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Biomedical subjects

J A Hokanson

Publications and source records attributed to J A Hokanson.

At least 19 recordsLinked to original sources

4-Hydroxylation of estradiol by human uterine myometrium and myoma microsomes: implications for the mechanism of uterine tumorigenesis.

Estradiol is converted to catechol estrogens via 2- and 4-hydroxylation by cytochrome P450 enzymes. 4-Hydroxyestradiol elicits biological activities distinct from estradiol, most notably an oxidant stress response induced by free radicals generated by metabolic redox cycling reactions. In this study, we have examined 2- and 4-hydroxylation of estradiol by microsomes of human uterine myometrium and of associated myomata. In all eight cases studied, estradiol 4-hydroxylation by myoma has been substantially elevated relative to surrounding myometrial tissue (minimum, 2-fold; mean, 5-fold). Estradiol 2-hydroxylation in myomata occurs at much lower rates than 4-hydroxylation (ratio of 4-hydroxyestradiol/2-hydroxyestradiol, 7.9 +/- 1.4) and does not significantly differ from rates in surrounding myometrial tissue. Rates of myometrial 2-hydroxylation of estradiol were also not significantly different from values in patients without myomata. We have used various inhibitors to establish that 4-hydroxylation is catalyzed by a completely different cytochrome P450 than 2-hydroxylation. In myoma, alpha-naphthoflavone and a set of ethynyl polycyclic hydrocarbon inhibitors (5 microM) each inhibited 4-hydroxylation more efficiently (up to 90%) than 2-hydroxylation (up to 40%), indicating > 10-fold differences in Ki (<0.5 microM vs. > 5 microM). These activities were clearly distinguished from the selective 2-hydroxylation of estradiol in placenta by aromatase reported previously (low Km, inhibition by Fadrozole hydrochloride or ICI D1033). 4-Hydroxylation was also selectively inhibited relative to 2-hydroxylation by antibodies raised against cytochrome P450 IB1 (rat) (53 vs. 17%). These data indicate that specific 4-hydroxylation of estradiol in human uterine tissues is catalyzed by a form(s) of cytochrome P450 related to P450 IB1, which contribute(s) little to 2-hydroxylation. This enzyme(s) is therefore a marker for uterine myomata and may play a role in the etiology of the tumor.

Benzoflavones

Pseudoepitheliomatous hyperplasia mistaken for cancer after delayed reconstruction.

Pseudoepitheliomatous hyperplasia (PEH) arises in areas of chronic inflammation and can be mistaken for squamous cell carcinoma, leading to unnecessary removal of more tissue. We present a study of 21 patients having delayed reconstruction of defects left by Mohs micrographic surgery (MMS) to remove facial skin cancers. Reconstruction was done at an average of 6 days after MMS. Four of these 21 patients (19%) had PEH in the wound margins. Presence of PEH did not correlate with age, sex delay in reconstruction, frequency of wound care, size or location of the defect, type of tumor, or smoking status. During an average 24-month follow-up, none of these four patients had tumor recurrence, suggesting that the benign diagnosis of PEH was correct. We detail the histologic features of PEH, and describe techniques for minimizing confusion with squamous cell carcinoma.

Carcinoma, Squamous Cell

Complications of endoscopic sinus surgery in a residency training program.

Endoscopic sinus surgery (ESS) is now taught in most otolaryngology residency programs in the United States. However, this is technically challenging surgery and concerns exist regarding patient safety early in the surgeon's learning curve. The authors reviewed 193 cases of ESS performed by residents, under faculty supervision at our program, between 1987 and 1992. Sixty-seven percent of patients underwent bilateral anterior ethmoidectomy, 40% had bilateral total ethmoidectomy, and 44% had bilateral middle turbinate reduction. The overall complication rate was 22% and included one major complication. Synechiae accounted for 50% of minor complications. There was no correlation between middle or inferior turbinate reduction and the formation of synechiae. Posterior ethmoidectomy was not associated with a significant increase in complications. We conclude that ESS can be safely performed by otolaryngology residents in carefully structured and supervised training programs.

Adolescent

Accuracy of dispensing in a high-volume, hospital-based outpatient pharmacy.

Accuracy of dispensing was studied in the outpatient pharmacy setting, and error rates were compared with workload. All prescriptions filled in an outpatient pharmacy over 12 weekdays were audited to determine the rate of dispensing errors. In this pharmacy, pharmacists filled prescriptions and technicians delivered the medications to the patients. Before the medication reached the patient, the auditors recorded any dispensing errors and determined whether they were potentially serious. Of the 9846 prescriptions filled, 1229 (12.5%) contained a total of 1371 errors. Of these errors, 155 (1.6%) were potentially serious. Statistical analysis of the data revealed differences between error rates and (1) the total number of prescriptions dispensed per hour and (2) the number of prescriptions filled per pharmacist hour. However, no correlation existed between the number of prescriptions dispensed per hour and the total number of errors made. No significant correlation was found between the rate of potentially serious errors and increasing work volume, suggesting that important factors in error avoidance are continuous quality improvement mechanisms and minimal interruption of dispensing. No association was found between work volume and the number of dispensing errors or potentially serious errors. Error rates were consistent with published estimates.

Ambulatory Care

Management of the thyroid isthmus in tracheostomy: a prospective and retrospective study.

The thyroid isthmus is often encountered while a tracheostomy is being performed. This study details retrospective and prospective comparison of electrocautery division of the isthmus with older techniques. In this study, electrocautery division of the thyroid isthmus during tracheostomy is faster and as safe as other techniques with respect to blood loss, perioperative complications, and airway outcome.

Blood Loss, Surgical

Distant metastases from head and neck squamous cell carcinomas.

Distant metastases (DMs) occurred in 83 (11.4%) of 727 retrospectively studied head and neck cancer patients. Primary tumor location and initial treatment did not influence DM development; larger primaries (P < .04) or more extensive neck disease (P < .007) more often caused DMs. Initial diagnosis to DMs averaged 11.7 months (range, 0 to 60 months), with 84% diagnosed within 24 months. With the exception of laryngeal primaries, no facet of tumor, host, or initial treatment influenced where or how rapidly DMs developed. Lung was the most common DM site (83.4%), then bone (31.1%) and liver (6.0%). Survival with DMs averaged 4.3 months (range, 1 day to 2.7 years); 86.7% died within 1 year. This report yields the following conclusions: 1. Initial tumor size and neck disease are the only predictors of DMs. 2. DMs usually occur within 2 years of the initial diagnosis. 3. Lung is the most common DM site, making chest x-ray the most effective DM screen. 4. Survival with DMs is usually less than a year.

Adult

Population pharmacokinetic models: effect of explicit versus assumed constant serum concentration assay error patterns upon parameter values of gentamicin in infants on and off extracorporeal membrane oxygenation.

Prior authors had hypothesized (but not clearly found) an increased apparent volume of distribution (Vd) for gentamicin in neonates undergoing extracorporeal membrane oxygenation (ECMO). We chose to study the question in our own clinical setting. To develop population pharmacokinetic models of the drug, we used the nonparametric expectation and maximization population modeling method and data from 11 neonates who received gentamicin on ECMO, including 6 infants who received gentamicin both on and off ECMO for severe respiratory failure. We found an increased Vd for gentamicin on ECMO and attributed much of the difference from prior investigations to our use of an explicitly determined laboratory assay error pattern for the measured serum concentrations rather than using constant weighting of the serum level data points. For six infants, while on ECMO their median Vd was 0.748 L/kg compared with a median Vd of 0.471 L/kg after ECMO was discontinued. The median clearance of gentamicin in the six infants while undergoing ECMO was 0.239 L/h compared with 0.350 L/h after ECMO was discontinued. The median half-time (T1/2) was 9.24 h while on ECMO compared with 3.87 h when off ECMO. We conclude that while undergoing ECMO, neonates have a higher volume of distribution for gentamicin, a lower clearance, and a much longer half-life.(ABSTRACT TRUNCATED AT 250 WORDS)

Algorithms

Incidence of sperm with two fluorescent bodies in men with impaired fertility.

OBJECTIVE: To determine the two fluorescent body (2FLB) frequency in males with impaired fertility. DESIGN: Males of couples were evaluated along with their female partners for reproductive function. They were classified as having the potential for fertility (control group) or as infertile (test group). This was based on the evaluation of both members of the couple. Semen parameters were determined and analyzed for differences among diagnostic groups. SETTING: The setting was clinical secondary care in both private and institutional practice. PATIENTS, PARTICIPANTS: The study population was composed of males of couples who were being evaluated for infertility. Classification as to reproductive potential and categories of abnormality was based on measurement of semen parameters and clinical judgment. INTERVENTIONS: Semen specimens were obtained and analyzed from 78 control and 93 test subjects. MAIN OUTCOME MEASURES: Semen parameters including volume, sperm count, sperm motility, percent morphologically abnormal sperm, and percent of quinacrine-stained sperm containing zero, one, or two FLBs were determined. RESULTS: The test group was found to have a 2FLB frequency that was significantly different from that of the control group. The data were then analyzed for significant differences in 2FLB frequencies in subpopulations. When subjects from all diagnostic subgroups that included varicocele were compared with the controls, the 2FLB frequency was significantly elevated (median percent of 2FLB was 1.2 versus 0.7). The 2FLB frequency in the remaining diagnostic groups was not elevated. CONCLUSIONS: This is the first report of an elevated 2FLB frequency associated with a biological abnormality. The cause of the elevated 2FLB frequency is not known. However, other anomalies that have been identified in varicocele patients have been associated with elevated intrascrotal temperatures. There are data available that associates elevated temperature with aneuploidy in mouse oocytes.

Humans

Age-related changes in oral sensation.

Oral sensation (including two-point discrimination, oral stereognosis, vibrotactile detection, somesthetic sensitivity, proprioception, and thermal sensitivity) was studied in 60 healthy adults in five age categories: 20 to 34, 35 to 49, 50 to 64, 65 to 79, and 80 years and above. Thermal and somesthetic sensitivity as well as proprioception did not change with age. Ability to differentiate tactile and vibratory sensation on the lip decreased after age 80 (P less than .01), but vibration detection on the soft palate did not change. Stereognostic ability remained good up to age 80, and then declined for four of the nine shapes tested (P less than .01). Two-point discrimination deteriorated on the upper lip (P less than .01), on the cheeks (P less than .02), and on the lower lip (P less than .06). Two-point discrimination on the tongue and palate did not change. It was noted that oral sensation remained good with aging, showing only a slight decline in function after age 80.

Adult

The relationship between the nasal cycle and mucociliary clearance.

Nasal airway resistances were measured bilaterally on subjects at 30-minute intervals over 6 hours using anterior rhinomanometry. The first 10 subjects found to exhibit alternating congestion and decongestion of the nasal mucosa (i.e., the nasal cycle) were included in the study. Using the saccharin method, nasal mucociliary clearance was determined for each subject in both the congested and decongested phases of the cycle. The results were statistically significant at the P less than .09 level, highly suggestive of a difference in nasal mucociliary clearance between the two phases of the cycle, with the congested phase having the more rapid clearance. However, when compared to the mucociliary clearance times in disease states, the difference in transport times between the two phases is probably not clinically significant.

Adult

Confirmation. Practice behavior for treatment of new morbidity disorders reflects residency experience.

The purpose of the present study was to evaluate congruence between practice and residency training in the treatment of children with five "new morbidity" disorders. Data were obtained through mailed questionnaires. Counseling and behavior modification, without medications, were used for all five disorders by respondents most recently completing pediatric residency. Medications were used more frequently by pediatricians who had completed their residency training longer ago, particularly for nocturnal enuresis and chronic abdominal pain. The most recent graduates tended to treat a larger number of children with temper tantrums and separation anxiety. This is believed to result from more recent graduates being more comfortable and confident in recognizing and treating these conditions. In contrast, no association was noted between year in which residency was completed and number of children treated for nocturnal enuresis and chronic abdominal pain. This results from parents volunteering these symptomatic conditions since they perceive them to be medical problems.

Behavior Therapy

Interobserver variability in the interpretation of brush cytologic studies from head and neck lesions.

A study was conducted to evaluate the usefulness of brush cytology as a diagnostic tool for lesions of the head and neck. Brush specimens were obtained from patients for whom surgical biopsy was recommended by the Otolaryngology Service of the University of Texas Medical Branch Hospitals, Galveston. Specimens were interpreted independently by three cytologists, and interobserver variability was calculated. If a surgical biopsy was performed, histopathologic diagnosis was used as the reference standard to assess the accuracy of each cytologic interpretation. Correspondence of cytopathologic interpretation with histologic diagnosis was sufficient to conclude that brush biopsy is a useful screening technique for unsuspected or clinically undetected malignant tumors of the upper aerodigestive tract. Because of its ability to sample large surface areas with minimal tissue trauma, brush biopsy can be a useful screening technique in combination with selective surgical biopsy for the detection of cytologic changes of malignant neoplasia. Brush cytology costs less than surgical biopsy, yet its relatively high sensitivity and specificity for both benign and malignant grades support its utility. Brush cytology, furthermore, has a low interobserver variability for the benign and malignant grades, suggesting that in the hands of an experienced cytopathologist it can be relied on with confidence. For grades 2 or 3 (inconclusive), brush cytology, however, demonstrated much higher interobserver variability. Based on the findings of this and other studies, brush cytology can be effective in identifying clinically unsuspected malignant tumors of the upper aerodigestive tract, especially in patients with mucosal changes suggestive of "field cancerization."

Biopsy

Effect of bFGF on the inhibition of contraction caused by bacteria.

Bacterial contamination of open wounds significantly inhibits wound contraction required in the healing process. Basic fibroblast growth factor (bFGF) has been shown to overcome contraction inhibition in wound-healing models impaired by diabetes or steroids. This study was designed to determine the effect of bFGF on wound contraction inhibition in an area contaminated with bacterial overgrowth. The topically applied bFGF reversed inhibition to wound contraction that normally occurs with bacterial contamination. This reversal does not appear to be due to increased collagen synthesis since bFGF has been shown to decrease collagen synthesis and the treated wounds showed no increase in breaking strength. The use of bFGF significantly decreased the number of days required for wound healing (P less than 0.01) despite active bacterial invasion and may be of value in the treatment of human contaminated wounds.

Animals

Gentamicin population pharmacokinetic models for low birth weight infants using a new nonparametric method.

Availability of personal computer programs for control of drug regimens has stimulated interest in modeling population pharmacokinetics. In this study, we found parameter values for gentamicin in two infant populations with low birth weights. The models were developed by use of a parametric (i.e., standard two-stage algorithm) and with a new nonparametric expected maximum algorithm. Data for the two populations (i.e., infants less than or equal to 31 weeks' and greater than 31 but less than or equal to 34 weeks' gestational age) were obtained from infants admitted to the University of Texas Medical Branch intensive care nursery between August 1, 1988, and July 31, 1989. The new nonparametric method was demonstrated to be not only the equal of the standard two-stage method for population modeling but better, especially in use of sparse data sets (e.g., single serum levels). It also obviates the need for selecting proper starting conditions for the least-squares fitting procedure used in the standard two-stage method.

Computer Simulation

CT evaluation of the paranasal sinuses in symptomatic and asymptomatic populations.

The frequency of concha bullosa, paradoxical middle turbinate, and septal deviation on coronal computed tomographic scans evaluating sinus disease is known, but the incidence in normal subjects is unknown. We compared 100 consecutive scans performed for evaluation of sinus disease with 82 consecutive scans performed for evaluation of orbital pathology. Patients with sinus disease had significantly more frequent findings of disease in the osteomeatal complex and all sinuses. Concha bullosa was more common in patients with sinus disease (p less than 0.05), as was septal deviation (p less than 0.01). Paradoxical turbinate was equally common. Concha bullosa was associated with anterior ethmoid disease (p less than 0.04). Septal deviation was associated with osteomeatal complex disease (p less than 0.01) and with anterior (p less than 0.04) and posterior (p less than 0.04) ethmoid disease. Paradoxical turbinate was not associated with sinus abnormalities. These data imply a possible causal relationship between concha bullosa or septal deviation and sinus disease.

Adolescent

Detection of 8-hydroxy-2'-deoxyguanosine in deoxyribonucleic acid by the 32P-postlabeling method.

Using synthesized 8-hydroxy-2'-deoxyguanosine 3'-monophosphate as a marker, the 32P-postlabeling method was adapted with minimum modifications for the analysis of 8-hydroxy-2'-deoxyguanosine (8-OH-dG) content in deoxyribonucleic acid (DNA). This method allows the analysis of one 8-OH-dG per 10(4) DNA nucleotides with only 10 pmoles of nucleotides required. The amounts of 8-OH-dG in DNA detected by the postlabeling method correlated well with the electrochemical detection method but were consistently lower.

8-Hydroxy-2'-Deoxyguanosine

The resident selection process in otolaryngology-head and neck surgery.

This study was undertaken to characterize the objective information available about applicants to otolaryngology-head and neck surgery residency positions, and to determine the influence of these factors on obtaining a residency position. Applicants to the otolaryngology-head and neck surgery programs at University of Utah, Salt Lake City, University of Texas Medical Branch, Galveston, and University of Louisville (Ky) were studied. Thirty-one variables were examined, representing demographic and academic factors. Excellent academic performance in medical school (as represented by medical school grade-point average greater than 3.4, National Board part I score greater than 650, class percentile rank greater than 85th percentile, honors grades in both junior medicine and surgery clinical clerkships, or [5] election to Alpha Omega Alpha) was significantly correlated with success in obtaining an otolaryngology-head and neck surgery residency position.

Adult

Ulnar-sided perilunate instability: an anatomic and biomechanic study.

A staging system for ulnar-sided perilunate instability is presented based on a series of cadaver dissections and load studies. Stage I: partial or complete disruption of the lunotriquetral interosseous ligament, without clinical and/or radiographic evidence of dynamic or static volar intercalated segment instability deformity; stage II: complete disruption of the lunotriquetral interosseous ligament and disruption of the palmar lunotriquetral ligament, with clinical and/or radiographic evidence of dynamic volar intercalated segment instability deformity; and stage III: complete disruption of the lunotriquetral interosseous and the palmar lunotriquetral ligaments, attenuation or disruption of the dorsal radiocarpal ligament, with clinical and/or radiographic evidence of static volar intercalated segment instability deformity.

Adult