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Biomedical subjects

R Christensen

Publications and source records attributed to R Christensen.

At least 55 records · Page 3Linked to original sources

Thermoregulatory vasoconstriction and perianesthetic heat transfer.

Heat transfer between the core and its environment in normothermic and slightly hypothermic situations is determined largely by the influence of vasomotion on convection. Tonic vasoconstriction, the normal barrier to heat loss from the core, is impaired upon induction of anesthesia. The resulting dilation of the arteriovenous shunts leads to redistribution of heat from the core to the periphery, diminishing the temperature gradient between the two compartments. With reemergence of thermoregulatory vasoconstriction at core temperatures near 34 degrees C, the core and the periphery are again separated, with metabolic heat being largely constrained to the core. Under normal conditions of mild thermal stress, thermoregulatory vasoconstriction is thus able to protect core temperature by reducing cutaneous heat transfer and functionally isolating the peripheral and core thermal compartments. Consequently, anesthetic-induced alterations in vasomotor tone is one of the major factors influencing core temperature in patients who are not actively cooled or warmed. In contrast, thermoregulatory tone is insufficient to prevent core temperature perturbations in patients undergoing vigorous cutaneous cooling or warming.

Anesthesia, General↗

Results of a phase I/II trial of recombinant human granulocyte-macrophage colony-stimulating factor in very low birthweight neonates: significant induction of circulatory neutrophils, monocytes, platelets, and bone marrow neutrophils.

Neonates, especially those of very low birthweight (VLBW), have an increased risk of nosocomial infections secondary to deficiencies in development. We previously demonstrated that granulocyte-macrophage colony-stimulating factor (GM-CSF) production and mRNA expression from stimulated neonatal mononuclear cells are significantly less than that from adult cells. Recombinant murine GM-CSF administration to neonatal rats has resulted in neutrophilia, increased neutrophil production, and increased survival of pups during experimental Staphylococcus aureus sepsis. In the present study, we sought to determine the safety and biologic response of recombinant human (rhu) GM-CSF in VLBW neonates. Twenty VLBW neonates (500 to 1,500 g), aged < 72 hours, were randomized to receive either placebo (n = 5) or rhuGM-CSF at 5.0 micrograms/kg once per day (n = 5), 5.0 micrograms/kg twice per day (n = 5), or 10 micrograms/kg once per day (n = 5) given via 2-hour intravenous infusion for 7 days. Complete blood counts, differential, and platelet counts were obtained, and tibial bone marrow aspirate was performed on day 8. Neutrophil C3bi receptor expression was measured at 0 and 24 hours. GM-CSF levels were measured by a sandwich enzyme-linked immunosorbent assay at 2, 4, 6, 12, and 24 hours after the first dose of rhuGM-CSF. At all doses, rhuGM-CSF was well tolerated, and there was no evidence of grade III or IV toxicity. Within 48 hours of administration, there was a significant increase in the circulating absolute neutrophil count (ANC) at 5.0 micrograms/kg twice per day and 10.0 micrograms/kg once per day, which continued for at least 24 hours after discontinuation of rhuGM-CSF. When the ANC was normalized for each patient's first ANC, there was a significant increase in the ANC on days 6 and 7 at each dose level. By day 7, all tested doses of rhuGM-CSF resulted in an increase in the absolute monocyte count (AMC) compared with placebo-treated neonates. In those receiving rhuGM-CSF 5.0 micrograms/kg twice per day, there was additionally a significant increase in the day 7 and 8 platelet count. Tibial bone marrow aspirates demonstrated a significant increase in the bone marrow neutrophil storage pool (BM NSP) at 5.0 micrograms/kg twice per day and 10.0 micrograms/kg once per day. Neutrophil C3bi receptor expression was significantly increased 24 hours after the first dose of rhuGM-CSF at 5.0 micrograms/kg once per day. The elimination half-life (T1/2) of rhuGM-CSF was 1.4 +/- 0.8 to 3.9 +/- 2.8 hours.(ABSTRACT TRUNCATED AT 400 WORDS)

Birth Weight↗

Midazolam minimally impairs thermoregulatory control.

Perioperative hypothermia usually results largely from pharmacologic inhibition of normal thermoregulatory control. Midazolam is a commonly used sedative and anesthetic adjuvant whose thermoregulatory effects are unknown. We therefore tested the hypothesis that midazolam administration impairs thermoregulatory control. Eight volunteers were studied on 2 days each, once without drug and once at a target total plasma midazolam concentration of 0.3 micrograms/mL (corresponding to administration of approximately 40 mg over approximately 4 h). Each day, skin and core temperatures were increased sufficiently to provoke sweating, and then reduced to elicit peripheral vasoconstriction and shivering. We mathematically compensated for changes in skin temperature using the established linear cutaneous contributions to control of each response. From these calculated thresholds (core temperatures triggering responses at a designated skin temperature of 34 degrees C), we determined the thermoregulatory effects of midazolam. The sweating threshold was decreased approximately 0.3 degrees C by midazolam administration: 37.3 +/- 0.2 degrees C vs 37.0 +/- 0.3 degrees C (P = 0.0004, paired t-test). Midazolam decreased the core temperature that triggered vasoconstriction somewhat more: 37.1 +/- 0.2 degrees C vs 36.3 +/- 0.5 degrees C (P = 0.0002). Similarly, midazolam decreased the shivering threshold: 35.9 +/- 0.3 degrees C vs 35.3 +/- 0.6 degrees C (P = 0.03). The sweating-to-vasoconstriction (interthreshold) range, therefore, increased from 0.2 +/- 0.1 degrees C to 0.7 +/- 0.3 degrees C (P = 0.002). Although statistically significant, this relatively small increase contrasts markedly with the 3-5 degrees C interthreshold ranges produced by clinical doses of volatile anesthetics, propofol, and opioids.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Heat balance and distribution during the core-temperature plateau in anesthetized humans.

BACKGROUND: Once triggered, intraoperative thermoregulatory vasoconstriction is remarkably effective in preventing further hypothermia. Protection results from both vasoconstriction-induced decrease in cutaneous heat loss and altered distribution of body heat. However, the independent contributions of each mechanism have not been quantified. Accordingly, we evaluated overall heat balance and distribution of heat within the body during the core-temperature plateau. METHODS: Nine minimally clothed male volunteers were anesthetized with propofol and isoflurane and maintained in an approximately 22 degrees C environment. They were monitored for approximately 2 h before vasoconstriction and for 3 h subsequently. Overall heat balance was determined from the difference between cutaneous heat loss (thermal flux transducers) and metabolic heat production (oxygen consumption). Arm and leg tissue heat contents were determined from 19 intramuscular temperatures, ten skin temperatures, and "deep" foot temperature. Heat constrained by vasoconstriction to the trunk and head was calculated by subtracting the expected change in that region (overall heat balance multiplied by the fractional weight of the trunk and head) from the actual change (change in distal esophageal temperature multiplied by the specific heat of human tissue and the weight of the trunk and head); the result represents the amount by which core heat exceeded that which would be expected based on overall heat balance, assuming that the change was evenly distributed throughout the body. RESULTS: Vasoconstriction and passive tissue cooling decreased heat loss but not to the level of heat production. Consequently, heat loss exceeded metabolic heat production throughout the study. Core temperature decreased approximately 1.3 C during the 2-h prevasoconstriction period; however, core temperature remained virtually constant during the subsequent 3 h. In the 3 h after vasoconstriction, arm and leg heat content decreased 57 +/- 9 kcal, and vasoconstriction constrained 22 +/- 8 kcal to the trunk and head. CONCLUSIONS: These results confirm the efficacy of thermo-regulatory vasoconstriction in preventing additional core hypothermia. Decreased cutaneous heat loss and constraint of metabolic heat to the core thermal compartment contributed to the plateau.

Adult↗

Heat flow and distribution during epidural anesthesia.

BACKGROUND: Core hypothermia after induction of epidural anesthesia results from both an internal core-to-peripheral redistribution of body heat and a net loss of heat to the environment. However, the relative contributions of each mechanism remain unknown. The authors thus evaluated regional body heat content and the extent to which core hypothermia after induction of anesthesia resulted from altered heat balance and internal heat redistribution. METHODS: Twelve minimally clothed male volunteers were evaluated in a approximately 22 degrees C environment for 2.5 control hours before induction of epidural anesthesia and for 3 subsequent hours. Epidural anesthesia produced a bilateral sympathetic block in only six volunteers, and only their results are reported. Shivering, when observed, was treated with intravenous meperidine. Overall heat balance was determined from the difference between cutaneous heat loss (thermal flux transducers) and metabolic heat production (oxygen consumption). Arm and leg tissue heat contents were determined from 19 intramuscular needle thermocouples, 10 skin temperatures, and "deep" foot temperature. To separate the effects of redistribution and net heat loss, we multiplied the change in overall heat balance by body weight and the specific heat of humans. The resulting change in mean body temperature was subtracted from the change in esophageal or tympanic membrane (core) temperatures, leaving the core hypothermia specifically resulting from redistribution. RESULTS: Arm heat content decreased approximately 5 kcal/h after induction of anesthesia, but leg heat content increased markedly. Most of the increase in leg heat content was in the lower legs and feet. Core temperature increased slightly during the control period but decreased 0.8 +/- 0.3 degrees C in the 1st hour of anesthesia. Redistribution, contributing 89% to this initial decrease, required a net transfer of 20 kcal from the trunk to the extremities. During the subsequent 2 h of anesthesia, core temperature decreased an additional 0.4 +/- 0.3 degrees C, with redistribution contributing 62%. Thus, only 7 kcal were redistributed during the 2nd and 3rd hours of anesthesia. Redistribution therefore contributed 80% to the entire 1.2 +/- 0.3 degrees C decrease in core temperature during the 3 h of anesthesia. CONCLUSIONS: Core hypothermia during the 1st hour after induction of epidural anesthesia resulted largely from redistribution of body heat from the core thermal compartment to the distal legs. Even after 3 h of anesthesia, redistribution remained the major cause of core hypothermia. Despite the greater fractional contribution of redistribution during epidural anesthesia, core temperature decreased only half as much as during general anesthesia because metabolic rate was maintained and the arms remained vasoconstricted.

Adjuvants, Anesthesia↗

Institutional respite care: benefits and risks for dementia patients and caregivers.

Thirty-seven dementia patients and their caregivers were studied before and after a two-week in-hospital respite stay. Institutional respite care did not alter behavior problems in dementia patients, nor did changes in performance of activities of daily living (ADLs) by Alzheimer's disease (AD) patients exceed those expected from disease progression. Caregivers exhibited an improvement in burden and depression during the respite study, but levels returned to baseline following the patient's return home.

Activities of Daily Living↗

Liver Biopsies Following Ileogastrostomy.

Patients who have had ileogastrostomy for the treatment of morbid obesity require close, long-term follow-up. One concern in patients undergoing any form of intestinal bypass surgery is that of possible liver damage. To assess for possible liver damage in morbidly obese patients undergoing ileogastrostomy, we undertook a prospective study of liver biopsies in 12 consecutive patients. Preoperative and 2-year postoperative biopsies of the liver were planned. There were six liver biopsies available for comparison both pre- and post-operatively. The biopsies showed changes of fatty infiltration both pro- and post-operatively. There were no differences in the degree of fatty infiltration, or of other histological parameters which we measured. There were no cases of cirrhosis of the liver recorded.

Journal Article↗

Stability of flumazenil with selected drugs in 5% dextrose injection.

The compatibility and stability of flumazenil mixed with aminophylline, dobutamine hydrochloride, dopamine hydrochloride, cimetidine hydrochloride, famotidine, ranitidine hydrochloride, heparin sodium, lidocaine hydrochloride, or procainamide hydrochloride were studied. Flumazenil (1.0 mg) was mixed with each of the other drugs in polyvinyl chloride minibags containing 50 mL of 5% dextrose injection to achieve concentrations commonly used when the drugs are administered by continuous i.v. infusion. All admixtures were analyzed for color change, pH, and particulate matter. Flumazenil concentrations were measured by a stability-indicating high-performance liquid chromatographic assay at baseline and 2, 4, 8, 12, and 24 hours after mixing. No detectable changes in color, pH, or particulate matter were observed. In the presence of each drug except dopamine hydrochloride, at least 95% of initial flumazenil concentration was present 24 hours after mixing. Flumazenil in the presence of dopamine hydrochloride was stable for 12 hours. Flumazenil was visually compatible and chemically stable when admixed with 5% dextrose injection and selected drugs.

Chemistry, Pharmaceutical↗

Pancreatic duct obstruction treated with percutaneous antegrade insertion of a metal stent: report of two cases.

Expanding metal stents were used to treat symptomatic pancreatic duct obstruction in two patients with chronic pancreatitis. Both patients initially underwent percutaneous external pancreatic duct drainage and then had metal stents inserted for internal drainage. Both patients remained asymptomatic, and the stents were patent during short-term follow-up periods of 6 and 9 months, respectively. Percutaneous insertion of metal stents, which can be performed to treat pancreatic duct obstruction after a trial of external drainage has been shown to relieve the patient's symptoms, should be considered as an alternative to endoscopic stent placement or surgical drainage.

Aged↗

The Mechanism of Weight Loss after Ileo-gastrostomy for Morbid Obesity.

Twelve patients (weight 107-178 kg and age range 19-43 years) were investigated following ileo-gastrostomy for morbid obesity. A number of variables were studied prospectively, pre- and postoperatively, to determine the cause of weight loss-previously attributed to malabsorption or decreased caloric intake. Weight loss of 10.9-36.5 kg, mean 22.9 kg, occurred. Three-day calorie counts demonstrated a postoperative decrease in daily caloric consumption of 320-3870, mean 1975 cal. Analysis of body compartment composition after derivation of lean body mass (from calculation of total body water with tritiated water) showed a mean decrease in adipose tissue of 17.7 kg. Postoperative weight loss, mainly fat, could not all be accounted for by decreased caloric consumption or steatorrhea (72-h stool fat increased by a mean of 30 g). Pulmonary studies showed no significant change in respiratory quotient, but a large decrease in both postoperative utilization of oxygen and the production of carbon dioxide. This may indicate an alternate, anaerobic, energy cycle utilization. Other statistically significant variables included a large fall in cholesterol, LDH cholesterol and triglycerides, and smaller decrease in HDL cholesterol. Changes in gastro-intestinal (GI) hormones and cell counts in stomach and small intestine were also measured and will be reported later.

Journal Article↗