Associations between maternal inflammation during pregnancy and infant birth outcomes in the Seychelles Child Development Study.

PROBLEM: Markers of maternal inflammation may determine infant birth outcomes. METHOD OF STUDY: Maternal serum samples were collected at 28 weeks gestation (n = 1418) in the Seychelles Child Development Study Nutrition Cohort 2 and analyzed for immune markers by MSD multiplex assay, including cytokines from the Th1 (IFN-γ, IL-1ß, IL-2 and TNF-α) and Th2 (IL-4, IL-5, IL-10) subsets, with IL-6, MCP-1, TARC, sFlt-1 and VEGF-D. Associations of log-transformed immune markers with birthweight, length, head circumference and gestational age were assessed by multiple linear regression models, which were adjusted for maternal age, BMI, parity, child sex, gestational age and socioeconomic status. RESULTS: Neither total Th1, Th2 nor Th1:Th2 were significantly associated with any birth outcome. However, the angiogenesis marker VEGF-D was predictive of a lower birthweight, (ß = -0.058, P = 0.017) and birth length (ß = -0.088, P = 0.001) after adjusting for covariates. Higher concentrations of CRP were predictive of a lower birthweight (ß = -0.057, P = 0.023) and IL-2 (ß = 0.073, P = 0.009) and the chemokine MCP-1 (ß = 0.067, P = 0.016) were predictive of a longer gestational age. CONCLUSIONS: In our cohort of healthy pregnant women, we found no evidence for associations between the Th1 or Th2 inflammatory markers with birth outcomes. However, VEGF-D and CRP appear to predict lower birthweight and IL-2 and MCP-1 a longer gestation. Greater understanding is required of the variation in these immune markers at different gestational stages, as well as the factors which may regulate their balance in healthy pregnancy. n = 233.

Validation of a food frequency questionnaire to determine vitamin D intakes using the method of triads.

BACKGROUND: Dietary sources of vitamin D (both natural and fortified) are increasingly contributing to consumers' vitamin D intake and status. Therefore, the present study aimed to validate a vitamin D food frequency questionnaire (FFQ) for the assessment of habitual vitamin D intake. METHODS: A total of 49 apparently healthy consenting adults (aged 18-64 years) from the local community were sampled at the end of winter. Dietary intakes were recorded using a 4-day weighed food record (4d-WFR) and a 17-item FFQ based on foods known to contribute to dietary vitamin D intake. Fasting vitamin D status was quantified by serum 25-hydroxyvitamin D [25(OH)D] using liquid chromatography tandem mass spectrometry. The method of triads was applied using these three measurements to determine the overall validity of the FFQ. RESULTS: Vitamin D intakes from 4d-WFR ranged between 0.42 and 31.65 µg day(-1), whereas intakes determined from the FFQ ranged from 1.03 to 36.08 µg day(-1). Serum 25(OH)D concentrations ranged between 12.89 and 279.00 nmol L(-1). The mean (SD) difference between the FFQ and 4d-WFR was +1.62 ( 3.86). There were strong correlations between the vitamin D intake estimated by the FFQ and that from the 4d-WFR (r = 0.562) and also with serum 25(OH)D concentrations (r = 0.567). Vitamin D intake estimated from the 4d-WFR was also strongly correlated with serum 25(OH)D concentrations (r = 0.411). The overall validity coefficient calculated using the method of triads was high (0.881). CONCLUSIONS: The vitamin D FFQ has been validated for use in future studies aiming to assess habitual vitamin D intake.

Indices of adiposity as predictors of cardiometabolic risk and inflammation in young adults.

BACKGROUND: Studies investigating obesity and cardiometabolic risk have focused on 'at-risk' populations and methodological inconsistencies have produced equivocal findings. The present cross-sectional study investigated indices of body composition as predictors of cardiometabolic risk and their relationship with inflammation in apparently healthy young adults. METHODS: A fasting blood sample was taken from consenting adults (160 males, 32 females, aged 18-40 years) for assessment of cardiometabolic risk markers (blood pressure, lipid profiles and insulin resistance) and inflammatory markers (C-reactive protein, tumour necrosis factor-α, interleukin-6, interleukin-10 and adiponectin). Together with anthropometry, fat mass (FM) and fat-free mass (FFM) were determined by dual-energy X-ray absorptiometry. FM was expressed in absolute terms (kg), as well as relative to total body weight (%), height [FM index (FMI, kg m(-2) )] and FFM (FM : FFM,%). RESULTS: Although anthropometric indices were associated with most cardiometabolic risk markers, the strongest relationship was observed with FMI. Relative to having a low cardiometabolic risk (≤2 markers above clinically relevant cut-offs), each kg m(-2) increase in FMI, increased the likelihood of having an increased cardiometabolic risk by 29% (odds ratio = 1.29; 95% confidence interval = 1.12-1.49). Inflammatory markers were not associated with body composition or cardiometabolic risk. CONCLUSIONS: FMI was the strongest predictor of overall cardiometabolic risk but not inflammation per se. However, anthropometric indices, such as body mass index and waist-to-height ratio, remain valuable surrogate measures of adiposity in this group, particularly when risk markers are considered independently.

Vitamin D, Muscle Function, and Cardiorespiratory Fitness in Adolescents From the Young Hearts Study.

CONTEXT: Vitamin D insufficiency is common among the adolescent population and may have implications for health outcomes in later life. Few studies have investigated the role of vitamin D status in muscle function and cardiorespiratory fitness (CRF) during adolescence. OBJECTIVE: The aim of this study was to investigate the association between vitamin D status and fat-free mass (FFM), muscle strength, muscle power, and CRF in a representative sample of adolescents from Northern Ireland. DESIGN, SETTING, AND PARTICIPANTS: This was a cross-sectional study involving 1015 adolescents (age 12 and 15 y), who had 25-hydroxyvitamin D [25(OH)D] data available as part of the Young Hearts Study 2000. MAIN OUTCOME MEASURES: The main outcome measures of this study were FFM (kg) and FFM corrected for height [fat-free mass index; FFM (kg)/height (m(2))], muscle strength (kg), peak muscle power (kW) and VO2 max (CRF; mL/kg/min). RESULTS: Multinomial regression analyses, controlling for environmental and lifestyle factors, demonstrated that boys age 15 years in the highest tertile of standardized serum 25(OH)D concentration (> 51 nmol/L) had significantly higher muscle strength (ß = 3.90; P ≤ .001) compared with those in the lowest tertile (< 32 nmol/L). These results were not evident in any other age-sex group and vitamin D status was not significantly associated with muscle power or CRF in any of the four age-sex groups. CONCLUSION: These results support a role for vitamin D in muscle function in adolescent males and suggest the need for more research in this vulnerable age group.

Prenatal methyl mercury exposure in relation to neurodevelopment and behavior at 19 years of age in the Seychelles Child Development Study.

BACKGROUND: Fish are important sources of protein and contain a variety of nutrients, such as n-3 long-chain polyunsaturated fatty acids (PUFA), essential for normal brain development. Nevertheless, all fish also contain methyl mercury (MeHg), a known neurotoxicant in adequate dosage. Our studies of the Seychelles Child Development Study (SCDS) Main Cohort enrolled in 1989-1990 (n=779) have found no consistent pattern of adverse MeHg effects at exposures achieved by daily fish consumption. Rather, we have observed evidence of improved performance on some cognitive endpoints as prenatal MeHg exposure increases in the range studied. These observations cannot be related to MeHg and may reflect the role of unmeasured covariates such as essential nutrients present in fish. To determine if these associations persist into young adulthood, we examined the relationship between prenatal MeHg exposure, recent PUFA exposure and subjects' neurodevelopment and behavior at 19 years of age. METHODS: We examined 533 participants using the following test battery: the Profile of Mood States-Bipolar (POMS-Bi); Finger Tapping; Kaufman Brief Intelligence Test (K-BIT); measures of Fine Motor Control and Complex Perceptual Motor Control; and Visual Spatial Contrast Sensitivity. We collected the following covariates: maternal IQ, family life course stressors, socioeconomic status, and subjects' recent postnatal MeHg, sex, and computer use. Primary analyses (based on N=392-475) examined covariate-adjusted associations in multiple linear regression models with prenatal MeHg as the primary exposure measure. Secondary analyses additionally adjusted for total n-6 and fish-related n-3 PUFA measured in the subjects' serum at the 19-year examination. RESULTS: Study participants had a mean prenatal MeHg exposure of 6.9 ppm, and a mean recent postnatal exposure of 10.3 ppm. There were no adverse associations between prenatal MeHg and any of the measured endpoints. For recent postnatal MeHg exposure, however, adverse associations were observed for Finger Tapping (non-dominant hand) among women and for the K-BIT Matrices for both sexes, with or without adjustment for PUFA. CONCLUSION: Our findings continue to provide no evidence for an adverse effect of prenatal MeHg exposure on development in a cohort that consumes fish daily. Observations for postnatal MeHg exposure will need to be confirmed using more comprehensive exposure measures.

Low glucose under hypoxic conditions induces unfolded protein response and produces reactive oxygen species in lens epithelial cells.

Aging is enhanced by hypoxia and oxidative stress. As the lens is located in the hypoglycemic environment under hypoxia, aging lens with diabetes might aggravate these stresses. This study was designed to examine whether low glucose under hypoxic conditions induces the unfolded protein response (UPR), and also if the UPR then generates the reactive oxygen species (ROS) in lens epithelial cells (LECs). The UPR was activated within 1 h by culturing the human LECs (HLECs) and rat LECs in <1.5 mM glucose under hypoxic conditions. These conditions also induced the Nrf2-dependent antioxidant-protective UPR, production of ROS, and apoptosis. The rat LECs located in the anterior center region were the least susceptible to the UPR, whereas the proliferating LECs in the germinative zone were the most susceptible. Because the cortical lens fiber cells are differentiated from the LECs after the onset of diabetes, we suggest that these newly formed cortical fibers have lower levels of Nrf2, and are then oxidized resulting in cortical cataracts. Thus, low glucose and oxygen conditions induce the UPR, generation of ROS, and expressed the Nrf2 and Nrf2-dependent antioxidant enzymes at normal levels. But these cells eventually lose reduced glutathione (GSH) and induce apoptosis. The results indicate a new link between hypoglycemia under hypoxia and impairment of HLEC functions.

The E-Z(easy) clamp--a new instrument to facilitate medial ectropion repair.

The medial spindle/retropunctal diamond procedure is a useful technique to correct medial ectropion. Unfortunately, the procedure is difficult, due to the limited size of the surgical field, the bleeding that is seen when the marginal artery is encountered and because of the ever present risk of damaging the canaliculus. We have developed a clamp that overcomes the anatomical opposition outlined above and at the same time improves access to the surgical field.

Synchronous reconstruction of the exenterated orbit with a pericranial flap, skin graft and osseointegrated implants.

Reconstruction of the exenterated orbit remains a surgical challenge. Here, the authors present a case in which orbital exenteration was performed for an extensive, infiltrating medial canthal basal cell carcinoma; the resulting defect was reconstructed with osseointegrated implants and a pericranial flap onto which a split thickness skin graft was placed. The second stage of the aesthetic rehabilitation of this patient (placement of the transcutaneous abutments) was completed under local anaesthetic 16 weeks later. Subsequently, the patient was fitted with an oculoplastic prosthesis four weeks later. The above technique accelerates the prosthetic rehabilitation of the patient by performing the primary reconstructive procedures simultaneously with the exenteration and by removing the need for secondary surgical procedures under general anaesthetics. The whole process from orbital exenteration to the fitting of an ocular prosthesis was completed in just five months.

Stability of reconstituted parecoxib for injection with commonly used diluents.

OBJECTIVE: The purpose of this study was to evaluate the effect of diluent type, storage conditions and the nature of package on the stability of reconstituted Parecoxib sodium for injection (PSI). METHODS: Parecoxib sodium for injection is a lyophilized product for single use. It is intended for the management of acute pain. Six diluent types were initially evaluated for physical compatibility with PSI. Reconstituted PSI was visually inspected at 8, 24 and 48 h after reconstitution with 0.9% sodium chloride injection (NS), lactated ringers injection (LR), bacteriostatic 0.9% NaCl injection (BNS), lactated ringers and 5% dextrose injection (LR + D5W), 5% dextrose injection (D5W), and 5% dextrose + 0.45% NaCl injection (D5W + 1/2NS). Reconstituted PSI, stored in glass vials and glass or plastic syringes at 5 degrees and 25 degrees C, under 500 lx light intensity for 48 h or subjected to freeze-thaw cycles, were tested for chemical stability by high-performance liquid chromatography (HPLC). RESULTS: The PSI reconstituted with NS, BNS, D5W, and D5W + 1/2NS met visual acceptance criteria and showed almost no (<0.5% total) degradation under all storage conditions. No significant differences were seen between storage in glass vials or polypropylene/glass syringes. PSI reconstituted with LR and LR + D5W showed visual precipitation in many vials which was confirmed by the decrease in the HPLC assay values at all time points. The needlelike crystals (precipitate), analyzed by Infrared Spectroscopy and Scanning Electron Microscopy-Energy Dispersive Spectrometry (SEM-EDS) analyses, were identified as the free acid form of the active drug. CONCLUSION: PSI is stable after reconstitution, with NS, BNS, D5W, and D5W + 1/2NS, when stored at room temperature in glass vials or glass/plastic syringes for up to 48 h* LR and LR + D5W are not recommended for reconstitution because of crystallization of the drug (free acid).

The use of autologous autoclaved bone in orbital reconstruction after exenteration for invasive cutaneous carcinoma.

PURPOSE: To describe a technique for reconstructing the orbital bony architecture after invasion by tumour. METHODS: Orbital bone invaded by tumour was osteotomized (post-exenteration), autoclaved to remove tumour cells, and then refixated in order to re-establish the normal orbital anatomy. RESULTS: Despite some shrinkage of the bone fragment in the autoclaving process, after refixation the contour and topography of the bony orbit was essentially normal. CONCLUSION: Autoclaved bone can be used to reconstruct the exenterated orbit; it is a fast and technically simple strategy for maintaining orbital anatomy when faced with bony invasion by tumour.

Endoscopic removal of periorbital lesions.

In this article, the authors describe the technique, indications and contra-indications for removing various periorbital lesions with an endoscope. The principal reason for using this technique is the excellent postoperative cosmesis. Seven patients in total had lesions removed in this manner. The only complication noted was some leakage of the contents of a dermoid cyst intraoperatively. Cosmesis postoperatively was excellent in all cases. None of the cases had to be converted to an 'open' procedure.

Tyrosinemia type II: nine cases of ocular signs and symptoms.

PURPOSE: To report nine cases of tyrosinemia type II, with ocular signs and symptoms. METHODS: Participants included nine patients (18 eyes) who were followed for a mean follow-up period of 6.5 years (range, 2 to 8 years). Intervention included dietary restriction of tyrosine and phenylalanine, which led to resolution of ocular and cutaneous lesions, improved behavior in one patient, and may have prevented developmental delay in others. The main outcome measures were visual acuity and serum tyrosine levels to determine the response to dietary therapy. Intelligence testing and developmental screening were performed when appropriate. RESULTS: All patients presented with ocular signs and symptoms as the primary manifestation of disease and serve to illustrate the typical ocular findings of this syndrome. Three patients presented with cutaneous manifestations, and one patient had mild mental impairment at the time of diagnosis. CONCLUSIONS: Recalcitrant pseudodendritic keratitis may be the presenting sign in tyrosinemia type II. Awareness of the presenting signs and symptoms may accelerate the diagnosis and dietary intervention. Initiation of a tyrosine-restricted and phenylalanine-restricted diet in infancy is most effective in preventing cognitive impairment.

Myopic and hyperopic laser in situ keratomileusis retreatments: indications, techniques, limitations, and results.

PURPOSE: To assess the efficacy of myopic and hyperopic laser in situ keratomileusis (LASIK) retreatment procedures. SETTING: Mater Private Hospital, Dublin, Ireland. METHODS: Retreatment was defined as either lifting the previously created flap or when this was not possible, cutting a new flap. Fifty-six patients were retreated, 17 with hyperopia (Group 1) and 39 with myopia (Group 2). The mean preoperative spherical equivalent in Group 1 was +3.79 diopters (D) +/- 1.53 (SD) (range +1.75 to +8.12 D) and in Group 2, -5.46 +/- 2.87 D (range -0.38 to -15.25 D). RESULTS: The indications for retreatment were undercorrection, decentration, epithelial ingrowth, and central island. Postoperatively, the mean spherical equivalents in Groups 1 and 2 were +1.11 +/- 2.02 D (range -1.75 to +5.50 D) and -1.02 +/- 2.20 D (range +4.75 to -9.00 D), respectively. In Group 1, the uncorrected visual acuity (UCVA) was 6/12 or better in 5.8% preoperatively and in 35% postoperatively. In Group 2, the UCVA was 6/12 or better in 5.1% preoperatively and in 59.0% postoperatively. Although 29% of the hyperopic eyes and 8% of the myopic eyes lost 1 Snellen line of best corrected visual acuity (BCVA), there was an improvement (of 1 or more lines) in BCVA in 12% and 49%, respectively. In cases that were decentered preoperatively, the postoperative optical zone ablation centration was better in 85.7% of Group 1 eyes and 61.5% of Group 2 eyes. Corneal complications following retreatment included peripheral scarring, epithelial ingrowth, Bowman's folds, and keratectasia. CONCLUSIONS: Both myopic and hyperopic retreatments resulted in a stable refractive outcome. Myopic retreatments were superior to hyperopic retreatments in both efficacy and safety.

Using the eye fixation speculum as an adjunct to pterygium surgery.

A technique is described that overcomes the two biggest problems facing the surgeon when dissecting a pterygium from the cornea-bleeding and eye movement. Our technique however, requires only minimal anesthesia (topical and subconjunctival) and the use of a disposable speculum and suction ring. An added advantage is this particular speculum gives good exposure of the superior bulbar conjunctiva; this facilitates harvesting a conjunctival autograft.

Visual and anatomical success with short-term macular tamponade and autologous platelet concentrate.

BACKGROUND: This study aimed to determine whether, in eyes treated for macular hole by vitrectomy and autologous platelet injection, short-term tamponade with SF6 gas was as effective as longer tamponade with C3F8 gas. METHODS: Patients in group 1 (n=31) had vitrectomy, injection of platelet concentrate, and 16% C3F8 gas/air exchange. Patients in group 2 (n=31) were similarly treated, except that 23% SF6 gas was used. Group 1 patients were required to posture prone for 2-4 weeks, group 2 for 6 days. RESULTS: All patients had 3 months' follow-up. Postoperatively, visual acuity improved faster in group 2. However, the final mean improvement in logMAR acuity was similar in both groups. Intraocular pressure (IOP) spikes occurred in 12 patients in group 2 and in 17 patients in group 1. Posterior subcapsular cataract (PSCC) occurred in 55% of cases in group 1 and in just 37% in group 2. The rate of anatomical success in group 1 was 96.7%, and in group 2, 93.5% (P=1.0). CONCLUSIONS: The combination of SF6 gas, platelet concentrate, and short-term prone posturing gave a degree of anatomical and visual success comparable to that of the group which had longer tamponade. Although no differences were statistically significant, several trends did emerge; in group 2, patients recovered visual acuity faster, had fewer IOP spikes, and there were fewer cases of PSCC formation.

The role of social desirability, negative affectivity, and female reproductive system symptoms in differences in reporting symptoms by men and women.

52 women and 38 men completed the Inventory of Health Status, Version 2, a measure of somatic health, and the Cornell Medical Index which provided separate scores for somatic and emotional health. The Personal Style Inventory was given, from which measures of Social Desirability and Negative Affectivity were utilized. Multiple regressions were done separately with scores on the Inventory of Health Status and the Cornell Emotional component, and scores on Social Desirability, Negative Affectivity, and sex as predictors. Scores on Social Desirability and Negative Affectivity were forced into the equation first. For the Inventory of Health Status, sex alone contributed significantly to the final equation. For scores on the Cornell Index's emotional component both sex and scores on negative affectivity had significant beta weights. Analysis of items from the Inventory of Health Status was done to examine the role of symptoms pertaining to women's reproductive system, and almost all the items that differed by sex were either clearly or possibly specific female reproductive items, e.g., "Abnormal menstruation." Similar analyses were not possible for the organic component of the Cornell Index, which has different items for reproductive systems of men and women. The complexity of the female reproductive system may play a central role in sex differences in symptom reporting and perhaps of emotional distress, but other interpretations are discussed.

Ocular complications of acoustic neuroma surgery.

AIM: To analyse the risk factors involved in the development of ocular complications after acoustic neuroma resection, in particular corneal complications and visual loss, and to identify measures that may reduce these. METHODS: 62 patients who underwent surgery for acoustic neuroma had a standardised ophthalmic examination and retrospective case note review. RESULTS: At final review (mean 37.6 months), although 38 patients reported ocular symptoms, only 22% saw 6/12 or worse. Patients with hypoaesthetic corneas had a higher incidence of corneal pathology (79%) than those with normal sensation (39%). Lagophthalmos increased the incidence of corneal pathology (to 80%); in those with normal closure, the incidence was only 46%. 20 patients required at least one ophthalmic surgical procedure. CONCLUSIONS: After acoustic neuroma resection patients place a considerable burden on the ophthalmologist. Immediate referral postoperatively, and frequent review of those with abnormal sensation may reduce the severity of long term ocular complications.

Validation of a self-report measure of somatic health.

The primary purpose was to assess the validity of a new self-report inventory of general somatic health status. In addition, we sought to examine the influence of social desirability and negative affectivity on health reports and to learn whether asking respondents to report concrete, memorable aspects of illness episodes such as seeing a doctor or staying home in bed for all or most of a day would enhance validity. The somatic component of the Cornell Medical Index was used as a criterion measure of health status because that Index has been shown to reflect medical records with great accuracy. Scores on the new health inventory correlated highly with the Cornell somatic scores, and this relationship was independent of negative affectivity and social desirability. The addition of the "concrete, memorable" aspects of illness accounted for no additional variance in the Cornell Index somatic scores beyond that accounted for by mere reporting of the presence of the symptom or illness. This study offers evidence supporting the validity of the Inventory of Health Status as a predictor of somatic health independent of social desirability and negative affectivity and also indicates that a simple indication of whether the patient had the symptoms is sufficient.