Orbitofacial neurofibromatosis: clinical characteristics and treatment outcome.

PURPOSE: To report clinical observations and surgical management in a large series of patients with orbitofacial neurofibromatosis type 1 (OFNF). PATIENTS AND METHODS: Patients were identified and medical records reviewed for demographic data, ophthalmologic examinations, surgical interventions, and procedure outcome to create a retrospective, non-comparative case series of patients with OFNF seen at one medical centre over a 23-year period. RESULTS: Sixty patients with OFNF (31 females and 29 males; mean age, 14 years) were followed for an average of 5.7 years. Presenting signs and symptoms included eyelid swelling in all patients, ptosis in 56 (93.3%), proptosis in 34 (56.6%), dystopia or strabismus in 30 (50%), and decreased visual acuity in 50 (83.3%). Surgical intervention included ptosis repair in 54 (90%; mean 1.6 surgical procedures), facial and orbital tumour debulking in 54 (90%; mean 2.3 surgeries), and canthoplasty in 28 (46.6%) patients. Eleven patients required enucleation or exenteration of a blind eye. CONCLUSION: Patients with OFNF often require multiple procedures to preserve vision, prevent additional disfigurement, and achieve cosmetic rehabilitation. Patients need regular ophthalmological monitoring given the potential for progressive visual and cosmetic consequences.

Inpatient preseptal cellulitis: experience from a tertiary eye care centre.

OBJECTIVE: To describe causes of preseptal cellulitis (PSC) and outcome of treatment in patients admitted to a tertiary eye-care centre. METHODS: A 15-year (January 1991 to December 2005) review of inpatients with clinical signs and symptoms or radiological evidence suggestive of PSC was conducted. Patients with infection anterior to the orbital septum which is characterised by acute onset of eyelid oedema, tenderness, erythema, warmth and chemosis were included in the study. RESULTS: Among the 104 patients (male:female 64:40) fulfilling the diagnostic criteria for PSC, acute dacryocystitis (ADC) was the most common predisposing cause in 32.6% patients, followed by sinusitis/upper-respiratory infection (URI) in 28.8% and trauma/recent surgery in 27.8% patients. Fifty-per cent required surgical intervention including dacryocystorhinostomy/probing/stenting in 74% and abscess/chalazian drainage in 28.8%. In 38.5% of the patients who had surgical intervention, microbiological investigations were carried out, cultures were positive in 90%. Most common micro-organisms recovered included Staphylococcus and Streptococcus species followed by Haemophilus influenzae and Klebsiella pneumonia. Blood cultures were positive in two of the 34 patients in whom blood was drawn. Most patients responded to systemic antibiotics with resolution of PSC. Seven patients developed late complications which included subacute lid abscesses, eyelid necrosis and cicatricial ectropion. CONCLUSIONS: Sinusitis/URI, ADC and recent history of trauma/surgery were the most common cause of PSC in admitted patients. Although most patients responded to systemic antibiotics, surgical intervention was necessary in some patients to prevent associated complications.

Development of early choroidal neovascular membrane in a young myope after LASIK.

PURPOSE: To describe development of early choroidal neovascular membrane (CNVM) after laser-assisted in situ keratomileusis (LASIK) procedure in a young myopic patient that was successfully managed by photodynamic therapy (PDT). METHODS: A retrospective interventional case report. RESULTS: A 20-year-old woman with myopic astigmatism underwent uneventful LASIK surgery resulting in best-corrected visual acuity (BCVA) of 20/20 bilaterally. One week later, the patient presented with decreased VA in the right eye and was found to have clinical evidence of central serous chorioretinopathy (CSC). She was treated with systemic corticosteroids without any improvement. Two weeks after LASIK, the patient's VA was 20/200 and clinical evidence of early CNVM was confirmed by fluorescein angiography, indocyanine green angiography, and optical coherence tomography (OCT). PDT resulted in the regression of her CNVM with improvement in her VA and OCT findings. CONCLUSIONS: Systemic corticosteroids may enhance CNVM in patients with LASIK-induced early CNVM. PDT may be effective in the resolution of LASIK-induced CNVM.

Orbital cellulitis following implantation of aqueous drainage devices.

PURPOSE: Orbital cellulitis (OC) as a complication of implanted aqueous drainage devices (ADD) for glaucoma is an uncommon phenomenon. The authors report two cases of infectious OC in patients with a history of congenital glaucoma and placement of ADD. METHODS: Clinical records of two patients with ADD who subsequently developed OC were reviewed for presenting symptoms, signs, medical and surgical management, and final outcome. RESULTS: In the first case, an 11-year-old girl was found to have evidence of OC 9 days after the implantation of a Krupin-Denver valve. In the second case, a 14-month-old girl presented with similar findings 8 months following the implantation of an Ahmed valve. In both cases, ultrasonography demonstrated evidence of orbital inflammation and in one patient computed tomography scan was consistent with OC. In both cases, prompt institution of systemic antibiotics resulted in resolution of the clinical signs. In the first case, diagnosis was made early and the patient was promptly treated with systemic antibiotics, resulting in resolution of her symptoms without the need for implant removal. Because of the delayed presentation in the second case, an infected implant had to be removed to achieve resolution in addition to aggressive with antibiotics treatment. CONCLUSIONS: Although rare, infectious OC may occur following implantation of ADD. Early recognition and intervention may be required to achieve resolution of the infection.

Progressive severe visual loss after long-term withdrawal from thioridazine treatment.

PURPOSE: To report advanced thioridazine-induced retinopathy in a 50-year-old woman with evidence of progressive severe loss of vision over 30 years after withdrawal from thioridazine treatment. METHODS: The ocular fundus examination revealed areas of retinal pigment epithelium (RPE) clumping as well as generalized atrophy of the RPE and choroid. The patient experienced visual loss to the level of no light perception in both eyes despite the fact that the funduscopic appearances of her optic nerves and retinal vasculature remained relatively normal. CONCLUSIONS: This case demonstrates that severe progressive visual loss can occur several years after the cessation of chronic thioridazine treatment.

Optic nerve avulsion from door-handle trauma in children.

AIM: To report severe visual loss caused by optic nerve avulsion (ONA) in children with door-handle trauma. METHODS: Clinical records at a tertiary eye care hospital, of 14 children who sustained severe visual loss as a result of door-handle injuries, were reviewed. The data were analysed for location, presenting symptoms and signs, diagnostic studies, intervention, and the cause of visual loss. RESULTS: There were 11 males and three females with an average age of 8 years and an average height of 125 cm. The place of trauma was home in 11 and school in three children. Presenting visual acuity (VA) was light perception (LP) in five patients and no light perception (NLP) in nine. All the 14 children had evidence of ONA and four patients had ruptured eye globes that required initial repair. The diagnosis of ONA was made clinically or by imaging studies and confirmed histopathologically in eyes that were enucleated. Average follow up was 28.8 months (range 4 months to 8 years). Final VA was LP in one patient and NLP in 13 patients, eight eyes required enucleation for painful blind eye or to achieve optimal cosmesis. CONCLUSION: ONA was the common cause of visual loss in children who sustained ocular trauma caused by door-handles.

A new short-acting non-depolarizing muscle relaxant (SZ1677) without cardiovascular side-effects.

BACKGROUND: In order to facilitate rapid tracheal intubation, the development of a rapid onset, short duration, non-depolarizing muscle relaxant without cardiovascular side-effects would be a significant accomplishment in the field of anesthesiology. The aim of the present study was to test the action of a new non-depolarizing muscle relaxant (SZ1677) on neuromuscular transmission, muscarinic (M2, M3) receptors and cardiovascular reactions and to compare it with clinically used muscle relaxants. METHODS: Neuromuscular transmission was studied by recording muscle contractions elicited by indirect electrical stimulation, using (i). in vitro isolated phrenic nerve-hemidiaphragm preparation of mice, rats and guinea pigs and (ii). in vivo sciatic nerve-anterior tibial muscle preparation of anesthetized rats, guinea pigs and cats. Cardiovascular effects of muscle relaxants were evaluated on the grounds of their effects on changes of blood pressure and heart rate induced by electrical stimulation of the right vagal nerve in anesthetized cats. To study postsynaptic antimuscarinic affinity of muscle relaxants on M3 receptors, oxotremorine-induced contractions of longitudinal muscle strip of guinea pig ileum were registered in their presence and absence. RESULTS: One of more than 120 newly synthesized non-depolarizing muscle relaxants compounds, 1-3[alpha-hydroxy-17beta-acetyloxy-2beta-(1,4-dioxa-8-azaspiro[4,5]dec-8-yl)-5alpha-androstane-16beta-il] -1-(2-propenyl)pyrrolidinium bromide (SZ1677), excelled with its advantageous pharmacological properties: relatively short duration of action, no accumulation and lack of unwanted side-effects. Pharmacodynamic studies show that SZ1677 is a non-depolarizing neuromuscular blocking agent with a relatively short duration and rapid onset of action in a variety of laboratory animal species. It is without cumulative effect, does not reduce blood pressure, and fails to produce tachycardia. Significant cardiac vagal blocking effects were not observed even at concentrations or dosages of 8 times the ED90. This compound, unlike many other muscle relaxants, does not have atropine-like effects on human atrial tissue; it does not increase the release of NA from sympathetic innervation in the heart. In all practical ways, at least from the vantage point of the preclinical study, SZ1677 compares favorably with all presently available short-acting muscle relaxants, including rapacuronium. CONCLUSION: In experiments, SZ1677 proved to be a short-acting neuromuscular blocking compound having a large safety margin between the doses required to produce neuromuscular block and those likely to lead to cardiovascular side-effects.

Randomized, controlled study of low-dose 5-fluorouracil in primary trabeculectomy.

PURPOSE: To report a randomized clinical trial of postoperative subconjunctival injections of low-dose 5-fluorouracil in patients undergoing primary trabeculectomy. METHODS: In a prospective, randomized clinical trial, 40 eyes of 40 patients were randomized to the low-dose 5-fluorouracil group and received three subconjunctival injections of 5 mg each over 11 postoperative days, and 40 eyes of 40 patients were randomized to trabeculectomy without 5-fluorouracil. RESULTS: Mean (+/-SD) preoperative and 1-year postoperative intraocular pressures in the 5-fluorouracil group were 26.9 (+/-9.5) and 15.3 (+/-5.8) mm Hg, respectively. In the control group these were 25.9 (+/-8.1) mm Hg, and 15.8 (+/-5.1) mm Hg, respectively. The patients who received 5-fluorouracil had a mean reduction in intraocular pressure of 11.5 (+/-9.1) mm Hg at a median follow-up of 52.3 weeks. The control group had a mean reduction in intraocular pressure of 10.2 (+/-8.7) mm Hg at a median follow-up of 52.6 weeks. These differences were not statistically significant. CONCLUSIONS: Three postoperative subconjunctival 5-fluorouracil injections of 5 mg each after trabeculectomy in eyes at low risk for failure had no statistically or clinically significant effect on reduction of intraocular pressure with 1-year follow-up. Enhancement of success in this group of patients may require a larger total dose of 5-fluorouracil.

Chemical composition of upper renal tract calculi in Multan.

OBJECTIVE: To study the chemical composition of upper renal tract (renal and ureteric) calculi in Multan. SETTING: Department of Urology, Nishtar Hospital, Multan. STUDY PERIOD: September 1992 to February 1999. MATERIAL AND METHODS: A total of 700 renal and ureteric calculi were analyzed by chemical method of Hodgkinson. RESULTS: The commonest were uric acid (28.1%) calculi, followed in frequency by calcium oxalate calculi (26.1%), mixed calculi containing calcium oxalate and uric acid (21.8%) and calculi containing calcium oxalate and calcium phosphate (10.4%). Other variety of calculi were less common. CONCLUSION: Uric acid, calcium oxalate and mixed uric acid and calcium oxalate calculi are the main types in Multan region (JPMA 50:145, 2000).

Bilateral ptosis and lower eyelid ectropion secondary to cutaneous leishmaniasis.

A 73-year-old white woman had a 14-month history of an extensive, disfiguring facial lesion involving the cheeks, nose, and eyelids, resulting in exposure keratopathy. A biopsy of the facial lesion established the diagnosis of cutaneous leishmania, and the lesion responded to treatment with itraconazole.

Orbital melanoma presenting as orbital cellulitis: a clinicopathologic report.

Most choroidal melanomas are diagnosed when the tumor is still relatively small and confined to the globe. Rarely, these tumors can escape detection and extend through the sclera. They can reach a large size and create significant orbital inflammation. The authors describe a 71-year-old man with orbital cellulitis secondary to a necrotic choroidal melanoma that invaded the orbit. This tumor had minimal intraocular involvement with a large extrascleral component. On histopathologic analysis, the lesion was best classified as a spindle B melanoma with epithelioid areas (mixed melanoma). The patient was treated with an enucleation and postoperative radiation. This report demonstrates that malignancies in the orbit can present as acute infections. Early suspicion, diagnosis, and treatment of these lesions offer the best chance for survival.

Neurochemical evidence that [Ca2+]o antagonizes the effect of neomycin on acetylcholine release from mouse hemidiaphragm preparation: an attempt to assess the margin to safety.

Although the neuromuscular junction is the most thoroughly studied synapse of any type and has become the model of our understanding of synaptic transmission, some questions remain unanswered; e.g. there has been no direct assessment of the size of margin of safety. In this study the [Ca2+]o-dependent, quantally released acetylcholine measured by a neurochemical method, and the contraction of the mouse hemidiaphragm in response to phrenic nerve stimulation were recorded, and the effect of neomycin was studied. It was found that a much higher concentration of neomycin was needed to depress contractions, than to reduce acetylcholine release to the same extent, and that there was an inverse correlation between [Ca2+]o and the inhibitory effect of neomycin on acetylcholine release. Ninety percent of the release of acetylcholine had to be reduced by neomycin before any reduction in muscle responses could be seen. This indicates that the margin of safety is about 10. In conclusion, at the neuromuscular junction any reduction in ACh release, whatever the mechanism, first produces a reduction in the margin of safety. The nondepolarizing neuromuscular blocking agents block primarily the nicotinic receptors located on the postjunctional site. Many receptors have to be blocked before a reduction of muscle response is observed. This is probably the reason why unexpected clinical problems (e.g. recurarization) have been described when a patients has been treated with antibiotics, even though the dose of muscle relaxant injected was relatively low.

The pre- and postjunctional components of the neuromuscular effect of antibiotics.

The relative contributions of the pre- and postsynaptic components of the myoneural blocking effect of different antibiotics were studied using: (a) a radio-active method that measures selectively the Ca(2+)-dependent, stimulation evoked, quantally released, (3)H-acetylcholine ((3)H-ACh) from the mouse in vitro phrenic nerve-hemidiaphragm preparation without cholinesterase inhibition; (b) measurement of the force of contraction of the indirectly or directly stimulated muscle. The antibiotics studied (neomycin, polymyxin B and lincomycin), reduced the release of (3)H-ACh evoked by stimulation (18 trains of 40 shocks at 50 Hz) in a concentration dependent manner. While the inhibitory effect of neomycin was inversely related to [Ca(2+)](o), that of lincomycin was moderately and that of polymyxin B was not affected by increasing [Ca(2+)](o) from 0.75 to 5.0 mM. Similarly, the d-tubocurarine (d-Tc)-induced inhibition of the release of (3)H-ACh was independent of [Ca(2+)](o). The K-channel blocking agent, 4-aminopyridine (4-AP), enhanced the release of ACh in a concentration dependent manner and prevented the neuromuscular effect of neomycin. However, the neuromuscular effect of polymyxin B and of lincomycin was not affected by 4-AP. Atropine, enhanced the release of (3)H-ACh. Antibiotics, however, were still able to reduce the release of ACh when the negative muscarinic feedback mechanism of ACh release was eliminated by atropine. Our findings indicate that the antibiotics studied possess both pre- and postsynaptic effects. Presynaptically they reduce the evoked release of ACh; postsynaptically they inhibit muscle contractility. The rank order of presynaptic action is neomycin >polymyxin B >lincomycin.

Amphetamine behavioral sensitization and the excitatory amino acids.

The effects of 8 selective neuroeffector agonists and antagonists were measured in mice in order to identify specific functional changes associated with behavioral sensitization to amphetamine-induced stereotypy. The changes observed included a decreased convulsive threshold to N-methyl-DL-aspartic acid, an increased convulsive threshold to bicuculline, and an increased head-twitch response to 5-hydroxytryptophan. Of these effects, only the persistence of the two convulsive threshold changes correlated with the persistence of the behavioral sensitization. The induction of behavioral sensitization was blocked by haloperidol, dizocilpine or ketamine, but not affected by cyproheptadine or diazepam: therefore, the mechanism of the enhanced responsiveness involves not only a functional dopamine system, but also a functional N-methyl-D-aspartic acid component of the excitatory amino acid system. The block of behavioral sensitization also prevented the amphetamine-induced changes in the convulsive thresholds. Finally, neither ketamine nor dizocilpine affected the expression of the enhanced response in the behaviorally sensitized animals. The data indicate that the characteristics of amphetamine behavioral sensitization to stereotypy are similar to those of long-term potentiation.

Inhibition of mobilization of acetylcholine: the weak link in neuromuscular transmission during partial neuromuscular block with d-tubocurarine.

The authors have demonstrated earlier, by direct measurement of acetylcholine (ACh), that d-tubocurarine (d-Tc) and other nondepolarizing muscle relaxants decrease the release of ACh from the indirectly stimulated mouse hemidiaphragm preparation. It was the purpose of the present study to determine whether the decrease of the stimulated release of ACh and the increase in the intensity of the partial neuromuscular block observed at higher stimulation rates is caused by the inhibition of mobilization of ACh from reserve depots to release sites or by inhibition of the release process itself. To attain our objective, the authors have investigated the influence of the progressive increase of the rate of stimulation from 0.1 to 1, 2, 3, and 5 Hz on the force of contraction on the in vitro phrenic nerve-hemidiaphragm and in vivo sciatic nerve-tibialis anterior preparation in the absence of drugs and after about 20% neuromuscular block produced by d-Tc or by Mg2+. The latter is known to inhibit the Ca2+ dependent release of ACh. In the absence of drugs increasing the stimulation rate increased the force of contraction, in vivo and in vitro, during both indirect and direct stimulation. In the phrenic nerve-hemidiaphragm preparation the increase was significant at 1, 2, 3, and 5 Hz (P less than 0.001) with both types of stimulation. In the sciatic nerve-tibialis anterior preparation the force of contraction was only higher at 3 and 5 Hz (P less than 0.01). The similar magnitude of the increase of the force of contraction during direct and indirect stimulation indicates that it is caused by facilitation of the contraction of the muscle fibers.(ABSTRACT TRUNCATED AT 250 WORDS)

In vitro comparison of the neuromuscular antinicotinic and intestinal antimuscarinic effects of different nondepolarizing muscle relaxants.

The postsynaptic antimuscarinic properties of different nondepolarizing muscle relaxants were compared with their postsynaptic antinicotinic effect. d-Tubocurarine, pipecuronium and vecuronium were the most selective antagonists on postsynaptic nicotinic receptors. Gallamine, diadonium and Duador (RGH-4201) had relatively greater effect on postsynaptic muscarinic receptors. Therefore, much less side effect is expected to occur when pipecuronium, d-tubocurarine or vecuronium are used.

Species variation in the site and mechanism of the neuromuscular effects of diadonium in rodents.

The unusually wide, 80-fold species variation observed by others (1,2) in the neuromuscular (NM) potency of diadonium, a nondepolarizing muscle relaxant (MR), between cat and man suggested that the site and mechanism of its NM effect may vary in different species. To obtain information on this question, the NM potency of diadonium and the reversibility of its NM effect by neostigmine and/or 4-aminopyridine (4AP) was investigated on the in vitro phrenic nerve--hemidiaphragm preparations of rats, mice and guinea pigs. The concentration of diadonium that caused 90% NM block (IC90) was much greater in guinea pigs, 1.74 +/- 0.02 and 1.28 +/- 0.01 mu, when the preparations were stimulated with single stimuli at 0.1 Hz or with 0.1 s trains of 50 Hz tetani every 10 s, respectively, than in rats (IC90 = 62.4 +/- 0.89 and 52.1 +/- 1.00 microM) or mice (IC90 = 51.9 +/- 0.98 and 44.4 +/- 0.22 microM). In guinea pigs, the NM blocking effect of diadonium could be antagonized by neostigmine. This indicates that in this species the NM blocking effect of diadonium is primarily caused by inhibition of the interaction of acetylcholine (ACh), released by the nerve impulse, with the cholinergic receptors (cholinoceptors) of the postjunctional membrane (p.j.m.). By contrast, in rats and mice diadonium was not antagonized by neostigmine but was reversed by 4-aminopyridine. This suggests that in these species, in contrast to other nondepolarizing MR, diadonium does not inhibit NM transmission postsynaptically, but by inhibiting the positive nicotinic feedback mechanism of mobilization of ACh from reserve depots to release sites, causes a presynaptic NM block.(ABSTRACT TRUNCATED AT 250 WORDS)

Blockade of "reverse tolerance" to cocaine and amphetamine by MK-801.

"Reverse tolerance" was produced in rats and mice by repeated exposure to either cocaine or amphetamine. The locomotorstimulant effect was studied in mice; stereotypy and convulsions in rats. MK-801, the NMDA antagonist, blocked the development of "reverse tolerance" to all three effects. In contrast, haloperidol selectively blocked "reverse tolerance" to cocaine-induced stereotypy but not to convulsions. The data suggest that the glutamate system participates in the mechanism of "reverse tolerance" to the dopaminergic effects of cocaine and amphetamine, as well as to the convulsant effect of cocaine.