Beta blocker overdose with propranolol and with atenolol

During a one-month period, two cases of beta-adrenergic blocker overdose were treated by the emergency staff at our hospital. One case of propranolol intoxication demonstrated profound cardiovascular collapse and generalized tonic-clonic seizures. The condition failed to respond to high-dose intravenous pressor agents, but did improve significantly with IV glucagon infusion. The second overdose involved atenolol. Although the blood levels reported were very high, the patient showed no cardiovascular compromise and required only inhaled bronchodilators for an exacerbation of her asthma.     

Colitis associated with biological agents

In the past, there has been considerable focus on a host of drugs and chemicals that may produce colonic toxicity. Now, a variety of new biological monoclonal antibody agents, usually administered by infusion, have appeared in the clinical realm over the last decade or so to treat different chronic inflammatory or malignant disorders.For some of these agents, adverse effects have been documented, including apparently new forms of immune-mediated inflammatory bowel disease. In some, only limited symptoms have been recorded, but in others, severe colitis with serious complications, such as bowel perforation has been recorded. In others, adverse effects may have a direct vascular or ischemic basis, while other intestinal effects may be related to a superimposed infection. Some new onset cases of ulcerative colitis or Crohn's disease may also be attributed to the same agents used to treat these diseases, or be responsible for disease exacerbation. Dramatic and well documented side effects have been observed with ipilimumab, a humanized monoclonal antibody developed to reduce and overcome cytotoxic T-lymphocyte antigen 4, a key negative feedback regulator of the T-cell anti-tumor response. This agent has frequently been used in the treatment of different malignancies, notably, malignant melanoma. Side effects with this agent occur in up to 40% and these are believed to be largely immune-mediated. One of these is a form of enterocolitis that may be severe, and occasionally, fatal. Other agents include rituximab (an anti-CD20 monoclonal antibody), bevacizumab (a monoclonal antibody against the vascular endothelial growth factor) and anti-tumor necrosis factor agents, including infliximab, adalimumab and etanercept.     

Water intoxication with seizures

Presented is the case of a normal two-month-old girl who developed seizures secondary to water intoxication. The infant had been fed 20 to 30 oz of water daily for three days, while her usual formula was withheld because of vomiting and diarrhea. On the day of admission, the infant exhibited signs of water intoxication in the form of lethargy, vomiting, and seizures. Hyponatremia, hypothermia, and hyperglycemia were noted on admission, and are common features of the syndrome. The patient responded well to fluid restriction and salt replacement. Previous reports have attributed water intoxication to feeding mismanagement, vigorous hydration, dilute formulas, and swimming lessons.     

Weber-Christian disease with ileocolonic involvement successfully treated with infliximab

Weber-Christian disease(WCD) is an inflammatory disease whose main histological feature is lobular panniculitis of adipose tissue. The location of panniculitis determines the clinical presentation,being the subcutaneous adipose tissue the most frequent one,followed by liver,spleen,bone marrow and mesenteric adipose tissue.Systemic corticosteroids are first line treatment,but other options should be considered if systemic symptoms are observed or in case of refractory clinical situation.We report herein a case with WCD showing orbital,mesenteric and ileocolonic involvement,which required surgical treatment and also developed postoperative recurrence.Symptoms were resolved by administration of thalidomide and,afterwards,infliximab.To our knowledge,this is the first report of Weber-Christian disease with luminal ileocolonic involvement,treated with infliximab.     

Anticoagulation with Bivalirudin during Deep Hypothermic Circulatory Arrest in a Patient with Heparin-Induced Thrombocytopenia

Heparin-induced thrombocytopenia is a well-recognized complication of anticoagulation with heparin. We present the case of a patient with recent heparin-induced thrombocytopenia who subsequently needed surgery on an emergency basis for acute type A aortic dissection. This article reports the successful use of bivalirudin, a direct thrombin inhibitor, as an alternative to heparin throughout cardiopulmonary bypass and deep hypothermic circulatory arrest. We contend that bivalirudin is a safe alternative to heparin when performing surgery for aortic dissection and should be considered as an option for use in patients who present with heparin-induced thrombocytopenia.     

Curing Cats with Feline Infectious Peritonitis with an Oral Multi-Component Drug Containing GS-441524

Feline infectious peritonitis (FIP) caused by feline coronavirus (FCoV) is a common dis-ease in cats, fatal if untreated, and no effective treatment is currently legally available. The aim of this study was to evaluate efficacy and toxicity of the multi-component drug Xraphconn^® in vitro and as oral treatment in cats with spontaneous FIP by examining survival rate, development of clinical and laboratory parameters, viral loads, anti-FCoV antibodies, and adverse effects. Mass spectrometry and nuclear magnetic resonance identified GS-441524 as an active component of Xraphconn^®. Eighteen cats with FIP were prospectively followed up while being treated orally for 84 days. Values of key parameters on each examination day were compared to values before treatment initiation using linear mixed-effect models. Xraphconn^® displayed high virucidal activity in cell culture. All cats recovered with dramatic improvement of clinical and laboratory parameters and massive reduction in viral loads within the first few days of treatment without serious adverse effects. Oral treatment with Xraphconn^® containing GS-441524 was highly effective for FIP without causing serious adverse effects. This drug is an excellent option for the oral treatment of FIP and should be trialed as potential effective treatment option for other severe coronavirus-associated diseases across species.     

Serum metabolome profiles characterized by patients with hepatocellular carcinoma associated with hepatitis B and C

AIM: To clarify the characteristics of metabolite profiles in virus-related hepatocellular carcinoma(HCC) patients using serum metabolome analysis. METHODS: The serum levels of low-molecular-weight metabolites in 68 patients with HCC were quantified using capillary electrophoresis chromatography and mass spectrometry. Thirty and 38 of the patients suffered from hepatitis B virus-related HCC(HCC-B) and hepatitis C virus-related HCC(HCC-C), respectively.RESULTS: The main metabolites characteristic of HCC were those associated with glutathione metabolism, notably 13 γ-glutamyl peptides, which are by-products of glutathione induction. Two major profiles, i.e., concentration patterns, of metabolites were identified in HCC patients, and these were classified into two groups: an HCC-B group and an HCC-C group including some of the HCC-B cases. The receiver operating characteristic curve for the multiple logistic regressionmodel discriminating HCC-B from HCC-C incorporating the concentrations of glutamic acid, methionine and γ-glutamyl-glycine-glycine showed a highly significant area under the curve value of 0.94(95%CI: 0.89-1.0, P 0.0001).CONCLUSION: The serum levels of γ-glutamyl peptides, as well as their concentration patterns, contribute to the development of potential biomarkers for virus-related HCC. The difference in metabolite profiles between HCC-B and HCC-C may reflect the respective metabolic reactions that underlie the different pathogeneses of these two types of HCC.     

Management of a child with acute thyroxine ingestion

We report a case of thyroxine overdose in a child. Despite extremely high thyroxine (T4RIA) levels on admission, the patient's only symptoms were mild hypertension and tachycardia. Both symptoms responded to propranolol, with a drop in pulse rate and a decrease in blood pressure to normal levels. After four days of cardiac monitoring, the patient was released and received propranolol for five additional days as an outpatient.     

Role of chemoprophylaxis with either NSAIDs or statins in patients with Barrett’s esophagus简

The incidence of esophageal adenocarcinoma, a poor prognosis neoplasia, has risen dramatically in recent decades. Barrett’s esophagus represents the best-known risk factor for esophageal adenocarcinoma development. Non-steroidal anti-inflammatory drugs through cyclooxygenase-2 inhibition and prostaglandin metabolism regulation could control cell proliferation, increase cell apoptosis and regulate the expression of growth and angiogenic factors. Statins can achieve equivalent effects through prenylation and subsequently control of cellular signaling cascades. At present, epidemiological studies are small and underpowered. Their data could not justify either medication as a chemo-preventive agent. Population based studies have shown a 43% reduction of the odds of developing an esophageal adenocarcinoma, leaving out or stating a 25% reduction in patients consuming non-aspirin nonsteroidal anti-inflammatory drugs and a 50% reduction in those patients consuming aspirin. They have also stated a 19% reduction of esophageal cancer incidence when statins have been used. Observational studies have shown that non-steroidal anti-inflammatory drugs could reduce the adenocarcinoma incidence in patients with Barrett’s esophagus by 41%, while statins could reduce the risk by 43%. The cancer preventive effect has been enhanced in those patients taking a combination of non-steroidal anti-inflammatory drugs and statins (a 74% decrease). Observational data are equivocal concerning the efficacy of non-steroidal anti-inflammatory drug subclasses. Non-steroidal anti-inflammatory drugs clearly have substantial potential for toxicity, while statins are rather safe drugs. In conclusion, both non-steroidal anti-inflammatory drugs and statins are promising chemopreventive agents and deserve further exploration with interventional studies. In the meanwhile, their use is justified only in patients with cardiovascular disease.     

Fecal Feline Coronavirus RNA Shedding and Spike Gene Mutations in Cats with Feline Infectious Peritonitis Treated with GS-441524

As previously demonstrated by our research group, the oral multicomponent drug Xraphconn^® containing GS-441524 was effective at curing otherwise fatal feline infectious peritonitis (FIP) in 18 feline coronavirus (FCoV)-infected cats. The aims of the current study were to investigate, using samples from the same animals as in the previous study, (1) the effect of treatment on fecal viral RNA shedding; (2) the presence of spike gene mutations in different body compartments of these cats; and (3) viral RNA shedding, presence of spike gene mutations, and anti-FCoV antibody titers in samples of 12 companion cats cohabitating with the treated cats. Eleven of the eighteen treated FIP cats (61%) were shedding FCoV RNA in feces within the first three days after treatment initiation, but all of them tested negative by day 6. In one of these cats, fecal shedding reoccurred on day 83. Two cats initially negative in feces were transiently positive 1–4 weeks into the study. The remaining five cats never shed FCoV. Viral RNA loads in feces decreased with time comparable with those in blood and effusion. Specific spike gene mutations linked to systemic FCoV spread were consistently found in blood and effusion from treated FIP cats, but not in feces from treated or companion cats. A new mutation that led to a not yet described amino acid change was identified, indicating that further mutations may be involved in the development of FIP. Eight of the twelve companion cats shed FCoV in feces. All but one of the twelve companion cats had anti-FCoV antibodies. Oral treatment with GS-441524 effectively decreased viral RNA loads in feces, blood, and effusion in cats with FIP. Nonetheless, re-shedding can most likely occur if cats are re-exposed to FCoV by their companion cats.     

Vaccine‐preventable disease hospitalized patients with heart failure with reduced ejection fraction

BackgroundOver five million Americans suffer from heart failure (HF), and this is associated with multiple chronic comorbidities and recurrent decompensation. Currently, there is an increased incidence in vaccine‐preventable diseases (VPDs). We aim to investigate the impact of HF with reduced ejection fraction (HFrEF) in patients hospitalized with VPDs.HypothesisPatient with HFrEF are at higher risk for VPDs and they carry a higher risk for in‐hospital complications.MethodsRetrospective analysis from all hospital admissions from the 2016‐2018 National Inpatient Sample (NIS) using the ICD‐10CM codes for patients admitted with a primary diagnosis of VPDs with HFrEF and those without reduced ejection fraction. Outcomes evaluated were in‐hospital mortality, length of stay (LOS), healthcare utilization, frequency of admissions, and in‐hospital complications. Multivariate regression analysis was conducted to adjust for confounders.ResultsOut of 317 670 VPDs discharges, we identified 12 130 (3.8%) patients with HFrEF as a comorbidity. The most common admission diagnosis for VPDs was influenza virus (IV) infection (75.0% vs. 64.1%; p < .01), followed by pneumococcal pneumonia (PNA) (13% vs. 9.4%; p < .01). After adjusting for confounders, patients with HFrEF had higher odds of having diagnosis of IV (adjusted [aOR], 1.42; p < .01) and PNA (aOR, 1.27; p < .01). Patients with VPDs and HFrEF had significantly higher odds of mortality (aOR, 1.76; p < .01), LOS, respiratory failure requiring mechanical ventilation, and mechanical ventilation for less than 96 h.ConclusionInfluenza and PNA were the most common VPDs admitted to the hospital in patients with a concomitant diagnosis of HFrEF. They were associated with increased mortality and in‐hospital complications.     

Viral co‐infections are associated with increased rates of hospitalization in those with influenza

BackgroundInfluenza causes significant morbidity and mortality in the United States. Among patients infected with influenza, the presence of bacterial co‐infection is associated with worse clinical outcomes; less is known regarding the clinical importance of viral co‐infections. The objective of this study was to determine rates of viral co‐infections in emergency department (ED) patients with confirmed influenza and association of co‐infection with disease severity.MethodsSecondary analysis of a biorepository and clinical database from a parent study where rapid influenza testing was implemented in four U.S. academic EDs, during the 2014–2015 influenza season. Patients were systematically tested for influenza virus using a validated clinical decision guideline. Demographic and clinical data were extracted from medical records; nasopharyngeal specimens from influenza‐positive patients were tested for viral co‐infections (ePlex, Genmark Diagnostics). Patterns of viral co‐infections were evaluated using chi‐square analysis. The association of viral co‐infection with hospital admission was assessed using univariate and multivariate regression.ResultsThe overall influenza A/B positivity rate was 18.1% (1071/5919). Of the 999 samples with ePlex results, the prevalence of viral co‐infections was 7.9% (79/999). The most common viral co‐infection was rhinovirus/enterovirus (RhV/EV), at 3.9% (39/999). The odds of hospital admission (OR 2.33, 95% CI: 1.01–5.34) increased significantly for those with viral co‐infections (other than RhV/EV) versus those with influenza A infection only.ConclusionPresence of viral co‐infection (other than RhV/EV) in ED influenza A/B positive patients was independently associated with increased risk of hospital admission. Further research is needed to determine clinical utility of ED multiplex testing.     

Metapopulations with habitat modification

Across the tree of life, organisms modify their local environment, rendering it more or less hospitable for other species. Despite the ubiquity of these processes, simple models that can be used to develop intuitions about the consequences of widespread habitat modification are lacking. Here, we extend the classic Levins metapopulation model to a setting where each of n species can colonize patches connected by dispersal, and when patches are vacated via local extinction, they retain a “memory” of the previous occupant—modeling habitat modification. While this model can exhibit a wide range of dynamics, we draw several overarching conclusions about the effects of modification and memory. In particular, we find that any number of species may potentially coexist, provided that each is at a disadvantage when colonizing patches vacated by a conspecific. This notion is made precise through a quantitative stability condition, which provides a way to unify and formalize existing conceptual models. We also show that when patch memory facilitates coexistence, it generically induces a positive relationship between diversity and robustness (tolerance of disturbance). Our simple model provides a portable, tractable framework for studying systems where species modify and react to a shared landscape.

Many interactions between species are realized indirectly, through effects on a shared environment. For example, consumers compete indirectly by altering resource availability (1, 2). However, the ways that species affect and are affected by their environment extend far beyond the consumption of resources. Across the tree of life and over a tremendous range of spatial scales, organisms make complex and sometimes substantial changes to the physical and chemical properties of their local environment (3–6). Many species also impact local biotic factors; for example, plant–soil feedbacks are often driven by changes in soil microbiome composition (4, 7–9).Numerous studies have recognized and discussed the ways that such changes can mediate interactions between species, as well as the obstacles to modeling these complex, indirect interactions (5, 7, 10–12). In some instances, the effects of environmental modification by one species on another can be accounted for implicitly in models of direct interactions (2, 13, 14) or within the well-established framework of resource competition (12, 15). But in many other cases, new modeling approaches are necessary.Because the range of ecosystems where interactions are driven by environmental modification is wide and varied, many parallel strands of theory have developed for them. Examples include “traditional” ecosystem engineers (16–20), plant–soil feedbacks (4, 7, 21), and chemically mediated interactions between microbes (5, 12). Similar dynamics underlie Janzen–Connell effects, where individuals (e.g., tropical trees) modify their local environment by supporting high densities of natural enemies (8, 22–24), and immune-mediated pathogen competition, where pathogen strains modify their hosts by inducing specific immunity (25–28). These last two examples highlight that environmental modification might be “passive,” in the sense that it is generated by the environment itself.While each of these systems has attracted careful study, it is difficult to elucidate general principles for the dynamics of environmentally mediated interactions without a simple, shared theoretical framework. Are there generic conditions for the coexistence of many species in these systems? What are typical relationships between diversity and ecosystem productivity or robustness? We especially lack theoretical expectations for high-diversity communities, as most existing models focus on the dynamics of one or two species (4, 7, 16, 17).To begin answering these questions, we introduce and analyze a flexible model for species interactions mediated by environmental modification. Two essential features of these interactions—which underlie the difficulty integrating them into standard ecological theory—are that environmental modifications are localized in space and persistent in time (10). To capture these aspects, we adopt the metapopulation framework, introduced by Levins (29), which provides a minimal model for population dynamics with distinct local and global scales. Metapopulation models underpin a productive and diverse body of theory in ecology (30, 31), including various extensions to study multispecies communities (32, 33). Here, we adopt the simplest such extension, by assuming zero-sum dynamics and an essentially horizontal community (34, 35). Our modeling framework accommodates lasting environmental modification by introducing a versatile notion of “patch memory,” in which the state of local sites depends on past occupants.In line with evidence from a range of systems, we find that patch memory can support the robust coexistence of any number of species, even in an initially homogeneous landscape. We derive quantitative conditions for species’ coexistence and show how they connect to existing conceptual models. Importantly, these conditions apply even as several model assumptions are relaxed. We also investigate an emergent relationship between species diversity and robustness, demonstrating that our modeling framework can provide insight for a variety of systems characterized by localized environmental feedbacks.     

Colonic tumorigenesis in rats with 1,2-dimethylhydrazine

Subcutaneous injections of the carcinogen dimethylhydrazine in inbred Fischer 344 male rats induced squamous-cell carcinomas in the ear canal, adenocarcinomas in the small bowel and duodenum, and adenomas and adenocarcinomas in the large bowel. The incidences of the tumors induced in the large bowel and ear canal were dose-related. As for tumors of the large bowel, the average size of adenomas was less than that of adenocarcinomas with massive infiltration beyond the muscularis mucosa. The average size of early adenocarcinomas was greater than that of adenomas but less than that of adenocarcinomas with massive infiltration beyond the muscularis mucosa. Supported by Medical Research Service, Veterans Administration Medical Center, Lexington, Kentucky.     

Detection of SHOX Gene Variations in Patients with Skeletal Abnormalities with or without Short Stature

Objective:SHOX gene mutations constitute one of the genetic causes of short stature. The clinical phenotype includes variable degrees of growth impairment, such as Langer mesomelic dysplasia (LMD), Léri-Weill dyschondrosteosis (LWD) or idiopathic short stature (ISS). The aim of this study was to describe the clinical features and molecular results of SHOX deficiency in a group of Turkish patients who had skeletal findings with and without short stature.Methods:Forty-six patients with ISS, disproportionate short stature or skeletal findings without short stature from 35 different families were included. SHOX gene analysis was performed using Sanger sequencing and multiplex ligation-dependent probe amplification analysis.Results:Three different point mutations (two nonsense, one frameshift) and one whole SHOX gene deletion were detected in 15 patients from four different families. While 4/15 patients had LMD, the remaining patients had clinical features compatible with LWD. Madelung’s deformity, cubitus valgus, muscular hypertrophy and short forearm were the most common phenotypic features, as well as short stature. Additionally, hearing loss was detected in two patients with LMD.Conclusion:This study has presented the clinical spectrum and molecular findings of 15 patients with SHOX gene mutations or deletions. SHOX deficiency should be especially considered in patients who have disproportionate short stature or forearm anomalies with or without short stature. Although most of the patients had partial or whole gene deletions, SHOX gene sequencing should be performed in suspected cases. Furthermore, conductive hearing loss may rarely accompany these clinical manifestations.     

Clinical presentation of patients with acute cervical spine injury

A retrospective review of 67 patients with acute cervical spine fracture and/or dislocation was conducted at two suburban community hospital emergency departments. The mean age was 39, and two-thirds of the patients were male. Motor vehicle accidents and falls accounted for more than 80% of all injuries. On emergency department evaluation, it was found that there was no history of loss of consciousness in 42 patients (63%), no associated cranio-facial injuries in 31 patients (46%), and a normal sensorimotor examination in 59 patients (88%). Thirty-four patients (50%) were evaluated for cervical range of motion, which was found to be normal in one-third of the cases. The absence of mental status changes, cranio-facial injuries, range of motion abnormalities, and focal neurological findings is, therefore, not uncommon in patients who have sustained cervical spine injury.     

The Decline of Pulmonary Function Among Patients with Chronic Asthma Treated with Inhaled Corticosteroid

We analyzed the rate of decline of pulmonary function annually over 2 years in 49 patients with chronic asthma, who were being treated with inhaled corticosteroid (beclomethasone). The coefficient of linear regression of pulmonary function based on dose of inhaled corticosteroid may be used to track the exact rate of the decline of pulmonary function. The declining rate of pulmonary function is faster in the early stages of the disease, in spite of the treatment with inhaled beclomethasone. In chronic asthmatics, the distal airway units appear to deteriorate, and the extent of deterioration probably changes with the progression of the disease.