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W T Phillips

Publications and source records attributed to W T Phillips.

46 records · Page 3Linked to original sources
PubMed1992

A simple method for producing a technetium-99m-labeled liposome which is stable in vivo.

A new method for labelling preformed liposomes with technetium-99m (99mTc) has been developed which is simple to perform and stable in vivo. Previous 99mTc-liposome labels have had variable labeling efficiencies and stability. This method consistently achieves high labeling efficiencies (greater than 90%) with excellent stability. A commercially available radiopharmaceutical kit--hexamethylpropyleneamine oxime (HM-PAO)--is reconstituted with 99mTcO4- and then incubated with preformed liposomes that encapsulate glutathione. The incubation takes only 30 min at room temperature. Liposomes that co-encapsulate other proteins such as hemoglobin or albumin, in addition to glutathione, also label with high efficiency. Both in vitro and in vivo studies indicate good stability of this label. Rabbit images show significant spleen and liver uptake at 2 and 20 h after liposome infusion without visualization of thyroid, stomach or bladder activity. This labeling method can be used to study the biodistribution of a wide variety of liposome preparations that are being tested as novel drug delivery systems. This method of labeling liposomes with 99mTc may also have applications in diagnostic imaging.

Animals↗
PubMed1992

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

A lower osmolar oral glucose solution (50 g glucose in 450 mL fluid, 0.62 mol/L) was administered in addition to the standard hyperosmolar oral glucose solution (100 g glucose in 300 mL fluid, 1.85 mol/L) for oral glucose tolerance testing 1 week apart to 102 pregnant women. The standard oral glucose solution creates delayed gastric emptying and is associated with frequent nausea and vomiting. Results using the modified, lower osmolar glucose solution, when compared to the standard hyperosmolar glucose solution showed (1) statistically equivalent glucose excursion values 30 minutes after ingestion, (2) statistically significant decreased plasma glucose values greater than or equal to 60 minutes, (3) no statistically significant difference in insulin excursion values 30 minutes after ingestion, (4) equal area under the curve for glucose at 30 minutes using either solution, and (5) a markedly decreased incidence of nausea and vomiting. These data suggest that the modified, lower osmolar glucose solution empties rapidly from the stomach and allows the glucose to be absorbed and enter the peripheral circulation in an expeditious manner.

Administration, Oral↗
PubMed1992

Biodistribution studies of liposome encapsulated hemoglobin (LEH) studied with a newly developed 99m-technetium liposome label.

A new method has been developed to label preformed liposomes with 99m-Technetium (99mTc) using hexamethylpropylenamine oxime (HMPAO). 99mTc is an ideal isotope for performing non-invasive dynamic biodistribution studies. This labeling method results in a high labeling efficiency (greater than 95%) and is stable as determined by both in vitro and in vivo studies. In vitro studies indicated that glutathione encapsulated in the LEH is important in the labeling process with 99mTc-HMPAO. In vivo studies with LEH were performed on 7 rabbits with dynamic scintigraphic 1 minute images performed from 1-120 minutes. Delayed images were performed at 20 hours followed by sacrifice and organ counting. Dynamic images reveal a gradual deposition of the LEH in the liver and spleen. Twenty hour biodistributions revealed 50% of the LEH remaining in the blood, 15% in the liver, 14% in the spleen, 3% in lungs, 3% in muscle with trace amounts in the brain, kidneys, and heart. Doses per gram were highest in the spleen with 12.5% of the injected dose per gram of spleen vs. 0.2% per gram of liver. This labeling technique is an effective method for non-invasively monitoring dynamic changes in liposome biodistribution and can be used to study the effects of various liposome modifications on biodistribution.

Animals↗
PubMed1992

Rapid gastric emptying of an oral glucose solution in type 2 diabetic patients.

Gastric emptying of a liquid glucose meal was measured with scintigraphic techniques in nine recently diagnosed Type 2 diabetic patients and nine sex- and age-matched nondiabetic control subjects. Seven of the nine Type 2 diabetic patients were receiving oral hypoglycemic therapy which was discontinued the evening prior to the study. The other two diabetic patients were taking no medication. The average gastric half-emptying time was 33.6 min (s.e.m. = 3.2) for the diabetic patients and 64.6 min (s.e.m. = 4.2) for the nondiabetic controls (p = 0.0005). These measurements indicate rapid gastric emptying in Type 2 diabetic patients which may contribute to worsening of glucose control in these patients.

Administration, Oral↗
PubMed1991

In vivo biodistribution of a radiolabeled blood substitute: 99mTc-labeled liposome-encapsulated hemoglobin in an anesthetized rabbit.

Liposome-encapsulated hemoglobin (LEH) is an erythrocyte substitute that is a potential resuscitative fluid for the in vivo delivery of oxygen. We have noninvasively imaged radiolabeled LEH in vivo with technetium-99m (99mTc) to study the biodistribution in an anesthetized rabbit. Rabbits (2.5 kg, n = 8) were infused with 30 ml of LEH (200 mg of phospholipid, 2.5 g of hemoglobin per kg of body weight) and imaged with a gamma camera continuously for 2 hr. At 20 hr postinfusion, the animals were imaged again and sacrificed; the organs were weighted and their radioactivity was determined for autopsy organ distribution. Organ uptake from the images was corrected for organ-associated blood pool, which was determined by infusion of 99mTc-labeled rabbit erythrocytes. Blood pool and decay-corrected biodistribution data reveal the kinetics of LEH distribution, with an initial rapid uptake by the liver, 8% at 30 min and 15% at 2 hr. The spleen accumulates less LEH initially, 3% at 30 min and 7% at 2 hr, with an apparent linear uptake of LEH over this time period. Image biodistribution data was also validated at 20 hr by tissue sampling. At 20 hr postinfusion, autopsy biodistribution data reveals approximately 42.6% of the total counts remaining in the blood, 15.4% in the liver, 18.1% in spleen, 3.2% in the lungs, 2.4% in muscle, 1.6% in urine, and trace levels in the kidney, brain, and heart (less than 1%). There is no evidence of hemoglobin release from LEH or kidney dysfunction (normal creatinine and blood urea nitrogen) at any time over the course of the study.

Alanine Transaminase↗
PubMed1991

Linear gastric emptying of hyperosmolar glucose solutions.

We performed a total of 12 gastric emptying studies on 6 normal subjects with a hyperosmolar (1.85 mol/l) 400-kcal glucose solution commonly used for diagnosing diabetes and a more dilute (0.62 mol/l) 200-kcal glucose solution. The gastric half-emptying time was greatly prolonged with both glucose solutions; 107 min for the (1.85 mol/l) 400-kcal glucose solution compared to 66 min for the more dilute (0.62 mol/l) 200-kcal glucose solution. Although the 200-kcal glucose solution contained one-half the amount of glucose (50 g) compared to the 400-kcal solution (100 g), the blood glucose values obtained during a 2-hr period were only slightly lower with the former solution. This study demonstrates significantly delayed gastric emptying of glucose solutions in normal subjects and a linear pattern of gastric emptying formerly associated only with solid meals.

Administration, Oral↗
PubMed1990

Revision of the oral glucose tolerance test: a pilot study.

Nausea and vomiting have been recurrent problems with the oral glucose tolerance tests (OGTT) used to diagnose diabetes. We believe the nausea is associated with delayed gastric emptying caused by the high osmolarity of the glucose solution. In our pilot study, both the "standard" 100-g glucose OGTT and our new modified (lower osmolar) glucose solution were evaluated. Considerably delayed gastric emptying (along with severe nausea) was consistently noted with the standard OGTT. No nausea and a much more rapid gastric emptying time were recorded when the modified glucose solution was administered. We were able to diagnose diabetes (by using Wilkerson's point system) when our modified OGTT was administered to type 2 diabetics. We plan to develop a more physiological, more reproducible, and better tolerated OGTT to diagnose diabetes more accurately in the general population.

Adult↗
PubMedDate not supplied

The use of scintigraphic imaging as a tool in the development of liposome formulations.

Scintigraphic imaging is a valuable tool that can be used during the development of liposome-based therapeutic agents. It provides the ability to non-invasively track and quantitate the distribution of liposomes in the body. This review article provides a general overview of the methods involved in producing scintigraphic images as well as methods of radiolabeling liposomes. Liposomes labeled with technetium-99m ((99m)Tc) are particularly useful for scintigraphic imaging due to the physical characteristics of (99m)Tc, which provides a high quality image. Examples of how scintigraphic imaging studies have contributed to the development of a variety of liposome-based formulations are covered in this article. These liposome formulations include long-circulating liposome-based oxygen carriers, liposome-based anti-cancer drugs, liposomes encapsulating antibiotics and anti-fungals, and liposomes targeted to lymph nodes. Studies using scintigraphic imaging for the investigation of immune responses to liposomes are also discussed. These examples demonstrate the usefulness of scintigraphic imaging for the development of novel liposome formulations.

Animals↗