Structural and functional maturation of distal femoral cartilage and bone during postnatal development and growth in humans and mice

The size and shape of joints markedly affect their biomechanical properties, but the macroscopic 3-dimensional (3-D) mechanism and extent of cartilage and joint maturation during normal growth are largely unknown. This study qualitatively illustrates the development of the bone-cartilage interface in the knee during postnatal growth in humans and C57BL/6 wild-type mice, quantitatively defines the 3-D shape using statistical shape modeling, and assesses growth strain rates in the mouse distal femur. Accurate quantification of the cartilage-bone interface geometry is imperative for furthering the understanding of the macroscopic mechanisms of cartilage maturation and overall joint development.     

Triple Innominate Osteotomy for Legg-Calvé-Perthes Disease in Children: Does the Lateral Coverage Change With Time?

Background  

Triple innominate osteotomy (TIO) is one of the modalities of surgical containment in Legg-Calvé-Perthes disease (LCPD). However, overcoverage with TIO can lead to pincer impingement.     

Animal models

Our understanding of bullous skin disorders has increased enormously since the beginning of the century, when a patient with generalized blisters was firmly diagnosed as having pemphigus vulgaris only upon his demise. Those fortunate patients who survived obviously did not have true pemphigus vulgaris. They very likely had “pemphigus of the aged” or “bullous dermatitis herpetiformis.” The key observations that defined these diseases more precisely were the careful histopathological studies of Lever¹ and the immunofluorescent studies of Beutner and Jordon.^2,3 The auto-antibodies in pemphigus vulgaris and bullous pemphigoid that can be detected both bound into and around lesions and circulating in the serum have not only proven to be crucial for the accurate diagnosis of these conditions, but also appear to be of primary importance in the pathogenesis of the diseases as well. There is now substantial evidence that pemphigus auto-antibodies bind specifically to a cell surface antigen on squamous epithelia, and can directly induce cell-to-cell detachment and acantholysis of those cells through mechanisms currently being investigated.

The cornerstone of our current knowledge of the mechanisms of tissue injury in pemphigus was the observation in 1964 by Beutner and Jordon that the majority of pemphigus patients have IgG class antibodies in the serum that bind in the intercellular spaces of stratified squamous epithelia.^2,3 Subsequently, much has been learned of the importance of these auto-antibodies in the disease process but much still remains poorly understood.

There is a large body of evidence that these epithelial autoantibodies are pathogenic in the disease and not merely an epiphenomenon. This is based on clinical observations, in vitro, and in vivo data. The clinical observations are as follows: (1) in many, but certainly not all patients with pemphigus, the titers of these antibodies, as measured by indirect immunofluorescence (IF), correlate with disease activity; (2) plasmapheresis has been reported to induce short-term remissions in pemphigus patients and may be an effective adjunct to therapy in acute cases^4–7; and (3) pemphigus has occurred in neonates born to mothers with active pemphigus, and the disease has resolved in the newborns after parturition.^{8, 9} Presumably, transplacental transfer of maternal IgG induces the disease, which resolves as their levels diminish in the neonates.

In vitro studies also support the pathogenic role of pemphigus antibodies in the induction of acantholysis. Bellone and Leone,¹⁰ Schiltz and Michel,¹¹ and Morioka et al.¹² have demonstrated that pemphigus serum, or IgG fractions from pemphigus serum, induce acantholysis in human skin expiants. Farb, et al.¹³ and Diaz and Marcelo¹⁴ have shown that pemphigus serum added to murine primary epidermal cell cultures will cause epidermal cell detachment. This effect is highly reproducible and specific, for it does not occur when cultures are treated with normal human IgG or with IgG fractions from bullous pemphigoid, lupus erythematosus, or anti-AB sera, as demonstrated by Woo, et al. in our laboratories.¹⁶

Finally, there is also convincing in vivo evidence of their pathogenicity. Despite previous reports that parenteral passive transfer or local injections of pemphigus auto-antibodies into animals failed to induce disease consistently,^16–20 our laboratory has demonstrated that, given in sufficient doses, IgG fractions purified from pemphigus serum induce a disease in neonatal mice that reproduces the clinical, histological, and immunological features of the human disease.²¹     

Correlation between clinical and histological findings in parathyroid tumors suspicious for carcinoma

Carcinoma of the parathyroid is a rare malignancy that can be cured surgically if the proper diagnosis and treatment is given initially. Arriving to the clinical suspicion of a malignancy preoperatively is by far the most important step for a good prognosis. Our goal is to review the correlation between clinical and final histopathological findings that can arouse the suspicion of such malignancy and their true predictive value in the diagnosis. All patients that underwent surgical removal of the parathyroid mass between March of 1992 and March of 2003 were reviewed retrospectively at Providence Hospital and Medical Centers. Among 168 patients who underwent parathyroid excision, 14 (8.3%) had hyperplasia of the parathyroid, 121 (72%) had benign adenoma, 25 (14.8%) had other benign lesions, and 8 (4.7%) patients had primary carcinoma of the parathyroid confirmed by pathology. Our mean serum calcium level was 11.57 mg/dL, which was lower than the mean level (12 mg/dL) for benign hyperparathyroidism. The mean tumor size was 2.18 cm, smaller than the proposed for malignant criteria, and none of the eight patients (0%) had any symptoms of hypercalcemia at the time of diagnosis. Seven of eight patients (87.5%) had frank signs of invasion together with other histological features, and two patients had associated papillary carcinoma of the thyroid. Five patients from our series did not meet clinical criteria for malignancy (tumor size > 3 cm, palpable mass, and serum calcium > 14 mg/dL), but had undisputable histological findings (high mitotic pattern, fibrous trabeculae, capsular invasion, vascular invasion, and nodular involvement). On the other hand, 17 patients with benign histology had tumors greater than 3 cm, and an additional 18 had palpable masses on physical examination. We believe that these patients need to be followed closely. The patients with diagnosis of parathyroid carcinoma, their kindred, and those with large adenomas may benefit from genetic screening for HRTP2 gene mutations in search of early detection of tumors suspicious for malignancy. This is based on the fact that we did not find correlation between the clinical presentation and the histological features in our patients with proven malignancy.     

Congenital varicella syndrome/ vericella zoster virus VZV fetopathy

An 18 hour old female newborn born to a 3rd gravida HIV -ve mother, presented with a large erythematous patch of skin on right forehead and hazy right eye since birth. There was history of Chicken pox in mother during fourteenth week of pregnancy.     

Characteristic MR spectroscopy in fucosidosis: in vitro investigation

Fucosidosis is a rare lysosomal storage disorder that results in the deposition of the sugar fucose within various organs, including the central nervous system. Neuroimaging abnormalities on MR, specifically T2 shortening in the basal ganglia, have been reported as suggestive of fucosidosis. A more recent report of MR spectroscopy (MRS) of one patient provided evidence that MRS is specific for fucosidosis. We present another confirmed case with nearly identical MR spectroscopic findings along with in vitro data that support the contention that MR spectroscopy, in the setting of typical clinical and imaging features, is characteristic for this rare disorder.