy cell leukemia variant with t(2;8)(p12;q24) abnormality.

Hairy cell leukemia variant is an uncommon chronic B-cell lymphoproliferative disorder characterized clinically by splenomegaly and marked leukocytosis. Cytologically, the leukemic cells are distinguishable from those of classical hairy cell leukemia by the presence of single, central, and vesicular nucleoli. Cytogenetic information for this uncommon leukemia is scanty, although structural abnormalities involving 7q34 have been reported in few cases. We report a patient with hairy cell leukemia variant who has t(2;8)(p12;q34) but without [corrected] c-MYC oncogene rearrangement.

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.

Hepatic angiomyelolipoma and tuberous sclerosis.

A patient with angiomyelolipoma of the liver, together with radiological evidence of pancreatic, renal and bony lesions characteristic of tuberous sclerosis, is described. Although the patient had no other clinical features of tuberous sclerosis, her daughter was found to suffer from the classical triad of this syndrome and also has had hepatic lipomatous lesions and bony involvement. This is the first histologically proven case of hepatic angiomyelolipoma associated with tuberous sclerosis.

Mucosal lymphangiectasia in gastric adenocarcinoma.

OBJECTIVE: To describe the occurrence and significance of mucosal lymphangiectasia in gastric adenocarcinoma. DESIGN: One hundred consecutive gastrectomies for adenocarcinoma were reviewed, using 25 consecutive gastroscopically biopsied gastrectomy specimens with peptic ulcers as negative controls. SETTING: The specimens were collected over a period of 25 months in two general hospitals and processed according to a standard protocol. PATIENTS: Chinese living in Hong Kong. RESULTS: Twenty cases of adenocarcinoma were found to show mucosal lymphangiectasia, which was arbitrarily defined as the presence of ectatic lymphatic channels in the lamina propria having maximum dimensions greater than that of a foveolar gland. The ectatic lymphatics were lined by simple endothelium, devoid of fibromuscular wall, and they either were optically empty or contained scant mononuclear leukocytes. None of the patients had preoperative evidence of malabsorption syndrome or protein-losing enteropathy. Lymphangiectasia was most readily seen in the superficial lamina propria near the main tumor. In 10 cases (50%), lymphangiectasia extended to the nonneoplastic part of the gastric mucosa, at a distance of at least 2 cm away from the main tumor. Tumor emboli were seen in the ectatic lymphatics in 11 cases (55%). In two cases (10%), the distal line of resection was involved by intramucosal lymphatic spread. The tumor permeating the lymphatics did not evoke any inflammatory or desmoplastic reaction in the perilymphatic lamina propria, similar to the phenomenon of so-called lymphangitis carcinomatosa. In eight cases (40%), there were foci beyond the main tumor where mucosal lymphangiectasia was present, but without tumor in its immediate vicinity. All (100%) of the 20 stomachs with mucosal lymphangiectasia had metastases in regional lymph nodes, whereas only 59 of the 80 cases (73.75%) without lymphangiectasia were node-positive (P < .025). All node-negative cases did not show lymphangiectasia. Twenty-five consecutive gastrectomies for peptic ulcer disease that had undergone preoperative mucosal biopsies showed no lymphangiectasia, suggesting that mucosal biopsy was not the cause of mucosal lymphangiectasia. CONCLUSIONS: (1) Gastric mucosal lymphangiectasia is associated with carcinoma but not peptic ulcer, (2) Mucosal lymphangiectasia in gastric carcinoma signifies lymph node metastases, and (3) Gastric carcinoma can spread along the mucosa via intramucosal lymphatics.

Primary lymphoepithelioma-like carcinoma of the lung. A clinicopathologic study of 11 cases.

BACKGROUND: Lymphoepithelioma-like carcinoma (LELC), best known to occur in the nasopharynx, can arise in a variety of sites, such as the salivary gland, thymus, lung, stomach, and skin. Primary LELC of the lung is very rare, with only limited information in the literature. METHODS: The clinicopathologic features of 11 patients with pulmonary LELC collected from two regional hospitals in Hong Kong are described. RESULTS: The patients, all Chinese, were aged 38 to 73 years (median, 54 years), with equal sex incidence. Two of the 8 patients were smokers. Four presented with coin lesions incidentally discovered on chest X-ray, five with cough and blood-stained sputum, and two with pleural effusion. The tumor formed a discrete (9 patients) or an ill-defined (1 patient) nodule in the lung, or, rarely, showed extensive bilateral pulmonary involvement (1 patient). The major bronchi were not involved except in 1 patient. Three patients had lymph node metastasis at presentation; two of them had bone metastasis, one at presentation and one after 9 months. The tumors had pushing margins, and grew in the form of anastomosing islands and sheets, comprising syncytial-appearing large cells with vesicular nuclei and prominent nucleoli. They were infiltrated by an appreciable number of small lymphocytes and plasma cells. Intratumoral amyloid globules were found in one tumor. In five patients, the tumor showed intraepithelial growth within the small bronchi; this could represent either the in-situ phase of the tumor or pagetoid spread into the bronchial epithelium. The neoplastic cells of all patients harbored Epstein-Barr virus (EBV) as demonstrated by in situ hybridization for EBV-encoded small nuclear RNAs. All eight Asian patients with pulmonary LELC previously reported in the literature similarly have been EBV-positive, whereas the four reported Caucasian patients all have been EBV-negative. CONCLUSION: Lymphoepithelioma-like carcinoma of lung occurring in Asians is an EBV-associated neoplasm; it also appears to occur at a higher frequency in Asians than Caucasians. It usually presents as a solitary subpleural nodule, and there is no strong association with cigarette smoking. Most patients have early stage disease at presentation. From the limited available data, the behavior of LELC of lung is highly variable, ranging from apparent curability by excision (particularly for localized disease) to highly aggressive, extensive disease at presentation.