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Biomedical subjects

David L Sigalet

Publications and source records attributed to David L Sigalet.

15 recordsLinked to original sources

Persistent post-transplant polyuria managed by bilateral native-kidney laparoscopic nephrectomy.

Polyuria is not considered an absolute indication for pre-transplant nephrectomy; however, it may complicate post-transplantation fluid management. Bilateral native-kidney laparoscopic nephrectomy was performed at our centre in two patients (four kidneys) 1 month after they had received a living related-donor renal transplant. The indication for nephrectomy was severe post-transplant polyuria secondary to the patient's underlying disease: juvenile nephronophthisis. Both patients had a persistent post-transplant daily urine output of 7-8 l/day and continued to have a variable serum creatinine level, dependent on intravenous hydration, more then 3 weeks after transplantation. Bilateral laparoscopic native-kidney nephrectomy in children has previously been reported. However, to the best of our knowledge, laparoscopic nephrectomy has not been described after kidney transplantation and certainly not in the immediate post-transplantation period. The procedure was well tolerated and did not affect renal graft function. In fact, following the procedure, serum creatinine levels stabilized, while daily fluid requirements decreased to 2.5-3.5 l/day in both patients. We concluded that bilateral native-kidney nephrectomy can be safely performed in paediatric renal transplant recipients in the immediate post-transplantation period. This new approach may allow preemptive transplantation and avoid the need for a transition period on dialysis in patients for whom pre-transplant nephrectomy is not absolutely indicated.

Child↗

The Calgary protocol for bracing of pectus carinatum: a preliminary report.

BACKGROUND: The optimal treatment of pectus carinatum (PC) deformities is unclear. We propose a nonoperative approach using a lightweight, patient-controlled dynamic chest-bracing device. MATERIAL AND METHODS: With ethical approval, 24 patients with PC were treated at the Alberta Children's Hospital between January 1998 and April 2005. There were 6 (25%) females and 18 (75%) males, with a mean age of 12.9 years at the onset of treatment. Treatment involved fitting of a lightweight, patient-controlled chest brace, worn for 23 hours per day (correction phase [CP]) until the convex deformity was corrected. Following correction of the deformity, bracing was reduced to 8 hours per day (maintenance phase) until axial skeletal maturation ceased. Monitoring was done by measurement of the external pectus carinatum protrusion as well as subjective patient and surgeon appraisal of appearance and exercise tolerance. RESULTS: Nineteen (79.2%) patients have completed initial treatment (mean CP time, 4.3 +/- 2.1 months). There were 3 patients (12.5%) who were noncompliant, and 2 (8.3%) are still in the initial CP phase of therapy. Fourteen (58.3%) patients are presently in maintenance phase, nocturnally braced, and 2 (8.3%) have completed therapy. In patients completing initial treatment, the protrusion pectus carinatum protrusion (pre 22 +/- 6 vs post 6.0 +/- 6.2) and subjective appearance (change + 1.8+/-0.4) showed a significant improvement (P < .001 for both) with no change in exercise tolerance. CONCLUSION: Compressive bracing results in a significant subjective and objective improvement in PC appearance in skeletally immature patients. However, patient compliance and diligent follow up appear to be paramount for the success of this method of treatment. Further studies are required to show the durability of this method of treatment.

Adolescent↗

Acute denervation alters the epithelial response to adrenoceptor activation through an increase in alpha1-adrenoceptor expression on villus enterocytes.

Loss of sympathetic input due to intestinal denervation results in hypersensitivity and increased intestinal secretion. It is unknown whether denervation-induced alterations in intestinal epithelial physiology are the result of changes in adrenoceptors on enterocytes (ENTs). The purpose of this study was to examine adrenoceptor distribution and pharmacology on small intestinal ENTs following acute intestinal denervation. Lewis rats underwent small bowel transplantation (SBT) or sham operation and proximal small intestinal segments were harvested 1, 2 and 4 weeks postoperatively. Intestinal electrolyte movement was assessed using short-circuit current (Isc) measurements of stripped epithelial sheets following stimulation with phenylephrine (PE), an alpha(1)-adrenoceptor agonist. The presence of adrenoceptor subtypes on separated villus and crypt ENTs was assessed using flow cytometry. Alpha(1)-adrenoceptors were found on approximately 27% of jejunal villus ENTs, but not crypt ENTs, following acute extrinsic denervation. ENTs from the Lewis rat have few beta-adrenoceptors. Alpha(1)-adrenoceptor stimulation of acutely denervated intestinal epithelial sheets decreased Isc by -13.45%. This effect was mediated by a reduction in chloride (Cl(-)) secretion; the absence of Cl(-) reversed the Isc to +13.79%. In conclusion, loss of sympathetic innervation to the gastrointestinal epithelium causes acute upregulation of alpha(1)-adrenoceptors on villus ENTs, leading to inhibition of Cl(-) secretion at the villus tip. The increase in adrenoceptors may reflect a compensatory mechanism to combat the increased secretory state of the bowel due to the loss of the sympathetic innervation and tonic control over intestinal secretion.

Animals↗

The effects of systemic hypoxia on colon anastomotic healing: an animal model.

PURPOSE: Acute postoperative systemic hypoxia occurs frequently in the clinical setting following intestinal resection, as a result of complications such as pneumonia, pulmonary edema, or the acute respiratory distress syndrome. Although it is well established that oxygen is essential for metabolism in general and intestinal anastomotic healing, the mechanisms by which systemic hypoxia affect this process are not clear. The purpose of this study was to establish an animal model to simulate acute systemic hypoxia and to examine the effects on anastomotic healing. We investigated the hypothesis that systemic hypoxia impairs anastomotic healing in the colon by disrupting revascularization via changes in the expression of two putative angiogenic factors: inducible nitric oxide synthase and vascular endothelial growth factor. METHODS: Phase I: Juvenile male Sprague-Dawley rats underwent carotid artery cannulation. In a controlled environment the FiO2 was incrementally decreased from 21 to 9 percent and the resultant PaO2 measured. Phase II: Animals underwent colonic transection with immediate reanastomosis and were placed in either a normoxic (FiO2 21 percent) or hypoxic (FiO2 11 percent) environment for seven days. Perianastomotic in vivo tissue oxygen saturation was measured before segmental colon resection in each of the animals and at seven days before measurement of anastomotic bursting pressure. Perianastomotic tissue samples were assessed by Western blot assay for the expression of vascular endothelial growth factor and inducible nitric oxide synthase protein. Sections from each tissue sample were taken and evaluated by a pathologist blinded to treatment group for determination of anastomotic healing score. RESULTS: Phase I: Incrementally decreasing the FiO2 resulted in a progressive decrease in PaO2 (r2 = 0.77). Phase II: Animals maintained in a hypoxic environment had a significant decrease in tissue oxygen saturation (73 +/- 9 percent vs. 94 +/- 3 percent; P < 0.0001) and anastomotic bursting pressure (118 +/- 18 mmHg vs. 207 +/- 30 mmHg; P < 0.0001) compared with normoxic controls. Systemic hypoxia induced a significant increase, when compared with normoxic controls, in vascular endothelial growth factor (247.1 +/- 9.5 vs. 142.2 +/- 10.6; P < 0.0001) and inducible nitric oxide synthase (259.6 +/- 21.1 vs. 120.2 +/- 10.9; P < 0.0001) protein expression and led to a significant decrease in the overall wound-healing score. CONCLUSION: This study validates a new animal model to study the effects of acute systemic hypoxia on colonic anastomotic healing. In this model, systemic hypoxia directly translated into local tissue hypoxia, and anastomotic healing was impaired. Contrary to our original hypothesis, hypoxia led to a significant increase in vascular endothelial growth factor and inducible nitric oxide synthase protein expression at the colonic anastomotic site. Impairment in anastomotic integrity despite upregulation of these angiogenic factors could be a result of the inability of wounded tissue to respond to vascular endothelial growth factor and inducible nitric oxide synthase or alternatively, hypoxia may adversely affect collagen synthesis and deposition directly.

Anastomosis, Surgical↗

A pilot study of the use of epidermal growth factor in pediatric short bowel syndrome.

BACKGROUND: This study examined the effects of enterally administered epidermal growth factor (EGF) on nutrient absorption and tolerance of enteral feeds in pediatric patients with short bowel syndrome (SBS). METHODS: Patients identified with severe SBS (<25% bowel length predicted for age) were prospectively enrolled in treatment using human recombinant EGF (1-53); 100 microg/kg per day given mixed with enteral feeds and patients were treated for 6 weeks. End points followed were patient weight, tolerance of enteral feeds, nutrient absorption, and intestinal permeability as determined using carbohydrate probes and hematologic values for liver function parameters. RESULTS: Five patients were treated with EGF; all showed a significant improvement in carbohydrate absorption (3-0 methylglucose): absorption 24.7% +/- 9.7% pretreatment vs 34.1% +/- 13.8% posttreatment and improved tolerance of enteral feeds (enteral energy as % of total energy, 25% +/- 28% pretreatment vs 36% +/- 24% posttreatment; mean +/- SD; P < .05 by Wilcoxon's signed rank test). Epidermal growth factor treatment was not associated with significant changes in intestinal permeability, the rate of weight gain, or liver function tests. During the treatment phase, no patients developed episodes of sepsis; however, within 2 weeks of discontinuation of EGF treatment, 3 patients developed septic episodes. No adverse effects of EGF administration were noted. CONCLUSIONS: These results suggest that enteral treatment with EGF in pediatric SBS improves nutrient absorption, increases tolerance with enteral feeds, and may improve the infection rate. Further studies exploring treatment strategies including the timing and duration of EGF administration are indicated.

3-O-Methylglucose↗

Midterm evaluation of cardiopulmonary effects of closed repair for pectus excavatum.

BACKGROUND/PURPOSE: Since the introduction of the closed technique for repair of pectus excavatum, increasing numbers of patients are presenting for surgery. However, controversy exists regarding the effects of repair on long-term cardiopulmonary outcome. This report details the effects over time of closed repair of pectus excavatum on pulmonary function, cardiac function, exercise tolerance, and the patient's perception of appearance and subjective ability to exercise. METHODS: All patients undergoing closed repair of pectus excavatum were evaluated prospectively. Preoperative computed tomography scan, static pulmonary function studies, exercise tolerance, and echocardiographic evaluation of cardiac function were done. Studies were repeated at 3 and 21 months post-bar placement, and then 3 months after bar removal. RESULTS: Pre- and postoperative data were available for an initial 48 patients, with 11 patients completing the full evaluation after bar removal. All measures of pulmonary function including forced expiratory volume in 1 second and forced vital capacity were reduced at 3 months postoperation, with a gradual increase during follow-up; however, pulmonary function remained below normative values for patients without pectus excavatum of similar age. Cardiac function as measured by cardiac output and index was increased at 3 months postoperation and maintained thereafter. Exercise tolerance declined initially and then increased by the 21-month evaluation point and after bar removal. Patients reported a subjective improvement in the ability to exercise immediately after bar insertion. CONCLUSIONS: These results corroborate previous studies which suggested that after closed repair of pectus excavatum there is an immediate subjective improvement in the ability to exercise which is paralleled by an improvement in cardiac output. However, there is an early postoperative decline in pulmonary function which does improve over time; however, this does not reach normal values for similar weight. Further studies are needed to determine whether these results are maintained, or whether after bar removal there is a further improvement in pulmonary status. These results do support the use of the closed repair of pectus excavatum for maintaining and possibly improving cardiopulmonary function in this patient population.

Adolescent↗

GLP-2 levels in infants with intestinal dysfunction.

Glucagon Like Peptide 2 (GLP-2) has been proposed as an important regulatory hormone in nutrient absorption. The present study was conducted in human infants with intestinal dysfunction undergoing surgery, correlating postprandial GLP-2 levels with intestinal length, nutrient absorption, and patient outcome. We hypothesized that GLP-2 levels would be inversely related to nutrient absorption; we further hypothesized that post prandial GLP-2 levels would be predictive of the ability to wean patients from total parenteral nutrition (TPN), and tolerance of enteral feeding. Infants prospectively identified with nutrient malabsorption following intestinal surgery were monitored and after initiation of feeds GLP-2 levels were measured in the fed state. Intestinal length was recorded intraoperatively and nutrient absorption was quantified using both a balance study, and carbohydrate probe method. 12 infants had GLP-2 levels successfully measured; two patients had repeated studies. Average gestational age was 32.7 +/- 3.4 wk, age at testing was 1.7 +/- 1.4 mo and average weight was 3.5 +/- 1.1 kg. Causes of intestinal loss were necrotizing enterocolitis, atresia and volvulus. Five patients had severe short bowel syndrome (<50% of normal small intestinal length), 3 died. GLP-2 levels were best correlated with residual small intestinal length (r2 = 0.75). Correlations with total intestinal length including colon were less significant; residual colon appeared to not contribute to measurable GLP-2 production. GLP-2 levels were well correlated with tolerance of enteral feeds. Contradicting the initial hypothesis, GLP-2 levels were directly correlated with nutrient absorptive capacity (correlation with fat absorption: r2 = 0.72, carbohydrate = 0.50 and protein = 0.54 respectively). There were no apparent changes in GLP-2 levels with gestational or postnatal age. As a corollary to the correlation with bowel length, a postprandial level of 15 pmol/L appeared to be discriminatory; infants with postprandial GLP-2 levels of > 15 pmol/L were able to be weaned from total parenteral nutrition, while 3 of 4 infants who had GLP-2 levels less than 15 could not be weaned by one year. These results show that in infants with intestinal dysfunction, GLP-2 levels are correlated with residual small bowel length and nutrient absorption, and may be predictive of outcome. In contrast to adults with intact colon and SBS, infants with SBS and intact colon do not appear able to produce GLP-2 in response to feeding stimulation. Further studies are suggested to examine the ontogeny of the GLP-2 axis and the possible therapeutic role of GLP-2 supplementation.

Adult↗

Glucagon-like peptide-2 induces intestinal adaptation in parenterally fed rats with short bowel syndrome.

Glucagon-like peptide-2 (GLP-2) is an intestinal trophic enteroendocrine peptide that is associated with intestinal adaptation following resection. Herein, we investigate the effects of GLP-2 in a total parenteral nutrition (TPN)-supported model of experimental short bowel syndrome. Juvenile Sprague-Dawley rats underwent a 90% small intestinal resection and jugular catheter insertion. Rats were randomized to three groups: enteral diet and intravenous saline infusion, TPN only, or TPN + 10 microg.kg(-1).h(-1) GLP-2. Nutritional maintenance was isocaloric and isonitrogenous. After 7 days, intestinal permeability was assessed by quantifying the urinary recovery of gavaged carbohydrate probes. The following day, animals were euthanized, and intestinal tissue was processed for morphological and crypt cell proliferation (CCP) analysis, apoptosis (caspase-3), and expression of SGLT-1 and GLUT-5 transport proteins. TPN plus GLP-2 treatment resulted in increased bowel and body weight, villus height, intestinal mucosal surface area, CCP, and reduced intestinal permeability compared with the TPN alone animals (P < 0.05). GLP-2 treatment induced increases in serum GLP-2 levels and intestinal SGLT-1 expression (P < 0.01) compared with either TPN or enteral groups. No differences were seen in the villus apoptotic index between resection groups. Enterally fed resected animals had a significant decrease in crypt apoptotic indexes compared with nontreated animals. This study demonstrates that GLP-2 alone, without enteral feeding, stimulates indexes of intestinal adaptation. Secondly, villus hypertrophy associated with adaptation was predominantly due to an increase in CCP and not to changes in apoptotic rates. Further studies are warranted to establish the mechanisms of action and therapeutic potential of GLP-2.

Adaptation, Physiological↗

Enteral nutrition and mucosal immunity: implications for feeding strategies in surgery and trauma.

Systemic inflammatory responses to severe trauma and surgical illnesses may be partly responsible for numerous complications, including sepsis, multiple organ failure and unregulated hypermetabolism leading to protein-calorie malnutrition. The integrity of the gastrointestinal tract appears to be an important factor in the pathogenesis of the systemic inflammatory response and sepsis. Resuscitation and nutrition support strategies for preserving gut mucosal integrity have therefore been strongly promoted. This review summarizes the scientific rationale for emphasizing enteral nutritional support of surgical patients, discusses some important limitations of enteral feeding and argues for a flexible approach to nutrition support for these complex patients.

Critical Illness↗

Acute abdominal pain in children.

Acute abdominal pain in children presents a diagnostic dilemma. Although many cases of acute abdominal pain are benign, some require rapid diagnosis and treatment to minimize morbidity. Numerous disorders can cause abdominal pain. The most common medical cause is gastroenteritis, and the most common surgical cause is appendicitis. In most instances, abdominal pain can be diagnosed through the history and physical examination. Age is a key factor in evaluating the cause; the incidence and symptoms of different conditions vary greatly over the pediatric age spectrum. In the acute surgical abdomen, pain generally precedes vomiting, while the reverse is true in medical conditions. Diarrhea often is associated with gastroenteritis or food poisoning. Appendicitis should be suspected in any child with pain in the right lower quadrant. Signs that suggest an acute surgical abdomen include involuntary guarding or rigidity, marked abdominal distention, marked abdominal tenderness, and rebound abdominal tenderness. If the diagnosis is not clear after the initial evaluation, repeated physical examination by the same physician often is useful. Selected imaging studies also might be helpful. Surgical consultation is necessary if a surgical cause is suspected or the cause is not obvious after a thorough evaluation.

Abdominal Pain↗

Absorbable mesh and skin flaps or grafts in the management of ruptured giant omphalocele.

PURPOSE: The authors report the use of absorbable mesh closure with subsequent skin graft or skin flap coverage for giant ruptured omphalocele. METHODS: Retrospective review of a single surgeon's experience was conducted from 1996 through 2001. RESULTS: Four infants were identified presenting an average of 4 weeks prematurely. All patients had an initial attempt at silo reduction but had either infection or respiratory compromise. The silo was removed, and the defect was covered with polyglycan mesh followed by subsequent skin coverage. In 2 patients, final coverage was obtained using skin flaps, whereas in 2 patients, split-thickness skin grafts were required. All patients were noted to have a distinct narrow chest contour with evidence of pulmonary hypoplasia. Three patients had respiratory failure requiring tracheostomy and prolonged ventilation. Two children were decannulated after one and 2 years, respectively; the third child is booked for decannulation at age 12 months. Although these children have required multiple reoperations, they are all presently doing well with an average of 4 years of follow-up. CONCLUSIONS: Patients with giant omphalocele have associated pulmonary hypoplasia, which limits the ability to reduce the abdominal contents. Absorbable mesh coverage followed by split-thickness skin graft or skin flap coverage provides a viable biological coverage and minimizes ongoing pulmonary morbidity. The authors recommend a minimally aggressive attempt at sac reduction in the initial treatment of giant omphalocele and, if necessary, the use of absorbable mesh as a staged coverage with subsequent split-thickness skin grafting to minimize the pulmonary effects of the abdominal operation.

Female↗

Cardiopulmonary effects of closed repair of pectus excavatum.

BACKGROUND/PURPOSE: Increasing numbers of patients with pectus excavatum defects are presenting for operative repair. Studies that follow-up with patients after open repair have found a decrease in pulmonary function with some improvement in cardiac output and exercise tolerance; however, these effects have not been examined systematically after closed or Nuss repair of pectus excavatum. This study examined the early postoperative effects of closed repair of pectus on pulmonary function, exercise tolerance, and cardiac function. METHODS: Patients were followed up prospectively after initial evaluation for operation. All patients underwent preoperative computed tomography (CT) scan, and pre- and postoperative (3 months) pulmonary function studies, exercise tolerance, and echocardiographic evaluation of cardiac function. RESULTS: Eleven patients underwent evaluation. Preoperative CT index was 4.1 +/- 0.9. Patients reported an improvement in subjective postoperative exercise tolerance (4.1 +/- 0.7; maximal, + 5). Pulmonary function studies (FVC and vital capacity) were significantly reduced at 3 months postsurgery: change in FVC, -0.67 +/- 0.92 L and VC, -0.5 +/- 0.72 L. Similarly, VO2 max was reduced: preoperative, 35.6 +/- 1.5 versus postoperative, 29.1 +/- 11.9 L/kg/min. Cardiac function was significantly improved postoperation (stroke volume preoperative, 61.6 +/- 25 versus 77.5 +/- 23 mL postoperative). All comparisons had a P value less than.05 by Student's paired t test. CONCLUSIONS: These results show that closed repair of pectus excavatum is associated with a subjective improvement in exercise tolerance, which is paralleled by an increase in cardiac function and a decline in pulmonary function. These findings support the use of closed repair of pectus excavatum in patients who complain of subjective shortness of breath; further study is required to delineate the long-term cardiopulmonary implications after closed repair.

Adolescent↗

A minimally invasive approach to bile duct injury after blunt liver trauma in pediatric patients.

A 12-year-old boy presented with a large liver laceration after blunt abdominal trauma. He was treated nonoperatively and subsequently had bile peritonitis from a bile leak. Endoscopic retrograde cholangiopancreatography (ERCP) visualized the bile duct injury and allowed decompression of the biliary tree with an endoscopically placed biliary stent. A drain also was placed over the laceration through a small subcostal incision. The patient recovered rapidly after this minimally invasive procedure and went home 9 days later.

Bile Ducts↗

3-0 methylglucose absorption in vivo correlates with nutrient absorption and intestinal surface area in experimental short bowel syndrome.

BACKGROUND: Inert carbohydrate probes are widely used to study intestinal permeability and examine the passive uptake of markers. This study examined the use of quantifying 3-0 methylglucose (3-0 MG) absorption as a marker of intestinal surface area and active nutrient transport capability. METHODS: Using a rat model, varying degrees of short bowel syndrome (SBS) were induced: sham operation (intestinal transection only), 50% resection (R50), 75% resection (R75), and 90% resection (R90; n = 6 to 8 in each group). Animals were pair fed, and over days 5 and 6 postoperation, a balance study was done to quantify absorption of dietary fat, protein, and carbohydrate. On day 7, animals were gavaged with the test solution containing 3-0 MG, lactulose, and mannitol, followed by a 16-hour urine collection. Urine recovery of probes was quantified using high-performance liquid chromotography. Animals were then killed, and the gross and microscopic intestinal morphology was determined. RESULTS: As expected, increased resection resulted in reduced absorption of dietary nutrients and 3-0 MG, which reached significance in the R90 resected animals. 3-0 MG absorption was significantly correlated with intestinal surface area and the absorption of dietary protein and fat (p < .01 for all comparisons). Interestingly, 3-0 MG absorption was not significantly correlated with the absorption of dietary carbohydrate. CONCLUSIONS: 3-0 MG absorption is a useful marker of functional intestinal surface area and of the absorption of dietary fat and protein in experimental SBS. 3-0 MG may be a useful marker of nutrient absorptive capacity in patients with SBS; further study is indicated.

3-O-Methylglucose↗

3-0 methylglucose uptake as a marker of nutrient absorption and bowel length in pediatric patients.

BACKGROUND: Inert carbohydrate probes are commonly used to assess intestinal permeability; we have previously shown that the actively transported moiety 3-0 methylglucose (3-0 MG) is a useful marker of intestinal surface area and nutrient absorption in animal models of short bowel syndrome (SBS). This study examines the correlation of 3-0 MG absorption with nutrient absorption, bowel length, and the tolerance of enteral feeds in pediatric patients. METHODS: Fifteen children (1 month to 15 years in age) were studied after intestinal surgery. All had a stoma, 2 were > 1 year of age, the remainder had surgical intervention as a neonate or within the first month of life. Eight had SBS (50% expected bowel length for age). Bowel length was measured intraoperatively. Nutrient absorption was quantified with a 48-hour bowel study, measuring fat, protein, and carbohydrate output directly. 3-0 MG absorption and intestinal permeability were quantified using a solution containing 30 mg/mL 3-0 MG, 20 mg/mL mannitol and 30 mg/mL lactulose (osmolarity 352, given at 1 mL/kg via feeding tube). Subsequent urine production was collected for 8 hours, and probe recovery measured using HPLC. RESULTS: 3-0 MG absorption was significantly correlated with nutrient absorption. The correlation with protein absorption was r2 = .59, fat r2 = .62 and carbohydrate r2 = .56. The correlation between 3-0 MG absorption and bowel length was r2 = .58. 3-0 MG absorption was significantly lower in SBS patients vs patients with normal bowel length (15.8 +/- 6.7 vs 30.5 +/- 10.2%). 3-0 MG absorption also correlated with the ability to tolerate enteral feeds (r2 = .38; p < .03 for all comparisons). CONCLUSIONS: 3-0 MG may be a useful marker of nutrient absorption and bowel length in pediatric patients with short bowel syndrome. The simplicity and reproducibility of the method make it an attractive option for following patient outcomes. Further studies are suggested to determine the utility of these markers in directing the clinical management of patients.

3-O-Methylglucose↗