PubMed Health⌕ Search

Biomedical subjects

D J Hamilton

Publications and source records attributed to D J Hamilton.

At least 19 recordsLinked to original sources
PubMed2006

[Diabetes and heart transplantation].

Diabetes is frequently encountered in patients presenting with end-stage heart failure to be listed for transplantation. While diabetes used to be a contra-indication for heart transplantation, careful preoperative evaluation and individualized postoperative medication lead to long-term outcome after heart transplantation equal to non-diabetic patients. About 1/3 of transplanted patients develop a post-transplant diabetes. Several risk factors have been identified leading to this condition. Mostly, post-transplant diabetes is of temporary nature. Several studies have shown no impact of diabetes on the incidence of rejection, malignancies, and transplant vasculopathy. However, glucose intolerance must be taken into consideration when planing immunosuppressive therapy since different medications have distinct impact on glucose metabolism after transplant. A multidisciplinary team allows for closely monitoring and treating patients with diabetes after heart transplant.

Diabetes Complications↗
PubMed1996

Properties of the endosomal-lysosomal system in the human central nervous system: disturbances mark most neurons in populations at risk to degenerate in Alzheimer's disease.

Specific antibodies and cytochemical markers combined with several imaging and morphometric techniques were used to characterize the endosomal-lysosomal system in mature neurons of the normal human central nervous system and to quantitate changes in its function in Alzheimer's disease. Compartments containing cathespin D (Cat D) and other acid hydrolases included a major subpopulation of mature lysosomes lacking mannose-6-phosphate receptors (MPR) and smaller populations of late endosomes (MPR-positive) and lipofuscin granules (MPR-negative). Antibodies to the pro-isoform of Cat D decorated perinuclear vacuolar compartments corresponding to late endosomes. Neurons and glia contained lysosomes with differing complements of acid hydrolases, implying different processing capabilities. Endosome/lysosome number per unit volume of cytoplasm was relatively well conserved within populations of normal neurons. By contrast, in morphometric analyses of Alzheimer's disease brains, 80-93% of pyramidal cells in the prefrontal cortex (laminae III or V) and hippocampus (CA2, CA3) displayed two- to eightfold higher numbers of hydrolase-positive vacuolar compartments than did corresponding cell populations in age-matched normal brains. Only 5-10% of cerebellar Purkinje cells, a less vulnerable population, showed the same statistically significant elevations. Most affected in these brain regions and in subcortical areas seemed otherwise normal by conventional histological staining and ultrastructural inspection. That both lysosomal and pro-Cat D- and MPR-positive endosomal compartments increased in number demonstrates that the endosomal-lysosomal system is activated markedly in vulnerable neuronal populations of Alzheimer's disease brains and implies that endocytosis or autophagy or both are accelerated persistently at an early stage of cellular compromise, greatly surpassing the degree of activity associated with normal aging. Early activation of the endosomal-lysosomal system represents a biological event potentially linking major etiological factors in Alzheimer's disease, including defective membrane proteins, apolipoprotein E function, and altered amyloid precursor protein processing.

Aged↗
PubMed1995

ANN compression of morphologically similar ECG complexes.

A compression algorithm for electrocardiogram signals is presented, based on an auto-associative neural network. Issues of weight and activation coding are considered, and compression performances of various network sizes are compared. A unique feature is the performance improvement achieved using DC level removal. A comparison with existing techniques is provided.

Algorithms↗
PubMed1994

Lysosomal abnormalities in degenerating neurons link neuronal compromise to senile plaque development in Alzheimer disease.

Antibodies to the lysosomal hydrolases, cathepsins B and D and beta-hexosaminidase A, revealed alterations of the endosomal-lysosomal system in neurons of the Alzheimer disease brain, which preceded evident degenerative changes and became marked as atrophy, neurofibrillary pathology, or chromatolysis developed. At the earliest stages of cell atrophy, hydrolase-positive lysosomes accumulated at the basal pole and then massively throughout the perikarya and proximal and proximal dendrites of affected pyramidal neurons in Alzheimer prefrontal cortex and hippocampus, far exceeding the changes of normal aging. Secondary lysosomes as well as tertiary residual bodies (lysosomes/lipofuscin) increased implying stimulated, autophagocytosis and lysosomal system activation. Less affected brain regions, such as the thalamus, displayed similar though less extensive alterations. Certain thalamic neurons exhibited a distinctive lysosome-related abnormality characterized by the presence of cell surface blebs of varying size and number filled with intense hydrolase immunoreactivity. At more advanced stages of degeneration in still intact neurons, hydrolase-positive lipofuscin, particularly in the form of abnormally large aggregates, nearly filled the cytoplasm. Similar lipofuscin aggregates were observed in abundance in the extracellular space following cell lysis and were usually associated with deposits of the beta-amyloid protein. Degenerating neurons and their processes were the major source of these aggregates within senile plaques which contained high concentrations of acid hydrolases. We have shown in previous studies that these lysosomal hydrolases in plaques are enzymatically-active. The persistence of lysosomal structures in the brain parenchyma after neurons have degenerated is a striking and potentially diagnostic feature of Alzheimer disease which has not been observed, to our knowledge, in other degenerative diseases. The lysosomal response in degenerating Alzheimer neurons represents a probable link between an early activation of the lysosomal system in at-risk, normal-appearing neurons and the end-stage contribution of lysosomes to senile plaque formation and emphasizes a slowly progressive disturbance of the lysosomal system throughout the development of Alzheimer disease.

Aged↗
PubMed1993

Underutilization of pneumococcal vaccine in nursing home in Washington State: report of a serotype-specific outbreak and a survey.

PURPOSE: To describe an outbreak of pneumococcal disease in a Washington state nursing home and to report a survey of pneumococcal vaccine utilization in Washington nursing homes. PATIENTS AND METHODS: Outbreak. Data were collected from nursing home residents' records. Nasopharyngeal cultures were obtained from residents and staff. Survey. Fifty-four randomly selected Washington nursing homes were surveyed about pneumococcal vaccine utilization and policies. RESULTS: Outbreak. Three confirmed and 4 possible cases of pneumococcal disease occurred over 9 days among 94 residents; 5 patients (71%) died. Cases were identified among 6 of 42 residents on 1 wing, compared with 1 of 52 on the other 2 wings (relative risk 7.4, 95% confidence interval 1.0, 398.5). Streptococcus pneumoniae serotype 9V was cultured from the blood of 3 confirmed case-patients and the nasopharynx of 2 of 73 residents. Only 7% of residents had received pneumococcal vaccine, including one case-patient who had received 14-valent vaccine without serotype 9V. Survey. Only 22% of residents were reported to have received pneumococcal vaccine; vaccination status was unknown for 66%. Physician discretion determined pneumococcal vaccination in 49 (91%) nursing homes; 9 (17%) had a written policy. Two major barriers to pneumococcal vaccination were cited: low priority among physicians (43%) and difficulty in determining residents' vaccine history (37%). CONCLUSIONS: A pneumococcal disease outbreak among undervaccinated nursing home residents probably resulted from person-to-person transmission. Pneumococcal vaccine appears to be underutilized in Washington state nursing homes.

Aged↗
PubMed1992

The lysosomal system in neurons. Involvement at multiple stages of Alzheimer's disease pathogenesis.

Disturbed lysosomal function may be implicated at several stages of Alzheimer's pathogenesis. Lysosomes and acid hydrolases accumulate in the majority of neocortical pyramidal neurons before typical degenerative changes can be detected, indicating that altered lysosome function is among the earliest markers of metabolic dysfunction in Alzheimer's disease. These early alterations could reflect accelerated membrane and protein turnover, defective lysosome or hydrolase function, abnormal lysosomal trafficking or any combination of these possibilities. Because APP is partly metabolized in lysosomes, early disturbances in lysosomal function could promote the production of abnormal and/or neurotoxic APP fragments within intact cells. Lysosomal abnormalities progressively worsen as neurons begin to degenerate. Based on existing literature on cell death, increased perturbation and instability of the lysosomal system may be expected to contribute to the atrophy and eventual lysis of the neuron. Finally, the release of hydrolase-filled lysosomes and lipofuscin aggregates from dying neurons accounts for the abundant deposition of enzymatically active acid hydrolases of all classes in the extracellular space--a phenomenon that may be unique to Alzheimer's disease. Acting on APP present in surrounding dystrophic neurites, cellular debris and astrocyte processes, dysregulated hydrolases may cleave APP in atypical sequential patterns, thereby generating self-aggregating protease-resistant APP fragments that can be only processed to beta-amyloid. Genetic mutations or posttranslational factors of APP should further enhance the generation of amyloidogenic fragments by a dysregulated lysosomal system. Given that very little, if any, beta-amyloid is detected intracellularly, yet extracellular beta-amyloid is very abundant, our data suggest that the final steps of APP processing and the generation of most beta-amyloid in the brain parenchyma occur extracellularly and may involve one or more lysosomal proteases.

Adolescent↗
PubMed1992

Detection of Chlamydia pneumoniae by polymerase chain reaction.

While criteria for serodiagnosis of Chlamydia pneumoniae infection are well established, isolation of the organism is often difficult. To increase detection of this organism, C. pneumoniae-specific sequences were identified to permit amplification of C. pneumoniae by polymerase chain reaction (PCR). A cloned C. pneumoniae 474-bp PstI fragment was shown by dot blot and Southern hybridization to differentiate C. pneumoniae from the other Chlamydia spp., react with all C. pneumoniae isolates tested, and not recognize DNA from normal throat flora or common respiratory tract agents. This cloned fragment was sequenced and primers for use in PCR were chosen on the bases of GenBank analysis, G + C ratio, and absence of secondary structure. All C. pneumoniae isolates tested were amplified by the HL-1-HR-1 primer pair or the HM-1-HR-1 primer pair, producing the expected 437- and 229-bp amplification products, respectively. None of the Chlamydia trachomatis serovars (B/TW-5/OT, C/TW-3/OT, D/UW-3/Cx, E/UW-5/Cx, F/UW-6/Cx, H/UW-4/Cx, I/UW-12/Ur, and L2/434/Bu), Chlamydia psittaci strains (Mn, 6BC, GPIC, FP, and OA), HeLa cells, or other organisms tested were amplified. Reaction conditions including MgCl2, oligonucleotides, and primer concentrations and temperature were optimized before application to clinical samples. Clinical specimens from patients from whom C. pneumoniae was isolated were also positive by PCR, while samples from patients with known C. trachomatis or C. psittaci infection were not amplified by PCR.

Base Sequence↗
PubMed1989

Effect of delay in processing on lysis-centrifugation blood culture results from marrow transplant patients.

The effect of delay in processing on results of lysis-centrifugation (LC; Isolator) blood cultures was assessed in 4,577 paired blood specimens. Blood specimens were obtained at all hours from 384 febrile marrow transplant patients with indwelling venous catheters and were processed by the LC technique and by a conventional two-bottle method. Most patients (84%) were receiving broad-spectrum antibiotics at the time of blood culture. Specimens were delivered to the laboratory, where Isolator tubes were held at 35 degrees C and processed in batches between 0700 and 1730 h daily. This procedure resulted in a delay beyond the manufacturer-suggested processing time of less than 8 h for 1,853 (42%) of the LC cultures. There was no overall difference in the recovery of organisms present in LC cultures processed after being held for 8 to 24 h compared with the conventional two-bottle method. LC methodology had shorter time to detection than the conventional method for detection of Candida spp. and Pseudomonas spp. (P less than 0.05). However, time to detection for Streptococcus spp. and members of the family Enterobacteriaceae, responsible for 16.3% of total isolates, was prolonged significantly by delay in processing when compared with the conventional two-bottle method (P less than 0.01). Results of this study support the recommendation of the manufacturer for processing of Isolator tubes within 8 h or less. Although one can safely delay processing beyond 8 h in terms of total recovery of organisms, such delays were associated with longer time to detection for certain important potentially pathogenic organisms which accounted for a sizeable proportion of blood culture isolates from marrow transplant patients.

Anti-Bacterial Agents↗
PubMed1988

Comparative in vitro activity of the new oral cephalosporin cefixime.

Cefixime was 8 to 10 times more active than cefaclor and augmentin against isolates of Escherichia coli, Klebsiella pneumoniae and Salmonella typhi, MIC90 values ranging from 0.06 to 0.25 micrograms/ml. However, none of these three drugs was particularly active against isolates of more resistant gram-negative bacilli such as Enterobacter, Serratia, Citrobacter, Acinetobacter, Providencia and Achromobacter spp. The lowest MIC values for gram-negative bacilli were seen with ciprofloxacin, except for isolates of Acinetobacter, where cotrimoxazole was the most active of the five drugs studied. Augmentin and ciprofloxacin exhibited the lowest MICs for isolates of streptococci and corynebacteria. Although cefixime may be among the most active oral beta-lactam drugs, it does not appear to be useful for treatment of infections caused by more resistant gram-negative bacilli.

Amoxicillin↗
PubMed1988

Evaluation of an immunofluorescent-antibody test for rapid identification of Pseudomonas aeruginosa in blood cultures.

An immunofluorescent-antibody test was developed for rapid detection of Pseudomonas aeruginosa in blood cultures. The test uses a murine monoclonal antibody specific for all strains of P. aeruginosa. In initial tests, bright uniform immunofluorescence signals were seen when each of the 17 international serotypes, as well as 14 additional isolates of P. aeruginosa, were examined. No immunofluorescent staining was observed when 37 other gram-negative and 15 gram-positive species were studied. In a clinical study, the assay was applied to broth smears of 86 gram-negative bacilli isolated from 74 bacteremic patients and 28 additional clinical isolates of Pseudomonas sp. and other oxidase-positive gram-negative bacilli recovered from various body sites. Smears were made directly from blood cultures which were positive for gram-negative bacilli by Gram staining. Eleven (15%) of 74 patients with gram-negative bacteremia had a positive test for P. aeruginosa. Including the results of these 11 isolates recovered in a prospective study and an additional 10 isolates from a retrospective study, we obtained a sensitivity and specificity of 100% (21 positive specimens and 103 negative specimens, respectively). These preliminary results suggest that this is a useful reagent for rapid presumptive identification of P. aeruginosa in blood cultures. With the immunofluorescent-antibody test, P. aeruginosa could be identified within 1 h of Gram stain evidence of gram-negative bacteremia.

Antibodies, Monoclonal↗
PubMed1987

Comparison of a novel trimethoprim-sulfamethoxazole-containing medium (XT80) with kanamycin agar for isolation of antibiotic-resistant organisms from stool and rectal cultures of marrow transplant patients.

A new medium (XT80) containing trimethoprim-sulfamethoxazole (TMP-SMZ) was characterized and compared with kanamycin-containing tryptic soy agar (KA) for the recovery of multiply resistant organisms (MRO) in rectal and stool cultures. Cultures from 151 patients hospitalized for bone marrow transplantation were screened for MRO. A total of 366 MRO were recovered from 702 cultures on 94 patients during a 6-month period. XT80 detected more gram-negative bacilli and Corynebacterium spp. than KA. Detection of Staphylococcus spp. was equivalent for the two media. Multiple-antibiotic resistance, defined as resistance to three or more classes of antibiotics, was confirmed by standard agar disk diffusion susceptibility testing. Growth on XT80 correctly identified heteroresistant strains of methicillin-resistant Staphylococcus spp. XT80 more rapidly detected thymidine-dependent mutants of Staphylococcus spp. and members of the family Enterobacteriaceae. Lipophilic Corynebacterium spp., including Corynebacterium group JK, also were more readily detected with XT80. TMP-SMZ given as prophylaxis against Pneumocystis carinii infection exerts a selective pressure on organisms that colonize immunocompromised patients and appears to select for colonization with MRO. Colonization with MRO preceded infection for 94% of 36 patients who developed bacteremia. XT80 is a useful screening tool; growth on this medium correlates closely with resistance to TMP-SMZ and is as accurate a predictor as KA for the carriage of MRO.

Anti-Bacterial Agents↗
PubMed1983

Anomalous drainage of the right superior vena cava into the left atrium.

A 22 year old man with asymptomatic hypoxemia was found to have a large right to left shunt due to a rare congenital anomaly: total drainage of the right superior vena cava into the left atrium. The anomaly was first suspected after radionuclide angiocardiography was performed using technetium-99m macroaggregated albumin and was confirmed by cardiac catheterization. Contrast echocardiographic and surgical findings are discussed. Other reports on this anomaly are reviewed.

Adult↗
PubMed1980

Gas chromatographic measurement of volatility of herbicide esters.

The vapour pressures of eleven herbicide esters were calculated from gas chromatographic measurement of relative retention volumes (dibutyl phthalate = 1) on a non-polar SE-30 column. Measurements were made at temperatures from 72 to 182 degrees C, but by assuming that the ratio of the latent heat of vaporization of the ester to that of dibutyl phthalate was independent of temperature, values for vapour pressure could be extrapolated to 25 degrees C. Vapour pressures at 25 degrees C ranged from 2.5.10(-4) mmHg for 2,4-D ethyl ester to 1.9.10(-7) mm Hg for picloram isoocytly ester.

Chromatography, Gas↗