Cardiovascular severe maternal morbidity in pregnant and postpartum women: development and internal validation of risk prediction models.

OBJECTIVES: To develop and internally validate risk prediction models identifying women at risk for cardiovascular severe maternal morbidity (CSMM). DESIGN: A retrospective cohort study. SETTING: An obstetric teaching hospital between 2007 and 2017. POPULATION: A total of 89 681 delivery hospitalisations. METHODS: We created and evaluated two models, one predicting CSMM at delivery (delivery model) and the other predicting CSMM postpartum following discharge from delivery hospitalisation (postpartum CSMM). We assessed model discrimination and calibration and used bootstrapping for internal validation. MAIN OUTCOME MEASURES: Cardiovascular severe maternal morbidity comprised the following confirmed conditions: pulmonary oedema/acute heart failure, myocardial infarction, aneurysm, cardiac arrest/ventricular fibrillation, heart failure/arrest during surgery or procedure, cerebrovascular disorders, cardiogenic shock, conversion of cardiac rhythm and difficult-to-control severe hypertension. RESULTS: The delivery model contained 11 variables and 3 interaction terms. The strongest predictors were gestational hypertension, chronic hypertension, multiple gestation, cardiac lesions or valvular heart disease, maternal age ≥40 years and history of poor pregnancy outcome. The postpartum model comprised eight variables. The strongest predictors were severe pre-eclampsia, non-Hispanic Black race/ethnicity, chronic hypertension, gestational hypertension, non-severe pre-eclampsia and maternal age ≥40 years at delivery. The delivery and postpartum models had an area under the receiver operating characteristic curve of 0.87 (95% CI 0.85-0.89) and 0.85 (95% CI 0.80-0.90), respectively. Both models were adequately calibrated and performed well on internal validation. CONCLUSIONS: These tools may help providers to identify women at highest risk of CSMM and enable future prevention measures. TWEETABLE ABSTRACT: Risk assessment tools for cardiovascular severe maternal morbidity were developed and internally validated.

Body mass index (BMI), postoperative appearance satisfaction, and sexual function in breast cancer survivorship.

PURPOSE: We sought to explore the correlation between BMI and postoperative sexual function, body image, and breast-specific sensuality before and after breast cancer surgery. METHODS: A cross-sectional survey of patients at least 1 year from surgery employed the Female Sexual Function Index (FSFI) and investigator-generated questions. Patients who underwent lumpectomy (L), mastectomy (M), and mastectomy with reconstruction (MR) were compared across three BMI groups: normal weight, overweight, and obese. RESULTS: Two hundred fifty-five patients underwent lumpectomy (L, n = 174), mastectomy (M, n = 22), or mastectomy with reconstruction (MR, n = 59). Median age was 57 (range 30-93) and median BMI was 28 (range 19-45). Obese and overweight women reported more appearance dissatisfaction (18.1 and 13.0%) than normal weight women (4.1%) (p = 0.01). Lower satisfaction was associated with increasing BMI within the MR group (p = 0.05). The obese group's median FSFI score met criteria for sexual dysfunction (25.90, range 11.30-33.10). More overweight women reported their chest played an important role in intimacy before and after surgery, but a postoperative decline in the importance of this role was observed in all groups. CONCLUSIONS: Greater post-treatment BMI is inversely related to postoperative appearance satisfaction, particularly in those undergoing mastectomy with reconstruction. The role of the breast in intimacy is greatest in overweight women, but decreases postoperatively in all BMI groups. IMPLICATIONS FOR CANCER SURVIVORS: Postoperative appearance satisfaction and sexual function seems to be correlated to post-treatment BMI, which highlights the need to encourage perioperative weight management for improved survivorship outcomes.

The impact of mastectomy type on the Female Sexual Function Index (FSFI), satisfaction with appearance, and the reconstructed breast's role in intimacy.

BACKGROUND: As mastectomy rates increase and overall survival for early breast cancer improves, a better understanding of the long-term consequences of mastectomy is needed. We sought to explore the correlation of specific mastectomy type with the Female Sexual Function Index (FSFI), body image satisfaction, and the reconstructed breast's role in intimacy. METHODS: This study is a secondary analysis of a cross-sectional survey including a retrospective chart review. Patients at least one year from primary surgery were invited to complete the survey between 2012 and 2014. Baseline characteristics and survey responses were compared between three mastectomy groups: total/modified radical (TMRM), skin-sparing (SSM), and nipple-sparing (NSM). All patients underwent reconstruction. RESULTS: Of 453 invited, 268 (59%) completed the survey. Sixty underwent mastectomy with reconstruction: 16 (27%) TMRM, 36 (60%) SSM, and 8 (13%) NSM. There were no significant differences in median total FSFI scores between groups, yet median FSFI scores for the NSM group indicated sexual dysfunction. After adjusting for receipt of chemotherapy and/or radiation, NSM had the lowest median desire score. There was a trend for the NSM group to be the least satisfied with postoperative appearance, but also more likely to report that the chest was "often" caressed during intimacy. However, nearly 40% of the NSM group reported that caress of the reconstructed breast was unpleasant. CONCLUSION: NSM offers patients the greatest opportunity for preservation of their native skin envelope and potentially enhanced cosmetic outcome, but our results did not demonstrate superior sexual function or body image outcomes in this group. By highlighting surgical consequences of mastectomy preoperatively, surgeons may better set realistic patient expectations regarding both aesthetic and functional outcomes after breast cancer surgery. With clearer expectations, patients will have a better opportunity for improved surgical decision-making.

Placental findings associated with maternal obesity at early pregnancy.

INTRODUCTION: Obesity during pregnancy is associated with a wide spectrum of maternal, fetal and neonatal complications. This study compared placental pathology in women with obesity and normal weight gravidas. MATERIALS AND METHODS: This is a retrospective case-control study. The sample was randomly selected from a total of 1000 deliveries of largely Caucasian population in a single institution, recruited for the study of sleep disordered breathing, where the placenta is submitted for pathological examination for clinical indications based on national guidelines. Cases (Body mass index - BMI ≥ 30 kg/m(2); n = 47) and controls (BMI < 25 kg/m(2), n = 45) were selected based on BMI obtained from the first prenatal visit. Placental pathology, clinical parameters and limited outcomes were extracted from medical records. Placental weight range was defined as small for gestational age (SGA) if < 10th percentile, large for gestational age (LGA) if > 90th percentile. RESULTS: Mean BMI was 36.2 ± 5.5 in the group with obesity and 21.7 ± 1.9 in the control group (p < 0.01). There was a significantly higher prevalence of diabetes in cases compared to controls (14/47 vs. 3/45, p = 0.006) while preterm birth was significantly higher in the control group (9/47 vs. 19/46, p = 0.02). There were more LGA placentas in cases versus controls (12/47 vs. 2/46, p = 0.007; even after adjusting for diabetes). More histological features of inflammation, marginal insertion of the umbilical cord and intervillous thrombi in the parenchyma were also noted in the case group. CONCLUSIONS: Results from the current study suggest that maternal obesity measured at early pregnancy may have effects on both placental implantation and growth, and further exacerbate the hypercoagulable state in placenta.

The menstrual bleeding questionnaire: development and validation of a comprehensive patient-reported outcome instrument for heavy menstrual bleeding.

OBJECTIVE: To develop and validate a patient-reported outcome measure for women with heavy menstrual bleeding (HMB). STUDY DESIGN: Prospective cohort and cross-sectional studies. SETTING: Outpatient women's health facility. POPULATION: Women aged between 18 and 55 years with and without self-reported HMB. METHODS: Using data from patients and clinicians, we developed a patient-reported outcome measure for HMB; the Menstrual Bleeding Questionnaire (MBQ). Participants in the validation studies completed demographic and general health questionnaires and either (1) bleeding and quality of life data collected daily on handheld computers and the MBQ after 1 month or (2) the MBQ at enrolment only. A subset of women also completed the Short-form-36 (SF-36) generic quality of life questionnaire. We performed psychometric analyses of the MBQ to assess its internal consistency as well as its content and concurrent validity and ability to discriminate between women with and without HMB. MAIN OUTCOME MEASURES: Psychometric properties of the questionnaire. RESULTS: Overall, 182 women participated in the MBQ validation studies. We found that the MBQ domains were internally consistent (Cronbach's α = 0.87-0.94). There was excellent correlation between daily bleeding-related symptom data and the MBQ completed at 1 month (ρ > 0.7 for all domains). We found low to moderate correlation between the MBQ scores and SF-36 scores (ρ = -0.15 to -0.45). The MBQ clearly discriminated between women with and without HMB (mean MBQ score = 10.6 versus 30.8, P < 0.0001). CONCLUSIONS: The MBQ is a valid patient-reported outcome measure for HMB that has the potential to improve the evaluation of women with self-reported HMB in research and clinical practice.

A prospective cohort study of pain with intrauterine device insertion among women with and without vaginal deliveries.

The purpose of this prospective cohort study was to compare pain during IUD insertion between women with a history of vaginal delivery and women without a history of vaginal delivery. First-time IUD users chose either the CuT380A or the levonorgestrel IUS. We enrolled 49 women with previous vaginal delivery and 49 women with no history of vaginal delivery (either only caesarean deliveries or nulliparous). The mean pain score on a 0-100 mm visual analog scale during insertion in the vaginal delivery group was 34.7 (SD 31.6) compared with 51.2 (SD 29.2) in the group without previous vaginal delivery (p = 0.009). In multivariable analysis controlling for age, breast-feeding, expected pain, baseline anxiety, insertion timing (6-12 weeks postpartum, 2-4 weeks post-abortion or interval), and insertion difficulty, history of vaginal delivery was associated with a 15.5 point reduction in pain (95% CI, -27.4, -3.7). Other significant predictors of pain were 'expected pain' and 'insertion difficulty'.

Demographic and relationship predictors of paternity establishment for infants born to adolescent mothers.

STUDY OBJECTIVE: To identify demographic and relationship characteristics associated with paternity establishment for children born to adolescent mothers. PARTICIPANTS, SETTING, AND DESIGN: This prospective cohort study included 300 pregnant adolescents 12-19 years old, presenting for prenatal care between March 2002 and February 2005. Demographic and relationship characteristics were compared based on paternity establishment (father's name on the infant's birth certificate). MAIN OUTCOME MEASURE: Paternity establishment (father's name on the infant's birth certificate). RESULTS: Of the 273 participants with outcome data, 54% established paternity. Paternity establishment differed by maternal race/ethnicity (69% Hispanic vs 36% non-Hispanic Black vs 52% non-Hispanic White, P = .01), maternal age (37% for 12-15 years vs 64% for 18-19 years, P = .01), maternal country of birth (48% U.S. born vs 76% non-U.S. born, P = .01), relationship with father of the infant, and father involvement at the time of delivery. CONCLUSION: Paternity establishment rates for children born to teens were low overall. To increase rates of paternity establishment, policies and programs need to consider the unique characteristics and circumstances of teen parents.

Pregnancy and fetal outcomes of symptoms of sleep-disordered breathing.

The physiological changes of pregnancy may predispose females to develop sleep-disordered breathing (SDB) or protect against it. Studies evaluating outcomes of SDB symptoms in pregnancy are scarce. The goal of this study was to evaluate the prevalence of SDB symptoms in pregnancy and their relationship with pregnancy and neonatal outcomes. A cross-sectional survey of randomly selected immediate postpartum females was performed using the multivariable apnoea prediction index. Record review, including demographics and medical history, was performed. Main outcome measures included pregnancy and neonatal outcomes. 1,000 subjects were recruited. Mean±sd age was 29.1±6.1 yrs. Factors used in the regression analysis included age, body mass index, diabetes, chronic hypertension, multifetal gestations, smoking and renal disease. Snoring was present in 35.1% of subjects. Symptoms of SDB were associated with a higher likelihood of pregnancy-induced hypertension and pre-eclampsia (adjusted OR 2.3, 95% CI 1.4-4.0), gestational diabetes (adjusted OR 2.1, 95% CI 1.3-3.4) and unplanned Caesarean deliveries (adjusted OR 2.1, 95% CI 1.4-3.2) after multivariable regression analysis. Gasping may have been associated with a higher likelihood of preterm delivery, after adjusting for age and multifetal pregnancies (adjusted OR 1.8, 95% CI 1.1-3.2) but this association appeared to be mediated by pre-eclampsia. Symptoms of SDB are common in pregnancy and associated with a higher likelihood of gestational hypertensive disorders, gestational diabetes and unplanned Caesarean deliveries.

Obstetric health care workers' attitudes and beliefs regarding influenza vaccination in pregnancy.

OBJECTIVE: To explore obstetric health care workers' attitudes and beliefs regarding influenza vaccination in pregnancy. METHODS: A survey consisting of 16 multiple-choice questions was administered to nurses, medical and nursing assistants, receptionists, and clinical administrators in obstetric settings. Survey questions addressed general knowledge of influenza and recommendations for vaccination during pregnancy, as well as personal beliefs about the acceptability of the vaccine in the pregnant population. The study was conducted at two sites, Women & Infants Hospital in Providence, RI, and Magee-Women's Hospital in Pittsburgh, PA. Variables were compared by Fisher exact test. RESULTS: Two hundred sixty-seven completed surveys were available for analysis, with a completion rate of 85%. Almost one third of health care workers surveyed do not believe that vaccines are a safe and effective way to decrease infections (31%) and a minority believe that vaccines are safe in pregnancy (36%). Just over half of health care workers know that pregnant women are at increased risk of complications from the flu (56.6%). Only 46% were able to correctly identify influenza symptoms, and only 65% would recommend influenza vaccination to a pregnant woman if indicated. A small percentage would be willing to give an avian influenza vaccine to pregnant women during a pandemic if it had not been tested in pregnancy (12.3%). CONCLUSION: Many obstetric health care workers lack knowledge regarding the safety and importance of influenza vaccination during pregnancy. Misinformed or inadequately informed health care workers may represent a barrier to influenza vaccine coverage of pregnant women. This lack of knowledge among the health care workforce takes on added importance in the setting of the H1N1 2009 swine-origin influenza pandemic. LEVEL OF EVIDENCE: III.

Willingness of gynecologic cancer patients to participate in clinical trials.

OBJECTIVES: Fewer than 5% of cancer patients enroll in clinical trials, delaying their completion and the progress of patient care. Patients who are elderly or members of ethnic minorities participate at even lower rates than the general population. The objective of this study was to identify the factors that motivate or inhibit patient enrollment specifically within the gynecologic oncology population. METHODS: An anonymous, voluntary survey was administered to all new patients presenting in the outpatient gynecologic oncology office for an initial consultation. The questionnaire was developed based on prior surveys in the general oncology literature and included questions about age, demographic information, interest in participation in research, and reasons for declining or desiring participation. Groups were compared with Fisher's Exact Test. RESULTS: There were 98 surveys submitted, of which 79 surveys were completed and included for analysis. The median age of patients was 50 years and the majority (86%) was Caucasian. Only 38% stated they would be unwilling to participate in clinical research, while 20% of the patient population stated they would be willing to participate in clinical trials and 42% were unsure. Factors that reached statistical significance (p=.05) in willingness to participate were age less than 50 years, education level beyond high school, and possession of private insurance. CONCLUSIONS: The percentage of women with gynecologic malignancies willing to participate in clinical trials greatly exceeds the number enrolled. Increasing the use of educational materials, improving patient awareness of clinical trials, and offering enrollment to all patients may increase accrual.

Mice transgenic for monocyte-tropic HIV type 1 produce infectious virus and display plasma viremia: a new in vivo system for studying the postintegration phase of HIV replication.

To generate an in vivo system for investigating the postintegration phase of HIV-1 replication, mouse lines transgenic for a full-length infectious proviral clone of a monocyte-tropic HIV-1 isolate, HIV-1JR-CSF, were constructed. Leukocytes from two independent JR-CSF transgenic mouse lines produced HIV-1 that infected human PBMCs. Plasma viremia was detected in these mice at levels (mean, >60,000 HIV RNA copies/ml) comparable to those reported for HIV-1-infected individuals. The levels of HIV RNA in these mice increased several-fold after either treatment with the superantigen Staphylococcus enterotoxin B or infection with Mycobacterium tuberculosis. Thus, a provirus encoding a monocyte-tropic HIV-1 strain under the control of its LTR expressed as a transgene in mice can proceed through the postintegration replication phase and produce infectious virus. In addition, the presence of plasma viremia that can be monitored by measuring plasma HIV-1 RNA levels permits these mice to be used to study the impact of different interventions on modulating in vivo HIV-1 production. Therefore, these mice provide a novel manipulable system to investigate the in vivo regulation of HIV-1 production by factors that activate the immune system. Furthermore, this murine system should be useful in delineating the role of human-specific factors in modulating HIV-1 replication and investigating the in vivo therapeutic efficacy of agents that target the postintegration stages of HIV-1 replication.

HIV type 1 infection of human fetal bone marrow cells induces apoptotic changes in hematopoietic precursor cells and suppresses their in vitro differentiation and capacity to engraft SCID mice.

To investigate the mechanism of HIV-1-induced hematopoietic abnormalities, we examined the effect of HIV-1 infection on the in vitro and in vivo behavior of precursor cells obtained from human fetal bone marrow (HFBM). After infection with the monocyte-tropic isolate HIV-1(ADA), HFBM cells displayed a significant decrease in their subsequent in vitro production of precursor cell colonies and a marked impairment in their engraftment of the bone marrow of irradiated SCID mice. By injecting retrovirally tagged, purified human CD34+ cells into HIV-1(ADA)-infected or uninfected human thymic tissue implanted in SCID mice, we demonstrated that HIV-1 infection also inhibited the in vivo differentiation of CD34+ cells into T cells. To determine the mechanism by which HIV-1 suppressed hematopoietic activity, we investigated whether HIV-1 infection induced apoptotic cell death in hematopoietic cells. Multiparameter flow cytometry with FITC-labeled annexin V and propidium iodide demonstrated that infection of the HFBM with monocyte-tropic, but not T cell line-tropic HIV-1, stimulated apoptosis in the CD34+ hematopoietic precursor population. The presence of a TNF-alpha inhibitor during exposure of the HFBM cells to HIV-1 substantially reduced the level of apoptosis of CD34+ cells and significantly decreased the repression of in vitro colony formation induced by HIV-1. However, inhibition of TNF-alpha during HFBM cell culture with HIV-1 did not restore their capacity to engraft SCID mice. Taken together, these results indicated that HIV-1 suppression of human hematopoietic cell maturation is a multifactoral phenomenon, a crucial element of which may be HIV-1-induced apoptosis of precursor cells mediated by TNF-alpha production.

thy/liv-SCID-hu mice: a system for investigating the in vivo effects of multidrug therapy on plasma viremia and human immunodeficiency virus replication in lymphoid tissues.

Modified, human immunodeficiency virus (HIV)-inoculated thy/liv-SCID-hu mice were used to evaluate the in vivo efficacy of antiretroviral drugs. Ritonavir treatment alone initially suppressed plasma viremia, but the viremia recurred with the appearance of ritonavir-resistant HIV isolates. Multidrug therapy suppressed plasma HIV RNA to undetectable levels; however, plasma viremia returned after therapy was stopped, showing that the therapy did not completely suppress HIV infection in the thymic implant. When thy/liv-SCID-hu mice were treated with a combination of zidovudine, lamivudine, and ritonavir immediately after inoculation with HIV, cocultures of the thymic implants remained negative for HIV even 1 month after therapy was discontinued, suggesting that acute treatment can prevent the establishment of HIV infection. Thus, these modified thy/liv-SCID-hu mice should prove to be a useful system for evaluating the effectiveness of different antiretroviral therapies on acute and chronic HIV infection.

Laryngoplasty with or without ventriculectomy for treatment of left laryngeal hemiplegia in 230 racehorses.

OBJECTIVE: The purpose of this study was to examine the influence of laryngoplasty on racing performance and to determine if any of the following variables had a significant effect on outcome: breed (Thoroughbred v Standardbred), endoscopic grade of laryngeal function, ventriculectomy versus no ventriculectomy, type of prosthetic suture used, and number of prostheses placed. STUDY DESIGN: Retrospective study of laryngoplasty with or without ventriculectomy for treatment of left laryngeal hemiplegia in racehorses between 1986 and 1993. ANIMALS OR SAMPLE POPULATION: 230 horses (174 Thoroughbreds, 56 Standardbreds). METHODS: The medical records of racehorses or horses intended for racing were reviewed. Signalment, admitting complaints, physical examination findings, resting endoscopic grade of laryngeal function, type of prosthetic suture material used, number of prosthetic sutures placed, presence or absence of ventriculectomy, and postoperative complications were recorded. RESULTS: Upper respiratory tract noise and exercise intolerance were the most common presenting complaints. Two horses had a laryngeal grade of 2, 109 horses a laryngeal grade of 3, and 119 horses a laryngeal grade of 4. Two double-strand braided polyester sutures were used in 147 horses, a single double-strand polyester suture was used in 49 horses, and a single double-strand nylon suture was used in 34 horses. Ventriculectomy was performed on 186 horses. The most common complication recognized during hospitalization was coughing in 50 horses. Telephone follow-up was obtained for 176 horses. For 168 horses, respiratory noise after surgery was decreased in 126 horses, the same in 28, and increased in 14. After hospital discharge, coughing occurred in 43 of 166 horses, and a nasal discharge occurred in 26 horses. Postoperative racing performance for 167 horses was subjectively evaluated by respondents as being improved in 69% of the horses. Overall owner satisfaction with the outcome after surgery was 81%. Of 230 horses, 178 raced at least one time after surgery. Overall, 117 horses raced three or more times before and after surgery, and 65 of these horses had improved performance index scores. None of the variables of surgical interest affected performance index scores. CONCLUSIONS AND CLINICAL RELEVANCE: Laryngoplasty with or without ventriculectomy allowed 77% of the horses to race at least one time after surgery, improved racing performance in 56% of the horses that completed three races before and after surgery, and improved subjectively evaluated racing performance in 69% of the horses.

Saquinavir-mediated inhibition of human immunodeficiency virus (HIV) infection in SCID mice implanted with human fetal thymus and liver tissue: an in vivo model for evaluating the effect of drug therapy on HIV infection in lymphoid tissues.

Treatment with protease inhibitors alone or in combination with inhibitors of reverse transcriptase potently suppresses levels of human immunodeficiency virus (HIV) RNA in plasma and thereby may significantly delay the progression of HIV-mediated disease. To investigate the effect of treatment with the protease inhibitor saquinavir on HIV replication in the lymphoid tissues, we used a SCID-hu mouse model that we developed, in which human thymic and liver tissues (hu-thy/liv) were implanted under both kidney capsules in SCID mice (thy/liv-SCID-hu mice). These mice are populated in the periphery with large numbers of human T cells and develop disseminated HIV infection after intraimplant injection. thy/liv-SCID-hu mice with established HIV infection that were treated for 1 month with saquinavir had a significantly lower viral load present in the implanted hu-thy/liv and mouse spleen than did the untreated HIV-infected thy/liv-SCID-hu mice. To examine the capacity of acute treatment with saquinavir to prevent HIV infection, some thy/liv-SCID-hu mice were inoculated with HIV and then immediately started on saquinavir. Although treated mice had markedly lower viral loads in the thy/liv implants and spleens, HIV infection was not completely prevented. Thus, the effect of antiviral therapy on HIV infection in the major site of HIV replication, the lymphoid tissues, can be readily evaluated in our thy/liv-SCID-hu mice. These mice should prove to be a useful model for determining the in vivo effectiveness of different therapeutic interventions on acute and chronic HIV infection.

Severe combined immunodeficiency mice engrafted with human T cells, B cells, and myeloid cells after transplantation with human fetal bone marrow or liver cells and implanted with human fetal thymus: a model for studying human gene therapy.

To develop an in vivo model wherein human hematopoiesis occurs, we transplanted severe combined immunodeficiency (SCID) mice with either human fetal bone marrow (HFBM) or human fetal liver (HFL). After transplantation of SCID mice with cultured HFBM (BM-SCID-hu mice) or HFL cells (Liv-SCID-hu mice), significant engraftment of the mouse bone marrow (BM) and population of the peripheral blood with human leukocytes was detected. Human colony-forming unit-granulocyte macrophage and burst forming unit-erythroid were detected in the BM of the BM-SCID-hu and Liv-SCID-hu mice up to 8 months after transplantation. When the HFBM or HFL cells were transduced with a retroviral vector before transplantation, integrated retroviral sequences were detected in human precursor cells present in the SCID mouse BM and in leukocytes circulating in the peripheral blood (PB) up to 7 months after transplantation. The PB of the BM-SCID-hu mice also became populated with human T cells after implantation with human thymic tissue, which provided a human microenvironment wherein human pre-T cells from the BM could mature. When the HFBM was retrovirally transduced before transplantation, integrated retrovirus was detected in sorted CD4+CD8+ double positive and CD4+ single positive cells from the thymic implant and CD4+ cells from the PB. Taken together, these data indicated that the BM of our BM-SCID-hu and Liv-SCID-hu mice became engrafted with retrovirally transduced human hematopoietic precursors that undergo the normal human hematopoietic program and populate the mouse PB with human cells containing integrated retroviral sequences. In addition to being a model for studying in vivo human hematopoiesis, these mice should also prove to be a useful model for investigating in vivo gene therapy using human stem/precursor cells.

Mice transgenic for human CD4 and CCR5 are susceptible to HIV infection.

HIV entry into human cells is mediated by CD4 acting in concert with one of several members of the chemokine receptor superfamily. The resistance to HIV infection observed in individuals with defective CCR5 alleles indicated that this particular chemokine receptor plays a crucial role in the initiation of in vivo HIV infection. Expression of human CD4 transgene does not render mice susceptible to HIV infection because of structural differences between human and mouse CCR5. To ascertain whether expression of human CD4 and CCR5 is sufficient to make murine T lymphocytes susceptible to HIV infection, the lck promoter was used to direct the T cell-specific expression of human CD4 and CCR5 in transgenic mice. Peripheral blood mononuclear cells and splenocytes isolated from these mice expressed human CD4 and CCR5 and were infectible with selected M-tropic HIV isolates. After in vivo inoculation, HIV-infected cells were detected by DNA PCR in the spleen and lymph nodes of these transgenic mice, but HIV could not be cultured from these cells. This indicated that although transgenic expression of human CD4 and CCR5 permitted entry of HIV into the mouse cells, significant HIV infection was prevented by other blocks to HIV replication present in mouse cells. In addition to providing in vivo verification for the important role of CCR5 in T lymphocyte HIV infection, these transgenic mice represent a new in vivo model for understanding HIV pathogenesis by delineating species-specific cellular factors required for productive in vivo HIV infection. These mice should also prove useful for the assessment of potential therapeutic and preventative modalities, particularly vaccines.

Epiglottic augmentation in the horse.

Epiglottic augmentation with injectable bovine collagen or an autogenous or allogenous auricular cartilage graft was performed in 12 horses with endoscopically and radiographically normal epiglottises. The grafting procedures were easy to perform and did not cause apparent discomfort. Cartilage graft extrusion or resorption may have occurred, but was not seen by endoscopy and lateral laryngeal radiography. Only collagen implants remained evident endoscopically, as smooth round submucosal bulges ventral to the epiglottic cartilage. Two horses with collagen implants, and all horses with cartilage autografts and allografts, were euthanatized at week 16. One horse with a collagen implant was euthanatized at week 4 and one at week 6. The epiglottis appeared thickened in three horses with collagen implants, two horses with autogenous grafts, and three horses with allogenous grafts. Pharyngeal lymphoid tissue was hyperplastic in two horses with autografts and three horses with allografts, but not in horses with collagen implants. Collagen grafts persisted as one or two smooth bulges 8 mm in diameter. Collagen incited a brisk foreign body reaction that was surrounded by a fibrous connective tissue capsule. Epiglottises of the horses with collagen implants were significantly thicker 20 mm from the tip than those of normal horses and horses with allografts. Cartilage graft incorporation was not evident grossly and was seen on microscopic examination in only one autograft. Thickening was caused by submucosal fibrosis.

Xeroradiographic evaluation of the equine larynx.

The normal radiographic anatomy of the equine larynx was determine by use of xeroradiography and dissection. The body and laminae of the thyroid cartilage, the muscular process of the arytenoid cartilages, and the dorsal lamina and arch of the cricoid cartilage had radiographic evidence of mineralization (calcification) and/or ossification in clinically normal horses. There was a significant (P less than 0.01) increase in the degree of mineralization of the thyroid and arytenoid cartilages with advancing age. Horses with diagnosis of arytenoid chondrosis (arytenoid chondral dysplasia, arytenoid chondropathy) by use of endoscopy had radiographic changes that included: enlargement with increased density of the arytenoid cartilage region, abnormal patterns of mineralization (dystrophic mineralization or osseous metaplasia), abnormal contour of the corniculate process(es) and laryngeal masses, sometimes obliterating part or all of the lateral laryngeal ventricles.

Sternothyrohyoideus myectomy in horses: 17 cases (1984-1985).

Review of medical records of 78 horses admitted to the George D. Widener Hospital for Large Animals with dorsal displacement of the soft palate revealed 94% of these horses to have evidence of an intermittent abnormal "gurgling" respiratory noise at the time of exercise. Sternothyrohyoideus myectomy was used as a primary treatment for 17 of these horses, with a success rate of 58%. Anatomic dissection of 30 horses indicated that the midcervical region is the optimal site for sternothyrohyoideus myectomy to alleviate dorsal displacement of the soft palate.