Prolonged Steroid Treatment Research Articles

A rationale for using steroids in the treatment of severe cases of H5N1 avian influenza

Acute hypercytokinaemia represents an imbalance of pro-inflammatory and anti-inflammatory cytokines, and is believed to be responsible for the development of acute respiratory distress syndrome and multiple organ failure in severe cases of avian (H5N1) influenza. Although neuraminidase inhibitors are effective in treating avian influenza, especially if given within 48 h of infection, it is harder to prevent the resultant hypercytokinaemia from developing if the patient does not seek timely medical assistance. Steroids have been used for many decades in a wide variety of inflammatory conditions in which hypercytokinaemia plays a role, such as sepsis and viral infections, including severe acquired respiratory syndromes and avian influenza. However, to date, the results have been mixed. Part of the reason for the discrepancies might be the lack of understanding that low doses are required to prevent mortality in cases of adrenal insufficiency. Adrenal insufficiency, as defined in the sepsis/shock literature, is a plasma cortisol rise of at least 9 microg dl(-1) following a 250 microg dose of adrenocorticotropin hormone (ACTH), or reaching a plasma cortisol concentration of >25 microg dl(-1) following a 1-2 microg dose of ACTH. In addition, in the case of hypercytokinaemia induced by potent viruses, such as H5N1, systemic inflammation-induced, acquired glucocorticoid resistance is likely to be present. Adrenal insufficiency can be overcome, however, with prolonged (7-10 or more days) supraphysiological steroid treatment at a sufficiently high dose to address the excess activation of NF-kappaB, but low enough to avoid immune suppression. This is a much lower dose than has been typically used to treat avian influenza patients. Although steroids cannot be used as a monotherapy in the treatment of avian influenza, there might be a potential role for their use as an adjunct treatment to antiviral therapy if appropriate dosages can be determined. In this paper, likely mechanisms of adrenal insufficiency are discussed, drawing from a broad background of literature sources.

Amount of Systemic Steroid Medication Is a Strong Predictor for the Use of Complementary and Alternative Medicine in Patients With Inflammatory Bowel Disease.

Previous studies have suggested that inflammatory bowel disease (IBD) patients rank high among users of complementary and alternative medicine (CAM). To further elucidate this phenomenon, we sent questionnaires to a large sample of IBD patients in Germany to determine the patterns and predictors of their CAM use. Pretested 73-item questionnaires were mailed to a randomly selected representative sample of 1000 IBD patients from the approximately 16,000 members and associates of the German Crohn's and Colitis Association. Predictors of CAM use were evaluated by logistic regression models. Completed questionnaires were returned by 684 patients (female patients, 61.4%; Crohn's disease patients, 58.3%; ulcerative colitis patients, 38.2%). Of the 671 adult respondents, 344 (51.3%) had experience with CAM, and significantly more of the ulcerative colitis patients (59.8%) than the Crohn's disease patients (48.3%) had experience with CAM. There was no difference by gender. Homeopathy (52.9%) and herbal medicine (43.6%) were the most commonly used types of CAM. The most frequent personal reasons for CAM use were the search for an "optimum treatment" (78.9%) and the wish to stop taking steroids (63.8%). Using logistic regression, we found that total cortisone intake (P = 0.0077), but not duration of disease, was a strong predictor of CAM use. Other predictors were experience with psychosomatic and psychotherapeutic support (P = 0.0029), relaxation techniques (P = 0.0284), an academic education (P = 0.0173), a diet utilizing whole grains (P = 0.0123), and a normal body weight (P = 0.0215). Although 80% of patients indicated that they were interested in using CAM in the future, only 24.7% felt sufficiently informed about it. More than 50% of a large group of German IBD patients had used CAM. Prolonged or intensive steroid treatment, an academic education, active ways of coping, and a health-conscious life-style are associated with CAM use. Given the potential side effects and interactions, the treating physician should focus on thorough information about the benefits and limitations of conventional and complementary treatment options, especially for IBD patients who have received prolonged or intensive steroid treatment.

Outcome of a conservative approach in severe ulcerative colitis

Background. Severe ulcerative colitis is potentially life threatening even though a policy of intensive medical management and early colectomy in recent years reduced mortality to almost zero. However, colectomy, with or without ileal–anal anastomosis, has its own problems (morbidity, pouchitis, cuffitis) and no reliable prognostic index of surgical outcome has been developed. Intravenous steroids are still the mainstay of medical therapy but their maximal duration before stating a ‘treatment failure’ has not been defined. Aim of the study. To evaluate the effectiveness, safety and outcome of an intensive medical approach in a series of patients with severe ulcerative colitis. Patients and methods. One hundred and forty-nine episodes of severe ulcerative colitis in 115 patients admitted to a Gastroenterology Unit in a 7-year period were retrospectively evaluated. Intravenous glucocorticosteroids—methylprednisolone 1 mg/kg/day—and topical steroids were administered, and supportive treatments with intensive monitoring were extended to all the patients. Second-line strategies for steroid–refractoriness were prolonged glucocorticosteroids treatment, oral ciclosporin, infliximab or surgery. Results. The median number of Truelove criteria at admission was 3 (range 2–5), median CRP 34 mg/l (range 10–196). Median follow-up after discharge was 49 months. In 84 (57%) episodes an early response was noted, while 65 (43%) did not respond within 10 days to the standard steroid treatment. In the non-responders group, 28 patients went into remission with a prolonged steroid treatment (slow responders); 15 patients were treated with ciclosporin (eight responders) and 6 with infliximab (four responders). A total of 24 colectomies was performed in this group of patients (in 21 cases within 30 days from admission). Slow responders showed lower albumin levels ( P=0.02), higher cumulative dose of glucocorticosteroids in the year prior to admission ( P=0.02) and higher age ( P=0.03), in comparison with early responders. Major complications were noted in four episodes which responded to medical treatment. Disease-related mortality was zero. Conclusions. Medical treatment and use of second-line therapies were effective in the present series of patients. A group of slow responders has been identified and, if an intensive medical monitoring is guaranteed, steroids can be safely prolonged after the first 10 days of treatment. Cumulatively, about 80% of the patients responded to short-term medical treatment, only 5% of the patients underwent colectomy in the follow-up period. Major adverse events were recorded in four patients, who had recovered completely after adequate medical treatment.

Atherosclerosis, oxidative stress and auto-antibodies in systemic lupus erythematosus and primary antiphospholipid syndrome

Overwhelming evidence spanning three decades has consistently shown that coronary artery disease is a major cause of morbidity and mortality in Systemic Lupus Erythematosus. Traditionally this was explained by abnormalities of the lipid profile induced by prolonged steroid treatment. Subsequently, antiphospholipid antibodies were presented as an additional cardiovascular risk factor. Recently, antibodies towards high-density lipoprotein and antiapolipoprotein A-I have been identified. These, together with anti-beta2 glycoprotein-1, interfere with the major antioxidant defence of patients with SLE and with primary antiphospholiqid syndrome exposing them to the atherogenic potential of enhanced oxidative stress. The present review discusses how the latter auto-antibodies, together with abnormalities of their target lipid auto-antigens, could enhance the risk of atherosclerosis in SLE and APS.

Immunosuppressants and operation in ulcerative colitis.

Ulcerative colitis (UC) has many pathophysiologic features characteristic of immune diseases. These features provide the rationale for immunomodulatory therapy offered for treatment of UC in recent years. The association between UC and other autoimmune diseases, such as autoimmune anemia, pernicious anemia, systemic lupus erythematosus, and Hashimoto’s thyroiditis, has been previously described but there is no increase in the incidence of these disorders in patients with UC. Both UC and Crohn’s disease are characterized by a production of mucosal immunoglobulin G, Tand B-cell mucosal lymphocytosis, and macrophage activation during exacerbation of the disease. Autoantibodies are known to be present in UC, the most common being antineutrophil cytoplasmic antibody (ANCA). In UC, the staining pattern is perinuclear (pANCA), as opposed to Wegner’s granulomatosis, which has a cytoplasmic staining pattern. pANCA is expressed by 60% to 80% of patients with UC and by only 20% to 30% of patients with Crohn’s disease. Of interest is the fact that the vast majority of patients with pouchitis express pANCA. Antibody-producing cells are synthesized in reaction to intestinal antigens. T helper cells and B cells regulate the immune response, activating cytokines and resulting in altered immunoglobulin production. Importantly, the absolute number of lymphocytes in UC is normal, as are both delayed hypersensitivity and the subset of circulating T cells. The ratio of CD4 (helper) to CD8 (suppressor) T cells is the variable factor, and although the ratio is normal in remission, it is altered in exacerbation with T helper predominance. The B-cell population is less affected in UC, and natural killer cells are not defective, but there is an increase in lymphocyte production of interleukin2. The peripheral lymphocytes of UC patients have cytotoxic properties; this cytotoxicity is non–complement-dependent and is completely eliminated after colectomy. In summary, the immunopathology of UC involves an initiating antigen triggering a disproportionate inflammatory cascade. This cascade consists of inflammatory cell recruitment from the colonic blood supply with resultant release of inflammatory mediators. Mucosal function is altered by these changes, with increased permeability, mucous secretion, platelet activation, and tissue damage. Immunosuppressive agents are known to affect T-cell function and modulate cytokine function. This is the basis for the addition of cyclosporine, azathioprine, and 6-mercaptopurine to the conservative armamentarium for treating UC. The impact of prolonged steroid treatment as another indication for operation was evaluated by Sher and colleagues. They compared a matched group of patients treated either medically or surgically. Each group consisted of 20 patients matched for duration and severity of disease. Medically treated patients who required at least one hospital admission were compared with patients treated by a three-stage restorative proctocolectomy. Weight loss and transfusion requirements were both notably increased in the medically treated group. Sixty-five percent of patients in this group had major steroid-related complications, but the major surgical complication rate was only 15%.

Pneumocystis carinii pneumonia in patients with malignant haematological diseases: 10 years' experience of infection in GIMEMA centres

A retrospective survey was conducted over a 10-year period (1990-99) among 52 haematology divisions in order to evaluate the clinical and laboratory characteristics and outcome of patients with proven Pneumocystis carinii pneumonia (PCP) complicating haematological diseases. The study included 55 patients (18 with non-Hodgkin's lymphoma, 10 with acute lymphoblastic leukaemia, eight with acute myeloid leukaemia, five with chronic myeloid leukaemia, four with chronic lymphocytic leukaemia, four with multiple myeloma, three with myelodysplastic syndrome, two with myelofibrosis and one with thalassemia) who developed PCP. Among these, 18 (33%) underwent stem cell transplantation; only two received an oral prophylaxis with trimethroprim/sulphamethoxazole. Twelve patients (22%) developed PCP despite protective isolation in a laminar airflow room. The most frequent symptoms were: fever (86%), dyspnoea (78%), non-productive cough (71%), thoracic pain (14%) and chills (5%); a severe hypoxaemia was present in 39 patients (71%). Chest radiography or computerized tomography showed interstitial infiltrates in 34 patients (62%), alveolar infiltrates in 12 patients (22%), and alveolar-interstitial infiltrates in nine patients (16%). Bronchoalveolar lavage was diagnostic in 47/48 patients, induced sputum in 9/18 patients and lung biopsy in 3/8 patients. The diagnosis was made in two patients at autopsy. All patients except one started a specific treatment (52 patients trimethroprim/sulphamethoxazole, one pentamidine and one dapsone). Sixteen patients (29%) died of PCP within 30 d of diagnosis. Multivariate analysis showed that prolonged steroid treatment (P < 0.006) and a radiological picture of diffuse lung involvement (P < 0.003) were negative diagnostic factors.

Prolonged ovarian sex steroid treatment of male rats produces antinociception: identification of sex-based divergent analgesic mechanisms

Simulation of the pregnancy blood concentration profile of 17β-estradiol (E 2) and progesterone (P) in nonpregnant ovariectomized rats has been shown to result in a significant elevation of nociceptive response thresholds. The present report demonstrates that spinal opioid antinociceptive responsiveness to these ovarian steroids is not sex-specific. Treatment of orchidectomized sexually mature males with an analogous regimen of E 2 and P also elicits an antinociception, the robustness and temporal profile of which is comparable with that previously observed in females. Neither E 2 nor P, alone, is sufficient to produce antinociception in male rats, as was previously demonstrated in females. Neurobiological substrates and antinociceptive mechanisms underlying ovarian sex steroid antinociception do, however, exhibit sex specificity. In males, the analgesia resulting from ovarian steroid treatment derives from the independent contributions of spinal κ and μ, not δ, opioid receptor pathways that are additive, not synergistic. Spinal α 2-noradrenergic receptor activity and its attendant analgesic synergy with spinal opioid systems do not contribute to ovarian sex steroid analgesia in males. This is in contrast to the previous demonstrations that ovarian sex steroid-induced antinociception in females results from antinociceptive synergy between activated spinal κ/δ opioid as well as α 2-noradrenergic receptor systems. The current data reveal that ovarian steroid-activated multiplicative spinal antinociceptive pathways that had been demonstrated in female rats are not manifest in their male counterparts.

A breath of fresh air?

Lung cancer remains the leading cancer in the developed world. It is usually inoperable at presentation but there is new optimism regarding chemotherapy in non-small-cell lung cancer after the publication of a meta-analysis suggesting that cisplatin-based chemotherapy, in combination with surgery, radical radiotherapy, or best supportive care, results in significant prolongation of survival (BMJ 1995; 311: 899). In chronic obstructive pulmonary disease (COPD) non-invasive ventilation is increasingly being used in patients with acute respiratory failure. The benefits have been shown in a recent randomised controlled trial, the outcome measures being needed for endotracheal intubation, duration of hospital stay, and mortality (N EnglJ Med 1995; 333: 817). Obstructive sleep apnoea, which affects up to 5% of the general population, is associated with an increased risk of road traffic accidents. The untreated condition impairs simulated driving performance to about the same extent as a blood alcohol of 95mg/dL (George). This risk is reduced by treatment with nasal continuous positive airways pressure (CPAP) (Chest 1996; 1096: 1470). A recent study has shown a reduction in fibrinogen levels on nasal CPAP (Am J Respir Crit Care Med 1996; 153: 1972). After the controversy surrounding the oral contraceptive pill, it has now been established that the risk of venous thromboembolism, including primary pulmonary embolism, is also increased with postmenopausal hormone-replacement (Grodstein). Diagnosis of pulmonary embolism may be aided by spiral computed tomography, (Thorax 1996; 51: 23). Concern regarding multidrug resistant tuberculosis has continued to increase (Lancet 1996; 348: 928). The understanding of the molecular basis of resistance, particularly to isoniazid, is improving and continuing advances in PCR technology are facilitating rapid and accurate diagnosis (Condos). In pulmonary sarcoidosis, a study has suggested that, in patients not requiring steroid treatment initially who do not show spontaneous radiographic improvement during 6 months of observation, prolonged steroid treatment thereafter, over at least 18 months, results in a better functional outcome than selective treatment (Gibson). There has been much interest in the adverse respiratory health effects of respirable particles (PM10: <10 gm diameter), ozone, sulphur dioxide, oxides of nitrogen, and acid aerosols. The main source of particulate pollution is diesel-vehicle exhausts. Both respiratory and cardiovascular mortality (and morbidity) are increased by acute exposure to PM~0 particles even at current ambient levels. Pollution, however, does not seem to be responsible for the doubling in incidence of asthma over the past 20 years. Although established asthma is made worse by

Wound healing and myopic regression following photorefractive keratectomy

Scrapings from the treated area of 17 patients who had undergone photorefractive keratectomy were analyzed. All patients had regressed to myopia and were scraped at the time of retreatment. Three scrapings from the epithelium of patients undergoing primary photorefractive keratectomy served as control. Formalin fixed and paraffin embedded, the specimens were sectioned and stained specifically for hyaluronic acid. Hematoxylin was used for counterstaining in all specimens. Scrapings revealed either epithelial hyperplasia (11 cases) or an increased amount of extracellular material (15 cases) or both (9 cases). Five of the specimens stained positive for hyaluronic acid. Four of these cases showed the highest degree of corneal haze. The latter suggests a role for hyaluronic acid formation in excessive wound healing, causing myopic regression. All patients had received prolonged topical steroid treatment, a measure that may suppress a normal occurrence of hyaluronic acid.

Cytometric study of the female Syrian hamster gallbladder epithelium following sex steroid administration

This report is a cytometric study of the female Syrian hamster gallbladder epithelium following 1-, 2-, and 3-month administration of female sex steroids. Nulliparous, multiparous, young, old and pregnant hamsters were used in this study. A 1 month treatment with estrogen alone significantly increases the nuclear volume of the gallbladder epithelial cells, while E + P treatment significantly affects the nuclear volume only after a 2 month treatment. On the other hand, E + P and P treatments significantly increase the cell volumes as compared to the E-treated groups, this effect is most striking following the 1 month period. Prolonged sex steroid treatment (2 and 3 month) does not appear to influence the gallbladder epithelial cell and nuclear volumes as dramatically as that observed following the 1 month treatment. The nulliparous, progesterone-treated hamsters appear to have a greater cytoplasmic volume than the multiparous group and this is substantiated by the bulging apices and the luminal cellular excrescences observed with scanning and transmission electron microscopy. These observations are similar to those reported in ovariectomized hamsters (Gilloteaux et al., 1992). Further, the gallbladder epithelial cells and nuclei of the older female hamsters demonstrate an accentuated response to a 1 month sex steroid treatment as compared to the younger hamsters for the same treatment duration. These results enable us to hypothesize that changes induced by a short term sex steroid treatment participate in the gallstone nucleation process, while longer duration of the treatments contribute to progressive enlargement and accumulation of gallbladder calculi.

Pulmonary sarcoidosis in children: serial evaluation of bronchoalveolar lavage cells during corticosteroid treatment.

The clinical course of sarcoidosis in children has not been well defined. Eight children with symptomatic sarcoidosis included in this study underwent pulmonary function tests and bronchoscopy with bronchoalveolar lavage (BAL) before treatment and during steroid therapy. At the start of therapy, functional parameters, mostly dynamic lung compliance and lung transfer factor for CO, were impaired. This was associated with abnormalities of BAL cell populations: increased total cell number with a high proportion of lymphocytes, modifications of lymphocyte subpopulation with an elevated CD4+/CD8+ ratio, and enhanced ability of alveolar macrophages to release hydrogen peroxide. Although respiratory abnormalities seemed to be similar at the initial stage of sarcoidosis in children and adults, the course of the disease appeared to be different. Despite the absence of respiratory symptoms and disappearance of chest radiographic abnormalities on prolonged steroid treatment, we found slow improvement of pulmonary functions associated with persistence of BAL lymphocytosis and elevated CD4+/CD8+ ratios. However, the ability of alveolar macrophages to release hydrogen peroxide was significantly reduced after 6 months of steroid treatment, and it remained identical to the control group. Therefore, the evaluation of disease activity appears to be critical for therapy in pediatrics, and for this purpose studies of alveolar macrophage activation may be of particular interest.

Intestinal calcium absorption and parathyroid hormone secretion in asthmatic patients on prolonged oral or inhaled steroid treatment

A secondary hyperparathyroidism resulting from decreased intestinal calcium (Ca) absorption has been proposed as a contributory factor to glucocorticoid-induced osteoporosis. Inhaled steroids do not usually suppress adrenal gland function unless daily doses above 1,500 microgram are used. A recent study, however, has shown a reduced total body calcium in patients on regular beclomethasone treatment. In theory, osteopenia in these patients could be due to a direct effect of inhaled steroids on bone or due to an impaired intestinal calcium absorption. In this study, Ca absorption and parathyroid hormone (PTH) secretion were evaluated in three groups: 1) asthmatics on continuous oral and inhaled steroid treatment (11.3 +/- 4.4, range 5-33.5 mg.day-1 prednisone and 660 +/- 265, range 400-1,600 microgram.day-1 beclomethasone, respectively); 2) asthmatics on regular beclomethasone therapy (585 +/- 210, range 400-1,200 microgram.day-1); and 3) healthy subjects. The prevalence of vertebral fractures was evaluated by a spinal X-ray. No differences were found in either Ca absorption or PTH serum levels between asthmatics and healthy subjects (analysis of variance-ANOVA). Vertebral fractures were significantly more frequent in patients from group 1 (14 of 25) than in those from group 2 (2 or 25). We conclude that both prolonged oral steroid treatment and inhaled steroids, at doses lower than 1,600 microgram.day-1 do not cause Ca malabsorption, and that hyperparathyroidism does not contribute to osteoporosis in these patients.

The Immune Response to Nematode Parasites: Modulation of Mast Cell Numbers and Function During Strongyloides Stercoralis Infections in Nonhuman Primates

Mucosal mast cell numbers are modulated in the intestines of rodents during parasitic infections. These mast cells can degranulate in response to worm antigens, and this event has been suggested to play a protective role for the host. To examine whether mast cells in higher animals play a role in protecting from disseminated parasitic disease, mast cell numbers and responsiveness to parasite antigens were evaluated in 5 Erythrocebus patas infected with the human intestinal nematode Strongyloides stercoralis. Initial infection and subsequent challenge infections were associated with increase in jejunal histamine and mast cell numbers, and these mast cells could release histamine in response to parasite antigens. Jejunal mast cell numbers returned to normal during a chronic phase of infection. The cells lost their ability to respond to antigenic stimulation following limited steroid treatment. Subsequent activation of chronic infections to fatal disseminated disease by more prolonged steroid treatment was associated with a marked decrease in jejunal mast cell numbers and histamine. In one animal which succumbed to severe disease without steroid treatment, jejunal mast cells were refractory to worm antigens.

MAJOR ABDOMINAL SURGERY IN PATIENTS ON MAINTENANCE HEMODIALYSIS

Various types of major abdominal surgery were performed from September 1972 through August 1984 in a consecutive series of 62 patients undergoing long-term hemodialysis because of chronic renal failure. Routine preoperative hemodialysis undertaken continuously starting two days before surgery improved the uremic condition with biochemical abnormalities seen in the 42 patients receiving elective surgery. For the 20 on whom emergency surgery was performed, however, there was only a brief period of preoperative hemodialysis, undertaken in an effort to alleviate at least hyperkalemia and marked anemia, if present. Postoperative treatment for renal failure consisted mainly of peritoneal dialysis, which was switched to hemodialysis one week later if the intraabdominal surgical procedure had been extensive. Various types of postoperative complications, including bleeding, pseudomembranous colitis and respiratory problems, occurred in 29% of the patients, and 16.1% of all patients had died within one month after the surgery. In order to ascertain whether or not there was any correlation between various preoperative risk factors and postoperative deaths, 10 factors were analyzed. Emergency treatment, reoperation, shock, prolonged steroid treatment, liver functional abnormalities, respiratory failure and intraabdominal infections were found to be signficantly correlated with postoperative deaths. If these risk factors were expressed as scores for the individual patient, the death rate was 8.9% for patients with scores of less than four. However, the fatality rate reached 83.3% for patients with scores of more than five. Therefore, in patients with high risk factors, less extensive surgery than the present procedures is recommended.

A Case of Fulminant Herpes Simplex Hepatitis in an Adult

The case presented documents HSV hepatitis in a 41 year old caucasian male with a history of prolonged steroid treatment and recent irradiation for brain tumor recurrence. The fulminant nature of the hepatitis, accompanied by gastric ulcer hemorrhage, lead to his death within 24 hours of symptomatic manifestation. The diagnosis of HSV hepatitis was made postmortem. The etiology of the hepatitis was established by light microscopic identification of Cowdry type A intranuclear inclusion bodies, electron microscopic identification of virus particles, and the immunohistochemical detection of herpes simplex virus antigens.

Leptomeningeal aspergillosis causing internal carotid artery stenosis

Fungus infection of the leptomeninges is uncommon. Aspergillosis is known to occur in patients with debillitating disease, drug addiction, chemotherapy and following prolonged steroid treatment (Dayal et al.,1974). It presents predominantly as proptosis and associated sinus disease due to involvement of the orbit and base of the skull. The diagnosis of aspergillosis of the central nervous system is rarely established pre-operatively and this case report highlights some of the difficulties. A 22-year-old housewife first complained of headache during the eighth month of pregnancy. This was followed by retrobulbar pain and blurring of vision 22 days after delivery necessitating admission to the Department for Neurological Services. Clinical examination revealed proptosis of the left eye with complete ophthalmoplegia in a patient in obvious pain. The EEG, ultrasound and brain scan were all normal. Radiographic examination showed widening of the left superior orbital fissure with reactive basal sclerosis of th...

Study of mitochondrial structure and function in rat liver after experimental administration of synthetic progesterones

Chlormadinone acetate and norethindrone acetate have been administered to female rats at doses 4–10 and 40–100 times higher than those currently used in human contraception for periods of one to nine months and of one week, respectively. Normal structure and function were retained by the mitochondrial fraction of the liver. Mitochondrial metabolism, measured as maximal rate of respiration, P:O and respiratory control ratios with different substrates, did not show statistically significant differences between control and steroid treated groups. The experiments failed to reproduce the morphological changes observed in liver mitochondria of women on long-term oral contraceptions with the same substances. The results could be explained as a species difference in the response to prolonged steroid treatment.

Effect of Hydrocortisone and Prednisone on the Excretion of Uropepsin in Rheumatic Subjects

SummaryThe effect of hydrocortisone and prednisone on the excretion of uropepsin has been studied in rheumatic patients.It was possible to determine that 40 mg. of hydrocortisone and correspondingly 10 mg. of prednisone daily in short-term administration in no way increased the uropepsin excretion. Only when 80 mg. of hydrocortisone and 20 mg. of prednisone were used was there a clear increase in the uropepsin excretion.The method of investigation employed did not show any sure difference between the gastric stimulation caused by hydrocortisone and that caused by prednisone when the hydrocortisone dose was four times greater than the prednisone dose.The customary small hormone doses used in the prolonged steroid treatment seemed to increase the uropepsin excretion only in a minority of the cases. There was a positive correlation between the increased uropepsin values and the stomach complaints.