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Biomedical subjects

M Lynn

Publications and source records attributed to M Lynn.

At least 37 records · Page 2Linked to original sources
PubMed1999

Lipoprotein distribution of a novel endotoxin antagonist, E5531, in plasma from human subjects with various lipid levels.

The purpose of this study was to determine the distribution profile of a novel endotoxin antagonist, [(14)C]E5531, at 1 microg/ml in plasma samples obtained from fasted human subjects with various lipid and protein concentrations. Our findings suggest that the majority of E5531 binds with high-density lipoproteins (HDLs) independently of plasma lipid and protein levels tested. Furthermore, it appears that an increase in triglyceride-rich lipoprotein (TRL) lipid and protein levels and an increase in low-density lipoprotein (LDL) lipid levels significantly increase TRL plus LDL binding of E5531. However, only an increase in HDL protein levels significantly increases HDL binding of E5531.

Endotoxins↗
PubMed1999

Emmetropization in the rhesus monkey (Macaca mulatta): birth to young adulthood.

PURPOSE: To provide baseline measurements on the postnatal changes in refractive error, corneal curvature, and axial elongation of the eyes of normal monkeys. Little is known about the course of normal eye growth from birth to adolescence, particularly how refractive parameters co-vary during development. In animal models of ametropia, usually one eye is manipulated and the fellow eye serves as a control. However, given individual differences, and without baseline data, it is impossible to determine whether either eye develops normally. METHODS: Measurements were obtained on 237 rhesus monkeys, whose ages ranged from birth to 5 years. Examinations included cycloplegic refraction by retinoscopy, keratometry measurements, and A-scan ultrasound measurements of axial length. The time course of development was evaluated using a growth curve analysis appropriate for a mixture of cross-sectional and longitudinal data. RESULTS: At birth, all three parameters were normally distributed and only weakly correlated. Monkeys had +7 D (SD=2.3 D) of hyperopia, corneal power of 58 D (SD=1 D), and axial length of 13.2 mm (SD=0.4 mm). Refractive error ranged from +0.5 D to +14.5 D, with a mean difference between the two eyes of 0.5 D. Corneal curvature ranged from 61 D to 54 D, with a mean difference between the two eyes of 0.8 D. Axial length ranged from 12.0 mm to 14.2 mm, with a mean difference between the two eyes of 0.1 mm. Although the degree of hyperopia achieved asymptote, of + 2 D, shortly after 1 year of age, corneal curvature and axial length did not achieve asymptote until nearly 5 years of age. By this time, refractive error had declined by 5 D, corneal curvature had declined by 7 D, and axial length had increased by 6 mm. CONCLUSIONS: The magnitude of the individual differences that can occur in a small sample of experimental subjects is large enough to necessitate reference to age norms derived from a large population. Our results provide a baseline for studies of normal and abnormal eye growth and ametropia in primates. Our results also led to the confirmation of a set of "rules" that have been offered as an explanation of how these three parameters interact during emmetropization.

Aging↗
PubMed1998

Contrast sensitivity and glare disability after radial keratotomy and photorefractive keratectomy.

OBJECTIVES: To study the effects of radial keratotomy (RK) and photorefractive keratectomy (PRK) on contrast sensitivity and glare disability using 4 different devices, and to correlate subjective complaints with obj ective scores of visual performance. METHODS: Preoperative contrast sensitivity for 30 eyes undergoing RK and 30 eyes undergoing PRK was compared with contrast sensitivity at 1, 3, and 6 months postoperatively using the CSV 1000, MCT (Multivision Contrast Tester) 8000, and Pelli-Robson chart. The BAT (Brightness Acuity Tester) and MCT 8000 were used to test for daytime and nighttime glare disability, respectively. At 3 and 6 months postoperatively, a questionnaire was administered to assess visual performance subjectively. RESULTS: Contrast sensitivity decreased after RK and PRK up to the sixth postoperative month, while glare disability was significantly increased at 1 month after PRK as determined by the MCT 8000 and the BAT, and at the third and sixth months after RK using the MCT 8000. Compared with RK, PRK significantly decreased contrast sensitivity as measured with the MCT 8000 at all spatial frequencies 1 month postoperatively. No significant difference in visual performance between patients undergoing RK and PRK was observed with the CSV 1000, the Pelli-Robson chart, or the BAT up to 6 months postoperatively. No consistent difference was found between glare disability scores of patients undergoing RK and PRK when measured with the MCT 8000. Subjective reports of problems with night driving and blurring correlated only with glare disability scores of the MCT 8000 3 months after RK. CONCLUSIONS: Both RK and PRK reduce contrast sensitivity and cause glare disability; however, the relative effect is highly dependent on the time postoperative testing is performed and the instrument used for testing. Contrast sensitivity and glare disability, as measured by the instruments used in this study, do not accurately reflect patients' subjective assessment of visual performance in daily life.

Adult↗
PubMed1998

An open-label dose comparison study of ondansetron for the prevention of emesis associated with chemotherapy prior to bone marrow transplantation.

Nausea and vomiting are significant side effects in bone marrow transplant (BMT) patients who receive high-dose preparative regimens. Higher than conventional ondansetron doses and continuous infusion might improve emetic control, because of the high doses and combinations of chemotherapy (CT) used in this setting. Our objective was to conduct a prospective, randomized study comparing two different administration methods of high-dose ondansetron during a BMT preparative regimen in breast cancer patients. Patients were eligible if they were nonpregnant women over 18 but under 65 years of age, undergoing highly emetogenic CT in preparation for autologous BMT. All patients received ondansetron as an intermittent (INT = 24 mg i.v. q 12 h/day) or continuous intravenous infusion (CIV = 8 mg i.v. loading dose followed by a continuous infusion of 2 mg/h per day). A total of 66 patients were enrolled in the study (n = 34, INT; n = 32, CIV). There was no statistical difference between treatment groups in the worst grade of emesis for the entire study period (P = 0.49). Greater than 90% of all patients were graded as failures (> or = 5 emetic episodes or need for rescue antiemetics). Complete control (no vomiting episodes) and complete plus major control (1-2 emetic episodes) per day ranged from 8% to 85% and 11% to 91%, respectively. There was no significant difference between the treatment arms in: grade of emesis, episodes of vomiting and retching, nausea scores, and mean number of rescue medications administered. There were no differences in efficacy when high-dose ondansetron was given as CIV or INT for the control of nausea and vomiting in breast cancer patients undergoing high-dose CT for autologous BMT. Ondansetron alone was not adequate to provide sustained control of CT-induced nausea and vomiting over the entire 5-day study period. A combination of antiemetics targeting various mechanisms of CT-induced nausea and vomiting may be necessary to improve response rates.

Adult↗
PubMed1998

The impact of antioxidant and splanchnic-directed therapy on persistent uncorrected gastric mucosal pH in the critically injured trauma patient.

BACKGROUND: Critically ill trauma patients with gastric intramucosal acidosis, as measured by gastric tonometry, have an increased incidence of multiple organ dysfunction syndrome despite supranormal O2 delivery. We altered our resuscitation protocol to maximize splanchnic blood flow and decrease oxygen-derived free radical damage. DESIGN: Prospective clinical trial with historical controls. METHODS: The protocol differed from control by including administration of folate, mannitol, and low-dose isoproterenol. All patients had gastric tonometers and pulmonary artery catheters. If the intramucosal pH (pHi) was less than 7.25, splanchnic-sparing inotropic and vasodilatory agents were used to optimize systemic cardiac output. Two groups of trauma patients with persistent intramucosal acidosis at 24 hours (pHi < 7.25) were compared: a control group (n = 7), and patients who received the splanchnic/antioxidant protocol (n = 13). RESULTS: The two groups were similar based on Acute Physiology and Chronic Health Evaluation II score, Injury Severity Score, age, cardiac index, oxygen delivery, and oxygen consumption. The "splanchnic therapy" group had fewer organ system failures as well as shortened length of intensive care unit and hospital stay. Three of 7 patients in the control group and 2 of 13 patients in the splanchnic therapy group had a final pHi < 7.25. CONCLUSION: Gastric tonometry-guided resuscitation and antioxidant/splanchnic therapy in critically ill trauma patients with persistent gastric mucosal acidosis may decrease multiple organ dysfunction syndrome.

APACHE↗
PubMed1998

Can surgeons evaluate emergency ultrasound scans for blunt abdominal trauma?

OBJECTIVE: To determine whether surgeons and residents with minimal training can evaluate accurately emergency ultrasound (US) examinations compared with radiologists for blunt abdominal trauma. METHODS: Over 7 months, we conducted a prospective study comparing the evaluation of emergency US for blunt abdominal trauma by surgeons and attending radiologists. US readings from the surgical team and the radiologists were correlated with outcome. RESULTS: One hundred-twelve patients were included in the study. Ninety-two patients had an US read as negative by the surgical and radiology services with no subsequent injuries identified. Eighteen patients had an US deemed positive by the surgical service and radiologists. Injuries were confirmed in this group by operation or computed tomography. One patient had an US deemed positive by the surgical team and subsequently negative by the radiologist. A diagnostic peritoneal lavage was performed which was negative. Another patient had an US interpreted as negative by the surgical evaluator and positive by the radiologist. Exploratory laparotomy was negative for intraabdominal hemorrhage or organ injury. Overall results reveal an accuracy on US reading of 99% for the surgical team and 99% for the attending radiologists. CONCLUSION: Surgeons and surgical residents at different levels of training can accurately interpret emergency ultrasound examinations for blunt trauma from the real-time images, at a level comparable to attending radiologists.

Abdominal Injuries↗
PubMed1998

In vivo human melanoma cytokine production: inverse correlation of GM-CSF production with tumor depth.

Melanomas produce multiple cytokines which may influence their growth in vivo. Experimental evidence suggests that granulocyte macrophage-colony stimulating factor (GM-CSF) can induce a potent anti-melanoma response. whereas interleukin-8 (IL-8) may act as a growth factor in human melanoma. Little is currently known regarding the production of these cytokines by human melanoma in vivo. In this study we tested the hypothesis that endogenous production of GM-CSF and IL-8 can be correlated with the depth of human malignant melanoma surgical specimens. We examined 45 melanocytic human tissue samples consisting of 27 primary cutaneous melanomas, 9 metastatic melanomas, and 9 dysplastic nevi for in vivo GM-CSF and IL-8 production using immunohistochemistry. The majority of thin melanomas (< or = 0.76 mm) stained highly positive for GM-CSF with little or no staining for IL-8 whereas the medium (>0.76- < or = 4.0 mm) and thick (>4.0 mm) melanoma specimens showed little or no staining for GM-CSF and significant amounts of IL-8 staining. Metastatic melanoma as well as dysplastic nevi specimens had little or no GM-CSF and IL-8 staining. These results support the hypothesis that endogenous melanoma cytokines such as GM-CSF and IL-8 with opposing effects on tumor progression play an important role in melanoma growth and regulation.

Biomarkers, Tumor↗
PubMed1998

Neoral conversion from Sandimmune in maintenance renal transplant patients: an individualized approach.

When converting maintenance renal allograft recipients from Sandimmune (cyclosporin A [CsA]) to Neoral (CsA-microemulsion [CsA-ME]), a dose conversion ratio of 1:1 may not be optimal, in part because of the variability in absorption of the CsA formulation of cyclosporine. After conversion using a 1:1 dose ratio, an individualized approach to the management of dosing was applied. In this article, close monitoring, which began at the time of conversion, and rapid response to potentially meaningful changes in cyclosporine trough levels early in the postconversion course were used to maintain patients' cyclosporine troughs at preconversion levels. The results of cyclosporine dose changes after converting stable, maintenance renal transplant patients from CsA (once daily and twice daily) to CsA-ME (twice daily) during 52 wk of follow-up are reported. Most patients (87.2%) required CsA-ME dose reduction to maintain preconversion trough levels, and 64% of the patients attained their CsA-ME maintenance dose by study week 4. Logistic regression analysis identified one significant predictor concerning the week 52 CsA-ME dose: patients converted from CsA doses > or = 4.0 mg/kg per d were more likely to require dose reduction (P < 0.0001). Although firm guidelines for dose modification after conversion from CsA to CsA-ME cannot be provided because of the individual nature of cyclosporine absorption, an individualized approach to patient management is recommended. Patients with higher CsA doses before conversion are particularly likely to require dose reduction early in the postconversion course. With CsA-ME, good absorbers of cyclosporine remain good absorbers, or become better absorbers, whereas poor absorbers become good absorbers.

Adult↗
PubMed1998

The role of liver transplantation in the subacute trauma patients.

Two case reports are presented involving complex liver traumas requiring the need for liver transplantation. Both of these patients were designated unsalvageable until the transplant team was consulted. It is imperative that surgeons involved with complex hepatic trauma not give up hope and include these patients as potential liver recipients when irreversible liver failure occurs.

Adult↗
PubMed1997

Tumor angiogenesis as a prognostic factor in laryngeal cancer.

BACKGROUND: Lymph node metastasis is the single greatest predictor of recurrence in laryngeal cancer. Prognostic factors are needed to target patients who may benefit from adjuvant therapy. Tumor angiogenesis correlates with metastasis in breast, bladder, and oral cavity cancer and may have prognostic value in other tumors. METHODS: In order to examine the relationship of tumor angiogenesis to recurrence, 51 patients with squamous cell carcinoma of the larynx were reviewed. In a blinded design, previously sectioned slides were chosen for advanced tumor and highest vessel concentration. Samples were cut and immunocytochemically stained for CD-31 (an endothelial marker). A computer image analyzer quantitated the percent area of staining. Variables were statistically examined against recurrence. RESULTS: Patients were stratified by percent tumor staining. Nodal involvement was seen in 9 (36%) patients with tumor staining < or = 20% and in 20 (77%) with tumor staining > 20% (P = 0.003). Patients with < or = 20% staining and without metastasis had a 13% rate of recurrence whereas patients with > 20% staining and without metastasis had a 67% rate of recurrence (P = 0.025). CONCLUSIONS: Though nodal status was suggestive of predictability, only angiogenesis is a statistically significant predictor of recurrence in node negative patients (P = 0.025). Angiogenesis shows strong correlation with regional recurrence and may be used as an independent prognostic indicator to determine clinically node negative patients who may be at higher risk for metastasis and require adjuvant therapy.

Carcinoma, Squamous Cell↗
PubMed1997

Neutrophil activation in acute human central nervous system injury.

The hypothesis that neutrophil activation exacerbates brain injury in acute stroke is currently receiving wide acceptance. However, the temporal relationship of neutrophil activation to the ischemic event in clinical states is not clear. Therefore, this study was undertaken to examine human neutrophil activation by the technique of luminol-dependent chemiluminescence in both acute bland and hemorrhagic stroke. Patients (bland, n = 18; hemorrhagic, n = 16) were entered into this study within six hours of the ictus. These results were compared to other clinical central nervous system insults: subarachnoid hemorrhage (n = 11), spinal trauma (n = 9) and isolated closed head injury (n = 19). All subjects were sampled upon presentation to the emergency room and 0.5, 1, 2, 3, 4 and 5 days following the event. Neutrophil activation, as determined by luminol-dependent chemiluminescence, was evident at day 1 following the ictus in the bland stroke group (p < 0.05), although this trend was not demonstrated for hemorrhagic stroke. Patients suffering a closed head injury demonstrated greater initial neutrophil activation with values being significantly lower than baseline at days 0.5 (p = 0.01) and 1 (p = 0.05). No significant change was demonstrated for the groups with spinal trauma or subarachnoid hemorrhage. These results support a role for neutrophil activation during various central nervous system insults and provide a temporal framework for considering drug therapy directed at transient suppression of neutrophil function.

Adult↗
PubMed1996

The effect of photorefractive keratectomy on the corneal endothelium.

PURPOSE: The authors prospectively investigated the effect of excimer laser photorefractive keratectomy (PRK) for myopia on the corneal endothelium. METHODS: Quantitative computer-assisted morphometric analysis of central and peripheral corneal endothelial cells was performed on 142 myopic eyes before and at 3 months, 1 year, and 2 years after PRK. The mean age of the subjects was 37 years (range, 21-66 years). Ninety-one (64%) of them had a history of contact lens wear. Mean attempted correction was -3.9 diopters (range, -1.6 to -6.0 diopters). RESULTS: The mean preoperative endothelial cell density was 2660 cells/mm2 centrally and 2776 cells/mm2 peripherally. There was no change in central endothelial cell density at any of the postoperative examinations. The peripheral cell density decreased 4.1% (P = 0.003) at 3 months and 6.2% (P = 0.0001) at 1 year. However, the peripheral cell density was not significantly different from the preoperative value at 2 years. The peripheral coefficient of variation of cell size was 7.8% lower 2 years postoperatively than it was preoperatively, and this improvement was attributable to cessation of contact lens wear after PRK. The decrease in peripheral endothelial cell density at 1 year correlated with the amount of attempted correction, but there was no correlation between attempted correction and the change in central or peripheral endothelial cell density 2 years postoperatively. CONCLUSION: For the correction of up to 6.0 D of myopia, PRK causes no detectable changes in central corneal endothelial cell density, but it does cause a transient, modest loss of peripheral corneal endothelial cells at 1 year. Variations in endothelial cell shape caused by contact lens wear resolve after PRK.

Adult↗
PubMed1996

Ciliary body endophotocoagulation during pars plana vitrectomy in eyes with vitreoretinal disorders and concomitant uncontrolled glaucoma.

PURPOSE: To investigate the efficacy of ciliary body endophotocoagulation during pars plana vitrectomy in eyes with medically uncontrolled glaucoma and concomitant vitreoretinal disorders. METHODS: The authors compared preoperative and postoperative intraocular pressure (IOP) and visual acuity in 21 eyes of 21 patients undergoing ciliary body endophotocoagulation with pars plana vitrectomy. RESULTS: Preoperative IOPs ranged from 22 to 59 mmHg (median, 46 mmHg). Visual acuity ranged from 20/200 to light perception (median, hand motions). Follow-up ranged from 3 to 18 months (median, 10 months). Postoperative IOPs ranged from 11 to 19 mmHg (median, 16 mmHg) at 6 weeks, 4 to 20 mmHg (median, 14 mmHg) at 3 months, 1 to 26 mmHg (median, 12 mmHg) at 6 months, and 0 to 48 mmHg (median, 12 mmHg) at 12 months. Postoperative visual acuity was statistically improved from preoperative visual acuity by 6 weeks. CONCLUSION: Ciliary body endophotocoagulation combined with pars plana vitrectomy can effectively treat concomitant glaucoma and vitreoretinal disorders.

Adult↗
PubMed1996

Donor factors associated with epithelial defects after penetrating keratoplasty.

The records of 39 patients undergoing 40 consecutive penetrating keratoplasties were reviewed to identify donor factors that might correlate with the presence of an epithelial defect on the first postoperative day. Of the 40 transplanted corneas, 13 (32.5%) had no epithelial defect, 18 (45%) had some epithelial defect, and nine (22.5%) had a total epithelial defect 1 day postoperatively. The status of the epithelium was correlated with several donor factors. The only factor that had a statistically significant association with the degree of epithelial defect was the time interval from preservation to surgery (p = .001). Based on a logistic regression model, the probability of having an epithelial defect 1 day after penetrating keratoplasty increased with respect to longer storage times. These results may aid the surgeon in the selection of donor tissue, particularly when performing penetrating keratoplasty on patients with ocular surface disorders.

Adolescent↗
PubMed1995

Case report: mannitol nephrotoxicity syndrome: role of hemodialysis and postulate of mechanisms.

High-dose intravenous mannitol infusion in various clinical settings may result in acute renal failure (ARF). This form of ARF is characteristically anuric and follows a distinctive clinical course. Most importantly, it occurs only after high doses of mannitol (> 200 g/day or cumulative dose of > 400 g in 48 hours), but not at lower doses. It appears that a low dose of mannitol acts as a renal vasodilator while high-dose mannitol is renal vasoconstrictor. Mannitol-induced ARF responds promptly to hemodialysis with rapid resolution of anuria and recovery of renal failure. This is a report of a case of anuric ARF after high-dose mannitol infusion for treatment of narrow-angle glaucoma that readily responded to acute hemodialysis. The literature is also reviewed for ARF associated with mannitol infusion in patients who received dialysis and those who did not receive dialysis; and the possible mechanism(s) of mannitol nephrotoxicity are discussed. Hemodialysis should be performed for rapid reversal of mannitol-induced ARF. Patients not treated with hemodialysis have increased morbidity and significant prolongation of their hospital course.

Acute Kidney Injury↗