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Biomedical subjects

S R Johnson

Publications and source records attributed to S R Johnson.

At least 19 recordsLinked to original sources
PubMed1998

Menopause and hormone replacement therapy.

Menopause is a normal part of life of most women and can be made easier with appropriate information about the events that occur. For those women who desire help for bothersome menopausal symptoms, effective therapy can be offered. The use of HRT for prevention is more complex. Several large randomized clinical trials, including the Women's Health Initiative (WHI) and the Heart and Estrogen Replacement Therapy Study (HERS) in the United States, are currently underway. These trials, which have as end points clinical events such as myocardial infarction, sudden death, fractures, and cancer, will provide answers to many of the questions raised in this discussion. Until the results of these trials are available, clinicians must be prudent in their recommendations and should keep their patients apprised of the relevant uncertainties of preventive HRT.

Alzheimer Disease↗
PubMed1998

Agreement in assessing endometrial pathology: the Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial.

We report on agreement in interpreting endometrial biopsy specimens between the local and central pathologists of the Postmenopausal Estrogen/Progestin Interventions (PEPI) trial. This trial was a 3-year, multicenter, randomized, double-masked, placebo-controlled trial of four groups taking estrogen or estrogen/progestin combinations. A total of 1804 follow-up biopsies were performed in 596 subjects. Relative sensitivity and relative specificity using the diagnosis from the central pathologist as the gold standard and overall agreement are presented. Almost 90% of the diagnoses were reported normal by both readers. There were significant differences in agreement among clinics and treatment arms (p < 0.0001). The visit at which the biopsy specimen was obtained, age at baseline, prior postmenopausal estrogen use, parity, and drug adherence were not associated with agreement between the two readers. Higher proportions of disagreement were seen in two clinics (13% and 11%) compared with the other five clinics (2%-5%). Biopsy specimens from participants who were taking conjugated equine estrogens (CEE) only were more likely to be diagnosed differently by both readers (11%) than biopsy specimens from women taking a placebo (2%) or CEE combined with progestins (5%). Relative specificity varied from 86.4% to 98.9% among the clinics (p < 0.0001). Relative sensitivity was based on a small number of diagnoses, as few biopsy specimens were classified abnormal by the central pathologist. In patients assigned to CEE combined with progestin, 5 of the 7 biopsy specimens that were recorded abnormal by the central pathologist received a normal diagnosis locally. Our findings show that sample size requirements for study designs in which a central reader is used can be at least threefold lower than the requirements for designs relying on local diagnoses. Centralized protocols for endometrial histopathology reading and staff training are highly desirable in multicenter trials.

Biopsy↗
PubMed1998

Non-cAMP-mediated bronchial arterial vasodilation in response to inhaled beta-agonists.

We studied the dose-dependent effects of inhaled isoetharine HCl, a beta-adrenergic bronchodilator (2.5, 5.0, 10.0, and 20.0 mg), on bronchial blood flow (Qbr) in anesthetized sheep. Isoetharine resulted in a dose-dependent increase in Qbr. With a total dose of 17.5 mg, Qbr increased from baseline values of 22 +/- 3.4 (SE) to 60 +/- 16 ml/min (P < 0.001), an effect independent of changes in cardiac output and systemic arterial pressure. To further study whether synthesis of endogenous nitric oxide (NO) affects beta-agonist-induced increases in Qbr, we administered isoetharine (20 mg) by inhalation before and after the NO-synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME). Intravenous L-NAME (30 mg/kg) rapidly decreased Qbr by approximately 80% of baseline, whereas L-NAME via inhalation (10 mg/kg) resulted in a delayed and smaller (approximately 22%) decrease. Pretreatment with L-NAME via both routes of administration attenuated bronchial arterial vasodilation after subsequent challenge with isoetharine. We conclude that isoetharine via inhalation increases Qbr in a dose-dependent manner and that beta-agonist-induced relaxation of vascular smooth muscle in the bronchial vasculature is partially mediated via synthesis of NO.

Administration, Inhalation↗
PubMed1998

Effect of aerosolized acetylcholine on bronchial blood flow.

We studied the effects of aerosolized as well as intravenous infusion of acetylcholine on bronchial blood flow in six anesthetized sheep. Intravenous infusion of acetylcholine, at a dose of 2 microg/kg, increased bronchial blood flow from 45 +/- 15 (SE) to 74 +/- 30 ml/min, and vascular conductance increased by 76 +/- 22%. In contrast, aerosolized acetylcholine at doses of 2 and 20 microg/kg decreased bronchial vascular conductance by approximately 10%. At an aerosolized dose of 200 microg/kg, the bronchial vascular conductance increased by approximately 15%, and there was no further increase in conductance when the aerosolized dose was increased to 2,000 microg/kg. Pretreatment of animals with a nitric oxide synthase inhibitor, Nomega-nitro-L-arginine methyl ester hydrochloride, partially blocked the vasodilatory effects of intravenous acetylcholine and completely blocked the vasodilatory effects of high-dose aerosolized acetylcholine. These data suggest that aerosolized acetylcholine does not readily penetrate the vascular wall of bronchial circulatory system and, therefore, has minimal vasodilatory effects on the bronchial vasculature.

Acetylcholine↗
PubMed1997

Transvaginal ultrasonography compared with endometrial biopsy for the detection of endometrial disease. Postmenopausal Estrogen/Progestin Interventions Trial.

BACKGROUND: Transvaginal ultrasonography is a noninvasive procedure that may be used to detect endometrial disease. However, its usefulness in screening for asymptomatic disease in postmenopausal women before or during treatment with estrogen or estrogen-progesterone replacement is not known. METHODS: We compared the sensitivity and specificity of transvaginal ultrasonography and endometrial biopsy for the detection of endometrial disease in 448 postmenopausal women who received estrogen alone, cyclic or continuous estrogen-progesterone, or placebo for three years. RESULTS: Concurrent ultrasonographic and biopsy results were available for 577 examinations in the 448 women, 99 percent of whom were undergoing routine annual follow-up. Endometrial thickness was less than 5 mm in 45 percent of the examinations, 5 to 10 mm in 41 percent, more than 10 mm in 12 percent, and not measured in 2 percent, and it was higher in the women receiving estrogen alone than in the other groups. Biopsy detected 11 cases of serious disease: 1 case of adenocarcinoma, 2 cases of atypical simple hyperplasia, and 8 cases of complex hyperplasia. Biopsy also detected simple hyperplasia in 20 cases. At a threshold value of 5 mm for endometrial thickness, transvaginal ultrasonography had a positive predictive value of 9 percent for detecting any abnormality, with 90 percent sensitivity, 48 percent specificity, and a negative predictive value of 99 percent. With this threshold, a biopsy would be indicated in more than half the women, only 4 percent of whom had serious disease. CONCLUSIONS: Transvaginal ultrasonography has a poor positive predictive value but a high negative predictive value for detecting serious endometrial disease in asymptomatic postmenopausal women.

Biopsy↗
PubMed1997

The frequency of human papillomavirus detection in postmenopausal women on hormone replacement therapy.

Postmenopausal women enrolled in the Iowa portion of the postmenopausal estrogen/progestin interventions randomized clinical trial (n = 105) during 1989-1991 were studied for (i) the prevalence of human papillomavirus (HPV) in this older age population (ages 45-64), and (ii) the association between hormone replacement therapies (HRTs) and changes in detection of HPV over a 2-year time period. HPV is causative in most cervical and some other genital cancers and in the presence of steroid hormones has been shown to increase neoplastic transformation by HPV in vitro. Using PCR to detect HPV DNA, the overall frequency of the virus regardless of time period was 50.3% (n = 53) with a baseline (BL) frequency of 38.1% and the second year follow-up (FU) of 22.9%. The oncogenic types HPV-16 (75.5%) and HPV-31 (20.8%) were the most commonly reported. All those with persistently detected infection (10.5%), defined as HPV+ at both BL and FU, were identified with HPV-16 or -18. Between these two time periods there were no significant differences in HPV frequency between the placebo and combined HRT groups (BL-/FU+, 21% vs 18%; BL+/FU-, 71% vs 80%). While the study is based on a small sample, the findings suggest that short-term use of HRTs is not associated with an increased risk of HPV detection, but assessment of effects from long-term use is needed. The data also indicate that the frequency of HPV found in older women is higher than previously suspected but that short-term changes in HPV detected in this age group are unrelated to the development of precancerous cervical lesions.

DNA Probes, HPV↗
PubMed1997

Synthetic functions of airway smooth muscle in asthma.

Studies now show that the airway smooth muscle cell, in addition to its contractile function, can participate in and coordinate the inflammatory response. In response to inflammatory cytokines, the airway smooth muscle cell produces cytokines, chemokines, growth factors and cell adhesion molecules leading to inflammatory cell chemotaxis, hyperplasia and hypertrophy. Anti-inflammatory mediators are also produced suggesting a dual role in inflammation. Moreover, in response to growth stimuli the cells may adopt a phenotype more suited to 'synthetic' function. These issues are discussed in this article by Simon Johnson and Alan Knox, who also point to ways in which some of these pathways offer future therapeutic potential in asthma.

Animals↗
PubMed1997

The Postmenopausal Estrogen/Progestin Interventions Study: primary outcomes in adherent women.

OBJECTIVE: To assess the efficacy of unopposed estrogen, and three estrogen/progestin regimens on selected heart disease risk factors among adherent women and to contrast those results with efficacy among all women in the PEPI study. DESIGN: A 3-year, multicenter, randomized, double-blinded, placebo-controlled clinical trial. PARTICIPANTS: A total of 847 healthy postmenopausal women aged 45 to 64 years of age with no known contraindication to hormone therapy, who attended their 36 month clinical visit. INTERVENTION: Participants were randomized in equal numbers to one of the following treatments: (1) placebo; (2) conjugated equine estrogen (CEE) 0.625 mg daily; (3) CEE 0.625 daily plus medroxyprogesterone acetate (MPA) 10 mg, days 1-12; (4) CEE 0.625 daily plus MPA 2.5 mg daily; or (5) CEE 0.625 daily plus micronized progesterone (MP) 200 mg, days 1-12. ANALYSIS: Analyses are based on adherent women, where adherence is defined as taking at least 80% of pills at each 6-month visit. RESULTS: Adherence rates were high in all groups except women with a uterus assigned to unopposed CEE. The difference in HDL-C levels resulting from the CEE vs. CEE+MP was approximately three times larger than in the intent-to-treat analyses, reaching statistical significance (P < 0.05). In each active treatment, LDL-C decreased 10-15%. Triglycerides increased 15-20% in each opposed CEE arm and over 25% in the CEE only arm; this difference was not statistically significant. Fibrinogen increased by 7% among placebo adherers, but decreased or remained fairly stable among the active arm adherers. Systolic blood pressure increased 3-5% in all treatment arms. Women adherent to the CEE+MPA arms had twice the increase of 2 h glucose levels as women adherent to CEE only, or CEE+MP (8-9% vs. 3-4%). Two-hour insulin levels decreased 3-12% for all arms. The patterns of change for fibrinogen, SBP, 2 h glucose and insulin were similar to those from the intent-to-treat analyses. CONCLUSIONS: In analyses limited to adherent women, all active treatments, compared to placebo, continued to have similar and favorable effects on LDL-cholesterol and fibrinogen and no significant effects on blood pressure or insulin levels. Given the overall high adherence rates in PEPI, the results are similar to the intent-to-treat analyses, as expected. Only the trend of HDL-C to have a larger increase in the CEE only arm (in the intent-to-treat analyses) gained statistical significance in analyses restricted to adherers.

Blood Glucose↗
PubMed1997

The effects of hormone replacement therapy on coronary heart disease.

The importance of cardiovascular disease as a cause of morbidity and mortality in women is well appreciated. Cardiovascular disease accounts for approximately 48% of deaths in women in the United States. In particular, coronary heart disease (CHD) accounts for approximately one-half of these deaths. This article describes current evidence that suggests it is premature to recommend hormone replacement therapy (HRT) as a proven prevention strategy for CHD.

Bias↗
PubMed1997

The clinical decision regarding hormone replacement therapy.

The complexity of the decision to recommend hormone replacement therapy (HRT) for the postmenopausal woman depends on the medical status of the patient, her concerns and goals, and the indications being considered. This article suggests a practical approach that leads to informed, collaborative decision making between the health care professional and patient.

Colonic Neoplasms↗
PubMed1997

Nitric oxide and beta-adrenergic agonist-induced bronchial arterial vasodilation.

In anesthetized sheep, we measured bronchial blood flow (Qbr) by an ultrasonic flow probe to investigate the interaction between inhaled nitric oxide (NO; 100 parts/million) given for 5 min and 5 ml of aerosolized isoetharine (1.49 x 10(-2) M concentration). NO and isoetharine increased Qbr from 26.5 +/- 6.5 to 39.1 (SE) +/- 10.6 and 39.7 +/- 10.7 ml/min, respectively (n = 5). Administration of NO immediately after isoetharine further increased Qbr to 57.3 +/- 15.1 ml/min. NO synthase inhibitor N(omega)-nitro-L-arginine methyl ester hydrochloride (L-NAME; 30 mg/kg, in 20 ml saline given i.v.) decreased Qbr to 14.6 +/- 2.6 ml/min. NO given three times alternately with isoetharine progressively increased Qbr from 14.6 +/- 2.6 to 74.3 +/- 17.0 ml/min, suggesting that NO and isoetharine potentiate vasodilator effects of each other. In three other sheep, after L-NAME three sequential doses of isoetharine increased Qbr from 10.2 +/- 3.4 to 11.5 +/- 5.7, 11.7 +/- 4.7, and 13.3 +/- 5.7 ml/min, respectively, indicating that effects of isoetharine are predominantly mediated through synthesis of NO. When this was followed by three sequential administrations of NO, Qbr increased by 146, 172, and 185%, respectively. Thus in the bronchial circulation, there seems to be a close interaction between adenosine 3',5'-cyclic monophosphate- and guanosine 3',5'-cyclic monophosphate-mediated vasodilation.

Animals↗
PubMed1997

Bacterial translocation in organ donors: clinical observations and potential risk factors.

Thirty-nine solid-organ donors were evaluated to determine the incidence of bacterial translocation to mesenteric lymph nodes. In addition, clinical variables from 59 local recipients of renal allografts from these donors were examined to assess whether translocation in donors was associated with increased morbidity in the recipients of organs from node-positive donors. Ileocecal lymph node cultures were positive in 18 of 39 donors (46%). Sixteen donors (41%) were hypotensive [systolic blood pressure (SBP) < 90 mmHg] and 27 (69%) received blood product transfusions before organ donation. The presence of hypotension and blood product transfusion were associated with positive and negative cultures, respectively. In 24 (41%) of 59 organs transplanted from donors with periods of hypotension, significantly more (16 of 24, 67%) were associated with positive lymph node cultures than with negative cultures (8 of 24, 33%; p = 0.029). In recipients of organs from node-positive versus node-negative donors there was a trend toward higher incidence of infection (32% vs. 25%), need for hemodialysis post-transplant (29% vs. 23%), graft loss within 1 yr (24% vs. 19%), and lack of blood transfusion prior to organ procurement (43% vs. 23%), although these variables were not significantly different between the groups. Hypotension or inadequate resuscitation may contribute to increased bacterial translocation to mesenteric lymph nodes. The overall impact upon the recipients of organs from donors with demonstrable translocation to lymph nodes remains undefined.

Bacterial Infections↗
PubMed1996

A percutaneous technique for venovenous bypass in orthotopic cadaver liver transplantation and comparison with the open technique.

Venovenous bypass minimizes the hemodynamic alterations during the anhepatic phase of liver transplantation. A new technique for the percutaneous placement of the bypass cannulae is described and compared to the cut-down ("open") technique. The records of 81 patients who underwent 94 liver transplants between August 1991 and April 1994 were reviewed for indications for transplant, United Network for Organ Sharing status, mean age, body surface area, bypass technique and time, flow rates, cardiac output, mean arterial pressure and central venous pressure during bypass, the development of deep venous thrombophlebitis, and lymphoceles. Femoral flow rates were higher in the open group (2054 +/- 74 mL/min), compared with the percutaneous group (1726 +/- 74 mL/min) (p = 0.003). Total flow rates in the open (2238 +/- 58 mL/min) and percutaneous (2197 +/- 67 mL/min) groups were not different. Maximum cardiac outputs (L/ min) were higher in the open (10.1 +/- 0.6) versus percutaneous group (7.0 +/- 0.5) (p < 0.0002). Similarly, minimum cardiac outputs (L/min) were higher in the open (8.9 +/- 0.7) versus percutaneous group (5.8 +/- 0.5) (p = 0.003). Other hemodynamic parameters (mean arterial pressure, central venous pressure) were not different between groups. Venous thrombosis occurred in 1/50 (2.0%) and 4/34 (11.8%) patients in the open and percutaneous groups, respectively (p = 0.153). Nineteen lymphoceles occurred in 102 (18.6%) at-risk sites in the open group, whereas no lymphoceles occurred in 66 at-risk sites in the percutaneous group (p < 0.001). Groin lymphoceles occurred in 7/50 (14%) and 0/34 at-risk sites in the open and percutaneous groups, respectively (p = 0.039). Axillary lymphoceles occurred in 12/52 (23.1%) and 0/32 at-risk sites in the open and percutaneous groups, respectively (p = 0.0031). Operative repair of a lymphocele was required in 11/16 (69%) patients. The percutaneous placement of catheters for venovenous bypass has the advantage of comparable flow rates with satisfactory hemodynamics without the lymphatic complications of the cut-down technique.

Adolescent↗
PubMed1996

Detection of intestinal bacterial translocation using PCR.

Microbial translocation has been suspected to be a major contributing factor in the development of sepsis of unknown origin and multiple organ failure syndrome, but there are currently no tests capable of detecting and quantitating translocation sequentially in humans. The purpose of this study was to develop a sensitive polymerase chain reaction (PCR) test to detect Escherichia coli (E. coli) DNA in the blood of animals after inducing bacterial translocation from the gut. DNA was extracted from blood and primers were used to amplify an 800-bp gene fragment of E. coli by 30-cycle PCR. Detection by southern blotting achieved a sensitivity of 10-100 organisms per 0.3 cc blood. Experimental groups included mice gavaged with 10(10) E. coli followed by 20% body surface area thermal injury, or no injury. Controls included burn only and no treatment groups. Blood was obtained by cardiac puncture 1 hr after burn. Cultures were done on blood samples from all groups. More animals in the burn/gavage group had positive bacterial cultures. All controls were culture negative. E. coli detection by PCR was 100% sensitive in culture positive animals with detection in the gavage/burn group higher than that in all other groups. PCR was negative for all mice without treatment. Several culture negative animals had detectable bacterial DNA by PCR. This highly sensitive and specific method can be used repeatedly to test the blood of patients for the presence of microbial DNA, which could be originating from the gut.

Animals↗
PubMed1996

Clinical features of patients with beta-lactamase producing Haemophilus influenzae isolated from sputum.

Ampicillin resistance amongst isolates of Haemophilus influenzae is of increasing concern but its clinical impact is unclear. We performed a retrospective study of 34 hospital patients with lower respiratory tract infection (LRTI) caused by beta-lactamase positive (beta+) H. influenzae and compared these with 34 control patients with LRTI caused by beta-lactamase negative (beta-) strains. Chronic obstructive pulmonary disease was the most common underlying condition in both groups (beta+ 23/24, beta- 25/34). A recent course of antibiotics, especially ampicillin/amoxycillin, was significantly (P < 0.05) more common in the beta+ group (beta+ 17/34, beta- 3/34). Other pathogens were isolated more frequently in the beta+ group (beta+ 10/34, beta- 4/34). There was no difference in outcome between the two groups.

Adult↗