Chronic Corticosteroid Administration Research Articles

Menthacarin treatment attenuates nociception in models of visceral hypersensitivity.

Chronic visceral hypersensitivity is closely associated with irritable bowel syndrome (IBS), a very common disorder which significantly impairs quality of life, characterized by abdominal pain, and distension. Imaging studies have found that IBS patients show higher metabolic activities and functional differences from normal controls in the anterior cingulate cortex (ACC), in response to visceral pain stimulation. Non-clinical data and clinical data suggest that medicinal products containing essential oils such as peppermint or caraway oil exert beneficial effects on IBS symptoms. We assessed acute and long-term treatment effects of a mixture of peppermint and caraway essential oils (Menthacarin) on brain electrophysiological markers of gut pain sensitivity in two rat models of visceral hypersensitivity. Chronic administration of corticosteroids and acute repeated mechanical hyperstimulation under anesthesia induced hyperalgesia and hypersensitivity, characterized by an increase in electrophysiological excitatory responses of ACC neurons to colorectal distension (CRD) and an increase in the proportion of neurons responding to otherwise subthreshold stimulation, respectively. Long-term, but not acute, oral administration of Menthacarin (60 mg kg-1 day-1) significantly reduced the net excitatory response to CRD in normally responsive control animals and counteracted the development of visceral hyperalgesia and hypersensitivity induced by repeated corticosterone administration and acute mechanical stimulation. The present study shows that, using the CRD method, chronic Menthacarin administration at a clinically relevant dose attenuates the neuronal discharge associated with visceral pain stimuli in the rat ACC, particularly in models of hypersensitivity, suggesting a potential for treating exaggerated visceral pain sensitivity.

Cervical vertebral veins and caudal cerebral sinuses thrombosis secondary to corticosteroid therapy for an immune‐mediated polyarthritis in a dog

AbstractA 3‐year‐old, crossbreed dog was presented for an acute onset of cervical pain 6 weeks after the initiation of corticosteroid treatment for an immune‐mediated polyarthritis. Except for cervical hyperesthesia, neurological examination was unremarkable. Computed tomography revealed thrombosis of cervical vertebral venous structures and caudal cerebral sinuses. The dural sac containing the cervical spinal cord was moderately to severely compressed. A decrease in antithrombin activity was measured and assumed to be caused by secondary altered production due to corticosteroid therapy as well as important active thrombosis. The hypercoagulable state was most likely caused by chronic corticosteroid administration as a treatment of immune‐mediated polyarthritis. Complete resolution of clinical signs and venous lesions was achieved by tapering off corticosteroids and initiating gabapentin and antithrombotic treatment (clopidogrel and rivaroxaban).

The Association of Early Corticosteroid Therapy With Clinical and Health-Related Quality of Life Outcomes in Children With Septic Shock.

Corticosteroids are commonly used in the treatment of pediatric septic shock without clear evidence of the potential benefits or risks. This study examined the association of early corticosteroid therapy with patient-centered clinically meaningful outcomes. Subsequent cohort analysis of data derived from the prospective Life After Pediatric Sepsis Evaluation (LAPSE) investigation. Outcomes among patients receiving hydrocortisone or methylprednisolone on study day 0 or 1 were compared with those who did not use a propensity score-weighted analysis that controlled for age, sex, study site, and measures of first-day illness severity. Twelve academic PICUs in the United States. Children with community-acquired septic shock 1 month to 18 years old enrolled in LAPSE, 2013-2017. Exclusion criteria included a history of chronic corticosteroid administration. None. Among children enrolled in LAPSE, 352 of 392 met analysis inclusion criteria, and 155 of 352 (44%) received early corticosteroid therapy. After weighting corticosteroid therapy administration propensity across potentially confounding baseline characteristics, differences in outcomes associated with treatment were not statistically significant (adjusted effect or odds ratio [95% CI]): vasoactive-inotropic support duration (-0.37 d [-1.47 to 0.72]; p = 0.503), short-term survival without new morbidity (1.37 [0.83-2.28]; p = 0.218), new morbidity among month-1 survivors (0.70 [0.39-1.23]; p = 0.218), and persistent severe deterioration of health-related quality of life or mortality at month 1 (0.70 [0.40-1.23]; p = 0.212). This study examined the association of early corticosteroid therapy with mortality and morbidity among children encountering septic shock. After adjusting for variables with the potential to confound the relationship between early corticosteroid administration and clinically meaningful end points, there was no improvement in outcomes associated with this therapy. Results from this propensity analysis provide additional justification for equipoise regarding corticosteroid therapy for pediatric septic shock and ascertain the need for a well-designed clinical trial to examine benefit/risk for this intervention.

Aseptic Necrosis of Femoral Head - Clinical Study.

Femoral head osteonecrosis is a disease characterized by the decrease of blood vascularization in the femoral head, which leads to death of the osteocytes, demineralization and resorption of bone spans, change of trabecular architecture, with the reduction of the bone mechanical resistance and collapse of the articular surface in the femoral head. Left untreated, the disease may have a rapid progression, leading to severe symptoms, with significant articular dysfunction, functional impotence and a serious impact on the patient’s quality of life. The prevalence of the disease is ever growing all over the world, affecting mainly people in their 30s, 40s or 50s. In the present study, we analyzed a number of 76 patients with femoral head osteonecrosis with severe symptoms that required a surgical treatment. There was observed that more than ¾ of the investigated patients were males, while 81.58% were younger than 60 years old. Among the identified risk factors, smoking came first, followed by alcohol intake, obesity and chronic administration of corticosteroids. A very high percentage of patients (84.21%) were diagnosed in stages III and IV of the disease.

Challenges in the diagnosis, treatment and management of asthma during COVID-19 pandemic

Abstract People over the age of 65 and those suffering from chronic diseases, such as asthma, are part of the risk group for severe acute respiratory syndrome-COV-2 (SARS-CoV-2) infection. In the past, a connection between viral infections and asthma has been presented. Patients with asthma appear to be at risk of contracting viral infections, and also viruses can cause asthma exacerbations. Another concern during this period was about the chronic administration of corticosteroids in asthmatic patients, because of the consideration that corticosteroid therapy would decrease the immunity of these patients, thus increasing the risk of infections, including the infection with SARS-CoV-2. Thus, several questions have emerged about the role of corticosteroid therapy in the development of COVID-19 in patients undergoing corticosteroid treatment. Most guidelines recommend continuing the administration of chronic treatment to this category of patients. At the same time, the health system had to adapt to the situation caused by the COVID-19 pandemic and deviate from the standard methods of managing most chronic diseases and these changes had an impact on these category of patients.

P095 Unusual side effects of systemic steroids in children with inflammatory bowel disease

CASE: 14 Y/M diagnosed with ileo-colonic Crohn disease at 5 Y of age. He was initially treated with oral prednisone (2 mg/kg/day) for 2 weeks and oral mesalamine. The steroids were weaned over a period of 2 months. As he continued to have persistent symptoms, he was started on infliximab infusions. After his third infliximab infusion he developed severe bilateral lower extremity pain and bilateral knee swelling requiring inpatient admission. X ray of bilateral knee joints was normal. The symptoms were attributed to an infusion reaction and he was then switched to mercaptopurine, which he did not tolerate. He was started on adalimumab, but developed antibodies within 2 months of therapy. He was also given 2–3 courses of oral steroids over 1–2 years to induce remission. The dose was 2 mg/kg/day for 1–2 weeks with weaning over 1–2 months. He developed necrosis of the left femoral head when he was 9Y. The diagnosis was based on typical x ray appearance. His BMI was 82 percentile when he developed osteonecrosis and his last course of steroid was >6 months ago. He was on apriso when he developed osteonecrosis. His symptoms improved with physiotherapy over the next 1–2 years. After he failed therapy on Humira, he was started on oral budesonide (6 mg daily) as he continued to have diarrhea and his repeat colonoscopy showed worsening disease. He was on the oral budesonide for 6–7 weeks and developed typical steroid facies—moon face, supraclavicular fat pads and gained 6 lbs in 6 weeks. His blood pressure was normal. The budesonide was quickly weaned and he was switched to subcutaneous methotrexate followed by entyvio due to lack of clinical response on methotrexate. Currently he is in remission on entyvio. He continues to walk with a limp and is not complaining of any limb pain. DISCUSSION: Osteonecrosis of the femoral head (ONFH) is a disabling condition of the hip joint that primarily affects adults (avg: 36–38 Y). Risk factors for ONFH include chronic corticosteroid administration, chronic alcohol ingestion, smoking, and various chronic diseases (renal disease, hematological disease, inflammatory bowel disease (IBD), post organ transplantation, hypertension, and gout). Although ONFH is seen in children with malignancy, post stem cell transplant and sickle cell disease, it is not commonly reported in children with IBD. The exact incidence of ONFH in children on chronic steroids with IBD is unknown. In our patient, we are not sure if the ONFH was from chronic steroid use or underlying IBD. He also developed steroid facies within 6 weeks on oral budesonide which is unusual. Iatrogenic Cushing's syndrome is not expected with budesonide because a “first pass effect” removes the drug from the circulation. Multi center studies are needed in children with IBD looking at serious side effects of all types of systemic steroids as they are frequently prescribed.

Topical Steroids in Rhinosinusitis and Intraoperative Bleeding: More Harm Than Good?

The aim of this study was to assess whether the chronic preoperative administration of intranasal corticosteroids (INCs) in chronic rhinosinusitis with/without nasal polyposis (CRSwNP/CRSsNP, respectively) could significantly influence bleeding during functional endoscopic sinus surgery (FESS). We prospectively enrolled 109 patients (56 CRSwNP and 53 CRSsNP) candidate for FESS who underwent clinical evaluation and anamnestic data collection. They were allocated to 2 groups depending on whether or not they were chronic INC users, as declared at their first medical evaluation: chronic "INC users" represented the treated group, while "INC nonusers" formed the control group. Lund-Mackay and American Society of Anesthesiology (ASA) scores, blood loss expressed both in milliliters and using the Boezaart scale, operation time in minutes, pre- and postoperative 22-item Sino Nasal Outcome Scores (SNOT-22) were collected. Each sample underwent histopathological evaluation. The results showed that anamnestic information, Lund-Mackay, and SNOT-22 scores were similar between the 2 groups (P > .05). The average blood loss expressed in milliliters and operative time were slightly, but not significantly, higher in the INC user group, while the Boezaart scores proved significantly higher in the INC users (P = .038). No differences emerged between CRSwNP and CRSsNP within each group in terms of bleeding. The pathologist described common features in the majority (78%) of INC group samples: ectatic venules embedded in a fibrous stroma and hypertrophy of the arterial muscular layer. In our experience, despite the presence of NP, chronic preoperative administration of INCs was associated with increased intraoperative bleeding according the Boezaart scale although objective recordings of blood loss were not statistically different between the INC users and nonusers.

Effect of long-term treatment with corticosteroids on skeletal muscle strength, functional exercise capacity and health status in patients with interstitial lung disease.

Corticosteroids are occasionally used in the treatment of ILD. Chronic corticosteroid administration induces skeletal muscle weakness. However, it is unclear whether chronic corticosteroid treatment could further reduce skeletal muscle strength in patients with ILD who are weaker than healthy controls. The aim of this study was to determine the effects of chronic corticosteroid administration on skeletal muscle strength, exercise capacity, activities of daily living (ADL) and health status in ILD patients. Forty-seven ILD patients treated with corticosteroids and 51 Medical Research Council dyspnea grade-matched ILD patients not treated with corticosteroids were assessed by isometric quadriceps muscle force (QF) and handgrip force (HF), pulmonary function, 6-min walk distance, ADL score and health status (Medical Outcomes Study 36-Item Short-Form Health Survey), and the two groups' results were compared. QF and HF were significantly lower in subjects on corticosteroids than in the control patients (QF, 52.6 ± 25.6 vs 77.1 ± 33.3 %predicted, P < 0.001; HF, 63.8 ± 22.4 vs 81.8 ± 28.3 %predicted, P < 0.001, respectively). There were no significant differences in the 6MWD, ADL score and all subscales of the SF-36 between the groups. Inverse correlations were found between skeletal muscle strength and total amount of corticosteroids administered (QF, r = -0.401, P = 0.005; HF, r = -0.403, P = 0.005). On multiple regression analysis, the total amount of corticosteroids was an independent predictor of HF. Chronic cor3ticosteroid treatment contributes to muscle weakness in ILD patients, and muscle weakness is inversely correlated to the total amount of corticosteroids administered.

Positive effect of erythrocyte-delivered dexamethasone in ataxia-telangiectasia.

Objective:Ataxia-telangiectasia (AT) is a rare, devastating neurodegenerative disease presenting with early-onset ataxia, oculocutaneous telangiectasia, immunodeficiency, radiosensitivity, and proneness to cancer. In a previous phase 2 study, we showed that 6 monthly infusions of autologous erythrocytes loaded with dexamethasone (EryDex; EryDel, Urbino, Italy) were effective in improving neurologic impairment in young patients with AT. The present article reports the results of the extension of this study for an additional 24-month period.Methods:After the end of the first trial, 4 patients continued to be treated with monthly EryDex infusions for an additional 24 months, and their clinical outcome was compared with that of 7 age-matched patients who stopped the treatment after the first 6 infusions. The protocol included serial assessment of ataxia (by International Cooperative Ataxia Rating Scale) and adaptive behavior (by Vineland Adaptive Behavior Scales) and clinical and laboratory tests revealing treatment- and steroid-dependent adverse effects, if present.Results:Patients in the extended study experienced a continuous neurologic improvement with respect to their pretreatment status, whereas controls showed a progressive neurologic deterioration (according to the natural history of the disease) after the discontinuation of the treatment. The delivery system we adopted proved to be safe and well-tolerated, and none of the side effects usually associated with the chronic administration of corticosteroids were observed during the entire trial.Conclusions:These promising preliminary results call for a large-scale controlled study on protracted treatment of patients with AT with dexamethasone-loaded erythrocytes.

The mortality associated with erythema nodosum leprosum in Ethiopia: a retrospective hospital-based study.

BackgroundErythema nodosum leprosum (ENL) is a debilitating multisystem disorder which complicates leprosy. It is characterised by fever, malaise and painful erythematous cutaneous nodules. ENL is often recurrent or chronic in nature and frequently severe. Patients often require prolonged treatment with high doses of oral corticosteroids. There are no data on the mortality associated with treated ENL.MethodologyThe notes of patients who were admitted, discharged, transferred to another facility or died with a diagnosis of leprosy or a leprosy-related complication for a five year period were reviewed.Result/Discussion414 individuals were identified from the ward database. 312 (75.4%) patient records were located and reviewed. Ninety-nine individuals had ENL and 145 had a Type 1 reaction. The median age of individuals with ENLwas 25 years. Eight patients with erythema nodosum leprosum died compared with two diagnosed with Type 1 reaction. This difference is statistically significant (p = 0.0168, Fisher's Exact Test). There is a significant mortality and morbidity associated with ENL in this Ethiopian cohort. The adverse outcomes seen are largely attributable to the chronic administration of oral corticosteroids used to control the inflammatory and debilitating symptoms of the condition.

Tissue-specific gene expression and regulation in liver and muscle following chronic corticosteroid administration.

Although corticosteroids (CSs) affect gene expression in multiple tissues, the array of genes that are regulated by these catabolic steroids is diverse, highly tissue specific, and depends on their functions in the tissue. Liver has many important functions in performing and regulating diverse metabolic processes. Muscle, in addition to its mechanical role, is critical in maintaining systemic energy homeostasis and accounts for about 80% of insulin-directed glucose disposal. Consequently, a better understanding of CS pharmacogenomic effects in these tissues would provide valuable information regarding the tissue-specificity of transcriptional dynamics, and would provide insights into the underlying molecular mechanisms of action for both beneficial and detrimental effects.We performed an integrated analysis of transcriptional data from liver and muscle in response to methylprednisolone (MPL) infusion, which included clustering and functional annotation of clustered gene groups, promoter extraction and putative transcription factor (TF) identification, and finally, regulatory closeness (RC) identification.This analysis allowed the identification of critical transcriptional responses and CS-responsive functions in liver and muscle during chronic MPL administration, the prediction of putative transcriptional regulators relevant to transcriptional responses of CS-affected genes which are also potential secondary bio-signals altering expression levels of target-genes, and the exploration of the tissue-specificity and biological significance of gene expression patterns, CS-responsive functions, and transcriptional regulation.The analysis provided an integrated description of the genomic and functional effects of chronic MPL infusion in liver and muscle.

Once-daily treatment with beclomethasone dipropionate nasal aerosol does not affect hypothalamic-pituitary-adrenal axis function

BackgroundIntranasal corticosteroids are effective in controlling allergic rhinitis (AR) symptoms; however, chronic administration of corticosteroids may suppress hypothalamic-pituitary-adrenal (HPA)-axis function. ObjectiveTo evaluate the effects of 6 weeks of treatment with beclomethasone dipropionate (BDP) hydrofluoroalkane nasal aerosol on HPA-axis function in subjects with perennial AR (PAR). MethodsIn this randomized, double-blind, placebo- and active-controlled study, subjects aged 12 to 45 years were randomized to receive BDP nasal aerosol 320 μg/day (n = 50), placebo (n = 46), or placebo/prednisone (prednisone 10 mg/day for the last 7 days of the treatment period [n = 11]). The primary end point was change from baseline in 24-hour serum cortisol (SC) weighted mean (expressed as geometric mean ratio [GMR]) in the BDP and placebo group after 6 weeks of treatment. ResultsGeometric SC-weighted mean values were similar in the BDP and placebo groups at baseline (9.04 and 8.45 μg/dL, respectively) and after 6 weeks (8.18 and 8.01 μg/dL, respectively). After 6 weeks of treatment, BDP was noninferior to placebo with respect to the ratio from baseline in SC-weighted mean (GMR: 0.96 [95% CI: 0.87, 1.06]). In contrast, 7 days of prednisone treatment substantially reduced geometric SC-weighted mean values from baseline (approximate 3-fold reduction [from 7.33 to 2.31 μg/dL]) compared with placebo. BDP nasal aerosol was well tolerated, and the safety profile was similar to that of placebo. ConclusionTreatment with BDP nasal aerosol, 320 μg once daily, was not associated with HPA-axis suppression in adolescent and adult subjects with PAR. Trial RegistrationClinicaltrials.gov Identifier: NCT01133626.

Diagnosis of hyperadrenocorticism in dogs

Hyperadrenocorticism is a common condition in older dogs. It arises when feedback mechanisms within the hypothalamic-pituitary-adrenal axis fail, resulting in a chronic excess of blood cortisol. The most common cause of canine hyperadrenocorticism is a microscopic, benign, pituitary gland tumour, with fewer cases caused by adrenal tumours or chronic corticosteroid administration. Diagnosis of the condition can be challenging. Clinical findings are varied, and many are common to other conditions. Screening tests are also nonspecific, and there is no single test available for its definitive diagnosis. Consequently, a combination of history, clinical signs, and laboratory findings are important in diagnosing hyperadrenocorticism.

Idiopathic Intracranial Hypertension in a Child With Duchenne Muscular Dystrophy

Duchenne muscular dystrophy is an X-linked, recessively inherited disorder characterized by progressive weakness attributable to the absence of dystrophin expression in muscle. In multiple studies, the chronic administration of corticosteroids slowed the loss of ambulation that develops in mid to late childhood. Corticosteroids, however, frequently produce unacceptable side effects, including Cushingoid appearance and weight gain. Deflazacort, an oxazoline analogue of prednisolone, produces equivalent benefits on muscle with fewer reported Cushingoid side effects. We present a 9-year-old boy with Duchenne muscular dystrophy who developed morbid obesity and subsequent idiopathic intracranial hypertension after 2 years of receiving deflazacort. Although deflazacort is typically thought to produce less obesity than prednisone, severe Cushingoid side effects may occur in some individuals. To our knowledge, this description is the first of idiopathic intracranial hypertension complicating chronic corticosteroid treatment of Duchenne muscular dystrophy.

Toward a Novel Endogenous Anxiolytic Factor, Fibroblast Growth Factor 2

Toward a Novel Endogenous Anxiolytic Factor, Fibroblast Growth Factor 2

Mycophenolate Mofetil Therapy Is a Steroid Sparing In Childhood and Young Adult Chronic ITP and Evans Syndrome.

AbstractAbstract 1441Chronic ITP and Evans syndrome are diseases characterized by autoantibody formation with resultant destruction of platelets or both platelets and red blood cells on neutrophils, respectively. Affected patients are at risk of life threatening bleeding complications and/or life threatening anemia. Conventional therapies are often ineffective or transiently effective and have significant toxicity. One of the most commonly used therapeutic strategies employs chronic corticosteroid administration with the attendant weight gain, hypertension, hyperglycemia, bone loss, infection risk, mood changes and protean other undesirable side effects. Mycophenolate Mofetil (MMF) is an immunosuppressive agent with a favorable side effect profile. It is converted to the active metabolite, mycophenolic acid, and interferes with purine metabolism in T-lymphocytes, effectively killing many of these cells and down-regulating autoimmune phenomena. With approval of our local IRB /HIC we retrospectively reviewed the charts of 11 chronic ITP/Evans syndrome patients who had received MMF, all such patients treated at a large urban Children's Hospital. Clinical variables included age, sex, duration of disease, steroid use, IVIG use, Anti-D use, platelet counts, hemoglobin concentrations and reticulocyte percentages. These data were analyzed using paired t-tests, one-sample t-test and descriptive statistics. The 11 patients ranged in age from 9–22 years old, with a mean age of 15 years. The mean time from diagnosis of disease was 41.8 months with a range of 6–95 months. There were 5 female subjects, 6 Evans syndrome patients and 5 with chronic ITP alone. The median platelet count over the 6 months prior to MMF was 70×109/L, (18-223), with a median of 90×109/L with (27-145) during the first 6 months of MMF therapy (p=0.4). In the Evans syndrome group, the mean hemoglobin prior to MMF was 10.9 g/dL, (9.1-14.6), with a mean of 12.1 g/dL, (6.9-16.7) on MMF (p=0.54). Similarly, the mean reticulocyte percentage was 2.7%, (0.5-14) prior to MMF, with a mean of 2.3%, (0.3-8.9) during MMF therapy. The mean total dose of steroids used in the 6 months prior to MMF was 84.2 mg/kg (prednisone equivalent), (11.2-170), compared to 62.2 mg/kg, (0-193.8) on MMF. 9 of 11 patients had reductions in steroid requirement by an average of 49.3% (p=0.0013). During the first 6 months of MMF both IVIG and anti-D usage decreased from total doses for the entire group of 17 and 3 doses to 8 and 1 dose, respectively. None of the patients experienced severe bleeding episodes or side effects more serious than a transient rash while on MMF. These data suggest that MMF may have a role as a steroid sparing therapy in the treatment of chronic ITP and Evans syndrome. Disclosures:Off Label Use: mycophenolate mofetil for ITP Evans syndrome.

Iatrogenic Cushing’s syndrome and secondary adrenal insufficiency after a single intra-articular administration of triamcinolone acetonide in HIV-infected patients treated with ritonavir

The development of an iatrogenic Cushing's syndrome (ICS) followed by secondary adrenal failure remains an exceptional event after a single dose administration of a synthetic glucocorticoid. Medical attention has been drawn recently on the possible impact of ritonavir-based antiretroviral regimens on the systemic deleterious effects of a chronic administration of corticosteroids in HIV-infected patients. Three HIV-infected patients treated by a ritonavir-boosted protease inhibitor (PI) regimen received a single intra-articular injection of 40 mg triamcinolone acetonide in our university hospital. The three patients rapidly developed signs and symptoms of ICS followed by secondary adrenal insufficiency. Special attention must be paid when a single administration of corticosteroids has to be given in HIV-positive patients under ritonavir-boosted antiretroviral treatment, as these patients are at risk of developing early cushingoid features and a prolonged suppression of their hypothalamic-pituitary-adrenal axis.

Chronic oral administration of dexamethasone to rats increases cytotoxicity, but not interleukin-1 elaboration, by alveolar macrophages

Chronic administration of corticosteroids has been used to induce pulmonary infection in animals. but the specific mechanisms by which corticosteroids modulate pulmonary host defence have not been clarified. Specifically, little is known about how corticosteroids influence the function of lung cells, such as alveolar macrophages. Cytotoxicity and interleukin-1 elaboration are two important mechanisms of macrophage defence against pathogens. To determine whether chronic administration of dexamethasone alters cytotoxicity and interleukin-1 elaboration by alveolar macrophages, we studied alveolar macrophages from rats treated with oral doses of dexamethasone for 2 weeks. We found that unstimulated alveolar macrophages from dexamethasone-treated rats exhibited increased cytotoxicity compared with alveolar macrophages from control rats. Moreover, alveolar macrophages from both groups of rats showed enhanced cytotoxicity after in vitro interferon-gamma and lipopolysaccharide treatment, in a dose-dependent manner. Although no spontaneous interleukin-1 elaboration was detected from alveolar macrophages from either group of rats, lipopolysaccharide increased interleukin-1 elaboration by alveolar macrophages from both groups of rats equivalently. These results indicate that chronic oral administration of dexamethasone to rats increases cytotoxicity, and does not alter the capacity of alveolar macrophages to elaborate interleukin-1. Therefore, chronic corticosteroid administration appears to produce selective alterations in these defence mechanisms of alveolar macrophages.

Relationship between abnormal fetal testing and adverse perinatal outcomes in intrauterine growth restriction

This study was undertaken to compare the efficacy of nonstress test, biophysical profile, or abnormal Dopplers in predicting adverse perinatal outcomes in intrauterine growth restriction. Retrospective cohort study of intrauterine growth restriction (birthweight < fifth percentile for gestation) over a 7-year period. We excluded twins or fetuses with aneuploidy or congenital malformations. Abnormal antenatal testing were defined as: nonstress test that was nonreactive or with significant decelerations, biophysical profile less than or equal to 6, and abnormal Doppler as umbilical artery with absent or reversed end diastolic flow. The outcomes studied included: umbilical artery pH less than 7, respiratory distress syndrome, periventricular leukomalacia, grades 3-4 intraventricular hemorrhage, perinatal mortality, necrotizing enterocolitis, and a composite of at least 1 adverse outcome. Statistical analysis included bivariate and multivariable techniques. We identified 151 singleton pregnancies with intrauterine growth restriction meeting the inclusion criteria. On bivariate analysis significant variables associated with adverse outcomes were as follows: history of chronic hypertension, corticosteroid administration, and gestational age of delivery. These were adjusted by using logistic regression. The positive predictive values of abnormal Doppler for respiratory distress syndrome and the composite of adverse outcomes were 36% and 42% respectively. Of the testing modalities compared, only abnormal Doppler significantly predicted respiratory distress syndrome and the composite of adverse outcome. In cases of intrauterine growth restriction, the presence of abnormal Doppler is the best predictor of adverse perinatal outcome.

Nocardiainfections in cats: a retrospective multi‐institutional study of 17 cases

To record 17 cases of nocardiosis in cats from eastern Australia and to compare this series with cases previously reported. Retrospective/prospective study. Nocardia spp infections were diagnosed in 17 cats over 14 years from the three eastern states of Australia. There were no isolates from dogs during this period, but one isolate from a koala and two from dairy cows. The majority of cats presented with spreading lesions of the subcutis and skin associated with draining sinus tract(s). Early cutaneous lesions consisted of circumscribed abscesses. Infections spread at a variable rate, generally by extension to adjacent tissues. Lesions were generally located in regions subjected to cat bite or scratch injuries, including limbs, body wall, inguinal panniculus and nasal bridge. In some other cases, lesions were situated on distal extremities. The clinical course was variable, from chronic, indolent, initially localised infections to acute fulminating disease. Of the 17 cats, 14 were domestic crossbreds and three were purebreds. There was a preponderance of male cats (12 castrated, 1 entire young adult, 1 entire kitten). Nine of 17 cats were 10 years or older. Interestingly, the majority of infections were attributable to N nova. Immediate and/or predisposing causes could be identified in all cases, and included: renal transplantation [one cat]; chronic corticosteroid administration [three cats]; catabolic state following chylothorax surgery [one cat]; fight injuries [seven cats]; FIV infections [three of seven cats tested]. Of the 17 cats, three were apparently cured. Four were thought to be cured, but infection recurred after several months. Three cats responded partially but were euthanased, while another was improving when it died of unrelated complications. Two died despite treatment and two were euthanased without an attempt at therapy. For two cats there were either insufficient records or the patient was lost to follow up. Nocardiosis is a rare, serious disease. Currently it is more common in cats than dogs. Nocardial panniculitis may be clinically indistinguishable from the syndrome caused by rapidly growing mycobacteria. Although the prognosis is guarded, patients with localised infections caused by N nova often respond to appropriate therapy. If definitive treatment is delayed because of misdiagnosis, the disease tends to become chronic, extensive and refractory. Insufficient duration of therapy leads to disease recurrence.