Use of aromatase inhibitors in menopausal deep endometriosis: a case report and literature review.

We report and review the clinical effectiveness of aromatase inhibitors in a patient with refractory, recurrent and infiltrating endometriosis. We demonstrate excellent clinical, radiological and endoscopic responses after failure of multiple other modalities. Our case and the literature show that single-agent letrozole is capable to treat deep infiltrative endometriosis involving the rectum and the urinary tract. The use of aromatase inhibitor treatment of endometriosis in postmenopausal women makes sense, is safe and is well tolerated. Difficult cases of deep infiltrative endometriosis might require use of combined surgical and medical treatment modalities. Multidisciplinary involvement of the gynecologist, bowel surgeon, urologist and invasive radiologist might be needed. Aromatase inhibitors should be considered to be an integral part of the armamentarium in the management of women with endometriosis, especially in refractory cases that have failed conventional therapeutic modalities.

Associations between body composition and vertebral fracture risk in postmenopausal women.

INTRODUCTION: Osteoporosis is a metabolic bone disease with low bone mineral density (BMD) and high incidence of vertebral fractures (VFs). Postmenopausal women with osteoporosis have decreased total fat and lean mass. This study aimed to investigate the associations between body composition and VF risk and explore the potential predictor of VF risk in postmenopausal women. METHODS: Enrolled 731 postmenopausal women were referred by various departments and outpatient clinics to assess vertebral status between October 2016 and November 2017. The main measures were total body lean mass, fat mass, and BMD. Patients were divided into osteopenia, osteoporosis, and normal groups based on T-scores. Logistic regression analyses were performed to evaluate associations between body composition parameters and VF. RESULTS: VF was significantly associated with increased age, lower height, and lighter weight in all participants, and higher BMI was observed in VF participants. Participants in the osteoporosis group were older and had lower height, weight, and BMD than those in normal and osteopenia groups. Femoral and total hip T-scores as well as T-scores for lumbar spine were significantly lower in participants with VF than in non-VF participants. Percentage of bone mass was also significantly lower in VF participants compared to that of non-VF participants. Women with increased BMD and lower bone mass had reduced odds for VF occurrence. Bone mass was significantly able to identify VF occurrence. CONCLUSIONS: Body composition analysis discerns differences in the bone status of postmenopausal women with and without VF. The cutoff value of the bone mass might be used effectively as an indicator of risk for VF occurrence.

Characterization of the endometrial, cervicovaginal and anorectal microbiota in post-menopausal women with endometrioid and serous endometrial cancers.

OBJECTIVE: To characterize the microbiota of postmenopausal women undergoing hysterectomy for endometrioid (EAC) or uterine serous cancers (USC) compared to controls with non-malignant conditions. METHODS: Endometrial, cervicovaginal and anorectal microbial swabs were obtained from 35 postmenopausal women (10 controls, 14 EAC and 11 USC) undergoing hysterectomy. Extracted DNA was PCR amplified using barcoded 16S rRNA gene V4 primers. Sequenced libraries were processed using QIIME2. Phyloseq was used to calculate α- and ß- diversity measures. Biomarkers associated with case status were identified using ANCOM after adjustment for patient age, race and BMI. PICRUSt was used to identify microbial pathways associated with case status. RESULTS: Beta-diversity of microbial communities across each niche was significantly different (R2 = 0.25, p < 0.001). Alpha-diversity of the uterine microbiome was reduced in USC (Chao1, p = 0.004 and Fisher, p = 0.007) compared to EAC. Biomarkers from the three anatomical sites allowed samples to be clustered into two distinct clades that distinguished controls from USC cases (p = 0.042). The USC group was defined by 13 bacterial taxa across the three sites (W-stat>10, FDR<0.05) including depletion of cervicovaginal Lactobacillus and elevation of uterine Pseudomonas. PICRUSTt analysis revealed highly significant differences between the USC-associated clades within the cervicovaginal and uterine microbiota. CONCLUSIONS: The microbial diversity of anatomic niches in postmenopausal women with EAC and USC is different compared to controls. Multiple bacteria are associated with USC case status including elevated levels of cervicovaginal Lactobacillus, depletion of uterine Pseudomonas, and substantially different functional potentials identified within cervicovaginal and uterine niches.

Low molecular weight serum cell-free DNA concentration is associated with clinicopathologic indices of poor prognosis in women with uterine cancer.

BACKGROUND: Serum cell-free DNA (cfDNA) holds promise as a non-invasive cancer biomarker. The objective of this study was to evaluate the association of cfDNA concentration with clinicopathologic variables of poor prognosis and overall survival among women with uterine cancer compared to benign cancer-free controls. METHODS: cfDNA was extracted from the serum of 91 women with multiple uterine cancer histologies and 22 post-menopausal controls without cancer. Low molecular weight (LMW) cfDNA was separated from contaminating genomic high molecular weight cfDNA using paramagnetic bead purification and its concentration was measured using fluorometric quantification. Clinicopathologic data was abstracted from the electronic medical record. The association between serum cfDNA concentration, clinicopathologic variables, and overall survival was assessed using linear regression modelling, Cox proportional hazards modelling, and the Kaplan-Meier method. RESULTS: Median total serum cfDNA concentration for the cohort was 69.2 ng/mL (IQR 37.4, 132.3) and median LMW cfDNA concentration was 23.8 ng/mL (IQR 14.9, 44.4). There were no significant differences in total serum cfDNA concentration with any clinicopathologic variables. However, LMW cfDNA concentration was significantly higher in serum of women with cancer (25.8 ng/mL IQR 16.0, 49.6) compared to benign controls (15.5 ng/mL IQR 9.3, 25.8 ng/mL) (p < 0.01). It is also significantly higher among women with early stage cancer than benign controls (p < 0.01). There were also significant associations between LMW cfDNA concentration and stage of cancer (p = 0.01) and histology (p = 0.02). Patients with leiomyosarcoma and carcinosarcoma had higher cfDNA concentrations than those with endometrioid cancer. Over a median follow-up of 51.9 months, 75th percentile for overall survival for women with cancer was 24.0 months. Higher LMW cfDNA concentrations is associated with lower survival among women with cancer (p < 0.01). CONCLUSIONS: Serum LMW cfDNA concentration is associated with overall survival in women with uterine cancer, and it is higher among women with uterine cancer compared to those of controls.

The association of sexual dysfunction with race in women with gynecologic malignancies.

Gynecologic cancer survivors report sexual health among their highest concerns. The aim of this study was to identify the prevalence of sexual dysfunction (SD) in survivors of gynecologic malignancies and to evaluate the association of sexual function with race, ethnicity and treatment modality. In this study, survivors of endometrial, cervical, vaginal, and vulvar cancer who presented to the gynecologic oncology practice were asked to self-administer the Female Sexual Function Index (FSFI) survey to evaluate their sexual function. The prevalence of SD was estimated and its association with demographic and clinical co-variates was analyzed. Of the 155 participants, the prevalence of SD was 44.5% (95%CI: 36.7-52.7). Patients were significantly more likely to report SD if they did not currently have a partner (69% vs 22% p < .01). Abstinence within six months of their cancer diagnosis was also associated with SD (72% vs 26% p < .01). Patients who self-identified as black race compared to white race were three times more likely to have SD (OR = 3.9, 95% CI 1.1-14.3). Patients who received adjuvant chemotherapy and radiation therapy compared to those who did not among the entire cohort had an increased risk of SD (OR = 3.4, 95% CI 1.2-9.6). In our diverse population, almost half of our patients were identified to have SD. Black as compared to white race reported significantly higher sexual dysfunction. An increased risk for sexual dysfunction was observed among those women who received chemotherapy and radiation with or without surgery. PRECIS: Survivorship is an important issue for women with gynecologic malignancies. This study addresses the high rates of sexual dysfunction in a racially diverse patient population.

Readability assessment of online gynecologic oncology patient education materials from major governmental, non-profit and pharmaceutical organizations.

OBJECTIVE: Patients are increasingly using online materials to learn about gynecologic cancer. Providers can refer patients to online educational materials produced by a number of different major medical organizations and pharmacology companies. The National Institutes of Health (NIH) and the American Medical Association (AMA) recommend that patient educational materials (PEMs) are written between a sixth and eighth grade reading level. In this study, we assess the readability of online PEMs published by major medical organizations and industry partners. METHODS: Websites from twelve websites providing educational materials for gynecologic oncology patients were surveyed. Online PEMs were identified and analyzed using seven validated readability indices. One-way ANOVA and Tukey's Honestly Significant Difference (HSD) post-hoc analysis were performed to detect differences in readability between publishers. RESULTS: Two-hundred and sixty PEMs were included in this analysis. Overall, PEMs were written at a mean 11th±0.6 grade reading level. Only 6.5% of articles were written at the AMA/NIH recommended reading grade level of 6th to 8th grade or below. ANOVA demonstrated a significant difference in readability between publishing associations (p<0.01). PEMs from the Centers for Disease Control had a mean 9th±1.2 grade reading level and were significantly lower than all other organizations. PEMs from The Foundation for Women's Cancer had a mean 13th±1.8 grade reading level and were significantly higher than most other organizations. PEMs from pharmaceutical companies (mean readability=10.1±1.1, N=30) required the lowest reading grade level and were significantly more readable than those from governmental organizations (11.1±1.7, p<0.05) and nonprofit medical associations (12.4±1.7, p<0.01) in ANOVA and Tukey-Kramer post hoc analysis. CONCLUSIONS: Gynecologic oncology PEMs available from twelve major organization websites are written well above the recommended sixth to eighth grade reading difficulty level.

Utilizing the Patient Reported Outcomes Measurement Information System (PROMIS®) to increase referral to ancillary support services for severely symptomatic patients with gynecologic cancer.

OBJECTIVE: The Patient-Reported Outcomes Measurement Information System (PROMIS®) Network has developed a comprehensive repository of electronic patient reported outcomes measures (ePROs) of major symptom domains that have been validated in cancer patients. Their use for patients with gynecologic cancer has been understudied. Our objective was to establish feasibility and acceptability of PROMIS ePRO integration in a gynecologic oncology outpatient clinic and assess if it can help identify severely symptomatic patients and increase referral to supportive services. METHODS: English-speaking patients with a confirmed history of gynecologic cancer completed PROMIS ePROs on iPads in the waiting area of an outpatient gynecologic oncology clinic. Symptom scores were calculated for each respondent and grouped using documented severity thresholds. Response data was compared with clinicopathologic characteristics across symptom domains. Severely symptomatic patients were offered referral to ancillary services and asked to complete post-exposure surveys assessing acceptability of the ePRO. RESULTS: Of the 336 patients who completed ePROs, 35% had active disease and 19% had experienced at least one disease recurrence. Sixty-nine percent of the cohort demonstrated moderate to severe physical dysfunction (60%), pain (36%), fatigue (28%), anxiety (9%), depression (8%), and sexual dysfunction (32%). Thirty-nine (12%) severely symptomatic patients were referred to services such as psychiatry, palliative care, pain management, social work or integrative oncology care. Most survey respondents identified the ePROs as helpful (78%) and easy to complete (92%). CONCLUSIONS: Outpatient PROMIS ePRO administration is feasible and acceptable to gynecologic oncology patients and can help identify severely symptomatic patients for referral to ancillary support services.

Mediation of oxidative stress in hypothalamic ghrelin-associated appetite control in rats treated with phenylpropanolamine.

Phenylpropanolamine (PPA)-induced appetite control is associated with oxidative stress in the hypothalamus. This study explored whether hypothalamic antioxidants participated in hypothalamic ghrelin system-associated appetite control in PPA-treated rats. Rats were given PPA daily for 4 days, and changes in food intake and the expression of neuropeptide Y (NPY), the cocaine- and amphetamine-regulated transcript (CART), superoxide dismutase, catalase, ghrelin, acyl ghrelin (AG), ghrelin O-acyltransferase (GOAT) and the ghrelin receptor (GHSR1a) were examined and compared. Results showed that both food intake and the expression of NPY and ghrelin/AG/GOAT/GHSR1a decreased in response to PPA treatment with maximum decrease on Day 2 of the treatment. In contrast, the expression of antioxidants and CART increased, with the maximum increase on Day 2, with the expression opposite to that of NPY and ghrelin. A cerebral infusion of either a GHSR1a antagonist or reactive oxygen species scavenger modulated feeding behavior and NPY, CART, antioxidants and ghrelin system expression, showing the involvement of ghrelin signaling and oxidative stress in regulating PPA-mediated appetite control. We suggest that hypothalamic ghrelin signaling system, with the help of antioxidants, may participate in NPY/CART-mediated appetite control in PPA-treated rats.

Naproxen-induced Ca2+ movement and death in MDCK canine renal tubular cells.

Naproxen is an anti-inflammatory drug that affects cellular calcium ion (Ca(2+)) homeostasis and viability in different cells. This study explored the effect of naproxen on [Ca(2+)](i) and viability in Madin-Darby canine kidney cells (MDCK) canine renal tubular cells. At concentrations between 50 µM and 300 µM, naproxen induced [Ca(2+)](i) rises in a concentration-dependent manner. This Ca(2+) signal was reduced partly when extracellular Ca(2+) was removed. The Ca(2+) signal was inhibited by a Ca(2+) channel blocker nifedipine but not by store-operated Ca(2+) channel inhibitors (econazole and SKF96365), a protein kinase C (PKC) activator phorbol 12-myristate 13-acetate, and a PKC inhibitor GF109203X. In Ca(2+)-free medium, pretreatment with 2,5-di-tert-butylhydroquinone or thapsigargin, an inhibitor of endoplasmic reticulum Ca(2+) pumps, partly inhibited naproxen-induced Ca(2+) signal. Inhibition of phospholipase C with U73122 did not alter naproxen-evoked [Ca(2+)](i) rises. At concentrations between 15 µM and 30 µM, naproxen killed cells in a concentration-dependent manner, which was not reversed by prechelating cytosolic Ca(2+) with the acetoxymethyl ester of 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid acetoxymethyl. Annexin V/propidium iodide staining data suggest that naproxen induced apoptosis. Together, in MDCK renal tubular cells, naproxen induced [Ca(2+)](i) rises by inducing Ca(2+) release from multiple stores that included the endoplasmic reticulum and Ca(2+) entry via nifedipine-sensitive Ca(2+) channels. Naproxen induced cell death that involved apoptosis.

Mechanisms of resveratrol-induced changes in cytosolic free calcium ion concentrations and cell viability in OC2 human oral cancer cells.

Resveratrol is a natural compound that affects cellular calcium (Ca(2+)) homeostasis and viability in different cells. This study examined the effect of resveratrol on cytosolic free Ca(2+) concentrations ([Ca(2+)]i) and viability in OC2 human oral cancer cells. The Ca(2+)-sensitive fluorescent dye fura-2 was used to measure [Ca(2+)]i, and water-soluble tetrazolium-1 was used to measure viability. Resveratrol evoked concentration-dependent increase in [Ca(2+)]i. The response was reduced by removing extracellular Ca(2+). Resveratrol also caused manganese-induced fura-2 fluorescence quench. Resveratrol-evoked Ca(2+) entry was inhibited by nifedipine and the protein kinase C (PKC) inhibitor GF109203X but was not altered by econazole, SKF96365, and the PKC activator phorbol 12-myristate 13 acetate. In Ca(2+)-free medium, treatment with the endoplasmic reticulum Ca(2+) pump inhibitor 2,5-di-tert-butylhydroquinone (BHQ) abolished resveratrol-evoked [Ca(2+)]i rise. Conversely, treatment with resveratrol inhibited BHQ-evoked [Ca(2+)]i rise. Inhibition of phospholipase C (PLC) with U73122 abolished resveratrol-evoked [Ca(2+)]i rise. At 20-100 µM, resveratrol decreased cell viability, which was not affected by chelating cytosolic Ca(2+)with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester. Annexin V-fluorescein isothiocyanate staining data suggest that resveratrol at 20-40 µM induced apoptosis in a concentration-dependent manner. Collectively, in OC2 cells, resveratrol induced [Ca(2+)]i rise by evoking PLC-dependent Ca(2+) release from the endoplasmic reticulum and by causing Ca(2+) entry via nifedipine-sensitive, PKC-regulated mechanisms. Resveratrol also caused Ca(2+)-independent apoptosis.

Central dopamine action modulates neuropeptide-controlled appetite via the hypothalamic PI3K/NF-κB-dependent mechanism.

Hypothalamic neuropeptides, including neuropeptide Y (NPY) and proopiomelanocortin (POMC), have been found to control the appetite-suppressing effect of amphetamine (AMPH). In this study, we have examined whether dopamine receptor (DAR), phosphatidylinositol 3-kinase (PI3K) and nuclear factor-kappaB (NF-κB) are involved in AMPH's action. We administered AMPH to rats once a day for 4 days and assessed and compared changes in hypothalamic NPY, melanocortin receptor 4 (MC4R), PI3K, pAkt and NF-κB expression. We found that the inhibition of DAR increased NPY, but decreased MC4R, PI3K and NF-κB expression, compared with AMPH-treated rats. Moreover, MC4R, PI3K, pAkt and NF-κB increased with the maximum response on Day 2, which was consistent with the response of feeding behavior, but was opposite to the expression of NPY. Furthermore, we found that the intracerebroventricular infusion of the PI3K inhibitor or NF-κB antisense could attenuate AMPH-induced anorexia, and partially reverse the expression of NPY, MC4R, PI3K, Akt and NF-κB back toward a normal level. We, therefore, suggest that DAR-PI3K-NF-κB signaling in the hypothalamus plays functional roles in the modulation of NPY and POMC neurotransmissions and in the control of AMPH-evoked appetite suppression.

Telemedicine collaboration improves perinatal regionalization and lowers statewide infant mortality.

OBJECTIVE: We assessed a telemedicine (TM) network's effects on decreasing deliveries of very low birth weight (VLBW, <1500 g) neonates in hospitals without Neonatal Intensive Care Units (NICUs) and statewide infant mortality. STUDY DESIGN: This prospective study used obstetrical and neonatal interventions through TM consults, education and census rounds with 9 hospitals from 1 July 2009 to 31 March 2010. Using a generalized linear model, Medicaid data compared VLBW birth sites, mortality and morbidity before and after TM use. Arkansas Health Department data and χ(2) analysis were used to compare infant mortality. RESULT: Deliveries of VLBW neonates in targeted hospitals decreased from 13.1 to 7.0% (P=0.0099); deliveries of VLBW neonates in remaining hospitals were unchanged. Mortality decreased in targeted hospitals (13.0% before TM and 6.7% after TM). Statewide infant mortality decreased from 8.5 to 7.0 per 1000 deliveries (P=0.043). CONCLUSION: TM decreased deliveries of VLBW neonates in hospitals without NICUs and was associated with decreased statewide infant mortality.

Bone and cartilage demonstrate changes localized to bone marrow edema-like lesions within osteoarthritic knees.

OBJECTIVE: Our objective is to understand the biological and mechanical pathways linking cartilage, bone, and marrow changes in the progression of osteoarthritis (OA). The aim of the present study was to evaluate bone structure and composition within bone marrow edema-like lesion (BMEL) regions associated with knee OA. METHODS: Tibial plateau specimens (n = 18) were collected from 10 subjects with knee OA during total knee arthroplasty (TKA). Magnetic resonance (MR) imaging was used to identify BMEL and quantify metrics of cartilage composition. Micro-computed tomography (µCT) and high-resolution peripheral quantitative computed tomography (HR-pQCT) were used to quantify density and microstructure of the subchondral trabecular bone. Fourier transform infrared (FTIR) spectroscopy was used to quantify tissue composition. RESULTS: Trabecular bone within BMEL was higher in volume fraction, with more and thicker trabeculae that were more plate-like in structure compared to unaffected regions. BMEL trabecular tissue composition had decreased phosphate and carbonate content. Marrow infiltration by a fibrous collagen network and evidence of increased bone remodeling were present. Structural and compositional changes were specifically localized to regions underlying cartilage degradation. CONCLUSION: These results support the paradigm of focal interactions among bone, marrow, and cartilage in the progression of knee OA. Quantitative evaluation of tissue changes and interactions may aid in the understanding of disease pathophysiology and provide imaging markers for disease progression.

A new set of PCR assays for the identification of multiple human adenovirus species in environmental samples.

AIMS: To assess human adenovirus (HAdV) diversity in environmental samples based on sequence comparisons of hexon gene fragments amplified using newly designed HAdV-specific polymerase chain reaction (PCR) assays. METHODS AND RESULTS: Six PCR primer sets were designed based on 56 aligned hexon sequences from NCBI GenBank to amplify different hexon gene sections (241-349 bp) of the six HAdV species. The amplified hexon genes from wastewater samples were cloned, sequenced, and compared with those in publicly accessible databases (i.e. NCBI GenBank) by using the Blast program. A total of 46 analysed positive clones were affiliated to five HAdV serotypes, i.e. 1, 2, 12, 31 and 41. Similarities between the cloned and database hexon sequences ranged from 95.9 to 100% (with an average of 98.1 +/- 1.0%). CONCLUSION: The designed primers showed higher amplification efficiencies when compared with the existing assays. Using the new assays, HAdV species A, C, and F (serotypes 1, 2, 12, 31 and 41 in particular) were identified in the studied municipal wastewater. SIGNIFICANCE AND IMPACT OF THE STUDY: The six PCR primer sets developed in this study can be used to efficiently amplify hexon gene fragments in HAdV. Multiple HAdV serotypes identified in the municipal wastewater provide new information about HAdV diversity in environmental samples.

Novel neurosensory testing in cancer patients treated with the epothilone B analog, ixabepilone.

BACKGROUND: We have previously established the recommended phase II dose (RPTD) of ixabepilone as 40 mg/m(2) administered over 1 h repeated every 3 weeks with neuropathy as a cumulative dose-limiting toxicity. We expanded the cohort at the RPTD to include detailed assessment of nerve damage in these patients. We report our findings on vibration perception threshold (VPT) and neuropathy. PATIENTS AND METHODS: Forty-four patients were treated with a median (range) of three (1-14) cycles of ixabepilone. The VPT (5-min duration) and nerve conduction test (NCT, 10-min duration) were carried out in the office, before ixabepilone dosing, and every two cycles thereafter. RESULTS: Neuropathy (grade 1 and grades 2-3) was observed in 17 (38.6%) and 11 (25%) patients, respectively. The mean increase in VPT as a function of grade 0-1 versus grades 2-3 neuropathy was 0.235 +/- 0.03 versus 0.869 +/- 0.09 (P = 0.049) vibration units. The F-wave frequency and distal motor latency, as assessed using the NCT, did not correlate with clinical neurotoxicity. CONCLUSION: The change in VPT is observed early and likely reflects early vibration perception change. Mean change in VPT correlates with the severity of clinical neuropathy. Whether VPT change predicts onset of severe neuropathy warrants prospective testing and validation.

Phase II trial of thalidomide for advanced and recurrent gynecologic sarcoma: a brief communication from the New York Phase II consortium.

OBJECTIVE: To define the efficacy of thalidomide on the overall survival of patients with metastatic recurrent gynecologic sarcomas. PATIENTS AND METHODS: All patients with sarcoma or carcinosarcoma of gynecologic origin and documented recurrence or persistence of disease after appropriate surgery, radiation therapy and/or chemotherapy were recruited to the study. All patients were ambulatory and had measurable disease that could be documented on CT scan. Patients were started on 200 mg/day of thalidomide orally every night and escalated by 100-200 mg every 7 to 14 days. The length of the treatment was separated into 2 cycles with the first 84 days defined as the first cycle and the next 56 days as the second cycle. Common Toxicity Criteria were used to record toxicities. Because thalidomide was postulated to induce cytostasis, the end-points were progression-free and overall survival in this mixed group of patients. RESULTS: Seventeen patients were enrolled. The drug was not well tolerated because of constipation, fatigue, worsening performance status, drowsiness and sleepiness. The total dosage of medication given to each patient ranged from 3200 mg to 40,500 mg. The maximum dosage reached in each patient ranged from 300 mg to 750 mg, with the total time of treatment ranging from 13 to 99 days. All patients had progression of disease with a median progression-free survival time of 1.84 months (CI 1.54-2.79 months) and a median overall survival of 6.64 months. DISCUSSION: Thalidomide has no activity in patients with advanced or recurrent gynecologic sarcomas and was not well-tolerated. The overall survival was <7 months. The progression-free survival was <3 months, and, since the therapy was not tolerated well, we unanimously decided to close the study at this point. Despite the poor result, we still believe in the strategy of anti-angiogenesis and will continue to pursue other potential treatment options using the same concept.

Outcome of congenital cystic adenomatoid malformation of the lung after antenatal diagnosis.

OBJECTIVE: We evaluated the outcome of fetuses diagnosed with having congenital cystic adenomatoid malformation (CCAM) on ultrasonographic examination and managed conservatively. METHODS: A retrospective study of 19 cases of CCAM diagnosed antenatally in our hospital was conducted between 1990 and 2001. Complete clinical information was available for all patients, with a mean follow-up of 62 months. RESULTS: The median gestational age at which CCAM was diagnosed was 23 weeks and there were eight live births. With conservative postnatal management, seven neonates had no major complications and one developed bronchopneumonia. CONCLUSION: Taken together, the findings of the present study and a review of the literature strongly support the conservative management of selected neonates with CCAM.

Resolving appendicitis: role of CT.

BACKGROUND: We assessed the role of computed tomography (CT) in the resolution of appendicitis. METHODS: This was a retrospective study over 2.5 years involving 155 patients and 172 CT scans for suspected appendicitis in an emergency setting. RESULTS: Sixty-nine studies were positive for appendicitis by CT criteria. Of these, 53 underwent surgery: 48 were positive for appendicitis, four had other pathologies (two with colon cancer, one with colitis, one with infectious enteritis), and one had a normal appendix that was removed. Three of the 69 patients were released or left the emergency room against medical advice. Twelve patients demonstrated acute appendicitis by CT criteria but were treated conservatively because their clinical conditions were stable; four of those patients had follow-up CT that showed resolution of findings. Six patients were followed clinically, without recurrence of symptoms, and two were lost to follow-up. CONCLUSION: Resolving appendicitis is an entity that should be considered in a patient who has signs positive for appendicitis on CT but is doing well clinically. CT positive for appendicitis does not necessarily indicate surgery, and the decision for operation should depend on clinical and radiologic features.

Evidence for the involvement of dopamine D(1) and D(2) receptors in mediating the decrease of food intake during repeated treatment with amphetamine.

Repeated treatment with amphetamine (AMPH), a well-known anorectic agent, into animals could induce anorexia on day 1 and produce a gradual reversion of food intake (tolerant anorexia) on the following days. It is unknown whether these feeding changes are related to dopamine (DA) and/or noradrenergic neurotransmission. Thus, the present study investigated the subtype of receptor mediating AMPH-induced anorexia. Daily food intake was measured after various drugs were given. Pretreatment with haloperidol, an antagonist of DA receptors, may lead to inhibition of AMPH-induced anorexia. However, pretreatment with the alpha-adrenoceptor antagonist phentolamine, and the beta-adrenoceptor antagonist propranolol, failed to modify the action of AMPH, suggesting the involvement of DA receptors but not adrenoceptors in the action of AMPH-induced anorexia. Furthermore, pretreatment with SCH 23390 at a dose sufficient to block D(1) receptors or pimozide at a dose sufficient to inhibit D(2) receptors blocked AMPH-induced anorexia, indicating the involvement of D(1) and D(2) receptors. In a study of tolerant anorexia, repeated treatment with the D(1)/D(2) agonist apomorphine, but not the D(1) agonist SKF 38393 or D(2) agonist quinpirole, induced an AMPH-like tolerant feeding response, providing evidence for conjoint action of D(1) and D(2) receptors in the effect. The present results suggest that both D(1) and D(2) receptors are involved in anorexia and tolerant anorexia induced by chronic intermittent administration of AMPH.