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Biomedical subjects

J Huffman

Publications and source records attributed to J Huffman.

At least 19 recordsLinked to original sources

Performance analysis of a new semiorthogonal spline wavelet compression algorithm for tonal medical images.

Lossy image compression is thought to be a necessity as radiology moves toward a filmless environment. Compression algorithms based on the discrete cosine transform (DCT) are limited due to the infinite support of the cosine basis function. Wavelets, basis functions that have compact or nearly compact support, are mathematically better suited for decorrelating medical image data. A lossy compression algorithm based on semiorthogonal cubic spline wavelets has been implemented and tested on six different image modalities (magnetic resonance, x-ray computed tomography, single photon emission tomography, digital fluoroscopy, computed radiography, and ultrasound). The fidelity of the reconstructed wavelet images was compared to images compressed with a DCT algorithm for compression ratios of up to 40:1. The wavelet algorithm was found to have generally lower average error metrics and higher peak-signal-to-noise ratios than the DCT algorithm.

Algorithms↗

Antiviral properties of a series of 1,6-naphthyridine and 7, 8-dihydroisoquinoline derivatives exhibiting potent activity against human cytomegalovirus.

A series of 1,6-naphthyridine (L. Chan, H. Jin, T. Stefanac, J. F. Lavallee, G. Falardeau, W. Wang, J. Bedard, S. May, and L. Yuen, J. Med. Chem. 42:3023-3025, 1999) and isoquinoline (L. Chan, H. Jin, T. Stefanac, W. Wang, J. F. Lavallee, J. Bedard, and S. May, Bioorg. Med. Chem. Lett. 9:2583-2586, 1999) analogues exhibiting a high level of anti-human cytomegalovirus (HCMV) activity were investigated in a series of studies aimed at better understanding the mechanism of action of some representatives of this class of compounds. In vitro antiviral profiling revealed that these compounds were active against a narrow spectrum of viruses, essentially the human herpesviruses and type 2 rhinovirus. In HCMV assays, a 39- to 223-fold lower 50% inhibitory concentration was obtained for compound A1 than for ganciclovir against strains AD 169 and Towne. In addition, ganciclovir, foscarnet, cidofovir, and BDCRB (2-bromo-5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole)-resistant HCMV strains remained susceptible to 1,6-naphthyridines and 7, 8-dihydroisoquinolines tested in this study, supporting the view that a novel mechanism of action could be involved. Drug combination studies showed a small but significant synergistic antiviral effect between compound B2 and ganciclovir. Cytotoxicity profiling of representative compounds under various cell growth conditions indicated a generally similar cytotoxic effect, relative to ganciclovir, in log-phase growing cells. However, in stationary cells, a relatively higher level of toxicity was observed than that for control compound. Effect of time of drug addition showed that the anti-HCMV activity of compound A1, ganciclovir, and cidofovir was lost at approximately the same time (72 h postinfection), indicating that the compound was affecting events at the early and late stage of virus replication. This interpretation is also supported by reduction of de novo synthesis of pp65 tegument protein and lack of any effect of the compound on viral adsorption. A reduction of the HCMV enhancer-promoter-directed luciferase expression was also observed in a stably transfected cell line when compound A1 was present at relatively high concentrations.

Antiviral Agents↗

Measuring quality in hospitals: is there a difference between for-profits and not-for-profits?

Health care professionals agree that by measuring quality, improvements can be made in care delivery. There are measurable differences between not-for-profit and for-profit hospitals, both in public perception and care outcomes. The ability by consumers, insurers and providers to easily access quality data will drive the health care industry to take a quality focus in their daily business. Quality providers with measurable results will gain a larger share of health care dollars and consumer trust. Physicians will choose to partner with the quality leaders and will refine their practices as part of the quality evolution.

Diagnosis-Related Groups↗

Comparative study of the anti-human cytomegalovirus activities and toxicities of a tetrahydrofuran phosphonate analogue of guanosine and cidofovir.

Cidofovir is the first nucleoside monophosphate analogue currently being used for the treatment of human cytomegalovirus (HCMV) retinitis in individuals with AIDS. Unfortunately, the period of therapy with the use of this compound may be limited due to the possible emergence of serious irreversible nephrotoxic effects. New drugs with improved toxicity profiles are needed. The goal of this study was to investigate the anticytomegaloviral properties and drug-induced toxicity of a novel phosphonate analogue, namely, (-)-2-(R)-dihydroxyphosphinoyl-5-(S)-(guanin-9'-yl-methyl) tetrahydrofuran (compound 1), in comparison with those of cidofovir. The inhibitory activities of both compounds on HCMV propagation in vitro were similar against the AD 169 and Towne strains, with 50% inhibitory concentrations ranging from 0.02 to 0.17 microgram/ml for cidofovir and < 0.05 to 0.09 microgram/ml for compound 1. A clinical HCMV isolate that was resistant to ganciclovir and that had a known mutation within the UL54 DNA polymerase gene and a cidofovir-resistant laboratory strain derived from strain AD 169 remained sensitive to compound 1, whereas their susceptibilities to ganciclovir and cidofovir were reduced by 33- and 10-fold, respectively. Both compound 1 and cidofovir exhibited equal potencies in an experimentally induced murine cytomegalovirus (MCMV) infection in mice, with a prevention or prolongation of mean day to death at dosages of 1.0, 3.2, and 10.0 mg/kg of body weight/day. In cytotoxicity experiments, compound 1 was found to be generally more toxic than cidofovir in cell lines Hs68, HFF, and 3T3-L1 (which are permissive for HCMV or MCMV replication) but less toxic than cidofovir in MRC-5 cells (which are permissive for HCMV replication). Drug-induced toxic side effects were noticed for both compounds in rats and guinea pigs in a 5-day repeated-dose study. In guinea pigs, a greater weight loss was noticed with cidofovir than with compound 1 at dosages of 3.0 and 10.0 mg/kg/day. An opposite effect was detected in rats, which were treated with the compounds at relatively high dosages (up to 100 mg/kg/day). Compound 1 and cidofovir were nephrotoxic in both rats and guinea pigs, with the epithelium lining the proximal convoluted tubules in the renal cortex being the primary target site. The incidence and the severity of the lesions were found to be dose dependent. The lesions observed were characterized by cytoplasm degeneration and nuclear modifications such as karyomegaly, the presence of pseudoinclusions, apoptosis, and degenerative changes. In the guinea pig model, a greater incidence and severity of lesions were observed for cidofovir than for compound 1 (P < 0.001) with a drug regimen of 10 mg/kg/day.

Animals↗

Five-year follow-up for adverse outcomes in males with at least minimally positive angiograms: importance of "denial" in assessing psychosocial risk factors.

The purpose of this study was to test the role of "denial" (spouse/friend minus self-ratings on parallel versions of the same questionnaire) in diluting the predictive value of emotional distress for cardiac events (deaths, new MIs, and/or revascularizations). One hundred forty-four men with no history of prior revascularization who had at least minimally positive diagnostic coronary angiograms, and someone they selected as "someone who knows you well," completed parallel versions of the Ketterer Stress Symptom Frequency Checklist (KSSFC). They were followed up by phone an average of 59.7 months after recruitment. Length of follow-up, baseline cardiac risk factors, and a number of baseline-obtained psychosocial risk factors were tested as prospective predictors of combined events (death by any cause, new MIs, and/or revascularizations) and current anginal frequency. Only spouse/friend observed anxiety on the KSSFC predicted current anginal frequency (p = 0.001). On the self-report version of the KSSFC, patients with one or more events reported less anger (p = 0.031), depression (p = 0.008), and anxiety (p = 0.003). These results may be attributable to "denial" because there were no differences in spouse/friend ratings, and difference scores (spouse/friend minus patient) on the KSSFC scales, particularly anger, were also related to events: AIAI (p = 0.002); depression (p = 0.063); and anxiety (p = 0.010). Denial may be a major limiting factor in accurately assessing emotional distress in cardiac populations, and may help account for a number of the previous findings.

Angiography↗

Oligonucleotide biological activity: relationship to the cell cycle and nuclear transport.

Previous studies suggest that oligodeoxynucleotide (ODN) cellular uptake is cell cycle-dependent which may have important implications in cancer cell targeting. To further our understanding of ODN transport and activity, this study examines the relationships between the cell cycle, ODN cellular uptake, intracellular transport, and activity. An antisense c-myc ODN 21-mer was used to study ODN cellular uptake in Rauscher erythroleukemia cells synchronized by either chemical methods or flow cytometry. ODN uptake was examined using subcellular fractionation and confocal fluorescence microscopy. Western blot analysis was used to measure ODN-mediated decreases in c-myc protein levels. Intracellular ODN distribution and extent of uptake was influenced by the phase of the cell cycle, but the mechanism of uptake was not. The relative activity of the antisense ODN was positively correlated to ODN distribution to the cytosol, but negatively correlated to total cellular uptake. Although ODN total cellular uptake is positively influenced by the cell cycle, retention of the ODN in the cytosol (presumably extra-vesicularly) appeared to be relevant in determining the activity of an antisense ODN. Novel methods to target cytosol-acting drugs to the cytoplasm may therefore be warranted.

Biological Transport↗

Advances in gynecologic care: the effect on an HMO.

The introduction of four endoscopic surgical procedures into the gynecology department at Fallon Community Health Plan (FCHP) is discussed. The use of these endoscopic procedures reduced average length of stay (ALOS), hospital days/1OOO members, and rate of postoperative complications compared to the open (laparotomy) method. These minimally invasive procedures are popular with patients and physicians, and their use has the potential to decrease an HMO's overall operational costs.

Cost Savings↗

Analysis of circulating phagocyte activity measured by whole blood luminescence: correlations with clinical status.

The present study was undertaken to determine if measurement and analysis of phagocyte function are useful for diagnosis and staging of infection. Circulating phagocyte activity was measured in healthy volunteers and sequentially in patients with acute infections of different types and severity, including those with diabetes mellitus or human immunodeficiency virus (HIV) infection. Using an automated luminescence system, these phagocyte functions were measured in whole blood: basal and phorbol 12-myristate 13-acetate (PMA)-stimulated oxidase activity, basal and PMA-stimulated simple dioxygenation (e.g., oxidase-driven haloperoxidase activity), and circulating and primed opsonin receptor-dependent dioxygenation. Multiple discriminant analysis of these data showed significant differences between healthy controls, diabetic patients, HIV-positive subjects, and patients with pneumonia or sepsis syndromes. Longitudinally, circulating phagocyte function correlated with clinical condition, severity of infection, and outcome. This methodology provides rapid, objective, and sensitive diagnostic and monitoring information for patients with infections.

Acquired Immunodeficiency Syndrome↗

The role of radical cystectomy in the management of high grade superficial bladder cancer (PA, P1, PIS and P2)

Between January 1979 and 1987, 411 consecutive patients were considered candidates for bilateral pelvic iliac lymph node dissection and radical cystectomy for the management of bladder cancer. From this group 160 were identified as having pathological stage P2 or less disease, including 11 who also had positive nodes. The 5-year actuarial survival rate for the respective stages at 95% confidence limits was 100% for stage P0/A, 80% for stage P1, 78% for stage P1 with stage PIS, 85% for pure stage PIS, 76% for stage P2 and 87% for stage P2 with stage PIS. Additionally, we identified a group of patients with stage P2 transitional cell carcinoma who were at significant risk for development of metastatic disease. Of 46 patients with stage P2 transitional cell carcinoma 18 had vascular space invasion resulting in 6 of 18 cancer-related deaths (33%). Our study demonstrates that radical cystectomy has been highly effective in curing patients with high grade superficial disease, including those with superficially invasive disease associated with nodal metastases.

Carcinoma, Transitional Cell↗

Colorectal cancer mortality and incidence in Campbell County, Kentucky.

Previous publications have reported an unusually high colon cancer mortality rate for several Kentucky counties. We investigated these high rates by examining incidence of colorectal cancer in one county with a high mortality. The objective was to determine whether the incidence of colorectal cancer was as high as mortality rates indicated and, if so, to look for possible etiologic factors for the high rates. We found the incidence of colon cancer to be significantly higher in Campbell County than expected. While we expected 162 cases of colon cancer, we actually observed 192 (P less than .01). The number of rectal cancers was no higher than expected (52 expected and 62 observed), in agreement with previously reported mortality figures. A geographic plot of cases by home residence showed a significantly higher rate of colon cancer for urban county regions than for rural regions. In fact, the population of rural Campbell County had a colon cancer rate significantly lower than either the county rate or the national rate. Several factors were analyzed to explain these rate differences. The only consistently associated factor was source of residential drinking water.

Adenocarcinoma↗

Endoscopic ureteropyelostomy: opening the obliterated ureteropelvic junction with nephroscopy and flexible ureteropyeloscopy.

Endoscopic re-establishment of a totally obstructed ureteropelvic junction was accomplished in 2 patients. The combined use of rigid percutaneous nephroscopy and flexible ureteropyeloscopy provided full visualization of the obliterated segment, and allowed accurate electroincision into the ureter and placement of a wire and catheter into the lumen. This technique demonstrates the potential therapeutic applications of flexible ureteropyeloscopy and should be considered for the initial treatment of the obliterated ureteropelvic junction.

Aged↗

Monitoring intravesical bacillus Calmette-Guerin treatment of bladder carcinoma with flow cytometry.

Flow cytometry of bladder irrigation specimens was studied in 22 patients with low stage bladder carcinoma who were treated by transurethral resection of visible tumor followed in 3 to 5 weeks by a course of intravesical bacillus Calmette-Guerin. The most informative examinations were just before the first bacillus Calmette-Guerin treatment, 6 weeks after completing a 6-week course of treatment (3 months) and at 9 months. Of the patients 10 had recurrent tumors after therapy; recurrence was anticipated correctly by flow cytometry at the 12-week followup examination in 6 of the 10 patients and suspected in another. Of 12 patients who remained clinically free of disease for a minimum of 15 months after bacillus Calmette-Guerin therapy flow cytometry identified correctly 7 at 12 weeks, while 1 had a partial response and the remaining 4 reverted to a negative status at 9 months. Of interest, only 4 of the 22 patients were free of disease by flow cytometry at the start of bacillus Calmette-Guerin treatment despite attempted ablation of the tumor by transurethral resection, suggesting that intravesical administration of bacillus Calmette-Guerin destroys existing carcinoma in situ in some cases.

BCG Vaccine↗

Acute abdominal pain caused by spontaneous perforation of the urinary bladder.

Patients with acute spontaneous bladder perforation have the symptoms and signs of an acute condition of the abdomen which, as a surgical emergency, requires prompt operative treatment. Bladder perforation should be suspected as the cause of this abdominal catastrophe if the history and findings indicate a urinary tract disorder. If the surgeon knows preoperatively that the bladder is perforated, he is able to plan and perform the appropriate surgical procedure with greater dispatch and certainty. The correct preoperative diagnosis should be made more frequently if the primary care physician develops a greater awareness of the possibility of spontaneous bladder perforation as the cause of an acute condition of the abdomen. With earlier diagnosis and earlier surgical treatment, the present reported mortality of 25 per cent for those patients with this condition is likely to be reduced.

Abdomen, Acute↗

Appearance of a partial nephrogram with an absent kidney.

A case is reported of a 16-year-old female who sustained a gunshot wound to the left upper abdomen. Early opacification of a structure in the left upper quadrant on an excretory urogram was suggestive of a nephrogram. The left kidney was absent at operation. The diagnostic limitations of excretory urography in the trauma patient and the alternative diagnostic techniques, radionuclide scanning, arteriography, or tomography, or possibly operative intervention, are recommended. Although not found in our patients, a thorough search for an ectopic kidney should be made.

Abdominal Injuries↗