Apolipoprotein D is a component of compact but not diffuse amyloid-beta plaques in Alzheimer's disease temporal cortex

Apolipoprotein D (apoD) is elevated in Alzheimer's disease (AD) cortex, localizing to cells, blood vessels, and neuropil deposits (plaques). The role of apoD in AD pathology and the extent of its co-distribution with diffuse (amorphous) and compact (dense fibrillar) amyloid-beta (Abeta) plaques are currently unclear. To address this issue, we combined apoD and Abeta immunohistochemistry with ThioS/X-34 staining of the beta-pleated sheet protein conformation in temporal cortex from 36 AD patients and 12 non-demented controls. ApoD-immunoreactive, Abeta-immunoreactive, and ThioS/X-34-stained plaques were detected exclusively in AD tissue. Dual-immunolabeling showed that 63% of Abeta plaques co-localized apoD. All apoD plaques contained Abeta protein and ThioS/X-34 fluorescence. Compared to controls, AD cases showed elevated vascular and intracellular apoD immunostaining which localized primarily to cells clustered within plaques and around large blood vessels. ApoD-immunoreactive cells within plaques morphologically matched MHC-II- and CD-68-immunoreactive microglia, and did not contain the astrocytic marker GFAP, which labeled a subset of apoD-immunoreactive cells surrounding plaques. These data suggest that neuropil deposits of apoD localize only to a subset of Abeta plaques, which contain compact aggregates of fibrillar Abeta. Elevated apoD in AD brain may influence Abeta aggregation, or facilitate phagocytosis and transport of Abeta fibrils from plaques to cerebral vasculature.     

Metastatic extraocular sebaceous carcinoma with an occult primary

The cytological diagnosis of sebaceous carcinoma is based on the aspiration of tumor lobules with extensive sebaceous differentiation. However, these tumors may show a spectrum of cells ranging from basaloid to well-differentiated sebaceous. Extraocular sebaceous carcinoma is an uncommon tumor. An occult primary at initial presentation has not been described previously. A 60-yr old woman was referred to the fine-needle aspiration (FNA) clinic with a submandibular mass. The cytological diagnosis was mucoepidermoid carcinoma. Histopathologically, it was a sebaceous carcinoma metastatic to the submandibular lymph node. No primary tumor was identified. Six months later, she presented with a nodule at the angle of her mouth and a recurrence of the submandibular swelling. FNA cytology (FNAC) and histopathologic examination revealed a primary cutaneous sebaceous carcinoma with submandibular lymph node metastasis. A metastatic sebaceous carcinoma in the submandibular region with limited sebaceous differentiation and occult primary is another pitfall in the cytomorphological diagnosis of mucoepidermoid carcinoma.     

Risk factors in the primary management of anorectal malformations in Northern India

The purpose of this study was to determine the major factors influencing the survival of babies with anorectal malformation (ARM) during the primary management in the neonatal period in a tertiary referral center. The outcome of 125 neonates with ARM, treated in a single hospital during a 2-year period, was analyzed retrospectively with particular reference to birth weight, time of arrival, and the type of ARM, including pouch colon and major associated anomalies, to see whether any of them had a significant effect on initial survival. High ARM (HARM) was present in 75, low ARM (LARM) in 36, and pouch colon in 14 babies. There were a total of 28 deaths (22%). In babies with isolated HARM weighing >2.5 kg and brought to the hospital within the first 48 h of life, the survival was 100%, which dropped to 80% when brought later than 48 h. Of the babies with birth weight <2.5 kg and isolated HARM but who were brought to the hospital within the first 48 h of life, 80% survived, whereas of those reaching the hospital after 48 h, only 55% survived. Two babies with pouch colon and two of the four babies with LARM and associated anomalies died. In the HARM group, of the 31 babies with major associated anomalies, only 37% with birth weight <2.5 kg and 58% with birth weight >2.5 kg survived. Low birth weight, major associated anomalies, and delay in referral were the three important factors that influenced the outcomes of babies with ARM during the neonatal period.     

Microsphere size, precipitation kinetics and drug distribution control drug release from biodegradable polyanhydride microspheres.

A thorough understanding of the factors affecting drug release mechanisms from surface-erodible polymer devices is critical to the design of optimal delivery systems. Poly(sebacic anhydride) (PSA) microspheres were loaded with three model drug compounds (rhodamine B, p-nitroaniline and piroxicam) with a range of polarities (water solubilities). The drug release profiles from monodisperse particles of three different sizes were compared to release from polydisperse microspheres. Each of the model drugs exhibited different release mechanisms. Drug distribution within the polymer was investigated by laser scanning confocal microscopy and scanning electron microscopy. Rhodamine, the most hydrophilic compound investigated, was localized strongly toward the microsphere surface, while the much more hydrophobic compound, piroxicam, distributed more evenly. Furthermore, all three compounds were most uniformly distributed in the smallest microspheres, most likely due to the competing effects of drug diffusion out of the nascent polymer droplets and the precipitation of polymer upon solvent extraction, which effectively "traps" the drug in the polymer matrix. The differing drug distributions were manifested in the drug release profiles. Rhodamine was released very quickly independent of microsphere size. Thus, extended release profiles may not be obtainable if the drug strongly redistributes in the microspheres. The release of p-nitroaniline was more prolonged, but still showed little dependence on microsphere size. Hence, when water-soluble drugs are encapsulated with hydrophobic polymers, it may be difficult to tailor release profiles by controlling microsphere size. The piroxicam-loaded microspheres exhibit the most interesting release profiles, showing that release duration can be increased by decreasing microsphere size, resulting in a more uniform drug distribution.     

Pelviureteric junction obstruction: how much is the extent of the upper ureter with defective innervation needing resection?

Background/Purpose: It is well realized that Anderson-Hyne’s pyeloplasty fails to improve the drainage pattern and renal functional parameters in a few cases of hydronephrosis because of pelviureteric junction (PUJ) obstruction. The purpose of this study is to delineate the lower extent of the abnormally innervated pelviureteric junction by S-100 immunohistochemistry, which requires surgical removal.Methods: Thirty pelviureteric junction (PUJ) specimens were analyzed by histology and by S-100 immunohistochemistry after serial sectioning of the resected ureter and compared with the variables age, calyceal separation, parenchymal thickness, differential renal function, glomerular filtration rate (GFR), and the measured constricted ureteral segment on gross examination.Results: No significant correlation was noted (P > .05) when the histology was analyzed to find any association with any of the variables studied. The length of the visible constricted segment ranged from 2 mm to 15 mm (mean, 5.37 mm). The abnormally innervated segment was much longer than the length of the visible constricted segment in 24 and of the same length in 5 specimens. However, in 1 case, the abnormal innervation segment was shorter than the macroscopic constriction by 3 mm. The maximum difference in length between the visible constriction and the lower limit of defective innervation was 8 mm.Conclusions: The abnormally innervated ureteral segment below the PUJ in hydronephrosis is longer than the visible constricted segment at the time of surgery, and the ureter should be excised at least 8 mm or more beyond the visible lower limit of the constricted segment in cases of Anderson-Hyne’s pyeloplasty.     

Ectopic scrotum and patent urachus

Ectopic scrotum is a rare condition and has been reported in association with other urological abnormalities. We present a case with an associated patent urachus and a brief discussion on the possible mechanism to explain this deformation. Accepted: 24 August 1999