Large Doses Of Corticosteroids Research Articles

Rhino-orbital-cerebral mucormycosis: An epidemiological study from a tertiary care referral center in Western India.

Purpose:Rhino-orbital-cerebral mucormycosis (ROCM) is a rare opportunistic fungal infection with a fulminant course and an often fatal outcome. It can occur in immune-compromised patients such as those having uncontrolled diabetes, on long-term corticosteroid or immunosuppressive therapy, with COVID-19 infection, renal failure, AIDS, malignancy, or organ transplant. The aim of our study was to study the epidemiology of mucormycosis in COVID-19 patients and identify its risk factors.Methods:Ours was an epidemiological study wherein we gathered the demographic, clinical, histopathological, and radiological data of 458 patients of mucormycosis who presented to us between August 2020 and May 2021. Mucormycosis was defined through clinical and radiological findings or positive culture reports.Results:Out of all, 20.74% of patients did not have any past or concurrent history of COVID-19. The most common symptom of mucormycosis was orbital/facial pain (38.64%) and the most common sign was periocular/facial edema (50.74%). Mucormycosis involving the nose and sinuses (94.54%) was most common followed by rhino-orbital (45.41%) and brain involvement (10.04%). The most common risk factor for mucormycosis was diabetes [81.92%], followed by corticosteroid use [79.69%] and supplemental oxygen [48.90%]. Most of the patients received similar treatment with IV amphotericin B [88.64%] and local debridement [80.74%]Conclusion:With the third wave of COVID-19 still lurking, a fatal fungal infection should be kept in mind in COVID-19 active as well as recovered patients, especially those who have co-morbid medical conditions such as uncontrolled diabetes and who are treated with large doses of corticosteroids.

Washed microbiota transplantation for the treatment of recurrent fungal infection in a patient with ulcerative colitis.

Washed microbiota transplantation for the treatment of recurrent fungal infection in a patient with ulcerative colitis.

Hydrocortisone inhibition of wild-type and αD200Q nicotinic acetylcholine receptors.

Short-term treatment with large doses of corticosteroids can result in acute weakness of muscles in processes that have not yet been fully characterized. Corticosteroids have been shown to exert direct inhibitory action on the muscle-type nicotinic acetylcholine receptor (AChR), and therefore can promote pharmacological muscle denervation. The mechanism of hydrocortisone (HC) blockage of AChR has not been fully established yet. It is uncommon for an electrically neutral molecule, for example, HC, to induce voltage-dependent changes in AChR kinetics. Our experiments aimed to determine the source of voltage-dependency in HC action. Wild-type (WT) and αD200Q receptors were transiently expressed in HEK293 cells. Recordings were performed in either the presence or absence of HC. We showed that the D-to-Q substitution is capable of suppressing the voltage dependency in the HC-induced block. We conclude that the distance between αD200 and the agonist-binding site depends on the membrane potential. The voltage-dependent changes of the αD200 position have not been considered yet. To our knowledge, the ability to induce voltage-dependency in blocker action has not been shown previously for an amino acid located outside the transmembrane portion of the receptor. Possible mechanisms of HC block (allosteric and knocking) in WT and αD200Q receptors are discussed.

Management of Subacute Thyroiditis with Conventional High-Dose Prednisolone; Shooting a Tree Sparrow with a Cannonball

Background: A well-established medical entity, and typically self-limited disorder, the subacute thyroiditis (SAT), has been conventionally treated with a large dose (40-80 mg) of prednisolone per day for decades: a nonevidence- based and utterly large dose of corticosteroid for a disease with clearly predictable self-limiting course. The current study was designed to evaluate the efficacy of prednisolone 15 mg/day instead of routinely prescribed large dose of 40-80 mg, and to investigate the rate of early relapse with low-dose protocol. Subjects and methods: In a prospective study, forty-five cases of SAT were consecutively included. The diagnosis of SAT was made based on defined criteria of persistent sore throat, rapidly developed painful goiter, suppressed TSH, high ESR, and low RAIU. They were treated with 15 mg of prednisolone per day during the first month, 10 mg per day for the second month, and finally 5 mg daily over the third month. All cases were carefully followed for a minimum of one year to track the clinical and biochemical response to therapy and to find out any evidence of early relapse after discontinuation of medication. Results: Of forty-five patients who completed the oneyear- course of follow-up, 38 were female and 7 were male (male/female ratio 5.4). Mean age of affected subjects was 39 ± 10 years, and mean ESR was 70 ± 23 mm/hr (median 75 mm/hr, range 30-117 mm/hr). Among all subjects with full-blown SAT, only one case (2.2%) remained noticeably symptomatic on 15 mg prednisolone daily after two weeks, requiring 30 mg of medicine per day for symptomatic relief and normalization of ESR. After corticosteroid withdrawal, significant relapse occurred in only two patients (4.4%). Conclusion: Our results, not only endorse the efficacy of low-dose prednisolone in management of subacute thyroiditis, but also demonstrate the remarkably less relapse with low dose corticosteroid.

Acute Respiratory Distress Syndrome (ARDS) Case Report after a Caesarean Section Related to the Immune Reconstitution Inflammatory Syndrome

During pregnancy, a cellular immunosuppressant status is produced. It is characterized by anti-inflammatory cellular responses that allow embryonic implantation. The reversal of these changes during the postpartum period may result in overt clinical manifestations of otherwise quiescent or latent infections. We present an Acute Respiratory Distress Syndrome (ARDS) case after a caesarean section related to the Immune Reconstitution Inflammatory Syndrome (IRIS) in a Guinean black woman. The patient was treated with large doses of corticosteroids showing a great clinical and radiological improvement.

Clinical characteristics, diagnostic criteria and therapeutic outcomes in autoimmune optic neuropathy

Background/aims:Autoimmune optic neuropathy (AON) is characterised by chronically progressive or recurrent visual loss associated with serological or cutaneous evidence of autoimmunity, without a defined systemic autoimmune illness. It may improve...

Behçet's disease – a delay in diagnosis: why look in the mouth?

AbstractA rare case of severe Behçet's disease in a young patient is presented. The patient unnecessarily suffered from the devastating effects of the disease as a result of a delay in diagnosis, and consequently, initiation of the appropriate treatment. However, once a diagnosis was made, he was successfully treated with large doses of corticosteroids together with azathioprine, warfarin and aspirin. We highlight the importance of oral examination in diagnosing systemic diseases.

Akute Pneumozystosen unter Polychemotherapie nach dem MACOP-B-Protokoll

Four out of eleven patients--none of them HIV positive--who received treatment for non-Hodgkin lymphoma by the MACOP-B protocol between June 1989 and February 1990 were taken ill during or shortly after the conclusion of the course with fulminant pneumonia necessitating artificial ventilation. In three cases Pneumocystis carinii was identified as the pathogen, and in one patient the diagnosis of pneumocystosis seemed probable. The mean cumulative doses given before the outbreak of pneumonia were as follows: cyclophosphamide 2753 +/- 1161 mg, methotrexate 1590 +/- 667 mg, bleomycin 36 +/- 16.8 mg and prednisone 4378 +/- 1734 mg. The mean haemoglobin concentration was 10.7 +/- 0.5 g/dl, leucocyte count 5250 +/- 2100/microliters, lymphocyte count 1300 +/- 300/microliters and lactate dehydrogenase 227 +/- 34 U/l. The cumulative doses and laboratory findings in the seven patients not affected by pneumocytosis were not significantly different. The patients with pneumonia were supported by mechanical ventilation for 6-26 days and treated with large doses of corticosteroids and co-trimoxazole. One patient died after 17 days' ventilation. Three patients were successfully weaned from the ventilator. Chemotherapy protocols such as MACOP-B predispose to acute Pneumocystis pneumonia. The risk of infection is independent of the cumulative doses of the drugs employed. For this reason, prophylaxis with co-trimoxazole is normally mandatory.

Intradermal tests in dermatology-II: Tests for noninfectious diseases

INTRODUCTION Although the tests could be done at any site, the proximal part of the flexor aspect of the forearm is Intradermal tests are widely used to support the conventionally used. This site can be conveniently diagnosis of dermatological and nondermatological exposed and the skin of the proximal area is more diseases. They are mainly indicated for the detection sensitive than the distal. of immediate (Type I hypersensitivity) and delayed type hypersensitivity (DTH, Type IV hypersensitivity) INTERPRETATION OF INTRADERMAL TESTS towards exogenous or endogenous antigens. Intradermal tests for the diagnosis of infectious The optimal time for reading the reaction depends diseases in relevance to dermatovenereology are upon the pharmacological agent used for the test discussed in this section. and the type of immunological reaction to be observed. Intradermal tests for the detection of DTH Intradermal tests for the diagnosis of infectious are read at 48h, although they can be read as early diseases are listed in Table 1. They are indicated to as 12h and as late as four days. (The lepromin test detect DTH to organisms or their antigens. is read at four weeks and depends on the formation of a granuloma, which is a measure of cell-mediated Before undertaking intradermal test, it is advisable to immunity.) The size of the induration is more stop or avoid systemic steroids or immunosuppressive important than erythema while interpreting Type agents at least three days before the procedure as IV hypersensitivity. moderate to large doses of corticosteroids may inhibit a DTH reaction.

Medical advice for international travelers.

Each year, approximately 30 to 40 million Americans travel outside the United States. Although the most popular destinations are Europe, Central America, and the Caribbean, travel to Africa and Asia is increasing substantially. International travel, particularly to developing countries, can be associated with the risk of infectious and noninfectious diseases. These risks can be decreased, eliminated, or modified with vaccinations, prophylactic medications, and education. Optimally, pretravel advice must be individualized to a person's medical history, itinerary, and risk behavior. In addition to risk assessment-based immunizations, issues such as traveler's diarrhea, malaria prophylaxis, sexually transmitted diseases, and management of underlying medical problems must form a part of pretravel management. Adventure or prolonged travel or persons with underlying medical diseases such as insulin-dependent diabetes mellitus, transplantation, immunodeficiencies, and dialysis warrant additional preventive measures. This review primarily updates pretravel management of adults.

Clinical Experience of 13 Cases with Severe Pulmonary Hemorrhage in Systemic Lupus Erythematosus with Active Nephritis

Pulmonary hemorrhage is a rare, but serious manifestation of systemic lupus erythematosus (SLE). Herein, we report 13 cases of severe pulmonary hemorrhage in SLE. Hemoptysis was present in 11 patients. All thirteen patients had active nephritis and were in the stage of nephrotic syndrome. A majority of the patients had neuropsychiatric manifestations and coagulopathy including thrombocytopenia or lupus anticoagulant. All episodes of pulmonary hemorrhage occurred after large dose of corticosteroid had been administered in treating nephritis. Recurrent pulmonary hemorrhage was noted in four patients. Ten (77%) of the 13 patients finally died. Respiratory failure was the main cause of death. Our observation suggests that active nephritis with hypoalbuminemia is a major risk factor for severe pulmonary hemorrhage in SLE patients and that high dose corticosteroid use can not prevent the occurrence of severe pulmonary hemorrhage in SLE.

High incidence of steroid complications related to cumulative steroid dose in systemic lupus erythematosus patients over the age of 50

In 6–20% of patients with Systemic Lupus Erythematosus (SLE), the onset occurs after the age of 50 years. Treatment with large doses of corticosteroids (CS) in these patients may be associated with severe side effects. The aim of this study was to describe the main clinical manifestations of elderly SLE patients and the CS related major complications.

The Anterior Pituitary, Snakebite and Sheehan's Syndrome

In Burma, Russell's viper bite is a major public health problem, especially in rice field workers. Death frequently occurs from renal and cardiac failure. Prompted by observation of hypoglycaemia and reported necropsy findings of pituitary damage after Russell viper bite, Warrell and his co-workers in Rangoon succeeded in showing pituitary function defects in the victims [1], despite the difficulties with studies of acute illness in a rural background. Now the Hammersmith group [2] with a different set of Burmese researchers have confirmed the findings, showing bite by this viper to be a common cause of anterior pituitary failure in Burma. Between them the two groups have studied 36 long-term survivors, and have found frequent clinical evidence of pituitary hormone failure. This is supported by firm laboratory evidence in patients not on replacement for the hormone concerned, as follows: low testosterone in 16 of 33 tested, oligoor amenorrhoea in two of two, low thyroxine in 13 of 34, cortisol response to hypoglycaemia <500 nmol/1 in 10 of 14, and GH response to hypoglycaemia <20 mU/1 in 15 of 17. Showing the contribution of acute pituitary failure to morbidity and mortality in the acute illness is more difficult. All but one of the 20 patients of Proby el al. studied acutely had (sensibly, and presumably following the previous report of Tun-Pe et al.) been given large doses of corticosteroids before the samples were drawn for hormone analysis. The resulting suppression of the normal cortisol and growth hormone responses to severe acute illness makes it impossible to assess agonal levels of these hormones except in the few patients who had (normal) elevated levels. Similarly suppression of gonadotrophin function and lowering of T4 levels by both the severe acute illness and the steroids is admitted by Proby et al., and makes those measurements uninterpretable also. That the extent of the lowering of T4 or steroid levels indicates pituitary failure, rather than the effects of acute illness plus steroids, is not a legitimate plea a control group matched for severity and therapy would be required. Neither is hypoglycaemia recorded by Proby et al., again perhaps because of the steroid support given. However the samples showing pituitary insufficiency drawn by Tun-Pe and co-workers were taken before any corticosteroid therapy, and they also showed hypoglycaemia in three of seven patients tested. There is no doubt about the occurrence of acute anterior pituitary failure within hours of Russell's viper bite. The empirical use of high-dose steroids in India rests not on this, but on reduced mortality in rats [3].

Antiinflammatory activity of a COOH‐terminal fragment of the neuropeptide α‐MSH

The endogenous neuropeptide alpha-melanocyte stimulating hormone (alpha-MSH 1-13), previously found to have marked antipyretic activity, inhibits histamine-induced increases in vasopermeability. The primary antipyretic amino acid message sequence is believed to be the COOH-terminal trieptide, lysine-proline-valine. In recent preliminary research this tripeptide inhibited increases in vasopermeability, raising the possibility that this portion of the alpha-MSH molecule has general antiinflammatory activity. To test this idea, the effects of graded doses of alpha-MSH [11-13] on ear swelling induced by picryl chloride in mice were compared with the effects of saline and a large dose of corticosteroid. Alpha-MSH [11-13] inhibited swelling in a dose-related fashion. This result, together with previous findings, suggests that endogenous circulating alpha-MSH and its COOH-terminal fragments may contribute to modulation of physiological responses in host defense. If this is true, it may be possible to develop new peptide drugs or mimetics based on the tripeptide that are useful in treating inflammation.

Angiotensin-converting enzyme. Investigation of diurnal variation, the effect of a large dose of prednisolone, and prednisolone pharmacokinetics in patients with sarcoidosis.

Serial assay of serum angiotensin-converting enzyme concentrations (SACE) is advocated for monitoring disease progress in sarcoidosis. Because little is known of nondisease factors affecting SACE, 10 patients with histologically proved sarcoidosis were assessed for diurnal fluctuation in SACE and as to whether a large dose of corticosteroid had an immediate effect on SACE independent of disease. The pharmacokinetics of prednisolone in 8 of these patients was also evaluated. On Day 1, serum samples were obtained for 24 h after placebo, and the next day at the same times after 75 mg of orally administered prednisolone. There was no obvious diurnal pattern on either day, and there was no significant difference in SACE after prednisolone. The mean maximal difference obtained within or between days was 8.8%. Prednisolone pharmacokinetics were comparable to normal volunteers. SACE concentrations can be confidently determined at any time of day, and changes of greater than 9% are probably significant. The use of prednisolone in patients with sarcoidosis can be safely based upon pharmacokinetic data obtained from normal volunteers.

Hepatomegaly following short-term high-dose steroid therapy.

Children treated with large doses of corticosteroids were found to develop hepatomegaly within a few days. No relationship could be established between the condition for which steroids were given and the liver enlargement. Liver biopsy was thought to be indicated, and thus was performed in three children because of diagnostic uncertainty. The light and electron microscopic examinations revealed normal liver architecture, without edema, sinusoid engorgement, or inflammatory changes. The hepatocytes were distended by increased amounts of glycogen. In a pattern reminiscent of some glycogen storage diseases, mitochondria and other cytosol components were displaced toward the cell membrane or around the nucleus, which occasionally contained glycogen. Moderate sinusoidal compression, interhepatocytic free glycogen particles, and mild increase in lipid droplets were also found. It is concluded that the hepatomegaly noted in patients given short-term, high-dosage steroid therapy is due to excessive glycogen accumulation within parenchymal cells. This finding is in accordance with observations in animals, as well as with biochemical studies demonstrating hepatocytic glycogen deposition after steroid therapy. Being benign and reversible, early hepatomegaly following administration of high-dose corticosteroids should not influence the initial therapeutic plan required by the basic disease.

Anterior ischemic optic neuropathy: sense and nonsense in diagnosis and treatment.

In 15 consecutive patients with AION the cause was found to be giant-cell arteritis in 3 cases and was thought to be local arteriosclerosis of the posterior ciliary arteries in 12 cases, in spite of rheumatic factors which were found initially. In 87% of cases symptoms or factors indicating generalised arteriosclerosis were found. In one case before the AION cilioretinal emboli had been found. It is reported that the second eye is affected after a varying interval of time in +/- 50% of cases. In our material the arteriosclerotic form of AION occurred bilaterally in +/- 40% of cases with an interval varying from a few days to 5 years. The average interval for this form of AION is 3 years. Cerebral angiography was of no help in tracing the cause of the AION. A fluorescein angiogram is often made too late to show the characteristic circulatory disturbance in the peripapillary choroid and is usually not necessary. Therapy should be started immediately, with large doses of corticosteroids in all cases of AION, until biopsy of the temporal artery proves negative or the ESR is practically normal. Hypertension and diabetes should be treated adequately as protection for the other eye in the arteriosclerotic form of AION. In addition long-term anticoagulant therapy should be considered: a prospective study into this aspect has been started.

Hepatomegaly Following Short‐Term High‐Dose Steroid Therapy

SummaryChildren treated with large doses of corticosteroids were found to develop hepatomegaly within a few days. No relationship could be established between the condition for which steroids were given and the liver enlargement. Liver biopsy was thought to be indicated, and thus was performed in three children because of diagnostic uncertainty. The light and electron microscopic examinations revealed normal liver architecture, without edema, sinusoid engorgement, or inflammatory changes. The hepatocytes were distended by increased amounts of glycogen. In a pattern reminiscent of some glycogen storage diseases, mitochondria and other cytosol components were displaced toward the cell membrane or around the nucleus, which occasionally contained glycogen. Moderate sinusoidal compression, interhepatocytic free glycogen particles, and mild increase in lipid droplets were also found. It is concluded that the hepatomegaly noted in patients given short‐term, high‐dosage steroid therapy is due to excessive glycogen accumulation within parenchymal cells. This finding is in accordance with observations in animals, as well as with biochemical studies demonstrating hepatocytic glycogen deposition after steroid therapy. Being benign and reversible, early hepatomegaly following administration of high‐dose corticosteroids should not influence the initial therapeutic plan required by the basic disease.

Effects of glucocorticoids on experimental allergic neuritis

Corticosteroids were administered to rats and guinea pigs with experimental allergic neuritis, from the time of inoculation with antigen or from the onset of signs of disease. No statistically significant effects were observed in guinea pigs. In rats, to which large doses of corticosteroids were administered, disease severity was slightly but significantly reduced in both groups and recovery was more rapid in the animals treated from the time of induction of disease. These results were comparable with those obtained in trials of corticosteroids in acute inflammatory polyneuropathy in man, which have also not demonstrated any striking effects.

Protection against cardiac anoxia--role and limitations of increased glycogen reserves in the isolated rat right ventricular strip.

The effects of drugs on rat cardiac glycogen reserves in vivo, and on the subsequent in vitro sensitivity of the right ventricular strip preparation to anoxia have been investigated. Isoproterenol (0.2 mg/kg i.p.) causes immediate cardiac stimulation and reduction of glycogen reserves, coupled with an increased susceptibility to anoxia. Several hours after administration, glycogen levels are found to be greatly (100-200%) increased, by a "supercompensation" mechanism, and a marked tolerance to anoxia can be simultaneously demonstrated. In contrast, large doses of corticosteroids (dexamethasone, 8 mg/kg i.m.) increase glycogen levels without initial stimulation and glycogen depletion; increased myocardial tolerance to anoxia parallels the increase in glycogen reserves in vivo. We conclude that the myocardial tolerance to anoxia in this model is related to increased glycogen reserves, which increase the rate and/or duration of anaerobic glycolysis during anoxia.