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Biomedical subjects

H C Sax

Publications and source records attributed to H C Sax.

At least 19 recordsLinked to original sources

Incidental appendectomy in the era of managed care and laparoscopy.

BACKGROUND: In a study carried out before laparoscopy or managed care, there was no cost or patient benefit for routine incidental appendectomy. With the onset oflaparoscopy, a change in indications for surgery, and increased prevalence of capitated contracts, a reanalysis of the cost-effectiveness of incidental appendectomy is warranted. STUDY DESIGN: Financial data from 251 patients undergoing appendectomy for acute appendicitis without complication at a single institution were identified. Age-specific epidemiology data from the Centers for Disease Control, Atlanta, were applied to assess risk and cost of future appendectomy. The net cost or savings for incidental appendectomies necessary to prevent one case of acute appendectomy was determined and stratified by gender and age to the population as a whole. Further adjustment was made for the variable level of surgeon reimbursement for incidental appendectomy. RESULTS: At 10% surgeon reimbursement, open incidental appendectomy was cost-effective in those less than 25 years of age (< 35 years of age in a capitated system). Applied to the general population, open incidental appendectomy in those less than 25 years represented savings of up to $1,100 per 10,000 population per year. A surgeon fee of greater than 50%, or the laparoscopic approach using staplers, accrued no savings in any age groups. CONCLUSIONS: Open incidental appendectomy at low physician reimbursement is a cost-effective procedure for patients of less than 35 years of age. A decrease in equipment cost for laparoscopic approach will extend these indications.

Acute Disease↗

Na(+)-dependent neutral amino acid transporter ATB(0) is a rabbit epithelial cell brush-border protein.

System B(0) activity accounts for the majority of intestinal and kidney luminal neutral amino acid absorption. An amino acid transport system, called ATB(0) (also known as ASCT2), with functional characteristics similar to those of system B(0), has been recently cloned. We generated polyclonal antibodies to human and rabbit ATB(0) COOH-terminal peptides and used Western blot analysis to detect ATB(0) protein in rabbit tissues, rabbit ileal brush-border membrane vesicles (BBMV), and HeLa cells transfected with plasmids containing ATB(0) cDNAs. Immunohistochemistry was used to localize ATB(0) in rabbit kidney and intestine. In Western blots of rabbit tissues, ATB(0) was a broad smear of 78- to 85-kDa proteins. In transfected HeLa cells, ATB(0) appeared as a smear consisting of 57- to 65-kDa proteins. The highest expression was found in the kidney. ATB(0) was enriched in rabbit ileal BBMV and in HeLa cells transfected with ATB(0) cDNAs. In the kidney and in the intestine, ATB(0) was confined to the brush-border membrane (BBM) of the proximal tubular cell and of the enterocyte, respectively. Tissue and intracellular distribution of ATB(0) protein parallels that of system B(0) activity. ATB(0) protein could be the transporter responsible for system B(0) in the BBM of epithelial cells.

Amino Acid Sequence↗

Epidermal growth factor receptor is increased in rabbit intestinal brush border membrane after small bowel resection.

A defective epidermal growth factor receptor (EGFR) abrogates adaptation, while overexpression of EGFR or exogenous epidermal growth factor (EGF) enhances adaptation following small bowel resection (SBR). EGFR is predominantly located on the enterocyte basolateral membrane, yet luminal EGF is increased in injured mucosa. We hypothesized that EGFR is both increased and redistributed to the enterocyte brush border membrane (BBM) after SBR and that parenteral EGF will reverse this redistribution. Rabbits (N = 20) were subjected to sham operation or SBR. EGF or vehicle were administrated one week postoperatively to SBR rabbits, and the gut was harvested one week later. EGFR levels in intestinal crude extracts and purified BBM were determined by Western blot analysis. No difference in EGFR level was detected in the crude extract among any of the groups. SBR more than doubled EGFR amount in BBM (P < 0.006). Parenteral EGF did not influence this redistribution. Thus, EGFR is partially redistributed to the BBM in the mucosa of SBR rabbits, and parenteral EGF does not reverse this redistribution.

Animals↗

Management of the patient with short bowel syndrome.

Extensive resection of the small bowel results in impaired digestion of macronutrients and malabsorption of nutrients, fluid, electrolytes, and minerals. Gastric acid hypersecretion and alterations in gut hormonal response further contribute to the problem. Diarrhea, dehydration, electrolyte and acid/base abnormalities, and macronutrient and micronutrient deficiencies ensue, and is termed the short bowel syndrome (SBS). Rare disorders, such as essential fatty acid deficiency and D-lactic acidosis, are a greater concern for the SBS patient. These patients' lives are significantly impacted, and they require close monitoring by a medical team knowledgeable about the disease and its nutritional, metabolic, and psychosocial consequences. Immediate therapies are directed toward fluid resuscitation, wound healing, and initiation of early nutrition support. After medical stabilization, multiple nutritional and medicinal therapies are used to aid bowel adaptation and prevent medical crisis. Advanced practice nurses should be knowledgeable about SBS to educate patients and families about this disease, associated therapies and changes in lifestyle, and how to detect and manage acute changes in medical condition.

Acidosis, Lactic↗

Small bowel adaptation is dependent on site of massive enterectomy.

BACKGROUND: Changes in amino acid transport after massive enterectomy occur in a nutrient-dependent fashion and may affect long-term outcome. Epidermal growth factor (EGF) can enhance nutrient transport and a defective epidermal growth factor receptor (EGF-R) has been noted to attenuate adaptation. Most animal studies, however, have examined only a single site of resection. This does not mimic the clinical situation where disease dictates the site of resection leading to proximal, middle, or distal enterectomies. We hypothesize that the site of massive enterectomy will alter nutrient transport and EGF-R levels in the residual gut. MATERIALS AND METHODS: New Zealand White rabbits were randomized to control, midgut division, or 70% resection (proximal, midgut, or distal). After 1 week, sodium-dependent transport of glucose, glutamine, alanine, and leucine into brush border membrane vesicles was quantitated. EGF-R protein was determined by Western blot analysis. RESULTS: At baseline, amino acid transport was greater in ileum than jejunum. Surgery alone elevated glutamine and leucine jejunal transport by 130 and 97%, respectively, over controls (P < 0.05). Midgut resection increased jejunal glutamine transport 61% over control (P < 0.05). In contrast, distal resection increased jejunal alanine transport by 150% over controls with no change in glutamine (P < 0.05). After midgut resection, EGF-R was significantly greater (124%) in ileum then in jejunum in whole mucosa homogenates. Proximal resection significantly lowered ileal EGF-R compared to that seen in midgut resected residual ileum. CONCLUSIONS: Site of massive resection is important in determining postoperative changes in nutrient transport and EGF-R.

Adaptation, Physiological↗

Characterization of L-leucine transport system in brush border membranes from human and rabbit small intestine.

The branched-chain amino acids (BCAAs) leucine, isoleucine, and valine are beneficial to catabolic patients by improving hepatic protein synthesis and nitrogen economy, yet their transport from the intestinal lumen is not well-defined. The leucine transport system in human and rabbit small intestine was characterized using a brush border membrane vesicle (BBMV) model. Sodium and pH dependence and transport activity along the longitudinal axis of the small bowel were determined. Transport kinetics and inhibition profiles were defined. Although previous studies in other tissues show leucine transport to be mostly a Na+-independent process, our studies show that leucine transport is a predominantly Na+-dependent process occurring mainly via a single saturable pH-independent transporter resembling system B0 in the intestine. This system B0 transporter demonstrates stereoisomeric specificity. There is also a minor Na+-independent transport component (<6% in rabbits). Leucine uptake in both rabbits and humans is significantly greater than the uptake of other clinically relevant nutrients such as glutamine. In the rabbit, ileal leucine transport is significantly greater than jejunal uptake. While the affinities of the human and rabbit transporters are similar, the rabbit transporter has greater carrier capacity (maximal transport velocity [Vmax]). These findings suggest that the transport of leucine in the gut mucosa is significantly different from the transport in other tissues.

Amino Acids↗

Intestinal adaptation and amino acid transport following massive enterectomy.

Morphological and physiological adaptation in residual small intestine occurs after massive enterectomy and is influenced significantly by different growth factors and hormones. The mechanism of adaptation occurs through hypertrophy and hyperplasia as well as nutrient transporter changes. These transporters are classified into different classes dependent on its biological properties. The adaptation process evolves over time and different nutrient absorption profiles occur at different postoperative stages. There is an initial decrease in amino acid transport after resection followed by a return to approximately normal levels. Glucose also follows a similar pattern of changes but returns to normal later than amino acids. The time course of these changes are different for different animals with rat adaptation being much faster than rabbit. Growth hormone (GH) induces increased amino acid transport during this adaptation period, however, appears not to affect small intestine hypertrophy or hyperplasia. The increase in transport occurs via an increase in transport numbers rather than affinity. Epidermal growth factor (EGF) also increases amino acid transport in postoperative animals. Its advantage is it is orally stable when given with a protease inhibitor. EGF also reverses the down-regulating effects of the somatostatin analogue Octreotide (SMS) post resection. EGF in combination with GH has additive effects. However, the effects of the growth factors are site specific. GH and EGF combination therapy significantly increased alanine and arginine transport in distal small bowel after 70 % enterectomy but not in the proximal small bowel. The same combination increases leucine and glutamine transport in the proximal small intestine only. Understanding the specific changes that occur with these therapies may improve quality of life for patients and also reduce that need for total parenteral nutrition.

Absorption↗

Human growth hormone induces system B transport in short bowel syndrome.

BACKGROUND: After massive enterectomy, remnant intestine undergoes compensatory adaptation. A combination of human growth hormone (hGH) and a glutamine-enriched modified diet induces further adaptation in patients with short bowel syndrome (SBS) on long-term total parenteral nutrition. The specific actions of each component, however, are not well-defined. METHODS: New Zealand White rabbits were randomized to control, sham operation, or SBS (70% midjejunoileal resection) groups and treated with either hGH or saline. Sodium-dependent uptake of glucose, glutamine, alanine, leucine, and arginine into brush border membrane vesicles was quantitated. Serum insulin-like growth factor-I (IGF-I) levels were determined by immunoradiometric assay. Mucosal mRNA expression of IGF-I and IGF binding protein 4 (IGFBP-4) was evaluated by northern blot analysis using rat cDNA probes. RESULTS: Glutamine and leucine transports were 33 and 39% greater, respectively, in the hGH-treated versus saline-treated SBS group (P < 0.05), supporting induction of system B amino acid transport. This upregulation was due, in part, to an 88% increase in glutamine carrier capacity (Vmax) with no change in carrier affinity (Km). Both hGH treatment and SBS increased serum IGF-I levels without direct correlation with increased nutrient transport. IGFBP-4 mRNA expression in small bowel mucosa of saline-treated SBS animals was significantly greater than saline-treated unoperated control values. Mucosal IGFBP-4 mRNA was not significantly altered from control in the other study groups. IGF-I mRNA expression was not detected in mucosa, but weak hybridization was noted in rabbit liver. CONCLUSIONS: Human growth hormone accelerates early adaptation in SBS by upregulation of system B carrier capacity. Serum IGF-I levels and mucosal IGF-I and IGFBP-4 mRNA expression did not directly correlate with this enhanced nutrient transport, suggesting that hGH might exert its adaptive effects by mechanisms that are independent from the IGF system in this model.

Amino Acids↗

Epidermal growth factor and human growth hormone accelerate adaptation after massive enterectomy in an additive, nutrient-dependent, and site-specific fashion.

BACKGROUND: After massive enterectomy (ME), remnant intestine undergoes compensatory adaptation. Epidermal growth factor (EGF) and human growth hormone (hGH) have each been shown to enhance total length small intestine nutrient transport after ME. This study aims to determine the differential effects of EGF and hGH on proximal and distal small intestinal remnants after ME. METHODS: New Zealand white rabbits underwent 70% mid-jejunoileal resection. After 1 week, animals received hGH (0.2 mg/kg/day), EGF (1.5 micrograms/kg/hr), hGH + EGF, or vehicle (equal volume) for 7 days. Sodium-dependent uptake of glucose, glutamine, alanine, leucine, and arginine into brush border membrane vesicles was quantitated. Serum insulin-like growth factor-I concentrations as well as proximal and distal villus and microvillus heights were measured. IGF binding protein-3 and -4 mRNA expression was determined in full-thickness proximal and distal gut remnants. RESULTS: Concomitant hGH and EGF treatment up-regulates glucose (100%), glutamine (80%), and leucine (60%) transport in the proximal remnant; alanine (150%) and arginine (400%) transport in the distal remnant; and microvillus height (25% to 35%) both proximally and distally. Serum IGF-I levels and gross villus heights were not different among groups. CONCLUSIONS: Co-infusion of hGH and EGF accelerates intestinal adaptation after ME in an additive, nutrient-dependent, and site-specific fashion via enhanced nutrient transport as well as microvillus hypertrophy.

Alanine↗

Are prophylactic antibiotics required for elective laparoscopic cholecystectomy?

BACKGROUND: Some clinicians administer prophylactic antibiotics routinely before laparoscopic cholecystectomy, and the results of some of the studies in the literature support this practice. We conducted a prospective randomized trial to determine whether administration of prophylactic antibiotics is necessary during routine laparoscopic cholecystectomy in low-risk patients. STUDY DESIGN: Two hundred fifty patients without evidence of acute inflammation, common duct stones, or other indications for antibiotics were randomized to receive three perioperative doses of cefazolin or no prophylaxis and followed up for complications up to 30 days postoperatively. The primary end point was the occurrence of a major infectious complication, defined as that causing a systemic response, delaying discharge, or leading to readmission. Minor infectious problems were also noted, defined as those causing local symptoms only. RESULTS: One hundred twenty-eight patients were randomized to receive prophylactic antibiotics (PA group), 122 to receive none (NONE group; two patients in this group were actually given preoperative antibiotics). Only one major complication occurred (in a patient in the NONE group), an abscess in the presence of a bile leak, despite the administration of antibiotics when the leak was discovered several days before infectious problems arose. There were four minor problems: two lower urinary tract infections and one superficial wound infection in a NONE patient and one urinary tract infection in a PA patient (not significant); all were easily managed. The prophylactic antibiotics did not sterilize the bile, and infectious complications were not associated with weight, inflammation found at the time of operation, reported stone or bile spill-age, or conversion to open operation. CONCLUSIONS: Prophylactic antibiotics are not necessary for elective laparoscopic cholecystectomy in low-risk patients.

Antibiotic Prophylaxis↗

Low-dose enteral feeding is beneficial during total parenteral nutrition.

BACKGROUND: Enteral support is the preferred feeding route for stressed patients due in part to the provision of gut-specific fuels. In those patients who must be maintained parenterally, small amounts of enteral stimulation might blunt gut atrophy and lead to improvement in host defense mechanisms decreasing macromolecular and/or bacterial translocation (BT). METHODS: Forty-eight rats were infused with TPN for 9 days, and were randomized to receive 0%, 6%, 12%, or 25% of their calories as partial enteral nutrition (PEN) in an isocaloric, isonitrogenous fashion. Twenty-four hours before harvest animals were gavaged with lactulose and urinary excretion quantified. At harvest, mesenteric lymph nodes were cultured to assess BT and intestinal histology determined. RESULTS: Provision of as little as 25% of total calories PEN improved nitrogen balance and reduced BT, in a dose dependent fashion. It did not alter TPN-associated increased macromolecular lactulose permeability (4.4% +/- 1.0%). CONCLUSION: Concurrent small amounts of PEN, aimed to support the gut's metabolic needs, are beneficial during periods of prolonged TPN.

Animals↗

Octreotide diminishes luminal nutrient transport activity, which is reversed by epidermal growth factor.

BACKGROUND: Octreotide (SMS) is a somatostatin analogue utilized in patients with short bowel syndrome (SBS) to decrease output. It may inhibit small bowel adaptation by blocking the secretion of trophic hormones such as epidermal growth factor (EGF). This study delineates the effects of SMS and EGF on nutrient transport in SBS. METHODS: One week after 70% jejunoileal resection, 20 New Zealand White rabbits (2 kg) received subcutaneous infusions of saline or EGF (1.5 micrograms/kg/hr) and injections of saline or SMS s.q.b.i.d. The study groups were EGF/saline, saline/saline, saline/SMS, and EGF/SMS. After 7 days of infusion, intestinal brush border membrane vesicles were prepared and nutrient transport measured. RESULTS: SMS reduced active nutrient transport. Kinetics confirmed this was secondary to a reduction in functional carriers in the brush border membrane, without a change in carrier affinity. The coinfusion of EGF ameliorated this effect. On an individual basis, EGF alone did not significantly increase nutrient transport, but when taken as a group, nutrients transport was upregulated 26%. CONCLUSIONS: SMS is detrimental to small bowel adaptation. EGF reverses this effect and may benefit patients with SBS who require SMS to control high intestinal output.

Amino Acids↗

Extrapelvic endometriosis: diagnosis and treatment.

BACKGROUND: Young women with nondescript abdominal pain can be difficult to diagnose. Although extrapelvic endometriosis is infrequent, we have treated 7 patients over the past 3 years with endometriosis in the abdominal wall, inguinal canal, or surgical incisions as the etiology of their symptoms. PATIENTS AND METHODS: We reviewed the medical records of patients whose final pathology report confirmed a diagnosis of extrapelvic endometriosis. Seven women who were treated at the University of Rochester Strong Memorial Hospital from May 1, 1991 through April 30, 1994 were identified. RESULTS: All patients were premenopausal with no history of pelvic endometriosis. In 4 patients, symptoms were cyclical. Surgical excision was initially curative in 5 patients. Two women required reexcision. The diagnosis of endometriosis was established at exploration by gross appearance and by frozen section. CONCLUSIONS: Endometriosis should be included in the differential diagnosis of a symptomatic mass in a celiotomy scar, the abdominal wall, or the inguinal canal. Principles of management include obtaining an accurate diagnosis and performing an adequate excision to prevent recurrence.

Abdominal Pain↗

Sequential alterations in gut mucosal amino acid and glucose transport after 70% small bowel resection.

BACKGROUND: Studies in animals with short bowel syndrome (SBS) suggest that up-regulation of nutrient transporter activity occurs as an adaptive response to the loss of absorptive area. It is unclear, however, whether nutrient transport is altered at the cell membrane in SBS. The purpose of this study is to clarify amino acid and glucose transport in small intestinal luminal mucosa after 70% small bowel resection in rabbits. METHODS: New Zealand white rabbits underwent 70% jejunoileal resection (n = 27) or a sham operation (n = 19). Brush border membrane vesicles were prepared from small intestinal mucosa at 1 week, 1 month, and 3 months by magnesium aggregation-differential centrifugation. Transport of L-glutamine, L-alanine, L-leucine, L-arginine, and D-glucose was assayed by a rapid mixing-filtration technique. RESULTS: We observed no difference in uptake of all amino acids and glucose at 1 week. The uptake of amino acids and glucose was decreased by 20% to 80% in animals with SBS at 1 month. By 3 months all uptake values except that of glucose returned to normal. Kinetic studies of the system B transporter for glutamine indicate that the decrease in uptake at 1 month was caused by a reduction in the Vmax (1575 +/- 146 versus 2366 +/- 235, p < 0.05) consistent with a decrease in the number of functional carriers on the brush border membrane. CONCLUSIONS: In addition to the anatomic loss of absorptive area after massive bowel resection, alterations in enterocyte transport function may be responsible for malabsorption in patients with SBS.

Amino Acids↗

Early nutritional support in critical illness is important.

The hypermetabolic state in critically ill patients is characterized by wasting of lean body mass and immunosuppression. The gut is among the most metabolically active organs. Failure to maintain gut function by way of early enteral nutrition can lead to increased infectious complications. Early enteral nutrition improves outcomes and may maintain muscle mass by blunting the cytokine-mediated hypermetabolic response.

Critical Care↗

Evaluation of a carboxymethylcellulose sponge for prevention of postoperative adhesions.

BACKGROUND: A novel lyophilized carboxy-methylcellulose (CMC) sponge has been developed for prevention of surgical wound adhesions. One potential mechanism for preventing abdominal adhesion is suppression of the cytokine transforming growth factor beta (TGF-beta) and other macrophage derived fibroblast stimulating factors that partially mediate adhesion formation. METHODS: To study the efficacy and mechanisms of action of the CMC sponge, we performed standard cecal denudation and abdominal wall apposition on rats. A CMC sponge or a commercially available adhesion preventive barrier (Interceed) was placed on the denuded surface. After 14 days, adhesion severity was graded blindly on a scale ranging from 0 (no adhesion) to 5 (severe adhesion). TGF-beta expression was determined by immunocytochemical staining. To assess the secretion of macrophage derived fibrogenic factors in control and CMC rats, labeled thymidine and proline uptake and hydroxyproline production were measured in NRK rat fibroblasts cultured with conditioned medium of peritoneal macrophages. RESULTS: The severity of adhesions in the CMC sponge group (0.7 +/- 0.3) was significantly lower than in the Interceed or control groups (2.2 +/- 0.3; 4.6 +/- 0.1). In control animals TGF-beta expression in endothelium and fibroblasts was maximal on day 3. Neither CMC nor Interceed reduced this expression. Conditioned media derived from sponge-exposed postsurgical peritoneal macrophages did not inhibit fibroblast growth or collagen formation. CONCLUSIONS: In this model the CMC sponge was more effective than Interceed in preventing postoperative adhesions. Its action was not due to inhibition of TGF-beta expression or macrophage derived fibrogenic factors. These data highlight the primary importance of local barrier effect in adhesion prevention.

Animals↗

Preoperative fasting improves survival after 90% hepatectomy.

OBJECTIVE: To assess whether alterations in preoperative fatty acid oxidation and gluconeogenesis induced by fasting will affect survival and liver regeneration following 90% hepatectomy in the rat. DESIGN: In a randomized, controlled trial, Wistar rats (N = 157) were separated into two groups. Rats in the first group fasted for 24 hours. Rats in the second group were allowed to eat ad libitum until the time of operation. These groups were further randomized to receive either 20% glucose or tap water ad libitum postoperatively. INTERVENTIONS: Ninety percent hepatectomy; 24-hour fast; 5% glucose feeding. MAIN OUTCOME MEASURES: Survival, DNA synthesis in the hepatic remnant along with glucokinase activity (GKA) and glycogen content, serum ketone bodies (KB), free fatty acid (FFA), glucose, and ad libitum glucose consumption (GC) were serially quantified. RESULTS: Fasting rats that were offered glucose (fasted/glucose) after hepatectomy demonstrated better survival at 48 hours than the rats that were fed before the procedure and given glucose following hepatectomy (fed/glucose), 95% vs 52% (P < .05). The fasted/glucose group also had a greater peak rate of DNA synthesis (550 +/- 110 vs 275 +/- 40 disintegrations per minute per 0.001 mg of DNA, P < .05). Survival was poor in both groups when only tap water was offered to the animals after hepatectomy (31% vs 12%). In the fasted/glucose group, GC 1 hour after hepatectomy was greater than that for fed rats (1.3 +/- 0.175 vs 0.73 +/- 0.176 g/h, P < .05), yet GKA was suppressed (3.4 +/- 0.42 vs 8.05 +/- 2.77 nmol/min per milligrams of protein, P < .05). Fasting before hepatectomy and consuming glucose after causes elevations in both FFA (1.26 +/- 0.19 vs 0.82 +/- 0.13 mol/mL., P < .05) and KB (18.96 +/- 2.82 vs 11.4 +/- 3.94 mmol/mL, P < .05). Normal glucose was maintained in the fasted/glucose group, but fell to 63 +/- 14 mg/dL at 8 hours after hepatectomy in the fed/glucose group. CONCLUSIONS: Fasting before hepatectomy shifts energy utilization to fat oxidation and gluconeogenesis, which appears to ameliorate liver failure after hepatectomy in this severe model of hepatic resection.

Animals↗