Prevalence of Steroid-Induced Hyperglycemia in King Abdulaziz Specialist Hospital, Taif City, Saudi Arabia.

Background Hyperglycemia is a common side effect of high-dose steroid therapy in hospitalized patients. Objectives To assess the prevalence of hyperglycemia among hospitalized patients receiving steroid therapy. Methods A retrospective study was conducted among 245 patients. The inclusion criteria were patients undergoing steroid therapy and admitted to a single tertiary care hospital due to medical complications or exacerbation of the diseases they were suffering from. Data encompassing patient demographics, admission, discharge dates, comorbidities, medication histories, laboratory results (including blood glucose levels), and documented corticosteroid administrations were meticulously gathered from electronic health records (EHRs). A logistic regression model analysis was done to predict the risk factors of poor glycemic control among hospitalized patients. Results The prevalence of hyperglycemia among the patients who were on steroid therapy was 34.2%. About 70.7% of the patients who required insulin at the time of admission required >17 units, and the insulin requirement was significantly higher among patients who received dexamethasone compared to other steroids (p<0.05). Older age (>65 years) was found to be independently associated with poor glycemic control (p<0.05). Conclusion The study revealed that almost one-third of patients on steroid therapy had hyperglycemia. Monitoring of patients for hyperglycemia after beginning high-dose steroid therapy should be done.

Refractive index sensors based on cascaded multimode interference hetero-core optical fibers.

In this work, we demonstrate refractive index (RI) sensors based on the cascade of hetero-core structures using multimode and no-core optical fibers in sequence. The sensor device is engineered to have resonances at different wavelengths using different sensing region lengths. The device fabrication involves simple fiber cleaving and fusion splicing. For the experiments, the two sensor regions are exposed to liquids with different RIs. For the hetero-core fiber insertion length of 45 mm, the transmission valley is centered at 1082.5 nm with 15.1 nm full width at half-maximum (FWHM) for an external medium RI of 1.3370. Additionally, it shifts 4.1 nm towards longer wavelengths as the RI of the external medium increases to 1.3840. For the 30 mm long hetero-core structure, the valley is centered at 1599.7 nm with 23.3 nm FWHM for an external medium RI of 1.3370, which shifts 7.4 nm as the RI increases to 1.3840. The sensor sensitivities are up to -476d B/r e f r a c t i v e index unit (RIU) and 270 nm/RIU. The resolution of the devices is estimated to be 2×10-5 R I U.

High Intrapulmonary Rifampicin and Isoniazid Concentrations Are Associated With Rapid Sputum Bacillary Clearance in Patients With Pulmonary Tuberculosis.

BACKGROUND: Intrapulmonary pharmacokinetics may better explain response to tuberculosis (TB) treatment than plasma pharmacokinetics. We explored these relationships by modeling bacillary clearance in sputum in adult patients on first-line treatment in Malawi. METHODS: Bacillary elimination rates (BER) were estimated using linear mixed-effects modelling of serial time-to-positivity in mycobacterial growth indicator tubes for sputum collected during the intensive phase of treatment (weeks 0-8) for microbiologically confirmed TB. Population pharmacokinetic models used plasma and intrapulmonary drug levels at 8 and 16 weeks. Pharmacokinetic-pharmacodynamic relationships were investigated using individual-level measures of drug exposure (area-under-the-concentration-time-curve [AUC] and Cmax) for rifampicin, isoniazid, pyrazinamide, and ethambutol, in plasma, epithelial lining fluid, and alveolar cells as covariates in the bacillary elimination models. RESULTS: Among 157 participants (58% human immunodeficiency virus [HIV] coinfected), drug exposure in plasma or alveolar cells was not associated with sputum bacillary clearance. Higher peak concentrations (Cmax) or exposure (AUC) to rifampicin or isoniazid in epithelial lining fluid was associated with more rapid bacillary elimination and shorter time to sputum negativity. More extensive disease on baseline chest radiograph was associated with slower bacillary elimination. Clinical outcome was captured in 133 participants, with 15 (11%) unfavorable outcomes recorded (recurrent TB, failed treatment, or death). No relationship between BER and late clinical outcome was identified. CONCLUSIONS: Greater intrapulmonary drug exposure to rifampicin or isoniazid in the epithelial lining fluid was associated with more rapid bacillary clearance. Higher doses of rifampicin and isoniazid may result in sustained high intrapulmonary drug exposure, rapid bacillary clearance, shorter treatment duration and better treatment outcomes.

Extensor mechanism tendinopathy in patients with lateral patellar maltracking.

OBJECTIVE: Patellar maltracking is an important subset of patellofemoral pain syndrome. We hypothesize that maltracking patients have an increased incidence of extensor mechanism dysfunction due to repetitive attempts at stabilization of the patella. Our purpose is to delineate imaging features to identify maltracking patients at risk for extensor mechanism tendinopathy. MATERIALS AND METHODS: Retrospective review of knee MRIs performed for anterior knee pain over a year was conducted to identify 218 studies with imaging findings of maltracking. The cases were evaluated for the presence and degree of patellar and quadriceps tendinopathy, tibial tuberosity-trochlear groove distance (TT-TG) and the distribution and grade of patellofemoral chondrosis. Cases were compared to 100 healthy, age-matched control knee MRIs. RESULTS: The mean age of maltracking patients with either patellar or quadriceps tendinosis was 41.2 years versus 48.2 years in the control population (p = 0.037). The TT-TG was significantly higher in maltracking patients with either patellar or quadriceps tendinosis at 16.49 mm versus 14.99 mm (p = 0.006). Maltrackers with isolated lateral patellofemoral chondrosis had a higher mean TT-TG at 17.4 mm versus 15.4 mm (p = 0.007). Extensor mechanism tendinosis was increased in the maltracking population compared to the controls at 57.8% versus 27.3% (p = 0.004). CONCLUSION: Extensor mechanism tendinosis is more common in the maltracking population and occurs at a younger age. TT-TG distance is significantly increased in patients with extensor mechanism dysfunction and in patients with isolated lateral patellofemoral chondrosis. TT-TG measurement can be used independently to identifying maltrackers who may be at risk for future complications.

Prevalence of Pterygium and Associated Risk Factors in the High-Altitude Area of Ta'if City, Saudi Arabia.

Background Pterygium is an important public health problem. The prevalence rates of this disease varies widely from 1.2% to 23.4%. Aim To determine the prevalence rates and the associated risk factors of pterygium in the high-altitude area - Ta'if city, Saudi Arabia. Material and method A cross-sectional study was carried out from September 2018 till September 2019 at the ophthalmology outpatient clinics of King Abdul-Aziz Specialist Hospital, Ta'if area. Results Prevalence rate of pterygium in the high-altitude area, Ta'if city, Saudi Arabia was 2.4%. It is significantly higher in older patients belonging to the age group of more than 40 years. As for gender, it was significantly higher in male patients compared to females (2.6% vs. 1.9%). Pterygium prevalence was significantly higher among patients with outdoor occupations compared to indoor occupations (2.9% vs. 2.1%), and among patients with sunlight exposure during daily activities for more than 5 hours (2.6% vs. 2%) (p =< 0.05). Conclusion The overall incidence of pterygium in Al-Ta'if area, Saudi Arabia, was 2.4% but still lower than overall worldwide incidence (10.2%). There was an increased incidence of pterygium with age, high-altitude areas, rural areas, outdoor occupations, which is directly proportional to dose of sunlight exposure. Furthermore, smoking might be reported as a protective factor against pterygium.

Amplified OTDR systems for multipoint corrosion monitoring.

We present two configurations of an amplified fiber-optic-based corrosion sensor using the optical time domain reflectometry (OTDR) technique as the interrogation method. The sensor system is multipoint, self-referenced, has no moving parts and can measure the corrosion rate several kilometers away from the OTDR equipment. The first OTDR monitoring system employs a remotely pumped in-line EDFA and it is used to evaluate the increase in system reach compared to a non-amplified configuration. The other amplified monitoring system uses an EDFA in booster configuration and we perform corrosion measurements and evaluations of system sensitivity to amplifier gain variations. Our experimental results obtained under controlled laboratory conditions show the advantages of the amplified system in terms of longer system reach with better spatial resolution, and also that the corrosion measurements obtained from our system are not sensitive to 3 dB gain variations.

High prevalence of genu varum/valgum in European children with low vitamin D status and insufficient dairy products/calcium intakes.

OBJECTIVE: The prevalence of lower limb deformities physiologically decreases after 5 years of age. It remains high in some tropical and subtropical regions where it has been associated with severe vitamin D deficiency, low calcium/milk intakes, malnutrition, and/or fluoride overexposure. Very little data is available in apparently healthy Caucasian children and adolescents. DESIGN: We evaluated the prevalence of genu varum/valgum and other clinical symptoms, and assessed vitamin D status and markers of calcium metabolism in 226 apparently healthy European full-time boarders (7-16 years) seen during winter-spring and fed a cereal-based diet with little access to meat, milk, and dairy products. A cohort of 71 white children and adolescents hospitalized for acute illness served as age-matched controls. RESULTS: Association studies showed a high prevalence of lower limb deformities (36%) and higher alkaline phosphate activities in the 21% of children and adolescent full-time boarders with serum 25-(OH)D levels ≤ 30 nmol/l, and low serum calcium in the 74% of boarders with 25-(OH)D levels ≤ 50 nmol/l, compared with boarders with higher vitamin D status. No such anomalies were found in the control cohort despite lower serum 25-(OH)D levels. CONCLUSIONS: Low 25-(OH)D levels, at least during winter-spring, combined with additional risk factors such as very low calcium/milk intakes and possibly digestive disorders, are associated with an increased risk of genu varum/valgum in European children and adolescents. Thus, dietary fortification, or supplementation with vitamin D, may be recommended, at least during the winter, to European children and adolescents with either none or insufficient calcium/dairy product intakes.

Season of birth and not vitamin D receptor promoter polymorphisms is a risk factor for multiple sclerosis.

Both genetic and environmental factors contribute to multiple sclerosis, the most common neurodegenerative disorder with onset in young adults. The objective of the current study is, based on the hypothesis that environmentally predisposed individuals are at risk for multiple sclerosis, to investigate whether they also carry genetic variants within the vitamin D machinery. Using medical files and DNA samples from 583 trios (a patient and both parents) of the French Multiple Sclerosis Genetics Group as well as data from the French Statistics Bureau, we aimed to assess whether: (1) a seasonality of birth was observed in French multiple sclerosis patients; (2) three single nucleotide polymorphisms within the promoter region of the vitamin D receptor were associated with multiple sclerosis susceptibility; and (3) the combination of a high risk month of birth and vitamin D receptor polymorphisms were correlated to multiple sclerosis incidence. We observed a significantly reduced number of individuals born in November who were later diagnosed as multiple sclerosis patients. However, we found no association between the three studied vitamin D receptor polymorphisms and multiple sclerosis. In conclusion, our data suggest that high levels of vitamin D during the third trimester of pregnancy could be a protective factor for multiple sclerosis.

Milk, rather than other foods, is associated with vertebral bone mass and circulating IGF-1 in female adolescents.

SUMMARY: Low calcium intake hampers bone mineral acquisition in adolescent girls. This study explores dietary calcium sources and nutrients possibly associated with vertebral mass. Milk intake is not influenced by genetic variants of the lactase gene and is positively associated with serum IGF-1 and with lumbar vertebrae mineral content and density. INTRODUCTION: Low calcium intake hampers bone mineral acquisition during adolescence. We identified calcium sources and nutrients possibly associated with lumbar bone mineralization and calcium metabolism in adolescent girls and evaluated the possible influence of a genetic polymorphic trait associated with adult-type hypolactasia. METHODS: Lumbar bone mineral content (BMC), bone mineral density (BMD), and area, circulating IGF-1, markers of bone metabolism, and -13910 LCT (lactase gene) polymorphism; and intakes of milk, dairy products, calcium, phosphorus, magnesium, proteins, and energy were evaluated in 192 healthy adolescent girls. RESULTS: After menarche, BMC, BMD, serum IGF-1, and serum PTH were tightly associated with milk consumption, but not with other calcium sources. All four parameters were also associated with phosphorus, magnesium, protein, and energy from milk, but not from other sources. Girls with milk intakes below 55 mL/day have significantly lower BMD, BMC, and IGF-1 and higher PTH compared to girls consuming over 260 mL/day. Neither BMC, BMD, calcium intakes, nor milk consumption were associated with -13910 LCT polymorphism. CONCLUSIONS: Milk consumption, preferably to other calcium sources, is associated with lumbar BMC and BMD in postmenarcheal girls. Aside from being a major source of calcium, milk provides phosphates, magnesium, proteins, and as yet unidentified nutrients likely to favor bone health.

Diplopia and ptosis following injection of local anesthesia without hyaluronidase.

In a university ophthalmology department, a cluster of postoperative diplopia and ptosis cases occurred in the initial 3 months after hyaluronidase (Wydase) became unavailable for use with injection anesthesia. These cases suggest that hyaluronidase, when used with injection anesthesia, may protect extraocular muscles and nerves from the toxic effects of local anesthetic agents. The spreading action of hyaluronidase facilitates uniform diffusion of anesthetic agents. This prevents elevated extracellular tissue pressure, a cause of ischemic damage to extraocular muscles or nerves. Hyaluronidase may also prevent focal accumulations and concentrations of local anesthetic agents, which at high enough levels may cause myotoxic or neurotoxic damage, fibrosis, and contracture of extraocular muscles or nerves.

Spontaneous late dislocation of intraocular lens within the capsular bag in pseudoexfoliation patients.

PURPOSE: To identify a delayed complication of cataract surgery in patients with zonular weakness caused by pseudoexfoliation syndrome. DESIGN: Retrospective observational case series. PARTICIPANTS: Eight eyes in seven patients with clinically diagnosed pseudoexfoliation syndrome who had undergone previous uncomplicated cataract extraction and placement of a posterior chamber intraocular lens. METHODS: This study evaluated eight cases of late spontaneous dislocation of posterior chamber intraocular lenses within the capsular bag in patients with pseudoexfoliation syndrome. Data were gathered retrospectively from patients' operative reports, medical records, and pathology reports. MAIN OUTCOME MEASURES: (1) Interval between original surgery and dislocation; (2) final best-corrected visual acuity and ocular outcome. RESULTS: All patients had a diagnosis of pseudoexfoliation syndrome and had previously undergone uncomplicated cataract surgery. No patient had any other predisposing factors that would lead to zonular dehiscence or weakness. Delayed dislocation of the entire capsular bag containing the intraocular lens (IOL) occurred spontaneously in all cases. Mean time from IOL implantation to dislocation was approximately 85 months (7 years and 1 month; range, 57-115 months) after surgery. Seven eyes were treated successfully with IOL exchange: six with placement of an anterior chamber IOL and one with scleral fixation of a posterior chamber IOL. The remaining case was treated by scleral fixation of the dislocated IOL. Gross pathology analysis of seven cases confirmed the presence of the IOL within the intact capsular bag. Six eyes have achieved final best-corrected visual acuity of 20/40 or better. CONCLUSION: Patients with pseudoexfoliation syndrome may be at risk for delayed spontaneous dislocation of IOL within the capsular bag after uncomplicated cataract surgery. Awareness of this newly recognized long-term complication may justify a reevaluation of surgical considerations for cataract removal in these patients.

The Wilms' tumor gene product (WT1) modulates the response to 1,25-dihydroxyvitamin D3 by induction of the vitamin D receptor.

The Wilms' tumor gene (wt1) encodes a transcription factor involved in urogenital development, in particular in renal differentiation, and in hematopoietic differentiation. Differentiation of a number of solid tumor and leukemic cells lines can be mediated by 1,25-dihydroxyvitamin D(3). This is predominantly mediated by the nuclear receptor for 1,25-dihydroxyvitamin D(3), the vitamin D receptor (VDR). In initial experiments addressing a possible link between WT1 and VDR, we observed a correlated expression of WT1 and VDR mRNA in samples from renal tissues. HT29 colon carcinoma cells, stably transfected to express WT1, exhibited elevated endogenous VDR levels compared with control cells transfected with a control construct. Elevated VDR expression was found in wt1-transfected human embryonic kidney 293 cells, as well. In transient cotransfection experiments, we observed an activation of a vdr promoter reporter by WT1 through a WT1 recognition element, indicating transcriptional regulation of the vdr gene expression by WT1. The responsive sequence element was specifically bound by wild-type, but not by mutated WT1, in electrophoretic mobility shift assays. HT29 colon carcinoma cells, which respond to 1,25-dihydroxyvitamin D(3) with slow induction of growth arrest, were investigated for the influence of WT1 on 1,25-dihydroxyvitamin D(3)-mediated growth suppression. Although HT29 cells transfected with a control construct responded moderately to 1,25-dihydroxyvitamin D(3), the response of HT29 cells expressing WT1 was strikingly enhanced. Stimulation with dihydroxyvitamin D(3) caused an up to 3-fold reduction in the growth rate of different HT29 clones expressing WT1 as compared with control cells lacking WT1 expression. Thus, induction of VDR by WT1 leads to an enhanced response to 1,25-dihydroxyvitamin D(3). We conclude that the vitamin D receptor gene is a target for transcriptional activation by WT1, suggesting a possible physiological role of this regulatory pathway.

The mouse vitamin D receptor is mainly expressed through an Sp1-driven promoter in vivo.

The availability of the mouse vitamin D receptor (mVDR) gene has allowed a characterization of a TATA-less promoter containing a cluster of four Sp1 sites named Sp1-1, Sp1-2, Sp1-3, and Sp1-4 (F. Jehan and H. F. DeLuca, 1997, Proc. Natl. Acad. Sci. USA 94, 10138-10143). By means of primer extension analysis, S1 nuclease mapping and ribonuclease protection assay, the start site has been deduced, as has the existence of other minor transcription start sites. Initiation of transcription at the major site is located 4 bp upstream of the 5' end of the mVDR cDNA sequence and very close to the putative Sp1 sites. A second minor promoter might exist between exon 1 and exon 2 of the mVDR gene. The nucleotide sequence of the Sp1 region is well conserved between the mouse, the human, and the chicken VDR genes, suggesting an important role for these Sp1 sites. Gel shift analysis of the four Sp1 sites of the mVDR promoter has confirmed specific binding complexes to Sp1-1, Sp1-2, and Sp1-4 (Sp1-3 rather binds an unknown complex that is unable to bind the canonical Sp1 GGGGCGGGGC). Deletion or mutation of all the Sp1 sites eliminates promoter activity. However, mutation or deletion of individual Sp1 sites did not dramatically change the promoter activity, except for mutation of Sp1-3 that increases promoter activity. We, therefore, conclude that the mVDR promoter is controlled by the Sp1 sites and is the main VDR promoter in intestine and kidney.

Isolation and characterization of the chicken vitamin D receptor gene and its promoter.

The sequences from several independent cDNA clones encoding the chicken vitamin D receptor as well as primer extension assay have clearly delineated the 5' terminus and the transcriptional start site. Screening a chicken genomic library produced genomic clones containing vitamin D receptor (VDR) gene fragments. Restriction map of clone 8 showed that the 18.6-kb chicken VDR fragment has exons 1 and 2, intron 1, part of intron 2, and 7-kb 5' flanking region. Exons 1, 2, and 3 found in the chicken VDR gene shares low homology with its mammalian counterparts (i.e., E1A, E1B, and E1C in human). By contrast, the fourth exon and following exons for the coding region of VDR gene are highly conserved between avian and mammalian species. While the fourth exon bears the ATG sites for translation initiation in mammals, the third exon in birds has two extra ATG sites for leaky translation as determined previously. Thus, the avian VDR has more N-terminal sequence than the mammalian VDR and is found in two distinct forms. The 5' flanking region from genomic clone 8 shares considerable homology in several regions with the human and mouse VDR promoters. Moreover, the 5' flanking region of chicken VDR gene possesses promoter activity, as shown by its ability to drive the luciferase reporter gene in cell transfection assays. Like other steroid receptor promoters, the chicken VDR promoter contains no TATA box but possesses several GC boxes or SP1 sites. A series of deletional promoter constructs established that the proximal GC boxes are the major drivers of gene transcription, while the more upstream sequences have repressive elements.

Postoperative sterile endophthalmitis (TASS) associated with the memorylens.

PURPOSE: To report 10 cases of delayed-onset acute intraocular inflammation following cataract extraction and posterior chamber implantation of the MemoryLens(R) intraocular lens (IOL). SETTING: John A. Moran Eye Center, Department of Ophthalmology, University of Utah, Salt Lake City, Utah, USA. METHODS: This retrospective study evaluated 10 cases of postoperative inflammation that occurred after cataract extraction with placement of the posterior chamber MemoryLens IOL. Protocols of the Intermountain Ocular Research Center used to analyze outbreaks of unexplained postoperative inflammation as well as medical records were reviewed. RESULTS: Nine patients had uneventful cataract extraction and 1 had a small anterior capsule tear with placement of the MemoryLens IOL. All 10 patients presented with increased anterior segment inflammation a mean of 7.8 days (range 1 to 21 days) after surgery. Three cases were tapped and were culture negative, and 7 were presumed noninfectious. The anterior segment inflammation improved in all patients. Treatment of the 7 patients included intensive topical steroids. Careful analysis of the inflammation has not revealed an obvious etiology; however, the MemoryLens was associated with all the cases. CONCLUSIONS: We postulate that these cases of noninfectious postoperative endophthalmitis may be associated with the MemoryLens.

DNA bending is induced by binding of vitamin D receptor-retinoid X receptor heterodimers to vitamin D response elements.

The ability of vitamin D receptor-retinoid X receptor (VDR-RXR) heterodimers to induce a DNA bend upon binding to various vitamin D response elements (VDRE) has been investigated by circular permutation and phasing analysis. Recombinant rat VDR expressed in the baculovirus system and purified recombinant human RXR beta have been used. The VDREs were from 1,25-dihydroxyvitamin D3 (1,25-[OH]2D3) enhanced genes (rat osteocalcin, rOC; mouse osteopontin, mOP, and rat 1,25-dihydroxyvitamin D3-24-hydroxylase, r24-OHase), and a 1,25-(OH)2D3 repressed gene (human parathyroid hormone, hPTH). As shown by circular permutation analysis, VDR-RXR induced a distortion in DNA fragments containing various VDREs. Calculated distortion angles were similar in magnitude (57 degrees, 56 degrees, 61 degrees, and 59 degrees, respectively for rOC, mOP, r24-Ohase, and hPTH). The distortions took place with or without a 1,25-(OH)2D3 ligand. The centers of the apparent bend were found in the vicinity of the midpoint of all VDREs, except for rOC VDRE which was found 4 bp upstream. Phasing analysis was performed with DNA fragments containing mOP VDRE and revealed that VDR-RXR heterodimers induced a directed bend of 26 degrees, not influenced by the presence of hormone. In this study we report that similar to other members of the steroid and thyroid nuclear receptor superfamily, VDR-RXR heterodimers induce DNA bending.

Parathyroid hormone activation of the 25-hydroxyvitamin D3-1alpha-hydroxylase gene promoter.

The DNA flanking the 5' sequence of the mouse 1alpha-hydroxylase gene has been cloned and sequenced. A TATA box has been located at -30 bp and aCCAAT box has been located at -79 bp. The gene's promoter activity has been demonstrated by using a luciferase reporter gene construct transfected into a modified pig kidney cell line, AOK-B50. Parathyroid hormone stimulates this promoter-directed synthesis of luciferase by 17-fold, whereas forskolin stimulates it by 3-fold. The action of parathyroid hormone is concentration-dependent. 1,25-Dihydroxyvitamin D3 does not suppress basal promoter activity and marginally suppresses parathyroid hormone-driven luciferase reporter activity. The promoter has three potential cAMP-responsive element sites, and two perfect and one imperfect AP-1 sites, while no DR-3 was detected. These results indicate that parathyroid hormone stimulates 25-hydroxyvitamin D3-1alpha-hydroxylase by acting on the promoter of the 1alpha-hydroxylase gene.