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1.
Int J Surg ; 74: 113-117, 2020 Feb.
Article in English | MEDLINE | ID: mdl-31911216

ABSTRACT

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) may induce gastro-oesophageal reflux disease and surgical techniques should be sought to reduce reflux after LSG. Gastropexy of the sleeve gastrectomy pouch to prevent kinks, torsion and intrathoracic sleeve migration was added to our standard LSG in 2012, and the aim of this study was to evaluate if adding gastropexy has influenced the occurrence of gastrooesophageal reflux symptoms (GORS) after LSG. METHODS: In this prospective two-cohort study, the group with LSG and gastropexy (G) was compared with a historical cohort who did not have gastropexy (NG). The use of acid-reducing medication (ARM) was used as a proxy measure of GORS. Gastropexy was performed by suturing the gastrocolic ligament (including the gastroepiploic arcade) to the staple line from the cardia to well below the incisura angularis. Non-resorbable sutures were used. Multiple logistic regression analysis was used to study differences in the use of ARM between the NG and G group two years after surgery. RESULTS: Patient characteristics as age, gender and BMI at baseline, and excess body mass index loss (EBMIL) and smoking at two years were similar between the NG group (n = 216) and G group (n = 116). The follow-up rate was 86.4% for the NG group and 85.3% for the G group. Adding gastropexy did not increase the morbidity rate. In the NG group, the number of patients using ARM was 21 (9.7%) preoperatively and 66 (30.6%) two years after surgery. In the G group, the number using ARM was 11 (10.4%) preoperatively and 18 (14.2%) two years after surgery. The adjusted odds ratio for postoperative GORS in group G compared to group NG was 0.32 (95% CI: 0.16-0.64, p < 0.001). CONCLUSION: Gastropexy may prevent postoperative reflux symptoms after LSG. We recommend to evaluate gastropexy in a randomized controlled trial.


Subject(s)
Antacids/therapeutic use , Gastrectomy/adverse effects , Gastroesophageal Reflux/prevention & control , Gastropexy/methods , Laparoscopy/methods , Obesity, Morbid/surgery , Postoperative Complications/prevention & control , Adult , Body Mass Index , Female , Gastroesophageal Reflux/surgery , Humans , Logistic Models , Male , Middle Aged , Prospective Studies
2.
Horm Metab Res ; 43(8): 587-90, 2011 Jul.
Article in English | MEDLINE | ID: mdl-21667427

ABSTRACT

Cortisol increases have been associated with psychological and physiological stress; however, cortisol dynamics after weight loss (bariatric) surgery have not been defined. Obese participants not using exogenous glucocorticoids were eligible to participate. Female participants (n=24) provided salivary cortisol samples at bedtime, upon awakening the following morning, and 30 min after awakening before, and at 6 or 12 months after bariatric surgery. The Medical Outcomes Study Short Form-12 version 2 questionnaire regarding health-related quality of life was also completed. Preoperatively, mean body mass index was 45.1±8.1 kg/m2. Mean late night (1.8±1.1 nmol/l), awakening (10.7±7.4 nmol/l), and after-awakening (11.5±7.9 nmol/l) salivary cortisol values were within normal ranges. The cortisol awakening response (mean 21.1±79.7%, median 13.7%) was at the low end of normal. Preoperatively, participants had lower mental and physical health-related quality of life scores than US adult norms (p<0.001). Salivary cortisol was not correlated with measures of health-related quality of life. Mean BMI decreased over time (p<0.001) and participants experienced improved physical and mental health-related quality of life (p≤0.011). Postoperative late night salivary cortisol was not different from preoperative values. Awakening and after-awakening cortisol levels were higher than preoperative values (15.3±7.7 nmol/l, p=0.013; 17.5±10.2 nmol/l, p=0.005; respectively), but the cortisol awakening response was not changed (mean 26.7±66.2%; median 7.8%). Morning salivary cortisol increased at long-term follow-up after bariatric surgery. Although self-evaluated mental and physical health improved after surgery, the cortisol awakening response is at the low end of normal, which may indicate continued physiological stress.


Subject(s)
Bariatric Surgery , Hydrocortisone/metabolism , Saliva/metabolism , Female , Humans , Middle Aged , Postoperative Care , Preoperative Care
3.
J Laparoendosc Adv Surg Tech A ; 11(2): 79-83, 2001 Apr.
Article in English | MEDLINE | ID: mdl-11327131

ABSTRACT

BACKGROUND AND PURPOSE: Biliopancreatic diversion with a duodenal switch is an emerging open procedure that appears as effective as other bariatric operations. Our goal was to determine the safety and feasibility of performing this procedure using a laparoscopic approach in a porcine model. MATERIALS AND METHODS: Six 50-kg pigs underwent surgery. Intake was restricted with a sleeve gastrectomy, and malabsorption was obtained by creating a Roux-en-Y. The Roux limb served as a 150-cm alimentary channel following anastomosis to a transected proximal duodenum, while the other limb, or biliopancreatic channel, transported digestive juices. Where the two limbs joined, a 100-cm common channel was formed. RESULTS: The operation was completed in a mean time of 4.5 hours. Two of the six pigs had an intraoperative duodenoenterostomy anastomotic leak detected on methylene blue testing. This leakage was thought to be related to pig anatomy and is not expected to be a problem in humans. At necropsy, all anastomoses were patent, and there were no enteroenterostomy leaks or mesenteric torsions. CONCLUSION: On the basis of the porcine model, laparoscopic biliopancreatic diversion with a duodenal switch is anticipated to be feasible and safe in humans. Substantial weight loss combined with the benefits of laparoscopic surgery can be expected.


Subject(s)
Biliopancreatic Diversion/methods , Duodenum/surgery , Laparoscopy , Obesity, Morbid/surgery , Anastomosis, Roux-en-Y , Animals , Disease Models, Animal , Feasibility Studies , Gastrectomy , Swine
4.
Surg Laparosc Endosc Percutan Tech ; 11(2): 116-8, 2001 Apr.
Article in English | MEDLINE | ID: mdl-11330376

ABSTRACT

Leiomyomas comprise fewer than 1% of esophageal neoplasms. Only 2% of leiomyomas are extraesophageal, and the remainder are intramural or intraluminal. A presumed intra-abdominal mass found at diagnostic laparoscopy was discovered to be an extraesophageal leiomyoma. Esophageal leiomyoma enucleation is most commonly accomplished via a thoracotomy. Increasingly, thoracoscopy has been used. An open transhiatal approach has also been described. Our patient underwent an uncomplicated transhiatal laparoscopic esophageal leiomyoma resection and benefited from the commonly recognized advantages associated with minimally invasive surgery.


Subject(s)
Abdominal Neoplasms/surgery , Esophageal Neoplasms/surgery , Laparoscopy , Leiomyoma/surgery , Abdominal Neoplasms/diagnostic imaging , Esophageal Neoplasms/diagnostic imaging , Female , Humans , Leiomyoma/diagnostic imaging , Middle Aged , Tomography, X-Ray Computed
6.
J Vasc Surg ; 32(4): 814-7, 2000 Oct.
Article in English | MEDLINE | ID: mdl-11013046

ABSTRACT

A 43-year-old woman presented with symptomatic mesenteric ischemia caused by median arcuate ligament compression of her celiac artery. Magnetic resonance angiography clearly demonstrated stenosis of the proximal celiac artery. She underwent laparoscopic decompression by division of the ligament and excision of the celiac plexus. Laparoscopic Doppler ultrasound scanning demonstrated markedly improved flow in the artery. She was discharged in 15 hours and reported complete resolution of her symptoms at the 3-month postoperative visit. Laparoscopy provides a less invasive but equally effective method for decompressing the celiac artery as well as assessing adequacy of flow after its release.


Subject(s)
Arterial Occlusive Diseases/surgery , Celiac Artery , Decompression, Surgical/methods , Laparoscopy , Ultrasonography, Interventional , Adult , Celiac Artery/physiology , Female , Humans , Postoperative Period , Regional Blood Flow
7.
Endocrinol Metab Clin North Am ; 29(1): 57-68, viii, 2000 Mar.
Article in English | MEDLINE | ID: mdl-10732264

ABSTRACT

Because widespread use of imaging techniques has led to the frequent detection of incidentalomas, radiologists, endocrinologists, and endocrine surgeons must be knowledgeable about the appropriate evaluation of patients, and the selection of the appropriate surgical approach, including conventional open and laparoscopic adrenalectomy. This article reviews the authors' preferences based on experience with nearly 200 laparoscopic adrenalectomies.


Subject(s)
Adrenal Gland Neoplasms/surgery , Adrenal Cortex Hormones/blood , Adrenal Gland Neoplasms/pathology , Adrenal Gland Neoplasms/physiopathology , Adrenalectomy/methods , Biopsy, Needle , Humans , Preoperative Care
8.
Thyroid ; 9(12): 1221-6, 1999 Dec.
Article in English | MEDLINE | ID: mdl-10646662

ABSTRACT

Models that demonstrate histological invasion of extracellular matrix barriers by tumor cell lines are useful for assessing new methods to treat or prevent tumor metastasis. An in vivo invasion model using acellular human dermal matrix has been described in a murine squamous cell carcinoma line. The present study examined the application of this tumor invasion model to another epithelial cell line derived from a different species. A human follicular thyroid carcinoma cell line, known to be invasive by other assays, was grown on the dermal-epidermal basement membrane surface of human acellular dermal matrix in culture and then grafted in athymic mice. Immunohistochemical staining of type IV collagen was used to identify the basement membrane and invasion was determined as penetration of the basement membrane by tumor cells. Identification of the human tumor cells in the in vivo grafts was done by in situ hybridization with species specific probes. FTC-133 tumor cells did not invade the matrix after 4 weeks of growth in in vitro culture, but there was extensive loss of the basement membrane and infiltration of the tumor cells into the dermis after 2 weeks growth in vivo. This study suggests that the in vivo dermal matrix model of invasion is applicable to a broad range of epithelial carcinoma cell lines to study their capability to penetrate basement membrane. A model such as this may be useful for studying the local effects of genetic manipulations of implanted tumor cell populations, leading to the development of therapeutic agents that block invasion.


Subject(s)
Adenocarcinoma, Follicular/pathology , Thyroid Neoplasms/pathology , Animals , Basement Membrane/metabolism , Basement Membrane/pathology , Collagen/metabolism , Cytological Techniques , Extracellular Matrix/metabolism , Humans , Mice , Mice, Nude , Neoplasm Invasiveness/pathology , Neoplasm Transplantation , Skin/metabolism , Skin/pathology , Tumor Cells, Cultured
9.
Surg Technol Int ; 8: 105-9, 1999.
Article in English | MEDLINE | ID: mdl-12451517

ABSTRACT

Laparoscopic hepatic cryotherapy, using intraoperative ultrasound monitoring, was introduced in the 1980s by Onik who combined the freezing process with intraoperative ultrasound for monitoring the extent of freezing. The results of open cryotherapy of the liver have been reported for more than 900 patients, the majority having received cryotherapy for liver metastases from colorectal carcinoma and primary hepatocellular carcinoma. While data on the long-term outcome of patients treated with cryotherapy are limited, some authors have documented survival comparable to that for hepatic resecrion. This is remarkable, considering these patients are often deemed unresectable and most do not even survive 1 year.

10.
Thyroid ; 8(6): 475-83, 1998 Jun.
Article in English | MEDLINE | ID: mdl-9669284

ABSTRACT

Hürthle cell carcinomas (HCC) of the thyroid are a variant of follicular thyroid tumors. In contrast to follicular thyroid carcinoma, HCC rarely take up radioiodine and frequently metastasize to the lymph nodes. Histologically they are indistinguishable from Hürthle cell adenomas except for evidence of invasion and metastasis. How these carcinomas develop and why they behave differently than other follicular tumors is not known. Although some differentiated thyroid cancer cell lines exist, none are from Hürthle cell tumors. We have established a well-differentiated thyroid cancer cell line from a metastasis of a HCC, designated XTC.UC1. In vitro, XTC cells display epitheloid morphology, grow with a population doubling time of 4.3 +/- 0.3 days, migrate, and invade through reconstituted basement membranes. The cells are immunoreactive for and release thyroglobulin, respond to thyrotropin (TSH) with increase of intracellular cyclic adenosine monophosphate (cAMP), proliferation, and invasion of reconstituted basement membrane, thus exhibiting characteristics of well-differentiated thyroid carcinoma. In vivo, xenografted XTC cells grow with a doubling time of 9.8 +/- 0.8 days. Tumors spontaneously metastasize to the lymph nodes and less frequently to the lungs and the liver. The cells retained their differentiated function in vivo as assessed by human thyroglobulin (hTG) secretion and immunohistochemistry. This is a first report of the establishment of a unique, highly differentiated thyroid carcinoma cell line derived from an HCC. Based on the ability to invade through reconstituted basement membrane in vitro and the potential to metastasize in vivo, this cell line may provide a unique model to study invasion and metastazation of well-differentiated thyroid cancer.


Subject(s)
Adenocarcinoma/pathology , Thyroid Neoplasms/pathology , Adenocarcinoma/metabolism , Adenocarcinoma/secondary , Carcinogenicity Tests , Cell Division/drug effects , Cell Movement/physiology , Cyclic AMP/metabolism , Female , Flow Cytometry , Humans , Intracellular Membranes/metabolism , Karyotyping , Middle Aged , Neoplasm Invasiveness/pathology , Thyroglobulin/metabolism , Thyroid Neoplasms/metabolism , Thyrotropin/pharmacology , Tumor Cells, Cultured
11.
World J Surg ; 22(6): 544-51, 1998 Jun.
Article in English | MEDLINE | ID: mdl-9597926

ABSTRACT

Desensitization is defined as a decreased functional response after continuous or repetitive stimulation of a receptor with its agonist. Thyrotropin (TSH) increases cAMP levels in normal and neoplastic thyroid tissue. The tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate (TPA) activates protein kinase C (PKC). The aim was to determine whether TPA induces heterologous desensitization of the TSH-adenylate cyclase (AC) signal transduction system. Three human thyroid neoplasms in culture for 6 months or longer (one papillary carcinoma, one Hurthle cell carcinoma, one follicular adenoma) were incubated with TSH (10 mU/ml) and TPA (1.6 x 10(-8) M) separately and together for various time periods (from 10 minutes to 24 hours). The mixture was subsequently incubated for 30 minutes with TSH. TPA alone had no effect on cAMP levels, but co-incubation of TPA and TSH caused a significant reduction in cAMP response when compared to the cAMP response that resulted after stimulation with only TSH (p < 0.001). cAMP levels in response to TSH decreased by 31%, 44%, and 57% after preincubation with TSH for 10 minutes, 4 hours, and 24 hours, respectively (p < 0.01; ANOVA). Co-incubation of cells with TPA and staurosporine (10 ng/ml), a PKC inhibitor, prevented the effect of TPA on desensitization at 10 minutes and blunted the effect at 4 hours. This is the first demonstration in human neoplastic thyroid cells that TPA induced heterologous desensitization of the cAMP response to TSH. This TPA-induced effect appears to involve PKC activation, as it can be blocked by staurosporine.


Subject(s)
Adenylyl Cyclases/physiology , Signal Transduction/physiology , Thyroid Neoplasms/metabolism , Thyrotropin/physiology , Type C Phospholipases/physiology , Carcinogens/pharmacology , Cyclic AMP/biosynthesis , Humans , Tetradecanoylphorbol Acetate/pharmacology , Thyrotropin/pharmacology , Tumor Cells, Cultured
12.
J Clin Endocrinol Metab ; 81(10): 3498-504, 1996 Oct.
Article in English | MEDLINE | ID: mdl-8855792

ABSTRACT

Mutations in the tumor suppressor gene p53 are the most-common mutations found in human cancers. In thyroid cancers, p53 mutations generally are found only in poorly differentiated and undifferentiated tumors and in cell lines. To determine the prevalence of p53 mutations in thyroid neoplasms and thyroid cell lines, we screened 58 thyroid tissues and 3 thyroid cell lines, p53 primers bracketing exons 4, 5/6, 7, and 8 were used to amplify genomic DNA using the PCR. Mutations were screened by denaturing gradient gel electrophoresis and confirmed by sequencing. The two papillary thyroid cancer cell lines and the follicular thyroid carcinoma cell line (positive control) had transitions (CGT->CAT) in exon 8, codon 273, resulting in the replacement of arginine with histidine. No normal thyroid tissues or primary tumors from which the cell lines were derived demonstrated exon 8 mutations, using this technique. p53 immunocytochemistry demonstrated a progression of p53 immunopositivity between synchronous and metachronous neoplasms, paralleling the neoplastic progression from a benign adenoma to primary carcinoma, regional, and distant metastasis and ultimately, the cell lines, where intense immunopositivity is noted. In addition, fluorescence in situ hybridization, using probes specific for the p53 locus, revealed the presence of 3 homologues of p53 in the follicular cell line and 2 homologues in the papillary and Hürthle cell lines. These results suggest that a point mutation present in a small number of original tumor cells and amplification of the mutant allele may be responsible for immortalizing well-differentiated thyroid cancer cells into cell lines.


Subject(s)
DNA, Neoplasm/analysis , Genes, p53/genetics , Immunohistochemistry , Point Mutation , Thyroid Neoplasms/genetics , Tumor Suppressor Protein p53/analysis , Adenocarcinoma, Follicular/genetics , Carcinoma, Papillary/genetics , DNA Probes , Humans , In Situ Hybridization, Fluorescence , Polymerase Chain Reaction , Sequence Analysis, DNA , Tumor Cells, Cultured , Tumor Suppressor Protein p53/genetics
13.
Cytogenet Cell Genet ; 75(4): 254-7, 1996.
Article in English | MEDLINE | ID: mdl-9067436

ABSTRACT

The sequence-tagged site (STS) D10S170, also referred to as H4, is a gene of unknown function. Its 5' end was found fused to the catalytic domain of the RET protooncogene to generate RET/PTC 1, the most common form of PTC oncogenes in human papillary thyroid carcinoma. This gene has previously been assigned to a very large genomic region, 10q11.22-->q22.1. Here, we describe the application of a novel hybridization scheme to the physical and genetic mapping of D10S170. First, we selected a homologous large-insert DNA clone from a human P1 library by filter hybridization and confirmed its authenticity by Southern blot analysis. Triple-color fluorescence in situ hybridization (FISH) experiments mapped this clone to l0q21.2-->q21.3. "Binning" experiments were performed using a quadruple-color FISH approach aimed toward placing the gene in a genetic interval defined by differentially labeled P1 DNA probes containing known polymorphic markers. We found that multicolor FISH greatly expedites chromosomal mapping. Finally, we applied our FISH approach to determine the extent of deletion involving this locus (D10S170) in a papillary thyroid cancer cell line, TPC-1.


Subject(s)
Carcinoma, Papillary/genetics , Chromosome Mapping/methods , Chromosomes, Human, Pair 10/genetics , Drosophila Proteins , Fluorescent Dyes , Genetic Markers , In Situ Hybridization, Fluorescence/methods , Oncogene Proteins, Fusion/genetics , Sequence Deletion , Thyroid Neoplasms/genetics , Carcinoma, Papillary/pathology , Chromosome Inversion , Chromosomes, Human, Pair 10/ultrastructure , Chromosomes, Human, Pair 21/genetics , Chromosomes, Human, Pair 21/ultrastructure , DNA Probes , DNA, Neoplasm/genetics , Humans , Protein-Tyrosine Kinases , Proto-Oncogene Proteins/genetics , Proto-Oncogene Proteins c-ret , Receptor Protein-Tyrosine Kinases/genetics , Thyroid Neoplasms/pathology , Translocation, Genetic , Tumor Cells, Cultured
14.
Surgery ; 118(6): 1018-23, 1995 Dec.
Article in English | MEDLINE | ID: mdl-7491517

ABSTRACT

BACKGROUND: Activation of the ret proto-oncogene by three different chromosomal rearrangements occurs in up to 25% of papillary thyroid carcinomas. We developed a rapid screening technique to detect ret rearrangements in human interphase and metaphase cells on the basis of multicolor fluorescence in situ hybridization (FISH) of locus-specific DNA probes. METHODS: DNA from individual clones representing the respective ends of a yeast artificial chromosome (YAC) contig spanning the entire ret gene locus were labeled with either digoxigenin (visualized in red) or biotin (green) and hybridized to normal human lymphocytes and the papillary thyroid cancer cell line TPC-1 expressing the ret/H4 chimeric transcript. Further detailed analysis was performed with whole chromosome painting probes and locus-specific probes (YACs, P1s, DNA repeat probes) on tumor metaphase spreads. RESULTS: Hybridization of the YACs to unrearranged ret loci in normal human lymphocyte interphase nuclei showed two yellow domains because of probe overlap. Hybridization to TPC-1 interphase nuclei showed one yellow domain, and 1 red and 1 green domain separated by a large physical distance. Further analysis of metaphase spreads revealed a complex translocation t(1;10;21)(1pter > 1q31::21q22.1 > 21qter; 10q11.2 > 10pter::1q31 > 1qter; 21pter > 21q22.1;;10q21.2 > 10q11.2::10q21.2 > 10qter) and loss of the H4 gene locus on the nontranslocated chromosome 10. CONCLUSIONS: Break point spanning probes can reliably detect ret rearrangements in interphase nuclei. Locus-specific and whole chromosome painting probes can be used to further characterize complex rearrangements by fluorescence in situ hybridization to metaphase spreads. The papillary thyroid cancer cell line TPC-1 carries the paracentric inversion 10q, inv(10)(q11.2q21) and a complex t(1; 10; 21) translocation. Deletion of the H4 gene on the chromosome 10 not involved in the t(1; 10; 21) translocation suggests lack of normal H4 expression in the TPC-1 cell line. Further studies will have to address the role of the H4 gene product in tumor genesis and progression.


Subject(s)
Carcinoma, Papillary/genetics , Chromosomes, Human, Pair 10 , Chromosomes, Human, Pair 1 , Chromosomes, Human, Pair 21 , Thyroid Neoplasms/genetics , Translocation, Genetic , Chimera , Chromosomes, Artificial, Yeast , DNA Probes , Humans , In Situ Hybridization, Fluorescence , Proto-Oncogene Mas , Tumor Cells, Cultured
15.
Thyroid ; 5(2): 101-5, 1995 Apr.
Article in English | MEDLINE | ID: mdl-7647568

ABSTRACT

Attempts to purify the thyroid-stimulating hormone receptor (TSHR) have been complicated by its susceptibility to proteolysis and its low level of expression in thyrocytes and many transfected cells. Controversy exists over its size and structure. Multiple, single-polypeptide forms of the TSHR (230, 187, and 95-100 kDa) have been recently identified in immunoblots of crude plasma membranes prepared from COS-7 cells transfected with rat or human cDNA, but the relationship of these receptor species to the TSHR in human thyroid tissue has been heretofore unknown. We have developed a technique for immunoprecipitation of the TSHR which employed IgG purified from a polyclonal rabbit antiserum to TSHR residues 352-366. We have used immunoprecipitation to isolate the previously characterized 95-100 kDa TSH-holoreceptor, 187 kDa intermediate, and 230 kDa precursor forms of the TSHR from plasma membrane prepared from transfected COS-7 cells and human thyroid tissue. The presence of all three forms was not altered by the addition of reducing agent to the sample buffer, demonstrating the single polypeptide structure of the TSHR. This is, to our knowledge, the first report of the purification from transfected COS-7 cells of these TSHR species identified previously only in immunoblots of crude plasma membrane, and the first report of the identification by any means of these TSHR forms in human thyroid tissue. The isolation of TSHR from human thyroid tissue requires confirmation by direct means, but promises to make the receptor available in a soluble form for studies of its structure and function.


Subject(s)
Receptors, Thyrotropin/isolation & purification , Thyroid Gland/chemistry , Cell Line , Cell Membrane/chemistry , Humans , Immunoblotting , Isomerism , Molecular Weight , Precipitin Tests , Transfection
18.
Pharm Res ; 11(6): 860-4, 1994 Jun.
Article in English | MEDLINE | ID: mdl-7937526

ABSTRACT

Antimicrobial treatment failures in children with acute otitis media and concomitant viral respiratory tract infection prompted us to study the effects of influenza A virus infection on middle ear antimicrobial drug penetration. Using a chinchilla model of Streptococcus pneumoniae we compared middle ear elimination rates in 4 groups of chinchillas: (1) control, (2) influenza A virus inoculation alone intranasally, (3) both influenza A and S. pneumoniae inoculation directly into the middle ear, and (4) S. pneumoniae inoculation alone into the middle ear. After infection was established, a solution containing amoxicillin, sulfamethoxazole, and trimethoprim was instilled into the middle ear and removed 4 hours later. The rate constant of elimination and half-life were calculated from measured drug concentrations initially and at 4 hours. S. pneumoniae infection alone significantly shortened the middle ear elimination half-life compared with the control group: amoxicillin, 2.65 +/- 0.73 vs. 6.63 +/- 2.55 hr; sulfamethoxazole, 1.75 +/- 0.28 vs. 2.74 +/- 0.6 hr; and trimethoprim, 1.06 +/- 0.14 vs. 1.56 +/- 0.34 hr (n = 16 ears, p values all < 0.01). The combined influenza virus and S. pneumoniae infection significantly lengthened the half-life compared with the S. pneumoniae infection alone: amoxicillin, 5.65 +/- 6.44 vs. 2.65 +/- 0.73 hr; sulfamethoxazole, 2.5 +/- 0.85 vs. 1.75 +/- 0.28 hr; and trimethoprim, 1.26 +/- 0.42 vs. 1.06 +/- 0.14 hr (n = 16 ears, p values all < 0.01). Influenza virus produced the longest half-lives for all 3 antimicrobials: amoxicillin 25.52 +/- 14.96 hr; sulfamethoxazole, 5.46 +/- 0.87 hr; and trimethoprim, 2.57 +/- 0.75 hr.(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Anti-Infective Agents/pharmacokinetics , Influenza A virus , Orthomyxoviridae Infections/metabolism , Otitis Media/metabolism , Pneumococcal Infections/metabolism , Amoxicillin/pharmacokinetics , Animals , Chinchilla , Half-Life , Mucous Membrane/metabolism , Orthomyxoviridae Infections/virology , Otitis Media/microbiology , Otitis Media/virology , Rabbits , Sulfamethoxazole/pharmacokinetics , Trimethoprim/pharmacokinetics
19.
Pharm Res ; 7(12): 1242-7, 1990 Dec.
Article in English | MEDLINE | ID: mdl-2095561

ABSTRACT

Bacteria are an important cause of acute otitis media and successful treatment depends on achieving inhibitory or bacteriacidal antimicrobial drug concentrations in the middle ear. To evaluate further otitis media treatment success and failure, we developed a chinchilla model to study antimicrobial drug penetration through the middle ear mucosa. Using quantitative histomorphometry, we measured the middle ear space in 10 chinchillas and found a mean +/- SD volume of 2.09 +/- 0.08 ml and a mean +/- SD surface area of 14.41 +/- 1.48 cm2. To measure the apparent rate constant (Kc) of antibiotic elimination from the middle ear, through the middle ear mucosa, an antibiotic solution was inoculated into the middle ear cavity, and samples were aspirated between 1 and 8 hr later. In normal ears, the mean Kc +/- SD for amoxicillin was 0.118 +/- 0.013 hr-1, that for a trimethoprim 0.461 +/- 0.090 hr-1, and that for sulfamethoxazole 0.265 +/- 0.062 hr-1. In ears inoculated with type 7F Streptococcus pneumoniae to induce acute otitis media, the Kc +/- SD increased for all three drugs (P less than 0.05): amoxicilin to 0.286 +/- 0.089 hr-1, trimethoprim to 0.662 +/- 0.118 hr-1, and sulfamethoxazole to 0.411 +/- 0.056 hr-1. These values demonstrate that amoxicillin had the lowest apparent penetration rate constant of the three antibiotics but the greatest increase from normal to infected mucosa (142%). Trimethoprim had the highest apparent penetration rate constant of the three antibiotics but the smallest increase from normal to infected mucosa (44%), while the sulfamethoxazone apparent penetration rate constant increased from normal to infected mucosa by 55%.(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Amoxicillin/pharmacokinetics , Ear, Middle/metabolism , Otitis Media, Suppurative/metabolism , Sulfamethoxazole/pharmacokinetics , Trimethoprim/pharmacokinetics , Animals , Chinchilla , Otitis Media, Suppurative/microbiology , Pneumococcal Infections , Solutions
20.
J Pharmacol Exp Ther ; 252(2): 733-8, 1990 Feb.
Article in English | MEDLINE | ID: mdl-2313597

ABSTRACT

Inasmuch as heparin has demonstrated immunosuppressive activity in vivo and in vitro, we utilized a canine renal transplant model to estimate the first-pass extraction of heparin during renal artery infusion and to examine the effect of regional heparin delivery on the histologic features of rejection and allograft survival. Four autotransplanted mongrel dogs with programmable, implantable pump/catheter systems received a continuous intrarenal heparin infusion which was increased daily in stepwise fashion. Activated coagulation time (ACT) rose linearly with local heparin dose, indicating that heparin clearance remained constant over the dosage range studied. Comparison of these ACT values with those measured during same-dose i.v. infusion and those predicted from i.v. bolus studies revealed that there was little or no first-pass renal extraction of heparin by the transplanted kidney. In nine allografted dogs, the heparin infusion rate was adjusted according to daily ACT to maximize local heparin delivery but still maintain the ACT close to 125% of base line. There was no difference in overall survival between the heparin-treated dogs and a group of 14 untreated controls, and vascular rejection was significantly more intense in the heparin-treated animals. We conclude that intrarenal dosing of heparin to the point of producing systemic anticoagulation is limited by failure of the transplanted kidney to eliminate drug and does not prolong canine renal allograft survival.


Subject(s)
Heparin/pharmacokinetics , Kidney Transplantation , Animals , Dogs , Female , Graft Survival/drug effects , Heparin/administration & dosage , Heparin/pharmacology , Infusions, Parenteral , Kidney/metabolism , Male , Metabolic Clearance Rate , Transplantation, Autologous , Transplantation, Homologous
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