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Biomedical subjects

K Barnhart

Publications and source records attributed to K Barnhart.

At least 19 recordsLinked to original sources
PubMed2006

An atypical case of Trypanosoma cruzi infection in a young English Mastiff.

A case of Trypanosoma cruzi infection in a young English Mastiff from Texas is presented. Clinical signs and laboratory findings included subcutaneous edema, lymphadenopathy, weight loss, and hypoalbuminemia. Cytology of a lymph node revealed numerous amastigotes. No trypomastigotes were observed in buffy coat preparation of peripheral blood, and on histologic evaluation, most organs contained numerous interstitial pseudocysts. Initial serology was positive for both T. cruzi and Leishmania, and immunohistochemistry supported a diagnosis of Leishmania. However, additional serology supported a T. cruzi infection, and cultivation of organisms isolated from a lymph node revealed morphology consistent with T. cruzi. In addition, PCR analysis resulted in a 504 bp fragment with 99% homology to a flagellar protein of T. cruzi. Although uncommon, autochthonous cases of both T. cruzi and Leishmania have been reported in the United States. Clinical signs observed with both diseases can show many similarities, cytology may be indistinguishable, as in this case, and serological cross-reactivity is common. This case demonstrates an unusual presentation of T. cruzi and the use of multiple testing strategies to support its diagnosis.

Animals↗
PubMed2005

Comparative sequence analysis and radiation hybrid mapping of the canine keratin 10 gene.

The type I keratin, K10, is expressed in epidermal keratinocytes undergoing terminal differentiation to form the stratum corneum, a barrier essential for life. In order to facilitate the study of keratinization disorders in the dog, the sequence and mapping of KRT10 is reported. The coding region of KRT10 is 1707 bp and is comprised of eight exons. Although the length of KRT10 has been reported to be polymorphic in humans, this was not observed in the eight domestic dog breeds studied, although one wild canid displayed a size difference. The structure and sequence of this gene is highly conserved across mammalian species. Canine K10 had an 86% amino acid identity with the human gene. KRT10 was localized to the on-going canine radiation hybrid map to chromosome 9 in the type I keratin gene cluster.

Amino Acid Sequence↗
PubMed2004

A serum proteomics approach to the diagnosis of ectopic pregnancy.

An ectopic pregnancy (EP) occurs when implantation of the embryo occurs outside of the uterus. If left untreated, the developing fetus will continue to grow, leading to life-threatening consequences for the mother. A major difficulty with the diagnosis of ectopic pregnancy is that methods of detection are limited, and some, such as ultrasound, are not very reliable in the earliest days of gestation. Currently, no effective serum test exists to distinguish an ectopic pregnancy from a normal intrauterine pregnancy. The incidence of ectopic pregnancy is increasing and has doubled in the last 20 years. It is now the second most common cause of maternal death in the first trimester of pregnancy. To address this issue, we initiated a project to identify serum markers of ectopic pregnancy. The subjects for these studies presented at the Hospital of the University of Pennsylvania. We obtained over 140 serum samples from women with suspected ectopic pregnancy: women presenting with pain and/or bleeding in the first trimester of pregnancy. The approximate racial breakdown of the subjects is as follows: African American, 36%; Caucasian, 3%; Asian, 2%; Hispanic, 1%; unknown, 58%. Serum samples from 139 women (62 with ectopic pregnancy and 77 with a normal intrauterine pregnancy) were applied to WCX2 (weak ion exchange) protein chip surfaces and analyzed for serum markers using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS). Several proteins in the 7500-18,000 Da mass range were identified that may discriminate an ectopic pregnancy from an intrauterine pregnancy. The most promising markers were analyzed using classification and regression tree analysis (CART) with and without clinical variables (serum hCG value, length of amenorrhea). Two different algorithms were developed that classify the patients on the basis of sensitivity (number of EPs who screen positive/# of EPs) or specificity (# of healthy patients who screen negative/# of healthy). Our current approach is to refine these two "rule sets" to segregate patients into three groups: those who need immediate intervention for a probable ectopic pregnancy, those who appear to have a normal pregnancy, and those who need further monitoring for diagnosis.

Biomarkers↗
PubMed2004

Comparison of two culture systems for the in-vitro growth and maturation of mouse preantral follicles.

The objective of our study was to compare to ability of collagen-treated membranes and bovine collagen gels to maintain murine preantral follicle growth and development in-vitro. To fulfill that objective, murine follicle and oocyte growth rates were followed for ten days in culture. Meiotic competence and the capacity to reach the two-cell stage after in-vitro maturation and fertilization, respectively, were then assessed. We used preantral follicles from 12 day-old CF-1 female mice that were isolated by enzymatic digestion from ovaries. Follicles were placed either on collagen-treated membranes or embedded in a bovine collagen matrix. The follicles were grown, changing the media and obtaining measurements every other day for ten days. Following culture, the granulosa-oocyte complexes were matured; the resultant metaphase II arrested oocytes were inseminated and cultured to the two-cell stage. The data was analyzed with significance considered for probability values of p < 0.05. We performed individual measurements on 650 follicles in seven separate experiments. Forty-eight hours after initial seeding and throughout the entire length of culture, both the follicles and oocytes grown in the collagen matrix were larger than follicles cultured on collagen-treated membranes (p < .0001). However, oocyte recovery rates were higher among follicles cultured on collagen-treated membranes (p < .01). Similar percentages of meiotically competent oocytes, fertilization and cleavage rates were observed in both groups. Our results show that mouse preantral follicles display a greater growth rate when grown embedded in a collagen gel matrix. This may be due to the maintenance of a normal three-dimensional organization of the follicle within the collagen matrix. However, this system does not enhance meiotic competency or fertilization rates in the mouse when compared to culture on collagen-treated membranes.

Animals↗
PubMed2001

Distribution of topical medication in the human vagina as imaged by magnetic resonance imaging.

OBJECTIVE: To assess the use of magnetic resonance imaging (MRI) to determine the varying distribution of a vaginally placed gel over time and with different levels of patient activity. DESIGN: Prospectives interventional trial. SETTING: University medical center. PATIENT(S): One nulliparous volunteer with normal menstrual cycles and no gynecologic disease who underwent seven MRI scans of the pelvis. INTERVENTION(S): Five mL of a commercially available topical spermicide was mixed with gadolinium-chelate magnetic resonance contrast material and introduced with a standard applicator. T1-weighted three-dimensional MRI was done to assess the distribution of the gel. MAIN OUTCOME MEASURE(S): Gel thickness and distribution. RESULT(S): The initial bolus of gel was delivered into the upper portion of the vagina, above the urogenital diaphragm. Thereafter, it spread into the vaginal fornices and "flattened" to cover the lateral aspects of the vagina. Without ambulation, the majority of spread was confined to the upper vagina. With ambulation and longer elapsed time, the gel spread further in the upper vagina and into the lower vagina, and significant vaginal surface coverage increased significantly. CONCLUSION(S): Magnetic resonance imaging can be used to monitor the spread of vaginally placed products and to evaluate coverage of topical drugs used for prevention and treatment, including those used for HIV prophylaxis.

Administration, Topical↗
PubMed2001

Norplant and other implantable contraceptives.

Implantable contraception represents a safe, reversible form of long-term family planning with distinct advantages. It does not contain estrogen, thus avoiding many of it contraindications. Importantly, it is extremely effective, has high continuation rates, and is well tolerated. The main side effects of Norplant are irregular menstrual bleeding and the occasional difficult removal. Although recent high-profile litigation has severely diminished enthusiasm for Norplant, the FDA has reaffirmed its safety and efficacy. Norplant remains a viable family planning option for carefully selected women. New contraceptive implants may soon be available accentuating the advantages of Norplant while minimizing the disadvantages.

Biodegradation, Environmental↗
PubMed2001

The pharmacology of methotrexate.

Ectopic pregnancy (EP) is a major cause of maternal morbidity and mortality. The treatment of this condition is primarily surgical, but medical management in selected cases is safe, effective, cost-effective and eliminates the morbidity of surgery. Methotrexate (MTX) is a folate antagonist that can be used for non-oncologic purposes including the treatment of EP. The dose and duration of MTX therapy for EP is much lower than that used in oncology cases, thus reducing side effects and increasing safety. MTX selectively acts on rapidly dividing cells, such as trophoblast cells which comprise the implantation site of the early gestation. The two most common methods of administering MTX to patients with EP are im. administration of a single-dose, based on body surface area and calculated by the equation 50 mg/m(2) (without the need for leucovorin rescue), or the multiple-dose regimen of 1 mg/kg of MTX, alternating with 0.1 mg/kg of leucovorin rescue. Both methods have a similar side effect profile, resulting in the rare occurrence of nausea, vomiting, stomatitis, elevated liver function tests, anorexia and diarrhoea. The two methods yield success rates similar to those of conservative surgical therapy with similar future fertility. The potential single- and multi-dose methods have never been directly compared, but it appears that the success of multiple dosing is more effective. As the efficacy of MTX therapy is not 100%, women must be followed clinically until there is compete resolution of human Chorionic Gonadotropin (hCG) titres from their serum.

Animals↗
PubMed2000

Spontaneous second trimester uterine rupture after classical cesarean.

BACKGROUND: Several cases of spontaneous second trimester uterine rupture have been reported, but none as early as 15 weeks' gestation after classical cesarean and with placenta percreta. CASE: A 23-year-old woman, gravida 5, para 3, at 15 37 weeks' gestation with a history of classical cesarean incision presented to the emergency department with abdominal pain, hypotension, and tachycardia. Ultrasound showed a normal intrauterine pregnancy. She developed worsening pain, abdominal rebound, and abdominal distention. On exploratory laparotomy, a large uterine rupture was found and hysterectomy was done. CONCLUSION: Spontaneous uterine rupture after classical cesarean can occur as early as 15 weeks' gestation. Uterine rupture must be considered in differential diagnoses of severe abdominal pain even in the early second trimester.

Abdominal Pain↗
PubMed2000

An update on the medical treatment of ectopic pregnancy.

Medical treatment of ectopic pregnancy with methotrexate has been shown to be effective and safe in appropriate patients. When considering medical management, the definitive diagnosis of an ectopic pregnancy and the assurance that the patient is a candidate are of paramount concern. An understanding of the mechanism of action and pharmacokinetics of methotrexate allows the clinician to better inform patients, recognize and treat side effects, and be cognizant when treatment is unsuccessful. Two common protocols, the "multi-dose" and the "single-dose" protocols, have excellent success rates; however, neither one of these is completely effective. The "multi-dose" protocol appears to have a higher success rate than the "single-dose" protocol.

Abortifacient Agents, Nonsteroidal↗
PubMed1999

Vaginal drug delivery. 7-8 June 1999, London, UK.

This meeting collected experts from the field of clinical medicine and pharmaceutical companies to discuss various issues concerning vaginal drug delivery. The conference was divided into large sub-categories, such as the advantages of a vaginal system, including its potential use in providing both disease-specific and systemic drug administration. The specific need for topical microbicides and anti-HIV systems were highlighted. Discussions included the unique anatomical and physiological characteristics of the human vagina as well as the potential lack of an animal model to predict clinical results. Specific formulation techniques discussed included: polycarbophil, as a bio-adhesive; a hydrogel, Hycor-V; membrane lipids, such as Q-vail; and a hybrid emulsion system, such as the Site Release system. The potential development of vaginal vaccines and vaginal rings to provide systemic drug delivery were also discussed. Finally, there was discussion regarding the information needed to evaluate and develop novel actives and delivery systems. The general agreement from representatives of regulatory bodies was that, because of the uniqueness of this anatomical area and technology used, early participation of regulatory agencies to assist with development is highly recommended. The conference was chaired by Dr Ian Wilding (Chief Executive, Pharmaceutical Profiles, Nottingham, UK) and Professor SS Davis (Chairman, West Pharmaceutical Services, formerly DanBioSyst UK Ltd, Nottingham, UK). Forty participants from industry and academia were in attendance. Speakers included representatives of academic institutions from Europe and the US, the FDA, the National Institutes of Health as well as from numerous international pharmaceutical corporations.

Journal Article↗
PubMed1998

A plasmid encoding murine granulocyte-macrophage colony-stimulating factor increases protection conferred by a malaria DNA vaccine.

Using the murine parasite Plasmodium yoelii (Py) as a model for malaria vaccine development, we have previously shown that a DNA plasmid encoding the Py circumsporozoite protein (PyCSP) can protect mice against sporozoite infection. We now report that mixing a new plasmid PyCSP1012 with a plasmid encoding murine granulocyte-macrophage colony-stimulating factor (GM-CSF) increases protection against malaria, and we have characterized in detail the increased immune responses due to GM-CSF. PyCSP1012 plasmid alone protected 28% of mice, and protection increased to 58% when GM-CSF was added (p < 0.0001). GM-CSF plasmid alone did not protect, and control plasmid expressing inactive GM-CSF did not enhance protection. GM-CSF plasmid increased Abs to PyCSP of IgG1, IgG2a, and IgG2b isotypes, but not IgG3 or IgM. IFN-gamma responses of CD8+ T cells to the PyCSP 280-288 amino acid epitope increased but CTL activity did not change. The most dramatic changes after adding GM-CSF plasmid were increases in Ag-specific IL-2 production and CD4+ T cell proliferation. We hypothesize that GM-CSF may act on dendritic cells to enhance presentation of the PyCSP Ag, with enhanced IL-2 production and CD4+ T cell activation driving the increases in Abs and CD8+ T cell function. Recombinant GM-CSF is already used in humans for medical purposes, and GM-CSF protein or plasmids may be useful as enhancers of DNA vaccines.

Animals↗
PubMed1998

Follicle stimulating hormone as a predictor of fertility.

Tests for diminished ovarian reserve provide valuable prognostic information for women considering assisted reproductive technology. The best characterized screening tool for a general infertility patient is the clomiphene citrate challenge test. These screening tests do not have absolute sensitivity or specificity. Additionally, the predictive value of these tests can be low if used in a population at low risk. Patients with abnormal testing should be counselled that their chances of conception with assisted reproductive technology are poor. This may impact on the choice of aggressive treatment; however, the results of these tests should never be used to exclude patients from care.

Female↗
PubMed1997

Neuroendocrine mechanism of anovulation in users of contraceptive subdermal implant of nomegestrol acetate (Uniplant).

OBJECTIVE: To evaluate a nomegestrol acetate subdermal contraceptive implant's (Uniplant; Thermex, Monaco) effect on the hypothalamus-pituitary-ovarian axis. DESIGN: A prospective clinical trial. SETTING: San Borja-Arriarán Clinical Hospital, University of Chile, School of Medicine. PATIENT(S): Normally cycling healthy women. INTERVENTION(S): Insertion of Uniplant. MAIN OUTCOME MEASURE(S): Luteinizing hormone pulse and endocrine profiles were assessed before, 48 hours after insertion, and after prolonged use of the implant. RESULT(S): Anovulation was noted in 100% of users in the first month. Seventy percent of subjects demonstrated follicular development with the absence of ovulation and an endocrine profile similar to the follicular phase: (LH pulse/8 hours 6.85 +/- 0.67, LH amplitude 3.54 +/- 0.65 mIU/mL (conversion factor to SI unit, 1.00), and E2 193 +/- 29.4 pg/mL (conversion factor to SI unit, 3.67), whereas 30% demonstrated no follicular activity with an endocrine profile similar to the luteal phase: (LH pulse/8 hours; 3.66 +/- 0.66, LH amplitude 5.76 +/- 1.73 mIU/mL, and E2 67.5 +/- 4 pg/mL. Clinical characteristics, serum gonadotropin concentration, and LH pulse characteristics failed to predict which subjects would initiate or remain devoid of follicular activity. CONCLUSION(S): Uniplant results in anovulation via two mechanisms: hypothalamic suppression in subjects who lack follicular development, and likely suppression of the pituitary LH surge in subjects who initiate follicular activity.

Adult↗
PubMed1997

Hormonal profile, endometrial histology and ovarian ultrasound assessment during 1 year of nomegestrol acetate implant (Uniplant).

The present study assesses the endocrinological, endometrial histology and vaginal ultrasound profiles of nomegestrol acetate subdermal implant users at varying times after insertion. Follicle stimulatory hormone, luteinizing hormone, oestradiol, progesterone, vaginal ultrasound assessment of the ovaries and the histological dating of the endometrium were serially assessed for a period of 50 days immediately after the insertion, and after at 6 months and 12 months of use. The endocrinological results of this prospective observational clinical trial indicated that 75% of the cycles across the study period in Uniplant users were anovulatory, 63% showing development of a persistent non-luteinized follicle. Anovulatory cycles devoid of follicular development were seen primarily in the first months after Uniplant insertion. Ovulatory cycles represented 25% of the Uniplant cycles. Inadequate luteal phase or disregulation of follicular growth was a common feature of ovulatory cycles. In conclusion, these findings suggest that the contraceptive mechanisms of a single nomegestrol acetate subdermal implant involve prevention of follicular growth, development of a persistent non-luteinized follicle, inadequate luteal phase and disruption of the endometrial architecture.

Adult↗
PubMed1997

Medical treatment of interstitial pregnancy. A report of three unsuccessful cases.

BACKGROUND: Medical management of ectopic pregnancy is effective in selected cases and is recommended to treat interstitial pregnancy to avoid surgery that may limit future fertility. Although successful medical management of interstitial pregnancy has been reported, evidence does not support success rates equal to that in other ectopic locations. CASES: Four cases of interstitial ectopic pregnancy were identified. Only one of the four was successfully treated with medical therapy. Case 1 was a confirmed, 2.5-cm interstitial pregnancy that failed a multiple-dose methotrexate protocol. Case 2 was an unrecognized interstitial pregnancy that failed single-dose therapy. Case 3 was a rupture of a medically managed interstitial pregnancy despite complete resolution of serum human chorionic gonadotropin. A literature review demonstrated an overall combined failure rate of 35% (7/20). CONCLUSION: Compared with an isthmic or ampullary pregnancy, a disproportionate number of patients with interstitial pregnancy fail medical management and require emergency surgery. The presence of a documented interstitial pregnancy is not an absolute contraindication to medical management. Patients should be counseled that medical management of an interstitial pregnancy may not have the same rate of success as it does in other locations in the fallopian tube. Surgery in this case may be the preferred treatment option.

Abdominal Pain↗
PubMed1996

An improved plasmid DNA expression vector for direct injection into skeletal muscle.

In previous work, the direct injection of 50 micrograms of a plasmid DNA vector encoding firefly luciferase (VR1205) into murine quadriceps muscle produced an average of 6.5 ng of luciferase per muscle at 7 days postinjection. In this report, various elements of the VR1205 vector were modified to increase gene expression levels or to eliminate undesired viral sequences. Expression of the modified vectors was then compared to VR1205 using the intramuscular injection assay. In general, modifications to promoter, enhancer, and intronic sequences either decreased luciferase expression levels or had no effect. However, modifications to the polyadenylation and transcriptional termination sequences, plasmid backbone elements, and the luciferase gene itself each increased luciferase expression levels. The best-expressing vector, designated VR1255, contained a combination of these incrementally beneficial changes. A single intramuscular injection of 50 micrograms of VR1255 produced 300 ng of luciferase at 7 days postinjection, an expression level 46-fold higher than the VR1205 vector (or 22-fold higher, excluding modifications to the luciferase gene) and 154-fold higher than a commercially available luciferase expression vector. Thus, VR1255 represents an improved plasmid DNA vector that may be useful for gene therapy applications.

Animals↗