Silent choker: Unveiling tracheal stenosis as an atypical manifestation of mucormycosis.

Airway mucormycosis is a fatal opportunistic infection typically seen in immunocompromised individuals. In this case report, we present an unusual instance of tracheal stenosis in a patient with diabetes mellitus who had recently recovered from coronavirus 2019 (COVID-19). Our patient was a 69-year-old male with poorly controlled type-II diabetes mellitus, on oral hypoglycemic agents, who had successfully completed treatment for COVID-19. Approximately one month later, he developed a cough, fever and breathlessness. Several factors, including advanced age, history of smoking and tobacco chewing, the nodular appearance of the trachea on bronchoscopy, hypermetabolic wall of the trachea on positron emission tomography scan and dysplasia on biopsy, initially raised suspicion of malignancy. However, repeated biopsies from multiple sites confirmed the diagnosis of tracheal mucormycosis. The patient was treated with amphotericin-B and posaconazole. We extensively reviewed the literature and found only 14 reported cases to discuss compared to ours.

Non-articular Felty's syndrome: An uncommon diagnosis.

Felty's syndrome is a triad of rheumatoid arthritis, neutropenia, and splenomegaly. We hereby report an unusual case of non-articular Felty's syndrome and its management along with discussing the importance of appropriately ruling out alternate causes of neutropenia with splenomegaly.

Clostridium difficile infection in liver transplant recipients: a retrospective study of rates, risk factors and outcomes.

Clostridium difficile infection (CDI) occurs in 3-7% of liver transplant recipients (LTR). However, few data exist on the recent epidemiology, predictors and outcomes of CDI in LTR. A cohort study was performed including LTR from 2000 to 2010 at a tertiary care hospital in Detroit. CDI was defined as diarrhea with a stool C. difficile positive test. Data analyzed included demographics, comorbidities, length of stay (LOS), severity of CDI, rates of recurrence (<12 weeks), relapse (<4 weeks) and overall mortality. Predictors of CDI were calculated using Cox proportional hazard model; 970 LTR were followed for years. Overall prevalence of CDI was 18.9%. Incidence of CDI within 1 year of transplant was 12.4%. Severe CDI occurred in 29.1%. CDI recurrence and relapse rates were 16.9% and 9.7%, respectively. Independent predictors of CDI were year of transplant (hazard ratio [HR] 1.137, 95% confidence interval [CI] 1.06-1.22; p < 0.001), white race (105/162 whites, HR 1.47, 95% CI 1.03-2.1; p = 0.035), Model for End-Stage Liver Disease score (HR 1.03, 95% CI 1.01-1.045, p = 0.003) and LOS (HR 1.01, 95% CI 1.005-1.02, p < 0.001). Significant mortality was observed among LTR with CDI compared to those without CDI (p = 0.003). We concluded that CDI is common among LTR and is associated with higher mortality.

Currently recommended BK virus (BKV) plasma viral load cutoff of ≥4 log10/mL underestimates the diagnosis of BKV-associated nephropathy: a single transplant center experience.

BACKGROUND: BK virus (BKV)-associated nephropathy (BKVAN) is a major cause of renal dysfunction and graft loss in renal transplant recipients. Monitoring plasma BK viral load (BKVL) is the recommended screening tool to predict BKVAN. American Society of Transplantation (AST) guidelines define a BKVL of ≥4 log10/mL (10,000 copies) as presumptive BKVAN and recommend reduction in immunosuppression. We evaluated the clinical sensitivity of the quantitative BKV DNA assay in predicting risk for BKVAN using the AST-recommended BKVL cutoff. METHODS: In a retrospective, single-center study, all patients who underwent renal transplant at Henry Ford Hospital from January 2008 to August 2011 were analyzed (n = 490). Plasma BKVL Assay A (commercial large T antigen-based polymerase chain reaction [PCR]) was done in all patients. Renal biopsy was done if there was a rise in serum creatinine ≥0.5 mg from baseline. BKVAN was confirmed by biopsy. As a subset to this study, from the same cohort, data for a set of 20 consecutive Assays A and B (in-house VP1-based PCR assay) from 15 patients over a period of 3 months were collected. Differences in physicians' clinical decision-making (CDM) were analyzed between the 2 assays using chi-square test. RESULTS: A total of 413 patients met the inclusion criteria, of which 222 patients had BK viremia. Among the 248 patients who had a renal biopsy done, 31 (12.5%) were found to have BKVAN. Eleven of the 31 (35%) patients had BKVL consistently <4 log10/mL, and thus were not diagnosed to have BKVAN using the AST-recommended BKVL cutoff of ≥4 log10/mL. A total of 8 patients lost their graft owing to BKVAN, including 3 patients with BKVL <4 log10/mL. Using a cutoff point of plasma BKVL of ≥4 log10/mL, the sensitivity, specificity, positive predictive value, and negative predicative value of the PCR Assay A for the diagnosis of biopsy-proven BKVAN were 64.5%, 98.4%, 87.0%, and 94.5%, respectively, and for the diagnosis of presumptive nephropathy were found to be 76.6%, 99.4%, 95.8%, and 96.4%, respectively. In the second part of the study, presumptive nephropathy was detected in 8 samples using Assay A and 14 samples using Assay B. Six samples in Assay A would have led to no changes in the CDM in terms of reduction in immunosuppression. Kidney biopsy was carried out in 5 patients, 4 of whom had BKVAN and had Assay B log count of ≥5. If Assay A had been used in CDM, BKVAN would have been missed in 1 patient. CONCLUSION: Utilizing the current AST guideline cutoff of ≥4 log10 /mL, the PCR Assay A underestimated the diagnosis of BKVAN. Urgent standardization of the various BKVL assays and establishment of universal cutoff points is imperative to avoid BKVAN-related graft loss.

Early Cognitive Impairment: Role of Clock Drawing Test.

BACKGROUND: Folstein's Mini Mental Status Examination (MMSE) often fails to identify executive dysfunction even if quite severe. Detailed neuropsychological tests and extensive bedside tests are available to evaluate executive function, but most of them are time consuming. This study was done to determine the value of a Clock Drawing Test (CDT) as a simple tool to identify cognitive dysfunction in various neurological disorders and to assess its utility as an adjunct to MMSE in identifying executive dysfunction in a a busy out patient department (OPD). METHODS: A total of 81 patients suffering from neurological disorders and 81 controls were studied. All subjects received the MMSE and the CDT. The CDT is divided into an unprompted task that is sensitive to executive control (CDT 1) and a copying task which is not (CDT 2). RESULT: All the three tests (CDT 1, CDT 2 and MMSE) could recognize cognitive and executive function deficits, when compared with age and sex matched controls (p < 0. 001). CDT scores correlated strongly with the level of executive function deficits. CDT+MMSE detected 95% cases as abnormal as compared to 47% detected by MMSE alone. CONCLUSION: CDT along with MMSE can detect executive control deficits and cognitive deficits. The CDT 1 tests executive control performance, while CDT 2 tests posterior cortical deficits.

The modulus of elasticity of equine hoof wall: implications for the mechanical function of the hoof.

During normal weight-bearing and locomotion, the equine hoof wall deforms in a consistent pattern; the proximal dorsal wall rotates caudo-ventrally about the distal dorsal border and there is latero-medial flaring posteriorly. The aim of this study is to examine whether there are regional differences in the modulus of elasticity of hoof wall material and whether such differences correlate with the pattern of deformation which occurs in vivo. The modulus of elasticity of equine hoof wall was determined in tension and compression for samples from six forefeet. Samples were tested at the mid-point of the inner and outer halves of the wall thickness at two positions along the proximo-distal axis of the dorsal wall, and from the mid-point of its thickness at the lateral and medial quarters. Test samples were oriented both parallel and perpendicular to the tubules that characterise the microstructure of the wall. The colour of each sample was noted, and the moisture content measured. The range in the mean modulus of elasticity for all samples and tests was 460-1049 MPa, the dorsal outer wall having the highest values, the dorsal inner wall the lowest, and the quarters having intermediate values. The mean value obtained for the quarters was similar to the average of the values for the dorsal inner and outer walls. At all sites, the modulus of elasticity was marginally higher in compression than in tension, possibly owing to microstructural defects. The difference in stiffness between the outer wall and the inner wall was inversely related to moisture content. The difference in stiffness between the dorsal outer and inner walls demonstrates that the equine hoof wall has a comparatively rigid external capsule with a lining of lower stiffness. This arrangement presumably provides some stress protection to the internally adjacent living tissues. The similarity in stiffness between the samples from the quarters and the mean of the two dorsal wall sites suggests that the wall at the quarters has a similar change in stiffness across its thickness as the dorsal wall. However, the reduced thickness of the wall at the quarters compared with the dorsal wall means that, functionally, the quarters are more flexible than the dorsal wall. This will facilitate the flaring of the lateral and medial walls which occurs during weight-bearing. Anisotropy was evident only in tensile tests of the dorsal wall samples. Contrary to popular assertions that white hooves are mechanically inferior, horn pigmentation had no detectable effect on stiffness.

Oxygen-radical/nitric oxide mediate calcium-dependent hormone action on cyclic GMP system: a novel concept in signal transduction mechanisms.

The broad objective of these studies was to understand the nature of cyclic GMP system and the mechanism(s) whereby hormone, autacoids and drugs alter this signal in various physiological systems. Studies were undertaken on the modulation of guanylate cyclase activity by oxygen-radicals/nitric oxide and the mechanism(s) of generation of nitric oxide by receptor-selective hormones. We observed that cytosolic guanylate cyclase undergoes significant stimulation in the presence of oxygen-radicals/nitric oxide. This activation by nitric oxide can be reversed by hemeproteins, thus, enabling guanylate cyclase system to cycle between activated and deactivated state. The evidence is presented that oxygen-radicals are required for the synthesis of nitric oxide by NO synthase as demonstrated by inhibition of NO formation by oxygen-radical scavengers. And finally, the data is presented that acetylcholine-induced elevations of intracellular levels of cyclic GMP can be attenuated by muscarinic antagonist, atropine and superoxide anion scavenger, nitroblue tetrazolium. These observations establish a novel concept that activation of hormone receptors on the cell surface, triggers generation of oxygen radicals and hydrogen peroxide which participates in the catalytic conversion of L-arginine to nitric oxide by nitric oxide synthase in the presence of calcium ion. The oxygen-radicals/NO, thus formed, oxidatively activate guanylate cyclase and transduce the message of calcium-dependent hormones.

Interaction of heavy metal toxicants with brain constitutive nitric oxide synthase.

This study was designed to evaluate the in vitro effects of transition heavy metal cations on activity of constitutive isoform of nitric oxide synthase (cNOS) in rat brain. NOS activity was determined in the cytosolic fractions of rat cerebral hemispheres by conversion of 3H-L-arginine to 3H-L-citrulline. Different concentrations of mercury (Hg2+), nickel (Ni2+), manganese (Mn2+), zinc (Zn2+), cadmium (Cd2+), lead (Pd2+) and calcium (Ca2+) were tested on NOS activity. While all the cations caused inhibition, there were differences in the apparent inhibition constants (Ki) among the cations. With the exception of calcium ion no other cation required preincubation with the enzyme preparation. These results indicate that while calcium ion modulate cNOS activity at regulatory site(s), inhibitory influence of toxic heavy metal cations may be exerted on the catalytic site(s) either by direct binding to it or by interfering with the electron transfer during catalysis.

Calcium-dependent inhibition of constitutive nitric oxide synthase.

The objective of these investigations was to study the regulatory properties of brain constitutive NO synthase. NOS activity was determined in 18,000 X g supernatant by conversion of 3H-L-arginine to 3H-L-citrulline in the presence of NADPH. The expression of catalytic activity of NOS required the presence of calcium ion and calmodulin. The preincubation of enzyme preparations at 37 degrees C in standard reaction mixture led to time-dependent inhibition of L-citrulline formation. This inhibition also required the presence of calcium ion during preincubation phase, and the enzyme remained calmodulin-dependent as exhibited by sensitivity to calmodulin antagonists trifluoperazine (TFP) and calcineurin. The modified enzyme showed significant decrease in the Vmax with NADPH and L-arginine without any change in apparent Km. Inclusion of protease inhibitors, leupeptin, pepstatin A, PMSF and soyabean trypsin inhibitor to the preparations did not alter preincubation-dependent inhibition of NO synthase. Thus, the calcium-dependent inhibitory phenomenon was not due to either the denaturation or proteolysis or the loss of calmodulin sensitivity of NO synthase. These observations indicate that cytosolic isoform of constitutive NO synthase undergoes dual regulation by physiological concentrations of calcium ion.

Use of medication data to validate an association in community-based symptom prevalence studies.

A chemical spill from an oil refinery in Texas City, Texas, exposed the community to more than 40,000 lbs (18,144 kg) of highly toxic and corrosive hydrofluoric acid. A symptom prevalence study indicated an association between symptom reports, most notably breathing symptoms, and hydrofluoric acid exposure. Although verification of self-reported symptoms by checking medical records or performing clinical tests is theoretically possible, it is not a feasible alternative in dealing with an entire community. Open-ended data on medication use collected in the prevalence study were coded by organ system and analyzed by cross-classification techniques and log linear models. Results showed that the reported use of medication for hydrofluoric acid-related problems was associated with the exposure; medication use for problems unrelated to hydrofluoric acid exposure was uniform across the exposure categories. Moreover, medication use was significantly associated with the severity of breathing-related problems for each exposure category. Medication use, however, may have been under-reported because it seems difficult to conjure up the names of medications that were not taken or medications not taken recently may not be recalled. Nonetheless, open-ended medication data may be a useful surrogate approach to validating an association between an exposure and health outcomes.

Decreased atrial natriuretic peptide receptors in the adrenal gland of genetically hypertensive rats.

In view of differential effects of atrial natriuretic peptide (ANP) in different models of hypertension, the present study was undertaken to assess ANP receptors in various target organs of spontaneously hypertensive rats (SHRs) and age-matched normotensive Wistar-Kyoto (WKY) rats. Membranes from kidney, thoracic aorta, and adrenal gland were labeled with [125I]-iodotyrosyl rat atrial peptide (28 amino acid sequence) at 25 degrees C. Each tissue exhibited uniphasic rectangular hyperbolic saturation isotherm indicative of high affinity single species binding sites. While there were no differences in the ANP receptor densities in thoracic aorta and kidney membranes from the two groups, adrenal gland exhibited lower ANP receptors in the SHRs compared to WKY rats. This study suggests that the lower density of ANP receptors in adrenal gland may be one of the underlying contributing factors in genetic hypertension.

Nitric oxide synthase: involvement of oxygen radicals in conversion of L-arginine to nitric oxide.

The objective of this study was to determine the role of superoxide ion in the formation of nitric oxide by brain NO synthase. NO synthase activity was detected by activation of guanylate cyclase in broken cell preparations. NO synthase activity was dependent on NADPH and was inhibited by EGTA, hemoglobin, Nw-methyl-L-arginine and nitroblue tetrazolium. While the addition of exogenous superoxide dismutase significantly enhanced NO synthase activity, bovine liver catalase completely abolished NO formation. None of these NO synthase modulators, however, altered NO-dependent stimulation of guanylate cyclase activity. These observations indicate that catalytic conversion of L-arginine to nitric oxide by cytosolic, isoform of brain NO synthase requires superoxide ion, hydrogen peroxide and possibly hydroxyl radical.

Phospholipase A2 modulation of cyclic GMP metabolism: characteristics of guanylate cyclase activation.

Characteristics of phospholipase A2 (PLA2) modulation of guanylate cyclase were evaluated. Addition of phospholipase A2 from Vipera russelli venom led to a significant increase in the activity of guanylate cyclase in various rat organs. The activation of the enzyme was selective and was only observed in the particulate fractions of tissue homogenate. The soluble guanylate cyclase from all the tissue tested exhibited lack of stimulation. The treatment of membranes with PLA2 resulted in solubilization of cyclase activity. The increase in enzyme by PLA2 was not altered by antioxidants or reducing agents. Addition of calcium ions led to further enhancement in PLA2-dependent increases in cyclic GMP formation. Peak calcium responses were observed in micromolar concentration ranges. These observations suggest a potential role for PLA2 and calcium ions in the hormonal regulation of cyclic GMP metabolism.