Therapeutic progress I: Current treatment of rheumatoid arthritis

Over recent years the pharmacological treatment strategy for rheumatoid arthritis (RA) has changed. An early, aggressive approach has been adopted with a view to maintaining functional capacity. The changing role of nonsteroidal antiinflammatory agents is discussed in the light of the potential toxicity of this class of drugs. The current use of second-line agents is dealt with in depth and includes guidelines to patient monitoring. Particular attention has been paid to the growing use of cyclosporin A in the treatment of RA as this drug represents the newest, most potent, nonexperimental form of treatment. The questions of when to introduce second-line agents, who should receive treatment and how many drugs should be prescribed are all addressed in this review. The relative efficacy and toxicity of these agents is discussed and a treatment protocol is proposed.     

THE TREATMENT OF ACUTE AND CHRONIC VAGINAL CANDIDOSIS

Vaginal candidosis is one of the most common infections of the vagina and the first accredited record of the disease appeared in 1849. Over the years the terms ‘candidiasis’ and ‘candidosis’ have been used, but it is generally accepted now that the terms are synonymous, and the term most commonly in use today is ‘candidosis’. Mainly caused by the yeast Candida albicans, the condition is characterised by intense inflammation of the vaginal mucosa and a curdy, off-white discharge; it is often associated with severe vulval itching and possibly burning pain. The severity of symptoms seems to vary greatly from patient to patient and the reason for this is unclear. It is suggested that in some patients there may be an element of hypersensitivity. Vaginal candidosis may occur in children but is most common in adults and only sometimes affects the elderly. The majority of women will suffer at least one attack of vaginal candidosis during their lifetime, and there are several predisposing factors such as diabetes, pregnancy and antibiotics. Some authorities consider the condition more frequent in those taking oral contraceptives or other hormones.     

Isolation and characterization of marine luminous bacteria from shallow coastal waters of Taiwan.

BACKGROUND AND PURPOSE: Marine luminous bacteria were isolated and identified from samples in shallow coastal waters of Taiwan during the relatively warm seasons. METHODS: Identification of the luminous isolates was performed based on differences of phenotypic and genotypic characteristics together with data from phylogenetic analysis. RESULTS: Twenty seven strains of marine luminous bacteria were isolated. They were divided into five types based on differences of phenotypic characteristics. However, they could be clustered into only two genotypes according to the analysis of restriction patterns of polymerase chain reaction-amplified 16S rRNA genes digested with various restriction enzymes. The characterization data together with the 16S rRNA gene-based phylogenetic analysis revealed that the isolates included in phenotype I (seven isolates) could be Photobacterium leiognathi, and those included in phenotypes II-V (twenty isolates) might be classified as Vibrio harveyi. However, phylogeny based on gyrB sequences indicated that phenotypes II-V could be classified into two species, V. harveyi and Vibrio campbellii. CONCLUSION: Culturable luminous bacteria in the shallow coastal waters of Taiwan during the sampling period are dominated by V. harveyi/campbellii and P. leiognathi, and the former species appeared to be more prevalent and numerous than the latter species in general.     

Deletion of aldose reductase leads to protection against cerebral ischemic injury.

Previously, we reported that transgenic mice overexpressing endothelin-1 in astrocytes showed more severe neurological deficits and increased infarct after transient focal ischemia. In those studies, we also observed increased level of aldose reductase (AR), the first and rate-limiting enzyme of the polyol pathway, which has been implicated in osmotic and oxidative stress. To further understand the involvement of the polyol pathway, the mice with deletion of enzymes in the polyol pathway, AR, and sorbitol dehydrogenase (SD), which is the second enzyme in this pathway, were challenged with similar cerebral ischemic injury. Deletion of AR-protected animals from severe neurological deficits and large infarct, whereas similar protection was not observed in mice with SD deficiency. Most interestingly, AR(-/-) brains showed lowered expression of transferrin and transferrin receptor with less iron deposition and nitrotyrosine accumulation. The protection against oxidative stress in AR(-/-) brain was also associated with less poly(adenosine diphosphate-ribose) polymerase (PARP) and caspase-3 activation. Pharmacological inhibition of AR by Fidarestat also protected animals against cerebral ischemic injury. These findings are the first to show that AR contributes to iron- and transferrin-related oxidative stress associated with cerebral ischemic injury, suggesting that inhibition of AR but not SD may have therapeutic potential against cerebral ischemic injury.     

Revision endoscopic frontal sinus surgery with surgical navigation.

BACKGROUND: Revision surgery of the frontal sinus remains one of the most difficult operations for the endoscopic surgeon. Most agree that knowledge and recognition of its complex anatomy and sparing of frontal recess mucosa are keys to a successful operation. The use of surgical navigation systems may allow for more precise dissections and greater rates of frontal recess patency. METHODS: Retrospective review of all patients undergoing revision endoscopic frontal sinus surgery with surgical navigation was performed with a minimum 24-month follow-up. RESULTS: Sixty-seven patients underwent revision endoscopic frontal sinus surgery with surgical navigation. The average follow-up was 32 months. Fifty-eight (86.6%) had a patent frontal recess and significant subjective improvement in symptoms. No patient underwent external frontal sinus obliteration, and there were no major complications. CONCLUSIONS: Endoscopic techniques with surgical navigation are effective in revision frontal sinus cases. The dissection of remnant agger nasi, obstructing frontal and supraorbital cells are necessary to widen the anterior-posterior as well as the medial-lateral dimensions of the recess. Computer navigational systems appear to serve as a valuable adjunct in preoperative planning and safe intraoperative dissection.     

Alpha-smooth muscle actin in pathological human disc nucleus pulposus cells in vivo and in vitro

That a contractile actin isoform has been found in cells of other cartilage tissues in healing and disease states prompted this investigation of the presence of alpha-smooth muscle actin (alpha-SMA) in pathological human intervertebral disc tissue. The presence of this isoform has been reported in human intervertebral disc specimens obtained at autopsy from subjects for whom there were no reported symptoms. An objective of this study was to evaluate the cell density and percentage of alpha-SMA-containing cells in pathological nucleus pulposus tissue obtained from lumbar disc surgery from 17 patients. Additionally, explants of nucleus pulposus material were cultured to determine how alpha-SMA expression changed with time in vitro. Seventy-six 5-mm diameter explants (approximately 2 mm thick) pooled from six lumbar surgeries were cultured for 1, 2, 4, or 6 weeks. Microtomed sections of paraffin-embedded specimens were stained with hematoxylin and eosin or a monoclonal antibody to alpha-SMA. Histologically, cells were categorized as to alpha-SMA phenotype (positive or negative), and the areal cell density was determined. The evaluation of the cultured nucleus pulposus explants also included documentation of the percentage of cells that were round or elongated and the percentage of the cells that were part of a group (group: >/= 2 cells). Every nucleus pulposus section exhibited the presence of alpha-SMA-containing cells, which accounted for approximately 24 percent of the cells in vivo. In vivo, the cell density was significantly higher in older individuals (p = 0.02). The average time for cell outgrowth from the explants was 8.6 days. Approximately 10-15 percent of the cells in the explants stained positive for alpha-SMA. The time in culture had no significant effect on any of the outcome measures except the percentage of alpha-SMA-containing cells that were round (p = 0.008), with values decreasing through 4 weeks and then slightly rising at 6 weeks. The role of alpha-SMA in intervertebral disc pathology warrants further investigation.     

Ocular findings in the chromosome 22q11.2 deletion syndrome.

PURPOSE: To identify the ocular features of the chromosome 22q11.2 deletion syndrome and to provide ophthalmologic examination recommendations for affected patients. METHODS: Ocular abnormalities were evaluated prospectively in patients with 22q11.2 deletion at the Children's Hospital of Philadelphia between 1997 and 1999. RESULTS: Ninety patients with confirmed 22q11.2 deletion were examined. Posterior embryotoxon was found in 49%, tortuous retinal vessels in 34%, eyelid hooding in 20%, strabismus in 18%, ptosis in 4%, amblyopia in 4%, and tilted optic nerves in 1%. CONCLUSIONS: The high incidence of ocular conditions that can potentially affect visual development suggest that children with 22q11.2 deletion should undergo a comprehensive eye examination upon diagnosis of the condition with follow-up as indicated by the findings in each case. In addition, knowledge of the ocular findings, in conjunction with certain cardiac, otolaryngologic, immunologic, and other systemic findings, may alert physicians to the possibility of a chromosome 22q11.2 deletion.     

Sleep apnea--an overview

Though distressing and potentially dangerous, sleep apnea may be an under-recognized disease in many countries. The obstructive type, which usually presents with loud snoring and excessive daytime sleepiness, is by far the commonest form. It causes a great deal of medical, social and psychological morbidity as well as an increased mortality. Doctors of different specialties have an important role in detecting and referring suspected patients for early assessment and treatment. Multidisciplinary management in a general hospital and accurate assessment with polysomnography are essential as modern and sometimes effective methods of treatment are becoming available.