Acinic cell carcinoma of the parotid gland: A diagnostic dilemma on cytology.

INTRODUCTION: Acinic cell carcinoma (ACC) represents 1-6% of parotid gland neoplasms. CASE REPORT: We report cytomorphological features of two uncommon variants of acinic cell carcinoma. The first case was an eleven-year-old female with a nodular mass in parotid and the FNA smears demonstrated a lymphoepithelial lesion composed of epithelial tumour cells with features of acinar cells in a lymphoid background. The second case was a 62-year-old male with a large parotid mass. The FNA smears revealed presence of extracellular, acellular amyloid-like material with tumour cells arranged in follicles. DISCUSSION: Awareness of cytomorphological features of these unusual variants of acinic cell carcinoma may help to avoid diagnostic pitfall.

Spectrum of esophageal dysmotility in systemic sclerosis on high-resolution esophageal manometry as defined by Chicago classification.

The classic manometric findings in systemic sclerosis are aperistalsis of the esophageal body with hypotensive lower esophageal sphincter. These changes contribute to gastroesophageal reflux disease in these patients. With widespread use of high-resolution esophageal manometry, diverse abnormalities are seen. The aim of this study is to characterize esophageal dysmotility in patients with systemic sclerosis undergoing high-resolution esophageal manometry and compare demographic features and diagnostic test results among patients with varying degrees of esophageal dysmotility. Patients with systemic sclerosis who underwent high-resolution esophageal manometry between January 2008 and October 2014 at our institution were identified. High-resolution esophageal manometry studies were reinterpreted using the Chicago Classification, v3.0 criteria. We also reviewed the patient charts for demographic data, indications for manometry, esophagogastroduodenoscopy findings, pH studies, medication use, and autoantibody panel. The cohort consisted of 122 patients with a mean age of 53.3 ± 15.3 years. High-resolution esophageal manometry was normal in 23, showed ineffective esophageal motility in 22, absent contractility in 73, and one case each of type II achalasia, esophagogastric junction outflow obstruction, hypercontractile esophagus, and distal esophageal spasm. Patients with absent contractility were younger and more likely to have erosive esophagitis, hiatal hernia, and esophageal strictures than patients with ineffective esophageal motility or normal manometry. There were no statistically significant differences in the groups based on autoantibodies or indications for manometry. Diverse esophageal motility abnormalities were noted in systemic sclerosis with ineffective esophageal motility or absent contractility observed in over three-fourth of the patients. Patients with absent contractility were younger and had more severe reflux. The severity of gastroesophageal reflux disease related endoscopic findings correlated with the degree of esophageal dysmotility on high-resolution esophageal manometry.

Cytokeratin 20 immunocytochemistry on urine sediments: A potential low-cost adjunct to cytology in the diagnosis of low-grade urothelial carcinoma.

BACKGROUND: Urine cytology is the corner-stone for the diagnosis of urothelial neoplasia; however, a substantial proportion of low-grade carcinomas are reported as inconclusive owing to scant cellularity and subtle cytological features. Biomarkers applied on urine sediment smears of such patients are likely to be clinically relevant. Access to Food and Drug Administration approved urinary biomarkers in resource limited setting is poor. Detection of cytokeratin 20 (CK20) in urine sediments, although still a research tool, is a promising marker as immunocytochemistry is performed regularly in several Indian laboratories. OBJECTIVE: We tested the clinical utility of CK20 immunocytochemistry as a potential low-cost adjunct to urine cytology in diagnosis of low-grade urothelial carcinoma. One hundred and fifty fresh, voided urine specimens from 42 cases of biopsy proven urothelial neoplasia (14 high grade, 28 combined low-grade [n=26]) and low malignant potential [n=2]), and 20 non-neoplastic lesions were included in the study sample. RESULTS: Confident diagnosis of malignancy was possible in five (17.8%) low-grade malignancies. Thirteen of 16 (81.3%) low-grade malignancies with inconclusive cytology showed positive CK20 expression. This reduced the proportion of low-grade cases with inconclusive cytology from 57.1% to 10.7% (P=.021). In addition, we could correctly classify one case of bladder lithiasis with false positive urine cytology. Discrepant CK20 staining (positive) was seen in one patient with acute cystitis. CONCLUSIONS: CK20 expression in non-umbrella cells is a robust marker of urinary bladder carcinoma. It has potential clinical utility for identification of low-grade urothelial malignancy with inconclusive cytological diagnosis.

Genetic instability in urinary bladder cancer: An evolving hallmark.

Bladder cancer is a major health-care concern. A successful treatment of bladder cancer depends on its early diagnosis at the initial stage. Genetic instability is an essential early step toward the development of bladder cancer. This instability is found more often at the chromosomal level than at the nucleotide level. Microsatellite and chromosomal instability markers can be used as a prognostic marker for screening bladder cancer. Bladder cancer can be distinguished in two different categories according to genetic instability: Cancers with chromosomal level instability and cancers with nucleotide level instability. Deoxyribonucleic acid (DNA) mismatch repair (MMR) system and its correlation with other biologic pathway, both are essential to understand the basic mechanisms of cancer development. Microsatellite instability occurs due to defects in DNA MMR genes, including human mutL homolog 1 and human mutL homolog 2. Chromosomal alterations including deletions on chromosome 3, 8, 9, 11, 13, 17 have been detected in bladder cancer. In the current review, the most recent literature of genetic instability in urinary bladder cancer has been summarized.

Evaluation of the impact of continuous Kangaroo Mother Care (KMC) initiated immediately after birth compared to KMC initiated after stabilization in newborns with birth weight 1.0 to < 1.8 kg on neurodevelopmental outcomes: Protocol for a follow-up study.

BACKGROUND: Preterm birth or low birth weight is the single largest cause of death in newborns, however this mortality can be reduced through newborn care interventions, including Kangaroo Mother Care (KMC). Previously, a multi-country randomized controlled trial, coordinated by the World Health Organization (WHO), reported a significant survival advantage with initiation of continuous KMC immediately after birth compared with initiation of continuous KMC a few days after birth when the baby is considered clinically stable. Whether the survival advantage would lead to higher rates of neurodevelopmental morbidities, or the immediate KMC will also have a beneficial effect on cognitive development also, has not been investigated. We therefore propose to test the hypothesis that low-birth-weight infants exposed to immediate KMC will have lower rates of neurodevelopmental impairment in comparison to traditional KMC-treated infants, by prospectively following up infants already enrolled in the immediate KMC trial for the first 2 years of life, and assessing their growth and neurodevelopment. METHODS: This prospective cohort study will enroll surviving neonates from the main WHO immediate KMC trial. The main trial as well as this follow-up study are being conducted in five low- and middle-income countries in South Asia and sub-Saharan Africa. The estimated sample size for comparison of the risk of neurodevelopmental impairment is a total of 2200 children. The primary outcome will include rates of cerebral palsy, hearing impairment, vision impairment, mental and motor development, and epilepsy and will be assessed by the age of 3 years. The analysis will be by intention to treat. DISCUSSION: Immediate KMC can potentially reduce low-birth-weight-associated complications such as respiratory disease, hypothermia, hypoglycemia, and infection that can result in impaired neurocognitive development. Neuroprotection may also be mediated by improved physiological stabilization that may lead to better maturation of neural pathways, reduced risk of hypoxia, positive parental impact, improved sleep cycles, and improved stress responses. The present study will help in evaluating the overall impact of KMC by investigating the long-term effect on neurodevelopmental impairment in the survivors. TRIAL REGISTRATION: Clinical Trials Registry-India CTRI/2019/11/021899. Registered on 06 November 2019. Trials registration of parent trial: ACTRN12618001880235; Clinical Trials Registry-India: CTRI/2018/08/015369.

Isolation and characterization of feather degrading enzymes from Bacillus megaterium SN1 isolated from Ghazipur poultry waste site.

The SN1 strain of Bacillus megaterium, isolated from soil of Ghazipur poultry waste site (India) produced extracellular caseinolytic and keratinolytic enzymes in basal media at 30 degrees C, 160 rpm in the presence of 10% feather. Feathers were completely degraded after 72 h of incubation. The caesinolytic enzyme was separated from the basal media following ammonium sulphate precipitation and ion exchange chromatography. We report 29.3-fold purification of protease after Q Sepharose chromatography. The molecular weight of this enzyme was estimated to be 30 kDa as shown by SDS-PAGE and zymography studies. Protease activity increased by 2-fold in presence of 10 mM Mn2+ whereas Ba2+ and Hg2+ inhibited it. Ratio of milk clotting activity to caseinolytic was found to be 520.8 activity for the 30-60% ammonium sulphate fraction in presence of Mn2+ ion suggesting potential application in dairy industry. Keratinase was purified to 655.64 fold with specific activity of 544.7 U/mg protein and 12.4% recovery. We adopted the strategy of isolating the keratinolytic and caesinolytic producing microorganism by its selective growing in enriched media and found that feather protein can be metabolized for production of animal feed protein concentrates.

Uterine leiomyoma causing urinary obstruction of the transplanted kidney.

Obstruction of the ureter as a cause of acute or chronic kidney injury in the transplanted kidney is unusual beyond the perioperative period. We present a case of ureteric obstruction, infection and septicemia caused by a large uterine leiomyoma in a patient 8 years post transplantation. Initial treatment comprised of intravenous fluid and antibiotics followed by urgent drainage of the collecting system. Subsequent hysterectomy resolved the obstruction with resolution of renal failure. In young female kidney transplant recipients, gynecologic causes, although rare, need to be considered as possible etiologies of urinary obstruction and renal dysfunction.

Pharmacogenomics-Based Point-of-Care Clinical Decision Support Significantly Alters Drug Prescribing.

Changes in behavior are necessary to apply genomic discoveries to practice. We prospectively studied medication changes made by providers representing eight different medicine specialty clinics whose patients had submitted to preemptive pharmacogenomic genotyping. An institutional clinical decision support (CDS) system provided pharmacogenomic results using traffic light alerts: green = genomically favorable, yellow = genomic caution, red = high risk. The influence of pharmacogenomic alerts on prescribing behaviors was the primary endpoint. In all, 2,279 outpatient encounters were analyzed. Independent of other potential prescribing mediators, medications with high pharmacogenomic risk were changed significantly more often than prescription drugs lacking pharmacogenomic information (odds ratio (OR) = 26.2 (9.0-75.3), P < 0.0001). Medications with cautionary pharmacogenomic information were also changed more frequently (OR = 2.4 (1.7-3.5), P < 0.0001). No pharmacogenomically high-risk medications were prescribed during the entire study when physicians consulted the CDS tool. Pharmacogenomic information improved prescribing in patterns aimed at reducing patient risk, demonstrating that enhanced prescription decision-making is achievable through clinical integration of genomic medicine.

Spectrum of Presentation of Anorectal Malignant Melanoma: Experience of a Tertiary Care Centre of North India.

Malignant melanoma of the anorectum is a rare but highly aggressive tumor. We report our experience of anorectal melanoma in five patients. Of these, two have advanced disease, two had localized disease and one patient had florid systemic metastases with a history of hemorrhoidectomy one year prior. One patient whose metastatic workup was negative, expired on post-op day 15 of abdominoperineal resection due to unsuspected but florid cerebral metastases. Another patient with localized disease underwent an APR with curative resection and post-op whole body PET scan negative for occult or residual disease. Advanced stage patients were referred for chemotherapy. To improve prognosis, it is important to detect anorectal melanoma at an early stage.

Characteristic Sizes of Life in the Oceans, from Bacteria to Whales.

The size of an individual organism is a key trait to characterize its physiology and feeding ecology. Size-based scaling laws may have a limited size range of validity or undergo a transition from one scaling exponent to another at some characteristic size. We collate and review data on size-based scaling laws for resource acquisition, mobility, sensory range, and progeny size for all pelagic marine life, from bacteria to whales. Further, we review and develop simple theoretical arguments for observed scaling laws and the characteristic sizes of a change or breakdown of power laws. We divide life in the ocean into seven major realms based on trophic strategy, physiology, and life history strategy. Such a categorization represents a move away from a taxonomically oriented description toward a trait-based description of life in the oceans. Finally, we discuss life forms that transgress the simple size-based rules and identify unanswered questions.

Proton transfer to residues of basic pK(a) during catalysis by carbonic anhydrase.

The maximal velocity in the hydration of CO(2) catalyzed by the carbonic anhydrases in well-buffered solutions is limited by an intramolecular proton transfer from zinc-bound water to acceptor groups of the enzyme and hence to buffer in solution. Stopped-flow spectrophotometry was used to accumulate evidence that this maximal velocity is affected by residues of basic pK(a), near 8 to above 9, in catalysis of the hydration of CO(2) by carbonic anhydrases III, IV, V, and VII. A mutant of carbonic anhydrase II containing the replacement His-64-->Ala, which removes the prominent histidine proton shuttle (with pK(a) near 7), allows better observation of these basic groups. We suggest this feature of catalysis is general for the human and animal carbonic anhydrases and is due to residues of basic pK(a), predominantly lysines and tyrosines more distant from the zinc than His-64, that act as proton acceptors. These groups supplement the well-studied proton transfer from zinc-bound water to His-64 in the most efficient of the carbonic anhydrases, isozymes II, IV, and VII.

Nuclear matrix binding protein SMAR1 regulates T-cell differentiation and allergic airway disease.

Asthma is a complex airway allergic disease involving the interplay of various cell types, cytokines, and transcriptional factors. Though many factors contribute to disease etiology, the molecular control of disease phenotype and responsiveness is not well understood. Here we report an essential role of the matrix attachment region (MAR)-binding protein SMAR1 in regulating immune response during allergic airway disease. Conditional knockout of SMAR1 in T cells rendered the mice resistant to eosinophilic airway inflammation against ovalbumin (OVA) allergen with low immunoglobulin E (IgE) and interleukin-5 (IL-5) levels. Moreover, a lower IgE/IgG2a ratio and higher interferon-γ (IFN-γ) response suggested aberrant skewing of T-cell differentiation toward type 1 helper T cell (Th1) response. We show that SMAR1 functions as a negative regulator of Th1 and Th17 differentiation by interacting with two potential and similar MAR regions present on the promoters of T-bet and IL-17. Thus, we present SMAR1 as a regulator of T-cell differentiation that favors the establishment of Th2 cells by modulating Th1 and Th17 responses.

The effect of oral metoclopramide on the absorption of cyclosporine.

This study was performed to determine the effect of coadministered oral metoclopramide on the absorption of oral cyclosporine in 14 kidney transplant patients. The study was conducted on two consecutive days. Ten patients were studied twice, and 4 patients once, giving 24 studies. The total dosage of metoclopramide was 20 mg. The day on which metoclopramide was administered was chosen randomly. Whole-blood cyclosporine levels were analyzed by high-performance liquid chromatography. Coadministration of cyclosporine with metoclopramide resulted in a significant increase in mean maximum blood concentration (567 ng/ml versus 388 ng/ml) and mean area under the blood-concentration-versus-time curve (4120 ng X hr/ml versus 3370 ng X hr/ml); and a significant decrease in mean time to reach maximum concentration. The mean increase in area under the blood-concentration-versus-time curve was 29%. No significant changes were observed in the elimination of cyclosporine when it was coadministered with metoclopramide. These observations suggest that coadministered metoclopramide increased the total absorption of cyclosporine. Metoclopramide has been shown to hasten gastric emptying; since cyclosporine is absorbed predominantly in the small intestine, coadministration of metoclopramide resulted in increased bioavailability of cyclosporine.

Improving adjustment to chronic illness through strategic self-presentation: an experimental study on a renal dialysis unit.

Laboratory studies show that strategic self-presentations strongly influence private self-evaluations. The present study experimentally manipulated self-presentations of dialysis patients' coping skills in order to influence their adjustment. In all, 42 renal dialysis patients matched for diabetes, gender, and dialysis years were randomly assigned to 3 conditions; adjustment was assessed at baseline, post-intervention, and 1 month follow-up. Patients in a self-presentation condition selectively presented themselves as successful copers in a videotaped interview, ostensibly as part of a training program for new patients. Patients in a problem disclosure condition discussed problems with managing their illness. Control group patients viewed a medical videotape about adjusting to dialysis. Patients in the self-presentation condition reported better adjustment, fewer physical symptoms, and more coping skills 1 month later, compared with patients in the other 2 conditions. In addition, coping skills were shown to mediate the relationship between strategic self-presentation and adjustment.

Fluid noncompliance and symptomatology in end-stage renal disease: cognitive and emotional variables.

Fluid noncompliance in patients with end-stage renal disease (ESRD) is a widespread problem with severe consequences for health. In addition, ESRD patients report considerable stress in relation to their illness and dialysis treatment. The present study examined the role of cognitive and emotional variables in fluid noncompliance, symptomatology, and stress. Fifty hemodialysis patients were assessed (a) on the cognitive variables of locus of control, self-evaluations of their past compliance, and self-efficacy to resist fluid intake and (b) on the emotional variables of depression, anger, and anxiety. Results showed that cognitive variables accounted for fluid noncompliance and predicted future adherence. Patients high in negative emotions complied equally as well as patients low in negative emotions but were found to report substantially more symptomatology and distress associated with their treatment. The implications of these findings for treatment of ESRD patients and future research are discussed.

Burden of self-care in seriously ill patients: impact on adjustment.

Perceived, but not actual, control over the treatment has been consistently related to better adjustment in chronic illness. This study examined the relationship between actual control over treatment and severity of illness and their influence on depression in a chronically ill population of end-stage renal disease (ESRD) patients. The authors hypothesized that as severity of illness increases, the burden of control over treatment would increase depression. Severity of illness and depression were assessed for 98 ESRD patients. Control over treatment was represented by whether dialysis patients were self-administering treatment (high control) or were receiving treatment from the medical staff (low control). Results indicated that for the most severely ill patients, high control over treatment resulted in poorer adjustment. Furthermore, this effect was due in part to how illness interferes with social relationships in seriously ill, self-care patients.

Interpersonal expectations, social support, and adjustment to chronic illness.

Chronic illness places considerable burdens on patients and their interpersonal relations with families. In this study, patients' perceptions of family and medical staff expectations regarding responsibility for care and routine functions were examined. The authors hypothesized that a patient's perceived inability to meet others' expectations about coping with illness would lead to poorer adjustment. Forty-two chronically ill patients were assessed prospectively for perceptions of others' expectations, social support, and psychological adjustment. Findings confirmed that expectations predicted subsequent decreases in psychological adjustment over a 3-month period, even when social support was controlled. A test of the reverse hypothesis showed that poorly adjusted patients did not misperceive others' expectations. Theoretical interpretations of the findings and their relation to social support research are discussed.

Recurrent severe anion gap metabolic acidosis secondary to episodic ethylene glycol intoxication.

Acute ethylene glycol toxicity and its attendant metabolic derangement is a well described clinical entity. Recurrent severe anion gap metabolic acidosis consequent to episodic ingestion of ethylene glycol has not been previously reported. We present a patient who developed severe anion gap metabolic acidosis with no osmolar gap and hypokalemia, consequent to episodic ethylene glycol ingestion. Modest artifactual elevation of the serum lactic acid level and rapid response to intravenous bicarbonate infusion may serve as diagnostic clues. Consideration of these aberrant features should be included in the clinical assessment of severe anion gap metabolic acidosis.

Plasminogen activator inhibitor-1 and peritoneal transport in diabetic and non-diabetic peritoneal dialysis patients.

Plasminogen activator inhibitor-1 (PAI-1) is an important regulator of plasminogen activators and has been shown to be involved in the accumulation of extracellular matrix (ECM) in various tissues. Since peritoneal interstitium is one of the main resistance sites of peritoneal transport, the level of PAI-1 in the peritoneum may have a significant effect on water and solute transport during peritoneal dialysis (PD) via its effect of peritoneal ECM. Therefore, we studied the associations between plasma or dialysate PAI-1 levels and the peritoneal transport during standard peritoneal equilibration test (PET) in 8 diabetic and 8 non-diabetic stable PD patients who were matched for their demographical data. There were no differences in plasma PAI-1 levels and PET variables between these two groups of patients. In each group, there was an increase in dialysate PAI-1 level with dwell time as a result of the diffusion of plasma PAI-1 into peritoneal cavity and the local production and release of PAI-1 in peritoneal tissue. However, the extent of this increase was less in the former. In non-diabetic patients, the change in dialysate PAI-1 amount was a significant positive predictor for the diffusive transports of urea and transport. These results are consistent with the hypothesis that peritoneal PAI-1 has a significant effect on peritoneal transport during PD. Further studies including more patients are needed to confirm our observations, and studies providing more direct evidence are needed to test this hypothesis.

Delayed renal allograft dysfunction and cystitis associated with human polyomavirus (BK) infection in a renal transplant recipient: a case report and review of literature.

Human polyomavirus type BK (BKV) associated nephritis (BKVAN) has recently emerged as an important cause of renal allograft dysfunction and failure. Early recognition of this entity as a cause of allograft dysfunction is extremely important since misdiagnosis can accelerate graft loss. We report a case of BKVAN that presented with symptoms related to cystitis, and review the risk factors, the diagnostic tools and the approach to treatment of BK virus associated allograft nephropathy.