Northern epilepsy: a novel form of neuronal ceroid-lipofuscinosis.

Northern epilepsy is an autosomal recessive childhood onset epilepsy syndrome, clinically characterized by generalized tonic-clonic seizures with onset at 5 to 10 years of age and subsequent slowly progressive mental deterioration. The patients may reach 50 or 60 years of age. A mutation responsible for the disease has recently been identified in a novel gene on chromosome 8p23, encoding a putative membrane protein with an unknown function. The present study, based on three autopsied patients, is the first neuropathological analysis of the disease, and showed intraneuronal accumulation of cytoplasmic autofluorescent granules. The granules were strongly stained by the Luxol fast blue, periodic acid-Schiff, and Sudan black B methods in paraffin sections, and were immunoreactive for subunit c of the mitochondrial ATP synthase and sphingolipid activator proteins A and D. The intraneuronal storage was highly selective: the third layer of the isocortex and the hippocampal CA2, CA3, and CA4 sectors were severely affected, while other layers of the isocortex, the CA1 sector, and the cerebellar cortex were only minimally involved. The membrane-bound storage cytosomes showed a curvilinear ultrastructure with admixture of some granular components. Western blotting and N-terminal sequence analysis of purified storage material identified subunit c as the major component. These findings establish Northern epilepsy as a new form of neuronal ceroid-lipofuscinosis with an exceptionally protracted course.

Survival and functional outcome after prolonged intensive care unit stay.

OBJECTIVE: To examine the functional outcome and costs of a prolonged illness requiring a stay in the surgical intensive care unit (SICU) of 7 of more days. SUMMARY BACKGROUND DATA: The long-term benefits and costs after a prolonged SICU stay have not been well studied. METHODS: All patients with an SICU length of stay of 7 or more days from July 1, 1996, to June 30, 1997, were enrolled. One hundred twenty-eight patients met the entry criteria, and mortality status was known in 127. Functional outcome was determined at baseline and at 1, 3, 6, and 12 months using the Sickness Impact Profile score, which ranges from 0 to 100, with a score of 30 being severely disabled. Hospital costs for the index admission and for all readmissions to Johns Hopkins Hospital were obtained. All data are reported as median values. RESULTS: For the index admission, age was 57 and APACHE II score was 23. The initial length of stay in the ICU was 11 days; the hospital length of stay was 31 days. The Sickness Impact Profile score was 20.2 at baseline, 42.9 at 1 month, 36.2 at 3 months, and 20.3 at 6 months, and was lower than baseline at 1 year. The actual 1-year survival rate was 45.3%. The index admission median cost was $85,806, with 65 total subsequent admissions to this facility. The cost for a single 1-year survivor was $282,618 (1996). CONCLUSIONS: An acute surgical illness that results in a prolonged SICU stay has a substantial in-hospital death rate and is costly, but the functional outcome from both a physical and physiologic standpoint is compatible with a good quality of life.

Production of membrane-type matrix metalloproteinase-1 (MT-MMP-1) in early human placenta. A possible role in placental implantation?

The extracellular matrix proteolytic machinery is known to play a major role in trophoblast invasion, a process that shares similar features with the pathology of tumor invasion. In this study we investigated the expression of the recently described membrane-type matrix metalloproteinase-1 (MT-MMP-1; MMP-14) in early human placenta and decidual membrane to determine whether it might play a role in invasion. With in situ hybridization, the cytotrophoblasts of trophoblastic columns and the infiltrating intermediate trophoblasts in the decidual membrane were found to be the main producers of MT-MMP-1 mRNA. Gene expression was also seen in the villous double-layered trophoblastic epithelium and in the decidual cells of the decidual membrane. In endothelial and fibroblastic cells, however, the hybridization signal was either very weak or nonexistent. Immunohistochemical analysis and immunoelectron microscopy correlated well with the in situ hybridization findings. The most significant exception to this consisted of pericytes of spiral arteries, which appeared to lack MT-MMP-1 mRNA but showed intensive intracytoplasmic staining for the antigen. Our results show that MT-MMP-1 mRNA production is highly characteristic of intermediate trophoblasts, and MT-MMP-1 may have general importance in the tissue organization of early human placenta. We propose that MT-MMP-1 could be one of the key enzymes in the process of trophoblast invasion, acting alone or as a cell-surface activator of other proteinases.

Risk of foot complications in long-term diabetic patients with and without ESRD: a preliminary study.

OBJECTIVE: The purpose of this preliminary study was to generate hypotheses for future research about the relationship between ESRD and foot complications in patients with long-term diabetes. DESIGN: A cross-sectional prevalence study was conducted comparing a sample of long-term diabetic patients with ESRD to a sample of long-term diabetic patients without ESRD. SAMPLE/SETTING: A convenience sample of 132 patients with long-term diabetes (> 15 years), with (N = 60) and without (N = 72) ESRD, was selected from ambulatory care settings and dialysis units. METHODS: Data were collected by chart audit, structured interview, and physical examination. RESULTS: Foot complications were greater in individuals with diabetes and ESRD (25%) than in diabetic individuals without ESRD (10%) (p = 0.02). Neither neuropathy, past or current smoking, race, gender, nor age were significantly associated with current foot complications (either current infection, ulcer, gangrene, or amputation). CONCLUSIONS: Research is needed to better understand foot complications in persons with long-term diabetes and ESRD so that the effectiveness of nursing and medical interventions to stabilize or prevent foot complications can be evaluated.