Biomedical subjects

J M Holmes

Publications and source records attributed to J M Holmes.

At least 37 records · Page 2Linked to original sources

PubMed1999

Retinopathy associated with enterococcus enteropathy in the neonatal rat.

PURPOSE: Preretinal neovascularization has been previously observed in neonatal rats with spontaneously occurring diarrhea. This neovascularization appears analogous to retinopathy of prematurity (ROP), which occurs in human neonates. A new enterococcus species, designated Enterococcus rattus, has been isolated from the duodenum of these rats. In the present controlled study, the effect of the enteropathy induced by this organism on the retinal vasculature in the neonatal rat was further investigated. METHODS: One hundred fifty newborn Sprague-Dawley rats were randomly assigned to 6 expanded litters (n = 25). On the second day of life, animals were gavaged with either 100 microl of E. rattus suspension (1.0 X 10(7) colony forming units, inoculated group, n = 100 rats) or 100 microl saline (control group, n = 50 rats). All rats were raised in room air and were killed on day 13 of life. Duodenal and blood samples were cultured. The retinal vasculature was assessed using fluorescent microscopy and ADPase staining in a masked manner. Two additional inoculated litters and one control litter were studied for evaluation of arterial blood gases and validation of the grading method for preretinal neovascularization. RESULTS: One hundred percent of rats in the inoculated group developed severe diarrhea and had duodenal cultures positive for E. rattus compared with 0% in the control group. Preretinal neovascularization similar to ROP occurred in 55% of rats in the inoculated group compared with 2% in the control group (P = 0.001). Retinal vascular areas were reduced in the inoculated group (mean +/- SD, 89% +/- 5% versus 96% +/- 2%; P < 0.001). Rats in the inoculated group demonstrated severe growth retardation (final weight, 9.7 +/- 2.2 versus 16.7 +/- 2.7 g, P < 0.001). Inoculated animals also experienced acidosis (pH 7.31 +/- 0.06 versus 7.39 +/- 0.06 control, P = 0.04). CONCLUSIONS: A previously undescribed enterococcal enteropathy was associated with preretinal neovascularization similar to ROP in the neonatal rat. This supports an independent role for factors other than inspired oxygen in the development of ROP.

Animals↗

PubMed1998

The natural history of acute traumatic sixth nerve palsy or paresis.

BACKGROUND: Spontaneous resolution of traumatic sixth nerve palsy or paresis has been reported to range between 12% and 54%. However, previous studies have been based in tertiary referral centers, have been retrospective in nature, have included a heterogeneous group of patients, and have included patients with long-standing palsies. To provide a more accurate estimate of the true recovery rate, we performed a prospective natural history study. METHODS: All members of the American Association for Pediatric Ophthalmology and Strabismus and the North American Neuro-Ophthalmology Society were invited to enroll patients with acute traumatic sixth nerve palsy or paresis between March 1996-February 1997. Recovery at 6 months after injury was defined as absence of diplopia in primary position and less than or equal to 10 PD distance esotropia in primary position. Patients who had been treated with botulinum toxin (n = 8) within 6 months after injury and patients with <6 months of follow-up (n = 3) were excluded. RESULTS: Thirty-three eligible patients were enrolled by 27 investigators. Twenty-five (76%) of the palsies were unilateral and 8 (24%) were bilateral. The overall spontaneous recovery rate was higher than previously reported (73%, 95% CI 54%-87%). Spontaneous recovery was more frequent in unilateral cases (84%, 95% CI 64%-95%) than in bilateral cases (38%, CI 9%-76%; P = .02). CONCLUSIONS: In this prospective multicenter study of acute traumatic sixth nerve palsy or paresis, the overall spontaneous recovery rate, particularly in unilateral cases, was much higher than previously reported. Our results have important sample size implications for the planning of any randomized treatment trial and may help guide early treatment decisions.

Abducens Nerve Diseases↗

PubMed1998

Activation of skinned muscle fibres from the Norway lobster Nephrops norvegicus L. by manganese ions.

Effects of Mn2+ and Ca2+ on the mechanical properties of glycerinated myofibrillar bundles originating from slow S1 type muscle fibres of superficial flexor muscles of the lobster Nephrops norvegicus were investigated. Mn2+ (5-20 microM) activated the preparations in a dose-dependent manner. The sensitivity of myofibrillar force generation for Mn2+ was around 30 times lower than that for Ca2+. The maximal tension produced under Mn2+ activation was about 75% of that under Ca2+ activation. At higher free Mn2+ concentrations (>2 mM), the steady-state force decreased; it was completely abolished at 30 mM free Mn2+. These high Mn2+ solutions were accompanied by changed in MgATP and MnATP concentrations, and in the ionic strength. Control experiments have shown that none of these parameters seemed fo account fully for the observed force depression in high Mn2+ solutions. It is likely that direct effects of Mn2+ such as a change of the myofilament surface charges are responsible. The maximal unloaded shortening velocity of the myofibrillar preparations was shown to be similar under maximal Mn2+ and Ca2+ activation. Conversely, the kinetics of stretch-induced delayed force increase were about two to three times faster under Mn2+ activation. These results suggest that certain steps of the cross-bridge cycle depend on the ion species bound to the regulatory proteins.

Adenosine Triphosphate↗

PubMed1998

Carbon dioxide-induced retinopathy in the neonatal rat.

PURPOSE: Hypercarbia has been suggested as a risk factor for retinopathy of prematurity (ROP). We investigated the effect of hypercarbia on the retinal vasculature of the neonatal rat to determine whether hypercarbia alone could induce preretinal neovascularization analogous to ROP. METHODS: In a preliminary blood gas study, 8-11-day-old rats were exposed to specific levels of inspired O2 and either 0.2% CO2 or 10% CO2. Arterial blood gases were obtained, and a level of inspired O2 was determined that, when combined with inspired 10% CO2, would produce a PaO2 equivalent to room air (pure hypercarbia). In the formal retinopathy study, 300 newborn rats raised in 12 expanded litters (n = 25 each) were exposed for 7 days to either room air, 10% CO2 in 21% O2 and nitrogen (high-inspired CO2 group) or 10% CO2 in 12.5% O2 and nitrogen (pure-hypercarbia group). Each type of exposure was followed by recovery in room air for 5 days. Animals were sacrificed on day 13 and retinae were analyzed, using fluorescein perfusion and ADPase staining techniques. RESULTS: Neovascularization occurred in 19% of rats in the high-inspired CO2 group, and 14% of rats in the pure-hypercarbia group, compared to 0% of rats exposed to room air alone (p = 0.001, Chi square). CONCLUSIONS: In the neonatal rat model, exposure to hypercarbia alone, followed by room air recovery, results in preretinal neovascularization similar to that seen in oxygen-induced retinopathy. Our results support the suggestion that hypercarbia may be a risk factor for retinopathy of prematurity.

Animals↗

PubMed1997

The effect of raised inspired carbon dioxide on normal retinal vascular development in the neonatal rat.

PURPOSE: Raised arterial carbon dioxide levels have been suggested as a risk factor for retinopathy of prematurity (ROP). We investigated the effect of raised inspired CO2 on normal postnatal vasculogenesis in the neonatal rat retina. METHODS: One hundred fifty newborn rat pups were divided among 15 mothers (n = 10 for each litter). Five litters were exposed to low CO2 (0.2%), 5 litters exposed to 6%, and 5 litters to 10% CO2. On day 7 of life the rats were sacrificed and the total retinal and vascularized retinal areas analyzed. RESULTS: The vascularized retinal area and ratio of vascularized to total retinal area were reduced in rats exposed to 6% and 10% CO2. CONCLUSIONS: Raised inspired CO2 was associated with retardation of normal retinal vascular development and increased peripheral avascular area in neonatal rats. Raised CO2 may be a risk factor for the development of abnormal neovascularization such as in ROP.

Animals↗

PubMed1997

The effect of carbon dioxide on oxygen-induced retinopathy in the neonatal rat.

PURPOSE: Hypercarbia has been suggested as a risk factor for retinopathy of prematurity. We investigated the effect of raised inspired carbon dioxide on oxygen-induced retinopathy in the neonatal rat. METHODS: Newborn rats raised in expanded litters (n = 25 each) were exposed to cycles of hyperoxia (80% O2) and hypoxia (10% O2 for 7 days, followed by room air recovery for 5 days. During cyclic oxygen exposure, 3 litters (n = 75) were exposed to 10% CO2 (PaCO2 78 mm Hg +/- 6; mean +/- SD) and 3 litters (n = 75) were exposed to 0.2% CO2 (PaCO2 45 mm Hg +/- 7). Animals were sacrificed on day 13 and retinae were analyzed using fluorescein perfusion and ADPase staining techniques. RESULTS: Neovascularization occurred in 85% of rats exposed to high CO2 compared to 52% of rats exposed to low CO2 (p = 0.001). The severity of neovascularization, in clock hours, was also greater in the rats exposed to high CO2 (p < 0.001). CONCLUSIONS: Exposure to high CO2 results in an increased incidence and severity of neovascularization in a rat model for oxygen-induced retinopathy. Our results support the suggestion that hypercarbia may be a risk factor for retinopathy of prematurity.

Administration, Inhalation↗

PubMed1996

Spontaneous recovery rate in traumatic sixth-nerve palsy.

PURPOSE: To estimate the spontaneous recovery rate of isolated traumatic sixth-nerve palsy. METHOD: A retrospective chart review over a 24-year period at a single institution, excluding patients who were first seen more than 6 weeks after injury, to reduce bias toward nonrecovery. RESULTS: The Kaplan-Meier survival estimate of spontaneous recovery at 6 months was 27% (95% confidence interval [CI], 5% to 44%) in unilateral traumatic sixth-nerve palsy and 12% (95% CI, 0% to 33%) in bilateral traumatic sixth-nerve palsy. CONCLUSION: Spontaneous recovery from isolated traumatic sixth-nerve palsy may be lower than previously reported. A prospective study is needed to provide a more accurate estimate of recovery rate.

Abducens Nerve Injury↗

PubMed1996

Improved stereoacuity: an indication for unilateral cataract surgery.

PURPOSE: To determine whether stereoacuity is an objective indicator of functional improvement following unilateral cataract surgery. SETTING: Department of Opthalmology, Loyola University Chicago, Maywood, Illinois. METHODS: Seventeen consecutive patients with unilateral cataracts (8 pseudophakic, 9 phakic in contralateral eye) were studied prospectively. Best corrected distance visual acuity in the eye with cataract ranged from 20/40 to 20/400. Distance acuity in the eye without cataract was 20/20 or 20/25. All patients had cataract surgery with posterior chamber intraocular lens implantation. Stereoacuity was measured preoperatively and postoperatively; at near by Titmus test (TT) and at distance by B-VAT BVS random dot E (BVRDE) and contour circles (BVC). Nonparametric Spearman rank correlation and Wilcoxon rank tests were used for analysis. RESULTS: Preoperatively, reduced near visual acuity in the cataractous eye correlated with reduced near stereo (TT), r = .6, P = .01. Postoperatively, near stereoacuity improved in all but one patient, from a median of 200 seconds of arc (sec arc) to 40 sec arc (P = .004); distance stereoacuity improved in all but two patients from a median of unrecordable to 120 sec arc (BVC) (P = .006). Preoperatively none of the patients could see the largest distance BVRDE target, whereas postoperatively 4 of 17 had BVRDE stereoacuity of 120 to 240 sec arc (P = .06). CONCLUSIONS: Patients with unilateral cataracts have reduced stereoacuity, correlating with their reduced monocular visual acuity. In this study, distance and near stereoacuity improved postoperatively. Decreased stereoacuity may provide an indication for unilateral cataract surgery.

Aged↗

PubMed1996

The effect of postnatal growth retardation on abnormal neovascularization in the oxygen exposed neonatal rat.

Severe retinopathy of prematurity (ROP) occurs in the smallest and sickest of premature infants. We hypothesized that, in a rat model of oxygen induced retinopathy, abnormal neovascularization would occur more frequently in larger litters where the pups are subject to postnatal growth retardation. Four litters of newborn Sprague-Dawley rats were studied; rats were randomly mixed to form two large litters (n = 25 each) and two small litters (n = 10 each). All litters were exposed to 7 days cyclic hyperoxia and hypoxia followed by 5 days in room air. ADPase stained retinae were evaluated in a masked manner for the presence and severity of abnormal neovascularization. Fluorescein perfused retinae were digitized and the ratios of vascularized:total retinal area were calculated using computer assisted image analysis. As expected, final weight in the large litters was less than in the small litters (15.3 +/- 3.8g vs. 23.4 +/- 2.1g, p < 0.001). Neovascularization occurred in 53% of rats in the large litters vs. 15% in the small litters (p = 0.009). Rats with retinae demonstrating neovascularization were smaller than those without (16.2 +/- 4.7g vs. 19.6 +/- 5.0g, p = 0.016). The severity of neovascularization in clock h was inversely correlated with final weight (rs = -0.35, p = 0.01) and ratio of vascularized:total retina area (rs = -0.46, p < 0.001). Smaller rat pups raised in larger litters, with resultant growth retardation, develop more frequent and more severe abnormal retinal neovascularization. Our results correlate with clinical experience in the premature infant.

Animals↗

PubMed1996

The kinetics of anterior chamber ofloxacin penetration.

Thirty-five patients received topical ofloxacin 0.3% before routine cataract surgery. Ofloxacin was administered one drop every 2 h for five doses 1 day before surgery and one drop every 5 min for five doses immediately before surgery. Aqueous sampling was performed at variable periods 30-150 min after the last topical dose. The mean aqueous ofloxacin concentration was 793 +/- 516 ng/ml (range, 143-2,400 ng/ml). A significant correlation between time from last dose and aqueous humor concentration was found (r = 0.39, p = 0.025). The mean ofloxacin concentration was greater in those patients who received their last dose >1 h before aqueous aspiration (957 +/- 559 ng/ml versus 554 +/- 338 ng/ml, p = 0.02). From a best-fit scatter plot of concentration versus time, the maximal aqueous concentration of 1,000 ng/ml occurs at approximately 2h after topical administration.

Administration, Topical↗

PubMed1995

Cross-linking of membrane immunoglobulin D, in the absence of T cell help, kills mature B cells in vivo.

In vivo experiments were performed to determine whether the cross-linking of membrane immunoglobulin (mIg) D on mature B cells, in the absence of T cell help, leads to B cell death. Mice were injected with either a monoclonal antibody (mAb) that cross-links mIgD effectively or a mAb that binds to mIgD avidly but cross-links it to a limited extent, and effects on B cell number and B cell Ia, mIgM, and mIgD expression were observed. In most experiments, mice were pretreated with anti-interleukin 7 mAb to prevent the generation of new bone marrow B cells, and with anti-CD4 mAb to prevent the generation of T cell help. In some experiments, mice also received anti-Fc gamma RII mAb to prevent cross-linking of mIgD with Fc gamma RII, and cobra venom factor to prevent possible mIg-complement receptor interactions and complement-mediated killing of B cells. The results of these studies demonstrate that (a) even limited cross-linking of mIgD on mature B cells can lead to B cell death; (b) increased cross-linking of mIgD leads to increased B cell death; (c) the loss of B cells is first detected 2 d after anti-IgD mAb injection and increases during the subsequent 3 d; (d) sustained modulation of mIgD may be necessary to cause B cell death; (e) mIgMdull but not mIgMbright B cells are lost in mice injected with anti-IgD mAbs; and (f) T cell help prevents or minimizes B cell death.

Animals↗

PubMed1995

The effect of litter size on normal retinal vascular development in the neonatal rat.

Many animal models of retinal disease use the neonatal rat. Raising rat pups in large litters has been shown to result in postnatal growth retardation. We investigated the effect of litter size on the normal postnatal vascularization of the neonatal rat retina. Sixty-six newborn rat pups were divided among 5 nursing mothers into 3 small litters (n = 10) and 2 large litters (n = 18). On day 6 of life the rats were sacrificed and total retinal and vascularized retinal areas analyzed. The total retinal area was reduced in the rats raised in larger litters (28.6 mm2 vs. 25.9 mm2 p < 0.001) but there was a more pronounced reduction in vascularized retinal area (67% vascularized vs. 54% vascularized, p < 0.001). Postnatal vascularization of the normal rat retina may be influenced by litter size.

Animals↗

PubMed1994

Synthesis and carbonic anhydrase inhibitory activity of 4-substituted 2-thiophenesulfonamides.

A series of 4-substituted 2-thiophenesulfonamides was prepared from 3-thiophenecarboxaldehyde using metalation chemistry developed for 3-furaldehyde. Several of these compounds inhibit carbonic anhydrase II in vitro at concentrations of less than 10 nM. In addition, none of these compounds exhibit sensitization potential as determined from in vitro measurement of cysteine reactivity.

Animals↗

PubMed1994

Induction of B cell and T cell tolerance in vivo by anti-CD23 mAb.

T cell tolerance can be induced by B cell presentation of Ags to naive T cells. To further characterize this mechanism of T cell tolerance induction, we have investigated the effects of injecting mice with an intact rat IgG2a Ab, which binds to the B cell low-affinity Fc epsilon receptor (CD23), on the responsiveness of B cells and T cells to rat IgG2a. Our observations indicate that 1) intravenous, subcutaneous, or intraperitoneal injection of this Ab induces antigen-specific B cell and T cell tolerance; 2) both forms of tolerance are induced more completely by injection of rat IgG2a anti-CD23 mAb than by injection of an equal dose of a control rat IgG2a Ig; and 3) reduced responsiveness to Ag is seen as early as 1 to 3 days after anti-CD23 mAb injection and reaches maximum levels by 7 days after injection. Although tolerance induced by the injection of soluble proteins has been reported to be characterized by reduced production of IL-2 and IFN-gamma, but normal production of IL-4, injection of mice with rat IgG2a anti-mouse CD23 mAb greatly decreases the IL-4 response to a rat IgG2a immunogen that normally induces a large IL-4 response.

Animals↗

PubMed1994

The effect of raised inspired carbon dioxide on developing rat retinal vasculature exposed to elevated oxygen.

Hyperoxia is a risk factor for retinopathy of prematurity (ROP), a blinding disease in infants. However, ROP develops in human infants without raised arterial oxygen levels, such as in cyanotic congenital heart disease. In these infants raised pCO2 may be a risk factor. We investigated the effect of inspired CO2 on oxygen induced retinopathy in the rat. 56 newborn Sprague-Dawley rats were exposed to high cyclical O2 for seven days. In a control group, 27 rats were exposed to negligible CO2 by the use of soda lime. In the high CO2 group, 29 rats were exposed to elevated CO2 by omitting soda lime from their chambers. Rats in both groups had a recovery period of three days in room air following cyclical O2 exposure. On the eleventh day all rats were sacrificed after intracardiac injections of fluorescein under deep anesthesia and the retinae were dissected and flat mounted for fluorescent microscopy. The ratio of vascularized:total retinal area was calculated using computer assisted image analysis. In the high CO2 group 62% +/- 7% SD of the retina was vascularized vs. 81% +/- 7% in low CO2 group (p < 0.001). Elevated inspired CO2 results in pronounced retardation of retinal vascular development in neonatal rats exposed to fluctuating raised oxygen.

Animals↗

PubMed1993

Depth of anisometropic amblyopia and difference in refraction.

Disagreement exists as to whether the depth of anisometropic amblyopia correlates with the degree of anisometropia. We reviewed the charts of 303 consecutive patients with the diagnosis of amblyopia. Thirty-five patients with untreated anisometropia without strabismus were identified. The best-corrected visual acuities, manifest refractions, and autorefractions were recorded. The differences in spherical equivalent, root mean square, and an index of anisometropia, which we defined, were calculated. The depth of amblyopia was strongly correlated to all three measures of anisometropia for both hyperopic and myopic individuals. Our new index of anisometropia was an excellent predictor of the depth of amblyopia.

Adolescent↗

PubMed1993

Anti-cytokine antibodies as carrier proteins. Prolongation of in vivo effects of exogenous cytokines by injection of cytokine-anti-cytokine antibody complexes.

Anti-cytokine antibodies that block interactions between cytokines and cytokine receptors have been used to inhibit endogenous cytokine function. However, injection of mice with mixtures of IL-4 and either of two neutralizing anti-IL-4 mAb, at a cytokine/anti-cytokine mAb molar ratio of approximately 2:1, enhances and prolongs in vivo IL-4 activity, as measured by induction of increased spleen cell Ia expression. Although splenocyte Ia expression returns to baseline two days after mice are injected with free IL-4, soluble IL-4-anti-IL-4 mAb complexes still induce several-fold increases in Ia expression 3 days after injection. Complexes that contain as little as 400 ng of IL-4 have considerable in vivo stimulatory activity, and a maximal effect on splenocyte Ia expression is induced by injection of 2 micrograms of complexed IL-4. The stimulatory effect of IL-4-containing complexes on splenocyte Ia expression can be blocked by increasing the ratio of anti-IL-4 mAb to IL-4, by injection of anti-IL-4R mAb, and by in vivo aggregation of the complexes. Complexes of IL-4 with a non-neutralizing anti-IL-4 mAb do not have increased IL-4 agonist activity in vivo. These observations are most consistent with the possibility that neutralizing anti-IL-4 mAb act as carrier proteins that increase the in vivo half-life of IL-4 by preventing its excretion, and possibly, by preventing modification of its active site. The enhanced agonist effect of IL-4-anti-IL-4 mAb complexes is not unique; complexes of IL-3 with a neutralizing anti-IL-3 mAb have a greatly increased ability, compared with free IL-3, to stimulate mucosal mastocytosis, and complexes of IL-7 with a neutralizing anti-IL-7 mAb have a greatly increased ability, compared with free IL-7 or IL-7 complexed with a non-neutralizing anti-IL-7 mAb, to stimulate an increase in pre-B cell number. These observations suggest that complexes of cytokines and neutralizing anti-cytokine mAb may provide a generally useful way to increase the magnitude and duration of cytokine effects in vivo.

Animals↗

PubMed1993

Aneuploidy detection in human sperm nuclei using fluorescence in situ hybridization.

Fluorescence in situ hybridization (FISH) was performed on human interphase sperm nuclei to determine the utility of this technique for aneuploidy detection. Repetitive DNA sequences specific for chromosomes 1, 12 and X were biotinylated and hybridized with mature sperm, which had been treated with cetyltrimethylammonium bromide and dithiothreitol to render them accessible to the probes. Detection of bound probe was accomplished with fluoresceinated avidin and antiavidin. For each of the chromosomes studied, chromosome number was determined by counting the fluorescent signals, representing hybridized regions, within the sperm nuclei. The frequencies for disomy, that is for nuclei containing two signals, for chromosomes 1, 12 and X were 0.06%, 0.04% and 0.03%, respectively. The congruence of these results with those determined by the cross-species hamster oocyte-human sperm assay, and the high efficiency of hybridization indicate that FISH is a sensitive and reliable tool for aneuploidy detection in human sperm.

Aneuploidy↗