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Biomedical subjects

J C Werner

Publications and source records attributed to J C Werner.

At least 19 recordsLinked to original sources

Sympathetic ophthalmia associated with pars plana vitrectomy without antecedent penetrating trauma.

PURPOSE: To evaluate, describe, and categorize the clinical presentation, clinical course, histopathology, and response to therapy in patients without a history of penetrating ocular trauma who developed sympathetic ophthalmia following pars plana vitrectomy. METHODS: The records of patients without a history of trauma who underwent pars plana vitrectomy and developed sympathetic ophthalmia were retrospectively reviewed. Cases were analyzed with respect to clinical presentation, fluorescein angiographic findings, anatomic and visual outcomes, histopathology, and response to therapy. RESULTS: Eight eyes were identified. The median age at presentation was 55 years, with a range of 14 to 62 years. The time from vitrectomy to diagnosis of sympathetic ophthalmia ranged from 2 months to greater than 2 years, with a median of 7 months. Six of eight patients (75%) presented with anterior chamber reaction. All eight patients presented with a vitreous inflammatory response. The optic nerve was inflamed clinically or angiographically in four of eight cases (50%). Small yellow-white sub-retinal pigment epithelial deposits were present in four of eight cases (50%). Two eyes had lesions characterized as multifocal choroiditis. One eye had larger yellow placoid-like lesions. One eye presented with vitritis but no retinal lesions. Subretinal choroidal neovascularization was noted in the inciting eye of one patient. Vision improved in the sympathizing eye with immunosuppressive therapy in five of eight cases (62.5%). CONCLUSIONS: Sympathetic ophthalmia can be seen following pars plana vitrectomy in patients without penetrating injuries or a history of trauma. Indeed, it may be seen after successful vitrectomy for retinal detachment. Diverse clinical presentations are possible, and persistent or atypical uveitis following vitrectomy should alert the surgeon to the development of sympathetic ophthalmia.

Adolescent↗

Presumed acquired ocular toxoplasmosis in deer hunters.

PURPOSE: To describe acquired ocular toxoplasmosis in deer hunters. METHODS AND RESULTS: The authors describe five young men presenting with flu-like symptoms followed by visual loss due to a unilateral, focal necrotizing retinitis. All five men gave a history of ingesting undercooked or uncooked venison. All five had elevated toxoplasma serology, and all five improved clinically with an antitoxoplasma regimen. CONCLUSION: In previously healthy young men, flu-like symptoms associated with visual loss and retinitis should prompt questioning about hunting and raw game meat ingestion, especially when toxoplasmosis is suspected.

Adolescent↗

Vitrectomy update for macular traction in ocular toxocariasis.

PURPOSE: To study the results of modern vitrectomy in traction and combined traction-rhegmatogenous retinal detachment involving the macula in cases of ocular toxocariasis. METHODS: This was a cohort study of patients seen in different institutions in the United States. Ten eyes of 10 patients were studied. Vitrectomy was performed in all eyes, combined with membrane removal, scleral buckle, fluid-gas exchange, silicone oil, or lensectomy in certain cases. The anatomic and visual results of surgery were reviewed. RESULTS: Ten eyes from 10 patients ranging in age from 2 to 33 years (median, 6 years) were reviewed. Follow-up ranged from 3 months to 8 years (median, 2 years). All eyes achieved macular attachment following surgery; vision improved in 5 (50%) eyes, and was unchanged in 5 (50%). Histologic specimens from six eyes were reviewed, and revealed combinations of fibrous tissue, eosinophils, plasma cells, lymphocytes, and giant cells. One specimen revealed an encysted Toxocara canis organism. CONCLUSION: Inflammation created in response to Toxocara larvae may lead to traction retinal detachment of the macula. Vitreoretinal surgery has a good chance of reattaching the macula and improving vision.

Adolescent↗

Pars plana vitrectomy and subretinal surgery for ocular toxocariasis.

The clinical course of ocular toxocariasis and the chronological development of peripheral retinal and macular granulomas are reported. Removing the epiretinal as well as subretinal component of the granuloma via pars plana vitrectomy and retinotomy techniques yielded an excellent clinical result. Clinicopathologic correlation of the specimen confirmed the diagnosis with histological evidence of degenerated larval structures in granulomatous inflammation.

Animals↗

Postnatal hemodynamic changes in very-low-birthweight infants.

The purpose of this study was to characterize postnatal changes in regional Doppler blood flow velocity (BFV) and cardiac function of very-low-birthweight infants and to examine factors that might influence these hemodynamic changes. Mean and end-diastolic BFV of the middle cerebral and superior mesenteric arteries, cardiac output, stroke volume, and fractional shortening were measured in 20 infants birthweight 1,002 +/- 173 g, gestational age 28 +/- 2 wk) at 6, 30, and 54 h after birth and before and after feedings on days 7 and 14. Postnatal increases in cerebral BFV, mesenteric BFV, and cardiac output were observed that were not associated with changes in blood pressure, hematocrit, pH, arterial PCO(2), or oxygen saturation. The postnatal pattern of relative vascular resistance (RVR) differed between the cerebral and mesenteric vasculatures. RVR decreased in the middle cerebral but not the superior mesenteric artery. Physiological patency of the ductus arteriosus did not alter postnatal hemodynamic changes. In response to feeding, mesenteric BFV and stroke volume increased, and mesenteric RVR and heart rate decreased. Postprandial responses were not affected by postnatal age or the age at which feeding was initiated. However, the initiation of enteral nutrition before 3 days of life was associated with higher preprandial mesenteric BFV and lower mesenteric RVR than was later initiation of feeding. We conclude that in very-low-birthweight infants over the first week of life 1) systemic, cerebral, and mesenteric hemodynamics exhibit region-specific changes; 2) asymptomatic ductus arteriosus patency and early feedings do not significantly influence these postnatal hemodynamic changes; and 3) cardiac function adapts to increase local mesenteric BFV in response to feedings.

Blood Flow Velocity↗

Effects of prophylactic low-dose indomethacin on hemodynamics in very low birth weight infants.

Indomethacin decreases cerebral and mesenteric blood flow velocities in premature infants with symptomatic patent ductus arteriosus. Low-dose indomethacin is recommended for the prevention of intraventricular hemorrhage in very low birth weight infants. The hemodynamic effects of prophylactic indomethacin have not been previously examined. We hypothesized that prophylactic indomethacin does not change cerebral and mesenteric blood flow velocities and cardiac function in very low birth weight infants. Twenty-one infants (775 to 1245 gm, 24 to 31 weeks' gestation) were studied before and after indomethacin (0.1 mg/kg) administration at 6, 30, and 54 hours of life. Mean and end-diastolic cerebral and mesenteric blood flow velocities decreased (ANOVA, p < 0.05) after prophylactic indomethacin. The 38% increase in cerebral relative vascular resistance was significantly greater than the 18% increase in mesenteric relative vascular resistance (ANOVA, p < 0.05). In five infants who were fed 1 hour after the third indomethacin dose, the postprandial mesenteric blood flow velocity was significantly greater than the mesenteric blood flow velocity before both indomethacin and feeding (ANOVA, p < 0.05). Cardiac output, stroke volume, fractional shortening, and blood pressure did not change after prophylactic indomethacin administration. We conclude that prophylactic indomethacin (1) reduces cerebral and mesenteric blood flow velocity without affecting cardiac function, (2) increases cerebral more than mesenteric relative vascular resistance, and (3) does not prevent postprandial increases in mesenteric blood flow velocity. We speculate that the increase in cerebral relative vascular resistance is a beneficial effect that contributes to protection against intraventricular hemorrhage.

Analysis of Variance↗

Inhibition of PCR by aqueous and vitreous fluids.

The detection of viral nucleic acids in intraocular fluids and tissues by PCR has become increasingly important in clinical ophthalmology. While much attention has been directed toward minimizing false-positive reactions resulting from specimen contamination or amplicor carryover, relatively little attention has been given to the causes of false-negative PCRs. This report describes a PCR inhibitor in normal aqueous and vitreous fluids that can produce false-negative PCR results. As little as 0.5 microliter of vitreous fluid and 20 microliters of aqueous fluid can completely inhibit DNA amplification in a 100-microliters PCR mixture. This inhibition was not primer specific, nor was it due to chelation of Mg2+ ions or DNase activity in the ocular fluid. The inhibitor was completely resistant to boiling for 15 min. However, the inhibitory effects were completely removed by a single chloroform-isoamyl alcohol (24:1) extraction. The extent of PCR inhibition depended upon the type of thermostable DNA polymerase used in the reaction. Taq DNA polymerase was very sensitive to the inhibitor, while thermostable DNA polymerases from Thermus thermophilus HB-8 (Tth) and Thermus flavus (Tfl) were completely resistant. Thus, the inhibitory effects of intraocular fluids on PCRs can be removed by diluting the specimen, by chloroform extraction, or by using Tth or Tfl DNA polymerases.

Alphaherpesvirinae↗

Glucocorticoid metabolism in the newborn rat heart.

A relative cardiac hypertrophy has been observed in newborns chronically treated with dexamethasone. To test the hypothesis--that dexamethasone might alter steroid metabolism within the heart--rat pups were injected with vehicle, corticosterone (dosages 20 or 200 micrograms/pup/injection, or 1 mg/pup/injection) or dexamethasone (5 micrograms/pup/injection) on Day 2-6 and sacrificed on Day 7-8. Injections with dexamethasone in this dosage have induced the cardiac changes in this rat model. 11 beta-Hydroxysteroid dehydrogenase (11 beta-OHSD) activity was assessed in hearts from these adrenally intact rat pups by incubating tissues with 3H-corticosterone 10(-8) M for 60 min. On Day 7-8, controls transformed 10.3% +/- 1.1% (mean +/- SE) of the corticosterone (Compound B) to 11-dehydrocorticosterone (Compound A) generating 1.25 +/- 0.35 x 10(-12) moles A/mg protein (n = 8). Tissues from pups pretreated with corticosterone at all three dosages were not different from controls in percent metabolized and moles A/mg generated. In contrast, hearts from dexamethasone treated pups transformed only 4.5% +/- 1.0% of the corticosterone to A generating 3.19 +/- 0.05 x 10(-13) moles A/mg protein (n = 10) (P < 0.05 versus control in moles/mg protein metabolized). Cultured cardiomyocytes exposed to dexamethasone for 4 days in vitro also decreased their expression of 11 beta-OHSD mRNA. Readily metabolized endogenous glucocorticoids produced little or no effect on developing heart muscle while treatment with dexamethasone, a potent synthetic glucocorticoid, induced relative cardiac hypertrophy and downregulated 11 beta-OHSD mRNA expression and enzyme activity.

11-beta-Hydroxysteroid Dehydrogenases↗

Insulin reduces basal release of atrial natriuretic factor by isolated, perfused neonatal pig hearts.

Plasma atrial natriuretic factor (ANF) levels are markedly altered in diabetic rodents suggesting that insulin might be a modulator of ANF release. Effects of insulin (25 mU/ml) on basal (nonstimulated) immunoreactive (ir)-ANF release by isolated neonatal pig hearts paced at 150 beats/min and perfused with no change in atrial stretch were examined. Release of ir-ANF decreased with age from 1-3 days postpartum (146.0 +/- 38.4 to 62.2 +/- 20.5 fmol/g/min). Insulin stimulated myocardial glucose utilization and lactate production approximately 2-fold, but uniformly decreased ir-ANF release by approximately 25%, regardless of age. Correlations between ir-ANF release and myocardial metabolism suggest independent influences of insulin on these two events. In addition, it appears that this model might be reasonably exploited to investigate episodic ANF release and its regulation during ontogeny and in a variety of physiological states.

Aging↗

Hypertrophic cardiomyopathy associated with dexamethasone therapy for bronchopulmonary dysplasia.

The potential induction of cardiac effects by high-dose dexamethasone therapy was evaluated prospectively in 13 respirator-dependent infants with bronchopulmonary dysplasia by means of two-dimensional and M-mode echocardiography. The initial divided dose of dexamethasone was 500 micrograms/kg per day, tapered progressively for as long as 6 weeks. Evaluations were made before treatment and at 3, 7, 14, 21, 28, 35, and 42 days after the start of dexamethasone therapy. This regimen was associated with a significant (p less than 0.01) increase in thickness of the interventricular septum (2.60 +/- 0.09 to 4.00 +/- 0.16 mm), diastolic left ventricular free wall (2.80 +/- 0.13 to 4.06 +/- 0.20 mm), and diastolic right ventricular free wall (1.55 +/- 0.08 to 2.02 +/- 0.12 mm). In addition, seven dexamethasone-treated infants but no control infants had systolic anterior motion of the mitral valve (p less than 0.001). These effects were transient, reached their maximal degree by the third week of treatment, and approached pretreatment conditions by the sixth week of treatment. Ejection fraction was not affected; heart rate and mean arterial pressure were transiently increased during dexamethasone therapy. We conclude that a transient absolute myocardial hypertrophy is associated with dexamethasone therapy in infants with bronchopulmonary dysplasia. The mechanism or mechanisms through which this hypertrophy arises and the cardiopulmonary implications are unclear.

Bronchopulmonary Dysplasia↗

Variation of perfluoropropane disappearance after vitrectomy.

In complex cases of retinal detachment, perfluoropropane (C3F8) is frequently used after vitrectomy for tamponade of retinal breaks. Results of previous studies of C3F8 disappearance using 10% C3F8 after vitrectomy in human eyes have differed significantly. A wide variation in the decay rate and half life of C3F8 after vitrectomy was observed in eyes that had similar clinical settings and received the same C3F8 concentration (15%, 20%, or 25%). This occurred even in those eyes where there was no change in the geometric contour of the eye after a repeat vitrectomy.

Eye↗

Atrial natriuretic peptide in newborn piglets with a patent ductus arteriosus.

Atrial natriuretic peptide (ANP) is a hormone involved in fluid and blood pressure homeostasis. We studied the effects of left-to-right shunting through a patent ductus arteriosus on blood pressure changes and plasma ANP concentrations in newborn piglets. In five experimental piglets, the ductus arteriosus was bathed with PGE1 and infiltrated with formalin to maintain its patency. In four age-matched control piglets, the ductus arteriosus was ligated. Plasma ANP concentrations and blood pressure determinations were obtained prior to (base-line) and 25 +/- 1 h (day 1), and 48 +/- 1 h (day 2) after surgery. Radionuclide-microsphere determinations of left-to-right patent ductus arteriosus shunts were performed on days 1 and 2 in the 5 piglets with a patent ductus arteriosus. Plasma ANP concentrations were significantly elevated in the left atrium on day 1 and the right atrium on day 2 in the PDA piglets. No correlation was demonstrated between plasma ANP concentrations and right or left atrial pressures. We conclude that left and right plasma atrial ANP concentrations are significantly elevated in newborn piglets with left-to-right patent ductus arteriosus shunts.

Animals↗

Dexamethasone induces a transient relative cardiomegaly in neonatal rats.

Effects of s.c. administration of dexamethasone (1-25 micrograms/rat pup/d) during the first 5 d postpartum on survival rates, body weight, heart weight, heart-to-body weight ratios, and heart dimensions were determined. Dexamethasone decreased survival, body weight, and heart weight, but increased heart-to-body weight ratios and myocardial percentage of dry weight (0.44 to 0.52-1.06 and 20 to 23%, respectively; p less than 0.05) by 7 d postpartum. By 21 d postpartum, differences in absolute body weight and heart weight between control and experimental animals were reduced; however, myocardial percentage of dry weight and heart-to-body weight ratios were indistinguishable. Microscopic analysis of 7-d-old hearts disclosed that interventricular septum, left ventricular free wall thicknesses, and left ventricle chamber diameter were reduced (0.93 to 0.76-0.85 mm, 1.19-1.34 to 0.92-1.07 mm, and 1.35-1.40 to 0.89-1.23 mm, respectively; p less than 0.05), whereas right ventricular free wall thickness was unaffected and right ventricle chamber diameter was increased (0.29-0.31 to 0.42-0.46 mm) by dexamethasone. Thus, dexamethasone reduced survival and retarded growth of neonatal rats. Retardation of heart growth was less severe, producing a transient relative cardiomegaly characterized by 1) increased myocardial percentage of dry weight, 2) increased left ventricular free wall-to-chamber ratio, and 3) retention of absolute right ventricular free wall thickness. This relative cardiomegaly appeared to be resolved by 21 d postpartum, as reflected in myocardial percentage of dry weight and heart-to-body weight ratios.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Palmitate oxidation by isolated working fetal and newborn pig hearts.

Palmitate oxidation and the effect of palmitate on glucose and lactate utilization were investigated in isolated, perfused, fetal (0.9 gestation), and neonatal (2 day old) pig hearts. Hearts were perfused under working conditions, developing a mean aortic pressure of 50-55 mmHg, paced at 180 beats/min for 30 min, with Krebs-Henseleit buffer containing 3% albumin, glucose (5 mM), and insulin (100 microU/ml). Palmitate (1 mM) and lactate (5 mM), either individually or in combination, were added to the perfusion buffer. Palmitate oxidation was assessed from 14CO2 production from [U-14C]-palmitate, glucose uptake as 3H2O production from D-[2-3H]-glucose, and lactate metabolism from changes in buffer lactate content. After perfusion, ATP, creatine phosphate, triglycerides, and glycogen were measured. Substantial palmitate oxidation was observed at both ages but was greater in neonatal hearts. Nevertheless, palmitate inhibited lactate utilization and glucose uptake similarly in fetal and neonatal hearts. Lactate also reduced palmitate uptake and oxidation by 40-60% in both fetal and neonatal hearts. During perfusions with palmitate, tissue concentrations of triglycerides increased approximately threefold in fetal hearts and were unaffected by lactate. Thus both palmitate and lactate can act as major energy substrates for the immature heart. Both substrates significantly (P less than 0.01) suppress glucose utilization, and each has suppressive effects on the other's metabolism.

Adenosine Triphosphate↗

Insulin responsiveness of neonatal pig myocardium.

The transition from preferential use of carbohydrates to fatty acids for energy production by neonatal mammalian myocardium might be hormonally influenced. In neonatal pigs (between 1 and 4 days of age), plasma glucose, lactate, and glucagon concentrations remained constant at adult levels, while plasma triglycerides and insulin content remained stable at substantially lower levels. Insulin, whether administered in vivo or during perfusion, increased myocardial glucose utilization [GU] and lactate production [LP]. Stimulation of GU and LP by insulin exposure in vivo persisted for at least 1 h during perfusions after insulin was removed. Exogenous lactate (0.5 mM) diminished insulin-stimulated GU and LP; and was used as a substrate at 1.25 mM. Thus, insulin augmented glycolytic activity of neonatal piglet myocardium; however, exogenous lactate, within the physiological range, altered the nature of the myocardium's response by, as yet, undetermined mechanisms. Therefore, the transition from carbohydrate to fatty acid utilization for energy production by the neonatal myocardium does not appear to result from decreased carbohydrate metabolism or reduced myocardial responsiveness to insulin.

Animals↗

Lactate metabolism of isolated, perfused fetal, and newborn pig hearts.

The role of lactate as an energy substrate in fetal (0.9 gestation) and newborn (2 day old) hearts was investigated in isolated, perfused hearts. Perfusions were performed with Krebs-Henseleit buffer supplemented with glucose (5 mM) in combination with varying concentrations of lactate. Isolated working heart perfusions, in which the heart ejects the buffer at controlled pressure, were carried out with glucose (5 mM) alone and with glucose (5 mM) and lactate (5 mM) combined. With glucose as sole substrate, lactate was produced by the heart and glucose uptake accounted for approximately two-thirds of oxygen consumption. When both glucose and lactate were provided, lactate accounted for more than 80% of oxygen consumption and profoundly suppressed glucose uptake. Further investigations using retrograde perfusion through the aorta demonstrated that lactate uptake was consistently observed when exogenous lactate concentrations exceeded 1.25 mM. Glucose uptake was suppressed with lactate concentrations as low as 0.5 mM and progressive suppression occurred with increasing lactate concentrations. Fetal and newborn pig hearts utilize lactate as a primary substrate for energy production when lactate concentrations are in the physiological range.

Adenosine Triphosphate↗

Coronary vascular responses to hypoxia in the diabetic lamb: independence from adenosine and autonomic mechanisms.

We have previously found that the coronary dilator response to infused adenosine is attenuated in diabetic (alloxan) lambs. Adenosine responsiveness is restored by administration of insulin. The present studies tested the hypothesis that coronary flow changes with hypoxia, if mediated by adenosine, would also be modified. Studies were carried out in eight control and six diabetic lambs. The animals were anesthetized and prepared to maintain constant arterial pressure (reservoir), cardiac output (pump), and heart rate (paced). Atropine and practolol were given. Forced inspired oxygen was reduced in steps. Arterial and coronary sinus blood samples were analyzed for Po2, oxygen content, pH, hematocrit, and glucose. Myocardial oxygen delivery and uptake (MVO2) were calculated. Coronary flow increased identically in both control and diabetic animals as PaO2 was reduced below 60 Torr. Oxygen delivery and MVO2 fell equally in both groups. Acidosis potentiated hypoxic coronary flow changes. Alpha blockade (phentolamine) was without effect in control lambs but caused coronary flow to increase in diabetic lambs. Changes in coronary flow with hypoxia were unaffected, however. Insulin caused no change in the coronary dilator response to hypoxia in either control or diabetic lambs. It is concluded that coronary alpha tone is increased in diabetes but does not modify changes in coronary flow during hypoxia. As coronary flow responses to hypoxia were unaltered in diabetic lambs, and unaffected by insulin, adenosine may not be the primary mediator of coronary vascular dilatation. Potentiation of adenosine by tissue acidosis is apparently insufficient to explain these findings. The mechanism for coronary dilatation during hypoxia is unclear but may involve direct effects of reduced oxygenation of coronary vascular smooth muscle.

Acidosis↗

Cardiac dysfunction during status epilepticus in the neonatal pig.

Cardiovascular complications frequently occur during status epilepticus. To determine the changes in systemic and pulmonary arterial pressure, cardi output, and left ventricular contractility during seizures, 1-week-old pigs were intubated, paralyzed, mechanicall entilated, and catheterized with a Swan-Ganz catheter. Seizures were induced with intravenous bicuculline. Early changes consisted of significant systemic and pulmonary arterial hypertension. After 2 hours of seizures, the animals developed progressive systemic hypotension and decreased cardiac output. M-mode echocardiography disclosed a decrease in left ventricular contractility. Cardiac tissue frozen in situ showed a significant increase in lactate and reductions in glucose, triglyceride, and adenosine triphosphate levels. Prolonged seizures in the neonatal pig result in cardiac dysfunction, which may play a role in the development of epileptic brain damage.

Acid-Base Equilibrium↗