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J M Watters

Publications and source records attributed to J M Watters.

At least 19 recordsLinked to original sources
PubMed1997

An optimized method for cell-based phage display panning.

BACKGROUND: Traditional methods of phage display panning, bind purified antigen to plates or other solid phases to which libraries are then applied, followed by vigorous washings in detergent-supplemented buffers to select for specific phage Fab. These methods are not directly applicable to antigens in their native environment on cell surfaces or in settings where the target antigen is unknown. OBJECTIVES: To develop a model antigen system employing whole cells rather than purified protein immobilized on a substrate; to optimize methods for phage display panning using a cell-based system. RESULTS: Specificity of binding of phage Fab to antigen on cells was demonstrated by output titer and by flow cytometry. Output titers showed a plateau and binding advantage, after four washes, corresponding to removal of most non-specifically bound phage. Enrichment advantage was independent of input phage number. Longer incubation times, to cell tolerance, improved specific binding. Temperature had modes impact as a variable in the panning and washing. An increase in output titers paralleled enrichment for specific phage Fab. CONCLUSION: An optimized method applied to whole cells can productively enrich specific phage Fab in mixtures with large excesses of non-specific phage Fab over several rounds of panning.

Animals↗
PubMed1997

Immediate postoperative enteral feeding results in impaired respiratory mechanics and decreased mobility.

OBJECTIVE: The authors set out to determine whether immediate enteral feeding minimizes early postoperative decreases in handgrip and respiratory muscle strength. SUMMARY BACKGROUND DATA: Muscle strength decreases considerably after major surgical procedures. Enteral feeding has been shown to restore strength rapidly in other clinical settings. METHODS: A randomized, controlled, nonblinded clinical trial was conducted in patients undergoing esophagectomy or pancreatoduodenectomy who received immediate postoperative enteral feeding via jejunostomy (fed, n = 13), or no enteral feeding during the first 6 postoperative days (unfed, n = 15). Handgrip strength, vital capacity, forced expiratory volume in one second (FEV1), and maximal inspiratory pressure (MIP) were measured before surgery and on postoperative days 2, 4, and 6. Fatigue and vigor were evaluated before surgery and on postoperative day 6. Mobility was assessed daily after surgery using a standardized descriptive scale. Postoperative urine biochemistry was evaluated in daily 24-hour collections. RESULTS: Postoperative vital capacity (p < 0.05) and FEV1 (p = 0.07) were consistently lower (18%-29%) in the fed group than in the unfed group, whereas grip strength and maximal inspiratory pressure were not significantly different. Postoperative mobility also was lower in the fed patients (p < 0.05) and tended to recover less rapidly (p = 0.07). Fatigue increased and vigor decreased after surgery (both p < or = 0.001), but changes were similar in the fed and unfed groups. Intensive care unit and postoperative hospital stay did not differ between groups. CONCLUSIONS: Immediate postoperative jejunal feeding was associated with impaired respiratory mechanics and postoperative mobility and did not influence the loss of muscle strength or the increase in fatigue, which occurred after major surgery. Immediate postoperative enteral feeding should not be routine in well-nourished patients at low risk of nutrition-related complications.

Age Factors↗
PubMed1997

Endogenous glucose production following injury increases with age.

To evaluate the influence of aging on the increase in endogenous glucose production that follows injury, we studied 22 fully resuscitated, clinically stable, previously healthy patients aged < or = 30 yr or > or = 60 yr admitted to hospital following injury, and 11 healthy volunteers in the same age groups. Endogenous glucose production was determined using a primed constant infusion of D-glucose-6,6-2d2. Urine cortisol and C-peptide were markedly higher in patients than volunteers (both P < 0.01), and urine C-peptide was lower in older than in younger patients (P < 0.05). Urine cortisol increased as a function of the interaction of age and Injury Severity Score (ISS) (r2 = 0.40, P < 0.001). Intracellular water was markedly lower and extracellular water greater in patients compared with volunteers (both P < 0.001), reflecting the loss of body cell mass and expansion of the extracellular space following injury. Endogenous glucose production (milligrams per minute per liter intracellular water) was best described as a function of ISS and age-ISS interaction (r2 = 0.35, all P < 0.05), and was increased 56% and 78% in younger and older patients, respectively, in comparison with the respective volunteer groups. Endogenous glucose production following injury increases in relation to the severity of injury and patient age. Greater cortisol elaboration and diminished insulin secretion in older patients may contribute to this age effect.

Adult↗
PubMed1996

A new method for blood velocimetry in the microcirculation.

We describe a simple new method for computing two-dimensional velocity vector fields of blood flows in microvascular networks. This method, known as optical flow, requires a time sequence of two or more images obtained by a process such as conventional videomicroscopy. There is no need to distinguish individual cells provided clear variations in the light intensity levels are present in the images. The result of the computation reveals the velocity distribution in the microvascular network and the geometry of the blood vessels. Although various implementations of the optical flow technique exist, we have found that the spatial correlation algorithm of Anandan performs best for microcirculatory flows. This report is an introduction to the application of optical flow to the microcirculation and provides instructions on how to obtain and run the codes.

Blood Circulation Time↗
PubMed1996

Alterations in respiratory mechanics after laparoscopic and open surgical procedures.

OBJECTIVE: To compare the effects of laparoscopic and open surgical procedures on postoperative strength and respiratory mechanics. DESIGN: Prospective cohort study. SETTING: Adult university hospital. PARTICIPANTS: Fifty-one women aged 21 to 62 years scheduled to undergo elective cholecystectomy or hysterectomy (or related procedures), otherwise in good health. INTERVENTIONS: Open or laparoscopic cholecystectomy or hysterectomy (or related procedures). MAIN OUTCOME MEASURES: Maximum voluntary handgrip strength (HGS), forced vital (VC), forced expiratory volume in 1 second (FEV1), and maximal inspiratory pressure (MIP) were each measured preoperatively and on the first postoperative morning. A visual analogue pain scale score was evaluated in relation to performance of the postoperative strength and respiratory measurements. RESULTS: VC, FEV1, and MIP, but not HGS, were decreased after surgery. Postoperative VC, FEV1, and MIP were lower after open procedures than after laparoscopic procedures and after cholecystectomy than after hysterectomy (all p < 0.001). Pain scores were lower after laparoscopic than after open procedures (p < 0.005) and could account in part for differences in postoperative respiratory mechanics. CONCLUSIONS: Cholecystectomy and hysterectomy do not result in generalized muscle weakness, unlike more major abdominal procedures. Postoperative alterations in respiratory mechanics are related to the site of the surgery, the use of an open versus a laparoscopic approach and postoperative pain.

Adult↗
PubMed1996

The influence of age on the severity of peritonitis.

OBJECTIVE: To evaluate the influence of age on the evolution and severity of peritonitis. DESIGN: A chart review. SETTING: An adult university hospital. PATIENTS: One hundred and twenty-two patients with acute appendicitis and 100 patients with acute colonic diverticulitis requiring operation or percutaneous drainage. MAIN OUTCOME MEASURES: Patient age and sex, presence of perforation or gangrene (appendicitis), extent of peritonitis (diverticulitis); duration of symptoms prior to admission; admission leukocyte count; duration of hospitalization before surgery; length of hospital stay; and death rate. RESULTS: Patients with acute appendicitis who were aged 65 years or older were three times more likely than younger patients to have a gangrenous or perforated appendix (odds ratio 3.1, 95% confidence interval 1.1 to 8.4, p < 0.05); older patients with perforated diverticulitis were three times more likely than younger patients to have generalized peritonitis than localized (pericolic or pelvic) peritonitis (odds ratio 2.9, 95% confidence interval 1.2 to 7.5, p < 0.05). CONCLUSION: These findings are consistent with the hypothesis that the biologic features of peritonitis differ in the elderly, who are more likely to present with an advanced or severe process than young patients.

Acute Disease↗
PubMed1996

Aging exaggerates the blood glucose response to total parenteral nutrition.

OBJECTIVE: To determine the effect of age on the blood glucose and insulin responses to a clinical model of glucose loading (i.e., total parenteral nutrition [TPN] with hypertonic glucose), in patients with a variety of conditions. DESIGN: A prospective cohort study. SETTING: An adult university hospital. PATIENTS: Seventy-one consecutive, clinically stable patients receiving central TPN, excluding those with metabolic disease or receiving relevant medications. INTERVENTION: None. MAIN OUTCOME MEASURES: Serum levels of glucose, insulin, C-peptide and cortisol determined in peripheral venous blood obtained immediately before initiating TPN and again 48 to 96 hours later; acute physiology score (APS) and habitual level of physical activity (HAL). RESULTS: Serum levels of glucose, insulin and C-peptide increased following initiation of TPN (all p < 0.001). The serum glucose level during TPN administration increased as a function of both patient age and severity of illness (APS) (r2 = 0.37, all p < 0.01), whereas the serum insulin level was inversely related to age and increased as a function of serum glucose, glucose rate of infusion and HAL (r2 = 0.57, all p < 0.05). The serum C-peptide: insulin molar ratio did not vary with age. CONCLUSIONS: Aging and severity of illness interact to exaggerate the increases in blood glucose that accompany TPN with hypertonic glucose. Serum insulin responses to TPN decline with aging, likely reflecting reduced insulin secretion. Diminished insulin responses may contribute to hyperglycemia and represent a diminished anabolic signal in such patients. The acutely ill elderly patient is predisposed to hyperglycemia and should be monitored carefully even when pre-TPN blood glucose values are normal.

Adult↗
PubMed1994

Critical care for the elderly patient.

Elderly individuals will continue to make up a major portion of patients requiring critical care. Age and chronic disease-related factors blunt the reserves with which the elderly can meet the demands of critical surgical illness. The clinician must remain vigilant to subtle changes in the patient's course which may indicate a developing complication and must pay attention to all the details of comprehensive critical care management. With careful attention and timely physiologic support, the elderly patient has as good a chance of surviving as a similarly ill younger patient, although his or her course may be more prolonged. The priorities are the same. Thus, the primary disease must be addressed: necrotic tissue débrided, pus drained, wounds closed, fractures set. Cardiopulmonary performance (oxygen delivery) must be maintained sufficiently to meet the heightened oxygen needs associated with critical illness. This may require invasive hemodynamic monitoring and pharmacologic support. Gas exchange in the lungs must be maintained without compromising cardiovascular function or exhausting the patient. Patients should be kept warm, pain free, and calm. Intravascular volume and the composition of the extracellular fluid must be maintained. Nutritional support should be provided early in amounts sufficient to meet the patient's basal nutritional requirements and increased needs associated with the critical illness. If at all possible, some or all of this nutritional support should be provided via the gastrointestinal tract. The use of specialized nutrients or of agents designed to minimize the catabolism of critical illness or to enhance anabolism is an area of active investigation. The indications for these therapeutic strategies in the elderly should become clearer in the years ahead.

Aged↗
PubMed1994

Aging exaggerates glucose intolerance following injury.

Hyperglycemia and glucose intolerance are characteristic of both the metabolic responses to injury and normal aging. To evaluate the interaction of such changes we conducted hyperglycemic glucose clamp studies (2-hour) in previously healthy young (20 +/- 4 years, Mean +/- SD) and older (73 +/- 9 years) trauma patients and volunteers (23 +/- 1 and 68 +/- 5 years), determining whole-body glucose disposal and insulin responses to hyperglycemia. Injury Severity Scores were similar in the young and older patient groups (range, 17-30). Plasma glucose levels were greater in patients than volunteers in both the basal and hyperglycemic periods. Basal serum insulin and C-peptide levels were similar among groups, but during hyperglycemia both were markedly higher in young patients than older (and both volunteer groups). Whole-body disposal of exogenous glucose was substantially lower in patients than volunteers and in the older groups. Aging has a major impact on postinjury metabolism, being associated with exaggerated glucose intolerance and diminished insulin responses to glucose infusion. These findings have important implications for the metabolic and nutritional care of older patients following trauma and during critical illness.

Adult↗
PubMed1993

Epidural anaesthesia and analgesia do not affect energy expenditure after major abdominal surgery.

Our objective was to determine the effect of perioperative epidural anaesthesia and analgesia on the increase in energy expenditure which accompanies major elective abdominal surgery in a prospective, randomized study. Eight patients undergoing elective resections of the colon and/or rectum received general anaesthesia alone (nitrous oxide, oxygen, and isoflurane, supplemented with intravenous fentanyl to a maximum of 10 micrograms.kg-1), and 12 patients received perioperative epidural anaesthesia and analgesia using lidocaine (carbonated lidocaine 2% with epinephrine 1:200,000, 20 ml over 30 min) and morphine (preservative-free morphine 0.10 mg.kg-1 after catheter insertion and 0.05 to 0.10 mg.kg-1 every 12 hr as needed until the morning following surgery) via a lower lumbar catheter in addition to general anaesthesia. Respiratory gas exchange was measured using a metabolic cart and canopy system early on the morning of surgery, six hours postoperatively, and on the first and second postoperative mornings. Parenteral analgesic administration (P < 0.001) and visual analogue pain scores (P < 0.05) were lower in the patients receiving epidural anaesthesia and time to first parenteral analgesia was longer (P < 0.005). Oxygen consumption, carbon dioxide production, and energy expenditure increased after surgery (all P < 0.001) but were very similar in the two groups (all P > or = 0.8) before and after surgery. Despite substantial effects on postoperative pain, we conclude that oxygen consumption and energy expenditure following major abdominal surgery are not diminished by perioperative epidural anaesthesia and analgesia.

Aged↗
PubMed1993

Impaired recovery of strength in older patients after major abdominal surgery.

OBJECTIVE: This study compared changes in muscle strength after major elective abdominal surgery in young and old patients, and related these changes to body composition and nitrogen balance. SUMMARY BACKGROUND DATA: The breakdown of muscle protein, erosion of lean tissue, and negative nitrogen balance are characteristic metabolic responses to surgical illness. With a substantial loss of muscle mass typical of advancing age, the authors postulated that older patients would be weaker during acute surgical illness and less able to maintain muscle function and meet metabolic demands. METHODS: Active, community-dwelling individuals undergoing major abdominal procedures who were 70 years of age or older or 50 years of age or younger were studied. Total body water (TBW) was determined preoperatively by deuterium oxide dilution. Maximal voluntary handgrip, respiratory muscle strength, and visual analog pain scores were measured preoperatively and on postoperative days 2, 4, and 6. All urine was collected postoperatively for 7 days for determination of total nitrogen, creatinine, and cortisol. RESULTS: The young (age, 36 +/- 9 years [mean +/- standard deviation]; n = 20) and old groups (age, 77 +/- 5 years; n = 20) were similar regarding weight, sex distribution, nutritional status, surgical procedures and anesthesia, and postoperative urine cortisol values. Age group, time after operation, and interaction effects were significant for each strength variable (all p < 0.005 by analysis of variance). Older patients had lower preoperative strength (29% to 41%) and mean 24-hour urine creatinine (27%). Postoperative strength was decreased most markedly on postoperative day 2, with similar proportional changes in the two age groups but lower absolute levels in the older patients. The rate of recovery of strength was substantially less rapid and complete in older patients. Older patients had less postoperative pain and received much less parenteral narcotic than younger patients. Postoperative urine nitrogen was similar in each group. Recovery of strength was not related to malignancy, preoperative strength, muscle mass (urine creatinine), lean body mass (TBW), sex, malignancy, pain, or narcotic administration. CONCLUSIONS: Older patients are weaker preoperatively than younger patients; their strength falls to lower levels after surgery and their postoperative recovery of strength is impaired. The lesser preoperative strength of older patients is due in large part but not totally to diminished muscle mass. Their impaired postoperative recovery appears to be related to more acute factors, such as muscle energetics or substrate availability.

Abdomen↗
PubMed1993

Uptake of glucose during continuous arteriovenous hemofiltration.

OBJECTIVE: To quantify glucose balance related to continuous arteriovenous hemofiltration (CAVH) when a glucose-rich replacement fluid is used for the plasma ultrafiltrate removed. DESIGN: Prospective, nonintervention study. SETTING: Medical/surgical and cardiac surgical intensive care units of a university hospital. PATIENTS: Critically ill patients (n = 20) with acute oliguric renal failure undergoing CAVH. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Timed collections of CAVH effluent were analyzed and other observations were made. Serum creatinine and blood urea nitrogen concentrations decreased substantially during CAVH in each patient. The mean measured glucose concentration of the replacement fluid (Dianeal 1.5%) was 1.40 +/- 0.11 (SD) g/dL (77 +/- 6 mmol/L) and rate of infusion was 1.39 +/- 0.43 L/hr. Effluent volume was 1.51 +/- 0.49 L/hr and glucose was 0.47 +/- 0.10 g/dL (26 +/- 5 mmol/L). The glucose content of the replacement fluid infused was consistently and substantially greater than that value of the effluent removed during the same period. Thus, the average net glucose uptake in relation to the CAVH circuit was 11.9 +/- 3.1 g/hr (range 4.3 to 17.6). Serum glucose concentrations increased in each patient with initiation of CAVH (from 135 +/- 44 to 278 +/- 80 mg/dL [7.4 +/- 2.4 to 15.3 +/- 4.4 mmol/L]; p < .001). Negative fluid balance achieved during CAVH was approximately 100 mL/hr. CONCLUSIONS: CAVH using predilution with replacement fluid is effective in managing uremia and fluid overload in critically ill patients. The use of a glucose-rich replacement fluid is accompanied by the net uptake of large amounts of glucose, approaching 300 g/day on average in our patients and representing a major exogenous calorie source. This finding has important implications for the metabolic management of critically ill patients during CAVH and should be taken into account in prescribing their nutritional support.

Acute Kidney Injury↗
PubMed1991

Preventive measures in the elderly surgical patient.

The death rates associated with all forms of surgical illness increase consistently with age but appear more closely related to physiologic and medical status than to age per se. Changes in physiologic function with advancing age are marked by a decreased sensitivity to perturbations and a decreased efficiency of homeostatic mechanisms. Recognition of the heterogeneity of the aging process is fundamental to appropriate decision-making in the elderly surgical patient and thus to avoiding complications. Careful preoperative assessment of medical problems and potential age-related changes in physiologic function, preoperative orientation and teaching, consideration of deep venous thrombosis prophylaxis, effective pain management, early postoperative mobilization and careful attention to drug and fluid and electrolyte therapy are essential in management of the elderly surgical patient.

Aged↗
PubMed1990

Effects of age and body composition on the metabolic responses to elective colon resection.

Advancing age tends to be accompanied by predictable changes in organ-system function and body composition, as well as an increased prevalence of various diseases. Our knowledge of the metabolic responses to surgical stress is derived largely from studies of young and middle-aged individuals. Whether these responses are altered in the elderly is not well established; the characteristic changes in metabolic function and body composition that occur in the elderly may limit their ability to respond adequately and to survive severe or complicated surgical procedures. To evaluate the effects of age and differences in body composition on the metabolic responses to surgery, we studied 20 active and otherwise healthy men aged 43 to 77 years, before and after elective colon resection. Age was not related to weight or total body water (TBW) in the patients studied. Resting preoperative energy expenditure was strongly dependent on TBW (reflecting lean body mass) and age (r2 = 0.80, p less than 0.001), and to TBW and creatinine excretion (reflecting muscle mass) (r2 = 0.85, p less than 0.001). Energy expenditure increased 18 +/- 2% (range, 4% to 40%) after operation but this response was unrelated to age. Postoperative urine nitrogen was related to body weight or TBW, but not to age. Serum glucose, cortisol, white blood cell count count, and C-reactive protein responses were also independent of patient age. The metabolic responses of generally healthy men to a moderate surgical stress do not vary with age in the range studied. The metabolic responses to more severe or prolonged stress may be altered with advancing age and changes in body composition, and in patients with concomitant diseases.

Adult↗
PubMed1990

Trauma outcome analysis of two Canadian centres using the TRISS method.

In this retrospective study, the TRISS method of trauma care analysis is used to compare trauma care at the Hamilton General Hospital (HGH) and the Ottawa Civic Hospital (OCH) with the standards reported in the Major Trauma Outcome Study (MTOS). A total of 274 adult patients with multiple-system injuries were studied; their demographic data, Trauma Scores (TS) on arrival to the Emergency Room, and Injury Severity Scores (ISS) were reviewed. The TRISS scores and Z and M statistics were then calculated. In the Hamilton group, 106 consecutive patients from April through July 1987 were studied. The majority of patients (72%) were male, and the median age was 26 years. The majority of patients (96.2%) sustained blunt trauma, with motor vehicle accidents (MVA) being the most common (76.4%) mechanisms of injury. Fifty-four (51%) of the patients were transferred from outlying hospitals. The Z and M statistics were -0.05 and 0.92, respectively. In the Ottawa group, 168 consecutive patients from April 1987 through October 1988 were studied. The majority of patients (73%) were male, and the median age was 39 years. Blunt trauma accounted for the majority (91.7%) of injuries, with MVAs being responsible for 58% of injuries. Most patients (63.5%) were transferred from regional hospitals. The Z and M statistics were 1.20 and 0.56, respectively. We conclude that the survival statistics of trauma patients treated at both centres are comparable to those of trauma patients in the MTOS.

Adult↗
PubMed1989

Hyperglycemia after trauma increases with age.

The metabolic responses to trauma and surgery have been well described and are observed most typically in otherwise healthy young and middle-aged individuals. To investigate the effect of age on blood glucose, insulin, and cortisol responses after mild to moderate trauma, we studied 33 patients (Injury Severity Scores, 5-38, and ages 16 to 81 years) before resuscitation and 24-96 hours postinjury. Age was associated with an increase in serum glucose during both "ebb" and "flow" phases of the injury response, but not with serum insulin. Serum glucose also increased with the degree of injury as reflected in Glasgow Coma Scale on admission and Injury Severity Score subsequently. Serum cortisol responses were increased in older patients and tended to decrease with time following injury. A more detailed knowledge of how age may alter the ability of elderly patients to respond to trauma and critical illness is essential to allow the continued development of rational therapies for such patients.

Adolescent↗
PubMed1988

Inhibition of cyclo-oxygenase attenuates the metabolic response to endotoxin in humans.

Acute infection initiates fever, acute-phase changes, and catabolic responses in the host, resulting in weight loss, hypermetabolism, and accelerated proteolysis. To test the hypothesis that cyclo-oxygenase inhibition might attenuate these responses, we administered Escherichia coli endotoxin intravenously to seven normal volunteers and to seven additional subjects pretreated with a cyclo-oxygenase inhibitor (ibuprofen). Control studies were also performed following administration of saline and ibuprofen alone. Vital signs, metabolic rate, and concentrations of pituitary and stress hormones, as well as those of other substrates, were serially measured. Endotoxin administration produced a response similar to an acute illness, with flulike symptoms, fever, tachycardia, increased metabolic rate, and stimulation of stress hormone release. These changes were markedly attenuated by cyclo-oxygenase inhibition. The leukocytosis, hypoferremia, and elevation of the C-reactive protein level induced by endotoxin were unaffected by cyclo-oxygenase inhibition. These data indicate that activation of the cyclooxygenase pathway is necessary to produce many of the metabolic changes observed during critical illness.

Adult↗