Biomedical subjects

John Gaughan

Publications and source records attributed to John Gaughan.

At least 19 recordsLinked to original sources

PubMed2006

Patterns of LHbetacf among women in health and disease.

Urine based gonadotropin assays provide a practical means of analyzing hormone secretion patterns. While research protocols have revealed pulsatile patterns of gonadotropins such as LH in the blood, these assays are of limited clinical use since daily venipuncture sampling is not feasible outside of a research environment. However, collection of several urine samples provides a method to achieve the same visualization of gonadotropin patterns in patients using a convenient and generally applicable technique based on analysis of the highly stable hLHbetacf for monitoring LH and hCGbetacf for monitoring pituitary hCG. We demonstrated that two different sampling techniques for analyzing these gonadotropin metabolites yielded the same information on their excretory patterns, either sampling of spot urines or collecting first morning void urines for several days. Next, we studied the core excretory patterns in several populations: menstruating and postmenopausal women from the general population, and two populations of women from a fertility center, one of which had polycystic ovaries (PCO). The PCO population was also subdivided into those with and without insulin resistance (IR). It was found that our hLHbetacf assay did not measure the form of the LH core (v-hLHbetacf) produced in subjects who were homozygous for a variant form of LH (v-LH). None of our patients tested were homozygous for the variant form of LH. It was also found that in most non-PCO (NPCO) patients, the hLHbetacf peak lasted for 7-9 days while among the PCO patients this peak frequently lasted for less than 7 days and an erratic pattern tended to appear. The overall differences in patterns between the PCO and NPCO patients were confirmed by spectral statistical methods. The prevalence of certain characteristic hLHbetacf patterns may be higher among women with PCO with a more severe clinical presentation. Use of urinary analysis of gonadotropin metabolites, especially hLHbetacf, may supplement subjective ultrasound studies with more sensitive biochemical measurements.

Adult↗

PubMed2006

Effects of mu, kappa or delta opioids administered by pellet or pump on oral Salmonella infection and gastrointestinal transit.

Our laboratory has shown previously that subcutaneously implanted, slow-release morphine pellets markedly enhanced susceptibility to oral infection with Salmonella typhimurium. Further, morphine, kappa and delta opioid receptor agonists infused via osmotic minipumps were immunosuppressive. The present study compared morphine pellets to morphine pumps and also examined the differential effects of morphine versus U50,488H (kappa agonist), deltorphin II (delta2 agonist), and (D-Pen2, D-Pen5)-enkephalin (DPDPE, delta1 agonist), administered via Alzet minipumps, on oral Salmonella infection and on gastrointestinal transit. The results show that all morphine-pelleted mice (26/26) had a marked increase in Salmonella burden in the Peyer's Patches, mesenteric lymph nodes and spleen. In comparison, only 8/20 mice receiving morphine by minipump at doses ranging from 1 to 25 mg/kg/day had any culturable Salmonella in their organs and the number of bacteria was very low. The level of Salmonella colonization correlated with blood morphine levels and gut transit measured using an intragastric charcoal meal. Morphine pellets inhibited gut transit by 38%, while mice receiving morphine by minipump at doses of 1 to 25 mg/kg/day showed only a dose-dependent 7% to 17% inhibition. Mice receiving various doses of U50,488H or DPDPE had no culturable Salmonella in the three sites. Deltorphin II given by minipump resulted in a moderate level of Salmonella in the spleen. Deltorphin II and U50,488H (0.1 to 10 mg/kg/day) did not suppress gut transit. The present studies indicate that a predominantly mu opioid receptor agonist, morphine, given by slow-release pellet, potentiated Salmonella infection and inhibited gastrointestinal transit. In contrast, morphine in pumps slightly inhibited intestinal transit, but did not sensitize to Salmonella infection. A delta1 opioid receptor agonist did not sensitize to infection, and a delta2 and a kappa opioid receptor agonist had minimal effects on either parameter.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

PubMed2006

Decreased mortality by normalizing blood glucose after acute ischemic stroke.

OBJECTIVES: Hyperglycemia after cerebral ischemia exacerbates brain injury and worsens the outcome of stroke patients. The authors sought to examine the effect of glycemic control on mortality after acute stroke. METHODS: This was a retrospective study of patients discharged with a diagnosis of ischemic stroke during a 40-month period from a large urban U.S. health system. Patients were compared by initial blood glucose (BG) levels and by glycemic control during the first 48 hours of hospitalization. RESULTS: Of 960 patients with thromboembolic stroke, 373 (38.9%) were hyperglycemic (BG > or = 130 mg/dL) on hospital admission. Admission hyperglycemia was associated with a higher mortality rate than was euglycemia (odds ratio [OR] = 3.15; 95% confidence interval [CI] = 1.45 to 6.85; p = 0.004). Persistent hyperglycemia (PerHyp) during 48 hours of hospitalization was associated with even higher mortality rate (unadjusted logistic regression, OR = 6.54; 95% CI = 2.41 to 17.87; p < 0.001). Glycemic control (normalization of BG to < 130 mg/dL) was associated with a 4.6-fold decrease in mortality risk as compared with the case of patients with PerHyp (p < 0.001). Multiple logistic regression showed glycemic control to be a strong independent determinant of survival (OR = 5.95; 95% CI = 1.24 to 28.6; p = 0.026) after acute stroke even after adjustment for age, gender, concomitant hypertension and diabetes, and stroke severity. CONCLUSIONS: Admission hyperglycemia is associated with a worse outcome after stroke than is euglycemia. Normalization of blood glucose during the first 48 hours of hospitalization appears to confer a potent survival benefit in patients with thromboembolic stroke.

Adult↗

PubMed2006

Three-dimensional US volume analysis of gastric pseudotumors in a porcine model.

BACKGROUND: Tumor burden is difficult to estimate by endoscopy and conventional EUS. OBJECTIVE: The purpose of this study was to determine the accuracy and the reliability of a new 3-dimensional (3D) EUS system in a pseudotumor model (Olympus EUS EXERA EU-M60). DESIGN: A pseudotumor model was developed in a porcine stomach. Pseudotumors were created by injecting various volumes of US gel (0.3, 0.5, 0.7, and 1 mL) into porcine stomach specimens, and then the volume was measured in vitro. Two investigators made volume measurements by outlining the cross-sectional area of the pseudotumor at different radial planes. The instrument then automatically calculated the volume based on the outlined cross-sectional areas. The measured volume was compared with the actual volume of the pseudotumor by using a Bland-Altman analysis. Every second, third, fourth, fifth, sixth, and tenth image was measured to calculate the tumor volume and to determine the optimum number of images required for accurate volume determination. Inter- and intraobserver variability, percentage error, Bland-Altman analysis, analysis of variance (ANOVA), and kappa statistic were performed. SETTING: This study was performed in an in vitro animal model. PATIENTS: There were no patients involved in this study. MAIN OUTCOME MEASUREMENTS: Accuracy and reliability of pseudotumor volume measurement. RESULTS: When averaging across all measurements, the overall average mean error was 3.25%. The overall inter-rater reliability as measured by intraclass correlation coefficient was 0.78. The overall intra-rater reliability as measured by intraclass correlation coefficient was 0.99. Bland-Altman analysis and ANOVA showed similar low variability for measured volumes based on image frequencies for volume calculations between every other and every sixth image but greater variability for measured volumes based on every tenth image. Larger pseudotumors were measured with a slight decrease in mean percentage error. The kappa statistic for interobserver variability was .61, which demonstrated substantial agreement among observers. LIMITATIONS: The major limitation of this technology is the penetration of the US beam to evaluate large tumors, because the US transducer is high frequency (20 MHz) and, therefore, has a limited penetration. CONCLUSIONS: In conclusion, the new Olympus EUS EXERA EU-M60 3D US probe allowed for accurate volume measurements of small pseudotumors in porcine stomach model in vitro. There was substantial evaluator agreement, with a low interobserver variability. Larger pseudotumors were measured with a slightly lower percentage error than smaller pseudotumors. Volumes measured with a greater number of radial images were measured slightly more accurately. We plan to test this device in patients with GI tumors in the near future.

Animals↗

PubMed2006

Abdominal aortic aneurysm is a specific antigen-driven T cell disease.

To determine whether monoclonal/oligoclonal T cells are present in abdominal aortic aneurysm (AAA) lesions, we amplified beta-chain T cell receptor (TCR) transcripts from these lesions by the nonpalindromic adaptor (NPA)-polymerase chain reaction (PCR)/V-beta-specific PCR followed by cloning and sequencing. Sequence analysis revealed the presence of substantial proportions of identical beta-chain TCR transcripts in AAA lesions in 9 of 10 patients examined, strongly suggesting the presence of oligoclonal populations of alphabeta TCR+ T cells. We have also shown the presence of oligoclonal populations of gammadelta TCR+ T cells in AAA lesions. Sequence analysis after appropriate PCR amplification and cloning revealed the presence of substantial proportions of identical VgammaI and VgammaII TCR transcripts in 15 of 15 patients examined, and of Vdelta1 and Vdelta2 TCR transcripts in 12 of 12 patients. These clonal expansions were very strong. All these clonal expansions were statistically significant by the binomial distribution. In other studies, we determined that mononuclear cells infiltrating AAA lesions express early- (CD69), intermediate- (CD25, CD38), and late- (CD45RO, HLA class II) activation antigens. These findings suggest that active ongoing inflammation is present in the aortic wall of patients with AAA. These results demonstrate that oligoclonal alphabeta TCR+ and gammadelta TCR+T cells are present in AAA lesions. These oligoclonal T cells have been clonally expanded in vivo in response to yet unidentified antigens. Although the antigenic specificity of these T cells remains to be determined, these T cells may play a significant role in the initiation and/or the propagation of the AAA. It appears that AAA is a specific antigen-driven T cell disease.

Antigens↗

PubMed2006

Advanced emphysema in African-American and white patients: do differences exist?

BACKGROUND: Emphysema is the only smoking-related disease in which white patients have higher prevalence and higher attributable mortality rates than African-American patients. Epidemiologic studies have not addressed, nor explained, the observed racial differences in emphysema. STUDY OBJECTIVES: To determine whether white and African-American patients differ with respect to the magnitude, anatomic distribution, and physiologic impairments of emphysema. PATIENTS: Characteristics of patients with severe and very severe emphysema enrolled in the National Emphysema Treatment Trial were examined and compared. Patient demographics, cardiopulmonary function, quality of life, and severity/distribution of the emphysema by quantitative CT were analyzed. RESULTS: Of the 1,218 patients enrolled in the trial, 42 were African American (3.4%) and 1,156 were white (95%). African Americans were younger (mean age +/- SD, 63 +/- 7 years vs 67 +/- 6 years) and smoked less (26 +/- 14 cigarettes per day vs 32 +/- 14 cigarettes per day) than white patients (p = 0.01). There was no difference between the two racial groups in pulmonary function (FEV1, 27 +/- 6% predicted vs 27 +/- 7% predicted), gas exchange (Pa(O2), 66 +/- 11 mm Hg vs 65 +/- 10 mm Hg), and exercise (33 +/- 14 W vs 36 +/- 21 W), respectively. Quality of life measures were similar between the groups, but African Americans had a lower socioeconomic status, lower education level, and fewer were married. Radiographic analysis of the extent of emphysema in African Americans, who were matched with selected white patients, revealed significantly less emphysema in the former group and different distribution of severe emphysema. CONCLUSIONS: African Americans with emphysema were younger and had a similar degree of lung impairment as the white study population despite smoking less. In a subgroup of matched patients, the severity and distribution of emphysema by quantitative radiographic analysis were different.

Black or African American↗

PubMed2006

Gynecologists' attitudes toward hysterectomy: is the sex of the clinician a factor?

OBJECTIVE: To assess the effect of gynecologists' sex on their clinical opinions of hysterectomy. STUDY DESIGN: A survey presenting a case of symptomatic uterine leiomyomas was randomly mailed to the fellows of the American College of Obstetricians and Gynecologists, who were asked to choose either hysterectomy or any uterus-sparing modality for the treatment of the presented case. The effects of gynecologists' sex, age, race, type and year of training, practice type, location and region on their clinical opinions were evaluated with univariate and multivariate logistic regression analysis. RESULTS: Among the 500 potential respondents, 245 (49.0%) responses were complete for analysis. One hundred forty-seven (60.0%) were males, and 98 (40.0%) were females. Hysterectomy choice was not significantly influenced by the gynecologist's sex (77.6% vs. 87.1%; OR 0.51; 95% CI 0.26, 1.01). Univariate logistic regression analysis indicated that only younger age and being in an academic practice significantly decreased the hysterectomy choice among the participants. In the multivariate model, both age (OR 1.66; 95% CI 1.27, 2.19) and academic practice type (OR 0.37; 95% CI 0.14, 0.94) remained independently significant. CONCLUSION: When presented with a case involving symptomatic leiomyomas, gynecologists' sex did not significantly affect their opinion for or against hysterectomy. Only age and practice type were independently significant in this decision making.

Adult↗

PubMed2006

Effect of antiplatelet agents clopidogrel, aspirin, and cilostazol on circulating tissue factor procoagulant activity in patients with peripheral arterial disease.

Tissue factor (TF) is the physiological initiating mechanism for blood coagulation. Platelets play an important role in monocyte TF expression, thrombosis and inflammation. Aspirin, clopidogrel and cilostazol, which inhibit platelet responses by different mechanisms, are widely used in patients with arterial diseases. We tested the hypothesis that platelet-inhibiting agents inhibit the levels of circulating TF procoagulant activity (TF-PCA) in patients with peripheral arterial disease (PAD). Twenty-six patients with lower extremity PAD, average age 65.9 +/- 8.4 years (mean +/- SEM), were studied at baseline and following sequential two-week treatment regimens with aspirin (325 mg daily), clopidogrel (75 mg daily) or a phosphodiesterase inhibitor cilostazol (100 mg twice daily) singly, and with each possible combination of these agents. Circulating TF-PCA in whole blood, and plasma factor VIIa, prothrombin fragment F1.2, thrombin-antithrombin complexes (TAT), and P-selectin were measured. Baseline TF-PCA levels in the patients were elevated (131 +/- 19 U/ml) compared to control subjects (23 +/- 2, p < 0.0001). TF-PCA levels declined following treatment with clopidogrel alone, and with combinations of clopidogrel with aspirin or cilostazol, with the lowest levels being with the triple-drug combination. Plasma P-selectin declined in all treatment groups. No changes were noted in plasma factor VIIa, F1.2 or TAT. In conclusion, treatment of PAD patients with antiplatelet agents decreases circulating TF, a molecule with prothrombotic and proinflammatory effects. These findings suggest an unrecognized mechanism, beyond inhibiting aggregation responses, for the efficacy of antiplatelet drugs in patients with arterial diseases.

Aged↗

PubMed2005

Identification of HLA-DQalpha and -DRbeta residues associated with susceptibility and protection to epithelial ovarian cancer.

Substantial evidence has been accumulated suggesting that T cells in patients with epithelial ovarian carcinoma (EOC) exhibit an antigen-driven immune response directed against the tumor cells. In the context of human leukocyte antigen (HLA), this suggests its possible involvement in the disease. Therefore, we examined the distribution of the HLA-DRB1*, -DQA1*, and -DQB1* alleles in 47 patients with EOC and 67 healthy Caucasian women. The frequency of D(70) and E(71) polymorphic residues of the DRB1 alleles was significantly reduced in EOC patients versus controls (pD(70)E(71) = 0.009), suggesting a protective role against the disease. The DQalpha residues R(52) and Y(11)R(55) were increased in the patients (p = 0.008 and 0.012, respectively). Because residues 11 and 55 participate in the formation of pocket 1, they may be functionally important amino acid positions that influence disease susceptibility. The frequency of the DQalpha susceptibility epitope (R(52)Y(11)R(55)) among the DRbetaD(70)E(71)-positive EOC patients was increased when compared with DRbetaD(70)E(71)-positive controls (EOC, 100%; control, 52%; p = 0.028). Among individuals without the DQalpha susceptibility epitope, the distribution of DRbetaD(70)E(71)-positive cases was significantly different between EOC patients and controls (EOC, 0%; control, 60%; p = 0.039). Therefore, it appears that the presence of DQalpha susceptibility elements overrides the protective effect of the DRbetaD(70)E(71) epitope and suggests an interactive relationship between DRbeta and DQalpha epitopes that may be of importance for disease susceptibility. Because positions DRbeta 70,71 and DQalpha 52 have been implicated in immunologic diseases, it is likely that besides being critical for T-cell recognition, they may also play a role in T-cell development and acquisition of the T-cell repertoire.

Amino Acid Sequence↗

PubMed2005

Substantial proportions of identical beta-chain T-cell receptor transcripts are present in epithelial ovarian carcinoma tumors.

To determine whether clonally expanded T cells are present in tumor specimens from patients with epithelial ovarian carcinoma (EOC) we amplified by the non-palindromic adaptor PCR (NPA-PCR) or by Vbeta-specific PCR beta-chain T-cell receptor (TCR) transcripts from these tumor specimens. The amplified transcripts were cloned and sequenced. Sequence analysis revealed the presence of substantial proportions of multiple identical copies of beta-chain TCR transcripts, suggesting the presence of clonal expansions of T cells in these patients, which were statistically significant by the binomial distribution in seven of nine patients. Independent amplification in separate experiments of beta-chain TCR transcripts from one patient by either NPA-PCR or by Vbeta-specific PCR, followed by cloning and sequencing, revealed identical clonal expansions irrespectively of the amplification method used. Multiple identical copies of beta-chain TCR transcripts can be derived only by specific antigen-driven proliferation and clonal expansion of the T-cell clones which recognize these antigens. Because of the very large size of the TCR repertoire, the probability of finding by chance multiple identical copies of these transcripts within an independent sample of T cells is negligible. These results demonstrate that T cells infiltrating solid tumor specimens or malignant ascites of patients with EOC contain monoclonal/oligoclonal populations of T cells.

Adult↗

PubMed2005

Impact of whole-body rehabilitation in patients receiving chronic mechanical ventilation.

OBJECTIVE: To evaluate the prevalence and magnitude of weakness in patients receiving chronic mechanical ventilation and the impact of providing aggressive whole-body rehabilitation on conventional weaning variables, muscle strength, and overall functional status. DESIGN: Retrospective analysis of 49 consecutive patients. SETTING: Multidisciplinary ventilatory rehabilitation unit in an academic medical center. PATIENTS: Forty-nine consecutive chronic ventilator-dependent patients referred to a tertiary care hospital ventilator rehabilitation unit. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: Patients were 58 +/- 7 yrs old with multiple etiologies for respiratory failure. On admission, all patients were bedridden and had severe weakness of upper and lower extremities measured by a 5-point muscle strength score and a 7-point Functional Independence Measurement. Postrehabilitation, patients had increases in upper and lower extremity strength (p < .05) and were able to stand and ambulate. All weaned from mechanical ventilation, but three required subsequent intermittent support. Six patients died before hospital discharge. Upper extremity strength on admission inversely correlated with time to wean from mechanical ventilation (R = .72, p < .001). CONCLUSIONS: : Patients receiving chronic ventilation are weak and deconditioned but respond to aggressive whole-body and respiratory muscle training with an improvement in strength, weaning outcome, and functional status. Whole-body rehabilitation should be considered a significant component of their therapy.

Adult↗

PubMed2005

Oxymetazoline is equivalent to ciprofloxacin in preventing postoperative otorrhea or tympanostomy tube obstruction.

OBJECTIVE: To compare the effectiveness of ciprofloxacin and oxymetazoline solutions instilled after tympanostomy tube placement in the prevention of postoperative otorrhea and tube occlusion. STUDY DESIGN: Prospective cross-sectional series. METHODS: We reviewed all bilateral myringotomy and tube placement operations performed by two full-time attending pediatric otolaryngologists during a 9 month period. Data from 488 patients who underwent surgery for otitis media were collected. Demographic and clinical variables including age, sex, number of tube insertions in the past, previous adenoidectomy, type of effusion present at surgery, and type of drop prescribed postoperatively were recorded. All patients were evaluated in the office 2 to 4 weeks postoperatively. Multivariate logistic regression analysis was used to estimate the relationship of these variables with the occurrence of otorrhea and tube patency. Odds ratios were calculated. RESULTS: No significant differences in postoperative otorrhea or tube patency were found between ciprofloxacin (Ciloxan) and oxymetazoline solutions (Afrin, Visine LR). CONCLUSION: Oxymetazoline and ciprofloxacin solutions are equivalent in the prevention of postoperative otorrhea and tube occlusion after tympanostomy tube placement. The implications for medication cost and potential adverse reactions are discussed.

Administration, Topical↗

PubMed2005

Elevated blood pressure in urban emergency department patients.

OBJECTIVES: There has been little systematic study of emergency department (ED) patients with elevated blood pressure (BP) values. The authors sought to characterize ED patients with elevated BP values, assess presenting symptoms, and determine the prevalence of elevated BP after discharge. METHODS: This was a cross-sectional study performed in four academic EDs. Adults presenting with systolic BP >or=140 mm Hg or diastolic BP >or=90 mm Hg were enrolled over a one-week equivalent period. Demographics, medical history, and symptoms were obtained by chart abstraction and structured interview. A random patient subset underwent a three-week follow-up interview. BP measurements were staged, using Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC-VI) criteria, according to the greatest value noted in the ED. RESULTS: A total of 1,396 patients were enrolled. Stage 1 BP values were noted in 44.3%, stage 2 in 25.3%, and stage 3 in 30.3%. African American patients more frequently had stage 2 and 3 BP values than other ethnic groups. BP measurements were repeated in 61.1% of patients and were the same or greater in 51.3% of patients. Dyspnea was associated with greater BP values. Among the 63.9% of patients who were interviewed, 52.7% were not being treated for hypertension, and 42.1% of those with hypertension had recently missed a medication dose. Follow-up was obtained in 74.7% of those targeted. A visit to a medical practitioner since discharge was reported by 63.2%; of these, 26.1% reported that their BP remained elevated. CONCLUSIONS: Elevated BP is common among ED patients. African American patients are more likely than those of other ethnic groups to have greater BP values. The ED visit may be a good opportunity to identify patients with unrecognized or poorly controlled hypertension.

Black or African American↗

PubMed2005

Effects of lung volume reduction surgery on sleep quality and nocturnal gas exchange in patients with severe emphysema.

STUDY OBJECTIVES: We hypothesized that associated with improvements in respiratory mechanics, lung volume reduction surgery (LVRS) would result in an improvement in both sleep quality and nocturnal oxygenation in patients with severe emphysema. DESIGN: Prospective randomized controlled trial. SETTING: University hospital. PATIENTS: Sixteen patients (10 men, 63 +/- 6 years [+/- SD]) with severe airflow limitation (FEV(1), 28 +/- 10% predicted) and hyperinflation (total lung capacity, 123 +/- 14% predicted) who were part of the National Emphysema Treatment Trial. INTERVENTIONS AND MEASUREMENTS: Patients completed 6 to 10 weeks of outpatient pulmonary rehabilitation. Spirometry, measurement of lung volumes, arterial blood gas analysis, and polysomnography were performed prior to randomization and again 6 months after therapy. Ten patients underwent LVRS and optimal medical therapy, while 6 patients received optimal medical therapy only. RESULTS: Total sleep time and sleep efficiency improved following LVRS (from 184 +/- 111 to 272 +/- 126 min [p = 0.007], and from 45 +/- 26 to 61 +/- 26% [p = 0.01], respectively), while there was no change with medical therapy alone (236 +/- 75 to 211 +/- 125 min [p = 0.8], and from 60 +/- 18 to 52 +/- 17% [p = 0.5], respectively). The mean and lowest oxygen saturation during the night improved with LVRS (from 90 +/- 7 to 93 +/- 4% [p = 0.05], and from 83 +/- 10 to 86 +/- 10% [p = 0.03], respectively), while no change was noted in the medical therapy group (from 91 +/- 5 to 91 +/- 5 [p = 1.0], and from 84 +/- 5 to 82 +/- 6% [p = 0.3], respectively). There was a correlation between the change in FEV(1) and change in the lowest oxygen saturation during the night (r = 0.6, p = 0.02). In addition, there was an inverse correlation between the change in the lowest oxygen saturation during the night and the change in residual volume (- r = 0.5, p = 0.04) and functional residual capacity (- r = 0.6, p = 0.03). CONCLUSION: In patients with severe emphysema, LVRS, but not continued optimal medical therapy, results in improved sleep quality and nocturnal oxygenation. Improvements in nocturnal oxygenation correlate with improved airflow and a decrease in hyperinflation and air trapping.

Female↗

PubMed2004

Premalignant lesions in the contralateral ovary of women with unilateral ovarian carcinoma.

OBJECTIVES: A limited number of studies have looked at premalignant lesions of ovaries and the results are conflicting. Our goal is to identify, histologically and by immunohistochemistry, any features that may represent premalignant changes in the ovaries. METHODS: Our cases included 29 patients with unilateral ovarian cancer. These were compared to 19 controls that had unilateral benign ovarian pathology and to 39 controls with bilateral normal ovaries. Tissue sections from the contralateral normal ovary were examined. Analysis of histological features and immunohistochemical staining for the apoptosis inhibitor Bcl-2, the proliferation marker Ki-67 and the tumor suppressor gene p53 was performed. RESULTS: Epithelial stratification, nuclear atypia, and inclusion cysts were more often seen in the cases than in the two control groups. Epithelial stratification and nuclear atypia was statistically significantly more common among the cases than the normal controls. Inclusion cysts were present in more of the cases (P = 0.017) and in higher numbers than in the normal controls. Bcl-2 overexpression was statistically more commonly seen in the cases with contralateral ovarian cancer (39%) than in the normal controls (15%), while it was present in 28% of cases with contralateral benign pathology. CONCLUSIONS: Epithelial alterations and Bcl-2 overexpression was seen in all three groups studied. However, the epithelial alterations and Bcl-2 overexpression was more commonly seen in the contralateral ovary of women with unilateral ovarian cancer. This suggests an association between these changes and ovarian cancer. Although it is tempting to label the above changes premalignant, women with the above changes are at possibly higher risk of developing ovarian cancer rather than having acquired an oncogenic change that would inevitably lead to ovarian cancer.

Apoptosis↗

PubMed2004

A monoclonal antibody to high-molecular weight kininogen is therapeutic in a rodent model of reactive arthritis.

We reported that high-molecular weight kininogen is proangiogenic by releasing bradykinin and that a monoclonal antibody to high-molecular weight kininogen, C11C1, blocked its binding to endothelial cells. We now test if this antibody can prevent arthritis and systemic inflammation in a Lewis rat model. We studied 32 animals for 16 days. Group I (negative control) received saline intraperitoneally. Group II (disease-treated) received peptidoglycan-polysaccharide simultaneously with C11C1. Group III (disease-untreated) received peptidoglycan-polysaccharide simultaneously with isotype-matched mouse IgG. Group IV (disease-free-treated) and group V (disease-free isotype-treated) received saline and C11C1 or mouse IgG. Analysis of joint diameter changes showed a decrease in the C11C1 disease-treated group compared to the disease-untreated group. The hind paw inflammatory score showed a decrease in the intensity and extent of inflammation between the disease-untreated and the C11C1 disease-treated group. Prekallikrein, high-molecular weight kininogen, factor XI, and factor XII were decreased in the disease-untreated group compared to the C11C1 disease-treated group. T-kininogen was increased in the disease-untreated group when compared with the C11C1 disease-treated group. Disease-free groups IV and V did not show any sign of inflammation at any time. This study shows that monoclonal antibody C11C1 attenuates plasma kallikrein-kinin system activation, local and systemic inflammation, indicating therapeutic potential in reactive arthritis.

Angiogenesis Inhibitors↗

PubMed2004

Incidence and degree of hip subluxation/dislocation in children with spinal cord injury.

BACKGROUND/OBJECTIVES: The purpose of this study was to verify the incidence and degree of hip subluxation/dislocation in children with spinal cord injury (SCI) and determine the association between age of injury and hip subluxation/dislocation. METHODS: All children from our SCI database with complete data through 2001, who had follow-up of > 2 years and were at least 14 years of age at follow-up, were included in the study. Hip subluxation was defined as a migration index (MI) > 20%. The medial joint space (MJS) was measured and considered abnormal if > 7 mm. The patients were divided into 2 groups: those < or = 10 years of age at the time of injury (group 1) and those > 10 years of age (group 2). There were 62 patients included in the study: 29 in group 1 and 33 in group 2. The mean age at the time of injury was 4.6 years for group 1 and 14.3 years for group 2. RESULTS AND CONCLUSION: Forty-eight percent of patients had at least one hip with subluxation/dislocation: 93% in group 1 and 9% in group 2. The mean MI (for those that were abnormal) was 44% in group 1 and 25% in group 2. The MJS was abnormal in 78% of hips in group 1 and 38% in group 2. Thirteen patients in group 1 and 1 patient in group 2 underwent surgery to better contain the hip. Numerous other radiographic hip irregularities were identified. This study demonstrates a high rate of hip subluxation/dislocation in children with SCI who had onset of injury before 10 years of age.

Adolescent↗

PubMed2004

Hysterectomy in obese women: a comparison of abdominal and vaginal routes.

OBJECTIVE: To compare perioperative outcome measures of abdominal and vaginal hysterectomies in obese women. METHODS: We reviewed the charts of all obese women (body mass index more than 30 kg/m(2)) who underwent abdominal or vaginal hysterectomy for benign gynecologic conditions in our institution between 1997 and 2002. Laparoscopically assisted vaginal hysterectomies and hysterectomies with concomitant major pelvic or abdominal surgery were excluded. The rate of operative and postoperative complications, length of hospitalization, operative time, and perioperative change of hemoglobin concentration were analyzed for abdominal hysterectomy and vaginal hysterectomy. RESULTS: The study group consisted of 369 obese women, of whom 189 (51.2%) underwent abdominal, and 180 (48.8%), vaginal hysterectomy. Patient characteristics were statistically comparable between the groups except for uterine weight, which was higher in the abdominal group, and parity, which was greater for women who underwent vaginal hysterectomy (P <.05). After controlling for all the significantly different variables, vaginal hysterectomy resulted in lower incidence of postoperative fever (odds ratio [OR] 0.22, 95% confidence interval [CI] 0.12-0.39), ileus (OR 0.21, 95% CI 0.06-0.75), urinary tract infection (OR 0.21, 95% CI 0.06-0.75), shorter operative time (126.8 +/- 58.7 minutes compared with 109.7 +/- 68.5 minutes) and length of hospital stay (3.5 +/- 1.9 days compared with 1.9 +/- 1.1 days). Seven women (3.7%) who underwent abdominal hysterectomy developed wound infections during their hospital stay compared with none in the vaginal hysterectomy group. CONCLUSION: For obese women, vaginal hysterectomy is superior due to its lower incidence of postoperative fever, ileus, and urinary tract infection and shorter operative time and hospital stay. LEVEL OF EVIDENCE: II-2

Female↗