bluuebunny/crossref_metadata_2025 huggingface dataset:
Cardiovascular safety of fenfluramine in the treatment of Dravet syndrome: Analysis of an ongoing long‐term open‐label safety extension study
Authors: Lai Wyman W. , Galer Bradley S. , Wong Pierre C. , Farfel Gail , Pringsheim Milka , Keane Martin G. , Agarwal Anupam
Published: August 2020

Objective

Fenfluramine, which was previously approved as a weight loss drug, was withdrawn in 1997 when reports of cardiac valvulopathy emerged. The present study was conducted in part to characterize the cardiovascular safety profile of low‐dose fenfluramine when used in a pediatric population to reduce seizure frequency in patients with Dravet syndrome.

Methods

Patients 2‐ to 18‐years‐old with Dravet syndrome who had completed any of three randomized, placebo‐controlled clinical trials of fenfluramine were offered enrollment in this open‐label extension (OLE) study. All patients were treated with fenfluramine starting at a dose of 0.2 mg/kg/day (oral solution dosed twice per day), which was titrated to maximal effect with a dose limit of 0.7 mg/kg/day (maximum 26 mg/day) or 0.4 mg/kg/day (maximum 17 mg/day) in patients receiving concomitant stiripentol. Standardized echocardiographic examinations were conducted at Week 4 or 6 and then every 3 months during the OLE study to monitor cardiac valve function and structure and pulmonary artery pressure. The primary end point for the echocardiography analysis was the number of patients who developed valvular heart disease or pulmonary artery hypertension (PAH) during treatment.

Results

A total of 232 patients were enrolled in the study. The average age of patients was 9.1 ± 4.7 years, and 55.2% were male. The median duration of treatment with fenfluramine was 256 days (range = 58‐634 days), and the mean dose of fenfluramine was 0.41 mg/kg/day. No cases of valvular heart disease or PAH were observed.

Significance

Longitudinal echocardiography over a median 8.4 months of treatment with fenfluramine suggests a low risk of developing cardiac valvulopathy and PAH when used to treat pediatric patients with Dravet syndrome.
Cross‐national disparities contribute to heterogeneity in patient outcomes following invasive monitoring: A hierarchical mixed‐effects analysis
Authors: Remick Madison , Ibrahim George M. , Mansouri Alireza , Abel Taylor J.
Published: August 2020

There is substantial variability in outcomes following invasive monitoring and surgical treatment of drug‐resistant epilepsy (DRE). Patients with DRE are uniquely vulnerable to cross‐national health care disparities, as their epilepsy is difficult to treat and requires extensive resources. In a large cross‐national database of patients undergoing invasive monitoring for epilepsy surgery, we sought to evaluate the association between social, economic, and educational indicators of the country of treatment and patient outcomes following invasive monitoring. We performed a mixed‐effects analysis of an individual patient database of 595 subjects enrolled in 33 studies encompassing 25 neurosurgical centers in 10 countries of invasive monitoring for epilepsy from 1996 to 2019. Upon preliminary univariate analysis, significant nation‐level predictors of seizure outcome following either stereoelectroencephalography or subdural electrodes were hospital beds per 100,000 population, physician density, gross domestic product (GDP) growth, male and female educational attainment, and unemployment rate. On multivariate mixed‐effects logistic regression, physician density (β = −0.5112, P<.00697) and GDP growth (β = 0.53822, P<.00404) were the only nation‐level covariates of significance associated with seizure outcome. A higher physician density was associated with lesser seizure freedom rates, whereas higher GDP growth was associated with greater seizure freedom rates. Although patient‐specific variables were the primary determinant of seizure outcomes, cross‐national disparities also contribute to heterogeneities. Our findings highlight the importance of a systems‐level dialogue to improve surgical outcomes for DRE patients.
Plasma gonadotropin levels in metformin‐treated men with prediabetes: a non‐randomized, uncontrolled pilot study
Authors: Krysiak Robert , Szkróbka Witold , Bednarska‐Czerwińska Anna , Okopień Bogusław
Published: August 2020

Metformin was found to reduce elevated, but not normal, thyrotropin and prolactin levels. This non‐randomized, uncontrolled pilot study investigated hypothalamic–pituitary–testicular axis activity in men with primary hypogonadism receiving metformin. The study population included 29 men with prediabetes, 10 of whom had been diagnosed with primary hypogonadism. Throughout the study, the participants were treated with metformin (2.55–3 g daily). Glucose homeostasis markers (fasting glucose, glycated hemoglobin, and HOMA1‐IR), as well as circulating levels of follicle‐stimulating hormone (FSH), luteinizing hormone (LH), testosterone, thyrotropin, prolactin, estradiol, and creatinine, were assessed at the beginning of the study and 16 weeks later. Both groups differed in baseline gonadotropin and testosterone levels. Fasting glucose, glycated hemoglobin, and HOMA1‐IR were lower after than before metformin treatment. The changes in fasting glucose and HOMA1‐IR were more pronounced in hypogonadal men than in subjects with testosterone levels within the reference range. Only in hypogonadal men, plasma concentrations of FSH and LH were lower at the end than at the beginning of the study. Levels of the remaining hormones remained unchanged throughout the study period. The reduction in FSH and LH levels correlated with their baseline levels and with the changes in HOMA1‐IR. The results of our study suggest that metformin may decrease FSH and LH levels in men with hypergonadotropic hypogonadism.
Experimental investigation of overload effects on fatigue crack growth behaviour of 7050‐T7451 aluminium alloy
Authors: Wang Hongxun , Zhang Jingyu , Li Yi , Wang Zongren , Wu Jifeng
Published: August 2020

Fatigue damage and fracture of metals are the major failure modes of mechanical structures. Studying the fatigue crack growth (FCG) behaviour under overload effects can better explain the loading interactions and develop more accurate FCG prediction models. This research innovatively designed and established the experimental system that is suitable for FCG test under variable amplitude loading (VAL). Systematically, FCG experiments were carried out by introducing single tensile overload, single compressive overload and tensile/compressive sequential overload in constant amplitude loading (CAL). The effects of overload ratio, stress intensity factor (SIF) range ∆K and tensile/compressive overload sequence on the FCG behaviour of 7050‐T7451 aluminium alloy were comparatively analysed. The retardation or acceleration effects on the macro FCG and the micro crack deflection, crack bifurcation and particle falling effects of different overloads as well as their interactions were revealed.
Fatigue crack growth determination based on cyclic plastic zone and cyclic J‐integral in kinematic–isotropic hardening materials with considering Chaboche model
Authors: Hosseini Reza , Seifi Rahman
Published: August 2020

For many materials, plastic deformations under cyclic loadings differ from monotonic loading. Cyclic plastic zone with considering the strain hardening effects becomes complicated during unloading step. In this research, the effects of nonlinear kinematic and isotropic hardening behaviours on the cyclic plastic reaction around the crack tip for different conditions are investigated. For study of various hardening characteristics, as‐received and annealed copper are tested under same symmetric cyclic loadings. The results indicate considerable isotropic hardening behaviour in annealed material. A Chaboche nonlinear hardening model was used to determine the hardening parameters. The cyclic plastic zone around the crack tip in C(T) specimen was measured by back stresses. The cyclic plastic zones are specified via variations of the back stresses in a cycle. The cyclic plastic zones predicted by Chaboche model are smaller than those for Irwin model because of the hardening effects. Also, Irwin model for prediction of the cyclic plastic zone size is modified with considering the cyclic plastic effects. According to the results, the cyclic plastic zone around the crack tip is almost constant in the same load range, and load ratio (R) has a slight effect on this zone. Whereas, for constant load range, cyclic J‐integral (∆J) is different for various R values. For studying of the fatigue crack growth, two parameters of ∆J and cyclic plastic zone area were evaluated. These parameters can apply in fracture mechanics especially in elastic–plastic conditions with considering the cyclic plastic responses.
Influence of heat input on microstructure and fracture toughness property in different zones of X80 pipeline steel weldments
Authors: Singh Mayur Pratap , Arora Kanwer Singh , Kumar Rajneesh , Shukla Dinesh Kumar , Siva Prasad S.
Published: August 2020

In this paper, microstructure observations and mechanical behaviour of fusion line and offsetting positions from fusion line by 1, 2 and 3 mm were analysed. For the welding of X80 pipeline steel plates, different magnitudes of heat inputs such as high heat input (HHI) 25 kJ/cm, medium heat input (MHI) 20 kJ/cm and low heat input (LHI) 15 kJ/cm were employed. Critical values of J‐integral (J0.2) and crack tip opening displacement (CTOD0.2) for predetermined regions in the X80 weldment were determined as per ASTM‐E1820a. M‐A constituents of different sizes such as small (1–2 μm), large >2 μm and slender (>4 μm) were observed in the microstructure of subzones of weldments for different heat inputs. Formation of granular bainite, M‐A constituents and inclusions of Ti, Si, Mo in the microstructure impaired fracture toughness property. In the X80 weldment, the fusion line (FL) for HHI was found weakest in terms of fracture resistance, which subsequently increases the risk of fracture.
Gingival squamous cell carcinoma mimicking a non‐neoplastic proliferative lesion in an older patient
Authors: Cunha John Lennon Silva , Déda Júnior Wilson Gonçalves , Sanchéz‐Romero Celeste , Bezerra Bruno Torres , de Albuquerque‐Júnior Ricardo Luiz Cavalcanti
Published: August 2020

Objective

To report a case of gingival squamous cell carcinoma (SCC) in an elderly patient mimicking a non‐neoplastic proliferative lesion.

Background

Oral SCC is a well‐recognised malignancy of the oral cavity that may mimic benign reactive proliferative processes.

Methods

An excisional biopsy was performed, and the diagnosis was gingival SCC.

Conclusion

It is essential that both the clinician and pathologist to be aware of such a presentation to allow for proper diagnosis and treatment.
Global value chains and supplier perceptions of corporate social responsibility: a case study of garment manufacturers in Myanmar
Authors: Bae Jinsun , Lund‐Thomsen Peter , Lindgreen Adam
Published: August 2020

Suppliers are embedded simultaneously in the global value chains (GVCs) of their lead firms and in the countries in which they conduct their production activities. To explain supplier perceptions of corporate social responsibility (CSR) in GVCs, in this article, we develop a new typology by integrating buyer governance modes in GVCs and forms of supplier embeddedness (societal, network, and territorial). We advance literature on supplier perspectives on CSR in GVCs through an analysis of 19 garment manufacturers in Myanmar and their CSR perceptions, using in‐depth field‐work, interviews, and secondary data. The empirical findings indicate a variety of supplier perceptions of CSR, depending on the governance mode of the GVCs and the variegated combinations of societal, network, and territorial embeddedness. Understanding supplier CSR perceptions and their implementation in GVCs thus requires moving away from a sole focus on supplier responses to standardized codes of conduct and towards a greater consideration of different types of supplier embeddedness.
A Physically Based Approach for Estimating Hydraulic Conductivity from HPT Pressure and Flowrate
Authors: Borden Robert C. , Cha Ki Young , Liu Gaisheng
Published: August 2020

The hydraulic profiling tool (HPT) is widely used to generate profiles of relative permeability vs. depth. In this work, prior numerical modeling results are used to develop a relationship between probe advance rate V (cm/s), probe diameter D (cm), water injection rate Q (mL/min), corrected pressure Pc (psi), and hydraulic conductivity K (feet/d)
urn:x-wiley:0017467X:media:gwat13039:gwat13039-math-0001where E is an empirically derived hydraulic efficiency factor. The relationship is validated by 23 HPT profiles that, after averaging K vertically, were similar to slug test results in adjoining monitoring wells. The best fit value of E for these profiles was 2.02. This equation provides a physically based approach for generating hydraulic conductivity profiles with HPT tooling.
Policy‐related implementational fluidity in subsistence marketplaces
Authors: Upadhyaya Shikha
Published: August 2020

This paper sheds light on policy‐related implementational fluidity—a context‐dependent adaptation of policies—adopted by policy implementers to address heterogeneous needs of subsistence consumer‐merchants (SCMs). In subsistence research, despite the emphasis on bottom‐up policymaking, implementational fluidity persists because of institutional and sociocultural factors that hinder policy implementers’ from effectively and accurately implementing the policies. To enrich the current bottom‐up policy process, this paper shares insights from an ethnographic study of Fijian market traders and marketplace personnel (policy implementers) and shares insights on how implementational fluidity manifests in subsistence marketplaces. Analysis reveals the interplay amongst sociohistorical context, marketplace relational dynamics and policies leading to policy adjustments and re‐negotiation by marketplace personnel and perceived injustices amongst the SCMs. The paper provides policy recommendations and practice ideas for subsistence researchers and policy practitioners to examine policy implementation gaps and the role of policy implementers in subsistence marketplaces.
Efficacy of high‐dose intralesional triamcinolone for hidradenitis suppurativa
Authors: Garelik Jessica , Babbush Kayla , Ghias Mondana , Cohen Steven R.
Published: August 2020

Background

Hidradenitis suppurativa (HS) is a chronic inflammatory disorder of hair follicles characterized by recurrent, painful nodules, abscesses, and sinus tracts (“tunnels”) typically refractory to treatment. This debilitating condition results in poor quality of life due to high disease burden. Intralesional triamcinolone (ILTAC) is a standard of care for acute inflammation and drainage associated with HS; however, the optimal therapeutic dose has not been determined. We investigated the utility of high‐dose ILTAC 20 mg/ml (ILTAC‐20) or 40 mg/ml (ILTAC‐40), for inflammatory lesions of HS.

Methods

A retrospective chart review and telephone questionnaire included HS patients treated with high‐dose ILTAC‐20 or ILTAC‐40 between April and December 2018. Patients with Hurley stages I–III were included. Data were obtained from electronic medical records and telephone interviews. A short questionnaire pertained to satisfaction with therapy, changes of disease state, and modifications in quality of life.

Results

Of 54 patients interviewed, the average age was 36.9 ± 11.6 years; 36 (66.7%) were female. Forty patients (76.9%) were very satisfied (n = 19) or satisfied (n = 21) with high‐dose ILTAC therapy. Fifty patients (92.6%) demonstrated improvements in disease state, and 41 patients (75.9%) experienced enhanced quality of life. Forty‐four patients (86.3%) were amenable to additional injections of high‐dose ILTAC, if clinically indicated. No adverse effects of therapy were reported.

Conclusions

The majority of patients reported improvements in disease state, quality of life, and overall satisfaction after administration of high‐dose ILTAC (20–40 mg/ml). These findings support the use of high‐dose ILTAC for acute lesions of HS.
Resolution of epoetin‐induced pure red cell aplasia, successful re‐challenge with roxadustat
Authors: Wu Yunzhou , Cai Xudong , Ni Jianing , Lin Xiaomeng
Published: August 2020

The application of erythropoietin (EPO) can bring about a rare but serious complication called anti‐EPO antibody‐mediated pure red cell aplasia (PRCA). Once the disease is diagnosed, EPO administration should be stopped immediately. However, after the removal of the anti‐EPO antibody, treating anaemia in these patients with chronic renal disease with EPO therapy is difficult, as restarting EPO therapy risks the recurrence of anti‐EPO antibody‐mediated PRCA. A 26‐year‐old man with anaemia related to renal failure, who was administered recombinant human EPO subcutaneously, developed anti‐EPO antibody‐mediated PRCA. After removal of antibodies by treatment with corticosteroids and cyclosporine, therapy for anaemia of chronic renal disease with roxadustat achieved good results. Roxadustat is a new type of drug for the treatment of anaemia, and it can stimulate endogenous EPO within or near the physiologic range and increase haemoglobin levels.
Exploring family participation in patient care on acute care wards: A mixed‐methods study
Authors: Mackie Benjamin R. , Marshall Andrea P. , Mitchell Marion L.
Published: August 2020

Background

Patient‐ and family‐centred care practices are a recommended part of contemporary care for the acutely ill hospitalized adult patients. However, how patient‐ and family‐centred care is enacted in an adult hospital setting is not well understood.

Aims and Objectives

The aim of this study is to explore the perceptions of patients, family members and nurses regarding family participation and collaboration in patient care within an acute care setting, including the barriers and facilitators.

Design

This study used a mixed‐methods sequential design.

Methods

Observer‐as‐participant observations and semistructured interviews were undertaken. Integration of the data was achieved through triangulation.

Results

Triangulation revealed two metathemes. The first metatheme, ‘continuum of family involvement’, explained the central viewpoint of how family participation and collaboration in the care of acutely ill hospitalized adult patients was enacted. The second metatheme, ‘nurses value family involvement’, helped to explain and understand the barriers and facilitators to enacting family participation in the acute care setting.

Conclusion

Promoting family participation in the acute care setting requires supporting multiple levels of engagement. Developing a relationship, clear communication and open sharing of information amongst patients, family members and nurses is critical to supporting family involvement.
Effect of a Rational Drug Use Policy on the prescribing safety in outpatient settings in Thailand
Authors: Rattanachotphanit Thananan , Waleekhachonloet Onanong
Published: August 2020

Objective

In Thailand, the ‘Rational Drug Use (RDU) policy’ has been implemented in the Ministry of Public Health (MOPH) hospitals since October 2016. This study aimed to explore the effects of the RDU policy on prescribing safety indicators for elderly patients and those with common chronic diseases.

Method

Electronic outpatient databases were obtained from 15 MOPH hospitals. The selected indicators were the (1) glibenclamide prescribing in patients with diabetes mellitus who were elderly or had renal impairment; (2) duplicate prescribing of renin angiotensin system (RAS) blockers in patients with hypertension; (3) non-steroidal anti-inflammatory drugs (NSAIDs) prescribing in patients with chronic kidney disease stages 3–5; and (4) long-acting benzodiazepines prescribing in patients ≥65 years. The policy effects in terms of changes in prescribing trends were estimated using interrupted time-series analysis based on quarterly (Q) data. The postpolicy trends (2016, Q4–2017, Q4) were compared with the prepolicy trend (2014, Q1–2016, Q3).

Key findings

The unsafe prescribing of glibenclamide in patients with diabetes mellitus was 19.2% in Q1, 2014 and decreased significantly due to the RDU policy to 11.0% in Q4, 2017 (−4.23 percentage points quarterly, P < 0.001). The unsafe prescribing of RAS blockers and long-acting benzodiazepines was relatively low in Q1, 2014 (1.0% and 1.1%, respectively) and did not decrease further after the RDU policy. The unsafe prescribing of NSAIDs was 4.2% in Q1, 2014, increased abruptly one quarter after the policy and decreased afterwards.

Conclusion

The RDU policy seemed to be a contributing factor that decreased the unsafe prescribing of glibenclamide, while the policy effect was minimal for the other indicators.
Oral mucositis in childhood cancer patients receiving high‐dose methotrexate: Prevalence, relationship with other toxicities and methotrexate elimination
Authors: Valer Jéssica Berté , Curra Marina , Gabriel Amanda de Farias , Schmidt Tuany Rafaeli , Ferreira Maria Beatriz Cardoso , Roesler Rafael , Evangelista Junior Mario Correa , Martins Marco Antonio Trevizani , Gregianin Lauro , Martins Manoela Domingues
Published: August 2020

Background

Oral mucositis (OM) is one of the main adverse effects of the chemotherapeutic agent methotrexate (MTX).

Aim

To evaluate the relationship of OM with MTX metabolism time and other toxicities in childhood, cancer patients receiving high‐dose of methotrexate (HD‐MTX).

Design

Seventy‐seven childhood patients receiving HD‐MTX for treatment of leukaemia, osteosarcoma or lymphoma were evaluated. MTX serum level, hepatic and renal function parameters, and presence and intensity of OM were analysed.

Results

The patients were submitted to 255 cycles of chemotherapy. OM was diagnosed in 191 (74.9%) cycles. Of these, 119 (46.6%) presented ulcerative lesions. Lymphoma was associated with severe OM (P = .01). OM was associated with higher serum levels of aspartate aminotransferase (P = .006), alanine aminotransferase (P = .04) and creatinine (P = .008). Increase of one unit of total bilirubin and indirect bilirubin associated, respectively, with 11% and 39% higher prevalence of OM. For each increase of one unit of creatinine serum level, it was observed a 37% higher prevalence of OM in patients with lymphoma. No association was found between delayed excretion of MTX and OM development.

Conclusions

OM is a prevalent complication of childhood cancer patients receiving HD‐MTX. Renal and hepatic toxicity could be considered risk factors for OM, especially in patients with lymphoma.
The conjugal‐parental dynamics of three lesbian couples and the role of the outside donor
Authors: Gratton Emmanuel
Published: August 2020

The use of a sperm donor is a means of access to parenthood for lesbian couples. Insemination by donor, whether through medical or non‐medical methods (such as self‐insemination at home), is still forbidden in France. Three different case examples are presented: an anonymous donor, a random donor, and specifically chosen one, in order to discover how the utilisation of a sperm donor affects relationships within the family, especially the dynamics between the couple and between the parents and the children. The position of the sperm donor vis‐à‐vis the family is also examined. A non‐directive interview with the parents and children as well as the completion of a family tree resulted in understanding how each couple's choice lay not only in the presumed interest of the child, but also in the dynamics of the couple as partners and parents, involving the personal and familial history of each partner, their representations of attachment, and the stakes they hold in becoming co‐parents. Complex issues were negotiated: the choosing of a donor, the place of the non‐biological mother vis‐à‐vis the children, the families’ connections with the couples’ families of origin, and the place of the sperm donor in relationship to the family. The resolution of these issues was linked to the family histories of the individuals in the couples as well as the history of their relationships. This study suggests that consideration of these historical factors in the decision‐making process for lesbian couples seeking sperm donation can lead to a fuller picture of options in the process and increased satisfaction with the outcome.
Evaluation of a subsidized dental program among rural Norwegians
Authors: Helöe Leif Arne
Published: August 2020

abstract

Of 280 medically and/or socially disadvantaged Norwegian rural dwellers aged 20‐60 years invited to participate in a subsidized dental program, 198 persons needed treatment and agreed to receive free or low‐cost treatment. Eight persons dropped out of the program, leaving 190 participants who were treated by the author and/or by private practitioners. The average treatment cost per person was Nor. kr. 697, but the cost varied considerably. Prosthetic services comprised three‐fourths of the total expenses. According to the criteria used, the participants' share of the cost averaged Nor. kr. 260. Approximately every fifth participant seemingly did not manage to cover his share. Predictability of treatment services and costs were elucidated by comparing estimates worked out by the author with data obtained from the practitioners on the services actually rendered. The pairs of data on extractions and fillings were in fairly good agreement, as were the cost estimates of such services. The cost of prosthetics, however, had been rather underestimated, while conversely, the cost of periodontal treatment had been heavily overestimated.
Spontaneous Malignant Lymphoma in an African Green Monkey Naturally Infected With Simian T‐Lymphotropic Virus (STLV)
Authors: Sakakibara Ippei , Sugimoto Yasuko , Sasagawa Akira , Honjo Shigeo , Tsujimoto Hajime , Nakamura Hideo , Hayami Masanori
Published: August 2020

An African green monkey naturally infected with simian T‐lymphotropic virus (STLV) developed spontaneous malignant lymphoma of diffuse pleomorphic type. The clinical, hematological and histopathological characteristics were very similar to those of human adult T‐cell leukemia.
Comparative Biology of Natural and Experimental SIVmac Infection in Macaque Monkeys: A Review
Authors: King Norval W. , Chalifoux Laura V. , Ringler Douglas J. , Wyand Michael S. , Sehgal Prabhat K. , Daniel Muthiah D. , Letvin Norman L. , Desrosiers Ronald C. , Blake Beverly J. , Hunt Ronald D.
Published: August 2020

Epidemiologic and clinicopathologic data from 11 macaques with naturally acquired SIV infection—10 of which have died—were compared with those from 34 rhesus monkeys that have died of experimental SIVmac infection. Several differences, including gender affected, age at time of death, and the occurrence of certain opportunistic infections, could be explained by the experimental design; others remained unexplained. The most striking difference was the 41% incidence of meningoencephalomyelitis in the experimental group and its absence in naturally SIV‐infected animals.
Comparison of SIV/SMM Replication in CD4+ T Cell and Monocyte/Macrophage Cultures From Rhesus Macaques and Sooty Mangabeys
Authors: Yehuda‐Cohen Tamar , Powell Jonathan D. , Villinger Francois , McClure Harold M. , Sell Kenneth W. , Ahmed‐Ansari Aftab
Published: August 2020

Monocytes from SIV/SMM infected sooty mangabeys and rhesus macaques were incubated in vitro with live SIV/SMM. The reverse transcriptase (RT) activity in the supernatant fluids of the monocyte cultures of the former species was higher than the RT activity in the latter species. No differences were found in the supernatant fluid of similar cultures of CD4+ T cells from both these species. Autologous (but not allogeneic) CD8 + T cells from S1V infected mangabeys and rhesus macaques inhibited SIV replication in vitro. The suppression appeared more marked in monocytes from the mangabcy species. These in vitro differences may relate to the clinically asymptomatic state of the sooty mangabeys and the disease‐susceptible state of the rhesus macaques.
Antibody‐Dependent Enhancement of SIV Infection: Further Characterization and Cross Reactivity Between Macaque and Sooty Mangabey Isolates
Authors: Montefiori David C. , Robinson W. Edward , Hirsch Vanessa M. , Modliszewski Ann , Mitchell William M. , Johnson Philip R.
Published: August 2020

Plasma from four rhesus macaques (Macaca mulatta), of which two were experimentally infected with the simian immunodeficiency virus (SIV) isolate SIVmac251, one with isolate SIVsmF236, and another with a SIVsmF236 molecular clone, SIVsmH‐4, enhanced SIVmac infection of MT‐2 cells. In addition to SIV‐positive plasma, infection‐enhancement required complement, CD4, and CR2. Titers of infection‐enhancing antibodies appeared to correlate with disease progression. The MT‐2/SIVmac251 system should be useful in future studies of complement‐mediated, antibody‐dependent enhancement of macaque and sooty mangabey SIV isolates.
Sequence Variability of Simian Immunodeficiency Virus in a Persistently Infected Rhesus Monkey
Authors: Burns Dawn P.W. , Desrosiers Ronald C.
Published: August 2020

A juvenile rhesus monkey that was inoculated intravenously with molecularly cloned SIVmac239 became persistently infected. A modified polymerase chain reaction (PCR) procedure was used to specifically amplify full‐length envelope (env) gene sequences from DNA extracted from peripheral blood mononuclear cells (PBMC), lymph node tissue, and cells infected with recovered virus at 69 and 93 weeks post‐infection. Extensive sequence variability accumulated in vivo in spite of infection with molecularly cloned virus. In the central portion of env, sequence variability was largely confined to three discrete regions.
Molecular Interactions of Cytomegalovirus and the Human and Simian Immunodeficiency Viruses
Authors: Barry Peter A. , Pratt‐Lowe Elissa , Linger Ronald E. , Marthas Marta , Alcendor Donald J. , Luciw Paul A.
Published: August 2020

In HuT 78 cells chronically infected with SIV, super‐infection with rhesus cytomegalovirus (rhCMV) stimulated an increase in SIV replication. Utilizing transient expression assays with the SIV long terminal repeat (LTR) driving expression of the chloramphenicol acetyltransferase (CAT) reporter gene, the increase in SIV replication, by coinfection with CMV, was due to transactivation of the SIV LTR by the immediate early gene products (IE) of rhesus CMV. Similarly, IE of human CMV stimulated expression from both the SIV and HIV LTRs.
Immunohistochemical Localization of Type D Retrovirus Serotype 1 in the Digestive Tract of Rhesus Monkeys With Simian AIDS
Authors: Lackner Andrew A. , Moore Peter F. , Marx Preston A. , Munn Robert J. , Gardner Murray B. , Lowenstine Linda J.
Published: August 2020

Type D retrovirus infection of rhesus macaques (Macaca mulatta) shares many features with AIDS in man including gastrointestinal signs such as chronic diarrhea and wasting. In some humans and macaques afflicted with these signs and symptoms no etiology can be established. In this study immunohistochemistry was employed to localize D/l/California in the digestive tract of ten animals with simian AIDS. This revealed that both epithelial and lymphoid cells of the digestive tract are commonly infected by this immunosuppressive type D retrovirus.
Molecular Changes Associated With Replication of Simian Immunodeficiency Virus in Human Cells
Authors: Kodama Toshiaki , Burns Dawn P.W. , Kestler Harry W. , Daniel Muthiah D. , Desrosiers Ronald C.
Published: August 2020

The SIVmac239 infectious clone does not have a premature stop codon in its transmembrane protein (TMP) region and it produces full‐length (41 kilodalton, kDa) TMP in macaque peripheral blood lymphocytes (PBL) in vitro and in vivo. However, viruses with truncated forms of TMP (28kDa) are selected during propagation in human cell types; truncated forms arise from point mutations. CAG (glutamine) to TAG (stop), in the viral genome. These results document molecular changes associated with adaptation of SIV‐mac for growth in human cells.
Control Data on Pre‐ and Neonatal Survival of Captive Chimpanzees
Authors: Meiss L. , Goosen C. , Schrama A.G.L.A. , Schonk J.
Published: August 2020

Colony breeding records were analyzed in order to obtain information on pre‐ and neonatal survival in chimpanzees. Biweekly urinary chorionic gonadotrophin testing appeared suitable for determining pregnancy age. The probability of pregnancy termination was low (0.008 per 10 days) to a pregnancy age of 180 days. Between the ages of 180–210 days it was 0.080 per 10 days, and it steadily increased to one per 10 days after 240 days of age. There were no livebirths before 190 days of pregnancy age. Thereafter, the probability of a delivery to be a livebirth rapidly increased to about 0.90 after 210 days of pregnancy age. Infant mortality was less than 0.026 during the first two years of life.
Construction of playgrounds for chimpanzees in biomedical research
Authors: Eichberg Jorg W. , Lee D. Rick , Butler Thomas M. , Kelley Jack , Brent Linda
Published: August 2020

An outdoor 9,000 sq. ft. playground connected to the indoor‐outdoor runs of the breeding facility at Southwest Foundation for Biomedical Research was constructed to simulate a near natural environment for chimpanzees in biomedical research. It is divided into three 75 × 40 ft. compounds to allow several groups of animals to utilize the area simultaneously. Environmental enrichment devices have been added to improve physical and psychological well‐being.
Juvenile rheumatoid arthritis in a rhesus monkey (Macaca mulatto)
Authors: Lipman Neil S. , Schelling Scott H. , Otto Glen , Murphy James C.
Published: August 2020

A juvenile rhesus macaque (Macaca mulatto) developed a symmetrical erosive polyarthritis involving both large and small diarthroidial joints. Neither an infectious nor a metabolic etiology could be determined. This case shares many clinical and pathological features with the polyarticular form of human juvenile rheumatoid arthritis.
The use of nonmetal electrodes in electroejaculation of restrained but unanesthetized macaques
Authors: Sarason R.L. , VandeVoort C.A. , Mader D.R. , Overstreet J.W.
Published: August 2020

A successful technique for electroejaculation with nonmetallic electrodes cut from defibrillation pads is described. Twenty‐six adult male cynomolgus and eleven adult male rhesus macaques were electroejaculated while immobilized with chair restraint. From 123 attempted electroejaculations in both species of macaques, 119 semen specimens were obtained. The volume, concentration, % motility, and % normal forms of cynomolgus and rhesus macaque semen are presented. The use of nonmetallic electrodes provides a high quality ejaculate while minimizing the risks of adverse affects on valuable populations of macaques.
Early SIV encephalopathy
Authors: Hurtrel Bruno , Chakrabarti Lisa , Hurtrel Maryse , Maire Marie Annick , Dormont Dominique , Montagnier Luc
Published: August 2020

SIV encephalopathy was studied in rhesus macaques early after intracerebral (IC) or intravenous (IV) inoculation. Although SIV was detected in the brain of all IC‐inoculated animals, the CNS showed moderate neuropathological changes. IV‐inoculated animals presented a spectrum of brain changes ranging from perivascular infiltrates to multinucleated giant cells. CNS infection was detected as early as seven days post‐IV‐inoculation, mostly in a perivascular localization. Using combined immunohistochemistry and in situ hybridization, infected cells were shown to express macrophage markers.
SIV of stump‐tailed macaque (SIVstm) is a divergent Asian isolate
Authors: Khan Arifa S. , Galvin Teresa A. , Jennings Myra B. , Gardner Murray B. , Lowenstine Linda J.
Published: August 2020

Analysis of molecularly cloned DNAs of SIVs isolated from Asian rhesus macaque (Macaca mulatta; SIVmac) and pig‐tailed macaque (Macaca nemestrina; SIVmne) has indicated a high degree of sequence homology between these viruses. Thus SIVmac and SIVmne might have originated from the same or very closely related viruses. We have cloned and sequenced a PCR‐amplified segment containing the LTR sequences of SIV originating from a stump‐tailed macaque (Macaca arctoides; SIVstm). Comparative sequence analysis indicates that SIVstm belongs to the SIV/HIV‐2 group; however, it is genetically distinct from the other members.
Molecular diversity of SIVsmm/PBj and a cognate variant, SIVsmm/PGg
Authors: Novembre Francis J. , Hirsch Vanessa M. , McClure Harold M. , Johnson Philip R.
Published: August 2020

The molecular diversity of SIVsmm/PBj proviral genomes in tissues of an infected macaque was analyzed. Molecular clones derived directly from intestinal tissue DNA were heterogenous, and contained LTRs with one or two NF‐kB binding sites. LTRs with one NF‐kB site predominated (~75%). Virions derived from biologically active chimeric DNA clones with one or two NF‐kB sites did not induce the acute death syndrome characteristic of PBj infection. These results suggest that either the duplicated NF‐kB site acts in concert with other important viral determinants, or plays no role in producing the PBj syndrome.
Interleukin‐6 and retroperitoneal fibromatosis from SRV‐2–infected macaques with simian AIDS
Authors: Roodman Stanford T. , Woon Ming Dar , Hoffmann Joseph W. , Theodorakis Paul , Tsai Cheng C. , Wu H‐N , Tsai Che‐Chung
Published: August 2020

We investigated the role of Interleukin‐6 (IL‐6) as an autocrine growth factor for the retroperitoneal fibromatosis (RF) cells present in macaques infected with the simian retrovirus type 2 (SRV‐2). Elevated levels of IL‐6 were found in serum of SRV‐2 antibody‐positive macaques, ascites from RF‐positive animals, and RF cell line culture media. IL‐6 mRNA levels increased approximately five‐fold in RF cells incubated with exogeneous SRV‐2. In RF cells, SRV‐2 functions to increase IL‐6 mRNA and protein production and presumably serves as autocrine growth factor.
Anti‐human red cell monoclonal antibodies produced by macaque‐mouse heterohybridomas
Authors: Blancher A. , Socha W.W.
Published: August 2020

Eight monoclonal antibodies (Mabs) against human red cells were produced by macaque‐mouse heterohybridomas. All Mabs uniformly reacted with all human red blood cells tested, but only some agglutinated the red cells of anthropoid apes occasionally detecting intraspecies polymorphisms. None was reactive with blood of Old and New World monkeys. One of the Mabs recognized the Vc antigen of the chimpanzee V‐A‐B‐D system, the homologue of the human M‐N blood group system.
Diseases of the Callitrichidae: A review
Authors: Potkay Stephen
Published: August 2020

The Callitrichidae contains four genera that embrace up to 50 species and subspecies found in neotropical habitats. Certain members have either naturally occurring or induced conditions that serve as important models of human disease. They include viral, bacterial, and parasitic infections, nutritional deficiencies, neoplasia, and various other conditions. The spontaneous diseases of captive callitrichids and those to which these species are experimentally susceptible were reviewed.
Spontaneous cardiomyopathy and nephropathy in the owl monkey (Aotus sp.) in captivity
Authors: Gozalo A. , Dagle G.E. , Montoya E. , Weiler R.E. , Málaga CA.
Published: August 2020

Clinical and pathologic data were reviewed for 72 owl monkeys that died between January 1987 and May 1990 at the Center for Reproduction and Conservation of Nonhuman Primates in Iquitos, Peru. Tissue samples from 39 animals were examined. Hypertrophic cardiac disease (51% of animals examined), dilative cardiomyopathy (26%), and nephropathy (87%) were the most common diagnoses. The incidence of all three diseases appeared to increase with time in captivity. Nephropathy was less severe in colony‐born animals.
Establishment and characterization of Macaca fascicularis lymphoblastoid cell lines
Authors: Manning Carolina H. , Heise Eugene R.
Published: August 2020

A panel of cynomolgus macaque lymphoblastoid cell lines (LCL) was established by transforming peripheral blood mononuclear cells (PBMC) with Herpesvirus papio (HVP), and selected lines were examined by flow cytometry. Results indicate that HVP‐transformed macaque LCL are phenotypically heterogeneous and resemble human Epstein‐Barr virus (EBV)‐transformed LCL in the abundant expression of major histocompatibility complex (MHC) class I and class II molecules. At least some lines are of B cell origin.
Torsion of the colon in vervet monkeys: Association with an atherogenic Western‐type of diet
Authors: Fincham J.E. , Seier J.V. , Lombard C.J.
Published: August 2020

The risk of torsion of the colon in adult male vervet monkeys (Cercopithecus aethipos) increased when they were fed with an atherogenic Western‐type of diet. No cases occurred in females and rapid diagnosis is necessary to prevent lethal consequences.
The importance of nonhuman primate research in the battle against AIDS: A historical perspective
Authors: Gardner Murray B.
Published: August 2020

Retroviruses have been the common foe in two recent “wars,” first against cancer, then against AIDS. Although neither war is close to over, some battles have been won, thanks in part to research using nonhuman primates. As useful as these animals were in studying retroviruses and cancer, their contribution to AIDS research is already far greater. This paper will briefly review the major contribution of nonhuman primates and their retroviruses to research on cancer and AIDS.
Immunization of Macaca fascicularis with inactivated SIV preparations: Challenge with human‐ or monkey‐derived SIV and the effects of a longer immunization schedule
Authors: Titti F. , Mogtomo M.L. Koanga , Borsetti A. , Geraci A. , Sernicola L. , Panzini G. , Turillazzi G.P. , Baroncelli S. , Giovannetti A. , Zamarchi R. , Amadori A. , Dianzani F. , Chieco‐Bianchi L. , Rossi G.B. , Verani P.
Published: August 2020

In cynomolgus monkeys, we compared two human‐derived SIVmac251 whole virus vaccines, a long vs short immunization schedule, and two different challenge viruses. Both vaccines induced protection after challenge with human‐derived SIVmac251/32H. There was no difference between the two schedules of immunization. Seven monkeys, five of which were protected following the first challenge, were reboosted and rechallenged with monkey‐derived SIVmac251, but no protection was observed. The titers of anti‐human cell or ‐SIV neutralizing antibodies were not related to protection.
Intra‐amniotic inoculation of pigtailed macaque (Macaca nemestrina) fetuses with SIV and HIV‐1
Authors: Ochs H.D. , Morton W.R. , Kuller L.D. , Zhu Q. , Tsai C.‐C. , Agy M.B. , Benveniste R.E.
Published: August 2020

Six pregnant pigtailed macaques (Macaca nemestrina) were inoculated intra‐amniotically (i.a.) with SIVMne. All became viremic and seroconverted; three viable offspring were SIV‐positive and at autopsy showed disseminated viral infection; one of three abortuses had SIV‐infected thymic macrophages. Three of five pregnant macaques inoculated i.v. and/or i.a. with HIV‐1LAI became virus‐positive, and four seroconverted, suggesting fetal‐maternal transmission. One abortus had HIV‐1‐antigen in lymph nodes and brain; one infant, culture‐positive at birth, died at age 11 days of disseminated HIV‐1 infection.
Early hematologic changes in rhesus macaques (Macaca mulatta) infected with pathogenic and nonpathogenic isolates of SIVmac
Authors: Mandell Carol P. , Jain Nemi C. , Miller Christopher J. , Marthas Marta , Dandekar Satya
Published: August 2020

Early hematologic changes were studied over a 14 day period in three groups of six rhesus macaques intravenously infected with pathogenic and nonpathogenic isolates of SIVmac. Abnormalities in blood included a mild blood loss anemia, sporadic lymphopenia, and variable CD4+ and CD8 + T lymphocyte numbers. Prominent bone marrow findings in macaques inoculated with pathogenic uncloned SIVmac and molecularly cloned pathogenic SIVmac‐239 were hypercellularity, myeloid and megakaryocytic hyperplasia, and lymphoid aggregates. Infrequent mild morphologic abnormalities were present in macaques infected with a nonpathogenic molecular clone, SIVmac‐1A11.
Arthritis of the spondyloarthropathy variety in Callithrix jacchus
Authors: Rothschild Bruce M.
Published: August 2020

Sixty skeletons of Callithrix jacchus were examined to identify spondyloarthropathy. Erosive disease in Callithrix was confirmed as spondyloarthropathy on the basis of diagnostic sacroiliac erosions, syndesmophyte formation, and the nature and distribution of the peripheral joint erosions.
Estradiol, progesterone, and sex hormone‐binding globulin in female rhesus monkeys (Macaca mulatta)
Authors: Longcope C. , Bukowski C. , Tast J.
Published: August 2020

We measured the concentrations of estradiol, progesterone, and the sex hormone‐binding globulin capacity (rhSHBG) in serum of female rhesus monkeys (Macaca mulatta). Although the serum rhSHBG capacity was altered by the removal of ovarian hormones, presumably estradiol, acute changes in serum estradiol and progesterone did not influence SHBG capacity. There appears to be a relatively low threshold for the effect of estradiol on rhSHBG capacity. The threshold must be present for a finite length of time to have that effect.
Exteriorized chronic aorto‐caval arteriovenous access shunts in the baboon (Papio cynocephalus)
Authors: Bass Arie , Krupski William C. , Hanson Stephen R. , Dodson Thomas , Lumsden Alan , White Deborah , Harker Laurence A. , Kelly Andrew B.
Published: August 2020

A chronic arteriovenous (AV) blood access shunt has been developed in baboons. It is composed of silicone rubber tubing extensions bonded to vascular graft polytetrafluoroethylene (ePTFE) cuffs, for creating anastomoses with the distal aorta and inferior vena cava. Following surgical implantation, shunts remain patent for months (X = 9 ± 2.5 months) and provides long‐term ex vivo access to non‐anticoagulated blood (Mean Blood Flow = 312 ± 69 mL/min).
Fast scan magnetic resonance imaging and Doppler ultrasonography of uteroplacental hemodynamics in the rhesus monkey (Macaca mulatta)
Authors: Panigel M. , Dixon T. , Constantinidis I. , Sheppard S. , Swenson R. , McLure H. , Campbell W.E. , Huddleston J. , Polliotti B. , Nahmias A.
Published: August 2020

Fast scan magnetic resonance imaging, color Doppler ultrasonography, and magnetic resonance angiography were used to demonstrate the uteroplacental hemodynamics in rhesus monkeys. “Jets” of maternal blood spurting into the placenta were observed with, or without, the use of a contrast medium from 114 days to the term of pregnancy. Cumulative intravenous doses of cocaine hydrochloride brought about changes in the sequences of imaging of the maternal blood inflow to the placenta. These methods appear suitable for non‐invasive monitoring of the effects of drugs on placental function.