67 research outputs found
Myocardial infarction due to septic thromboembolism in chronic rheumatic heart disease
Chronic rheumatic heart disease (RHD) is the most troublesome complication of rheumatic fever. Extensive valvular scarring and ventricular remodeling due to pressure and volume overload occur in chronic RHD. Deformed valves are at potential risk for developing infective endocarditis (IE) with further systemic embolism. We hereby describe a case of a patient diagnosed with chronic rheumatic heart disease and severe ventricular dysfunction, planned for aortic valve replacement. The patient developed septic shock during a hospital stay. The autopsy revealed infective endocarditis in the aortic valve with septic thromboembolism in the peripheral branches of the coronary artery and early multifocal myocardial infarction changes
Vascularity of human atrioventricular valves: A myth or fact?
BackgroundKnowledge of heart valve vascularity is an important factor for understanding the valvular pathology and to develop tissue-engineered valves for repair procedures. Some investigators believe that blood vessels may exist in normal human heart valves whereas some recent publications have proposed that the presence of blood vessels in the valves is secondary to inflammation.MethodsTissues from 60 normal formalin-fixed human hearts were examined microscopically for type, location, and number of vessels in atrioventricular valves. The age of the patient ranged from 10 to 70 years, and an attempt was made to study the age-related morphologic changes in atrioventricular valves.ResultsOf the 60 tricuspid and 60 mitral valves examined, 12 tricuspid (20%) and 14 mitral (23.33%) valves were found to have vessels without the presence of an inflammatory process. In tricuspid valves the vessels were observed mainly in the fibrosa layer with a range of 1 to 4 vessels, whereas in mitral valves the vessels were situated mainly in the spongiosa layer with a range of 1 to 2 vessels. The maximum vascularity was seen in the fourth decade of life, in which the vessels were found in 40% of both tricuspid and mitral valves. The mean transverse diameter of these vessels was 0.23 ± 0.18 mm, with a range of 0.06 to 0.79 mm in tricuspid valves, whereas it was 0.15 ± 0.08 mm, with a range of 0.04 to 0.4 mm in mitral valves. The capillaries (3-11 capillaries) were found scattered in the fibrosa and spongiosa with an average lumen area of 0.39 ± 0.18 mm2.ConclusionsThe blood vessels in atrioventricular valves also can be seen in the absence of inflammation and are likely to be a necessary component of valve leaflets. Thus, when performing procedures involving in situ tissue engineering and valve repair the physician needs to be aware of the presence of these vessels in human heart valves
Inclusion body fibromatosis
Inclusion body fibromatosis is a benign, often locally recurring myofibroblastic tumor with distinctive intracytoplasmic eosinophilic inclusions. In 1965, Reye1 was the first to document this entity through a series of 6 cases of digital fibrous tumors of childhood, where he observed intracytoplasmic inclusion bodies. This entity was later termed Reye’s tumor.2 As per the recent 2020 World Health Organization (WHO) classification, the other accepted terminologies include infantile digital fibroma/fibromatosis, recurring digital fibrous tumor(s) of childhood, and recurring digital fibroma(s) of childhood/infancy, where the etiology and pathogenesis remain unclear.3 It is a rare and slow-growing tumor that usually affects infants and children (mostly in less than 5 years) with equal gender distribution.4 These lesions most commonly affect the lateral and dorsal aspects of the last four digits, sparing the thumb, hand, or foot. Rarely, extremities, tongue, and breast act as the primary extradigital site. Grossly, the lesion appeared firm to rubbery and polypoidal dermal nodule with intact overlying stretched-out skin surface. Microscopically, the tumor cells contain characteristic intracytoplasmic 1.5 to 24 μm, rounded, pale pink round bodies located mainly in para nuclear location, highlighted better on Masson Trichrome (red color), phosphotungstic acid-hematoxylin (dark purple color), and Movat (pink color) stains. Ultrastructurally, the inclusions correspond to localized collections of non-membrane-bound, granular fibrillary material contiguous with the rough endoplasmic reticulum. These inclusions show strong immunoreactivity with actin and anti-calponin-1 antibody (inclusion containing calponin 1 as its possible content) but an occasional weak expression for caldesmon (the reason is still unknown). The recurrence rate is common with incomplete excision.5Figure 1 refers to a 2-year-old female child presented with nodular swelling over the dorsal aspect of the proximal phalanx of the right second toe (Figure 1A). The swelling appeared firm, slightly mobile, and non-tender, with a history of gradual increase in size since birth. The overlying skin was erythematous and stretched out. The mass was seen in close approximation with the nail bed. The respective interphalangeal and metatarsophalangeal joints were mobile. The plastic surgeons kept the possibility of fibromatosis and performed a Ray amputation of the right second toe. The specimen was submitted for histopathological examination.Figure 1Inclusion body fibromatosis. A - a nodular swelling over the dorsal aspect of the proximal phalanx of the right second toe measuring 1.6x1.4cm in size (scale bar = 1 cm). The overlying skin was intact, erythematous, and stretched out; B - the spindle-shaped uniform tumor cells show many intracytoplasmic and para-nuclear eosinophilic bodies causing nuclear indentation of one of the poles at places- black arrows (H&E; x200); C - Masson Trichrome stain highlights these inclusions as red-coloured – black arrows (x200); D - ultrastructurally, the tumor cell within the cytoplasm shows a round, dense body (size: 3.12 µm) located in the para-nuclear region with corresponding nuclear indentation.: The specimen grossly included a dislocated right second toe comprising proximal, middle, and distal phalanges, measuring 5.5cm in length and 1cm in width. In close proximity to the nail bed, the dorsal aspect showed a nodular mass measuring 1.6x1.3x0.4cm. The cut surface revealed a relatively well-demarcated lesion that was firm, homogenous, and white. The lesion was not reaching the underlying bone and also the surgical margins. Microscopically, the dermis showed a relatively well-circumscribed tumor with hyperkeratosis, parakeratosis, and flattened rete ridges of the overlying epidermis. The tumor was composed of spindle-shaped cells arranged in intersecting short fascicles and, at places, in whorls. These cells are benign and uniform and contain elongated nuclei, bland chromatin, inconspicuous nucleoli, and pale eosinophilic cytoplasm with indistinct cell membrane. Mitotic activity is infrequent (less than 1/10hpf) with no significant nuclear atypia or necrosis. In addition, many intracytoplasmic and para-nuclear eosinophilic bodies causing nuclear indentation of one of the poles at places were noted (Figure 1B). These inclusions appeared red-colored on the Masson Trichrome stain (Figure 1C), magenta-colored on the Periodic Acid-Schiff stain, and showed weak-to-moderate immunoreactivity for calponin immunostain. The surgical margins and the underlying bone were not involved in the tumor. Taking into account the clinical findings and histopathological aspects, a diagnosis of inclusion body fibromatosis was given. Subsequently, tissue was retrieved from a representative formalin-fixed, paraffin-embedded block and subjected to transmission electron microscopy. Ultrastructurally, the tumor cells showed round, dense bodies of varying sizes (2.97 µm to 4.32 µm) located in the para-nuclear region within the cytoplasm with corresponding nuclear indentation (Figure 1D). The tumor cells also contained bundles of myofilaments. Thus, the characteristic ultrastructural features further confirmed the diagnosis. Postoperatively, the patient was kept on close observation with no adjuvant therapy. At 4 months follow-up, no local recurrence was evident
GCM2 Silencing in Parathyroid Adenoma is associated with Promoter Hypermethylation and Gain of Methylation on Histone 3
PURPOSE: Glial cells missing 2 (GCM2), a zinc finger-transcription factor, is essentially required for the development of parathyroid glands. We sought to identify if the epigenetic alterations in the GCM2 transcription are involved in the pathogenesis of sporadic parathyroid adenoma. In addition, we examined the association between promoter methylation and histone modifications with disease indices.
EXPERIMENTAL DESIGN: mRNA and protein expression of GCM2 were analyzed by RT-qPCR and immunohistochemistry in 33 adenomatous and 10 control parathyroid tissues. DNA methylation and histone methylation/acetylation of GCM2 promoter were measured by bisulfite sequencing and ChIP-qPCR. Additionally, we investigated the role of epigenetic modifications on GCM2 and DNA methyltransferase 1 (DNMT1) expression in PTH-C1 cells by treating with 5-aza 2\u27deoxycytidine (DAC) and BRD4770 and assessed for GCM2 mRNA and DNMT1 protein levels.
RESULTS: mRNA and protein expression of GCM2 were lower in sporadic adenomatous than in control parathyroid tissues. This reduction correlated with hypermethylation (P\u3c0.001) and higher H3K9me3 levels in GCM2 promoter (P\u3c0.04) in adenomas. In PTH-C1 cells, DAC treatment resulted in increased GCM2 transcription and decreased DNMT1 protein expression, while cells treated with the BRD4770 showed reduced H3K9me3 levels but a non-significant change in GCM2 transcription.
CONCLUSION: These findings suggest the concurrent association of promoter hypermethylation and higher H3K9me3 with the repression of GCM2 expression in parathyroid adenomas. Treatment with DAC restored GCM2 expression in PTH-C1 cells. Our results showed a possible epigenetic landscape in the tumorigenesis of parathyroid adenoma and also that DAC may be promising avenues of research for parathyroid adenoma therapeutics
Transcriptional Profile of Mycobacterium tuberculosis in an in vitro Model of Intraocular Tuberculosis
Background: Intraocular tuberculosis (IOTB), an extrapulmonary manifestation of tuberculosis of the eye, has unique and varied clinical presentations with poorly understood pathogenesis. As it is a significant cause of inflammation and visual morbidity, particularly in TB endemic countries, it is essential to study the pathogenesis of IOTB. Clinical and histopathologic studies suggest the presence of Mycobacterium tuberculosis in retinal pigment epithelium (RPE) cells.Methods: A human retinal pigment epithelium (ARPE-19) cell line was infected with a virulent strain of M. tuberculosis (H37Rv). Electron microscopy and colony forming units (CFU) assay were performed to monitor the M. tuberculosis adherence, invasion, and intracellular replication, whereas confocal microscopy was done to study its intracellular fate in the RPE cells. To understand the pathogenesis, the transcriptional profile of M. tuberculosis in ARPE-19 cells was studied by whole genome microarray. Three upregulated M. tuberculosis transcripts were also examined in human IOTB vitreous samples.Results: Scanning electron micrographs of the infected ARPE-19 cells indicated adherence of bacilli, which were further observed to be internalized as monitored by transmission electron microscopy. The CFU assay showed that 22.7 and 8.4% of the initial inoculum of bacilli adhered and invaded the ARPE-19 cells, respectively, with an increase in fold CFU from 1 dpi (0.84) to 5dpi (6.58). The intracellular bacilli were co-localized with lysosomal-associated membrane protein-1 (LAMP-1) and LAMP-2 in ARPE-19 cells. The transcriptome study of intracellular bacilli showed that most of the upregulated transcripts correspond to the genes encoding the proteins involved in the processes such as adherence (e.g., Rv1759c and Rv1026), invasion (e.g., Rv1971 and Rv0169), virulence (e.g., Rv2844 and Rv0775), and intracellular survival (e.g., Rv1884c and Rv2450c) as well as regulators of various metabolic pathways. Two of the upregulated transcripts (Rv1971, Rv1230c) were also present in the vitreous samples of the IOTB patients.Conclusions:M. tuberculosis is phagocytosed by RPE cells and utilizes these cells for intracellular multiplication with the involvement of late endosomal/lysosomal compartments and alters its transcriptional profile plausibly for its intracellular adaptation and survival. The findings of the present study could be important to understanding the molecular pathogenesis of IOTB with a potential role in the development of diagnostics and therapeutics for IOTB
Tumor-induced osteomalacia: experience from three tertiary care centers in India
Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome characterized by recalcitrant hypophosphatemia. Reports from the Indian subcontinent are scarce, with most being single center experiences involving few patients. Herein, we conducted a retrospective analysis of 30 patients of TIO diagnosed at three tertiary care hospitals in India. Patients with persistent hypophosphatemia (despite correction of hypovitaminosis D), normocalcemia, elevated alkaline phosphatase, low TmP/GFR and elevated or ‘inappropriately normal’ FGF23 levels were labeled as having TIO. They were sequentially subjected to functional followed by anatomical imaging. Patients with a well-localized tumor underwent excision; others were put on phosphorous and calcitriol supplementation. The mean age at presentation was 39.6 years with female:male ratio of 3:2. Bone pain (83.3%) and proximal myopathy (70%) were the chief complaints; 40% of cases had fractures. The mean delay in diagnosis was 3.8 years. Tumors were clinically detectable in four patients (13.3%). The mean serum phosphate was 0.50 mmol/L with a median serum FGF23 level of 518 RU/mL. Somatostatin receptor-based scintigraphy was found to be superior to FDG-PET in tumor localization. Lower extremities were the most common site of the tumor (72%). Tumor size was positively correlated with serum FGF23 levels. Twenty-two patients underwent tumor resection and 16 of them had phosphaturic mesenchymal tumors. Surgical excision led to cure in 72.7% of patients whereas disease persistence and disease recurrence were seen in 18.2% and 9.1% of cases, respectively. At the last follow-up, serum phosphate in the surgically treated group was significantly higher than in the medically managed group
Idiopathic restrictive cardiomyopathy - perspectives from genetics studies. Is it time to redefine these disorders?
Idiopathic restrictive cardiomyopathy (IRC) is a rare form of heart muscle disease. Genetic studies have revealed that in about half the cases, IRC forms part of the hereditary sarcomeric contractile protein disease spectrum. Mutations in several sarcomere protein encoding genes are detected in 33-66% of cases. Among these, the mutations most commonly involve <em>TNNI3</em> and <em>MYH7</em>. There is a disproportionately high incidence of <em>TNNI3</em> mutations in patients with restrictive physiology. <em>De novo </em>mutations are also frequently seen in this group of patients. IRC and hypertrophic cardiomyopathy (HCM) with restrictive phenotype reflect the same or very similar disorders with different names due to arbitrary cut offs in the left ventricular wall thickness rather than two separate distinct diseases. HCM with restrictive physiology should be considered part of a continuous spectrum with IRC. This is because patients with HCM with restrictive phenotype bear far greater clinical and genetic resemblance to IRC than to rest of the HCM cohort
Wolf′s isotopic response: Report of a case and review of literature
"Wolf′s isotopic response" refers to the occurrence of a new dermatosis at the site of previously healed dermatosis. A number of factors including viral, neural, vascular, and immunologic factors have been implicated in the causation of this peculiar response but none has been proven conclusively. Here, we report a case where lichen planus developed at the site of dermatofibrosarcoma protruberans that had been previously treated with surgery and radiotherapy. We also put forth a hypothesis on the genesis of isotopic response considering the above mentioned factors
Primary Leiomyosarcoma of Breast in an Adolescent Girl: A Case Report and Review of the Literature
Leiomyosarcoma of the breast is a rare neoplasm, primarily reported in older women. Only 44 cases have been reported in world literature and to the best of our knowledge, no case has been reported from India till date. We report a case of primary breast leiomyosarcoma in an adolescent girl who underwent a lumpectomy for rapidly increasing lump in the left breast. Here we report the histological findings and immunohistochemical profile of this entity, along with a review of existing literature
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