Severe Gastrointestinal Disturbances Research Articles

Cross-sectional study using the University of California, Los Angeles, Scleroderma Clinical Trials Consortium Gastrointestinal Tract Instrument 2.0 (UCLA SCTC GIT 2.0) for gastrointestinal disorders of systemic sclerosis.

This study aimed to identify severe gastrointestinal ailments in patients with systemic sclerosis (SSc), investigate the role of antibodies in gastrointestinal disorders, and explore the relationship between limited cutaneous SSc (lcSSc) and diffuse cutaneous SSc (dcSSc) in terms of gastrointestinal involvement and its association with skin stiffness. We used the University of California, Los Angeles, Scleroderma Clinical Trials Consortium Gastrointestinal Tract Instrument 2.0 (UCLA SCTC GIT 2.0) questionnaire to assess gastrointestinal disturbances in 100 patients with SSc. Gastrointestinal impairment was categorized into three levels: absence of or minor symptoms, moderate symptoms, and severe symptoms, as indicated by the total gastrointestinal tract (GIT) score. Comparing 27 patients with dcSSc and 73 patients with lcSSc, severe gastrointestinal disturbances were found in 7.4% of patients with dcSSc and 4.1% of patients with lcSSc. A total of 18.0% of anticentromere antibody (ACA)-positive patients exhibited moderate to severe symptoms, while 9.1% of antitopoisomerase 1 antibody-positive patients displayed similar symptoms. The average disease duration in patients with severe symptoms was 15.0 years, in those with moderate symptoms was 10.3 years, and in those who were symptom-free or mildly affected was 8.5 years. Among 16 patients with moderate to severe gastrointestinal disorders, a positive correlation was observed between the modified Rodnan skin thickness score (mRSS) and total GIT score. In addition, a positive correlation was identified between fecal incontinence and mRSS, with weaker correlations for reflux and bloating symptoms. Patients with gastrointestinal disorders showed a tendency to worsen over time, particularly in ACA-positive patients with dcSSc. Furthermore, a correlation was observed between mRSS and fecal incontinence, reflux, and abdominal bloating in patients with moderate to severe gastrointestinal disturbances.

Clinical Symptoms Influencing Parkinson's Patients' Quality of Life in Latvia: A Single-Center Cohort Study.

Background and Objectives: Parkinson's disease (PD) is a chronic, progressive illness with a profound impact on health-related quality of life, and it is crucial to know what factors influence the quality of life throughout the course of the disease. This study aimed to evaluate PD patients' motor and non-motor symptoms to compare symptom severity between PD clinical phenotypes and to assess the impact of disease symptoms on quality of life in a cohort of Latvian patients. Materials and Methods: We evaluated 43 patients with Parkinson's disease. Fourteen patients had tremor dominant (TD) PD, twenty-five patients had postural instability/gait difficulty (PIGD), and four patients had a mixed phenotype. Results: The patients' mean age was 65.21 years, and the disease's mean duration was 7 years. The most common non-motor symptoms were fatigue (95.3%), sleep disturbance (83.7%), daytime sleepiness (83.7%), and pain and other sensations (81.4%). PIGD patients had a higher prevalence of depressed mood, daytime sleepiness, constipation, lightheadedness on standing, cognitive impairment, and severe gastrointestinal and urinary disturbances (as assessed using the SCOPA-AUT domains) compared with TD patients. A high prevalence of fatigue was assessed in both disease subtypes. Health-related quality of life significantly statistically correlated with MDS-UPDRS parts III and IV (r = 0.704), the Hoehn and Yahr scale (r = 0.723), as well as the SCOPA-AUT scale's gastrointestinal (r = 0.639), cardiovascular (r = 0.586), thermoregulatory (r = 0.566) and pupillomotor domains (r = 0.597). Conclusions: The severity of motor symptoms, as well as non-motor symptoms, such as fatigue, apathy, sleep problems and daytime sleepiness, pain, and disturbances in gastrointestinal and cardiovascular function, negatively affect PD patients' health-related quality of life. Thermoregulatory and pupillomotor symptoms also significantly affect PD patients' well-being.

Suicidal intoxication with mercury chloride

PurposePoisoning with elemental metals and metallic compounds was much more frequent in the past, and was related, among other things, to lifestyle and the lack of appropriate toxicological diagnostics. One example is mercury, which is being gradually eliminated but still has many different applications as a pure metal or in the form of various compounds. The paper presents a case of suicidal poisoning with mercury chloride (corrosive sublimate).MethodsForensic and toxicological tests including inductively coupled plasma mass spectrometry (ICP-MS) were at the Department of Forensic Medicine, PMU in Szczecin.ResultsThe patient before death had a range of symptoms such as epigastric pain, vomiting of the stomach contents, central cyanosis with tachycardia, tremors, severe shortness of breath with wheezing, difficulty swallowing, slurred speech, rales in the lungs, and diarrhea. The concentration of mercury measured by ICP-MS was 191 mg/L for a blood sample collected antemortem, and 147 mg/L for a blood sample collected at autopsy. Both concentrations of mercury are regarded as lethal. The post-mortem examination revealed signs of extensive thrombotic necrosis in some internal organs.ConclusionsMercuric chloride has an estimated human fatal dose of between 1 and 4 g. It can produce a range of toxic effects, including corrosive injury, severe gastrointestinal disturbances, acute renal failure, circulatory collapse, and eventual death. The presented case of fatal poisoning with mercury chloride, due to the type of agent used, is now interesting in toxicological practice.

Synthesis and biological evaluation of orally active prodrugs and analogs of para-aminosalicylic acid (PAS)

Tuberculosis (TB) is one of the world's most deadly infectious diseases resulting in nearly 1.3 million deaths annually and infecting nearly one-quarter of the population. para-Aminosalicylic acid (PAS), an important second-line agent for treating drug-resistant Mycobacterium tuberculosis, has moderate bioavailability and rapid clearance that necessitate high daily doses of up to 12 g per day, which in turn causes severe gastrointestinal disturbances presumably by disruption of gut microbiota and host epithelial cells. We first synthesized a series of alkyl, acyloxy and alkyloxycarbonyloxyalkyl ester prodrugs to increase the oral bioavailability and thereby prevent intestinal accumulation as well as undesirable bioactivation by the gut microbiome to non-natural folate species that exhibit cytotoxicity. The pivoxyl prodrug of PAS was superior to all of the prodrugs examined and showed nearly quantitative absorption. While the conceptually simple prodrug approach improved the oral bioavailability of PAS, it did not address the intrinsic rapid clearance of PAS mediated by N-acetyltransferase-1 (NAT-1). Thus, we next modified the PAS scaffold to reduce NAT-1 catalyzed inactivation by introduction of groups to sterically block N-acetylation and fluorination of the aryl ring of PAS to attenuate N-acetylation by electronically deactivating the para-amino group. Among the mono-fluorinated analogs prepared, 5-fluoro-PAS, exhibited the best activity and an 11-fold decreased rate of inactivation by NAT-1 that translated to a 5-fold improved exposure as measured by area-under-the-curve (AUC) following oral dosing to CD-1 mice. The pivoxyl prodrug and fluorination at the 5-position of PAS address the primary limitations of PAS and have the potential to revitalize this second-line TB drug.

Microbiome & Autism Spectrum Disorders

Autism Spectrum Disorders (ASD) are neurodevelopmental disorders. People with ASD have communication and social interactions difficulties along with sterotyped and repetitive behaviors (DSM-5). The symptoms are present from early childhood between 18 and 36 months, and persist into adulthood. Our body is made up of several microbiota : gut, oral, skin and vaginal. The gut microbiota is the most important because it contains 100 trillion microorganisms. Research teams have established links between dysbiosis and certain pathologies (DeGruttola A.K., et al., 2016). Several studies are being conducted to assess the effectiveness of Fecal Microbiota Transplantation (TFM) on chronic inflammatory bowel disease, metabolic disease, obesity and autism spectrum disorders (ASD). It involves introducing stool from a healthy donor into the digestive tract of a recipient patient to rebalance the host's altered gut flora. A major study of Kang et al., 2017 , on the treatment with TMP of 18 children diagnosed with ASD, aged 7 to 16 years, associated with moderate to severe gastrointestinal disturbances, showed that two years after the treatment, the intensity of the digestive disturbances decreased by 58% and the severity of typical symptoms is reduced by 47%. Sequencing analyzes showed an increase of bacterial diversity (Kang et al., 2019) . It’s important to mention that several companies have already positioned themselves in the niche of the intestinal flora aimed at producing TMF as a drug and placing it on the market starting 2023.
 Keywords: autism, ASD, microbiome, neurodevelopmental disorders

Necrotising enterocolitis in newborns receiving diazoxide

BackgroundFrequent and severe gastrointestinal disturbances have been reported with the use of diazoxide in adults and older children. However, no studies have investigated the incidence of necrotising enterocolitis (NEC) in...

Safety and effectiveness of hypodermoclysis compared to intravenous fluid infusion for rehydrating children with mild to moderate dehydration: a systematic review protocol.

The objective of this review is to summarize the evidence on the effectiveness and safety of hypodermoclysis (HDC) for the rehydration of children with mild or moderate dehydration. Children are particularly susceptible to dehydration, which can lead to severe gastrointestinal disturbances. Hypodermoclysis, the infusion of fluids and electrolytes via subcutaneous tissue, is an alternative route of administering fluid replacement when oral or intravenous routes are contraindicated. Although HDC is primarily used in elderly patients, there are no restrictions on its use in children. A review is needed to synthesize the evidence on the effectiveness of HDC for treating dehydration in children. Eligible studies will include infants and children up to 10 years of age with mild or moderate dehydration based on the Gorelick scale. Studies that compare fluid infusion with HDC to intravenous administration, at either hospital or home, will be considered. Outcomes of interest will include dehydration level, safety and pain. Studies published in English, Spanish or Portugese since database inception will be considered for inclusion. PubMed, CINAHL, Web of Science, Embase and Scopus will be searched, as well as multiple sources of unpublished studies. Two independent reviewers will screen titles and abstracts against the inclusion criteria, retrieve and assess the full text of selected studies, critically appraise studies for methodological quality and extract data using a standardized extraction tool. Data will be pooled in a statistical meta-analysis, when feasible. A Grading of Recommendations, Assessment, Development and Evaluation (GRADE) Summary of Findings will be presented.

Self-Assembling Organogels Based on Pluronic and Lecithin for Sustained Release of Etodolac: In Vitro and In Vivo Correlation.

Etodolac, a member of non steroidal anti-inflammatory drugs (NSAIDs), has a poor aqueous solubility. Long term administration of etodolac causes severe gastrointestinal disturbances such as peptic ulcer and bleeding. These disturbances could be overcome by alternative routes such as a topical administration. In the present study, pluronic lecithin organogels (PLOs) were prepared by simple mixing of pluronic solution with lecithin solution. Etodolac was loaded into the prepared gels or added during the gel formation. The physicochemical properties of the modified organogels were investigated by different analysis including visual inspection, pH determination, viscosity, spreadability and extrudability. Also, the in vitro release studies of etodolac in the presence of different penetration enhancers were carried out. The anti-inflammatory behavior of the prepared etodolac organogel was investigated using carrageenan induced paw edema test. The results indicated that the prepared organogels showed good physicochemical properties. The organogels, containing a combination of tween 80 and oleic acid as penetration enhancers, showed the highest percentage of drug release. All tested organogels showed a significant oedema inhibition compared with oral indomethacin ® and Voltaren® as a topical marketed anti-inflammatory drug. Moreover, the increase of drug concentration from 1% to 5% w/w is accompanied with a longer duration of action up to 12 hrs. Therefore, the formulated organogels are considered as a promising vehicle for controlled topical delivery of etodolac.

Is There a Role for the Enteral Administration of Serum-Derived Immunoglobulins in Human Gastrointestinal Disease and Pediatric Critical Care Nutrition?

Twenty years ago, there was profound, international interest in developing oral human, bovine, or chicken egg-derived immunoglobulin (Ig) for the prevention and nutritional treatment of childhood malnutrition and gastrointestinal disease, including acute diarrhea and necrotizing enterocolitis. Although such Ig products were shown to be effective, with both nutritional and antidiarrheal benefits, interest waned because of their cost and because of the perceived risk of bovine serum encephalitis (BSE). BSE is no longer considered a barrier to use of oral Ig, because the WHO has declared the United States to be BSE-free since the early 2000s. Low-cost bovine-derived products with high Ig content have been developed and are regulated as medical foods. These new products, called serum bovine Igs (SBIs), facilitate the management of chronic or severe gastrointestinal disturbances in both children and adults and are regulated by the US Food and Drug Administration. Well-established applications for use of SBIs include human immunodeficiency virus (HIV)-associated enteropathy and diarrhea-predominant irritable bowel syndrome. However, SBIs and other similar products could potentially become important components of the treatment regimen for other conditions, such as inflammatory bowel disease, by aiding in disease control without immunosuppressive side effects. In addition, SBIs may be helpful in conditions associated with the depletion of circulating and luminal Igs and could potentially play an important role in critical care nutrition. The rationale for their use is to facilitate intraluminal microbial antibody coating, an essential process in immune recognition in the gut which is disturbed in these conditions, thereby leading to intestinal inflammation. Thus, oral Ig may emerge as an important "add-on" therapy for a variety of gastrointestinal and nutritional problems during the next decade.

Ensuring Quality and Standardizing Care for BMT Patients in an Expanding Program

s / Biol Blood Marrow Transplant 21 (2015) S374eS390 S384 Findings & Interpretation: Since adoption of this new algorithm only 3 of 45 patients have experienced side-effects (P1⁄40.04). One patient had severe nausea, one had severe diarrhea and one experienced paresthesias. Discussion & Implications: The new dosing algorithm has not had a negative impact on stem cell mobilization. Standard doses of plerixafor can cause severe gastro-intestinal disturbance in patients with low body weight. Adjustment for body weight can prevent most of these side-effects.

In-Vivo Toxicity Assessment of Aspartame in Drosophila melanogaster and Danio rerio

Background/Objectives: Aspartame is a synthetic sweetener used as an alternate for sugar in food and beverages. Many research observations and findings have related to adverse health effects of aspartame. The medical symptoms include severe headache, giddiness, gastrointestinal and psychological disturbances. In the present study we have evaluated the genotoxicity of aspartame in two animal models; Drosophila melanogaster and Danio rerio . Methods: In the present study we have evaluated the genotoxicity of aspartame in two animal models; Drosophila melanogaster (Phenotypic analysis and DNA fragmentation assay) and Danio rerio (Embryo toxicity, Fin regeneration and DNA fragmentation assay). The flies and fishes were exposed to 4 concentrations of aspartame (500 mg/ml, 250 mg/ml, 125 mg/ml and 62.5 mg/ml). An important aspect that was considered was to measure the sugar levels (by biochemical analysis) in flies post exposure to aspartame and the same was compared with normal sugar intake and in combinations with coconut oil, sugar and aspartame. The fact of increasing blood glucose level and cholesterol levels has been a regular complaint amongst many diabetics and the usage of aspartame has also been higher in patients with diabetes. Findings: The present biochemical assay was carried out to compare and contrast the difference in glucose levels in flies exposed to increasing concentrations of sugar, oil, aspartame and combinations of sugar+coconut oil, aspartame+coconut oil. The results suggested marked phenotypic changes in flies and distinct shearing of DNA on DNA fragmentation assay in both flies and fishes. The extent of fin regeneration was also found to be reduced with increasing concentrations of aspartame. Embryo toxicity assay in zebra fish demonstrated inactivity, neurological disturbances followed by death. The biochemical analysis revealed the efficiency of aspartame to decrease glucose levels in hemo lymph of flies but the presence of oil hindered the efficacy of aspartame to reduce the glucose levels. Applications: The study reflects the toxicity of aspartame and brings awareness in general public about its risk in regular usage.

Neurodegeneration-induced cognitive deficits are associated with severe gastrointestinal disturbances, which were attenuated by dietary, but not pharmacological intervention: Implications for novel therapies

Neurodegeneration-induced cognitive deficits are associated with severe gastrointestinal disturbances, which were attenuated by dietary, but not pharmacological intervention: Implications for novel therapies

Full Recovery from a Potentially Lethal Dose of Mercuric Chloride

Mercuric chloride poisoning is rare yet potentially life-threatening. We report a case of poisoning with a potentially significant amount of mercuric chloride which responded to aggressive management. A 19-year-old female presented to the Emergency Department with nausea, abdominal discomfort, vomiting of blood-stained fluid, and diarrhea following suicidal ingestion of 2-4g of mercuric chloride powder. An abdominal radiograph showed radio-opaque material within the gastric antrum and the patient's initial blood mercury concentration was 17.9μmol/L (or 3.58mg/L) at 3h post-ingestion. Given the potential toxicity of inorganic mercury, the patient was admitted to the intensive care unit and chelation with dimercaprol was undertaken. Further clinical effects included mild hemodynamic instability, acidosis, hypokalemia, leukocytosis, and fever. The patient's symptoms began to improve 48h after admission and resolved fully within a week. Mercuric chloride has an estimated human fatal dose of between 1 and 4g. Despite a reported ingestion of a potentially lethal dose and a high blood concentration, this patient experienced mild to moderate poisoning only and she responded to early and appropriate intervention. Mercuric chloride can produce a range of toxic effects including corrosive injury, severe gastrointestinal disturbances, acute renal failure, circulatory collapse, and eventual death. Treatment includes close observation and aggressive supportive care along with chelation, preferably with 2,3-dimercapto-1-propane sulfonate or 2,3-meso-dimercaptosuccinic acid.

Food contaminant analysis at ultra‐high mass resolution: application of hybrid linear ion trap – orbitrap mass spectrometry for the determination of the polyether toxins, azaspiracids, in shellfish

The biotoxins, azaspiracids (AZAs), from marine phytoplankton accumulate in shellfish and affect human health by causing severe gastrointestinal disturbance, diarrhea, nausea and vomiting. Specific and sensitive methods have been developed and validated for the determination of the most commonly occurring azaspiracid analogs. An LTQ Orbitrap mass spectrometer is a hybrid instrument that combines linear ion trap (LIT) mass spectrometry (MS) with high-resolution Fourier transform (FT) MS and this was exploited to perform simultaneous ultra-high-resolution full-scan MS analysis and collision-induced dissociation (CID) tandem mass spectrometry (MS/MS). Using the highest mass resolution setting (100,000 FWHM) in full-scan mode, the methodology was validated for the determination of six AZAs in mussel (Mytilus galloprovincialis) tissue extracts. Ultra-high mass resolution, together with a narrow mass tolerance window of ±2 mDa, dramatically improved detection sensitivity. In addition to employing chromatographic resolution to distinguish between the isomeric azaspiracid analogs, AZA1/AZA6 and AZA4/AZA5, higher energy collisionally induced dissociation (HCD) fragmentation on selected precursor ions were performed in parallel with full-scan FTMS. Using HCD MS/MS, most precursor and product ion masses were determined within 1 ppm of the theoretical m/z values throughout the mass spectral range and this enhanced the reliability of analyte identity.For the analysis of mussels (M. galloprovincialis), the method limit of quantitation (LOQ) was 0.010 µg/g using full-scan FTMS and this was comparable with the LOQ (0.007 µg/g) using CID MS/MS. The repeatability data were; intra-day RSD% (1.8-4.4%; n = 6) and inter-day RSD% (4.7-8.6%; n = 3). Application of these methods to the analysis of mussels (M. edulis) that were naturally contaminated with azaspiracids, using high-resolution full-scan Orbitrap MS and low-resolution CID MS/MS, produced equivalent quantitative data.

Liver Status in a Cohort of Polytransfused B-Thalassemia Major (BTM) on Long Term Desferrioxamine (DfO) or Deferiprone (L1).

The liver is the main body site for iron storage. Iron chelators as DFo and L1 had problems of compliance and intolerance respectively. This prospective study enrolled 76 BTM patients aged from 9–33 years, mean of 14±4.4 to evaluate the effectiveness of both chelators judged by serum ferritin (sf) and liver iron content (LIC) using repeated liver biopsies. Fifty patients were on DFo 35 mg/kg/day 5 days per week and twenty-six were on L1 75 mg/kg/day on daily bases. Mean baseline sf values were 3678±1922 and 3573±1879 ng/ml while mean baseline LIC was 19.2±7.9 and 18.9±8.1 mg fe/g dw, while 12% and 14% showed evidence of liver fibrosis (score ≥ 3) respectively. Twenty-four months later; a decline in sf by 287±837 in Dfo (In Dfo compliant group [number = 30]who had received ≥ 75% of planned dose; sf dropped by 890±437 while increased in DFo non compliant by 621±513). While falling by 729±633 in L1 group. A decrease in LIC by 3.9±2.8 mg fe/g dw (−5.8±3.1 in Dfo compliant,+2.6±3.3 in Dfo non compliant) and falling by 2.2±3.4 mg fe/g dw in L1 group, the difference was statistically significant P< 0.05 between compliant and non compliant DFo and insignificant difference between Dfo and L1.The mean iron excretion: intake was 1.61,0.86 and 1.48 in Dfo compliant, non compliant and L1 respectively. A positive correlation was found between sf and LIC in both groups. Fibrosis was improved in Dfo compliant group better than L1 but no statistically significant difference was observed, while progressive fibrosis in 10% of Dfo non compliant group. All Dfo compliant group completed study, 18 out of 20 Dfo non compliant while six L1 patients discontinued the drug prematurely (3 severe gastrointestinal disturbances, 2 severe arthralgia and one repeated neutropenia). Conclusion: Both Dfo and L1 are effective iron chelators evident by drop in sf, LIC and improved fibrosis, however compliance and intolerance are still troublesome.

Effect of somatostatin on gastrointestinal contractility in Schistosoma mansoni infected mice

Schistosoma mansoni infection induces severe gastrointestinal motility disturbances which are characterised by hyperactivity of intestinal muscle, abdominal pain, diarrhoea, vomiting and nausea. During schistosomiasis, the neuropeptide somatostatin is generated within inflammatory granulomas. However, somatostatin is also an important inhibitory modulator of gastrointestinal motility. In the present study, we have investigated the potential of somatostatin to reduce schistosomiasis-induced hyperactivity of gastrointestinal smooth muscle. Organ bath experiments were performed to study the contractility of isolated smooth muscle strips of intestine from control mice and from mice that were infected with S. mansoni for 2, 4, 8 and 16 weeks. Electrical field stimulation (0.5–8 Hz) of enteric nerves induced frequency-dependent neurogenic contractions of cholinergic origin in all regions of the small intestine. Somatostatin (0.1–1 μM) concentration-dependently inhibited the contractions to enteric nerve stimulation in the small intestine from uninfected control mice and from acutely S. mansoni infected mice (2 and 4 weeks of infection). After 8 weeks of infection with S. mansoni, this inhibitory effect of somatostatin was less pronounced and after 16 weeks of infection it was completely abolished. Histology demonstrated that chronic infection of mice with S. mansoni was associated with significant alterations in the musculature of the small intestine. These alterations may be associated with physiological changes in the responsiveness to somatostatin and suggest that the somatostatin neuroregulatory circuit of enteric neurotransmission in the small intestine is disturbed during chronic schistosomiasis mansoni.

Combination antiretroviral therapy in 100 HIV-1-infected pregnant women.

In recent years, combination antiretroviral therapy has substantially improved the prognosis of human immunodeficiency virus type-1 (HIV-1) infection. However, at present, information regarding the effects of these regimens during pregnancy is limited. Side-effects, vertical transmission rate and neonatal outcome associated with different combination therapies were evaluated retrospectively in a consecutive series of 100 women who attended the II Department of Obstetrics and Gynecology for the management of HIV-1 infection in pregnancy. Antiretroviral treatment was initiated at a median of 16 weeks gestation with a range from pre-pregnancy until 31 weeks gestation. Twentythree women continued their pre-pregnancy therapy during the first trimester of gestation. Protease inhibitors were incorporated in 23 of the final therapeutic regimens. Twentyfive women did not receive zidovudine. Most women (97) delivered by Caesarean section and none breast-fed. Prematurity rate for the entire series was 19%. When women who actively used illicit drugs were excluded, only seven of 69 (10%) women were found to deliver prematurely. The use of protease inhibitors was limited by an elevated frequency of severe gastrointestinal disturbances. The rate of congenital malformations did not appear to differ significantly from that reported in the literature for the general population. Only one of 102 live newborns was found to be HIV-1-infected (1.0%, 95% confidence interval; 0.3-4.6%). The present findings confirm the remarkable efficacy of combination antiretroviral therapy, Caesarean section and refraining from breast-feeding in lowering the rate of vertical HIV-1 transmission. Moreover, they are suggestive that combination antiretroviral therapy may not be related to major neonatal toxicity. The necessity to discontinue the therapy during the first trimester of pregnancy and to systematically incorporate zidovudine into combination regimens is discussed.

Insuffisance surrénale périphérique au cours du sida

Lesions of adrenal glands are common findings at autopsy of patients with acquired immunodeficiency syndrome (AIDS). In contrast the diagnosis of symptomatic adrenal insufficiency is rarely established during the lifetime of these patients. We report four new cases and review the literature. All four patients had full blown AIDS with a mean CD4 cell count of 19 mu/L. One or more opportunistic disease was present at the time of diagnostic: cytomegalovirus retinitis in two cases, disseminated Mycobacterium avium infection in two, Kaposi's sarcoma in two and Candida esophagitis in one. The clinical presentation constantly included fatigue, weight loss, severe orthostatic hypotension and gastrointestinal disturbances. Cutaneous hyperpigmentation was present in three cases. In most cases biological abnormalities were typical, such as hyponatremia, urinary Na/K ratio > or = 1, and hyperkalemia. Serum cortisol levels were within the range of normal in three cases but response to the cosyntropin challenge was typically impaired in all cases. Clinical and biological manifestations returned to normal in 1 to 3 weeks after initiation of therapy with cortisol, associated to fludrocortisone in three cases. However, 13 months after diagnosis, three patients were dead. Usually asymptomatic, diagnostic of symptomatic adrenal insufficiency must be suspected even when clinical presentation is atypical because rapid efficiency of hormonal treatment.

Management of Nonobstetric Pain During Pregnancy and Lactation

Management of Nonobstetric Pain During Pregnancy and Lactation

Management of nonobstetric pain during pregnancy and lactation.

Management of nonobstetric pain during pregnancy and lactation.