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Biomedical subjects

B L Johnson

Publications and source records attributed to B L Johnson.

At least 37 records · Page 2Linked to original sources
PubMed1998

Kenny-Caffey syndrome and microorchidism.

We report on two adolescent boys with Kenny-Caffey syndrome and microorchidism. The first patient had elevated levels of serum follicle-stimulating hormone, but normal levels of luteinizing hormone and testosterone. There was no evidence of a microdeletion of the Y chromosome. The second patient had Leydig cell hyperplasia with normal seminiferous tubules and spermatogenesis, and normal pituitary histologic findings at autopsy. The presence of microorchidism in these patients confirms the previous observations and suggests subfertility, but does not fully clarify the pathogenesis.

Abnormalities, Multiple↗
PubMed1998

A model of wound healing in chronically radiation-damaged rat skin.

The aim of this investigation was to develop a model for studying the chronic effects of radiation on wound healing in the rat. Six months after rats received a single radiation exposure of 20 Gy, a random-pattern dorsal skin flap was elevated. Two weeks after the flap was elevated, irradiated animals showed diminished scar formation and wound breaking strength, as compared with controls (P < 0.05). The effect of hyperbaric oxygen treatment was investigated in some rats who received 20 sessions at 2.4 atmospheres absolute for 90 min daily, 5 days per week, prior to flap elevation and 10 sessions after creation of the flap. Treated animals showed a trend toward improvements in wound breaking strength and scar formation (P = 0.06). A reproducible model of chronic radiation damage in the rat was established. Further studies involving investigations at times more that 2 weeks post-wounding are needed.

Animals↗
PubMed1998

Potent cyclic urea HIV protease inhibitors with 3-aminoindazole P2/P2' groups.

Cyclic ureas containing 3-aminoindazole P2/P2' groups are extremely potent inhibitors of HIV protease. The parent 3-aminoindazole 6 showed a Ki < 0.01 nM but poor translation of enzyme activity to antiviral activity was observed. A series of 3-alkylaminoindazoles revealed that translation improved with increasing lipophilicity. An X-ray crystal structure of 6 bound to HIV protease was obtained.

Crystallography, X-Ray↗
PubMed1998

Design and selection of DMP 850 and DMP 851: the next generation of cyclic urea HIV protease inhibitors.

BACKGROUND: Recent clinical trials have demonstrated that HIV protease inhibitors are useful in the treatment of AIDS. It is necessary, however, to use HIV protease inhibitors in combination with other antiviral agents to inhibit the development of resistance. The daunting ability of the virus to rapidly generate resistant mutants suggests that there is an ongoing need for new HIV protease inhibitors with superior pharmacokinetic and efficacy profiles. In our attempts to design and select improved cyclic urea HIV protease inhibitors, we have simultaneously optimized potency, resistance profile, protein binding and oral bioavailability. RESULTS: We have discovered that nonsymmetrical cyclic ureas containing a 3-aminoindazole P2 group are potent inhibitors of HIV protease with excellent oral bioavailability. Furthermore, the 3-aminoindazole group forms four hydrogen bonds with the enzyme and imparts a good resistance profile. The nonsymmetrical 3-aminoindazoles DMP 850 and DMP 851 were selected as our next generation of cyclic urea HIV protease inhibitors because they achieve 8 h trough blood levels in dog, with a 10 mg/kg dose, at or above the protein-binding-adjusted IC90 value for the worst single mutant--that containing the Ile84-->Val mutation. CONCLUSIONS: In selecting our next generation of cyclic urea HIV protease inhibitors, we established a rigorous set of criteria designed to maximize chances for a sustained antiviral effect in HIV-infected individuals. As DMP 850 and DMP 851 provide plasma levels of free drug that are sufficient to inhibit wild-type HIV and several mutant forms of HIV, they could show improved ability to decrease viral load for clinically significant time periods. The ultimate success of DMP 850 and DMP 851 in clinical trials might depend on achieving or exceeding the oral bioavailability seen in dog.

Animals↗
PubMed1998

Trichophytic granuloma of the vulva.

Fungal infections causing deep tissue involvement are known as trichophytic granulomas. We describe an unusual case of trichophytic granuloma presenting in the vulva of a 39-year-old woman.

Adult↗
PubMed1998

A new, non-destructive method for analysis of clinical samples with FT-IR microspectroscopy. Breast cancer tissue as an example.

A new method for infrared analysis of tissues and cells is presented. The method is based on Fourier transform infrared microspectroscopy coupled with attenuated total reflectance. The technique allows spectroscopic measurements on the same samples used by pathologists for histopathological evaluation, e.g. stained samples on plain glass slides. Since the same specimen can be used as for histopathology, the method does not require sample preparation or modification. Significantly, the sample is not damaged. Glass absorbs in the infrared and thus has not been used previously in infrared analysis of tissues and cells. Conventional infrared techniques utilize expensive substrates, such as BaF2 windows and gold coated slides which do not absorb infrared radiation. However, these measurements require special preparation and result in the destruction of the sample. Breast cancer tissues were examined to demonstrate the feasibility and reproducibility of the new method. Linear discriminant analysis was used to discriminate and classify three types of cells: benign, atypical hyperplasia and malignant. It was demonstrated that benign vs. malignant cells were discriminated with 100% accuracy, benign vs. atypical hyperplasia were discriminated with 100% accuracy and malignant vs. atypical hyperplasia were discriminated with an accuracy of 90% and higher.

Breast Neoplasms↗
PubMed1997

Epidemiology of sepsis syndrome in 8 academic medical centers.

CONTEXT: Sepsis syndrome is a leading cause of mortality in hospitalized patients. However, few studies have described the epidemiology of sepsis syndrome in a hospitalwide population. OBJECTIVE: To describe the epidemiology of sepsis syndrome in the tertiary care hospital setting. DESIGN: Prospective, multi-institutional, observational study including 5-month follow-up. SETTING: Eight academic tertiary care centers. METHODS: Each center monitored a weighted random sample of intensive care unit (ICU) patients, non-ICU patients who had blood cultures drawn, and all patients who received a novel therapeutic agent or who died in an emergency department or ICU. Sepsis syndrome was defined as the presence of either a positive blood culture or the combination of fever, tachypnea, tachycardia, clinically suspected infection, and any 1 of 7 confirmatory criteria. Estimates of total cases expected annually were extrapolated from the number of cases, the period of observation, and the sampling fraction. RESULTS: From January 4, 1993, to April 2, 1994, 12759 patients were monitored and 1342 episodes of sepsis syndrome were documented. The extrapolated, weighted estimate of hospitalwide incidence (mean+/-95% confidence limit) of sepsis syndrome was 2.0+/-0.16 cases per 100 admissions, or 2.8+/-0.17 per 1000 patient-days. The unadjusted attack rate for sepsis syndrome between individual centers differed by as much as 3-fold, but after adjustment for institutional differences in organ transplant populations, variation from the expected number of cases was reduced to 2-fold and was not statistically significant overall. Patients in ICUs accounted for 59% of total extrapolated cases, non-ICU patients with positive blood cultures for 11%, and non-ICU patients with negative blood cultures for 30%. Septic shock was present at onset of sepsis syndrome in 25% of patients. Bloodstream infection was documented in 28%, with gram-positive organisms being the most frequent isolates. Mortality was 34% at 28 days and 45% at 5 months. CONCLUSIONS: Sepsis syndrome is common in academic hospitals, although the overall rates vary considerably with the patient population. A substantial fraction of cases occur outside ICUs. An understanding of the hospitalwide epidemiology of sepsis syndrome is vital for rational planning and treatment of hospitalized patients with sepsis syndrome, especially as new and expensive therapeutic agents become available.

Adult↗
PubMed1997

The Triennial International Symposium on Neurobehavioral Methods: the history and hope.

In 1982 in Milan, Italy, a series of triennial international symposia on neurobehavioral methods and their application commenced. Five of these symposia have been conducted. This paper reviews the origin of this neurobehavioral symposium and recounts the key findings and observations produced during each. In particular, the commitment of the symposium's organizers to meeting the needs of developing countries is discussed. An examination of the five symposia found that more than 250 papers have been published as proceedings. Furthermore, the symposia have maintained the original intent to assist developing countries. The symposium continues to emphasize the need to relate basic mechanisms of neurotoxicity to various neurobehavioral test batteries and methods.

Behavior↗
PubMed1997

Natural history of infrainguinal vein graft stenosis relative to bypass grafting technique.

PURPOSE: To determine whether the incidence of vein graft stenosis is related to bypass grafting technique and thus modification of postoperative surveillance protocols may be required. METHODS: From 1991 to 1996, 338 infrainguinal vein bypasses constructed using in situ (n = 131), reversed (n = 120), nonreversed translocated (n = 48), or spliced/upper extremity vein (n = 39) grafting techniques were evaluated by intraoperative duplex scanning to optimize bypass construction and serially thereafter to detect developing vein graft stenoses. Bypass procedures were performed in 322 patients for critical limb ischemia (83%), claudication (13%), or popliteal aneurysm (4%). Using life-table analysis, graft patency and revision/failure rates were compared relative to grafting technique, need for operative revision, and intraoperative duplex scan results. RESULTS: Three-year primary and secondary graft patency rates were higher (p < 0.001) for in situ bypass grafts (85%/97%) compared with reversed (57%/83%), nonreversed translocated (62%/78%), or alternative (51%/76%) vein bypass grafts. During a mean follow-up interval of 19 months, the incidence of graft revision was higher for reversed saphenous (23%) and alternative (28%) vein bypass grafts compared with in situ (10%) or nonreversed (16%) saphenous vein bypass grafts. Despite a normal intraoperative graft duplex scan, the revision/failure rate of reversed vein grafts was 2.5 times greater than in situ/nonreversed translocated vein conduits (primary patency rate at 3 years, 60% vs 87%, p = 0.009). Bypass grafts modified at operation on the basis of duplex scanning were two times more likely to require postoperative revision than grafts with normal intraoperative scans. CONCLUSIONS: The incidence of postoperative graft stenosis and need for revision varies with bypass grafting technique. Reversed vein bypasses and grafts modified at operation may be more prone than in situ vein bypass grafts to develop stenosis and thus require intensive surveillance. Infrainguinal vein graft failure and the need for revision may be reduced by the adoption of bypass grafting techniques that include valve lysis and intraoperative duplex scan assessment.

Adult↗
PubMed1997

Predicting bacteremia in patients with sepsis syndrome. Academic Medical Center Consortium Sepsis Project Working Group.

The goal of this study was to develop and validate clinical prediction rules for bacteremia and subtypes of bacteremia in patients with sepsis syndrome. Thus, a prospective cohort study, including a stratified random sample of 1342 episodes of sepsis syndrome, was done in eight academic tertiary care hospitals. The derivation set included 881 episodes, and the validation set included 461. Main outcome measures were bacteremia caused by any organism, gram-negative rods, gram-positive cocci, and fungal bloodstream infection. The spread in probability between low- and high-risk groups in the derivation sets was from 14.5% to 60.6% for bacteremia of any type, from 9.8% to 32.8% for gram-positive bacteremia, from 5.3% to 41.9% for gram-negative bacteremia, and from 0.6% to 26.1% for fungemia. Because the model for gram-positive bacteremia performed poorly, a model predicting Staphylococcus aureus bacteremia was developed; it performed better, with a low- to high-risk spread of from 2.6% to 21.0%. The prediction models allow stratification of patients according to risk of bloodstream infections; their clinical utility remains to be demonstrated.

Adult↗
PubMed1997

Microbiological cultures of heart valves and valve tags are not valuable for patients without infective endocarditis who are undergoing valve replacement.

We evaluated the significance of the results of microbiological cultures of heart valves and identification tags from newly inserted prosthetic valves that were removed from patients with valvular heart disease; none of these patients had a preoperative diagnosis of endocarditis. We reviewed the charts of patients with positive cultures for evidence of infections before or after surgery. Cultures were positive for 11.9% of 219 valves (206 native valves and 13 prosthetic or bioprosthetic valves) and 11.6% of 224 tags. The most common isolates were coagulase-negative staphylococci. Typical agents of endocarditis--viridans streptococcus, Enterococcus faecalis, and Staphylococcus aureus--were cultured from five specimens, and Mycobacterium avium complex was identified in six valves. None of the patients with positive valve or tag cultures developed postsurgical endocarditis or wound infection. Findings on histopathologic examination of the valves were not consistent with endocarditis. We conclude that the results of cultures of valves from patients without preoperative diagnoses of endocarditis lack clinical significance, and positive tag cultures are not predictive of postsurgical infection. Positive cultures are most likely a result of contamination during surgery or thereafter.

Adolescent↗
PubMed1996

Elevated levels of recombinational DNA repair in human somatic cells expressing the Saccharomyces cerevisiae RAD52 gene.

The Saccharomyces cerevisiae RAD52 gene was introduced into the human fibrosarcoma-derived cell line HT1080. Transfected cell lines that expressed the yeast transgene catalyzed inter-plasmid homologous DNA recombination at frequencies approx. 12-fold higher than did control cells. Additional experiments revealed that yeast RAD52 gene expression increased the level of resistance to the DNA damaging agents diepoxybutane, and methyl methanesulfonate, but did not alter sensitivity to ultraviolet radiation. These results indicate that the S. cerevisiae Rad52 protein can function in a human somatic cell background and provide support for the idea that a homologous recombination-based DNA repair process functions in mammalian somatic cells.

Anti-Bacterial Agents↗
PubMed1996

Identification of a human RAD52 pseudogene located on chromosome 2.

A human testis cDNA library was screened with a hybridization probe encoding the mouse RAD52 gene. Two classes of clones were identified, one derived from the human RAD52 homolog (hRAD52), the other derived from a pseudogene. In addition to many point mutations, several of which encode stop codons, the pseudogene contains a number of frame shifts and a 103-bp deletion. We further determined that the pseudogene is processed and is located on human chromosome 2, in contrast to hRAD52 which is found on chromosome 12. Reverse transcription-PCR analysis of cultured human diploid fibroblasts, as well as fibrosarcoma cells, revealed that while hRAD52 is expressed at low, but detectable levels in these cells, the pseudogene is not.

Animals↗
PubMed1996

Rosai-Dorfman disease presenting with multiple orbital and intracranial masses.

Rosai-Dorfman disease is an idiopathic histocytic proliferative disorder typically characterized by painless cervical adenopathy, fever, and weight loss. Extranodal manifestations are responsible for presentation in approximately 25% of patients. Orbital involvement has been described in about 10% of patients. There have been only 16 reported cases of Rosai-Dorfman disease presenting with an intracranial mass. We report an unusual case of a patient presenting with bilateral orbital tumors as well as multiple intracranial masses. Clinical, magnetic resonance imaging, and histopathological features are discussed.

Adult↗
PubMed1996

Anatomic patterns of carotid endarterectomy healing.

BACKGROUND: Restenosis after carotid endarterectomy is a dynamic process likely influenced by surgical technique as well as by anatomic, hemodynamic, and patient factors. METHODS: To characterize the healing of carotid endarterectomy sites, intraoperative and serial postoperative color duplex scans were performed in 126 patients (136 repairs). Vessel-wall imaging, midstream spectral analysis, and measurements of diameter and cross-sectional area from common carotid artery (CCA) and internal carotid artery (ICA) segments were compared (at 3, 6, 15, and 30 months) and severity of lumen stenosis was determined. RESULTS: After primary closure (n = 15), patch angioplasty (n = 121), or intraoperative revision based on duplex scanning (n = 5), 12 repairs had mild residual flow abnormalities and 1 repair had a moderate flow abnormality. Mean ICA bulb diameter was greater in patched repairs (0.81 cm, range 0.6 to 1.1 cm) than primary closed repairs (0.7 cm, range 0.45 to 0.8 cm). No ICA occluded during follow-up (mean 24 months), and three repairs, two in the ICA and one in the CCA, demonstrated 50% to 75% diameter reduction at 9 months. Lumen cross-sectional area of vein-patched repairs increased 0.6 cm2 to 0.76 cm2 (P < 0.01) in the ICA and 0.69 cm2 to 1.1 cm2 (P < 0.01) in the CCA segments by 3 months compared with intraoperative measurement. Four patients with progressive dilatation of the patch segment to a mean of 1.77 cm2 developed asymptomatic posterior wall mural thrombus. Postoperative blood flow velocities measured through the repair were similar to intraoperative values. Minor intraoperative hemodynamic abnormalities were not associated with the development of restenosis, and changes in repair site anatomy occurred within 3 months with little change thereafter. CONCLUSIONS: We have found intraoperative scanning useful for detection of anatomic defects and associated turbulence, lesions that should be immediately corrected. Surgical technique that achieves normal intraoperative carotid flow hemodynamics and B-mode ultrasonic vessel wall appearance should predict an endarterectomized segment free of significant residual plaques and neointimal hyperplasia. Tailoring of the vein patches to achieve lumen diameters < 1 cm is recommended because of the dilataton likely to develop after surgery that may lead to vessel wall mural thrombus.

Analysis of Variance↗
PubMed1996

Nature and management of duplex abnormalities encountered during infrainguinal vein bypass grafting.

PURPOSE: This study was undertaken to evaluate the application of duplex scanning during infrainguinal vein grafting procedures to verify vein conduit preparation, anastomotic patency, and graft hemodynamics. METHODS: Between 1991 and 1995, 275 infrainguinal vein bypasses (in situ, 114; reversed, 82; nonreversed translocated, 48; spliced alternative/arm vein, 31) to the popliteal (n = 116) or an infrageniculate artery (n = 159) were scanned during surgery for sites of color Doppler flow abnormality. Duplex-detected defects were graded with peak systolic velocity and velocity ratio criteria. Sites that demonstrated highly disturbed flow (peak systolic velocity > 180 cm/sec, velocity ratio > 2.4) were immediately revised by direct repair, patch angioplasty, or interposition grafting. RESULTS: Intraoperative duplex scanning prompted revision of 50 abnormalities in 43 of the 275 grafts (16%), including 32 vein and seven anastomotic stenoses, nine vein segments with platelet thrombus, and two bypasses with low flow. The intraoperative revision rate was lowest (p < 0.02) for reversed saphenous vein bypasses (7%) compared with other grafting techniques (in situ, 20%; nonreversed translocated, 15%; spliced alternative vein, 23%). The revision rates of popliteal and tibial bypasses were similar (14% vs 17%). A normal result shown by intraoperative scan (235 bypasses) was associated with a low 90-day thrombosis (0.4%) and revision (2%) rate, whereas six of 15 grafts (40%) with residual and 13 of 25 grafts (52%) with unrepaired duplex abnormalities required corrective procedures (p < 0.001). One graft failed within 3 months (secondary patency rate, 99%). CONCLUSIONS: Intraoperative duplex scanning accurately predicted the technical adequacy of infrainguinal vein grafts and was particularly useful in assessing bypasses constructed with valve lysis techniques or alternative veins. Early graft revisions indicated by duplex monitoring for thrombosis or stenosis were the result of a progression of residual defects and platelet thrombus formation rather than inadequate graft run-off flow.

Aneurysm↗