Search PubMed⌕ Search

Biomedical subjects

D E Brooks

Publications and source records attributed to D E Brooks.

At least 37 records · Page 2Linked to original sources

Inhibition of liposome-induced complement activation by incorporated poly(ethylene glycol)-lipids.

Complement activation causes opsonization of foreign particles leading to particle elimination from the blood. Complement-mediated opsonization of charged and large liposomes presents a fundamental problem in their use to deliver therapeutic agents in vivo. To prolong the circulation half-lives of such liposomes, complement activation must be curtailed. The aim of this study was to assess the ability of poly(ethylene glycol)-lipids (PEG-lipids) to inhibit the in vitro activation of the classical pathway of complement in human serum by anionic liposomes. Incorporation of cholesterol-PEG600 (CH-PEG600), cholesterol-PEG1000 (CH-PEG1000), or phosphatidylethanolamine-PEG2000 (PE-PEG2000) resulted in dose-dependent inhibition of C1q binding and complement activation. The dose of PEG-lipid at which complement activation was blocked was inversely related to the PEG chain length. Complement activation was strongly inhibited when 15 mole% of CH-PEG600, 10 mole% CH-PEG1000, or 5 mole% PE-PEG2000 was incorporated into 100-nm anionic liposomes. PEG-lipid incorporation into larger liposomes (240 nm) was also successful in blocking C1q binding and complement activation. Radiolabeled cholesterol-PEG approximately 1400 was prepared and used to determine both the percentage of CH-PEG incorporated into the liposomes and the percentage maintained in the liposomes in the presence of 50% human serum at 37 degrees C for up to 24 h.

Cholesterol↗

Assessment of cocaine use in patients with chest pain syndromes.

BACKGROUND: Patients with myocardial ischemia may have different dispositions and/or pharmacologic interventions based on whether they have recently used cocaine. OBJECTIVE: To determine the prevalence of assessment of cocaine use in patients with acute chest pain syndromes. METHODS: In phase 1 of the study, we reviewed the medical records of all patients with chest pain who presented to the emergency department during February 1996 to assess historical documentation of the presence or absence of cocaine use. In phase 2, we evaluated whether cocaine questions were asked but not documented. After hospital admission, patients were interviewed to see if they were asked about cocaine use. In phase 3, we evaluated possible recall bias by using standardized questioning in the emergency department and used subsequent interviews to assess recall. Assessment of other cardiac risk factors served as the comparison group. RESULTS: In phase 1, 129 charts were reviewed, 13% of which revealed myocardial infarction. The presence or absence of cocaine use (13%) was less frequently documented than the presence or absence of hypercholesterolemia (58%), hypertension (82%), smoking (90%), diabetes (73%), or family history (77%) (chi 2, P < .05 for all comparisons). In phase 2, 27 (31%) of the 86 patients who were interviewed recalled cocaine questioning. There was chart documentation of the cocaine questioning in only 44% of the 27 cases. In phase 3, while in the emergency department, 20 patients were asked about cocaine use: 19 (95%) recalled being asked about cocaine use when interviewed the next day. CONCLUSIONS: Patients with chest pain often are not asked about recent cocaine use. When they are asked, their answers are poorly documented. These findings cannot be explained by poor recall. In cases of chest pain, efforts to improve questioning of patients about cocaine use are needed, since recent cocaine use may change treatment, disposition, and need for counseling.

Adult↗

Equine ulcerative keratomycosis: visual outcome and ocular survival in 39 cases (1987-1996).

The medical records of 39 horses treated for ulcerative keratomycosis over a 10 year period were reviewed. Records were evaluated to determine the medical and/or surgical treatment protocol, visual outcome, globe survival and whether the outcome was influenced by the fungal species isolated. Stromal abscesses and iris prolapses caused by fungi were not included. Twenty of the horses underwent medical treatment only, and 19 horses had combined medical and surgical treatment. Most horses had been treated with topical antibiotics (n = 32) and atropine sulphate (n = 23) prior to referral; topical antifungals had been employed less frequently (n = 14). Fungi were identified by cytology (n = 31), culture (n = 33) and/or surgical histopathology (n = 6). Aspergillus (n = 13) and Fusarium (n = 10) were the most commonly isolated fungi. Miconazole (n = 35) was the most common topical antifungal medication utilised. Median duration of treatment was 48 days (range 31-192 days). Associated bacterial infection (n = 13) was frequently encountered. Visual outcome was favourable in 36/39 (92.3%) eyes. All eyes (20/20) retained vision following medical management only, and 16/19 (84%) retained vision following combined medical and surgical therapy. All medically treated horses (20/20), and 17/19 (89%) of those treated medically and surgically retained their globes. Overall ocular survival was favourable in 37/39 (94.9 %) eyes. Aggressive therapy can result in successful results for equine ulcerative keratomycosis.

Animals↗

Antimicrobial susceptibility patterns of fungi isolated from horses with ulcerative keratomycosis.

OBJECTIVES: To evaluate in vitro susceptibility to topical antifungal medications, as measured by minimum inhibitory concentration (MIC) and 50% inhibitory concentration (IC50%), of fungal isolates from horses with ulcerative keratomycosis in Florida; to compare results with those of other studies to identify differences in susceptibility patterns among fungi isolated from horses in different geographic regions; and to note indications of fungal resistance to drugs tested in other studies. SAMPLE POPULATION: Corneal fungal cultures from client-owned horses from Florida with ulcerative keratomycosis (n = 22). PROCEDURE: Fungal cultures were plated on Emmons modified Sabouraud dextrose agar and mycobiotic agar, examined weekly for growth, and kept for a total of 30 days. In vitro MIC and IC50% of fluconazole, itraconazole, ketoconazole, miconazole, and natamycin were measured for each fungal isolate. RESULTS: Aspergillus (n = 9; 41%), Fusarium (7; 32%), Penicillium (2; 9%), Cylindrocarpon (1; 4%), Scytalidium (1; 4%), and Torulopsis (1; 4%) spp and an unidentified yeast (1; 4%) were isolated. Fungi were most susceptible to antifungal drugs in the following order: natamycin and miconazole equally, itraconazole, and ketoconazole, although no significant difference was found among drugs. Fungi were significantly less susceptible to fluconazole (P < 0.0001) than to the other 4 drugs. CONCLUSIONS: Initial antifungal therapy with topically applied natamycin, miconazole, itraconazole, or ketoconazole is recommended for ulcerative keratomycosis in horses in the subtropical environment of Florida. CLINICAL RELEVANCE: Specific antifungal treatment of horses with ulcerative keratomycosis should be based on history, results of ophthalmic examination, cytologic findings, isolation of the pathogenic fungus, and known prevalence of unique ocular fungi in specific geographic areas. In vitro antifungal susceptibility testing may be most beneficial in aiding documentation of pharmacologic susceptibility patterns of fungi in specific geographic regions.

Analysis of Variance↗

Diurnal intraocular pressure curves in healthy rhesus macaques (Macaca mulatta) and rhesus macaques with normotensive and hypertensive primary open-angle glaucoma.

PURPOSE: The authors identify any diurnal intraocular pressure (IOP) variation in healthy Cayo Santiago macaques, as well as Cayo Santiago macaques with normotensive and hypertensive primary open-angle glaucoma (POAG), to further evaluate their potential value as a model for human POAG. METHODS: Twenty-four monkeys (eight animals each of the healthy control, normotensive glaucoma, and hypertensive glaucoma groups) were sedated with ketamine hydrochloride and the IOP measured hourly from 8:00 AM until 3:00 PM with a Tonopen XL applanation tonometer (Mentor, Norwell, MA, U.S.A.). Mean IOP time profiles, mean IOPs at each observation time, and linear trends in mean IOP over time were compared among groups. Intraocular pressure rate-of-change over time and residual variation about the regression line for each individual eye were analyzed. Cup/disc ratio (C/D) was compared with baseline IOP, IOP profile mean and slope, and IOP residual variation. RESULTS: A significant group and time effect on mean IOP (p = 0.0001 and 0.011, respectively), with highest values at 2:00 PM or 3:00 PM, and a significant increasing linear trend in mean IOP over time in the hypertensive group were observed (p = 0.012). Intermediate readings between control and hypertensive mean IOPs were identified for the normotensive glaucoma group. The biggest range of IOP variation was found in the hypertensive glaucoma monkeys. Higher variations in IOP did not lead to an increase in C/D. CONCLUSIONS: This study provides evidence that the Cayo Santiago macaques are a valuable model for human normotensive and hypertensive POAG.

Animals↗

Indirect enzyme-linked immunosorbent assay for the quantitative estimation of lysergic acid diethylamide in urine.

A new antibody to lysergic acid diethylamide (LSD) was used to develop a novel indirect ELISA for the quantification of drug in urine. Evaluation of the new assay with the commercially available LSD ELISA (STC Diagnostics) shows improved performance. The test requires 50 microL of urine, which is used to measure concentrations of drug in the microg/L to ng/L range. The limit of detection was 8 ng/L compared with 85 ng/L in the commercial assay, and analytical recoveries were 98-106%. Our test detected 0.1 microg/L of LSD in urine with an intraassay CV of 2.4% (n = 8) compared with 6.0% for a 0.5 microg/L sample in the commercial assay (n = 20). The upper and lower limits of quantification were estimated to be 7 microg/L and 50 ng/L, respectively. Specificity was evaluated by measuring the extent of cross-reactivity with 24 related substances. Drug determination using the new assay offers both improved sensitivity and precision compared with existing methods, thus facilitating the preliminary quantitative estimation of LSD in urine at lower concentrations with a greater degree of certainty.

Benzidines↗

Signs of glaucoma in rhesus monkeys from a restricted gene pool.

PURPOSE: To investigate the distribution of intraocular pressure (IOP) and cup properties in a colony of rhesus monkeys that has had no outside genetic input since 1938 (approximately 12 generations). This sample of sequestered monkeys is significantly larger than any previously reported. Comparisons are made with a sample of random-source monkeys to develop population estimates defining the limits of normalcy. METHODS: The IOP and cup/disc ratio estimates were collected from 701 eyes of 354 adult rhesus monkeys from the closed colony on Cayo Santiago, Puerto Rico. Results for IOP were compared with the normal rhesus IOP population distribution function calculated from an earlier sample of genetically heterogeneous rhesus. RESULTS: The mean +/- standard deviation IOP in the Cayo Santiago monkeys (15.8+/-3 mmHg) related well to the calculated "normal" rhesus distribution (14.5+/-2 mmHg) below and around the mean IOP only. Above the mean rhesus IOP, the samples from the Cayo monkeys were strongly skewed: 129 eyes had IOP more than two standard deviations above the normal mean IOP, and 54 eyes had IOP more than three standard deviations above the normal mean IOP. Cup/disc ratio estimations tended to cluster as higher values in the higher IOP quartiles. Some eyes with IOP below the mean had cup/disc ratios > 0.5. Values for IOP that were more than two standard deviations above the mean and cup/disc ratios > 0.4 were not uniformly distributed across social groupings, although incidence of high IOP was more than 25% in one group. CONCLUSION: After 12 generations with the same genetic pool, expression of ocular hypertension and large optic disc cups is high but not uniform.

Animals↗

Photoreceptor outer segments in aqueous humor from dogs with rhegmatogenous retinal detachments.

OBJECTIVE: To determine whether photoreceptor outer segments can be found in aqueous humor from dogs with rhegmatogenous retinal detachment (RRD). DESIGN: Case series. ANIMALS: 4 dogs with unilateral RRD, 2 dogs with bilateral RRD, 1 dog with unilateral non-RRD, and 1 dog with glaucoma without retinal detachment. PROCEDURE: Aqueous humor samples were fixed in 2% glutaraldehyde and examined by means of transmission electron microscopy. RESULTS: Outer segments were found in aqueous humor from 7 of 8 eyes with RRD but were not found in aqueous humor from dogs with non-RRD or glaucoma. CLINICAL IMPLICATIONS: Photoreceptor outer segments may move into the anterior chamber of eyes with RRD.

Animals↗

Viscoelastic characteristics of muscle: passive stretching versus muscular contractions.

This study compared the effects of repeated contractions and repeated passive stretches on the viscoelastic properties of muscle. The tibialis anterior (TA) muscles of eight anesthetized male New Zealand white rabbits were studied. In each rabbit, one hindlimb was randomly assigned to the repeated muscular contraction group (CON) and the contralateral hindlimb to the repeated passive stretch group (STRETCH). The passive tension at neutral length was measured in all muscles before and after both repeated muscular contractions or repeated passive stretches. In the CON hindlimb, the peroneal nerve was stimulated with a nerve stimulator for 1 s, and the resulting contractile force was measured. Stimulations were repeated every 10 s for a total of 10 contractions. In the STRETCH hindlimb, the TA was stretched from its shortest in vivo length to its maximum in vivo length 10 times at 20 cm x min-1. The maximum force generated during the first contraction in the CON group averaged 21.74 +/- 1.41 N, with a subsequent reduction with each muscle contraction to 13.66 +/- 0.81 N by the tenth contraction. The average peak tensile force in the STRETCH group was 17.39 +/- 2.61 N for the first passive stretch, decreasing to 13.57 +/- 1.84 by the tenth stretch. After repeated muscular contractions in the CON hindlimbs, the passive tension at neutral length decreased from 0.88 +/- 0.22 N to 0.42 +/- 0.08 N. After repeated passive stretches in the STRETCH hindlimbs, the passive tension at neutral length decreased from 1.16 +/- 0.17 N to 0.67 +/- 0.09 N. The percentage decreases in passive tension between the CON and STRETCH groups were not statistically significant (P = 0.24). The results show that stretching and contracting both result in tissue relaxation of the muscle-tendon unit. This finding may be a result of changes in the viscous elements of the connective tissue secondary to the forces generated by either stretches or contractions. This study suggests that well controlled isometric muscular contractions may result in decreased passive tension in a muscle at neutral length, a finding that one normally associates with passive stretching.

Animals↗

Visual outcome and ocular survival following iris prolapse in the horse: a review of 32 cases.

The medical records of 32 horses treated for iris prolapse (IP) during an 8 year period, at the University of Florida Veterinary Medical Teaching Hospital, were reviewed. Iris prolapse was associated with perforated corneal ulcers in 15 horses (47%), ruptured stromal abscesses in 2 horses (6%), and full thickness corneal lacerations in 15 horses (47%). Initial ophthalmic examinations revealed IP with severe iridocyclitis in all eyes and keratomalacia in 8 eyes with corneal ulcers, one with a stromal abscess and 1 with a corneal laceration. Hyphema was present in 7 eyes with corneal lacerations. Thirty horses were managed with combined medical and surgical therapy. Two horses were only treated medically with topically administered antibiotics. Of the 24 perforations surgically repaired, 21 were closed primarily and 13 were then covered with a conjunctival graft. After combined therapy and a minimum of 4 months of follow-up, vision was retained in 6 of the horses (40%) with perforating corneal disease and 5 of the horses (33%) with perforating corneal lacerations. Post operatively, of the 11 (37%) horses blind at discharge, 6 (55%) subsequently developed phthisis bulbi. Enucleations were performed in 4 cases with extensive keratomalacia and/or endophthalmitis, 2 cases with limbal rupture and total hyphema, and one case with a chronic IP. One horse was subjected to euthanasia after 3 surgical treatments failed to stabilise stromal melting. Horses presented with ulcerative keratitis of fewer than 15 days duration, or horses with corneal lacerations less than 15 mm in length, tended to have a favourable visual outcome. Keratomalacia, hyphema, corneal lacerations longer than 15 mm and lacerations extending to, along, or beyond the limbus, adversely influenced visual outcome. Iridectomy did not appear clinically to exacerbate anterior uveitis or adversely affect visual outcome. Ocular survival following combined therapy was 80% (12/15) in horses with corneal lacerations and 67% (10/15) in horses with ulcerative keratitis.

Animals↗

Vitreous body glutamate concentration in dogs with glaucoma.

OBJECTIVE: To analyze the vitreal amino acid concentrations in dogs with breed-related primary glaucoma to determine whether excitotoxic amino acids associated with retinal genglion cell death in other species were present in affected dogs. SAMPLES: 11 normal control and 10 glaucomatous canine eyes. PROCEDURE: Amino acid analyses were performed by high-pressure liquid chromatography in masked manner. RESULTS: Eyes from dogs with primary glaucoma had significantly high vitreal glutamate concentration, compared with values for eyes of clinically normal control dogs. Mean (+/-SD) glutamate concentrations were 31.7 +/- 12.4 and 6.9 +/- 6.3 microM in glaucomatous and normal eyes, respectively (P < 0.0001). Eyes from dogs with glaucoma also had lower vitreal glycine (37.0 +/- 17.0 vs 59.4 +/- 28.2 microM; P < 0.043) and higher of vitreal tryptophan (39.0 +/- 22.8 vs 17.5 +/- 11.2 microM; P < 0.012) concentrations, compared with values for normal eyes. CONCLUSION: Glutamate concentration potentially toxic to retinal ganglion cells is associated with the pathogenesis of primary glaucoma in dogs. Increased glutamate concentration provides evidence of an ischemic mechanism for retinal ganglion cell death and optic nerve atrophy in dogs with glaucoma. CLINICAL RELEVANCE: The emphasis on reduction and normalization of high intraocular pressure as the primary focus of treatment for glaucoma in dogs should be augmented by other therapeutic approaches.

Amino Acids↗

Ocular hypertension following cataract surgery in dogs: 139 cases (1992-1993).

OBJECTIVE: To document the incidence of postoperative ocular hypertension (POH) after cataract surgery in dogs. DESIGN: Retrospective analysis of medical records. SAMPLE POPULATION: 88 dogs that had had cataract surgery. PROCEDURE: The effect of several categorical variables on the development of POH was evaluated statistically. Postoperative ocular hypertension was defined as intraocular pressure > 25 and > 30 mm of Hg. RESULTS: The incidence of POH > 25 mm of Hg was 48.9%; > 30 mm of Hg, 33.8%; > 40 mm of Hg, 20.1%; and > 50 mm of Hg, 5.8%. Mean onset of POH > 25 mm of Hg was 4.9 hours. The incidence of POH was not affected by the type of surgery. Eyes that had phacoemulsification developed POH significantly more rapidly (mean, 3.9 hours), compared with those that had extracapsular lens extraction (8.4 hours). Mean phacoemulsification duration was greater in eyes that developed POH, and older dogs were more likely to develop POH. Development of POH was not correlated with sex, stage of cataract, type of surgical procedure performed, intraocular lens placement, preoperative lens-induced uveitis, or posterior lens capsule tears and vitrectomy. However, eyes that received intraocular lens implants developed POH more rapidly, compared with eyes without implants. CLINICAL IMPLICATIONS: The high incidence and early onset of POH after cataract surgery suggests that routine use of antiglaucoma medications in the first 12 hours after surgery is warranted.

Animals↗

Poly(ethylene glycol) amphiphile adsorption and liposome partition.

Surface localized poly(ethylene glycol) (PEG) amphiphiles of type C16:0-EO151 and C18:2-EO151 were studied via ellipsometry at macroscopic, flat methylated silica (MeSi), phosphatidic acid (PA), and phosphatidylcholine (PC) surfaces. At these surfaces the amphiphiles adsorb similarly, in a non-cooperative manner, achieving a plateau (approximately 0.1 PEG chains/nm2) well below amphiphile critical micelle concentration (CMC). The resultant PEG-enriched layers were 10-15 nm thick, with a polymer concentration (approximately 0.07 g/cm3) greater than the PEG-enriched phase of many dextran, PEG aqueous two-phase systems. PEG-amphiphile adsorption (mg/m2) at hydrophobic and phospholipid flat surfaces correlated with changes in the partition (log K) of PC liposomes in such two-phase systems. PEG-amphiphile adsorption at macroscopic surfaces appears to represent a balance between hydrophobic attraction and repulsive intra-chain interactions which promote chain elongation normal to the surface.

Adsorption↗

Effects of postmortem freezing on tensile failure properties of rabbit extensor digitorum longus muscle tendon complex.

The tensile failures of extensor digitorum longus muscle tendon units from 16 male New Zealand White rabbits were studied in the fresh state (less than 30 minutes after death) and in the frozen/thawed state (frozen at -80 degrees C for 28 days and then warmed to 38 degrees C). Frozen/thawed extensor digitorum longus muscle tendon units had significantly lower values for load to failure (p < 0.01), energy absorbed to failure (p < 0.01), and strain at failure (p < 0.01), and they tended to fail at a different anatomic location (p < 0.01) (broadly at the fascia-muscle interface as compared with horizontally at the musculotendinous junction) than fresh units. The results of this study suggest that freezing muscle tendon units significantly alters their tensile failure characteristics.

Animals↗

Interfacial thickness of liposomes containing poly(ethylene glycol)-cholesterol from electrophoresis.

The electrophoretic mobilities of liposomes incorporating a polyethylene glycol (PEG) headgroup coupled to cholesterol for PEG of average chain index 3.0, 13.2, and 22.3 have been determined as a function of PEG-cholesterol mole fraction between 5% and 40% and ionic strength between 2 and 200 mM. The liposome compositions were 40 mole % cholesterol plus PEG-cholesterol, 10 mole % 1,2-dipalmitoyl-sn-glyerco-3-phosphoglycerol, and 50 mole % egg phosphatidylcholine. The mobilities were fit to a model in which the PEG forms a surface layer of polymer subject to viscous drag arising from electroosmotic flow within this layer. The model provides estimates of the average layer thickness that are comparable to those determined from contemporary models of surface-attached polymer.

Biophysical Phenomena↗