Adrenal Dysfunction in Hemodynamically Unstable Patients in the Emergency Department

OBJECTIVE: Adrenal failure, a treatable condition, can have catastrophic consequences if unrecognized in critically ill ED patients. The authors' objective was to prospectively study adrenal function in a case series of hemodynamically unstable (high-risk) patients from a large, urban ED over a 12-month period. METHODS: In a prospective manner, critically ill adult patients presenting to the ED were enrolled when presenting with a mean arterial blood pressure < or =60 mm Hg requiring vasopressor therapy for more than one hour after receiving fluid resuscitation (central venous pressure of 12-15 mm Hg or a minimum of 40 mL/kg of crystalloid). Patients were excluded if presenting with hemorrhage, trauma, or AIDS, or if steroids were used within the previous six months. An adrenocorticotropic hormone (ACTH) stimulation test was performed and serum cortisol was measured. Treatment for adrenal insufficiency was not instituted. RESULTS: A total of 57 consecutive patients were studied. Of these, eight (14%) had baseline serum cortisol concentrations of <20 microg/dL (<552 nmol/L), which was considered adrenal insufficiency (AI). Three additional patients (5%) had subnormal 60-minute post-ACTH-stimulation cortisol responses (<30 microg/dL) and a delta cortisol < or =9 microg/dL, which is the difference between the baseline and 60-minute levels. This is functional hypoadrenalism (FH). There were no laboratory abnormalities that distinguished patients with AI or FH from those with preserved adrenal function (PAF). Rates of survival to discharge did not differ between the AI group (7 of 8) and PAF patients (21 of 46; p = 0.052). CONCLUSIONS: Adrenal dysfunction is common in high-risk ED patients. Overall, it has a frequency of 19% among a homogeneous population of hemodynamically unstable vasopressor-dependent patients. The effect of physiologic glucocorticoid replacement in this setting remains to be determined.     

A Medical Curriculum for all seasons - a dialogue

Ten years have now passed since the College of Medicine of the University of Malawi was opened. The College''s Curriculum is firmly based on community needs. We describe the genesis and implementation of the curriculum of the College of Medicine and how it has persisted over the past ten years. The challenges that have so far been met are outlined.     

Surgical bacterial infections and antimicrobial susceptibility patterns at Lilongwe Central Hospital

A cross sectional study was done between October 1999 and February 2000 to determine antimicrobial susceptibility patterns of consecutive bacterial isolates of 102 clinical samples among surgical in-patients at Lilongwe Central Hospital (LCH), Malawi. Antimicrobial susceptibility was determined using comparative disc diffusion techniques. 83 (81.4%) samples were culture positive for bacterial growth while 19 (18.6%) grew nothing. Of the 93 culture positive specimens, Staphylococcus aureus was the predominant organism 43(51.8%) followed by Proteus species 8(9.6%) and E. coli 7(8.4%). Overall, 98.6% of all isolates tested against ciprofloxacin were susceptible, and against gentamicin and flucloxacin were 84.8% and 66.7% respectively. 59.3% of isolates tested against chloramphenicol were resistant. We recommend a review on the use of chloramphenicol as first-line antimicrobial therapy among surgical in-patients at Lilongwe Central Hospital. We also recommend restricted use of antimicrobials so as to minimise development of drug resistance. Periodic susceptibility studies are necessary to guide judicious use of antibiotics.     

Emergence of biopharmaceutical innovators in China, India, Brazil, and South Africa as global competitors and collaborators

Biopharmaceutical innovation has had a profound health and economic impact globally. Developed countries have traditionally been the source of most innovations as well as the destination for the resulting economic and health benefits. As a result, most prior research on this sector has focused on developed countries. This paper seeks to fill the gap in research on emerging markets by analyzing factors that influence innovative activity in the indigenous biopharmaceutical sectors of China, India, Brazil, and South Africa. Using qualitative research methodologies, this paper a) shows how biopharmaceutical innovation is taking place within the entrepreneurial sectors of these emerging markets, b) identifies common challenges that indigenous entrepreneurs face, c) highlights the key role played by the state, and d) reveals that the transition to innovation by companies in the emerging markets is characterized by increased global integration. It suggests that biopharmaceutical innovators in emerging markets are capitalizing on opportunities to participate in the drug development value chain and thus developing capabilities and relationships for competing globally both with and against established companies headquartered in developed countries.     

Autologous and allogeneic bone marrow transplantation for poor prognosis patients with B-cell chronic lymphocytic leukemia

Twenty patients with poor prognosis B-cell chronic lymphocytic leukemia (B-CLL) underwent uniform high-dose chemoradiotherapy followed by rescue with multiple monoclonal antibody-purged autologous bone marrow (BM) (12 patients) or T-cell-depleted allogeneic BM from HLA-identical siblings (8 patients) in a pilot study to assess the feasibility of BM transplantation (BMT) in this disease. All had poor prognosis disease by either staging, BM pattern, tumor doubling time criteria, or cytogenetics. All patients achieved remission criteria (defined as < or = 2 adenopathy, absence of splenomegaly, < or = 20% of the intertrabecular space involved on BM biopsy) before BMT. Despite the use of fludarabine, a median of three treatment regimens were required to achieve BMT eligibility. After BMT, all patients achieved complete hematologic engraftment. Toxicities were not significantly different between autologous versus allogeneic BMT. Two toxic deaths were observed. Of 19 evaluable patients, 17 clinical complete clinical remissions (89%) were observed, with 2 patients (1 allogeneic and 1 autologous) exhibiting persistent BM disease. Complete clinical remissions were documented at the phenotypic and molecular level for the majority of patients in whom dual fluorescence for CD5 and CD20 (15 of 15; 100%) and Ig gene rearrangements (11 of 14; 79%) were performed. Although long-term follow-up is needed to assess any potential impact on the disease-free and overall survival of these patients, this study shows the feasibility of using high-dose chemoradiotherapy and BMT in patients with poor prognosis B-CLL.     

Fractionated total-body irradiation and high-dose etoposide as a preparatory regimen for bone marrow transplantation for 94 patients with chronic myelogenous leukemia in chronic phase

Ninety-four consecutive patients with chronic myelogenous leukemia in first clinical chronic phase, median age of 34.0 years (range, 6.8 to 52.4 years), with a histocompatible sibling donor, were treated with fractionated total body irradiation (1,320 cGy) and high-dose etoposide (60 mg/kg) followed by allogeneic bone marrow transplantation (BMT). The median time from diagnosis to BMT was 7.0 months (range, 2.3 to 72.0 months). Sixty patients were treated before BMT with hydroxyurea alone, four patients with busulfan alone, one patient with interferon alone, and the other 29 patients were treated with various combinations of these drugs. Cumulative probabilities of overall survival, event- free survival, and relapse at 5 years were 73%, 64%, and 14%, respectively. The median follow-up time for surviving patients was 38 months, ranging from 12 to 88 months. By stepwise Cox regression analysis, significant prognostic variables were age at transplant, acute graft-versus-host disease > or = grade II, cytomegalovirus- associated interstitial pneumonitis, and years from diagnosis to BMT.     

Assessment of stool colour in community management of prolonged jaundice in infancy

Jaundice persisting beyond the first 2 wk of life is often regarded as an indication for investigation to exclude cholestatic liver disease. Most babies with prolonged jaundice have breast milk-related jaundice, which is a benign condition. Cholestatic liver disease is usually accompanied by pale stools and yellow or orange urine. A community programme was established to ascertain the incidence of prolonged jaundice and determine whether abnormal stool and urine colour could be used to assist primary care staff in referral decisions. Data were collected on normal stool and urine colour and used to devise a colour chart and information sheet for parents. Babies with prolonged jaundice were identified and referred for investigation. In all, 3661 babies were recruited into the study, of which 127 were jaundiced at 28 d of age. Of these, 125 were breastfed. The incidence of jaundice in breastfed babies at 28 d was 9.2% (95% CI 7.8%-11.0%) Abnormal liver function tests (LFTs) were common, but no baby had abnormal stool or urine colour and none was found to have liver disease. Jaundiced breastfed babies who are well are unlikely to have serious disease. Elevated LFTs are compatible with a diagnosis of breast milk-related jaundice. Prolonged jaundice in bottle-fed babies, and persistent pallor of stools or yellow/orange urine, are rare and merit immediate referral. Parents and professionals can be advised to report pale stools without generating a large number of unnecessary referrals. Further work is needed to determine whether a colour chart reduces the mean age of referral and treatment of infants with cholestatic liver disease.