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The case fatality of WHO-defined 'severe falciparum malaria' remains unacceptably high, at 10-20%. However, a gradual decline in case fatality in adults and children treated in hospitals may reflect use of improved regimens of antimalarial chemotherapy and increased awareness of important complications of the disease. The development of severe, perhaps inevitably-fatal, malaria might be prevented by early appropriate chemotherapy of uncomplicated disease. At the most peripheral levels of the health service, suppository formulations of artemisinin derivatives can be administered even to patients who are vomiting or prostrated. At dispensaries, clinics or hospitals, where intramuscular or intravenous administration of antimalarial drugs is possible, quinine and artemisinin derivatives are the treatments of choice. There is growing evidence of the safety and efficacy of the quinine loading dose and of the use of artemether and artesunate, based on large, randomised, controlled clinical studies. No safe and effective form of prophylactic ancillary treatment has yet emerged. Results of studies of antipyretics, anticonvulsants (phenobarbitone), anticytokine/anti-inflammatory agents (anti-TNF antibodies, pentoxifylline, dexamethasone), iron chelators and hyperimmune sera have been disappointing. Only blood transfusion and treatment of respiratory, circulatory and renal failure are of obvious benefit. New ideas are needed, based on what is known of the pathophysiology of severe disease.
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PMID:Management of severe malaria. 1069 70

METHODS: Evaluated are surgical difficulties, management problems and weight loss in patients with distal gastric bypass as a revisionary procedure. Eighty patients were followed up to 3 years; four were lost to follow-up. Mean age was 43; mean prebariatric surgery weight 134 kg; height 1.65 meters; body mass index 40.1; ideal body weight 62.7 kg; excess weight 70.5 kg; per cent excess weight 214%. A 250 cm stomach-to-ileocecal valve segment of small bowel was used, and the biliopancreatic secretions were brought into the terminal ileum 100 6 in from the ileocecal valve. Mean pouch size was 63 cc; length of hospital stay 5 days; operative blood loss 616 cc; operative time 130 min. RESULTS: Intraoperative complications included three splenic injuries (without splenectomy). Early complications included one deep vein thrombosis, two marginal ulcers, one GI hemorrhage, one wound dehiscence, one pouch outlet obstruction and one pancreatitis. Late complications included: one death from protein malnutrition/ ARDS; 21 hypoproteinemia; six protein malnutrition, and of these, three had hyperalimentation; three cholecystitis; 27 anemia; 22 incisional hernia; two staple-line disruption (reoperated); 26 low serum iron; 11 prolonged (>6 months) diarrhea; three prolonged frequent vomiting; and two unrelated deaths (chronic myelogenous leukemia and amyotrophic lateral sclerosis). Mean excess weight loss was 83% at 12 months; 89% at 24 months; and 94% at 36 months. CONCLUSION: The distal gastric bypass is fraught with the operative and immediate post-operative complications experienced in any revisionary bariatric surgery. Distal gastric bypass is very effective in producing long-term weight loss. Nutritional problems are common but usually easily corrected. The most serious nutritional complication is protein malnutrition, which must be identified and corrected early. Success of this procedure is dependent upon patient compliance with proper nutrition and supplements, and regular office follow-up with monitoring of laboratory data. Patients who are noncompliant are at significant risk for complications.
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PMID:The Gastric Bypass for Failed Bariatric Surgical Procedures. 1072 55

BACKGROUND: Major complications of modern bariatric operations are infrequent but can be quite disabling to the patient and pose therapeutic challenges to the surgeon. We present our experience with five patients who underwent gastrectomy for complications following gastric reduction procedures. PATIENTS AND METHODS: Between 1991 and 1995, four women and one man, average age 46.8 years (34-66), underwent total gastrectomy and Roux-en-Y end-to-side esophagojejunostomy (4), or near-total gastrectomy with esophagogastrostomy (1). The decision to perform total gastrectomy was based on the poor quality of the remaining gastric pouch and the surgeon's judgement. Preoperative diagnoses included gastric outlet obstruction secondary to anastomotic ulcer or stricture, gastroesophageal reflux with esophagitis, chronic gastrocutaneous fistula, and iatrogenic linitis secondary to gastric wrap with mesh. Preoperatively, the patients complained of intolerable nausea, vomiting, abdominal pain, and dysphagia. RESULTS: in the five patients who underwent total or near-total gastrectomy, there was no operative mortality or morbidity; however, one patient (near-total gastrectomy) has required a second operation for pyloroplasty. Although one patient was lost to follow-up 6 months after surgery, the average follow-up for the remaining four patients is 2 years. These four patients were interviewed and all report complete satisfaction with their surgery and much improvement in their symptoms. Presently, they consume an average of three meals per day (range 2-6), with each meal measuring about 2 cups in size. All report the sensation of satiety after meals. All patients receive supplemental iron, B12, and multivitamins. From a nutritional standpoint, there has not been a significant change in the levels of albumin, total protein, hematocrit, weight and BMI since total gastrectomy. CONCLUSIONS: In our experience, total gastrectomy with Roux-en-Y end-to-side esophagojejunostomy is an appropriate therapy with low morbidity and mortality in highly selected patients with complications resulting from gastric reduction procedures.
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PMID:Gastrectomy for Complications of Bariatric Procedures. 1072 78

The best procedure for the treatment of morbid obesity has not yet been defined. Biliopancreatic diversion is one of the techniques available, but its results have not been sufficiently documented and the addition of a subtotal gastrectomy to the diversion so as to avoid leaving a blind non-functioning stomach, is still questionable. The purpose of this paper is to report our experience with our first 149 consecutive patients who were treated by biliopancreatic diversion with subtotal gastrectomy for morbid obesity. Operative mortality was 3% and morbidity 12%. The weight loss was marked during the first 6 months and decreased during the following 12 months. The weight stabilized at 2 years and there was subsequently a small increase. In only two out of 48 cases was the weight loss less than 25% of the initial weight at 2 years. The undesirable side-effects were diarrhea in 6%, vomiting in 9% and dyspepsia in 4%. The intervention leads to a malabsorption of carotene, iron, albumin and calcium. Except for carotene the deficiencies were corrected by oral supplement. In two patients, with resistant deficiencies, the diversion was reversed. Eighty-eight percent of the patients are satisfied with this intervention. At 2 years, 70% have reached their weight loss objective without any major side-effects or nutritional deficiencies, but in 14% the outcome of the procedure must be considered unsatisfactory. Biliopancreatic diversion with subtotal gastrectomy is a major operation, but it gives encouraging results so far.
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PMID:Biliopancreatic Diversion with Gastrectomy as Surgical Treatment of Morbid Obesity. 1077 39

The more widely used divalent forms of iron (Fe2+) supplementation often lead to gastrointestinal symptoms in preterm infants although little is known about the use of nonionic trivalent iron preparations (FeIII) in these patients. It is especially under this nonionic form that dietary iron is available. For this reason, a randomized controlled study was undertaken to compare the efficacy and the extent of possible side effects in two groups of preterm infants. In one group, the elemental iron was given in the Fe2+ form, while the other group received a nonionic trivalent iron (FeIII) complexed with polysaccharides of low molecular weight. Both groups received 7.5 mg elemental iron daily. Measured parameters in the two study groups did not differ significantly throughout the study period of 14 weeks. Both forms of iron supplementation were well tolerated. However, vomiting, diarrhea, or constipation occurred slightly more often in the group receiving iron supplementation in the Fe2+ form without reaching statistical difference. The authors found a nonionic trivalent polysaccharide-iron complex given as iron supplementation as effective as the generally more favored ferrous sulphate. Since iron therapy is mandatory in the preterm infant, the use of trivalent iron complexes can be considered as a good alternative.
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PMID:Iron supplementation in preterm infants: a study comparing the effect and tolerance of a Fe2+ and a nonionic FeIII compound. 1118 65

Our objective was to survey obstetrician/gynecologists concerning their management of nausea and vomiting in pregnancy. We mailed a survey on nutrition during pregnancy to the 230 ACOG Fellows who are members of the Collaborative Ambulatory Research Network and to a control sample of 800 non-Network Fellows. Results presented here are for the questions concerning prevalence and management of pregnancy-induced nausea. A total of 488 surveys (47.4% response rate) were analyzed. Respondents reported that on average, 51.4% of patients complain of nausea during pregnancy, and 9.2% complain of severe or prolonged nausea with vomiting. Respondents reported that on average, 2.4% of patients require hospitalization because of hyperemesis gravidarum. Treatments recommended by a majority of respondents for moderate nausea were eating frequent small meals (95.5%), snacking on soda crackers (88.5%), avoiding strong odors (75.6%), taking a prescribed antiemetic (71.3%), taking ginger (51.8%), and eliminating iron supplements (50%). Women physicians were more likely to recommend ginger and less likely to prescribe an antiemetic. For severe and sustained nausea with vomiting, with additional symptoms such as dehydration or weight loss, intravenous hydration (88.7%) and antiemetics (74.0%) were the most common treatment options. Almost half (48.8%) of respondents would hospitalize such patients. We conclude that obstetrician/gynecologists appear to be knowledgeable concerning current opinion on managing nausea and vomiting of pregnancy. Improvements in the management of nausea during pregnancy are more likely to come from further research, not education of physicians.
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PMID:A survey on the management of nausea and vomiting in pregnancy by obstetrician/gynecologists. 1124 31

Despite the use of recombinant erythropoietin, anemia remains a significant problem for patients with end-stage renal disease, in part related to chronic dialysis-related blood loss and resultant iron deficiency. Because oral iron preparations have been relatively ineffective and poorly tolerated in this population, intravenous (IV) iron dextran has been widely prescribed, despite a finite risk for adverse effects associated with its use. We analyzed data from Fresenius Medical Care North America (FMCNA) clinical variance reports to determine the incidence of suspected iron dextran-related adverse drug events (ADEs) and associated patient characteristics, dialysis practice patterns, and outcomes. We used a case-cohort study design, comparing individuals who experienced suspected ADEs with the overall FMCNA population. Among 841,252 IV iron dextran administrations from October 1998 through March 1999, there were 165 reported suspected ADEs, corresponding to an overall rate of 0.000196%, or approximately 20 per 100,000 doses. Forty-three patients (26%) required an independent emergency department evaluation, 18 patients (11%) required hospitalization, and 1 patient (0.6%) died. Dyspnea (43%), hypotension (23%), and neurological symptoms (23%) were the most common major ADEs; nausea (34%), vomiting (23%), flushing (27%), and pruritus (25%) were the most common other ADEs. ADEs were 8.1-fold more common among patients administered Dexferrum (American Regent Laboratories, Inc, Shirley, NY) compared with those administered InFed (Watson Pharmaceuticals, Phoenix, AZ). In summary, serious adverse reactions to IV iron dextran are rare in clinical practice. The risk appears to depend on the specific formulation of IV iron dextran. Otherwise, iron dextran-related ADEs are difficult to predict.
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PMID:Suspected iron dextran-related adverse drug events in hemodialysis patients. 1127 88

Cefmatilen hydrochloride hydrate (S-1090) was administered at 500 and 1000 mg potency/kg once orally to beagle dogs. No deaths occurred. Vomiting, diarrhea or mucous feces occurred on the dosing day, and reddish-brown feces (due to chelated products of S-1090 and its decomposition products with Fe3+ in the diet) were also observed on the dosing and next day. Increases of plasma urea nitrogen and iron were observed on the next day after dosing. No remarkable changes were noted in other examination items. The animals in both groups were considered to be exposed to a similar level of S-1090 based on the toxicokinetic data. The oral lethal dose of S-1090 in dogs was estimated to be more than 1000 mg potency/kg.
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PMID:[Toxicity study of cefmatilen hydrochloride hydrate (S-1090) (2)--Single oral dose toxicity study in dogs]. 1140 Mar 18

Exposure of rats to high-energy iron particles (600 MeV/amu) has been found to alter behavior after doses as low as 10 rads. The performance of a task that measures upper body strength was significantly degraded after irradiation. In addition, an impairment in the regulation of dopamine release in the caudate nucleus (a motor center in the brain), lasting at least 6 months, was also found and correlated with the performance deficits. A general indication of behavioral toxicity and an index of nausea and emesis, the conditioned taste aversion, was also evident. The sensitivity to iron particles was 10-600 times greater than to gamma photons. These results suggest that behavioral and neurobiological damage may be a consequence of exposure to low doses of heavy particles and that this possibility should be extensively studied.
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PMID:Behavioral and neurochemical abnormalities after exposure to low doses of high-energy iron particles. 1153 13

Pentoxifylline, a methylxanthine derivative and nonspecific type 4 phosphodiesterase inhibitor, has been used to improve survival of animals with sepsis and to attenuate lung injury in acute lung inflammation. The purpose of this study was to examine whether pentoxifylline would inhibit the expression of inflammatory cytokines, particularly tumor necrosis factor alpha (TNF), and thereby decrease the pathophysiology of acute porcine pleuropneumonia. E. coli lipopolysaccharide (LPS) and bacterial extracts of A. pleuropneumoniae--induced elevations in TNF mRNA which were fully abrogated by addition of pentoxifylline in both alveolar macrophage and neutrophil cultures. A 30% reduction in the level of LPS-induced interleukin (IL)-1beta mRNA levels also was achieved in macrophages. Pentoxifylline did not affect either IL-1alpha or IL-8 expression in vitro. Pentoxifylline therapy in vivo significantly reduced the number of band neutrophils in swine but did not reduce the pathology associated with pleuropneumonia, including changes in serum zinc, iron, or haptoglobin. Neither did it alter TNF, IL-1, IL-6, or IL-8 expression. Measurement of pentoxifylline and its metabolites in pig sera suggested that efficacious doses of pentoxifylline were probably not achieved in vivo. However, subcutaneous doses of pentoxifylline higher than 25 mg/kg produced transient diarrhea, vomiting, and tremors. These results suggest that pentoxifylline is an effective pharmacological tool for the dissection of cytokine regulation in vitro, but inhibitory concentrations may not be achievable for in vivo pharmacological use in swine.
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PMID:Effects of pentoxifylline on inflammatory cytokine expression and acute pleuropneumonia in swine. 1199 42


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