Case report: Disseminated Cladophialophora bantiana phaeohyphomycosis in a dog with hepatic dysfunction, and concurrent ehrlichiosis.

A 1-year-old mixed breed dog initially presented with marked ascites due to a low-protein transudate resulting from portal hypertension. Laboratory evaluation revealed non-regenerative anemia, lymphopenia, thrombocytopenia, evidence of hepatic insufficiency [hypoalbuminemia, decreased urea, increased post-prandial bile acids, prolonged activated partial thromboplastin time (aPTT)] and Ehrlichia canis infection. Approximately a week later, the dog was declining and was euthanized. On autopsy, multifocal hepatic granulomas and acquired portosystemic shunts (APSS) were seen. Imprint cytology revealed fungal hyphae and pyogranulomatous inflammation in the liver and brain. Disseminated Cladophialophora bantiana phaeohyphomycosis was diagnosed by histologic examination, culture and PCR. Immunosuppression due to ehrlichiosis is suspected to have predisposed this animal to fungal infection. To the authors' knowledge, this is the first report of C. bantiana in the West Indies.

Transudative Malignancy: Uncommon and Real.

Light's criteria are the cornerstone to differentiate exudates from transudates. The traditional literature states that malignant pleural effusions are rarely transudative; therefore, cytology tends to be low yield and not a cost-effective decision. This case describes an 82-year-old female who developed a transudative pleural effusion despite having an underlying malignancy, highlighting the importance of integrating clinical judgment into pursuing thoracentesis with the cytological examination.

Rhinorrhea and increased chloride secretion through the CFTR chloride channel-a systematic review.

PURPOSE: Allergic and non-allergic rhinorrhea in the forms of acute or chronic rhinosinusitis can mean a watery nasal discharge that is disabling. Primary objective was to review the evidence supporting the hypothesis that rhinorrhea is due to increased chloride secretion through the CFTR chloride channel. METHODS: The structure of the evidence review followed the EQUATOR Reporting Guidelines. Databases searched from inception to February 2022 included Pubmed, EMBASE and the Cochrane library using keywords "Rhinorrhea", "chloride", "chloride channel", "CFTR" and "randomized controlled trial". Quality assessment was according to the Oxford Centre for Evidence-based Medicine. RESULTS: 49 articles were included. They included randomized controlled trials out of which subsets of data with the outcome of rhinorrhea on 6038 participants were analysed and in vitro and animal studies. The review revealed that drugs, which activate CFTR are associated with rhinorrhea. Viruses, which cause rhinorrhea like rhinovirus were found to activate CFTR. The chloride concentration in nasal fluid showed an increase in patients with viral upper respiratory tract infection. Increased hydrostatic tissue pressure, which is an activator of CFTR was observed in allergic upper airway inflammation. In this condition exhaled breath condensate chlorine concentration was found to be significantly increased. Drugs, which can reduce CFTR function including steroids, anti-histamines, sympathomimetic and anticholinergic drugs reduced rhinorrhea in randomized controlled trials. CONCLUSIONS: A model of CFTR activation-mediated rhinorrhea explains the effectiveness of anticholinergic, sympathomimetic, anti-histamine and steroid drugs in reducing rhinorrhea and opens up avenues for further improvement of treatment by already known specific CFTR inhibitors.

Diagnostic utility of LDH measurement for determining the etiology of modified transudate pleural effusion in cats.

Fluid analysis is an initial approach for determining the underlying causes of body cavity effusions. Modified transudate is commonly diagnosed in pleural effusion in cats, however, it provides limited diagnostic information. Aims of this study were to investigate common etiologies causing different pleural fluid types and to evaluate the usefulness of lactate dehydrogenase (LDH) for differentiating the etiology in modified transudates in cats. Pleural effusion samples from 122 cats were analyzed and classified into three types: transudate, modified transudate, and exudate. Causes of pleural effusion were classified into four conditions: cardiac disease, neoplasia, feline infectious peritonitis (FIP), and pyothorax. The relationship of underlying etiology and fluid types was described. The LDH levels in pleural fluid and plasma were compared between the causes in the samples classified as modified transudate. The fluid analysis of pleural effusion showed that modified transudate was the most common fluid type (44.2%). Neoplasia was predominantly diagnosed (38.5%) as the etiology of pleural effusion. There was no significant correlation between pleural fluid and plasma LDH level in any type of pleural fluid, suggesting that pleural fluid LDH does not appear to be affected by plasma LDH. The occurrence of modified transudate was not associated to its etiologies, however, the LDH level in modified transudates showed significant differences between etiologic groups. The LDH level in modified transudate was excellent in separating cardiac from non-cardiac diseases with a cut-off value of <535 U/L and separating FIP from non-FIP diseases with a cut-off value of >641 U/L. Based on the current findings, pleural fluid LDH can be a useful adjunctive marker for differentiating some causes of modified transudate pleural effusion and should be added in the routine diagnostic work-up of feline patients with pleural effusions.

Diagnostic value of pleural cholesterol in differentiating exudative and transudative pleural effusion.

Background: Pleural effusions are most commonly classified as transudative or exudative based on Light's criteria which has shown misclassification in 10%-20% of cases. Studies have demonstrated lesser misclassification with pleural fluid cholesterol criteria. Thus, this study aimed to find the diagnostic properties of pleural fluid cholesterol in differentiating the type of effusion. Materials and methods: This cross-sectional study involving 72 patients was undertaken in a tertiary center in Nepal for a duration of 2 years. On the basis of Light's, Heffner's, etiological, and pleural fluid cholesterol criteria, pleural effusion was classified as exudative or transudative. The findings were then evaluated to determine the diagnostic value of each approach in identifying the effusion type and comparing them on the basis of sensitivity, specificity, positive predictive value and negative predictive value. Result: Pleural fluid cholesterol detected effusion as exudative with sensitivity of 91.94% and specificity of 80.00% against Light's criteria; with a sensitivity of 98.28% and specificity of 85.71% against the etiological diagnosis. Additionally, against the etiological diagnosis, sensitivity of both Light's and Heffner's criteria was 100%; however, specificity was 71.43% and 64.29% respectively, which is far less than that of pleural fluid cholesterol (85.71%). Furthermore, pleural fluid cholesterol was also found to have better results than protein ratio, LDH ratio and pleural fluid protein ratio in determining the type of effusion. Conclusion: When considering the avoidance of confusing outcomes in equivocal instances and cost effectiveness in developing nations, pleural fluid cholesterol can be one of the most useful alternative diagnostic methods for differentiating between exudative or transudative effusions.

Serous fluid: Reactive conditions.

This chapter highlights the steps that would help to analyze any fluid. It highlights importance of knowing gross analysis of fluid along with biochemical information. These parameters along with clinical information are very important in arriving at a differential diagnosis. Morphologic appearances in the fluid can often become challenging and occasionally reactive conditions can reveal changes that may mimic malignancies. This chapter provides not only a framework of approach to assessment of fluid cytology but also shows how to distinguish some of the challenging reactive conditions from the diagnosis of carcinoma. The chapter also utilizes two cases to demonstrate approach to reactive conditions. This review article will be incorporated finally as one of the chapters in CMAS (CytoJournal Monograph/Atlas Series) #2. It is modified slightly from the chapter by the initial authors in the first edition of Cytopathologic Diagnosis of Serous Fluids.

Comparative Study of Vascular Endothelial Growth Factor in Exudative and Transudative Pleural Effusion.

Background: Increased vascular permeability is one of the main mechanisms in the production of pleural effusion (PE) and vascular endothelial growth factor (VEGF) has a significant role in its pathogenesis. This study aimed to compare pleural levels of VEGF in transudative and exudative PEs besides the other pleural markers. Materials and Methods: In this prospective cross-sectional study, 80 patients with PE were divided into 4 groups as transudative (N=15), parapneumonic (N=15), tuberculosis (N=25), and malignant (N=25) PE. Biochemical tests measured the pleural protein, LDH, cholesterol, glucose, polymorphonuclear cell (PMN), and lymphocyte. ELISA measured the pleural VEGF level. Results: Out of 80 patients, 51 were male, and the total mean age was 55.34±18.53. There were significant differences in pleural VEGF between exudative and transudative effusion (P<0.001) and between malignant and benign effusion (P=0.014). The highest mean difference in pleural VEGF levels was seen in the comparison of transudative and malignant groups (Mean difference=-136.56; P<0.002). The VEGF level in 3 groups was not significantly different; transudative vs tuberculous, parapneumonic vs tuberculous, and parapneumonic vs malignant. Furthermore, VEGF higher than 73.09 pg/ml had a 64% sensitivity and 82% specificity for the diagnosis of malignancy. Among pleural markers (VEGF, protein, LDH, and glucose), VEGF had the highest area under curve (AUC=0.734). Moreover, pleural protein, LDH, and glucose levels significantly correlated with pleural VEGF; however, pleural cholesterol, PMN, and lymphocyte were not correlated. Conclusion: VEGF is assumed as an important factor in the pathogenesis of exudative PE, especially malignant effusion. It can distinguish between lymphocytic exudative PEs.

Adolescents' and caregivers' perceptions of caregiver-provided testing and HIV self-testing using oral mucosal transudate tests in Zimbabwe: a short report.

Uptake of HIV testing remains lower among children and adolescents compared to adults. This study explored adolescents' perceptions of HIV self-testing (HIVST) and caregivers' perceptions of testing their children using an oral mucosal transudate (OMT) rapid HIV test (caregiver-provided testing). We conducted 31 interviews with adolescents aged 16-18 years and caregivers of children aged 2-15 years who received an OMT test. Participants described barriers to HIV testing including lack of privacy and the potential for discrimination by community members towards children and adolescents who received an HIV test. Most participants felt caregiver-provided testing and HIVST could address these barriers through increased privacy. Some participants expressed worry about their ability to correctly perform the OMT and their anxious reactions to a positive result. Counseling and assistance from health care workers were viewed as ways to alleviate concerns. Concerns shaped participants' preferences for facility-based HIVST and caregiver-provided testing. Findings demonstrate HIVST performed by adolescents and caregiver-provided testing could increase the uptake of HIV testing. Concerns related to being able to test correctly and the availability of post-test counseling must be addressed in any future delivery mechanisms.

Transudative Pleural Effusion Associated with Extramedullary Hematopoiesis.

The authors report a case of transudative pleural effusion associated with extramedullary hematopoiesis due to the presence of a myeloproliferative neoplasm, which was unclassified. A 71-year-old man presented with right pleural effusion during an exacerbation of thrombocytosis. The pleural effusion was transudative, although there was no history of cardiac failure or hypoalbuminemia, and treatment with diuretics failed. Extramedullary hematopoiesis was diagnosed in bilateral paravertebral soft tissue and the liver on 111In bone marrow scintigraphy. The administration of hydroxyurea simultaneously reduced peripheral blood platelet count and pleural effusion within 2 weeks. The possible cause of transudative pleural effusion in association with extramedullary hematopoiesis is discussed.

Cytological-energy analysis of pleural effusions with predominance of neutrophils.

BACKGROUND: The predominance of neutrophils in pleural effusions of patients with different serious impairments of the pleural cavity organs is often found. The aim of this study was to identify the type of injury using the cytological-energy analysis of pleural effusions. METHODS: We analysed 635 samples of pleural effusions with predominance of neutrophils. We compared the values of the coefficient of energy balance (KEB), lactate dehydrogenase (LDH) and aspartate aminotransferase (AST) catalytic activities in the following subgroups of patients: with transudative effusions, purulent pneumonia, chest empyema and after chest surgery with and without purulent complications. Statistical analysis was performed using the ANOVA Kruskal-Wallis test (p < 0.05 was considered as significant). RESULTS: We found the lowest KEB values in pleural effusions of patients with chest empyema and their gradual increases in patients with purulent pneumonia and with transudative effusions. We observed the highest LDH and AST enzymes activity in patients with chest empyema and their gradual decrease in patients with purulent pneumonia and with transudative effusions. LDH and AST enzymes activity was significantly higher in pleural effusions of patients after chest surgery with purulent complications compared with non-purulent cases. CONCLUSION: The most intensive inflammation and the most extensive tissue destruction in the pleural cavity were found in patients with chest empyema. Significantly better parameters were observed in patients with purulent pneumonia. The absence of serious inflammation and the absence of tissue destruction were typical for patients with transudative effusions. Finally, our results confirmed an anticipated higher tissue destruction in patients after chest surgery. Significantly worse injury was found in surgical patients with purulent complications compared with non-purulent ones. The reviews of this paper are available via the supplemental material section.

Contemporary biochemical analysis of normal pericardial fluid.

OBJECTIVE: Biochemical analysis of pericardial fluid (PF) is commonly performed for the initial assessment of PF, and the results are usually interpreted according to Light's traditional criteria for the differential diagnosis of transudates versus exudates. However, Light's criteria have been formulated for the biochemical analysis of pleural fluid. The aim of the present paper is to evaluate the normal composition of PF in candidates for cardiac surgery. METHODS: Cohort study with analysis of PF from candidates for cardiac surgery. Exclusion criteria were previous pericardial disease or cardiac surgery, prior myocardial infarction within 3 months, systemic disease (eg, systemic inflammatory diseases, uremia) or drug with potentiality to affect the pericardium. RESULTS: Fifty patients (mean age was 67 years; 95% CI 64 to 71, 29 males, 58.0%) were included in the present analysis. Levels of small molecules were similar in blood and PF. Total proteins in PF was, on average, 0.5 times lower than corresponding plasma levels (p=0.041), while the level of pericardial lactate dehydrogenase was, on average, 1.06 times higher than plasma (p=0.55). Moreover, mononuclear cells were more concentrated in PF than plasma (p=0.17). Traditional Light's criteria misclassified all PFs as exudates. CONCLUSIONS: Traditional Light's criteria misclassified normal PFs in candidates for cardiac surgery as exudates. This study suggests their futility for the biochemical analysis of PF in clinical practice.

Pyloric outflow obstruction secondary to sclerosing encapsulating peritonitis in a dog.

A 6-year-old, male neutered mixed breed dog was presented emergently with a three-week history of hyporexia, vomiting, diarrhoea and weight loss. Upon examination, the patient was dull, had generalised muscle atrophy, moderate abdominal pain and a mild amount of peritoneal effusion. A fluid-filled, distended, corrugated small bowel with marked gastroparesis and moderate peritoneal effusion was noted on abdominal ultrasonography. Endoscopy revealed hyperaemic and friable mucosa and a subjectively narrowed pylorus. Emergency exploratory celiotomy was performed due to worsening patient condition and revealed thick, diffuse, fibrous adhesions of the abdominal cavity. Based on these findings, sclerosing encapsulating peritonitis (SEP) was suspected. A large mass of omentum adjacent to the greater curvature of the stomach had caused a pyloric outflow obstruction. Adhesiolysis was attempted but was unsuccessful due to the friability of the small intestines. The dog was humanely euthanased under anaesthesia. A diagnosis of SEP was confirmed via necropsy. No underlying cause was identified. This is the first known case of a pyloric outflow obstruction secondary to SEP in a dog. Although rare, this condition should be considered as a differential for dogs with signs of a pyloric outflow obstruction with concurrent ascites and abdominal pain, hyporexia, vomiting and diarrhoea.

A Predictive Model for the Identification of Cardiac Effusions Misclassified by Light's Criteria.

OBJECTIVES: The application of Light's criteria misidentifies approximately 30% of transudates as exudates, particularly in patients on diuretics with cardiac effusions. The purpose of this study was to establish a predictive model to effectively identify cardiac effusions misclassified by Light's criteria. METHODS: We retrospectively studied 675 consecutive patients with pleural effusion diagnosed by Light's criteria as exudates, of which 43 were heart failure patients. A multivariate logistic model was developed to predict cardiac effusions. The performance of the predictive model was assessed by receiver operating characteristic (ROC) curves, as well as by examining the calibration. RESULTS: It was found that protein gradient of >23 g/L, pleural fluid lactate dehydrogenase (PF-LDH) levels, ratio of pleural fluid LDH to serum LDH level (P/S LDH), pleural fluid adenosine deaminase (PF-ADA) levels, and N-terminal pro-brain natriuretic peptide (NT-pro-BNP) levels had a significant impact on the identification of cardiac effusions, and those were simultaneously analyzed by multivariate regression analysis. The area under the curve (AUC) value of the model was 0.953. The model also had higher discriminatory properties than protein gradients (AUC, 0.760) and NT-pro-BNP (AUC, 0.906), all at a P value of <.01. CONCLUSION: In cases of suspected cardiac effusion, or where clinicians cannot identify the cause of an exudative effusion, this model may assist in the correct identification of exudative effusions as cardiac effusions.

Derrames pleurales trasudados y exudados: clasificación

Es importante saber diferenciar los derrames pleurales como resultado de un exudado o de un trasudado para poder diagnosticar las diferentes causas de esta enfermedad. Se describieron las características y la formación del líquido pleural, las causas según el tipo de derrame, así como los procedimientos necesarios para tomar muestras útiles para un mejor análisis en el laboratorio clínico. Se planteó una estrategia actualizada para diferenciar los líquidos trasudados y exudados mediante métodos bioquímicos propuestos por Light y el progresivo enriquecimiento de esta estrategia por otros investigadores. Se plantea la utilidad del recuento de las células. Se analizaron algunas limitaciones que existen para diferenciar los tipos de derrames y la de algunos marcadores bioquímicos para diferenciar un exudado de un trasudado, así como los procedimientos que pueden aplicarse en el laboratorio clínico. Encontramos que el criterio de Light es el más eficiente para diferenciar los exudados de los trasudados en los derrames pleurales de causa desconocida.

It is important to know how to differentiate pleural effusions resulting from whether an exudate or transudate in order to diagnose the different causes of this disease. We describe the characteristics and formation of pleural fluid, the causes for each type of effusion, as well as the necessary procedures to take useful samples that allow better analysis in the clinical laboratory. An updated strategy was designed to differentiate transudate and exudate fluids through the biochemical methods proposed by Light and by other researchers who have developed and enriched their methods. We also mentioned the usefulness of cell count. We analyzed some limitations to differentiate the types of effusions and those some biochemical markers present to distinguish an exudate from a transudate, as well as the procedures that can be applied in the clinical laboratory. We concluded that Light's criterion is the most efficient to differentiate exudates from transudates in pleural effusions of unknown cause.

Pediatric pleural tuberculosis.

Background: Pleural tuberculosis (TB) diagnosis is sometimes controversial because the microbiologic confirmation ratio is very low in pleural fluid. There are few pediatric pleural TB case series in the literature. Methods: We retrospectively evaluated our TB cases below 18 years of age and extracted pleural TB cases. Results: Seven cases with pleural TB were identified. About 42.9% of the patients had isolated pleural TB whereas 57.1% of the patients had accompanying pulmonary TB. Lymphocytic pleural effusion and increased adenosine deaminase (ADA) (>40 U/L) level are found in 85.7% of the patients. Six patients had uncomplicated effusion (transudate) according to Light's criteria and one had complicated effusion (exudate). Lung decortication was needed in three patients. All patients were given 6 months anti-TB medication and recovered completely. Conclusion: In the lymphocyte-predominant pleural effusion, an increased ADA level highly supported TB disease. The complicated effusion (exudate) in pleural TB is not rule; uncomplicated effusion (transudate) could be seen.

Salivary cytokine panel indicative of non-small cell lung cancer.

Objective To develop a combinatorial panel of salivary cytokines that manifests the presence of non-small cell lung cancer (NSCLC) that will eventually improve prognosis by facilitating the early diagnosis and management of this common cancer. Methods We performed a case-control study comparing salivary cytokine profiles of 35 adult subjects with NSCLC with those of 35 matched, healthy nonsmokers. Multiplex bead array assays were used to quantify 27 cytokines in saliva, serum, and oral mucosal transudate samples. Logistic regression analysis was used to develop an informative cytokine panel. Receiver operating characteristic (ROC) curves were generated to evaluate the discriminant ability of the panel. Results A combinatorial 12-cytokine panel (interleukin receptor antagonist [IL1RN], IL1B, IL6, IL7, IL8, IL10, C-C motif chemokine ligand 11 [CCL11], tumor necrosis factor, C-X-C motif chemokine ligand 10 [CXCL10], C-C motif chemokine ligand 3, C-C motif chemokine ligand 4, and platelet-derived growth factor-BB) distinguished patients with NSCLC from healthy controls. Further, ROC analysis revealed that a cytokine panel comprising IL10 (odds ratio, 1.156) and CXCL10 (odds ratio, 1.000) discriminated NSCLC with a sensitivity of 60.6% and specificity of 80.8% (area under the ROC curve, 0.701). Conclusion A combinatorial panel of select salivary cytokines indicates the presence of NSCLC.

Transudative pleural effusion of malignant etiology: Rare but real.

A 62-year-old female presented to the emergency room with one-month history of epigastric abdominal pain, nausea and vomiting. She endorsed progressive dyspnea over two weeks. CT of the abdomen demonstrated bilateral pleural effusions and pancreatic inflammation, so the working diagnosis was pancreatitis. A diagnostic thoracentesis was performed and the pleural fluid analysis was classified as transudate by Light's criteria. Given the atypical features in history and concern for malignancy, fluid was sent for cytological examination and immunohistochemistry which suggested a mucinous malignancy. EGD revealed poorly differentiated signet ring cell adenocarcinoma of stomach. Patient underwent placement of indwelling pleural catheters for symptomatic improvement and was discharged to hospice. The decision whether to routinely send transudative effusions for cytological evaluation remains controversial. This case demonstrates the importance of using clinical judgement to guide that decision.

Loculated transudative pleural effusion masquerading as right upper lobe consolidation in a haemodialysis patient.

Pleural effusion is a common encounter in renal failure patients and frequently possess a diagnostic challenge to clinician especially when it was exudative. Fortunately, transudative pleural effusion secondary to fluid overload remains the commonest cause of pleural effusion in haemodialysis patients. Frequent thoracocentesis enhance pleural inflammation and potentially complicate further this challenging clinical presentation. We report a middle-aged gentleman with advanced chronic kidney disease presented with dyspnea and new right upper lobe consolidation on chest roentograph. He had a history of recurrent bilateral pleural effusion secondary to fluid overload and hence multiple attempts of thoracocentesis were performed. Medical thoracoscopy performed previously yielded non-specific pleuritis. Flexible bronchoscopy demonstrates normal airway with negative microbiological studies. Computed tomography (CT) of the thorax shown a loculated hypodense pleural effusion at the apical region of the right upper lobe. Ultrasound guided thoracocentesis anteriorly yield 400 mL of clear straw color fluid which was transudative by Light's criteria. Post tapping chest X-ray shown complete resolution of right upper lobe consolidation and patient reports immediate relieve of dyspnea. Patient was started on regular effective haemodialysis and pleural effusion did not recur during follow up. Loculated pleural effusion masquerading as mediastinal tumour had been reported but pleural effusion that conformed to the contour of a lung lobe is rare. This case highlights the atypical but unique presentation of a transudative pleural effusion and demonstrates the risk of repeated thoracocentesis complicating a simple clinical presentation.

Hepatic hydrothorax: clinical review and update on consensus guidelines.

Hepatic Hydrothorax (HH) is defined as a pleural effusion greater than 500 ml in association with cirrhosis and portal hypertension. It is an uncommon complication of cirrhosis, most frequently seen in association with decompensated liver disease. The development of HH remains incompletely understood and involves a complex pathophysiological process with the most acceptable explanation being the passage of the ascetic fluid through small diaphragmatic defects. Given the limited capacity of the pleural space, even the modest pleural effusion can result in significant respiratory symptoms. The diagnosis of HH should be suspected in any patient with established cirrhosis and portal hypertension presenting with unilateral pleural effusion especially on the right side. Diagnostic thoracentesis should be performed in all patients with suspected HH to confirm the diagnosis and rule out infection and alternative diagnoses. Spontaneous bacterial empyema and spontaneous bacterial pleuritis can complicate HH and increase morbidity and mortality. HH can be difficult to treat and in our review below we will list the therapeutic modalities awaiting the evaluation for the only definitive therapy, which is liver transplantation.

Pathogenesis of Rushton bodies: A novel hypothesis.

Rushton bodies (RBs) are one of the characteristic features seen in the epithelial lining of odontogenic cysts mainly radicular, dentigerous and odontogenic keratocyst. It has two different histo-morphological appearances; granular and homogeneous. Although widely investigated, the exact pathogenesis and histogenesis of RBs is still an enigma. Many hypotheses were made in the literature but none has explained conceivably the two histo-morphological appearances of RBs and their association with inflammation. In the present paper the various pathogenesis for the formation of RBs proposed till date are discussed along with proposal for a novel hypothesis. The given hypothesis is mainly related to inflammation and its effect on pore size of basement membrane of odontogenic cystic epithelium. It explains RBs association with inflammation as well as existence of two histo-morphological appearances. The proposed hypothesis also justifies the RB's presence inside the lining epithelium of odontogenic cyst despite its hematogenous origin. Future studies are advocated for isolating RBs using laser capture microdissection and subsequent biochemical, histochemical and electron microscopic analysis to substantiate the proposed hypothesis.