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Biomedical subjects

N Pfeiffer

Publications and source records attributed to N Pfeiffer.

At least 19 recordsLinked to original sources
PubMed1992

Misdirected regeneration of abducens nerve neurons into the parasympathetic pupillary pathway.

A 16-year-old girl suffered a severe head trauma with paralyses of the right oculomotor, trochlear, and abducens nerves. Three years later, only the abducens nerve had recovered. The pupil did not react to light or near. However, the diameter of the pupil correlated with horizontal gaze: with the gaze to the left, the diameter of the pupil was 8 mm, with the gaze straight ahead, 6 mm, and with the gaze to the right, 4 mm. With saccades to the right, the pupil started to constrict immediately and reached its smallest diameter after about 2 s. We conclude that the constriction of the pupil was due to misdirected regeneration of abducens nerve neurons into the parasympathetic pathway of the oculomotor nerve.

Abducens Nerve↗
PubMed1992

Improved suture for fornix-based conjunctival flap in filtering surgery.

Major problems in the early postoperative phase in filtering surgery are hypotony, flattening of the anterior chamber and choroidal detachment. We describe a new suture technique for the closure of the conjunctiva in goniotrephination with a fornix-based conjunctival flap which is helpful in reducing these complications. After dissecting the conjunctiva from the limbus, a shallow groove is cut directly behind the former conjunctival insertion. At the end of the operation the conjunctiva is sutured into this groove using a running 10.0 nylon suture in a meander-like fashion. A very tight wound closure results. We used this technique in 104 consecutive goniotrephinations. We found a low incidence of only mild external fistulation, hypotony, flattening of the anterior chamber and choroidal detachment. Astigmatism induced by the operation was -1.2 +/- 1.2 D, usually with the rule.

Aged↗
PubMed1992

Sezolamide: additivity to timolol twice daily.

Sezolamide, a potent topical carbonic anhydrase inhibitor previously known as MK-417, was studied to determine its ocular hypotensive activity in patients with elevated intraocular pressure while on continuing therapy with topical timolol. This was a three-centre, double-masked, randomised, placebo-controlled, parallel study in 36 patients with bilateral primary open angle glaucoma or ocular hypertension on therapy receiving 0.5% timolol twice daily, with a morning intraocular pressure greater than or equal to 22 mmHg in both eyes 2-4 hours following an 8 a.m. dose of timolol. Sezolamide 1.8% or placebo twice daily was added to treatment with timolol on the evening of day 1 and continued for 2 weeks. Twelve-hour diurnal curves were performed before the study on day 1 (timolol alone) and on day 15. Intraocular pressure measurements were also taken on days 2 and 8 at 8 a.m. and 9 a.m. Patients who received timolol and sezolamide showed additional intraocular pressure reductions from day 1 (timolol alone) of 8.0 to 15.5%, which were significant at all times. At hours 1, 2, 4 and 8 the reductions in intraocular pressure observed in the group receiving sezolamide and timolol were significantly greater than those in the group receiving timolol and placebo.

Aged↗
PubMed1992

The pattern-electroretinogram in glaucoma and ocular hypertension. A cross-sectional and longitudinal study.

The pattern electroretinogram (PERG) is an indicator of retinal ganglion cell function. We studied the PERG in 65 normal eyes, in 52 eyes in early stages of glaucoma, and in 28 ocular hypertensive (OHT) eyes. The PERG was recorded using steady-state high contrast (98%) counterphasing checkerboard patterns at check sizes of 0.8 degrees and 15 degrees at 16 reversals/s and 98% contrast. Stimulation area was 27 degrees x 30 degrees. When compared to normals, in glaucoma eyes PERG amplitudes are reduced to 56 +/- 3.6%, (P < 0.0001) for 0.8 degrees and to 79 +/- 4.0% (P < 0.001) for 15 degrees check sizes. Preferential reduction for the small check size allows classification of patients on an individual basis: using discriminant analysis, normal and glaucoma eyes were classified with a sensitivity of 82.7% and a specificity of 90.8%. Nineteen of 28 OHT eyes were classified as pathological. Eyes with OHT were followed up to test whether the PERG can be used to predict visual field damage. At the repeat visit 5 to 35 months later (mean follow-up 20.2 +/- 8.2 months), in eyes with normal PERGs the average loss in mean sensitivity was -0.61 +/- 0.5 dB, while in eyes with pathological PERGs it was -2.6 +/- 0.7 dB (P = 0.05). Findings suggest that the PERG can be used to discriminate between OHT patients who will develop visual field loss and those who will not. Thus, the PERG may be a test of visual function helpful to decide which OHT patients require treatment before visual field deterioration and optic nerve damage have begun.

Adult↗
PubMed1991

Comparative tolerability of topical carbonic anhydrase inhibitor MK-927 and its S-enantiomer MK-417.

A single-dose, randomised, double-masked, placebo-controlled, five-period cross-over comparative ocular tolerance study was undertaken with the topical carbonic anhydrase inhibitor (CAI) MK-927 (1% and 2% concentrations) and its S-enantiomer MK-417 (1% and 1.8% concentrations) in 20 healthy, normal volunteers. Subjects received one drop of placebo (common vehicle) or CAI in each eye on five different days that were separated by washout intervals of 1 week. The incidence of burning increased significantly after treatment with 2% MK-927 (P less than 0.01) and 1.8% MK-417 (P less than 0.05) as compared with placebo. The mean duration of burning following placebo was 16.8 s, somewhat less than that following CAI application (23-37.1 s). The duration of tearing following CAI treatment was also significantly prolonged (P less than 0.05). Pupil size was not changed by CAIs. No other side effects were observed. At 3 h after instillation, intraocular pressure (IOP) was found to be decreased following all four CAI treatments, significantly so with 1% and 1.8% MK-417. The reasonable single-dose tolerability of MK-927 and MK-417 in this sensitive normal-volunteer model supports their potential as topical glaucoma medications. This study suggests that MK-417 may possess greater IOP-lowering activity than MK-927 in man.

Administration, Topical↗
PubMed1991

[Pattern ERG in ocular hypertension and glaucoma. Effect of pattern size, contrast and retinal eccentricity].

We have previously shown that check-size-specific changes of the Pattern-Electroretinogram (PERG) can be used to detect early glaucoma. This time we conducted a study to determine whether different check sizes, contrasts and eccentricities can improve the diagnostic yield. We examined 15 normal eyes (15 subjects), 32 eyes (24 patients) in stage I or II glaucoma and 36 eyes (25 patients) with ocular hypertension (OHT). Visual acuity was always better than 0.8. The stimuli were checkerboards, phase-reversing at 16 rev/s. The check sizes were 0.8 degrees or 15 degrees with contrast at 60% or 98%. The stimulation area was either "full-field" (27 degrees x 30 degrees), "central" (less than or equal to 7 degrees) or "paracentral" (greater than 7 degrees). In the glaucoma group, all PERG amplitudes were significantly reduced compared to normals: maximally for stimuli of 0.8 degrees, 98% contrast, full-field to 51% +/- 18%, and least for stimuli of 15 degrees, 98% contrast, central (to 70% +/- 20%). Under paracentral stimulation, the amplitude was reduced to 55% and in the central condition to 64%. The single-most-sensitive stimulus to separate normal and glaucoma patients was 0.8 degrees, 60% contrast and full-field, as the variance was low for this condition. Only 4 patients (8.5%) were incorrectly classified using these parameters; when 8 different stimuli were entered into the discriminant analysis, the rate was marginally reduced to 3 patients (6.4%). Seventy-five percent of the OHT eyes were classified as pathological. These results confirm previous findings that in early glaucoma, PERG amplitudes are more reduced using check sizes of 0.8 degrees compared to 15 degrees.(ABSTRACT TRUNCATED AT 250 WORDS)

Electroretinography↗
PubMed1991

[Additive effect of timolol and the local carbonic anhydrase inhibitor MK-417 (sezolamide)].

MK-417 (sezolamide) is a topically active carbonic anhydrase inhibitor. The effect of additional treatment with sezolamide 1.8% twice daily to patient already receiving timolol 0.5% twice daily was investigated. For this purpose, 12-h diurnal curves were used in a double-masked, randomized, placebo-controlled, parallel study in 36 patients with bilateral primary open angle glaucoma or ocular hypertension who during beta blocker therapy had intraocular pressures (IOP) greater than or equal to 22 mmHg. For 15 days patients received sezolamide or placebo 10 min after 0.5% timolol given at 8 a.m. and 8 p.m. On treatment day 15, this addition of sezolamide twice daily induced a further mean decrease in IOP of approximately 4 mm Hg (about 15%) at 1, 2 and 4 h and of approximately 2-3 mm Hg at 0, 6, 8, 10 and 12 h after drug administration, thus demonstrating a partial additive effect of sezolamide and timolol. Thus, sezolamide may be a useful addition to the treatment of glaucoma in patients not adequately controlled by beta blocker therapy.

Aged↗
PubMed1990

A single dose of the topical carbonic anhydrase inhibitor MK-927 decreases IOP in patients.

MK-927 is a novel topical carbonic anhydrase inhibitor (CAI). We present the first single-dose clinical trial of MK-927 in 24 patients with bilateral primary open-angle glaucoma or ocular hypertension. This investigation was conducted as a two-centre, double-masked, randomised, placebo controlled study. Patients received one drop of 2% MK-927 in one eye and placebo in the other eye. Modified diurnal intraocular pressure (IOP) curves were performed before the study and on one treatment day. A single dose of 2% MK-927 induced a peak mean IOP decrease of 10.5 mmHg at 4.5 hours postdose. With compensation for diurnal variation, as determined by the prestudy diurnal pressure curve, the net peak mean reduction of IOP caused by MK-927 was 7.5 mmHg versus a corresponding net change of 1.4 mmHg in the contralateral placebo treated eye. Thus a single dose of MK-927 gave a clinically significant IOP reduction in patients.

Carbonic Anhydrase Inhibitors↗
PubMed1990

[The pattern electroretinogram in early glaucoma and ocular hypertension].

The pattern electroretinogram (PERG) reflects the activity of the retinal ganglion cells. To assess its value to detect early glaucoma damage, we recorded the PERG in 44 normal eyes, in 52 eyes with early stages of glaucoma, and in 34 eyes with elevated intraocular pressure but normal visual fields (ocular hypertension, OHT). All eyes had a decimal acuity of greater than or equal to 0.8. We used checkerboard patterns for the stimulation with check sizes of 0.8 degrees and 15 degrees, a contrast of 98% and a reversal rate of 16/s. Compared to the controls, in eyes with early glaucoma PERG amplitude was reduced to 50% using 0.8 degrees (p less than or equal to 0.0001) and to 74% using a check size of 15 degrees (p less than or equal to 0.001). However, due to the high interindividual variability, confidence limits overlapped to a large extent. Based on the preferential reduction at 0.8 degrees vs 15 degrees, a sensitivity of 74% and a specificity of 92% were achieved using a two-dimensional logistic regression; 50% of the OHT eyes were thus classified as pathological. These results suggest that the PERG can detect retinal ganglion cell damage before measurable changes in the visual field occur if responses to two check sizes are evaluated.

Adult↗
PubMed1990

[Local carbonic anhydrase inhibitors MK-927 and Mk-417. Effect and tolerance].

A comparative ocular tolerance study was undertaken with the topical carbonic anhydrase inhibitor (CAI) MK-927 (1% and 2%) and its S-enantiomer MK-417 (1% and 1.8%) in 20 healthy normal volunteers. In this randomized, double-blind cross over study, placebos were used for control over five periods. The subjects received one drop of placebo (common vehicle) or CAI in each eye in successive periods separated by a washout period of 1 week. Three hours after the dose, the IOP was found to be decreased by 5.3% to 9.1%, depending on the dose, with all four CAI treatments and significantly so with MK-417. Pupil-size and central vision were unchanged by CAIs. External and anterior segment examination revealed no changes following any of the treatments. The incidence of burning was significantly increased by 2% MK-927 (p less than 0.01) and 1.8% MK-417 (p less than 0.05) compared to placebo. The mean duration of burning placebo was 16.8 s, but it was significantly longer (23 to 37.1 s) following CAI application. Duration of tearing following CAI application was also significantly prolonged (p less than 0.05).

Adult↗
PubMed1990

[Decrease in intraocular pressure following administration of the local carbonic anhydrase inhibitor (MK-927)--comparison of the effect with pilocarpine].

We studied the effect of a single dose of the local carbonic anhydrase inhibitor, MK-927, on lowering IOP in 24 patients with bilateral primary open-angle glaucoma or ocular hypertension and compared it with the effect of pilocarpin in 9 patients. Following a washout of any glaucoma medication of 3 to 14 days, a diurnal IOP curve was performed. Two to seven days later one eye received a single drop of 2% MK-927 while the other eye received placebo and the diurnal IOP curve was repeated. MK-927 treated eyes showed a peak mean IOP change of 10.5 mmHg (33.1%) occurring at 4.5 h postmedication. In nine eyes treated with pilocarpin 1% q.d., the mean reduction of the mean IOP was 7.0 mmHg (22.1%) compared to no treatment. The same eyes showed a mean reduction of mean IOP of 6.1 mmHg (18.9%) following a single dose of MK-927. In contrast, the mean reduction of the maximal IOP treated with pilocarpin was 7.3 mmHg (25.8%) and 10.2 mmHg (34.2%) following MK-927. Considering the IOP lowering of MK-927 shown here, the possibility of a topically effective glaucoma therapy by local carbonic anhydrase inhibitor seems to be established. The IOP lowering effect of MK-927 appears to be similar to that of pilocarpin 1%.

Carbonic Anhydrase Inhibitors↗
PubMed1989

Limbus-based versus Fornix-based conjunctival flap in filtering surgery. A randomized prospective study.

A randomized prospective study was performed to compare the results of filtering surgery using a Limbus-based versus a Fornix-based conjunctival flap. The wound closure of the Fornix-based flap was performed using a running 10/0 nylon suture at the limbus. No statistical significant difference of IOP regulation was found between the two groups. There was a tendency of reduced occurrence of shallow anterior chamber and of less vascularized filtering blebs in the Fornix-based technique.

Conjunctiva↗
PubMed1989

[Treatment of glaucoma chronicum simplex with a combination of 0.5 percent timolol with 0.5 percent adrenaline plus 0.3 percent guanethidine].

The effect on the intraocular pressure of patients with primary open-angle glaucoma of a combination of timolol 0.5% with epinephrine 0.5% plus guanethidine 3% was studied and compared with the effects of timolol alone, of epinephrine 0.5% plus guanethidine 3%, and of other glaucoma drugs. The combination of timolol 0.5% with epinephrine 0.5% plus guanethidine 3% had a stronger effect on intraocular pressure (reduction 10.9 +/- 1.1 mm Hg) than epinephrine 0.5% plus guanethidine 3% (7.6 +/- 0.9 mm Hg) or timolol alone (5.8 +/- 1.1 mm Hg) or other glaucoma drugs. However, when the three substances are administered in combination therapy may show an addition of both pressure-lowering and side effects.

Clinical Trials as Topic↗
PubMed1985

Presynaptic opioid receptor subtypes in the rabbit ear artery.

In segments of rabbit ear arteries preincubated with [3H]noradrenaline, Leu-enkephalin, D-Ala2-D-Leu-enkephalin and ethylketocyclazocine concentration dependently reduced the overflow of tritium and the vasoconstriction elicited by field stimulation (120 pulses every 14 min, 1 Hz, 0.3 msec pulse duration). The effects of Leu-enkephalin and ethylketocyclazocine were antagonized by naloxone which, given alone, increased the evoked overflow of tritium at the high concentration of 10 microM. Morphine failed to produce inhibition, and at 100 microM actually increased evoked 3H-overflow. Continued exposure to Leu-enkephalin desensitized the tissue to this opioid; there was no cross-desensitization to ethylketocyclazocine. In arteries not preincubated with [3H]noradrenaline, normorphine, fentanyl and morphiceptin did not change the vasoconstrictor response (5 pulses every min, 5 Hz, 0.3 msec pulse duration). Among various peptide agonists, Leu-enkephalin, D-Ala2-D-Leu-enkephalin and Met-enkephalin were the most potent inhibitors. In a series of peptides with C-terminal extensions of the Met-enkephalin chain, the potency decreased in the order Met-enkephalin greater than Met-enkephalin-Arg-Gly-Leu greater than Met-enkephalin-Arg-Phe greater than BAM-12P greater than beta-endorphin. In a series of peptides with C-terminal extensions of the Leu-enkephalin chain, the potency decreased in the order Leu-enkephalin greater than dynorphin1-13 greater than dynorphin1-9 greater than alpha-neo-endorphin greater than dynorphin1-8 greater than dynorphin1-6 greater than dynorphin1-17. The delta-selective antagonist ICI 154129 counteracted the effect of Met-enkephalin but not that of dynorphin1-13, whereas naloxone counteracted the effect of either agonist.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗