Genetic variants in SCNN1B and AHCYL1 are associated with eggshell quality in Chinese domestic laying ducks (Anas platyrhynchos).

1. The objective of this study was to investigate the evolution of SCNN1B and AHCYL1 proteins among 10 domestic avian and mammalian animal species, to uncover the expression patterns of SCNN1B and AHCYL1 genes in ducks, identify the genetic variants of the SCNN1B and AHCYL1 genes and analyse their effects on eggshell quality.2. Expression profiles of the SCNN1B and AHCYL1 genes in Sansui female ducks were determined using real-time fluorescence quantitative PCR to identify SNPs. The duck SCNN1B and AHCYL1 genes were amplified to identify SNPs. A total of 502 Sansui female ducks were genotyped by sequencing, and the associations between the mRNA expression/SNP genotypes and 6 eggshell quality indices were analysed using PASW Statistics 18.0.3. The results showed that the SCNN1B and AHCYL1 proteins are highly conserved in different mammalian or domestic animals, especially the AHCYL1 protein. The SCNN1B and AHCYL1 genes were widely expressed in different tissues of male and female ducks, and expression level in the uterus was greater than in other tissues. The expression of SCNN1B and AHCYL1 during the oviposition cycle indicated that expression levels were related to the eggshell mineralisation stage.4. The mRNA expression levels of the uterine SCNN1B and AHCYL1 genes were positively correlated with eggshell strength (ESS), percentage (ESP) and weight (ESW) (P < 0.05), respectively. Ten novel SNPs in SCNN1B and AHCYL1 genes from Chinese domestic laying ducks were identified through PCR amplicon sequencing.5. Genetic association analysis indicated g.797509 C > T, g.797573 C > T and g.797834 C > T in SCNN1B gene and g.169244 T > A, g.169265 T > C and g.175311 T > C in AHCYL1 gene had a significant effect on eggshell quality. Correlation analysis between the SNP genotype and SCNN1B and AHCYL1 genes expression in the uterus showed that the genotypes of g.797509 C > T, g.797573 C > T, g.797834 C > T, g.169244 T > A and g.175311 T > C sites affected the expression of SCNN1B and AHCYL1 genes in utero (P < 0.05).6. The study indicated SCNN1B and AHCYL1 as candidate genes to improve eggshell traits in ducks.

Association of PRKCA expression and polymorphisms with layer duck eggshell quality.

1. Eggshell quality is important for the poultry industry. Calcium is deposited during eggshell formation, and protein kinase C alpha (PRKCA) is involved in transmembrane transport of calcium ions in cells. However, the biological function of PRKCA in poultry is still not understood. Therefore, the aim of this study was to explore the association of mRNA expression and single nucleotide polymorphisms (SNPs) of the PRKCA gene with eggshell quality in laying ducks. 2. The mRNA expression and SNPs of the PRKCA gene were detected by real-time fluorescence quantitative PCR (qRT-PCR) and sequencing of PCR products in 45-week-old female Sansui ducks, which is a high production layer duck breed in China. The association of mRNA expression and SNPs in the PRKCA gene with layer duck eggshell traits was analysed using SPSS (v18.0) software. 3. The results demonstrated that PRKCA mRNA was widely expressed in all examined tissues, and expression was highest in kidney and lowest in the gizzard. Furthermore, the PRKCA mRNA level in uterus was significantly positively correlated with eggshell strength and eggshell weight (P < 0.05). Three novel SNPs, the synonymous mutations of g.9571770 T > C in exon 5, g.9583222 C > T and g.9583227 G > A in exon 7, were found in the PRKCA gene, giving four haplotypes and 10 diplotypes, which affected the mRNA secondary structure and free energy. The g.9583222 C > T and g.9583227 G > A mutations were significantly associated with eggshell strength (P < 0.05). Diplotype H1H1 was advantageous for increasing the strength and thickness of an eggshell. 4. In conclusion, the study showed that the mRNA transcription and genetic variation in the PRKCA gene could significantly affect the strength of duck eggshell and that the PRKCA gene is an important candidate gene for improving eggshell quality in poultry.

Utility of pre-treatment neutrophil-lymphocyte ratio and platelet-lymphocyte ratio as prognostic factors in breast cancer.

BACKGROUND: Peripheral blood-derived inflammation-based scores such as the neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) have recently been proposed as prognostic markers in solid tumours. Although evidence to support these markers as unfavourable prognostic factors is more compelling in gastrointestinal cancers, very little is known of their impact on breast cancer. We investigated the association between the NLR and PLR, and overall survival after breast cancer. METHODS: Data from the University of Malaya Medical Centre Breast Cancer Registry was used. Of 2059 consecutive patients diagnosed from 2000 to 2008, we included 1435 patients with an available pre-treatment differential blood count (∼70%). Patients were stratified into quintiles of the NLR/PLR. Multivariable Cox regression was used to determine the independent prognostic significances of the NLR/PLR. RESULTS: Compared with the first quintile of the NLR, women in quintile 5 were younger, had bigger tumours, nodal involvement, distant metastases and higher tumour grades. Higher NLR quintiles were significantly associated with poorer survival with a 5-year relative survival ratio (RSR) of 76.4% (95% CI: 69.6-82.1%) in quintile 1, 79.4% (95% CI: 74.4-83.7%) in quintile 2, 72.1% (95% CI: 66.3-77.3%) in quintile 3, 65.6% (95% CI: 59.8-70.8%) in quintile 4 and 51.1% (95% CI: 43.3-58.5%) in quintile 5. Following adjustment for demography, tumour characteristics, treatment and the PLR, the adjusted hazard ratio (HR) for quintile 5 vs quintile 1 was 1.50 (95% CI: 1.08-1.63); Ptrend=0.004. Results were unchanged when the NLR was analysed as a dichotomous variable using different cutoff points. Although patients in PLR quintile 5 had lower survival than in quintile 1 (5-year RSR: 53.2% (95% CI: 46.9-59.2%) vs 77.0% (95% CI: 70.9-82.2%)), this association was not significant after multivariable adjustment. However, a PLR >185 was significantly associated with poorer survival; adjusted HR: 1.25 (95% CI: 1.04-1.52). CONCLUSIONS: Both the NLR and PLR are independently associated with an increased risk of mortality in breast cancer. Their added value in the prognostication of breast cancer in clinical practice warrants investigation.

Breast Cancer Outcomes as Defined by the Estrogen Receptor, Progesterone Receptor, and Human Growth Factor Receptor-2 in a Multi-ethnic Asian Country.

INTRODUCTION: Breast cancer can be divided into four subtypes based on the expressions of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor-2 (HER2). Each subtype has different clinicopathological features and outcomes. OBJECTIVE: To compare the clinicopathological features and survival of ER and/or PR positive HER2 negative (ER+PR+HER2-, ER+PR-HER2- or ER-PR+HER2-), ER and/or PR positive HER2 positive (ER+PR+HER2+, ER+PR-HER2+ or ER-PR+HER2+), ER negative PR negative HER2 positive (ER-PR-HER2+), and ER negative PR negative HER2 negative (ER-PR-HER2-) subtypes. METHODS: 1957 patients with Stage 1-3 breast carcinoma diagnosed between Jan 2005 and Dec 2011 were categorized into the four subtypes. The clinicopathological features between the subtypes were compared using χ (2) test. Kaplan-Meier analysis was performed to estimate 5-year overall survival. Multivariate Cox regression was used to determine the association between subtypes and mortality adjusted for age, ethnicity, stage, pathological features, and treatment. RESULTS: ER-PR-HER2+ and ER-PR-HER2- subtypes were associated with younger age, larger tumors, and higher grade. There was no difference in the 5-year survival of the ER-PR-HER2+ and ER-PR-HER2- subtypes (75.1 and 74.4 %, respectively) and survival was poorer than in the ER and/or PR positive HER2 negative and ER and/or PR positive HER2 positive subtypes (87.1 and 83.1 %, respectively). Only 9.5 % of women with HER2 positive breast cancer had access to trastuzumab. CONCLUSION: In a low resource setting with limited access to trastuzumab, there is no difference in survival between the ER-PR-HER2+ and ER-PR-HER2- subtypes of breast cancer.

Spectrum of very early breast cancer in a setting without organised screening.

BACKGROUND: Within a setting without organised breast cancer screening, the characteristics and survival of very early breast cancer were determined. METHODS: All 4930 women diagnosed with breast cancer in University Malaya Medical Center, Malaysia from 1993 to 2011 were included. Factors associated with very early presentation (stage I) at diagnosis were identified. Tumour characteristics, management patterns, and survival of very early breast cancer were described, and where appropriate, compared with other settings. RESULTS: Proportion of women presenting with stage I breast cancer significantly increased from 15.2% to 25.2% over two decades. Factors associated with very early presentation were Chinese ethnicity, positive family history of breast cancer, and recent period of diagnosis. Within stage I breast cancers, median tumour size at presentation was 1.5 cm. A majority of stage I breast cancer patients received mastectomy, which was associated with older age, Chinese ethnicity, postmenopausal status, and larger tumours. Chemotherapy was administered in 36% of patients. Five-year age-adjusted relative survival for women with stage I breast cancer was 99.1% (95% CI: 97.6-99.6%). CONCLUSIONS: The proportion of women presenting with very early breast cancer in this setting without organised screening is increasing. These women seem to survive just as well as their counterparts from affluent settings.

Prediction of lymph node involvement in patients with breast tumors measuring 3-5 cm in a middle-income setting: the role of CancerMath.

BACKGROUND: In settings with limited resources, sentinel lymph node biopsy (SNB) is only offered to breast cancer patients with small tumors and a low a priori risk of axillary metastases. OBJECTIVE: We investigated whether CancerMath, a free online prediction tool for axillary lymph node involvement, is able to identify women at low risk of axillary lymph node metastases in Malaysian women with 3-5 cm tumors, with the aim to offer SNB in a targeted, cost-effective way. METHODS: Women with non-metastatic breast cancers, measuring 3-5 cm were identified within the University Malaya Medical Centre (UMMC) breast cancer registry. We compared CancerMath-predicted probabilities of lymph node involvement between women with versus without lymph node metastases. The discriminative performance of CancerMath was tested using receiver operating characteristic (ROC) analysis. RESULTS: Out of 1,017 patients, 520 (51 %) had axillary involvement. Tumors of women with axillary involvement were more often estrogen-receptor positive, progesterone-receptor positive, and human epidermal growth factor receptor (HER)-2 positive. The mean CancerMath score was higher in women with axillary involvement than in those without (53.5 vs. 51.3, p = 0.001). In terms of discrimination, CancerMath performed poorly, with an area under the ROC curve of 0.553 (95 % confidence interval CI 0.518-0.588). Attempts to optimize the CancerMath model by adding ethnicity and HER2 to the model did not improve discriminatory performance. CONCLUSION: For Malaysian women with tumors measuring 3-5 cm, CancerMath is unable to accurately predict lymph node involvement and is therefore not helpful in the identification of women at low risk of node-positive disease who could benefit from SNB.

Saxagliptin added to a submaximal dose of sulphonylurea improves glycaemic control compared with uptitration of sulphonylurea in patients with type 2 diabetes: a randomised controlled trial.

AIMS: Assess the efficacy and safety of saxagliptin added to a submaximal sulphonylurea dose vs. uptitration of sulphonylurea monotherapy in patients with type 2 diabetes and inadequate glycaemic control with sulphonylurea monotherapy. METHODS AND PATIENTS: A total of 768 patients (18-77 years; HbA(1c) screening >or= 7.5 to

Humoral and cellular immunity induced by tumor cell vaccine based on the chicken xenogeneic homologous matrix metalloproteinase-2.

Matrix metalloproteinase-2 (MMP-2) has been used as a target for cancer immunotherapy. The activation of immunization by breaking immune tolerance to self-MMP-2 may be one of the promising approaches for the treatment of MMP-2-positive tumors. In this study, we constructed the xenogeneic tumor cell vaccine c-MMP-2 by transfecting CT26 and LLC cells with chicken MMP-2 cDNA constructs. MMP-2-specific autoantibodies in sera and tumor cells were found in mice immunized with c-MMP-2. Protection against tumor growth was evaluated in respect of the relative contributions of autoantibodies, CD4+, and CD8+ T cells. Treatment with this vaccine (c-MMP-2) also prolonged the survival time of mice bearing cancer. The specific cytotoxic T-cell responses suggested that the treatment increased CD8+ T-cell activity. The antitumor activity of c-MMP-2 was abrogated by in vivo depletion of CD4+ and CD8+ T-lymphocytes and improved by adoptive transfer of CD4+ and CD8+ T-lymphocytes from the mice treated with c-MMP-2. An alternative DNA vaccination strategy for cancer therapy was identified in this study by eliciting humoral and cellular immunoresponse with a crossreacting transfectant.

The modified Glasgow prognosis score predicts for overall and disease-free survival following cytoreductive surgery and HIPEC in patients with pseudomyxoma peritonei of appendiceal origin.

BACKGROUND: The modified Glasgow prognostic score (incorporating C-reactive protein and albumin) predicts survival in patients with gastro-intestinal tract cancer but has not been evaluated in patients with peritoneal malignancy. The aim was to evaluate the modified Glasgow score preoperatively in patients undergoing complete cytoreductive surgery (CCRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) for pseudomyxoma peritonei (PMP) of appendiceal origin. METHODS: Prospectively collected data from patients with PMP of appendiceal origin following CCRS and HIPEC between January 2007 and December 2011 were analysed. The mGPS was calculated from preoperative C-reactive protein and albumin. Predicted overall survival (OS) and disease-free survival (DFS) for each mGPS score were calculated using the Kaplan-Meier model. In a separate analysis, a comparison was made between mGPS and Tumour Markers (TM). RESULTS: 260 patients were included in the study. The mGPS of 0, 1, and 2 were found in 111, 130, and 19 patients respectively. The median follow-up was 48 months. For mGPS-0, -1, and -2, the predicted OS was 82.2, 73.7, and 69.2 months and the DFS was 73.5, 62.9, and 54.4 months respectively. As mGPS increases, there is a reduction in long-term survival. There was no difference between mGPS and TM. CONCLUSION: Preoperative mGPS may be a cost effective prognostic tool for predicting OS and DFS in patients following complete CRS-HIPEC, and performs well compared to TM for predicting patients at high risk of recurrence.

Management of para-aortic lymph node metastasis in colorectal patients: A systemic review.

INTRODUCTION: Para-aortic lymph node (PALN) involvement occurs in up to 2% of colorectal cancer (CRC) patients. While resection for isolated hepatic and pulmonary metastases in colorectal cancer is standard practice, the role of PALN dissection (PALND) in CRC has not been established and remains a controversy. We aim to perform a systematic review of the literature to determine if extensive lymphadenectomy improves survival, and is an acceptable strategy for PALN metastasis (PALNM). MATERIALS AND METHODS: A systematic search of PubMed and Embase databases for studies reporting on patients with isolated PALNM in CRC was performed. Studies including patients with synchronous and metachronous PALN were included, and studies including patients with other metastases were excluded. RESULTS: Eighteen retrospective, single-centre studies were included in the final analysis. The reported incidence of isolated PALNM ranged from 1.3 to 1.7%. A total of 370 patients with PALNM were evaluated, of which 145 had synchronous, and 225 had metachronous PALNM. For synchronous PALNM, the 5-year overall survival (OS) after metastatectomy, ranged from 22.7% to 33.9%. For metachronous PALNM, the 5-year OS ranged from 15 to 60%; median OS was 34-40 months in the PALND versus 3-14 months for patients who did not undergo PALND. There were no reported surgery related mortalities, and overall surgical morbidity was 7.8-33%. CONCLUSION: PALND for isolated PALNM from colorectal cancer can be performed with minimal morbidity and confers a survival advantage, in comparison with conventional palliative chemotherapy or chemoradiation therapy.

Solitary thyroid nodule. Comparison between palpation and ultrasonography.

OBJECTIVE: To determine the accuracy of clinical palpation in the diagnosis of solitary thyroid nodule in comparison with ultrasonographic findings. METHODS: From a computerized database of 1774 patients with the diagnosis of nodular thyroid disease made from January 1990 through December 1991 at our institution, we retrieved and reviewed the medical records of the 193 patients who underwent ultrasonography of the thyroid (42 patients with multinodular glands on palpation were excluded). Nodules were categorized as "solitary" or "dominant nodule of a multinodular gland." Concordance rates were measured between results of palpation and ultrasonographic findings. RESULTS: Of 151 patients included in the study, 78 had solitary nodules on ultrasonography and 73 had multiple nodules. Of those with multiple nodules, 49 had two nodules and 24 had three or more nodules. Of clinically palpable nodules, 89% were 1 cm or greater in diameter. In 72% of the patients with multiple nodules, the other nodules not identified on palpation were less than 1 cm in diameter. The overall concordance rate between the size of the solitary nodule or the dominant nodule in a multinodular gland estimated with clinical palpation and the actual size seen on ultrasonography was 72%. The relationship between multiple nodules and malignancy was not statistically significant. CONCLUSIONS: Our results suggest that (1) a palpable solitary nodule represents a multinodular gland in about 50% of patients, (2) clinical palpation is less sensitive than thyroid ultrasonography in identifying multiple nodules, and (3) palpation is reliable only if a nodule is at least 1 cm in diameter. We recommend that small, occult (impalpable) thyroid nodules not be considered clinically important; they do not warrant further evaluation unless ultrasonographic features suggest malignancy or the nodule increases in size.

Management of thyroid nodules in pregnancy.

BACKGROUND: Disorders of the thyroid are common in pregnancy. In particular, a thyroid nodule is frequently discovered before or during pregnancy. OBJECTIVE: To develop guidelines for the management of thyroid nodules during pregnancy. METHODS: We reviewed the cases of 40 pregnant patients with thyroid nodules evaluated during a 10-year period Cytological findings were compared with available histological findings, and concordance rates were determined. The rank sum test was used for statistical analysis. RESULTS: Fine-needle aspirations of thyroid nodules in 62% of patients were benign cytologically (25 patients). Of 8 patients with negative cytological results who had thyroidectomy, all had benign disease histologically (100% concordance rate). Cytological findings of papillary cancer (3 patients) strongly correlated with final histological diagnosis (100% concordance rate), whereas papillary cancer was confirmed histologically in only 2 of 4 patients with cytological findings suspicious for this disease (50% concordance rate). All 3 nodules with cytological findings suspicious for follicular neoplasm were benign adenomas histologically. Of 2 nodules suspicious for Hürthle cell neoplasm, l was Hürthle cell adenoma and the other was Hürthle cell carcinoma (100% concordance rate). Thyroidectomy during the second trimester of pregnancy or the early postpartum period was successful. CONCLUSIONS: The approach to thyroid nodules in pregnancy should be similar to that for nonpregnant patients. Thyroidectomy should be performed (1) during the second trimester for malignant lesions and cytological findings suspicious for papillary cancer and (2) in the postpartum period for cytological findings suspicious for follicular neoplasm.

Progressive supra-axial cervical instability in Down syndrome: a case report emphasising the role of extended short-segment fusion.

We report a case of upper cervical instability associated with Down syndrome to highlight its potential progression to inflict cord compression and the rationale for surgical decompression and extended short segment occipito-axial fusion.

Bone graft substitute using hydroxyapatite scaffold seeded with tissue engineered autologous osteoprogenitor cells in spinal fusion: early result in a sheep model.

Spinal fusion using autologous bone graft is performed in an increasing rate for many spinal disorders. However, graft harvesting procedure is associated with prolonged operation time and potential donor site morbidity. We produced an engineered 'bone graft' substitute by using porous hydroxyapatite (HA) scaffold seeded with autologous bone marrow osteoprogenitor cells (OPCs) and fibrin. This obviates bone graft harvesting, thus eliminates donor site morbidity and shortens the operation time. The aim of this study is to evaluate Hydroxyapatite (HA) ceramics as scaffold for autologous tissue engineered bone construct for spinal fusion in a sheep model. The sheep's marrow was aspirated from iliac crest. The bone marrow mesenchymal stem cells (BMMSCs) were cultured for several passages in the presence of growth and differentiation factors to increase the number of OPCs. After the cultures reached confluence, they were trypsinized and seeded on Hydroxyapatite scaffold (HA). Approximately 5 million cells were generated after 3 weeks of culture. Microscopically, very tight Colony Forming Units (CFU-Fs) were seen on monolayer culture. The Von Kossa and Alizarin Red staining of monolayer culture showed positive mineralization areas; indicating the presence of OPCs. Sheep underwent a posterolateral spinal fusion in which scaffolds with or without OPCs seeded were implanted on both sides of the lumbar spine (L1-L2). Intended fusion segments were immobilized using wires. At the end of third month, the fusion constructs were harvested for histological examination. Fibrous tissue infiltration found in the inter-connecting pores of plain HA ceramics indicates inefficient new bone regeneration. New bone was found surrounding the HA ceramics seeded with autologous cells. The new bone is probably formed by the sheep BMMSCs that were initially encapsulating HA while it remained intact. The new bone is naturally fused with the vertebrae. In conclusion, the incorporation of autologous bone marrow cells improved the effectiveness of HA ceramics as 'bone graft' substitute for spinal fusion.

The Will Rogers phenomenon in the staging of breast cancer - does it matter?

INTRODUCTION: Changes in the American Joint Commission on Cancer staging for breast cancer occurred when the 5th Edition was updated to the 6th Edition. OBJECTIVE: To investigate how these changes affected stage and survival. METHODS: 3127 cases of breast cancer were restaged. RESULTS: Late stages increased from 27.7% to 38.1%. The five-year survival improved in Stage 2 (82.9-86.1%) and Stage 3 (50.6-59%). DISCUSSION: Stage shift leads to an erroneous impression that women are presenting with later stages and stage-specific survival is improving. CONCLUSION: Standardizing cancer staging is important when reporting stage and survival in different time periods.

Preferential Use of Carbon Sources in Culturable Aerobic Mesophilic Bacteria of Coptotermes curvignathus's (Isoptera: Rhinotermitidae) Gut and Its Foraging Area.

The lower termite, Coptotermes curvignathus, is one of the most prominent plantation pests that feed upon, digest, and receive nourishment from exclusive lignocellulose diets. The objective of this study was to examine the utilization of sole carbon sources by isolated culturable aerobic bacteria among communities from the gut and foraging pathway of C. curvignathus. We study the bacteria occurrence from the gut of C. curvignathus and its surrounding feeding area by comparing the obtained phenotypic fingerprint with Biolog's extensive species library. A total of 24 bacteria have been identified mainly from the family Enterobacteriaceae from the identification of Biolog Gen III. Overall, the bacteria species in the termite gut differ from those of foraging pathway within a location, except Acintobacter baumannii, which was the only bacteria species found in both habitats. Although termites from a different study area do not have the same species of bacteria in the gut, they do have a bacterial community with similar role in degrading certain carbon sources. Sugars were preferential in termite gut isolates, while nitrogen carbon sources were preferential in foraging pathway isolates. The preferential use of specific carbon sources by these two bacterial communities reflects the role of bacteria for regulation of carbon metabolism in the termite gut and foraging pathway.

Interleukin-1 (IL-1) receptor antagonist and soluble IL-1 receptor inhibit IL-1-induced glycosaminoglycan production in cultured human orbital fibroblasts from patients with Graves' ophthalmopathy.

An accumulation of glycosaminoglycans (GAG) is a feature characteristic of orbital connective tissues from patients with Graves' ophthalmopathy (GO) that leads directly to the clinical expressions of the disease. Interleukin-1 (IL-1), produced by macrophages and fibroblasts within the diseased orbit, stimulates GAG synthesis by orbital fibroblasts. We designed the current study to determine whether particular agents might block this effect and thus be useful in the treatment of GO. Orbital fibroblast cultures were grown to confluence and incubated for 48 h with IL-1 (1-10 U/mL) alone or IL-1 (10 U/mL) in combination with IL-1 receptor antagonist (IL-1ra; 1-40 ng/mL) or soluble IL-1 receptor (sIL-1R; 0.25-10 micrograms/mL). Cells were labeled with [3H]glucosamine and processed for GAG quantitation. The addition of IL-1 alone stimulated GAG synthesis by 73-176% (mean, 104%; P < 0.05). Significant inhibition of IL-1-stimulated GAG synthesis was observed after treatment of normal fibroblasts with IL-1ra at a concentration of 5 ng/mL (12.5-fold molar excess; mean, 33%; P < 0.05); essentially complete inhibition was achieved at 40 ng/mL (100-fold molar excess; mean, 86%; P < 0.05). Significant inhibition of GAG synthesis by sIL-1R was observed at a concentration of 0.5 microgram/mL (720-fold molar excess; mean, 79%; P < 0.05), and inhibition was essentially complete at 1 microgram/mL (1440-fold molar excess; mean, 89%; P < 0.05). IL-1ra and sIL-1R are potent inhibitors of IL-1-induced GAG production by cultured human orbital fibroblasts. Our results suggest that these two compounds, shown in early trials to be safe when administered parenterally, may be useful in the prevention or treatment of GO.

Pharmacologic treatment options for non-insulin-dependent diabetes mellitus.

Non-insulin-dependent diabetes mellitus (NIDDM) is a major health concern for clinicians who are responsible for the care of an aging population. The relationship between hyperglycemia and the chronic complications of retinopathy, nephropathy, and neuropathy has been established in patients with insulin-dependent diabetes mellitus, and it is extremely likely that such a relationship exists in patients with NIDDM as well. Diet and exercise are the cornerstone for the management of NIDDM. The assessment of glycemic control should determine which patients with NIDDM need more aggressive intervention to control hyperglycemia. Pharmacologic treatment options include oral administration of the sulfonylureas, a biguanide, and an alpha-glucosidase inhibitor and subcutaneous administration of insulin. Extensive education about diabetes and self-monitoring of blood glucose levels are important components in maximizing glycemic control. Additional pharmacologic treatment options are necessary when adequate individualized treatment goals are not attained. The goal of therapy is to prevent the onset or progression of long-term microvascular and macrovascular complications. In this review, we present the therapeutic options and outline our approach to the pharmacologic treatment of NIDDM. Relevant medical literature on each treatment modality is reviewed, and the cost of therapy with use of each medication is provided.

Transient hypopituitarism.

Spontaneous recovery of pituitary function in patients with hypopituitarism is rare. We report the case of a 30-year-old man in whom hypopituitarism and sudden onset of bilateral hearing loss developed after a viral infection. No evidence of a mass lesion was detected on computed tomography or magnetic resonance imaging of the pituitary gland. The patient received a 3-week course of treatment with a high dose of glucocorticoids; in a period of 6 weeks, he felt clinically well, and biochemical tests showed spontaneous return of normal anterior pituitary function. We speculate that an immune response triggered by the viral infection initiated an inflammatory process that involved the hypothalamus or pituitary gland and caused the hypopituitarism. The treatment with high-dose glucocorticoids could have prompted the resolution of the hypothalamic-pituitary inflammatory process and facilitated spontaneous recovery of pituitary function. This case shows that hypopituitarism may be transient an outcome that should be considered in patients with idiopathic hypopituitarism.

Recurrent hyperthyroidism after radioiodine-induced hypothyroidism: report of two cases and literature review.

The practice at the Mayo Clinic in treating Graves' disease with radioiodine (131 I) is to achieve a hypothyroid state. Less than 10% of the patients need more than one dose. Although cases of transient hypothyroidism have been reported after treatment with 131 I, the recurrence of hyperthyroidism is unusual after hypothyroidism has been induced with 131 I. We studied two cases seen at our institution in the past year in which the circumstances behind the recurrence have never been reported previously. The first case illustrates a recurrence of hyperthyroidism after the patient had received 38.5 mCi of 131 I. The second patient had recurrence of hyperthyroidism after 22 years of replacement therapy with levothyroxine. Both patients had increased levels of thyroid-stimulating immunoglobulin. We believe that the recurrence of the hyperthyroid state in these two patients was due to incomplete ablation of the thyroid. Apparently 131 I caused hypothyroidism, but residual cells remained viable and under continuous stimulation of thyroid-stimulating immunoglobulin produced recurrent thyrotoxicosis.