Some more about unfavourable results after corrective surgery as seen in leprosy

The paper describes unfavourable outcomes of some of the commonly performed surgical procedures in leprosy affected persons and the underlying causes. An awareness about unfavourable outcomes of surgery is helpful to the beginners because they can anticipate the problems and take appropriate measures to prevent that and failing which prepare themselves to face and sort that out. Careful pre-operative evaluation of the patient is an important first step.     

Evolution of histoid leprosy (de novo) in lepromatous (multibacillary) leprosy

A 26-year-old man presented with persistent redness of the face over the past 2 years and thickening of the ears for a year. The current state was preceded by three to four episodes of epistaxis, 2–3 months previously. The patient had not received any treatment. Cutaneous examination revealed indurated (infiltrated) plaques on the face and ears over an apparently normal-looking skin, and numerous, small, ill-defined, slightly hypopigmented, shiny macules all over the body. They were bilateral and symmetric ( Fig. 1a,b ). There was no variation in the cutaneous sensations of temperature, touch, and pain. The patient showed loss of the lateral eyebrows and conjunctival congestion. Examination of the nerves revealed enlargement of the ulnar, radial, posterior tibial, and right common peroneal nerves; however, there was no tenderness of the nerves. Systemic examination was within normal limits. Examination of a slit-skin smear (under oil immersion), prepared from a representative lesion (plaque), demonstrated an abundance of solid and uniform-staining acid-fast bacilli, occurring either singly or in parallel clumps/globii, in an average field (6+). Furthermore, a scraping mount (10% KOH) prepared from the lesion on the back was negative.

Figure 1 Open in figure viewer PowerPoint (a, b) Histoid leprosy     

Role of lysophospholipid growth factors in the modulation of aqueous humor outflow facility

PURPOSE: To investigate the role of lysophospholipid growth factors in the regulation of aqueous humor outflow in the trabecular meshwork (TM). METHODS: The expression profile of the endothelial differentiation gene (Edg) family of G-protein coupled receptors was determined by RT-PCR of human TM (HTM) cell-derived total RNA and by PCR amplification of HTM cell-derived and tissue-derived cDNA libraries. The effects of lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) on actin cytoskeleton and focal adhesions and on myosin light-chain (MLC) phosphorylation in HTM cells were evaluated by immunofluorescence microscopy and Western blot analysis, respectively. Activation of Rho GTPase in HTM cells was quantified by "pull-down" assays. Mobilization of intracellular calcium in HTM cells was determined using spectrofluorometric digital-imaging microscopy. The effects of LPA and S1P on aqueous humor outflow facility were evaluated by perfusion of enucleated porcine eyes. RESULTS: Each of the receptor isoforms Edg1, -2, -3, and -4 was readily detectable in three of four HTM cell-derived libraries, whereas Edg2 was detectable in the HTM tissue library. LPA (20 microM) and S1P (1 microM) stimulated actin stress fiber and focal adhesion formation, increased MLC phosphorylation, and induced marked activation of Rho GTPase in HTM cells. Both LPA (20 microM) and S1P (10 microM) also stimulated increases in intracellular calcium concentration in HTM cells. LPA- and S1P-induced effects on MLC phosphorylation in HTM cells were markedly inhibited by pretreatment with the Rho kinase-specific inhibitor Y-27632 (5 microM). Perfusion of LPA (50 microM) and S1P (5 microM) in enucleated porcine eyes produced a significant decrease in aqueous humor outflow facility from baseline of 37% (n = 6) and 31% (n = 5), respectively. CONCLUSIONS: These studies demonstrate that LPA and S1P, the physiological agonists of Edg receptors, decrease outflow facility in perfused porcine eyes in association with increased MLC phosphorylation and Rho guanosine triphosphatase (GTPase) activation. These data provide evidence for a novel mechanism for negative regulation of outflow facility, which may contribute to overall physiological homeostasis of aqueous humor outflow facility.     

Alpha and gamma tocopherols in cerebrospinal fluid and serum from older, male, human subjects

OBJECTIVE: The major forms of vitamin E in human physiological fluids are alpha and gamma tocopherols which exhibit different biological activities under a variety of assay conditions. The goal of this study was to obtain indirect information about the transport of tocopherols across the blood/spinal fluid barrier by comparing the concentrations of alpha and gamma tocopherols in serum and cerebrospinal fluid (CSF). METHODS: CSF and serum samples were obtained simultaneously from 28 human, male subjects excluding those with known pathology during the performance of spinal anesthesia procedures. The samples were centrifuged and frozen, and analyzed for tocopherols by HPLC with electrochemical detection. RESULTS: The concentrations of alpha and gamma tocopherols in CSF correlated significantly with their respective concentrations in serum. This would be expected since these nutrients have to be supplied by diet to serum followed by transport to the brain. The ratios of alpha to gamma tocopherols in the CSF and serum were highly correlated. High concentrations of alpha in serum tended to suppress gamma in both serum and CSF. CONCLUSIONS: These data suggest that the processes involved in the entry of tocopherol from blood to the CSF do not discriminate between the alpha and gamma tocopherols. In contrast, alpha tocopherol is highly preferred during the packaging of plasma lipoproteins by the liver. Our data also suggest that alpha and gamma tocopherols will be available to the human brain via transport from blood.     

Hemophagocytic, non-secretory multiple myeloma

A 70-year-old woman presented with pancytopenia associated with plasma cell infiltration of her bone marrow. The plasma cells were often multinucleated and demonstrated phagocytosis of erythroid and granulocytic cells. Atypical immunophenotypic features included the expression of CD117 and CD13 and the lack of expression of CD56. Although kappa chains were demonstrable in the cytoplasm, no paraprotein was found in the serum or urine. Osteolytic lesions were absent. The pancytopenia of this unusual patient with non-secretory, hemophagocytic myeloma has improved on dexamethasone monotherapy, although her hemophagocytosis persists.     

Immunocontraceptive potential of recombinant bonnet monkey (Macaca radiata) zona pellucida glycoprotein-C expressed in Escherichia coli and its corresponding synthetic peptide

Zona pellucida (ZP) glycoproteins have been proposed as candidate antigens for development of immunocontraceptive vaccines. In this study, the efficacy to block fertility by immunization with recombinant bonnet monkey (Macaca radiata) zona pellucida glycoprotein-C (r-bmZPC) expressed in Escherichia coli and its synthetic peptide (P(4): KGDCGTPSHSRRQPHVVSQWSRSA, aa residues 324-347) conjugated to diphtheria toxoid (DT) has been evaluated in a homologous system. Female bonnet monkeys, immunized with P(4)-DT conjugate showed better immunocontraceptive potential as compared to an r-bmZPC-DT immunized group. In spite of high anti-P(4) antibody titres, animals continued to have ovulatory cycles and showed no disturbance in cyclicity (except summer amenorrhoea). No ovarian pathology was observed in the P(4) immunized group. These results suggest that immunization with the P(4) may lead to block in fertility without obvious ovarian dysfunction. However, further inputs are required to identify additional ZP based B-cell epitopes to enhance the contraceptive efficacy.     

Who to screen and how to screen for celiac disease

Celiac disease (CeD) is a chronic gluten-induced enteropathy with plethoric manifestations. The typical manifestations of CeD such as chronic diarrhea and malabsorption are widely recognized, however, many patients have atypical manifestations like iron deficiency anemia, idiopathic short stature, hypertransaminesemia or infertility, etc. These patients often present to the primary care physicians and/or non-gastrointestinal specialties. However, due to a lack of awareness among the healthcare professionals about the various atypical manifestations, many patients are not screened for CeD. In this review, we have summarized the available literature about the prevalence of CeD in various gastrointestinal (chronic diarrhea) and non-gastrointestinal conditions (iron deficiency anemia, short stature, cryptogenic hypertransaminesemia, cryptogenic cirrhosis or idiopathic ataxia etc.) where the diagnosis of CeD should be con-sidered. In addition, we also discuss special scenarios where screening for CeD should be considered even in absence of symptoms such as patients with type 1 diabetes, Down’s syndrome, and first-degree relatives of patients with CeD. Further, we discuss the diagnostic performance and limitations of various screening tests for CeD such as IgA anti-tissue transglutaminase antibodies, anti-endomysial antibodies and anti-deamidated gliadin antibodies. Based on the current recommendations, we propose a diagnostic algorithm for patients with suspected CeD.     

Are alterations of tight junctions at molecular and ultrastructural level different in duodenal biopsies of patients with celiac disease and Crohn's disease?

Abnormalities of transmembrane and cytoplasmic proteins of tight junctions (TJ) have been implicated in pathogenesis of both celiac (CeD) and Crohn’s diseases (CD). Since disease pathogenesis in CeD and CD are different, we planned to study if there is any differential expression pattern of TJ marker proteins and ultrastructural changes, respectively, in duodenal villi vs crypts. Endoscopic duodenal biopsies from treatment naïve patients with CeD (n?=?24), active CD (n?=?28), and functional dyspepsia (as controls, n?=?15), both at baseline and 6 months after treatment, were subjected to light microscopic analysis (modified Marsh grading); immune-histochemical staining and Western blot analysis to see the expression of key TJ proteins [trans-membrane proteins (claudin-2, claudin-3, claudin-4, occludin, and JAM) and cytoplasmic protein (ZO-1)]. Transmission electron microscopy and image analysis of the TJs were also performed. There was significant overexpression of claudin-2 (pore-forming) and occludin (protein maintaining cell polarity) with under-expression of claudin-3 and claudin-4 (pore-sealing proteins) in treatment naïve CeD and active CD with simultaneous alteration in ultrastructure of TJs such as loss of penta-laminar structure and TJ dilatation. Normalization of some of these TJ proteins was noted 6 months after treatment. These changes were not disease specific and were not different in duodenal villi and crypts. Overexpression of pore-forming and under-expression of pore-sealing TJ proteins lead to dilatation of TJ. These changes are neither disease specific nor site specific and the end result of mucosal inflammation.     

Fatal CNS vasculopathy in a patient with refractory celiac disease and lymph node cavitation

Celiac disease is an enteropathy occurring in genetically predisposed individuals due to a dietary intolerance to gluten. Patients with celiac disease may develop a neurological disorder of unknown cause, although autoimmune mechanisms are suspected. We report on a 56-year-old man with celiac disease, who became refractory to a gluten-free diet and died of a rapidly progressive encephalopathy. Magnetic resonance imaging indicated focal lesions of the cerebellum and brainstem, and electrodiagnostic studies suggested an axonal neuropathy. Autopsy revealed a flattened small-bowel mucosa with intraepithelial lymphocytosis, a spectrum of degenerative changes of the intra-abdominal and mediastinal lymph nodes, including cavitary degeneration, and splenomegaly. Histologically, the lymph nodes showed pseudocyst formation and lymphocytic vasculitis with fibrinoid necrosis, and sections of the brain exhibited fibrinoid degeneration of small blood vessels, sparse perivascular lymphocytic infiltrates, and perivascular ischemic lesions. Identical T-cell clones were identified in the duodenum, stomach, lymph nodes, and spleen. This patient had an unusual neurological disorder related to a vasculopathy, probably mediated by a circulating neoplastic clone of activated T cells.