Pharmacy-coordinated infusion device evaluation.
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California↗
Biomedical subjects
S Klein
Publications and source records attributed to S Klein.
Reduced cardiotoxicity and nephrotoxicity with preservation of antitumor activity of doxorubicin entrapped in stable liposomes in the LOU/M Wsl rat.
LOU M/Wsl rats inoculated s.c. with 10(4) immunoglobulin immunocytoma cells have a palpable tumor at Day 17. Doxorubicin (DXR) has been entrapped in negatively charged liposomes (lip- DXR) composed of egg phosphatidylcholine, cholesterol, and phosphatidylserine and in positively charged liposomes (lip+ DXR) composed of phosphatidylcholine, cholesterol, and stearylamine. DXR, lip- DXR, and lip+ DXR were administered i.v. (0, 0.25, 0.5, 1.0, and 2.0 mg/kg) at Day 17 for 5 consecutive days and then weekly. Control animals showed progressive tumor growth leading to death 27 days after inoculation. Antitumor activity for all three preparations was dose dependent. DXR and lip- DXR showed the same antitumor activity; lip+ DXR had less antitumor activity. The overall survival of tumor-bearing animals treated with 2.0-mg/kg lip- DXR was significantly prolonged (p less than 0.05) in comparison to the animals treated with 2.0-mg/kg free DXR. Grade III cardiomyopathy was observed 47 days after treatment with free DXR; treatment with lip- DXR resulted in Grade I cardiomyopathy. In animals treated with 1.0-mg/kg and 2.0-mg/kg free DXR urinary albumin concentrations of 10 g/liter were observed. Treatment with 1.0-mg/kg lip- DXR and 1.0-mg/kg lip+ DXR resulted in urinary albumin concentration of less than 3.0 and less than 1.0 g/liter, respectively. Free DXR, 1.0 mg/kg, resulted in a decline of serum albumin concentration from 27.8 +/- 3.2 g/liter to 9.6 +/- 4.2 g/liter. No such decline was observed after treatment with lip- DXR and lip+ DXR. Treatment with a 1.0-mg/kg dose of free DXR resulted in severe glomerular and tubular lesions which were not found after treatment with 1.0-mg/kg lip- DXR and 1.0 mg/kg lip+ DXR. Administration of lip- DXR resulted in lower DXR levels in cardiac and renal tissue compared to administration of free DXR. After administration of lip+ DXR, very low tissue and tumor DXR levels were found. In conclusion, treatment with lip- DXR or lip+ DXR resulted in a prolonged survival, less albuminuria, and higher serum albumin levels. Also, fewer lesions in heart and kidney were found, correlating with lower DXR levels in these organs. Only lip- DXR had the same antitumor effect as free DXR.
Animals↗
Renal arcuate veins: new microangiographic observations.
Standard references state that arcuate veins at the corticomedullary junction form continuous arcades. Because some preliminary anatomic observations seemed to disagree with this traditional teaching, the arcuate veins were systematically studied in normal human kidneys. Microangiographic studies indicate that, unlike the occasional anastomoses that exist between proximal interlobar and segmental veins, arcuate venous communications in humans are extremely rare. Arcuate veins, like the corresponding arteries, should be considered "end vessels."
Adult↗
Effect of healing on small internal diameter arterial graft compliance.
Porosity is an essential component for long term function of small internal diameter synthetic vascular prostheses. Theoretically, porosity is required for healing by providing a scaffold for ingrowth of periprosthetic tissues. Porosity may be required for transfer of fluids and ions in prostheses even if tissue ingrowth does not occur. Increased permeability of vascular grafts has been shown to enhance tissue incorporation. Implants with pore sizes greater than 10 microns but less than 45 microns become ingrown with fibrohistiocytic tissue and capillaries. Implants with pore sizes greater than 45 microns are ingrown with organized fibrous tissue and minimal histiocytic response. The phenomenon of differential ingrowth may have important functional significance. Prostheses which heal with organized fibrous tissue have the potential for long term contracture, strangulation of vascularity and calcification. Fibrohistiocytic tissue has low mechanical strength and does not appear to contract or calcify. Elastomeric microporous vascular prostheses which are minimally ingrown or ingrown with fibrohistiocytic tissue maintain compliance after months of implantation. This study was designated to determine the effects of healing on the compliance of small internal diameter vascular replacements and to correlate the compliance to patency rates.
Animals↗
Thrombogenicity and the interaction of proteins, platelets and white cells.
Radioactive labeled protein and platelet studies suggest that an ideal vascular surface absorbs albumin and prevents platelet adherence and aggregation. This study examines the interaction of serum and plasma proteins, white cells, and platelets in the thrombotic response to small internal diameter vascular prostheses. Thirty-seven replamineform silicone rubber vascular prostheses, 4 mm internal diameter and 6 cm length, had 5% aspirin and 5% theophylline by weight dispersed in a luminal coating (D); the remaining 37 control (C) prostheses had an identical silicone rubber coating without drugs. Scanning electron and darkfield microscopy confirmed similar surface topography in C and D grafts. One C and one D graft were studied in parallel using a modified canine arteriovenous fistula. Consistently, D prosthesis had increased bleeding through the graft wall. The 7 serum and 8 plasma experiments demonstrated greater accumulation on the D prostheses, the greatest deposition occurring within the first 30 minutes. In 8 platelet experiments, D grafts accumulated more radioactivity at both the 5 and 30 minute intervals. Six mononuclear and 8 PMN experiments had less accumulation on the D grafts at 15 minutes and no consistent difference at 60 minutes. Elution of C and D Grafts demonstrated significant drug levels in only the D grafts at the beginning of the experiments and after 15 minutes of exposure of blood. We conclude: (1) aspirin and theophylline have an effect on the initial interaction of plasma proteins, platelets and white cells in the thrombogenic response, (2) the effect diminishes as time released drug levels decrease.
Animals↗
A case of acebutolol intoxication.
A case of a nonfatal acebutolol intoxication in a 15 year old female is described. Ingestion of 7600 mg acebutolol resulted in a plasma acebutolol concentration of 15 mg/1 one hour after ingestion. The patient remained conscious, had a severe hypotension and the electrocardiogram showed a 1st degree AV-block and severe intraventricular conduction disturbances at a rate of 70 bpm. After the administration of calcium gluconate and plasma the blood pressure gradually increased to normal values in 2 hours time. Plasma halflife of acebutolol was 8 hours. Pathophysiology of acebutolol intoxication is discussed.
Acebutolol↗
[Correlation of diabetic irido- and retinopathy].
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Adult↗
[Tin and organotin compounds - with special reference to biotransformation reactions].
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Alkylation↗
Hyperacuity and amblyopia.
The most frequent cause of visual loss in childhood is functional amblyopia, an abnormality of visual acuity usually associated with either anisometropia (unequal refractive errors) or strabismus (turned eye) during early development. The usual clinical investigation of the visual acuity of amblyopes involves discrimination of the high contrast letters of a Snellen chart; however, there are other aspects of acuity, for example, grating acuity (the high spatial frequency limit of vision) and Vernier acuity (the smaller perceptible misalignment). Because of the extreme precision of Vernier acuity compared with either grafting or Snellen acuity, it is considered to be a form of hyperacuity which requires very precise positional information. In an effort to understand the nature of the neural abnormalities which cause the reduced acuity of amblyopes, we have measured here the Vernier acuity of amblyopic observers using an extended Vernier grating stimulus, and compared these results with their Snellen acuity and grating acuity. The results showed that different acuity losses are associated wih anisometropic versus strabismic amblyopia. When scaled with respect to their grating acuity, anisometropic amblyopes, like normals, showed hyperacuity, even at high spatial frequencies, while strabismic amblyopes showed severe losses in Vernier acuity. Snellen letter acuity showed a similar deficit relative to grating acuity in strabismic but not in anisometropic amblyopes. Contrary to some previous theories which have considered that all forms of amblyopia share a common neural basis, these results strongly support the view that different neural losses are associated with amblyopias of different aetiologies.
Amblyopia↗
[Modification of the graft versus host response (G.V.H.R.) in maternal lymphoid cells during allogenic gestation evolution (author's transl)].
This study evaluates the maternal immunological response at different stages of gestation in the mouse. This response has been measured by the local G.V.H.R. of lymphocytes from uterine draining lymph nodes and spleens. The results reported here show that the maternal immunological reaction-against paternal antigens carried by the foetus-is lower at the beginning of gestation (on days 6-7) and increases significantly during the last period between 14 and 18 days. In contrast, the temporal G.V.H.R. response of maternal splenocytes is inverted, with lower values from day 14 to day 18.
Animals↗
Effects of lithium on the activities of phosphofructokinase and phosphoglucomutase and on glucose-1,6-diphosphate levels in rat muscles, brain and liver.
Incubation of rat diaphragm muscle in the presence of lithium chloride (a drug used widely in the therapy of patients with mental illness), resulted in a sharp decrease in the level of glucose-1,6-diphosphate (Glc-1,6-P2), the powerful regulator of carbohydrate metabolism. This decrease in Glc-1,6-P2, the most potent activator of phosphofructokinase and phosphoglucomutase, was accompanied by a marked reduction in the activities of both enzymes, when assayed in the absence of exogenous Glc-1,6-P2 under conditions in which these enzymes are sensitive to regulation by endogenous Glc-1,6-P2. A decrease in Glc-1,6-P2 and the concomitant reduction in the activities of phosphofructokinase and phosphoglucomutase, were also obtained in the rat gastrocnemius and tibialis anterior muscles, as well as in brain, following Li+ injection. In contrast to its effects in muscles and brain, Li+ did not exert any effect on Glc-1,6-P2 level and on the enzymes' activities in the liver. The marked inhibition of brain and muscles phosphofructokinase (the rate-limiting enzyme in glycolysis) induced by Li+, may play an important role in the mechanism of the therapeutic action of this agent in the manic state.
Animals↗
Antigen-specific suppressor cell activity in procainamide therapy.
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Aged↗
Noninvasive evaluation of peripheral vascular disease using transcutaneous oxygen tension.
Transcutaneous oxygen tension (PtcO2) was used for noninvasive determination of blood supply in 25 patients evaluated for peripheral arterial disease. PtcO2 values were compared with segmental Doppler pressure, pulse volume recording, pulse reappearance time, and angiography in patients being evaluated for wound healing problems, amputations, and peripheral bypass procedures. PtcO2 was measured using a heated (45 degrees C) Clark polarographic electrode to quantitate the oxygen which diffuses from the dermal capillaries to the skin surface. Control PtcO2 values recorded over the chest or shoulder taken while patients were breathing room air were 78 +/- 8 mm Hg. PtcO2 values greater than 50 mm Hg predicted success for levels of amputation and for wound healing without reconstructive procedures; values of 40 mm Hg or less were associated with continued wound problems and complication after amputation. Increased PtcO2 values after vascular reconstruction of the legs predicted improved clinical status on follow-up examinations up to 6 months. PtcO2 predicted the extent of vascular disease as well as the other noninvasive tests and angiography. We conclude that (1) PtcO2 tension is a simple, accurate, noninvasive method to determine the appropriate level of amputation, wound healing potential, and effectiveness of bypass procedures, and (2) PtcO2 values correlate well with angiography and noninvasive evaluations.
Aged↗
The participation of glucose-1,6-diphosphate in the regulation of hexokinase and phosphoglucomutase activities in brains of young and adult rats.
1. The level of glucose-1,6-diphosphate (Glc-1,6-P2), the powerful regulator of carbohydrate metabolism, was found to be strikingly decreased in brains of adult rats (5 months of age) as compared to young (10-14 days of age). 2. This age-related decrease in Glc-1,6-P2, the potent inhibitor of hexokinase and activator of phosphoglucomutase, was accompanied by a correlated increase in the activity of hexokinase and a reduction in phosphoglucomutase. 3. Evidence is provided showing that Glc-1,6-P2 participates in the regulation of these enzymes' activities with age. 4. The age-related changes in Glc-1,6-P2 and in the enzymes' activities in brain were opposite to those which we previously found in skeletal muscle. 5. These results suggest that Glc-1,6-P2 is involved in the regulation of carbohydrate metabolism during growth in both brain and muscle, as well as in the interrelationship between these two tissues.
Adenosine Triphosphate↗
Low spatial-frequency channels in human vision: adaptation and masking.
Previous work showed that adapting to low spatial frequency gratings (below 1.5 cycles/degree) may cause maximal spatial adaptation at a significantly higher spatial frequency. It has been suggested that there are no adaptable spatial-frequency channels tuned to below 1.5 c/deg. Contrary to this view, we found that adaptation and masking with low spatial frequencies (0.12-1.0 c/deg) produced maximal threshold elevations when the test patterns were the same spatial frequency as the adapting or masking pattern. These results were obtained using test patterns that turned on and off gradually or sharply. The results suggest that there are form mechanisms optimally sensitive to very low spatial frequencies. Adaptation was selective to position (phase) and orientation at low spatial frequencies; masking was observed to be selective to orientation at a spatial frequency as low as 0.2 c/deg. A clear dichotomy between transient, motion channels and sustained, form channels at low spatial and temporal frequencies may represent an unrealistic simplification. There may exist directionally-selective motion mechanisms sensitive to very slow motion, and these may play a role in the discrimination of form. The discussion considers the bandwidths of the low spatial frequency mechanisms.
Adaptation, Ocular↗
Cost-benefit analysis of a behavioral program for geriatric inpatients.
A behaviorally oriented treatment program was developed for geriatric patients at a state psychiatric hospital, in an attempt to demonstrate that active treatment for the elderly can be both socially beneficial and economically wise. Outcome data indicated that the program was successful in decreasing the average length of hospital stay, decreasing the percentage of patients discharged to more dependent living settings than those from which they were admitted, and increasing placements to independent living settings. An economic analysis demonstrated benefit-to-cost ratios of between ten and 20 to one, depending on assumptions used. The authors believe that ratios were especially encouraging as they were calculated using conservative assumptions.
Aged↗
Immune reactivity of spleen cells in advanced stages of tumor growth.
In a syngeneic tumor model by an indirect migration inhibition technique, using spleen cells from mice bearing large tumors (ATB-SC) no detectable amounts of migration inhibition factor (MIF) was found in response to either tumor cells or tumor extract. Although lymphokine production was suppressed, ATB-SC were able to respond to exogenous MIF and also to transfer a positive delayed foot-pad reaction (DFR) when co-inoculated with both forms of antigen into normal mice. These observations showed that in advanced stages of tumor development, when the ability of spleen cells to produce MIF toward tumor cells or tumor extract is lost, neither their capability to transfer a positive DFR not their responsiveness to MIF-rich culture supernatants were impaired.
Animals↗
Differences in vernier discrimination for grating between strabismic and anisometropic amblyopes.
Two gratings composed of lines were displayed one above the other, and the vernier threshold was measured as a function of spatial frequency and vertical separation between gratings for 12 strabismic and/or anisometropic amblyopes. The vernier acuity of the anisometropic amblyopes was similar to that of nonamblyopic eyes when scaled proportionally to their reduced grating acuity. Strabismic amblyopes, on the other hand, have poorer vernier acuity than might be predicted from their grating resolution, even at low spatial frequencies. In addition, the strabismic amblyopes showed "crowding effects" for vernier gratings well within their resolution limit, while anisometropic amblyopes, like normals, showed no such effects.
Adult↗