Epilepsy in very preterm infants: neonatal cranial ultrasound reveals a high-risk subcategory

Osteoporotic fractures, and in particular, hip fractures result in significant morbidity and mortality. Low bone mass is the main risk factor of enhanced bone fragility, resulting in an increased risk for hip fracture. Bone density of osteoporotic women with and without hip fractures show a considerable overlap. Therefore, other bone-independent factors also play an important role for the development of hip- and other osteoporotic fractures. One other important factor is falling. In 90% of hip fractures falling was involved [10-15], but only 5% or less of these falls resulted in a subsequent fracture. The view that adequate exercise is beneficial for skeletal health of children and for prevention and treatment of osteoporosis in adults is supported primarily by two lines of evidence: longitudinal and cross-sectional trials in children and young adult athletes showing a significant increase of muscle- and bone mass after strenuous (children) or chronic exercise (athletes) as compared to normally active (children) or sedentary control subjects. What are the potential benefits and limits of specific exercise programs with respect to bone mass, prevention of falls and fractures? In this review these questions are discussed and a specific exercise program in osteoporotic patients with fractures is delineated.     

Dysfunctional uterine bleeding

Alzheimer's disease (AD) is characterized by progressive dementia and distinct neuropathology at autopsy. In order to test the relationship between dementia severity and loss of brain volumes, we prospectively documented the neurological/medical health of 26 male and 26 female controls and AD cases, and evaluated a subset of controls and AD cases using the Mini Mental State Examination (MMSE). At autopsy, Consortium to Establish a Registry for Alzheimer's Disease (CERAD) criteria confirmed diagnoses in 33 AD cases and 19 controls, and using unbiased stereology we quantified total volumes of cortical gray matter, subcortical grey matter including white matter, and forebrain. For ages of death between 50 to 100 years, controls showed minor cortical atrophy in the absence of cognitive decline. Cortical atrophy in AD cases was 20 to 25% greater than that in controls; AD patients dying at older ages showed less severe cortical atrophy than those dying at younger ages. Across all AD cases there was a strong correlation between cognitive performance on the Mini Mental State Examination and cortical volume loss. These findings confirm fundamental differences in the temporal patterns of cortical volume loss in aging and AD, and support cortical degeneration as the primary basis for cognitive decline in AD.     

Translation of some maize small heat shock proteins is initiated from internal in-frame AUGs

Etiolated maize radicles (inbred Oh43) subjected to a brief heat shock synthesize a family of small heat shock proteins (approximately 18 kD) that is composed of at least 12 members. We previously described the cDNA-derived sequence of three maize shsp mRNAs (cMHSP18-1, cMHSP18-3, and cMHSP18-9). In this report, we demonstrate that the mRNA transcribed in vitro from one of these cDNAs (cMHSP18-9) is responsible for the synthesis of three members of the shsp family, and we suggest that cMHSP18-3 may be responsible for the synthesis of three additional members and cMHSP18-1 for the synthesis of two other members of this family. The fact that these genes do not contain introns, coupled with the observations reported herein, suggest that maize may have established another method of using a single gene to produce a number of different proteins.     

Inhibition of experimental autoimmune encephalomyelitis in Lewis rats by nasal administration of encephalitogenic MBP peptides: synergistic effects of MBP 68-86 and 87-99

Induction of mucosal tolerance by inhalation of soluble peptides with defined T cell epitopes is receiving much attention as a means of specifically down-regulating pathogenic T cell reactivities in autoimmune and allergic disorders. Experimental autoimmune encephalomyelitis (EAE) induced in the Lewis rat by immunization with myelin basic protein (MBP) and Freund's adjuvant (CFA) is mediated by CD4+ T cells specific for the MBP amino acid sequences 68-86 and 87-99. To further define the principles of nasal tolerance induction, we generated three different MBP peptides (MBP 68-86, 87-99 and the non-encephalitogenic peptide 110-128), and evaluated whether their nasal administration on day -11, -10, -9, -8 and -7 prior to immunization with guinea pig MBP (gp-MBP) + CFA confers protection to Lewis rat EAE. Protection was achieved with the encephalitogenic peptides MBP 68-86 and 87-99, MBP 68-86 being more potent, but not with MBP 110-128. Neither MBP 68-86 nor 87-99 at doses used conferred complete protection to gp-MBP-induced EAE. In contrast, nasal administration of a mixture of MBP 68-86 and 87-99 completely blocked gp-MBP-induced EAE even at lower dosage compared to that being used for individual peptides. Rats tolerized with MBP 68-86 + 87-99 nasally showed decreased T cell responses to MBP reflected by lymphocyte proliferation and IFN-gamma ELISPOT assays. Rats tolerized with MBP 68-86 + 87-99 also had abrogated MBP-reactive IFN-gamma and tumor necrosis factor-alpha mRNA expression in lymph node cells compared to rats receiving MBP 110-128 nasally, while similar low levels of MBP-reactive transforming growth factor-beta and IL-4 mRNA expressing cells were observed in the two groups. Nasal administration of MBP 68-86 + 87-99 only slightly inhibited guinea pig spinal cord homogenate-induced EAE, and passive transfer of spleen mononuclear cells from MBP 68-86 + 87-99-tolerized rats did not protect na?ve rats from EAE. Finally, we show that nasal administration of MBP 68-86 + 87-99 can reverse ongoing EAE induced with gp-MBP, although higher doses are required compared to the dosage needed for prevention. In conclusion, nasal administration of encephalitogenic MBP peptides can induce antigen-specific T cell tolerance and confer incomplete protection to gp-MBP-induced EAE, and MBP 68-86 and 87-99 have synergistic effects. Non-regulatory mechanisms are proposed to be responsible for tolerance development after nasal peptide administration.     

The discovery and structure-activity relationships of nonpeptide, low molecular weight antagonists selective for the endothelin ET(B) receptor

The systematic modification of the ETA selective N-(5-isoxazolyl)benzene-sulfonamide endothelin antagonists to give ETB selective antagonists is reported. The reversal in selectivity was brought about by substitution of the 4-position with aryl and substituted aryl groups. Of all the aromatic substituents studied, the para-tolyl group gave rise to the most active and selective ETB antagonist. Larger substituents caused a decrease in both ETB activity and selectivity. A similar trend was observed by substitution at the 5-position of the N-(5-isoxazolyl)-2-thiophenesulfonamide ETA receptor antagonists. The para-tolyl group was again found to be optimal for the ETB activity and selectivity. The structural features that were found to be favorable for binding to the ETB receptor, that is, the presence of a linear, conjugated pi-system of definite shape and size, have been successfully incorporated into the design of ETB selective polycyclic aromatic sulfonamides antagonists.     

Combined Feedback and Noise Suppression in Hearing Aids

In this paper, solutions for combined feedback and noise suppression in hearing aids are developed. The techniques presented are based on the generalized sidelobe canceller (GSC) and adaptive feedback canceller (AFC), with a prediction error method (PEM) adaptation to avoid speech distortion. Two possible cascades of GSC-based noise reduction and AFC, namely an ldquoAFC firstrdquo and a ldquoGSC first,rdquo as well as a truly integrated solution that jointly suppresses feedback and noise are discussed. The integrated solution (called PEM-GFIC) achieves optimum synergies between noise and feedback suppression at the lowest computational cost. In addition, it cancels more feedback than the generalized echo and interference canceller, a joint solution for echo and noise suppression. In the cascaded solutions, the feedback and noise suppression filters are not always optimally exploited. For high input SNRs, ldquoAFC firstrdquo scheme generally may achieve better feedback cancellation because of its larger number of degrees of freedom. However, noise reduction by the GSC-stage seriously affects the feedback cancellation performance. At low SNRs, ldquoGSC firstrdquo generally achieves more feedback cancellation than PEM-GFIC at the expense of worse noise reduction. At high hearing aid gains and/or large SNRs, the noise reduction stage however negatively affects the performance of the feedback cancellation filter, resulting in a worse feedback and noise suppression compared to PEM-GFIC.     

Elevated inosine monophosphate levels in resting muscle of patients with stable chronic obstructive pulmonary disease

From January 1981 through October 1995, a total of 28 patients underwent surgery for metastatic lung tumors in our institute. A retrospective review and survival analysis of these patients are reported. There were 12 males and 16 females, with the mean age of 57 years. Of them, 20 patients had solitary lesions. Pulmonary metastasis was from the colon in 8 patients, from the breast in 5, from the stomach and the uterus in each 3, from the bladder, the rectum and the soft tissue in each 2, and from the kidney, the ovarium and the thyroid in each 1. A lobectomy was performed in 22 patients, 17 of whom were accompanied with mediastinal lymph node dissection (R2a). Partial resection without lymph node dissection was performed in 6 patients (R0). Overall 5-year survival was 24.7%. Four-year or over survivor were 4 patients who underwent a lobectomy with R2a. The patients undergoing lobectomy had a significantly better prognosis compared with patients with partial resection (p<0. 05). The patients with R2a had significantly less local recurrence than patients with R1 or R0 (p<0.05). We conclude that lobectomy with R2a is suitable treatment for metastatic lung cancer.     

Thoracic duct-cutaneous fistula in a patient with cirrhosis of the liver: successful treatment with a transjugular intrahepatic portosystemic shunt

Patients with cirrhosis of the liver have increased hepatic and gastrointestinal lymph flow that may contribute to the formation of ascites and pleural effusions. Increased lymph flow, which is due to postsinusoidal portal hypertension, causes a high rate of flow through the thoracic duct. Because of the high flow rates, disrupted lymphatic vessels in patients with cirrhosis of the liver may fail to close, a situation that results in chylous ascites, pleural effusions, or chylous fistulas. Chylous fistulas deplete proteins, fluid, and lymphocytes and thus lead to volume depletion and coagulopathy. Herein we describe an unusual case in which a high-output traumatic thoracic duct-cutaneous fistula developed in a patient with cirrhosis and led to volume depletion and coagulopathy. Correction of the portal hypertension with placement of a transjugular intrahepatic portosystemic shunt led to closure of the fistula and normalization of accompanying metabolic abnormalities.