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loss. A spinal tap yielded an opening pressure of 17 cm Intracranial Pressure Returns to Normal
H2O. Acetazolamide treatment was discontinued and fol- About a Month After Stopping
low-up examinations showed eventual resolution of the Tetracycline Antibiotics
Case 2. An 18-year-old woman received minocycline for 2 months. This was stopped when she developed head- T etracyclineantibioticsareusedwidely,espe- ache.Examination2weekslatershowedfloridpapill-
cially for the treatment of teenage acne vul- edema and bilateral abducens nerve pareses. A spinal tap garis. Raised intracranial pressure with fulmi- yielded an opening pressure of only 22 cm H nant papilledema can occur as a rare, idiosyncratic adverse ably because minocycline use had been stopped 2 weeks effect.1-3 The diagnosis is often delayed because obesity, earlier. Treatment was commenced with acetazolamide a diagnostic clue associated with pseudotumor cerebri, but was discontinued 3 weeks later when her papill- is usually absent. Consequently, patients may have ad- vanced visual field loss and impending blindness. To guide Case 3. A 16-year-old girl had received tetracycline for treatment, it would be useful to know how long intra- 4 months. She developed headache, obscurations, and ad- cranial pressure remains elevated after halting the use oftetracycline-class antibiotics.
vanced visual field loss (Figure 1). Examination re-
Eight patients were treated by a single neuro- vealed bilateral papilledema. The opening pressure was ophthalmologist (J.C.H.) from 1991 to 2006 for pseudo- 60 cm H2O. Tetracycline use was discontinued and treat- tumor cerebri caused by tetracycline antibiotics. In 4 cases, ment with acetazolamide was started. Four subsequent lumbar punctures were performed after stopping the use spinal taps were performed to lower intracranial pres- of the antibiotic. Measurement of the opening pressure (per- sure by removing cerebrospinal fluid. The pressure re- formed in the lateral decubitus position) revealed how long turned to normal 3 weeks after stopping tetracycline treat- it takes for intracranial pressure to return to normal. All of ment (Figure 2). A final measurement was obtained a
the patients had negative magnetic resonance imaging re- week after discontinuing acetazolamide use to make sure sults and normal cerebrospinal fluid results.
that her intracranial pressure did not rebound. Fundusexamination 6 weeks after cessation of tetracycline use Report of Cases. Case 1. A 15-year-old girl with an
showed residual papilledema, although her intracranial 8-month history of minocycline hydrochloride use had neck pain, obscurations, peripheral visual field loss, and Case 4. An 18-year-old woman received doxycycline diplopia. She had bilateral papilledema and an opening for a month. She developed headache, diplopia, and pap- pressure of 49 cm H2O. Minocycline use was discontin- illedema. The doxycycline use was stopped and acetazol- ued and acetazolamide treatment was started. Three weeks amide was started. A spinal tap performed 19 days later later, there was still severe papilledema and visual field yielded an opening pressure of 49 cm H2O. Two subse- Figure 1. Case 3. Humphrey 24-2 threshold perimetry, size III stimulus, showing severe visual field loss from papilledema. Three months later, the visual fields
had improved but the patient was left with permanent constriction. Fundus pictures show papilledema observed just after stopping tetracycline use (top) and 6
weeks later (bottom). Mild papilledema persisted, although the intracranial pressure had returned to normal 3 weeks earlier.
(REPRINTED) ARCH OPHTHALMOL / VOL 125 (NO. 8), AUG 2007 2007 American Medical Association. All rights reserved.
Bradyopsia in an Asian Man
B radyopsiaisarareretinaldisorder,firstdescribed
in 3 unrelated Dutch families.1 Patients withbradyopsia have difficulty tracking moving ob- jects and adapting to sudden changes in luminance levelsowing to a defect in the photoreceptor deactivation mecha- nism within the phototransduction cascades. Homozy-gous mutations in either the regulator G-protein signal- ing 9 (RGS9) or RGS9 anchor protein (R9AP) gene that encode the photoreceptor GTPase accelerating protein andits anchor protein, respectively, have been identified in pa- Figure 2. Time course for return of intracranial pressure to normal after
tients with bradyopsia.2 We report a case of bradyopsia stopping tetracycline antibiotics, shown by plotting pressure vs time for our in an Asian man with characteristic electrophysiologi- 4 cases and the case previously reported by Mochizuki et al.4 cal and genetic findings. This study was approved bythe institutional review board of the Singapore EyeResearch Institute.
quent lumbar punctures documented decreasing intra- Case Description. A 19-year-old Chinese man sought care
because he had reduced vision in bright lights and froma young age had difficulty tracking moving objects. He Comment. The elimination half-life of tetracycline an-
had no noteworthy medical history. His refractive error tibiotics is less than 24 hours, even for minocycline, the was ϩ0.50/−2.25 ϫ 160 OD and ϩ1.25/−3.50 ϫ 15 OS.
longest-acting drug in this class.5 Therefore, one might Best-corrected visual acuity was 20/25 (6/7.5) OD and expect intracranial pressure to return to normal within 20/30 (6/9) OS, and he had normal color vision. Exami- a few days of stopping tetracycline antibiotics. If so, treat- nation results of both anterior and posterior segments were ment to lower intracranial pressure would be useful for unremarkable. His parents, elder brother, and younger only a narrow time window after halting antibiotics.
sister were asymptomatic and had normal ophthalmic ex- In fact, intracranial pressure remains elevated longer than one would predict from the brief elimination half- The full-field electroretinogram (ERG) showed nor- life of tetracyclines. Mochizuki et al4 described a 16-year- mal scotopic responses (Figure 1). The maximal ERG
old girl treated with minocycline whose intracranial pres- responses were normal but only for the initial flash. Re- sure remained elevated for several weeks. This case, sponses from the subsequent flashes were reduced with combined with our 4 cases, indicates that raised intra- a 20-second interstimulus interval but normal with a 60- cranial pressure persists for 2 to 5 weeks after stopping second interstimulus interval. The scotopic red-flash ERG the use of tetracyclines. During this interval, patients responses indicated the presence of cone system func- should be monitored closely and treated aggressively to tion. However, the photopic ERG and 30-Hz flicker were prevent permanent visual loss. One should not inter- undetectable. The ERG findings of the patient’s family vene surgically, however, without verifying that intra- members were normal (data not shown).
cranial pressure is still elevated, as it can return to nor- Both the RGS9 and R9AP genes of the patient and his family were screened for mutations by direct sequenc-ing after informed consent was obtained. This showed a novel compound heterozygous mutation in the single- exon gene R9AP. The mutation in the paternal allele was a 2–base pair deletion (c.277-278delAT) (Figure 2). The
Correspondence: Dr Horton, Beckman Vision Center,
maternal allele had a deletion of an undetermined size University of California, San Francisco, San Francisco, that encompassed at least the entire coding region of R9AP.
CA 94143-0730 (
Hemizygosity was observed in the patient and his mother Financial Disclosure: None reported.
for 2 single-nucleotide polymorphisms located 2 kilo- Funding/Support: This work was supported by an un-
bases apart in the 5Ј and 3Ј untranslated regions of the restricted grant from Research to Prevent Blindness.
R9AP gene, confirming that this genomic deletion en-compasses the entire coding region of the R9AP gene. Real- 1. Gardner K, Cox T, Digre KB. Idiopathic intracranial hypertension associated time quantitative polymerase chain reaction performed with tetracycline use in fraternal twins: case reports and review. Neurology.
on genomic DNA also confirmed that only 1 copy of the 2. Chiu AM, Chuenkongkaer WL, Cornblath WT, et al. Minocycline treatment R9AP gene was present in both the mother and the pa- and pseudotumor cerebri syndrome. Am J Ophthalmol. 1998;126(1):116-121.
tient relative to the father and a normal control (data not 3. Friedman DI, Gordon LK, Egan RA, et al. Doxycycline and intracranial hypertension. Neurology. 2004;62(12):2297-2299.
4. Mochizuki K, Takahashi T, Kano M, Terajima K, Hori N. Pseudotumor cere- bri induced by minocycline therapy for acne vulgaris. Jpn J Ophthalmol. 2002; Comment. To our knowledge, this is the first report of
5. Smilack JD. The tetracyclines. Mayo Clin Proc. 1999;74(7):727-729.
(REPRINTED) ARCH OPHTHALMOL / VOL 125 (NO. 8), AUG 2007 2007 American Medical Association. All rights reserved.


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