Biomedical subjects

W T Phillips

Publications and source records attributed to W T Phillips.

At least 37 records · Page 2Linked to original sources

PubMed1997

Platelet reactivity with liposome-encapsulated hemoglobin in the rat.

Infusion of liposome-encapsulated hemoglobin (LEH) induces a transient thrombocytopenia in rats (Rabinovici R, Rudolph AS, Ligler FS, Smith EF, III, Feuerstein G [1992] Biological responses to exchange transfusion with liposome-encapsulated hemoglobin. Circ Shock 37:124). A specific mechanism such as a localization of platelets during this transient LEH-induced thrombocytopenia has not been reported previously in the literature. In this study, platelets were isolated and labeled with indium-111 (111In), then retransfused into the same animal. Fifteen minutes after the 111In platelets were retransfused and allowed to equilibrate with the blood pool, a 10% top load volume of either LEH (1.8 mL, 262 mg phospholipid/kg body weight, 92 mg hemoglobin (Hb)/kg body weight), liposome vehicle (LV) (1.8 mL, 262 mg phospholipid/kg body weight), or free bovine Hb (1.8 mL, 92 mg Hb/kg body weight) (n=6 per group) was infused. Serial blood samples were drawn to determine platelet counts by radioactivity and light scattering methods. LV and Hb demonstrated no significant changes from baseline levels in circulating platelet levels, whereas LEH caused a transient 50% decrease in 111In platelet activity 2-5 minutes postinfusion, which returned to baseline levels by 15 minutes. Platelet counts based on traditional light scattering methods were not significantly different among the three treatment groups over this same time course. Localization of these 111In platelets was monitored with a gamma scintigraphic camera. After infusion of LEH, 111In platelets rapidly moved out of the circulation and sequestered in the lungs and liver with subsequent return to the circulation by 15 minutes. In contrast, no significant changes in 111In platelet activity were noted in the lungs and liver after infusion of LV and Hb. 111In platelet activity in the spleen nearly doubled 30 minutes after Hb infusion and was significantly different than spleen 111In platelet activity in the LEH and LV groups. In vitro platelet aggregation studies were also performed to determine the direct effect of LEH, LV, and Hb on platelet aggregation. The rate of thrombin-induced aggregation did not differ among control samples and samples containing LEH, LV, or Hb; none of these agents induced platelet aggregation. We conclude that LEH-induced thrombocytopenia is associated with a transient (within minutes) sequestration of platelets in the lungs and liver, with subsequent release to the circulation within 15 minutes. Tetrameric bovine Hb is associated with increased platelet accumulation in the spleen. Light scattering methods for measuring platelet levels in blood samples containing LEH are unreliable because of particulate interference.

Animals↗

PubMed1996

Gastric emptying of beer in Mexican-Americans compared with non-Hispanic whites.

Gastric emptying studies were performed on 11 nondiabetic Mexican-Americans and 11 nondiabetic non-Hispanic whites following ingestion of 450 mL beer. Plasma glucose, serum insulin, and serum alcohol levels were measured in the fasting state and at 7, 15, 30, 45, and 60 minutes following ingestion of the beer. The area under the gastric emptying curve was significantly larger for non-Hispanic whites compared with Mexican-Americans (P = .0492), indicating that Mexican-Americans had faster stomach emptying. Partial correlation coefficients (adjusted for ethnicity, gender, age, and body mass index [BMI]) showed the gastric half-emptying time was inversely related to the incremental levels of glucose (r = -.709, P = .0010) and alcohol (r = -.650, P = .0035). The faster the rate of gastric emptying of beer, the higher the glucose and alcohol levels. There were no significant correlations between insulin and the rate of gastric emptying. The caloric emptying rate for the beer was much more rapid than previously reported for other liquid meals.

Adult↗

PubMed1996

Pancreatic secretion stimulated by CCK is not mediated by capsaicin-sensitive vagal afferent pathway in awake rats.

A capsaicin-sensitive vagal afferent pathway was reported to mediate the effect of endogenous cholecystokinin (CCK) on pancreatic secretion in anesthetized rats. Because neural blockade affects pancreatic secretion much less in awake than in anesthetized rats, the effect of capsaicin ablation of vagal afferent pathways on pancreatic secretion stimulated by endogenous CCK was examined in awake rats. During surgery, abdominal vagal trunks were exposed, and 0.1 ml of capsaicin (10 mg/ml) was applied to the vagal trunks. Ablation of the vagal afferent pathway was assessed by the ability of intraperitoneal cholecystokinin octapeptide (CCK-8) to suppress food intake and inhibit gastric emptying. Endogenous CCK release was stimulated by diversion of bile pancreatic juice from the intestine and by intraduodenal infusion of casein. Pancreatic protein and fluid secretion were significantly increased by both treatments, and the responses were unaffected by capsaicin. Intraperitoneal CCK-8 markedly inhibited food intake and gastric emptying, and both effects were significantly attenuated in capsaicin-treated rats, indicating that capsaicin treatment successfully ablated vagal afferent fibers. It is concluded that CCK-stimulated pancreatic secretion in rats is not mediated by a vagal afferent pathway.

Afferent Pathways↗

PubMed1996

Lifestyle activity. Current recommendations.

An accumulation of international scientific evidence indicates that physical inactivity is detrimental to health and that moderate levels of physical activity confer significant health benefits. Unfortunately, in countries where major surveys of physical activity have been conducted, the prevalence of sedentary behaviour has been found to be as high as 40%. In the US, where approximately 30% of adults report little or no physical activity, the Centers for Disease Control and the American College of Sports Medicine recently issued guidelines and recommendations on the amount and frequency of moderate levels of physical activity necessary to elicit health benefits in predominantly sedentary adults. These guidelines utilise a physical activity-health paradigm and, uniquely, recommend the potential effectiveness of activities of daily living or "lifestyle activity' for achieving health benefits. This article briefly reviews the rationale behind these guidelines and, in view of the historical association of the exercise training-fitness model to health, highlights some challenges and potential problems in applying these new guidelines to the general population.

Adult↗

PubMed1996

Rapid gastric emptying of a solid pancake meal in type II diabetic patients.

OBJECTIVE: To estimate the rate of gastric emptying of a solid pancake carbohydrate meal in recently diagnosed asymptomatic type II diabetic patients compared with nondiabetic control subjects. RESEARCH DESIGN AND METHODS: Gastric emptying studies using radiolabeled meals were performed on eight recently diagnosed asymptomatic diabetic patients and on eight sex-, BMI- and age-matched nondiabetic control subjects. Although a liquid protein drink was administered along with the pancake meal, the radioactivity was adherent to only the pancake portion of the meal. Plasma glucose and serum insulin levels were measured in fasting and postprandial blood samples collected at 15-min intervals up to 120 min after ingestion of the mixed nutrient meal. RESULTS: The average gastric half-emptying time (time it takes for one-half of the meal to empty) was significantly more rapid for the diabetic patients (45.3 +/- 4.8 min) when compared with the nondiabetic control subjects (60.4 +/- 5.1 min; P = 0.05). The serum insulin concentrations were not statistically different between the two groups. Plasma glucose values were significantly higher in the diabetic patients compared with the nondiabetic control subjects. CONCLUSIONS: Type II diabetic patients with no clinical evidence of neuronal dysfunction have a significantly more rapid rate of gastric emptying of a solid high-carbohydrate meal when compared with nondiabetic control subjects.

Adult↗

PubMed1996

Blood-pool imaging using technetium-99m-labeled liposomes.

UNLABELLED: This study evaluated two 99mTc-liposome formulations as potential blood-pool agents in comparison with standard 99mTc-red cells and 99mTc-human serum albumin (HSA). METHODS: Liposomes with no surface modification or coated with polyethylene glycol (PEG) were labeled with 99mTc using the lipophilic chelator, HMPAO. Autologous red cells were labeled with 99mTc using in vitro or in vivo techniques. Technetium-99m-HSA was supplied commercially. Rabbits were injected intravenously with 99mTc-liposomes, 99mTc-red cells or 99mTc-HSA. Static images were acquired and blood samples collected. RESULTS: Technetium-99m-liposome images showed prominent blood-pool activity compared to lung and liver activities, which were similar to those acquired for 99mTc-red cells, but better than 99mTc-HSA. Heart-to-lung ratios were not significantly different between 99mTc-liposome formulations or for either formulation compared to 99mTc-red cells. The ratios were higher, however, than for 99mTc-HSA. Heart-to-liver ratios were higher for PEG 99mTc-liposomes than they were for neutral 99mTc-liposomes and 99mTc-HSA, but were not significantly different than 99mTc-red cells. Bladder activities for both 99mTc-liposome formulations were 3-6 times lower than for the other agents. PEG 99mTc-liposomes remained in circulation 1.6 times longer than any of the other agents. CONCLUSIONS: Technetium-99m-liposomes, independent of surface modification, had excellent circulation persistence and in vivo stability when compared to 99mTc-red cells and 99mTc-HSA. PEG 99mTc-liposomes performed better than neutral 99mTc-liposomes due to lower liver background activity. Advantages of PEG 99mTc-liposomes compared to 99mTc-red cells include: (a) only one venipuncture, (b) little exposure to patient's blood, (c) excellent in vitro and in vivo stability and (d) lack of drug interference.

Animals↗

PubMed1996

Decelerating gastric emptying: therapeutic possibilities in type 2 diabetes.

There is clear evidence of a positive correlation between carbohydrate absorption, plasma concentration of glucose, and the rate of gastric emptying. This suggests that clinical manipulation of gastric emptying rates may have therapeutic potential in glycaemic control. Cholecystokinin (CCK-8) has been shown to delay gastric emptying in individuals with Type 2 diabetes, but its potential as a therapy is limited by the need to administer it intravenously. The preferred routes of administration would be intramuscular injections, an intranasal spray or the use of orally ingested CCK analogues. Alternatively, the oral administration of an agent that enhances endogenous release of CCK could represent an important approach to the treatment of Type 2 diabetes. Agents such as POT II may have a therapeutic indication in patients with recently diagnosed Type 2 diabetes.

Blood Glucose↗

PubMed1996

Use of a physiologic oral glucose solution for screening for impaired glucose tolerance and non-insulin-dependent diabetes mellitus.

OBJECTIVE: To evaluate a lower osmolar, more physiologic oral glucose solution as part of an oral glucose tolerance test and to compare it to the standard glucose solution to see if it could serve as an effective screening agent for patients with impaired glucose tolerance or non-insulin-dependent diabetes mellitus. METHODS: A total of 100 subjects were given both the standard (1.38 mol/L) 75-g oral glucose tolerance test solution and the lower osmolar (0.62 mol/L) 50-g glucose solution. Each test was separated by at least 3 days. Blood samples were drawn at baseline and 30, 60, and 120 minutes after ingestion of each glucose solution. The 1- and 2-hour blood glucose values obtained using the 75-g oral glucose tolerance test beverage were used as the gold standard to diagnose diabetes according to World Health Organization criteria. RESULTS: Both solutions were shown to have a high sensitivity and specificity for detecting diabetes and impaired glucose tolerance at 30 and 60 minutes. CONCLUSIONS: The physiologic 50-g solution uses less glucose, is highly palatable, and is similar in sweetness and carbohydrate concentration to commonly consumed soda beverages. A larger study including more patients with impaired glucose tolerance will need to be performed to verify our conclusions. The ability to perform high-sensitivity and high-specificity screening for patients with diabetes or impaired glucose tolerance with a single timed blood sample could make mass screening more practical.

Adolescent↗

PubMed1995

Anterior, posterior, left anterior oblique, and geometric mean views in gastric emptying studies using a glucose solution.

Previous research has shown that the single anterior view of the stomach overestimates the gastric half-emptying time of a solid meal compared to the geometric mean of the anterior and posterior views. Little research has been performed comparing the various views of gastric emptying of a glucose solution. After an overnight fast, 49 nondiabetic subjects were given a 450 ml solution containing 50 g of glucose and 200 microCi of technetium-99m sulfur colloid. Sequential 1-min anterior, posterior, and left anterior oblique views were obtained every 15 min. The mean percent solution remaining in the stomach for all three views differed from the geometric mean by 1.9% or less at all time points. Average gastric half-emptying times were: geometric mean, 62.7 +/- 3.3 min; anterior, 61.9 +/- 3.2 min; posterior, 63.5 +/- 3.5 min; and left anterior oblique, 61.6 +/- 3.3 min. These half-emptying times were not statistically different. For individual patients, differences between all three views and the geometric mean were not clinically important. Approximately 95% of all patients are expected to have gastric half-emptying times measured by any of the three single views within 17 min of the gastric half-emptying time obtained using the geometric mean. The imaging of gastric emptying using glucose solutions can be performed using a convenient single view which allows continuous dynamic imaging.

Adult↗

PubMed1995

Gastric emptying in Mexican Americans compared to non-Hispanic whites.

Mexican Americans, a group at high risk for type II diabetes mellitus, have higher postprandial insulin and glucose levels when compared to non-Hispanic whites. A rapid rate of gastric emptying contributes to an increased rate of nutrient absorption and subsequent greater elevation of postprandial glucose and insulin levels. A more rapid rate of gastric emptying and hyperinsulinemia have been observed in patients with recently diagnosed type II diabetes mellitus. In this study, we examined whether Mexican Americans have a more rapid rate of gastric emptying than non-Hispanic whites. Gastric emptying studies were performed on 32 nondiabetic Mexican Americans and on 31 nondiabetic non-Hispanic whites. The rate of gastric emptying following a liquid glucose meal was measured. Serum insulin, plasma glucose, and GIP levels were measured in fasting and postprandial blood samples collected at 15-min intervals for 2 hr. Adjusting for age, body mass index, and gender, the gastric half-emptying time of a glucose meal was significantly (P < 0.05) more rapid for the Mexican American subjects (56.5 +/- 3.4 min) compared to the non-Hispanic white subjects (66.4 +/- 3.5 min). Nondiabetic Mexican Americans empty a liquid glucose meal more rapidly from their stomachs than nondiabetic non-Hispanic whites. Rapid gastric emptying is associated with hyperinsulinemia as a normal physiologic response to increased nutrient availability. The rapid gastric emptying observed in nondiabetic Mexican Americans is associated with hyperinsulinemia and could be a contributing factor for the increased risk of obesity and type II diabetes in this population.

Blood Glucose↗

PubMed1995

Physiological responses, organ distribution, and circulation kinetics in anesthetized rats after hypovolemic exchange transfusion with technetium-99m-labeled liposome-encapsulated hemoglobin.

Physiological responses and circulation properties of liposome-encapsulated hemoglobin (LEH) labeled with technetium-99m (99mTc) were measured in rats after a 10% (170 mg/kg hemoglobin; 430 mg/kg phospholipid) or a 50% (450 mg/kg hemoglobin, 2.3 g/kg phospholipid) hypovolemic exchange transfusion (n = 5 per exchange group). Mean arterial pressure returned to baseline values (105 +/- 8 mmHg) by 90 min post-infusion for both groups. By 20 h, mean arterial pressure remained at baseline values for the 10% group, but dropped to 30 +/- 14 mmHg for the 50% group. For both groups, bradycardia was seen after the exchange period, but heart rate recovered by 30 min for the 10% group and by 90 min for the 50% group. The 99mTc-LEH remained in circulation longer for the 50% group (18.2 h half-life) than for the 10% group (2.4 h half-life). Removal of 99mTc-LEH from the bloodstream was via the liver and spleen. At 20 h, 99mTc-LEH accumulation in these organs was greater for the 10% group (liver, 36.2 +/- 1.7%; spleen, 37.5 +/- 2.5%) than for the 50% group (liver, 17.0 +/- 1.4%; spleen, 17.1 +/- 1.4%). The data show that there is less clearance of 99mTc-LEH from the bloodstream by the reticuloendothelial system after a 50% hypovolemic exchange transfusion, thus supporting the possible use of LEH as an oxygen-carrying resuscitative fluid in situations of severe blood loss.

Anesthetics↗

PubMed1994

Use of a more physiologic oral glucose solution during screening for gestational diabetes mellitus.

OBJECTIVES: We sought to compare in pregnant women deviations in glucose values, insulin values, and the occurrence of side effects between a "standard" 50 gm oral glucose solution (50 gm of glucose in 150 ml of fluid, 1.85 mol/L) versus a modified "physiologic" 50 gm oral glucose solution (50 gm of glucose in 450 ml of fluid, 0.62 mol/L) as a screening test for gestational diabetes mellitus. STUDY DESIGN: A total of 132 pregnant women underwent (1) a standard 50 gm, 1-hour oral glucose screening test, (2) a 50 gm, 1-hour oral glucose screening test using the modified solution, and (3) a 3-hour oral glucose tolerance test (with 100 gm of glucose in 300 ml of fluid, 1.85 mol/L). RESULTS: Compared with the "standard" regimen, both glucose and insulin values were significantly higher in the "modified" regimen 30 minutes after ingestion, indicating a more rapid absorption of glucose. Nausea and vomiting were greatly decreased with the modified glucose solution. The 1-hour glucose values were not statistically different. CONCLUSIONS: A more dilute, more palatable oral glucose solution can be used to screen for gestational diabetes mellitus, yielding more accurate results and eliminating unpleasant side effects.

Administration, Oral↗

PubMed1994

Circulation persistence and biodistribution of lyophilized liposome-encapsulated hemoglobin: an oxygen-carrying resuscitative fluid.

OBJECTIVE: To evaluate the circulation persistence and organ biodistribution of a freeze-dried, oxygen carrying resuscitative fluid: liposome-encapsulated hemoglobin. DESIGN: Randomized, animal studies. SETTING: Accredited animal research facilities. SUBJECTS: Normal female Balb/c mice and male New Zealand rabbits. INTERVENTIONS: Two groups of normal female Balb/c mice were injected in the tail vein with either lyophilized liposome-encapsulated hemoglobin (n = 9) that was reconstituted just before administration, or with unlyophilized liposome-encapsulated hemoglobin (n = 9) as a comparison. Two groups of male New Zealand rabbits were injected in the ear vein with either lyophilized 99mTc-liposome-encapsulated hemoglobin (n = 6) or unlyophilized 99mTc-liposome-encapsulated hemoglobin as a comparison (n = 6). After injection, mice were anesthetized by brief inhalation of halothane followed by blood sampling through the retro-orbital sinus. Rabbits were anesthetized 30 mins before liposome-encapsulated hemoglobin administration with an intramuscular injection of a 5:1 mixture of ketamine (50 mg/kg) and xylazine (10 mg/kg). Rabbits were then dynamically imaged for 90 mins, housed, and at 20 hrs, imaging again followed by autopsy and tissue sampling to validate imaged organ biodistributions. MEASUREMENTS: Circulation persistence in the mouse was measured by removing a blood sample at various time points up to 24 hrs after injection. The blood sample was centrifuged in a hematocrit capillary tube and the disappearance of the sedimented liposome-encapsulated hemoglobin fraction was measured. The change in the sedimented fraction of the liposomes with time was used to generate circulation persistence profiles in mice. The circulation persistence and organ biodistribution of 99mTc-liposome-encapsulated hemoglobin was measured by circling regions of interest on computer-generated gamma camera images. These image intensities were then calculated as a function of total injected dose which was measured from a known volume and activity of 99mTc-liposome-encapsulated hemoglobin. Actual tissue uptake was estimated from images by subtracting blood pool contribution which was measured by injecting 99mTc-labeled rabbit red cells. Imaged organ biodistribution was validated at 20 hrs by measuring activity in weighed portions of tissue after autopsy. MAIN RESULTS: The mean circulation half-life of liposome-encapsulated hemoglobin in mice injected at a dose of 1.0 g phospholipid/kg mouse and 1.95 g hemoglobin/kg was approximately 10.4 +/- 0.5 (SD) hrs. The circulation half-life of lyophilized liposome-encapsulated hemoglobin was 10.7 +/- 0.7 hrs. The circulation profiles demonstrate a rapid removal phase over the first 4 hrs after injection, followed by a secondary slow removal measured up to 24 hrs. The rapid removal phase of liposome-encapsulated hemoglobin and lyophilized liposome-encapsulated hemoglobin in the rabbit (injected at the same dose) indicated that lyophilized liposome-encapsulated hemoglobin persists longer than the unlyophilized form in the first 4 hrs after injection. The organ biodistributions of unlyophilized 99mTc-liposome-encapsulated hemoglobin and lyophilized 99mTc-liposome-encapsulated hemoglobin in the rabbit demonstrate that the reticuloendothelial system is the primary site of removal, with significant uptake of lyophilized 99mTc-liposome-encapsulated hemoglobin by the liver (15.6 +/- 1.0%), bone marrow (12.6 +/- 1.6%), and spleen (9.7 +/- 1.1%). The kidneys showed little accumulation of unlyophilized 99mTc-liposome-encapsulated hemoglobin or lyophilized 99mTc-liposome-encapsulated hemoglobin (1.6 +/- 0.2% and 1.8 +/- 0.1%, respectively), an important result for the efficacy and safety of this hemoglobin-based blood substitute. (ABSTRACT TRUNCATED)

Animals↗

PubMed1994

Treatment with an oral proteinase inhibitor slows gastric emptying and acutely reduces glucose and insulin levels after a liquid meal in type II diabetic patients.

OBJECTIVE: To determine whether an oral trypsin/chymotrypsin inhibitor, POT II, will delay the rate of gastric emptying in recently diagnosed type II diabetic patients and improve their postprandial metabolic parameters. RESEARCH DESIGN AND METHODS: Two gastric emptying studies were performed on each of six type II diabetic patients. During one study, the patient ingested a glucose/protein solution, and during the other study, the patient ingested the same glucose/protein solution with the addition of 1.5 g of POT II, a putative stimulant of cholecystokinin (CCK) release. Each patient served as their own control subject. Each of the two oral solutions were administered to the patients in a counter-balanced order separated by at least 1 week. RESULTS: Serum insulin, plasma glucose, plasma gastric inhibitory polypeptide (GIP) values, and the rate of gastric emptying were all significantly (P < 0.05) decreased over the 2-h testing period when POT II was added to the oral glucose/protein meal. The area under the curve above baseline for glucose with POT II was 75% of the glucose value without POT II. The area under the curve above baseline for insulin with POT II was 68% of the value without POT II. Plasma CCK was significantly increased by POT II 15 min postprandially. CONCLUSIONS: A trypsin/chymotrypsin inhibitor, POT II, can delay the rate of gastric emptying, and decrease postprandial plasma glucose levels, GIP levels, and serum insulin levels in type II diabetic patients diagnosed recently. Delay of gastric emptying in diabetic patients may provide a unique or adjunctive approach to the treatment of type II diabetes.

Administration, Oral↗

PubMed1994

Circulation profile of technetium-99m labeled liposome encapsulated hemoglobin in a 10% or 50% rat hypovolemic shock model.

The circulation kinetics and organ biodistribution of liposome encapsulated hemoglobin (LEH) was determined non-invasively in hypovolemic rats using a technetium-99m (Tc-99m) liposome labeling procedure. Rats with an indwelling catheter had either 10% or 50% of their blood volume removed and replaced with an equal volume of LEH labeled with Tc-99m (Tc-99m LEH). Mean arterial pressures and heart rates were monitored throughout the experiment. Gamma camera images were acquired during the first 90 minutes following infusion of the Tc-99m LEH and at 20 hours post-infusion. Blood capillaries were drawn at various times to monitor Tc-99m activity and the amount of LEH remaining in circulation. There were significant differences in the kinetics and biodistribution for the two groups. In the 10% group, the LEH was removed quickly from circulation with only 0.9% remaining at 20 hours, while the 50% group had 51.2% at 20 hours. The liver and spleen were the major organs responsible for LEH clearance. The 20 hour biodistribution by tissue sampling showed that the 10% group had 37.6% in the liver and 34.3% in the spleen, while the 50% group had only 18.4% in the liver and 14.6% in the spleen.

Animals↗

PubMed1994

Use of technetium-99m-liposomes in tumor imaging.

UNLABELLED: In this study, liposomes labeled with 99mTc have been evaluated as tumor imaging agents. METHODS: Liposomes containing reduced glutathione and carrying either a negative surface charge or no surface charge were labeled with 99mTc using the lipophilic chelator, hexamethylpropyleneamine oxime (HMPAO). The 99mTc-liposomes were intravenously injected into the tail vein of nuce mice which had been implanted intramuscularly in the thigh with nontransfected Chinese hamster ovary cells. Gamma camera images were acquired at 1, 4 and 22 hr and compared with tissue biodistribution studies at 24 hr postinjection. RESULTS: Tumors could be distinguished from normal thigh muscle at 4 hr postinjection for both formulations. Tumor-to-muscle ratios were not significantly different for the two formulations due to the increased normal muscle activity at 24 hr for the neutral liposomes. Liver-to-tumor, liver-to-blood, spleen-to-tumor and spleen-to-blood ratios were significantly lower for the neutral 99mTc-liposomes than for the negative 99mTc-liposomes. Neutral 99mTc-liposomes were cleared slower by the reticuloendothelial system, and therefore remained in the circulation for a longer period of time. CONCLUSION: The results of this study indicate that both formulations could be used as tumor imaging agents, but that neutral 99mTc-liposomes would be more suitable as a drug delivery agent due to their increased total uptake by the tumor and decreased nonspecific uptake by the reticuloendothelial system.

Animals↗

PubMed1993

Reduced postprandial blood glucose levels in recently diagnosed non-insulin-dependent diabetics secondary to pharmacologically induced delayed gastric emptying.

In a previous study we demonstrated that patients with recently diagnosed non-insulin-dependent diabetes mellitus (NIDDM) had significantly increased gastric emptying rates of glucose solutions compared with those of nondiabetic sex- and age-matched controls. This finding of rapid gastric emptying contrasts with the delayed gastric emptying often exhibited as a late manifestation of diabetes mellitus that is attributed to autonomic neuropathy. The purpose of this study was to determine, in seven of the patients previously studied, whether (1) an intravenous infusion of cholecystokinin-8 (CCK-8) would delay the gastric emptying of a liquid glucose meal and, if so, (2) whether the delay in gastric emptying would result in reduced postprandial blood glucose concentrations due to prolongation of the absorption of the glucose in the liquid meal. Each patient underwent two separate gastric emptying studies, one during a saline infusion and one during a CCK-8 infusion. Blood samples were obtained at 15-min intervals for measurement of glucose, insulin, CCK-8, and gastric inhibitory polypeptide (GIP) concentrations. The average gastric half-emptying time was 41 min with the saline infusion and 94 min with the CCK-8 infusion (P = 0.0042). The average glucose concentration over the 2-hr period following glucose ingestion was 17.1 mmol/liter with the saline infusion and 14.0 mmol/liter with the CCK-8 infusion (P = 0.0073). The average glucose excursion value over the 2-hr period was reduced from 5.6 mmol/liter to 3.7 mmol/liter with the CCK-8 infusion (P = 0.0550).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993

Biodistribution and imaging studies of technetium-99m-labeled liposomes in rats with focal infection.

We have recently developed a procedure to label liposomes containing reduced glutathione (GSH) with 99mTc using the lipophilic chelator, hexamethylpropyleneamine oxime (HMPAO). In the present study, we evaluated the use of 99mTc-liposomes to detect focal infection sites in rats. Rats were infected in the thigh by intramuscular injection with Staphylococcus aureus followed 24 hr later by an intravenous injection of 99mTc-liposomes, 67Ga-citrate, or 99mTc-human serum albumin (HSA). The animals were imaged under a gamma camera and subsequently killed at 4, 24 or 48 hr for tissue biodistribution studies. In contrast to infected rats receiving 67Ga-citrate or 99mTc-HSA, abscesses were prominently localized within 2 hr in rats after 99mTc-liposome injection, and continued to increase in activity up to 24 hr. Abscess-to-muscle ratios calculated from 24-hr biodistribution data obtained from tissue sampling were 35.3 +/- 7.6 for 99mTc-liposomes, 4.1 +/- 0.7 for 67Ga-citrate and 8.0 +/- 1.0 for 99mTc-HSA. These studies show the potential of using 99mTc-liposomes to localize infection.

Animals↗