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Biomedical subjects

M B Zimmerman

Publications and source records attributed to M B Zimmerman.

At least 37 records · Page 2Linked to original sources

A randomized study of mitomycin augmentation in combined phacoemulsification and trabeculectomy.

PURPOSE: The purpose of the study is to determine whether the intraoperative application of subconjunctival mitomycin C (MMC), during combined phacoemulsification and trabeculectomy, is an effective means of improving filtration, defined as overall lower intraocular pressure (IOP) and less antiglaucoma medication use. METHODS: Twenty-nine patients with a visually significant cataract and glaucoma were randomized, in a double-masked fashion, to receive intraoperative MMC (0.5 mg/ml) or placebo. RESULTS: Follow-up ranged from 6 to 30 months (mean, 20 months). Postoperative visual acuity at 1 year was 20/40 or better in 14 of 15 eyes operated on in the placebo group and 13 of 14 eyes operated on in the MMC group. Intraocular pressure at 8 months averaged 15.2 +/- 1.5 mmHg in the placebo-treated eyes versus 12.3 +/- 1.6 mmHg in the MMC-treated eyes. At 12 months, IOPs averaged 16.2 +/- 1.5 mmHg in the placebo-treated eyes versus 12.6 +/- 1.0 mmHg in the MMC-treated eyes. On average, the MMC group had postoperative IOP levels 3.0 mmHg lower than did the placebo group (P = 0.04) throughout the study. In the placebo group, laser suture lysis was required in a greater number of patients (80% versus 43%) and to a greater extent (mean = 2.0 versus 0.7 suture lysed) (P < 0.05). At 12 months, 5 of the 15 patients in the placebo group required an average of 1.8 medications for IOP control, whereas 0 of the 14 patients in the MMC group needed IOP-lowering medications. A late endophthalmitis developed through an intact bleb in one patient in the MMC group; otherwise, complications were minimal in each group. CONCLUSION: These results suggest that intraoperative MMC application, during combined phacoemulsification and trabeculectomy surgery, does improve early filtration as shown by overall lower IOPs and less antiglaucoma medication use.

Aged↗

Assessment of the tear film with tandem scanning confocal microscopy.

PURPOSE: To evaluate the confocal microscopic appearance of the tear film by correlating the interference pattern created by the lipid surface with physiologic measurements of tear function and with clinic diagnosis. METHODS: A series of 53 patients was examined with a battery of tests to evaluate the tear film and with confocal microscopy to evaluate the interference pattern created by the lipid surface of the tear film. Assessment of the tear-film appearance involved five nonparametric scales: degree of debris in the tear film, variability of the interference pattern over time, linearity of the interference pattern, number of dry spots seen, and relative thickness of the lipid layer. For 10 other subjects, the confocal appearance of the tear film and evaporation from the ocular surface was tested for before and after meibomian gland expression. RESULTS: The confocal appearance correlated with multiple physiologic variables and clinical diagnosis. Patients with seborrheic meiboman gland dysfunction had a thicker lipid layer, greater variability, and more debris than did patients with obstructive meibomiam gland dysfunction. After meibomian gland expression, lipid thickness and linearity increased, whereas pattern variability and evaporation decreased significantly. The mean reduction in evaporation was 48%. CONCLUSIONS: Confocal microscopy can be used to examine the tear film, and its appearance correlates significantly with physiologic variables in normal-individuals and in disease states. The confocal appearance of the lipid interference patterns and evaporation from the ocular surface are altered after lipid expression from meibomian glands.

Adolescent↗

Model for ocular tear film function.

Blepharitis patients have a number of disturbances in their tear film associated with meibomian gland dysfunction that affect evaporation and tear osmolarity. We tested a series of 156 consecutive patients, with a presumed diagnosis of blepharitis, dry eye, or allergic disease, and a series of 72 normals. We compared their tear film characteristics using tear osmolarity, tear volume, tear production (fluorophotometric and Schirmer test), tear turnover (decay constant), tear evaporation, and meibomian gland function evaluated by gland drop-out, expressed lipid viscosity, and volume. Of the 156 patients tested, we found 37 had dry eye, 10 had only allergic disease, 73 had meibomian gland dysfunction and dry eye, and 36 had only meibomian gland dysfunction. We created a model of the relative influence some of these factors had on each other using their correlation coefficients. The highest correlations for osmolarity were Schirmer test (-0.44), lipid volume low (-0.44), lipid viscosity high (0.39), gland drop-out (0.39), and tear evaporation (0.36). With regression analysis we accounted for 47% of the total variation in osmolarity, but only 17% of the variation in tear evaporation. We also present our classification system for blepharitis and dry eye patients based on our measurable physiologic parameters.

Blepharitis↗

Tear film changes associated with normal aging.

We examined a group of normal subjects to evaluate the tear film function by measuring reflex tear capacity using the Schirmer test without anesthetic, steady state tear flow using fluorophotometry, meibomian gland function based on gland drop-out, expressible lipid volume and viscosity, tear loss from evaporation, and tear osmolarity. We found the average tear flow to be 0.19 +/- 0.19 microliters/min, lower than previously measured. The average tear volume was also correspondingly less, 2.74 +/- 2.0 microliters. We found there was a decline associated with advancing age for all parameters except the decay constant and lipid volume. The highest correlations with aging were tear volume (-0.64), Schirmer test (-0.63), and tear osmolarity (0.59). Our results indicate that there is a decline in tear film function throughout life and that tear flow is considerably less than previously estimated.

Adolescent↗

Craniofacial growth in rabbits after rigid or semi-rigid fixation of the frontonasal suture.

Treatment of craniofacial dysostosis involves complex remodeling of the cranium and facial bones. Maintenance of the newly positioned segments may be achieved by rigid fixation using plates; however, there is concern that, over time, these plates may interfere with normal growth. The purpose of this study was to test a method of "semi-rigid" fixation of an osteotomy of the frontonasal suture in juvenile rabbits by comparing standardized parameters of craniofacial growth after conventional suture plating with the experimental plating method and with growth after sham operation. Forty-five, 6-week-old, weanling rabbits were divided into three groups of 15 each (12 for cephalometry, 3 for histological examination): (group 1) control, sham operated; (group 2) rigid fixation; (group 3) semi-rigid fixation. Rabbits were maintained for 14 weeks. Craniofacial growth was assessed using three-dimensional image analysis techniques. Measurements were subjected to statistical analysis (one-way analysis of variance) to compare the three treatment groups. Pairwise comparison of means between the treatment groups was done using Bonferroni's method at the 0.05 significance level. Semi-rigid fixation permitted significantly more normal growth of the developing rabbit head than rigid fixation in total snout length, total vault length, left and right midface height, and left orbital length. Both semi-rigid and rigid fixation significantly restricted growth compared with sham operated animals in left and right posterior midface height, right orbital length, right and left nasal bone length, and left parietal width. There were no significant differences in the growth of all other parameters measured.

Animals↗

Investigating the relationship between stroke and obstructive sleep apnea.

BACKGROUND AND PURPOSE: We aimed to prospectively determine whether the incidence of obstructive sleep apnea in patients with recent stroke was significantly different from that of a sex- and age-matched control group with no major medical problems. METHODS: We prospectively performed overnight polysomnography in 24 patients with a recent stroke (13 men and 11 women; mean age [+/- SD], 64.6 +/- 10.4 years) and 27 subjects without stroke (13 men and 14 women; mean age, 61.6 +/- 8.8 years). Patients with either ischemic or hemorrhagic stroke were entered into this study. Polysomnographic evaluations were performed within approximately 2 to 5 weeks after each patient's stroke. RESULTS: Obstructive sleep apnea was found in 10 of 13 men with stroke (77%) and in only 3 of 13 male subjects without stroke (23%) (P=.0169). Seven of 11 women with stroke (64%) had obstructive sleep apnea, while only 2 of 14 female subjects without stroke (14%) had obstructive sleep apnea (P=.0168). For men with stroke, the mean apnea/hypopnea index (+/- SE) was 21.5 +/- 4.2 events per hour, while for male subjects without stroke it was 4.8 +/- 1.8 events per hour (P=.0014). For women with stroke the mean apnea/hypopnea index was 31.6 +/- 8.8 events per hour, while for female subjects without stroke it was 2.9 +/- 1.6 events per hour (P=.0024). The 4-year mortality for patients with stroke was 20.8%. All patients with stroke who died had obstructive sleep apnea. CONCLUSIONS: Patients with stroke have an increased incidence of obstructive sleep apnea compared with normal sex- and age-matched control subjects. Hypoxia and hemodynamic responses to obstructive sleep apnea may have predisposed these patients to stroke.

Aged↗

Craniofacial growth in rabbits. Effects of midfacial surgical trauma and rigid plate fixation.

OBJECTIVE: To examine the effects of soft-tissue manipulation, rigid microplate fixation, and multiple osteotomies on the growing midface in rabbits. DESIGN: Randomized, controlled experiment. SUBJECTS: Forty 6-week-old male New Zealand white rabbits. INTERVENTIONS: Group 1, exposure of the left nasofrontal and midzygomatic arch regions with periosteal elevation; group 2, osteotomies at left nasofrontal suture and midzygomatic arch; group 3, rigid plate fixation of osteotomies; and group 4, rigid plate fixation alone. Animals were killed at age 20 weeks; growth was assessed by linear and spatial measurements of craniofacial regions. RESULTS: Linear data disclosed shortening of the left nasal bone (P < .05) in groups 2 through 4. Groups 3 and 4 also had shortened left zygomatic arches and orbital diameters (P < .05). Euclidean distance matrix analysis showed significant restrictive shape alterations in groups 2 through 4 (P < .05). Significant contralateral shape alterations also were found in group 3. CONCLUSION: Rigid plate fixation does not cause more severe growth disturbance than bony trauma. Use of rigid plate fixation after bony trauma does not seem to increase the restrictive effects of trauma on growth. Furthermore, removal of rigid plate fixation may not prevent growth disturbances and may induce further harmful trauma to the growing midface.

Animals↗

Avoidant personality traits distinguish social phobic and panic disorder subjects.

The purpose of this study was to show that, as a group, patients with social phobia and panic disorder differ with respect to personality traits, further validating the distinction between these anxiety disorders. To show this, we compared the response of 46 subjects with social phobia with the response of 72 subjects with panic disorder with or without agoraphobia on the Personality Diagnostic Questionnaire. The subjects, who were recruited for treatment studies, completed this personality questionnaire after they had been off psychotropic medication for at least 1 week. Responses to the Personality Diagnostic Questionnaire showed that the social phobics had more severe personality pathology. These subjects had higher anxious and schizoid cluster scores and differed from panic subjects in having more avoidant personality traits. Panic subjects had more dependent traits. The results indicate that social phobic and panic disorder patients are distinguishable on the basis of personality characteristics. They also show that the generalized situational subtype of social phobia is closely associated with avoidant personality disorder and that these may be differing categorizations of a single disturbance.

Adult↗

Nocturnal arterial hypotension and its role in optic nerve head and ocular ischemic disorders.

We measured 24-hour ambulatory blood pressure monitoring and diurnal curve of the intraocular pressure in 166 white patients with anterior ischemic optic neuropathy, normal-tension glaucoma, primary open-angle glaucoma, and other optic nerve head disorders. Hourly average blood pressure data analyses showed a significant (P < .0001) decrease in mean systolic (26%) and diastolic (33%) blood pressure measurements at night. A significantly (P = .0028) lower nighttime mean diastolic blood pressure and a significantly (P = .0044) greater mean percentage decrease in diastolic blood pressure were noted in normal-tension glaucoma than in anterior ischemic optic neuropathy. Patients with arterial hypertension taking oral hypotensive therapy showed a significant association between progressive visual field deterioration and nocturnal hypotension, particularly in anterior ischemic optic neuropathy. Intraocular pressure showed no significant correlation with visual field deterioration in any of these conditions. Our findings suggest that nocturnal hypotension, in the presence of other vascular risk factors, may reduce the optic nerve head blood flow below a critical level, and thereby may play a role in the pathogenesis of anterior ischemic optic neuropathy and glaucomatous optic neuropathy; that is, nocturnal hypotension may be the final insult in a multifactorial situation. The same mechanisms may be true of a number of other ocular ischemic disorders. This finding opens a new dimension in the understanding and management of these visually disabling diseases.

Adult↗

Incidence of various types of retinal vein occlusion and their recurrence and demographic characteristics.

We analyzed data on 1,108 patients (1,229 eyes) with various types of retinal vein occlusion. Retinal vein occlusion was classified into six distinct clinical types: (I) nonischemic and (II) ischemic central retinal vein occlusion, (III) nonischemic and (IV) ischemic hemicentral retinal vein occlusion, and (V) major and (VI) macular branch retinal vein occlusion. Retinal vein occlusion occurred more often in men than women. The age range of patients was between 14 and 92 years, with 570 of 1,108 patients (51%) 65 years or older; however, 99 of 620 (16%), 15 of 154 (10%), and 17 of 375 (5%) of the patients with central, hemicentral, and branch retinal vein occlusion, respectively, were younger than 45 years. The cumulative probability of developing a second episode of the same or a different type of retinal vein occlusion in the same eye was 0.9% within two years and 2.5% within four years, and in the fellow eye was 7.7% and 11.9%, respectively. The cumulative probability of conversion of nonischemic to ischemic central retinal vein occlusion at six months and 18 months was 13.2% and 18.6%, respectively, in persons 65 years of age or older and 6.7% and 8.1%, respectively, in persons 45 to 64 years of age.

Adolescent↗

Initiation of cardiac hypertrophy in response to thyroxine is not limited by age.

We examined the role of age in the initiation of thyroxine-induced (T4) cardiac hypertrophy. T4 (0.4 mg/kg sc) was administered to prepubescent (2 mo), young adult (6 mo), and senescent (24 mo) Fischer 344 rats for 4 days. While significant increases in left ventricular (LV) mass and RNA/LV were evident at 4 days in all T4-treated groups, the elevation in RNA/LV occurred earlier (2 days) in the senescent group. A 0.2-mg/kg dose of T4 elevated RNA values within 24 h in senescent, but not in prepubescent, rats. LV norepinephrine levels were measured to determine whether it plays a role in this model of cardiac hypertrophy. When synthesis of this catecholamine was blocked with alpha-methyl-p-tyrosine, tissue levels fell significantly in all groups, and the decrement was similar in T4-treated and control rats in the two younger groups. We conclude that: 1) the initiation of T4-induced cardiac hypertrophy is not compromised in senescent rats, 2) hearts of senescent rats respond earlier and to a lower dose of T4 than young rats, and 3) the cardiac hypertrophy that occurs in hyperthyroidism is not due to enhanced levels of available cardiac norepinephrine.

Aging↗

Seasonal variations in the onset of retinal vein occlusion.

Seasonal variation in the development of retinal vein occlusion in 1003 consecutive patients with various types of retinal vein occlusion was studied prospectively from 1973 to 1990. No seasonal variation in the onset of any type or combination of types of retinal vein occlusion was found. This refutes previous reports of such seasonal variation, which were based on small retrospective series.

Adult↗

Degradation of atrial natriuretic peptide: pharmacologic effects of protease EC 24.11 inhibition.

Several processes participate in the clearance of atrial natriuretic peptide (ANP) from the circulation, one of which is enzymatic degradation. Endoprotease EC 3.4.24.11 (NEP 24.11), present within the kidney in high concentration, has been shown in vitro to degrade ANP. Phosphoramidon and thiorphan, two potent NEP 24.11 inhibitors, have been shown to prevent the enzymatic degradation of ANP. The purpose of the present study was to determine if phosphoramidon or thiorphan would alter the in vivo time course of the pharmacologic effects of ANP. The magnitude and duration of the ANP-induced increase in urine output and sodium and cyclic GMP excretion were examined with and without either thiorphan or phosphoramidon. Six separate groups of anesthetized rats received either a low, medium, or high infusion rate of thiorphan or phosphoramidon. Renal responses to ANP were potentiated and prolonged during the low phosphoramidon infusion (3 Ki) and the medium thiorphan infusion (150 Ki). At high inhibitor infusion rates in the anesthetized rat, ANP elicited a marked depressor response. In the conscious spontaneously hypertensive rat (SHR), a 15-min intravenous (i.v.) infusion of ANP (1 microgram/kg/min) lowered mean arterial pressure (MAP 23 +/- 6 mm Hg), with an approximately 35-min duration of action. A simultaneous i.v. infusion of phosphoramidon (high dose) produced both a potentiation (33 +/- 3 mm Hg) and a prolongation (greater than 65 min to return to baseline) of the depressor response. These data lend support to the hypothesis that enzymatic breakdown of ANP may play an important role in regulating the actions of atrial natriuretic peptide.

Animals↗

Thromboxane synthase inhibition enhances action of converting enzyme inhibitors.

Mean arterial blood pressure was measured over a 24-hour period from the femoral artery of conscious, unrestrained spontaneously hypertensive rats. Oral administration of the angiotensin converting enzyme inhibitor CGS 16617 significantly lowered mean arterial pressure. In contrast, both the thromboxane synthase inhibitor CGS 12970 and the thromboxane receptor antagonist BM 13505 lacked an antihypertensive action in the spontaneously hypertensive rat. When administered concurrently, the thromboxane synthase inhibitor CGS 12970 potentiated the antihypertensive action of the angiotensin converting enzyme inhibitor CGS 16617. This effect was not observed with the thromboxane receptor antagonist BM 13505. In addition to CGS 16617, CGS 12970 also potentiated the hypotensive effect of two structurally dissimilar angiotensin converting enzyme inhibitors, benazapril HCL and captopril. Indomethacin blocked the thromboxane synthase inhibition-induced potentiation of the antihypertensive action of angiotensin converting enzyme inhibitors. The thromboxane synthase inhibitor CGS 12970 had no effect on the hypotension induced by hydralazine, indicating that the hypotension is not a nonspecific action related to the fall in blood pressure. These results may suggest that converting enzyme inhibition augments the levels and actions of a hormone that stimulates prostaglandin formation. It is well established that thromboxane synthase inhibitors eliminate the formation of the vasoconstrictor thromboxane A2 and allow reorientation of eicosanoid production toward the formation of vasodilating prostaglandins, which could enhance the antihypertensive action of angiotensin converting enzyme inhibitors.

Angiotensin-Converting Enzyme Inhibitors↗

Enkephalinase inhibition increases plasma atrial natriuretic peptide levels, glomerular filtration rate, and urinary sodium excretion in rats with reduced renal mass.

To investigate the in vivo effects of inhibition of endopeptidase 24.11, an enkephalinase enzyme shown to be involved in atrial natriuretic peptide (ANP) breakdown in vitro, we infused phosphoramidon, a specific inhibitor of endopeptidase 24.11, into rats with reduced renal mass (and chronic extracellular volume expansion) and into normal rats. Relative to baseline values in rats with remnant kidneys, phosphoramidon led to elevations of plasma ANP levels and concomitant increases in urinary sodium excretion, fractional excretion of sodium, glomerular filtration rate, filtration fraction, and urinary cyclic GMP excretion. Similar changes in renal function and urinary cyclic GMP excretion were obtained with thiorphan, another endopeptidase 24.11 inhibitor. These enhanced ANP levels and renal actions were not observed with phosphoramidon in normal rats. These results show that plasma ANP levels can be modulated in rats with reduced renal mass by inhibition of endopeptidase 24.11.

Animals↗

CGS 21680C, an A2 selective adenosine receptor agonist with preferential hypotensive activity.

CGS 21680C (2-[p-(2-carboxyethyl)phenethylamino]-5'-N-ethyl-carboxamido adenosine) a 2-substituted analog of the riboside uronamide, 5'-N-ethylcarboxamido adenosine and the related analog CGS 21577 (2-phenethylamino-5'-N-ethylcarboxamido adenosine), have high in vitro affinity for brain striatal adenosine A2 receptors (IC50 values = 22 and 13 nM, respectively). Both compounds were considerably less active at A1 receptors with CGS 21577 and CGS 21680C having respective IC50 values of 0.76 and 3.1 microM. The former compound was thus 59-fold selective for A2 receptors whereas CGS 21680C was 140-fold selective. In contrast, the reference A2 selective ligand, CV 1808 (2-phenylaminoadenosine), showed only 8-fold selectivity as an A2 ligand, having an IC50 of 115 nM in the [3H]-5'N-ethylcarboxamide adenosine assay and an IC50 of 910 nM at the N6-[3H] cyclohexyladenosine site. Further examination of CGS 21680C showed that the compound was without effect on binding to 17 other putative neurotransmitter/neuromodulator sites indicating its selectivity as an adenosine receptor ligand. In an isolated perfused working rat heart model, CGS 21680C effectively increased coronary flow with an ED25 value of 1.8 nM. The corresponding value for CGS 21577 was 3 nM whereas that for CV 1808 was 110 nM. The EC25 for eliciting bradycardia for all three compounds was greater than 1000 nM. The effects of all three compounds could be reversed by treatment with the xanthine adenosine antagonist, xanthine amine congener.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗

Effects of two nonsulfhydryl angiotensin-converting enzyme inhibitors, CGS 14831 and CGS 16617, on myocardial damage and left-ventricular hypertrophy following coronary artery occlusion in the rat.

The present study was designed to examine the effects of two new angiotensin-converting enzyme (ACE) inhibitors, CGS 14831 and CGS 16617 (3 mg/kg i. v. 1 min prior to occlusion and 4 and 24 h after occlusion), on myocardial ischemic (MI) damage and left-ventricular hypertrophy in rats. Administration of CGS 14831 or CGS 16617 inhibited angio-tensin-I-induced pressor responses by 40-100% for 4 h after each dose. Myocardial creatine phosphokinase (CK) levels were 10.6 +/- 0.6 U/mg protein in sham-MI animals, and following coronary artery occlusion for 48 h were decreased to 4.1 +/- 0.2 U/mg protein in MI + vehicle animals (p less than 0.01). CGS 14831 and CGS 16617 attenuated the decrease in CK content and resulted in 47 and 40% sparing, respectively, of the left-ventricular free wall. Neither agent attenuated the left-ventricular hypertrophy which developed following coronary artery occlusion. These data indicate that the nonsulfhydryl ACE inhibitors CGS 14831 and CGS 16617 have a significant cardioprotective effect in rats surviving 48 h, and suggest a potential therapeutic usefulness of these agents for the treatment of ischemia-induced heart failure.

Angiotensin-Converting Enzyme Inhibitors↗