Homology-Aware Phylogenomics at Gigabase Scales.

Obstacles to inferring species trees from whole genome data sets range from algorithmic and data management challenges to the wholesale discordance in evolutionary history found in different parts of a genome. Recent work that builds trees directly from genomes by parsing them into sets of small $k$-mer strings holds promise to streamline and simplify these efforts, but existing approaches do not account well for gene tree discordance. We describe a "seed and extend" protocol that finds nearly exact matching sets of orthologous $k$-mers and extends them to construct data sets that can properly account for genomic heterogeneity. Exploiting an efficient suffix array data structure, sets of whole genomes can be parsed and converted into phylogenetic data matrices rapidly, with contiguous blocks of $k$-mers from the same chromosome, gene, or scaffold concatenated as needed. Phylogenetic trees constructed from highly curated rice genome data and a diverse set of six other eukaryotic whole genome, transcriptome, and organellar genome data sets recovered trees nearly identical to published phylogenomic analyses, in a small fraction of the time, and requiring many fewer parameter choices. Our method's ability to retain local homology information was demonstrated by using it to characterize gene tree discordance across the rice genome, and by its robustness to the high rate of interchromosomal gene transfer found in several rice species.

Metabolic acidosis and thiamine deficiency.

We describe a 19-year-old patient who was receiving home parenteral nutrition in whom lactic acidosis developed. A review of her home parenteral nutrition formula revealed the absence of multivitamins, most significantly thiamine. After thiamine administration, the acidosis resolved, and the patient experienced pronounced clinical improvement. Clinicians must be aware that thiamine is essential for normal glucose metabolism and that thiamine deficiency can lead to lactic acidosis. Thiamine deficiency should be included in the differential diagnosis of lactic acidosis. The recent shortage of intravenous multivitamin preparations has led to documented cases of lactic acidosis as a result of thiamine deficiency, and a previous shortage led to several deaths due to lactic acidosis as a consequence of thiamine deficiency. All patients receiving parenteral nutrition must also receive adequate vitamin supplementation.

Percutaneous endoscopic gastrostomy after acute stroke: complications and outcome.

OBJECTIVE: To review the complications and outcome of percutaneous endoscopic gastrostomy placement (PEG) in 74 patients with acute stroke. PATIENTS AND METHODS: Medical record review and follow-up of patients with acute stroke admitted to a referral center. RESULTS: There were no immediate procedure-related complications. Late complications included aspiration pneumonia (11%), PEG occlusion and replacement (6%), accidental PEG removal (6%), wound infection (3%) and fatal gastrointestinal bleeding in 1 patient. In 18 patients (28%), PEG could be subsequently removed due to improvement in swallowing. CONCLUSION: PEG provides an effective alternative method of enteral feeding, but its impact on outcome remains uncertain. Late complications occurred in one third of the patients, but were seldom life threatening. Removal of the gastrostomy tube and resumption of oral feeding was possible in more than a quarter of the patients. All our patients who received PEG placement after acute stroke remained severely disabled; one third of the patients died from systemic complications of their stroke.

Parenteral feeding in a patient with hypertriglyceridemia and increased liver enzyme levels.

OBJECTIVE: To discuss nutritional support in a patient with hypertriglyceridemia and liver dysfunction. METHODS: We describe the hospital course of a critically ill patient with hepatic dysfunction and hypertriglyceridemia who required nutritional support, and we provide an overview of lipid metabolism. RESULTS: A 27-year-old man with hepatic dysfunction and hypertriglyceridemia, who had undergone kidney transplantation 4 months previously, was admitted to the intensive-care unit with upper gastrointestinal bleeding. He was unable to tolerate enteral feeding, and central parenteral nutrition was initiated. Calories from dextrose and fat were limited because of the presence of increased liver enzyme levels and hypertriglyceridemia. A modified regimen of parenteral nutrition was developed for the patient. The short-term reduction of total calories to 75% of the predicted need is safe. CONCLUSION: Nutritional support in patients with liver dysfunction and hypertriglyceridemia is complicated and may require temporary underfeeding because of the need to limit fat and dextrose intake.

Nutrition support in hospitalized patients with diabetes mellitus.

Many physicians will manage the care of hospitalized patients with diabetes mellitus who require parenteral nutrition or enteral tube feeding. The nutritional assessment, indications for nutrition support, estimate of nutritional needs, and biochemical monitoring guidelines for critically ill patients with diabetes are similar to those for nondiabetic patients. In general, a weight loss of up to 10% of body weight is well tolerated and, in the absence of severe stress, the provision of dextrose-containing crystalloid solutions and electrolytes is adequate for as long as 7 to 10 days. Studies that demonstrate a beneficial influence of nutrition support on clinical outcome administered nutrition for a minimum of 1 week. No data have established that support for a briefer duration is of clinical benefit. An important goal in the care of the hospitalized patient with diabetes is to avoid the extremes of hypoglycemia and hyperglycemia. Herein we provide our approach to achieving glucose control in stressed hospitalized patients with diabetes mellitus who are receiving parenteral and enteral nutrition. Although evidence is increasing that hyperglycemia impairs immune function, well-designed prospective randomized trials are needed to determine the risks, costs, and benefits of achieving glucose control and of providing nutrition support to hospitalized patients with diabetes mellitus.

Host defenses and susceptibility to infection in patients with diabetes mellitus.

The recently completed Diabetes Control and Complications Trial (DCCT) provided compelling evidence that intensive treatment of people with insulin-dependent diabetes mellitus can delay or prevent diabetic microvascular complications. Although not studied in the DCCT, patients with noninsulin-dependent diabetes mellitus likely will benefit from near-normoglycemia. Although it is difficult to prove a similar causal relation between hyperglycemia and infection (this outcome was not looked for in the DCCT), there is substantial in vitro data and evolving clinical studies that support this hypothesis. This information is presented in this article following a review of the regulation of glucose levels.

Nutritional support of critically ill patients.

Severe depletion of body protein stores can result from prolonged starvation or from hormonal and cytokine-mediated effects during critical illness. Recent advances in the understanding of cytokine actions have substantially refined the interpretation of the nutritional assessment of critically ill patients. In addition, the design of nutritional programs for hospitalized patients has changed considerably during the past decade. Although nutritional support of critically ill patients will not lead to positive nitrogen balance, nutrition can increase protein synthesis, enhance immune function, and beneficially modify the body's response to an illness.

C-peptide during the prolonged fast in insulinoma.

C-Peptide, a marker for insulin secretion, is purported to be elevated in patients with insulinoma but diagnostic criteria have not been established. Thirty-seven patients with histologically confirmed insulinoma studied preoperatively, 19 normal subjects, and 2 patients who subsequently acknowledged self-administration of insulin underwent the prolonged fast (< or = 72 h) according to a standard protocol. Plasma glucose, C-peptide, and insulin were measured every 6 h until plasma glucose was less than or equal to 3.3 mmol, then hourly until Whipple's triad was demonstrated or until 72 h without symptoms was reached. At the termination of the fasts, plasma was analyzed for sulfonylurea. Statistical analysis was by rank sum test. Data are expressed as median (range). The durations of fasts were 20 (2.5-68) h for patients with insulinomas and 72 h for normal subjects. At the end of fasts plasma glucose, C-peptide, and insulin concentrations were 2.2 (1.4-2.9) vs. 3.6 (2.7-5.5) mmol, P < 0.001; 0.60 (0.20-1.92) vs. 0.13 (0.07-0.43) nmol, P < 0.001; and 126 (35-840) vs. 35 (35-126) pmol, P < 0.001, respectively, for insulinoma patients and normal subjects. All plasma samples were negative for sulfonylurea. Insulinoma patients had C-peptide values at the end of the fasts greater than or equal to 0.20 nmol whereas normal subjects and patients with insulin factitial hypoglycemia had C-peptide concentrations less than or equal to 0.10 nmol when plasma glucose was less than or equal to 2.8 mmol. Insulinoma is confirmed in a sulfonylurea negative patient with Whipple's triad during the prolonged fast and a concomitant C-peptide concentration greater than or equal to 0.20 nmol.

Functioning insulinoma--incidence, recurrence, and long-term survival of patients: a 60-year study.

For the 60-year period from 1927 through 1986, we assessed the incidence, recurrence, and long-term survival among all Mayo Clinic patients with histologically confirmed functioning insulinoma. With use of the complete medical record system at Mayo and the comprehensive epidemiologic data base of residents of Olmsted County, Minnesota, we found 224 patients in whom an initial pancreatic exploration at Mayo had confirmed the presence of insulinoma. The median age (and range) of these patients at surgical diagnosis was 47 (8 to 82) years, and 59% were female patients. During the study period, eight cases of insulinoma occurred among residents of Olmsted County; their age and gender distributions were similar to those of the total cohort. The incidence of insulinoma among residents of Olmsted County increased during the study period to a stable level during the last 2 decades of 4 cases per 1 million person-years. For the total cohort, 7.6% had multiple endocrine neoplasia type I (MEN I), and 5.8% had malignant insulinoma. The risk of recurrence was greater among patients with MEN I (21% at 10 and 20 years) than in those without MEN I (5% at 10 years and 7% at 20 years). Although survival of the total cohort was not significantly impaired, it was significantly worse than expected for patients with malignant insulinoma (29% versus 88% expected at 10 years postoperatively). We conclude that insulinoma is less rare than previously suspected. After successful surgical removal, the long-term risk of recurrent insulinoma is relatively high in patients with MEN I; for patients with benign disease, the long-term survival is normal.

Comparison of extracellular and net glucose oxidation measured isotopically and by indirect calorimetry during high and low glucose turnover.

To determine the extent to which glucose oxidation measured by indirect calorimetry reflects glucose oxidation measured isotopically, subjects were studied during a 6-h hyperinsulinemic euglycemic clamp (1 mU.kg-1.min-1) and during infusion of saline. [6-14C]glucose was infused on both occasions. Breath was collected for determination of the specific activity of carbon dioxide, oxygen consumption, and carbon dioxide production. Glucose turnover during hyperinsulinemia was approximately eightfold higher than during saline infusion. During the final 1.5 h of the hyperinsulinemic glucose clamp, oxidation measured isotopically remained slightly but consistently lower (P less than 0.05) than that measured by indirect calorimetry (13.8 +/- 1.1 vs 16.5 +/- 1.7 mumol.kg-1.min-1, respectively). In contrast, during the saline infusion, glucose oxidation measured isotopically did not differ from that measured by indirect calorimetry (8.3 +/- 0.6 vs 7.2 +/- 2.8 mumol.kg-1.min-1, respectively). We conclude that although net glucose oxidation measured isotopically was slightly lower than that measured by indirect calorimetry, both techniques provide similar estimates of glucose oxidation over a wide range of glucose disposal.

Overzealous resuscitation of an extremely malnourished patient with nutritional cardiomyopathy.

Overzealous resuscitation of the severely malnourished patient may be associated with life-threatening complications. A variety of electrolyte, hemodynamic, septic, and nutritional derangements may result in sudden decompensation and even death. We present a case that dramatically illustrates these complications and focuses on the key role of underlying nutritional cardiomyopathy.

Guidelines for refeeding the marasmic patient.

Nutritional support of the malnourished patient can be lifesaving. However, the efficacy of total parenteral nutrition in this setting depends on: a) careful estimation of energy requirements, using the Harris-Benedict equation or indirect calorimetry; b) minimizing the fluid retention which invariably complicates refeeding in marasmus; c) adequate repletion of P, K, and Mg on a daily basis; and d) accurate assessment of the rate of weight regain.

A clinical application of exercise physiology and nutritional support for the mechanically ventilated patient.

A challenging problem facing the clinician is the management of critically ill patients in whom repeated attempts at weaning from mechanical ventilation are unsuccessful. The difficulty weaning these patients from the ventilator can be augmented in the presence of detraining of respiratory muscles, malnutrition, stress and the metabolic response to injury, and/or immobilization. An understanding of basic concepts of established tenets of exercise physiology and of nutritional support will allow their application to respiratory muscle function with the goal of facilitating the endurance and strength of respiratory muscles needed to sustain spontaneous ventilation.