Etiopathological differentiation of diabetes mellitus in lean, young adults.

OBJECTIVE: Classification of diabetes mellitus (DM) into type 1 or type 2 is difficult in lean, young individuals. We studied the ß-cell function, insulin resistance (IR) and autoimmunity in young patients with recent onset DM. METHODS: In this cross-sectional study, we included patients (age below 35 years) with recent onset DM (<6 months) and normal body weight for evaluation. The detailed clinical examination was done to identify markers of IR. Autoimmune DM was diagnosed using glutamic acid decarboxylase 65 (GAD65), insulin autoantibody (IAA) and islet cell antibody (ICA). Homeostasis model assessment (HOMA) models of HOMA-B and HOMA- IR were used for estimation of ß-cell function and IR respectively. The patients were divided into four groups based on, the autoimmunity (A) and ketosis (K) as group 1 (A+K), group 2 (A-K+), group 3 (A+K-) and group 4 (A-K-). Appropriate statistical tests +)were used to analyze the results. RESULTS: The study population (n=75, all males) had a mean age of 28.9±4.3years, body mass index 20.6±1.9kg/m2, fasting plasma glucose 177.1±31.4mg/dl and HbA1c of 9.9±2.1% at presentation. The number of patients in groups 1 to 4 are 8, 5, 10 and 52 respectively (p<0.0001). HOMA-IR was higher in groups 2 and 4 (4.1±1.3, 3.6±1.1 respectively), whereas HOMA-B was higher in group 4 (3.6±1.5) alone (p=0.0005). CONCLUSION: Type 2 DM is the most common etiology even in young, lean adults in India. Further studies with large numbers are required to confirm our findings.

Changes in bone mineral density and bone turnover markers in patients undergoing hematopoietic stem cell transplant.

INTRODUCTION: Hematopoietic stem cell transplant (HSCT) is frequently complicated by endocrine abnormalities and loss of bone mass. This prospective study was conducted to evaluate the bone loss post-HSCT. MATERIALS AND METHODS: A total of 50 patients was evaluated pretransplantation, and 25 had HSCT (17 males, 8 females; 19 allogenic, 6 autologous). Bone mineral density (BMD) and bone markers were measured at baseline, 3-6 months and 12 months. RESULTS: The mean age and body mass index were 25.1 ± 16.3 years and 19.4 ± 4.5 kg/m(2), respectively. There were 15 adults (60%), and 10 adolescents (40%). There was a significant decline in BMD from the baseline at total femur (-8.7%; P < 0.0001), femoral neck (-5.0%; P = 0.003), femoral trochanter (-6.0%; P = 0.001), and Ward's triangle (-9.9%; P < 0.0001) at 6 months posttransplantation. From the 6 months to 12 months, there was a significant improvement in BMD at above sites except at Ward's triangle. The decline in BMD was nonsignificant at the whole body (-0.3%, P = 0.748) and the lumbar spine (-2.7%, P = 0.130) at 6 months posttransplant. Younger patients with allogenic graft and steroid use are more likely to have significant loss of BMD at hip posttransplant. Serum osteocalcin decreased, and N-telopeptide increased at 3-6 months, which return to baseline at 1-year posttransplant. CONCLUSIONS: A significant bone loss is observed at 6 months in patients with post-HSCT. The bone loss occurs predominantly at cortical bone. There is recovery of bone mass at 12 months posttransplant except at Ward's triangle. Bone loss after HSCT is multifactorial.

Initial application of EPIC-µCT to assess mouse articular cartilage morphology and composition: effects of aging and treadmill running.

OBJECTIVE: The current study was undertaken to adapt Equilibrium Partitioning of an Ionic Contrast agent via microcomputed tomography (EPIC-µCT) to mouse articular cartilage (AC), which presents a particular challenge because it is thin (30 µm) and has a small volume (0.2-0.4 mm(3)), meaning there is only approximately 2-4 µg of chondroitin sulfate (CS) glycosaminoglycan per joint surface cartilage. DESIGN: Using 6 µm isotropic voxels and the negatively charged contrast agent ioxaglate (Hexabrix), we optimized contrast agent concentration and incubation time, assessed two methods of tissue preservation (formalin fixation and freezing), examined the effect of ex vivo chondroitinase ABC digestion on X-ray attenuation, assessed accuracy and precision, compared young and skeletally mature cartilage, and determined patterns of degradation in a murine cartilage damage model induced by treadmill running. RESULTS: The optimal concentration of the contrast agent was 15%, formalin fixation was preferred to freezing, and 2 h of incubation was needed to reach contrast agent equilibrium with formalin-fixed specimens. There was good agreement with histologic measurements of cartilage thickness, although µCT over-estimated thickness by 13% (5 µm) in 6-week-old mice. Enzymatic release of 0.8 µg of chondrotin sulfate (about 40% of the total) increased X-ray attenuation by 17%. There was a 15% increase in X-ray attenuation in 14-week-old mice compared to 6-week-old mice (P < 0.001) and this corresponded to 65% decrease in CS content at 14 weeks. The older mice also had reductions of 33% in cartilage thickness and 44% in cartilage volume (P < 0.001). Treadmill running induced a 16% decrease in cartilage thickness (P = 0.012) and a 12% increase in X-ray attenuation (P = 0.006) in 14-week-old mice. CONCLUSION: This technique enables non-destructive visualization and quantification of murine femoral AC in three dimensions with anatomic specificity and should prove to be a useful new tool in studying degeneration of cartilage in mouse models.

Juvenile Graves' disease with opthalmopathy, lymphadenopathy, accelerated growth and congestive cardiac failure.

Graves' disease in childhood is a rare clinical entity. The authors report a case of Graves' disease in a 3-year-old child, who had opththalmopathy, accelerated growth, cervical lymphadenopathy, hepatosplenomegaly and congestive cardiac failure; and responded well to treatment.

Thyroid dyshormonogenesis.

Dyshormonogenesis is an uncommon cause of congenital hypothyroidism. The most common abnormality is absent or insufficient thyroid peroxidase enzyme. Perchlorate discharge test can be used to diagnose thyroid peroxidase deficiency. We report three siblings with hypothyroidism due to thyroid dyshormonogenesis. Early institution of therapy in these patients can prevent mental retardation and other features of hypothyroidism.

Polyglandular autoimmune syndrome type 1 without chronic mucocutaneous candidiasis in a 16 year-old male.

A 16 year-old boy presented with adrenal crisis and was incidentally found to have features of latent tetany. Also detected were Hashimoto's thyroiditis, alopecia and subnormal T cell function, and he was diagnosed as having polyglandular autoimmune syndrome type 1 (PGA-1), although chronic mucocutaneous candidiasis, a hallmark of PGA-1, was absent. The presentation of several components of this disorder at one time and at this age is uncommon, and the features of overt hypoparathyroidism were probably masked by associated adrenal insufficiency.

Stretching skin: undermining is more important than intraoperative expansion.

The efficacy of intraoperative expansion in reducing the tension of wound closure was tested in young pigs. The young piglet as a model for studying human skin was characterized by finding a close similarity between the modulus of elasticity of young piglet skin and human abdominoplasty and mammaplasty skin (range 12.8 to 23.7 N/mm2 for piglet skin, 14.3 to 19 N/mm2 for human skin). The tension required to close a standardized wound was determined before undermining, after undermining, and finally after intraoperative expansion. These measurements were performed in 10 young pigs with an average weight of 11.5 kg. Undermining the wound edges resulted in a significant decrease in the force required to close the wounds (p less than 0.0001). Intraoperative expansion did not significantly decrease the tension. Previous work showing the importance of site and direction of pull on the tension for wound closure was confirmed in this study. Analysis of variance demonstrated that the tension required to close a standard wound is greater high on the pig's back than near the belly and near the shoulder as opposed to the hip for midflank wounds (p less than 0.0001). Increasing the extent of undermining from 62 to 136 cm2 significantly decreased the tension for wound closure (p less than 0.05). Further undermining did not result in a significant decrease in wound closure tension. In this model, intraoperative expansion offers no advantage over simple undermining. We suggest that the benefit reported by clinicians using intraoperative expansion may derive from an increase in the extent of undermining required to place expanders under the wound margins.

Types of tumor lymphoid response and sinus histiocytosis. Relationship to five-year, disease-free survival in patients with breast cancer.

Diffuse (D), perivascular (PV), and a combination form (DPV) of lymphoid infiltrates were found in 95% of invasive breast cancers. The DPV and D patterns were associated with tumor necrosis, and the D pattern with cancers of nuclear grade 3 (most anaplastic) and histologic grade 3 (most malignant). An absent cell reaction was significantly related to absent nodal metastases. Life-table analyses disclosed a higher incidence of patients' being disease free for five years when no cell reaction was encountered. There was no significant association between the presence or absence of any particular type of sinus histiocytosis (SH) of regional lymph nodes and five-year, disease-free survival. It is uncertain whether lymphoid reactions and SH represent immunologic host responses, but if they do, they appear to be biologically ineffectual and, in the former instance, perhaps even detrimental.

A nonencapsulated sclerosing lesion of the breast.

A histological study of 15 examples of a unique proliferative and tubular lesion (Fenoglio and Lattes) of the breast was performed. Although it consistently lacked infiltration of adipose tissue, the commonality of some of its morphologic features and those of tubular cancer provokes the possibility that these lesions may represent incipient tubular cancers. Nevertheless, such lesions may be satisfactorily treated by simple excision. Since we are certain only about its topographic and clinical behavior, but not its precise biologic nature, we regard the designation nonencapsulated sclerosing lesion most appropriate. Stromal and periductal elastosis was not infrequently encountered in examples of overt sclerosing and blunt ductal adenosis which may mimic, but can readily be distinguished from, the nonencapsulated sclerosing lesion.