ABSTRACT
Altered synaptic function is considered one of the first features of Alzheimer disease (AD). Currently, no treatment is available to prevent the dysfunction of excitatory synapses in AD. Identification of the key modulators of synaptopathy is of particular significance in the treatment of AD. We here characterized the pathways leading to synaptopathy in TgCRND8 mice and showed that c-Jun N-terminal kinase (JNK) is activated at the spine prior to the onset of cognitive impairment. The specific inhibition of JNK, with its specific inhibiting peptide D-JNKI1, prevented synaptic dysfunction in TgCRND8 mice. D-JNKI1 avoided both the loss of postsynaptic proteins and glutamate receptors from the postsynaptic density and the reduction in size of excitatory synapses, reverting their dysfunction. This set of data reveals that JNK is a key signaling pathway in AD synaptic injury and that its specific inhibition offers an innovative therapeutic strategy to prevent spine degeneration in AD.
Subject(s)
Alzheimer Disease/enzymology , JNK Mitogen-Activated Protein Kinases/metabolism , Synapses/enzymology , Alzheimer Disease/drug therapy , Alzheimer Disease/genetics , Animals , Disease Models, Animal , Female , Humans , JNK Mitogen-Activated Protein Kinases/antagonists & inhibitors , JNK Mitogen-Activated Protein Kinases/genetics , Male , Mice , Mice, Transgenic , Peptides/administration & dosage , Signal TransductionABSTRACT
Cough is considered an early sign of many respiratory diseases. Recently, there has been increased interest in measuring, analyzing, and characterizing the acoustical properties of a cough. In most cases the main focus of those studies was to distinguish between involuntary coughs and ambient sounds over a specified time period. The objective of this study was to develop a system to measure high fidelity voluntary cough sounds to detect lung diseases. To further augment the analysis capability of the system, a non-invasive flow measurement was also incorporated into the design. One of the main design considerations was to increase the fidelity of the recorded sound characteristics by increasing the signal to noise ratio of cough sounds and to minimize acoustical reflections from the environment. To accomplish this goal, a system was designed with a mouthpiece connected to a cylindrical tube. A microphone was attached near the mouthpiece so that its diaphragm was tangent to the inner surface of the cylinder. A pneumotach at the end of the tube measured the airflow generated by the cough. The system was terminated with an exponential horn to minimize sound reflections. Custom software was developed to read, process, display, record, and analyze cough sound and airflow characteristics. The system was optimized by comparing acoustical reflections and total signal to background noise ratios across different designs. Cough measurements were also collected from volunteer subjects to assess the viability of the system. Results indicate that analysis of cough characteristics has the potential to detect lung disease.
Subject(s)
Auscultation/instrumentation , Cough/diagnosis , Cough/physiopathology , Diagnosis, Computer-Assisted/instrumentation , Signal Processing, Computer-Assisted/instrumentation , Sound Spectrography/instrumentation , Adult , Aged , Equipment Design , Equipment Failure Analysis , Female , Humans , Male , Middle Aged , Reproducibility of Results , Sensitivity and SpecificityABSTRACT
BACKGROUND: Clinical trials of risperidone, a recently approved novel antipsychotic, included elderly healthy patients, but more data are needed on the effects of risperidone in this population, especially those with comorbid medical illnesses. METHOD: Risperidone was used to treat 11 elderly hospitalized patients between 61 and 79 years of age who manifested signs of psychoses related to schizophrenia, schizoaffective disorder, bipolar disorder, or senile dementia. All patients had been treated previously with classic antipsychotics. Response was assessed by clinical observation of the patients' behavior. RESULTS: Eight patients responded to treatment, 1 did not respond, and 2 had treatment discontinued because of hypotension or dizziness. Positive and negative symptoms decreased markedly in 7 of the responding patients. Four patients had preexisting extrapyramidal symptoms (EPS) and symptoms of tardive dyskinesia that also decreased in response to risperidone treatment. In addition, 4 patients were able to discontinue anti-parkinsonian medications, and 2 were able to discontinue antihypertensive medications. Side effects related to blockade of dopamine, histamine, and serotonin were negligible. No adverse consequences occurred when electroconvulsive therapy, carbamazepine, or lithium was given concurrently. CONCLUSION: The reduction of both positive and negative symptoms of schizophrenia and the lack of significant EPS, tardive dyskinesia, sedation, and anticholinergic side effects indicate that risperidone is a safe and effective medication for the elderly.
Subject(s)
Psychotic Disorders/drug therapy , Risperidone/therapeutic use , Aged , Bipolar Disorder/drug therapy , Chronic Disease , Comorbidity , Dementia/drug therapy , Female , Hospitalization , Humans , Hypotension/chemically induced , Male , Middle Aged , Risperidone/adverse effects , Schizophrenia/drug therapy , Treatment OutcomeABSTRACT
Liver transplantation is an effective therapy for end stage liver disease. Nevertheless in many areas of the world organ availability remains a major problem. We report here the success of the first living-related liver transplantation in Africa. The left lateral lobe of the mother was transplanted orthotopically to her 6 year old child suffering from liver cirrhosis complicating glycogen storage disease. The social and medical problems encountered are discussed. Living-related liver transplantation is a viable option in countries where cadaveric organ donation is either illegal or socially unacceptable.
Subject(s)
Liver Transplantation/methods , Tissue Donors , Adult , Child , Egypt , Female , Glycogen Storage Disease/complications , Glycogen Storage Disease/surgery , Hepatectomy/methods , Humans , Liver Cirrhosis/etiology , Liver Cirrhosis/surgery , Male , Postoperative CareABSTRACT
False aneuploidy was detected on flow cytometric DNA analysis of paraffin embedded axillary lymph nodes negative for tumor. It was hypothesized that "clearing" of axillary fat in Carnoy's solution to facilitate lymph node dissection might be responsible for false aneuploidy. Various tissues fixed overnight in Carnoy's were compared to formalin fixed paraffin embedded controls. Under these conditions no false aneuploid peaks were detected, but Carnoy's fixation did shift the G0/G1 histogram peak to the left, increase the G0/G1 CV and increase the S phase fraction relative to formalin fixed controls. It was then hypothesized that partial fixation of nodes in Carnoy's followed by formalin fixation might result in false aneuploid peaks. Twenty-two lymph nodes were partially fixed in Carnoy's for periods ranging from 5 to 60 min followed by complete fixation in formalin. Seven of these nodes did show false aneuploid peaks. By contrast, no aneuploidy was detected in formalin fixed controls. It was concluded that tissues in contact with Carnoy's solution may be a source of false aneuploidy and/or false elevation of S phase fraction. This reinforces the need for matched negative tissue controls for DNA analysis of paraffin embedded specimens whenever possible.
Subject(s)
Acetates/pharmacology , Acetic Acid , Aneuploidy , Chloroform/pharmacology , DNA/analysis , Ethanol/pharmacology , Flow Cytometry/methods , DNA/genetics , Fixatives/pharmacology , G1 Phase , Humans , Lymph Nodes/chemistry , Lymph Nodes/cytology , Lymph Nodes/ultrastructure , Palatine Tonsil/chemistry , Palatine Tonsil/cytology , Palatine Tonsil/drug effects , Paraffin Embedding , Resting Phase, Cell Cycle , S Phase , Spleen/chemistry , Spleen/cytology , Spleen/ultrastructureABSTRACT
PIP: The author examines the changes in life expectancy during the period 1970-1979 in Kuwait. Causes of death and age and sex differentials in life expectancy at birth are presented. Data are from official Kuwaiti sources.^ieng
Subject(s)
Age Factors , Cause of Death , Life Expectancy , Sex Factors , Asia , Asia, Western , Demography , Developing Countries , Kuwait , Longevity , Middle East , Mortality , Population , Population Characteristics , Population DynamicsABSTRACT
PIP: Abaza presents abridged Kuwaiti life tables to aid in estimating the future need for Kuwaiti social security and old age pensions. He uses the Chiang method of constructing Kuwaiti mortality rates and presents them in graphs and tables. According to these tables, the life expectancy at birth for 1965-1970 was 61.75 years for Kuwaiti males and 61.11 years for females. During 1975-1980, life expectancy rose to 66.39 years for males and 71.99 years for females. The possibility of dying is high in infancy, falls to a minimum from ages 10-14, rises slowly toward middle life, and rises rapidly with increasing age. Abaza links the high infant mortality with the low educational level of Kuwaiti mothers and the practice of allowing uneducated domestic servants to feed and care for Kuwaiti children. He also feels that the presence of servants may contribute to a mother's uncontrolled fertility and subsequent short birth intervals, leading ultimately to higher infant mortality. Abaza speculates that the large number of Bedouins who have higher than average fertility and mortality rates may be responsible for the high overall Kuwaiti infant mortality rate. It is noted that mortality is lower for females than males at almost all ages; this is attributed to greater male exposure to hazardous environments, accidents, and violence, and to female genetic superiority.^ieng
