Evaluating the inclusion of tympanometry in population-based surveys of hearing loss.

OBJECTIVE: This study aimed to determine the implications of including tympanometry in the Rapid Assessment of Hearing Loss survey protocol. A comparative study design was employed, with findings from otoscopy compared with the results of tympanometry. METHOD: A population-based survey of the prevalence and causes of hearing loss among adults aged over 35 years in The Gambia was conducted. Clinical assessments included air conduction audiometry, otoscopy and clinical history. Otoscopy outcome was recorded and for those with hearing loss, a probable cause was assigned. Following otoscopy, tympanometry was completed. Otoscopy outcome was not changed as a result of tympanometry. Clinician assigned cause was compared to the results of tympanometry. The proportion of causes potentially misclassified by excluding tympanometry was determined. RESULTS: Among people with hearing loss, including tympanometry led to a higher proportion diagnosed with middle-ear conditions. CONCLUSION: The value of adding tympanometry to population-based survey protocols is a higher estimated proportion of hearing loss being attributed to middle-ear disease rather than sensorineural causes. This can inform service needs as more people will be classified as needing medical or surgical services, and a slightly lower number will need rehabilitative services, such as hearing assistive devices. It is highly recommended that tympanometry is included in the protocol.

Prevalence of common mental disorders among Syrian refugee children and adolescents in Sultanbeyli district, Istanbul: results of a population-based survey.

AIMS: Research demonstrates elevated levels of common mental disorders among Syrian refugees, but the majority of studies have, to date, focused on adult populations. This study aims to estimate the prevalence of depression, anxiety and post-traumatic stress disorder (PTSD) among Syrian children and adolescents living in Sultanbeyli district of Istanbul, Turkey. METHODS: A population-based survey among Syrian children and adolescents aged 8-17 years living in Sultanbeyli district was conducted in 2019, as part of an all-age survey of disability. 80 clusters of 50 participants (all-ages) were selected from the local municipality's refugee registration database using probability proportionate to size sampling. Children aged 8-17 years were assessed for symptoms of common mental disorders using the Child Revised Impact of Event Scale (CRIES-8) and abbreviated versions of the Center for Epidemiologic Studies Depression Scale for Children (CES-DC) and the Screen for Child Anxiety Related Disorders (SCARED). RESULTS: Of the 852 participants, 23.7% (95% CI 19.9-27.2) screened positive for symptomatic depression, PTSD and anxiety. The prevalence estimates for depression, PTSD and anxiety were 12.5% (95% CI 9.8-15.6), 11.5% (95% CI 9.1-14.4) and 9.2% (95% CI 6.8-12.1), respectively. Depression and PTSD were significantly more common in older adolescents, whilst anxiety and PTSD were significantly more common in girls. Depression was more common in children from poorer households and those who had received no education. Children coming from larger households were less likely to show symptoms of PTSD. CONCLUSIONS: Syrian refugee children and adolescents are vulnerable to common mental disorders, and culturally appropriate prevention and intervention support are needed for this population.

Outcome of cataract surgery at one year in Kenya, the Philippines and Bangladesh.

AIMS: To assess the change in vision following cataract surgery in Kenya, Bangladesh and the Philippines and to identify causes and predictors of poor outcome. METHODS: Cases were identified through surveys, outreach and clinics. They underwent preoperative visual acuity measurement and ophthalmic examination. Cases were re-examined 8-15 months after cataract surgery. Information on age, gender, poverty and literacy was collected at baseline. RESULTS: 452 eyes of 346 people underwent surgery. 124 (27%) eyes had an adverse outcome. In Kenya and the Philippines, the main cause of adverse outcome was refractive error (37% and 49% respectively of all adverse outcomes) then comorbid ocular disease (26% and 27%). In Bangladesh, this was comorbid disease (58%) then surgical complications (21%). There was no significant association between adverse outcome and gender, age, literacy, poverty or preoperative visual acuity. CONCLUSIONS: Adverse outcomes following cataract surgery were frequent in the three countries. Main causes were refractive error and preoperative comorbidities. Many patients are not attaining the outcomes available with modern surgery. Focus should be on correcting refractive error, through operative techniques or postoperative refraction, and on a system for assessing comorbidities and communicating risk to patients. These are only achievable with a commitment to ongoing surgical audit.

Quality of life and visual impairment from cataract in Satkhira district, Bangladesh.

AIMS: To evaluate a vision-related quality of life (QOL) scale (World Health Organization Prevention of Blindness and Deafness Visual Function 20-WHO/PBD VF20) and explore the impact of cataract visual impairment on vision- and health-related QOL in people >or=50 years from Satkhira district, Bangladesh. METHOD: 217 cases visually impaired from cataract and 280 controls with normal vision were interviewed about vision-related QOL (WHO/PBD VF20), generic health-related QOL (EuroQol generic health instrument, EQ-5D) and socio-demographic information. The validity and reliability of the WHO/PBD VF20 were evaluated using standard psychometric tests and criteria. RESULTS: Evidence for validity and reliability of the WHO/PBD VF20 was found. Worsening general functioning, psychosocial and overall eyesight scores were associated with increased visual loss (p for trend<0.001). Cases were more likely to report problems with each EQ-5D descriptive domain and had poorer self-rated health than controls with normal vision (p<0.001). CONCLUSION: Demonstration of the validity and reliability of the WHO/PBD VF20 in this population supports its suitability as a tool for assessing vision-related QOL in low-income settings. The poorer health-related QOL in cases compared with controls suggests an impact of cataract visual impairment on perceived health and well-being, beyond vision-specific experience.

Causes of poor outcome after cataract surgery in Satkhira district, Bangladesh.

AIMS: Recent data have raised concerns about visual outcome following cataract surgery. The aim of this study was to assess the frequency and causes of poor and borderline outcome after cataract surgery in a population-based case series in Satkhira district, Bangladesh. METHODS: A population-based case series was conducted within a population-based cluster survey of people aged over 50 years in Satkhira district where 4868 people underwent visual acuity (VA) screening. Eyes operated for cataract with VA<6/18 were examined in detail by an ophthalmologist, including a full history and dilated fundoscopy, to determine the cause of the visual outcome. RESULTS: Cataract surgery was performed on 213 eyes. Outcome was good (VA>6/18) for 128 eyes (60.1%), borderline (VA<6/18 to 6/60) for 35 eyes (16.4%), and poor (VA<6/60) for 50 eyes (23.5%) with available correction. Borderline and poor outcomes were most commonly due to lack of spectacles (25.8%), poor selection (33.8%), or surgical complications (30.6%). Surgical sequelae, namely posterior capsule opacification, was a less common cause of poor or borderline outcome (9.7%). CONCLUSIONS: Quality of surgical outcomes is of concern in Satkhira district. Increased emphasis on selection of subjects for surgery, provision of spectacles, and monitoring of surgery may improve outcomes.

Regulation of GnRH I receptor gene expression by the GnRH agonist triptorelin, estradiol, and progesterone in the gonadotroph-derived cell line alphaT3-1.

The secretion of luteinizing hormone (LH) and the GnRH receptor (GnRH-R) concentration are modulated by ovarian steroids and GnRH. To elucidate whether this regulation is due to alterations at the transcriptional level, we examined the GnRH I-R mRNA expression in the gonadotroph-derived cell line alphaT3-1 treated with different estradiol and progesterone paradigms and the GnRH I agonist triptorelin. alphaT3-1 cells were treated with different steroid paradigms: 1 nM estradiol or 100 nM progesterone for 48 h alone or in combination. Cells were exposed to 10 nM or 100 pM triptorelin for 30 min, 3 h, 9 h, or, in pulsatile way, with a 5-min pulse per hour. The GnRH I-R mRNA was determined by Northern blot analysis. GnRH I-R mRNA from cells treated with continuous triptorelin decreased in a time- and concentration-dependent manner. Pulsatile triptorelin increased GnRH I-R gene expression. Progesterone alone further enhanced this effect, whereas estradiol and its combination with progesterone diminished it. Continuous combined treatment with estradiol and progesterone lead to a significant decrease of GnRH I-R mRNA by 30% and by 35% for estradiol alone. The addition of 10 nM triptorelin for 30 min or 3 h could not influence that steroid effect. In conclusion, estradiol and progesterone exclusively decreased GnRH I-R mRNA in alphaT3-1 cells no matter whether they are treated additionally with the GnRH I agonist triptorelin. The enhanced sensitivity of gonadotrophs and GnRH I-R upregulation by estradiol is not due to increased GnRH I gene expression because GnRH I-R mRNA is downregulated by estradiol and progesterone. Other pathways of the GnRH I-R signal transduction might be involved.

Short-term effects of IGF-I and estradiol on LH secretion from female rat gonadotrophs.

OBJECTIVE: Growth factors and ovarian steroids modulate LH-secretion from pituitary gonadotrophs. Our previous studies demonstrated that long-term IGF-I treatment enhanced LH-secretion from female rat pituitary cells and estradiol facilitated this effect. The effects of estradiol on LH secretion are time-dependent. Short-term treatment inhibited, long-term treatment enhanced GnRH-induced LH-secretion in serum-containing medium. Here we tested the short-term actions of IGF-I and its interaction with estradiol and whether IGF-I is a prerequisite for the negative effect of short-term estradiol treatment in female rat pituitary cells. DESIGN: Pituitary cells were incubated with a series of increasing concentrations of estradiol (1 pM, 10 pM, 50 pM, 100 pM, 500 pM, 1 nM, 10 nM and 100 nM) for 4 h, IGF-I (10 pM, 100 pM, 1 nM and 10 nM) for 4 h and 14 h and their combinations for 4h in serum-free medium, and then stimulated with 1 nM GnRH during the last 3h of incubation. To clarify the role of IGF-I, cells were incubated simultaneously with estradiol, IGF-I and antibody against IGF-I. LH was measured by radioimmunoassay. RESULTS: Short-term IGF-I treatment did not modify basal or GnRH-induced LH-secretion. Short-term treatment with estradiol did not affect basal or GnRH-induced LH-secretion in serum-free medium. The addition of 100 pM IGF-I to serum-free medium established the negative effect of estradiol short-term treatment on GnRH-induced LH-secretion. The addition of IGF-I antibody fully abolished the negative effect of estradiol. CONCLUSIONS: In conclusion, effects of IGF-I on LH-secretion in female rat pituitary cells require long-term treatment. The negative effect of estradiol short-term treatment on GnRH-induced LH-secretion is dependent on serum-containing medium or the addition of 100 pM IGF-I to serum-free medium.

Rapid assessment of avoidable blindness and needs assessment of cataract surgical services in Satkhira District, Bangladesh.

AIMS: To estimate the magnitude and causes of blindness in people aged > or =50 years in Satkhira district, Bangladesh, and to assess the availability of cataract surgical services. METHODS: 106 clusters of 50 people aged > or =50 years were selected by probability-proportionate to size sampling. Households were selected by compact segment sampling. Eligible participants had their visual acuity measured. Those with visual acuity <6/18 were examined by an ophthalmologist. A needs assessment of surgical services was conducted by interviewing service providers. RESULTS: 4868 people were examined (response rate 91.9%). The prevalence of bilateral blindness was 2.9% (95% confidence interval (CI) 2.4% to 3.5%), that of severe visual impairment was 1.6% (95% CI 1.2% to 2.0%) and that of visual impairment was 8.4% (95% CI 7.5% to 9.3%). 79% of bilateral blindness was due to cataract. The cataract surgical coverage was moderate; 61% of people with bilateral cataract blindness (visual acuity <3/60) had undergone surgery. 20% of the 213 eyes that had undergone cataract surgery had a best-corrected poor outcome (visual acuity <6/60). The cataract surgical rate (CSR) in Satkhira was 547 cataract surgeries per million people per year. CONCLUSIONS: Although the prevalence of blindness and visual impairment was lower than expected, the CSR is inadequate to meet the existing need, and the quality of surgery needs to be improved.

Distance to water source and altitude in relation to active trachoma in Rombo district, Tanzania.

OBJECTIVES: To investigate the relationship between distance to water source, altitude and active trachoma in children in Rombo district, Tanzania. METHODS: In each of Rombo's 64 villages, 10 balozis (groups of 8-40 households) were selected at random and all resident children aged 1-9 years were examined for clinical signs of active trachoma. The households of these children and village water sources were mapped using differentially corrected global positioning system data to determine each household's altitude and distance to the nearest water supply. RESULTS: We examined 12 415 children and diagnosed 1171 cases of active trachoma (weighted prevalence=9.1%, 95% CI: 8.0, 10.2%). Active trachoma prevalence ranged from 0% to 33.7% across villages. Increasing distance to the nearest water source was significantly associated with rising trachoma prevalence (age-adjusted odds ratio for infection (OR) for highest quartile compared to lowest=3.56, 95% CI 2.47, 5.14, P for trend <0.0001). Altitude was significantly inversely associated with trachoma prevalence (age-adjusted OR for highest quartile compared to lowest=0.55, 95% CI 0.41, 0.75, P for trend <0.0001). These associations remained significant after adjustment in multivariate analysis. CONCLUSIONS: Trachoma is endemic in Rombo district, although the prevalence varies considerably between villages. Spatial mapping is a useful method for analysing risk factors for active trachoma.

The household distribution of trachoma in a Tanzanian village: an application of GIS to the study of trachoma.

The distribution of active trachoma in Kahe Mpya, Tanzania, an endemic village of approximately 1000 people, was mapped spatially and analysed for associated risk factors and evidence of clustering. An association between distance to water source and active disease was demonstrated, although this was reduced after accounting for the lack of independence between cases in the same household. Significant clustering of active trachoma within households was demonstrated, adding support to the hypothesized importance of intra-familial transmission. The spatial distribution of trachoma was analysed using the spatial scan statistic, and evidence of clustering of active trachoma cases detected. Understanding the distribution of the disease has implications for understanding the dynamics of transmission and therefore appropriate control activities. The demonstrated spatial clustering suggests inter-familial as well as intra-familial transmission of infection may be common in this setting. The association between active trachoma and geographical information system (GIS) measured distance to water may be relevant for planning control measures.

Interactions of insulin-like growth factors and estradiol in rat pituitary gonadotrophs.

Insulin-like growth factors are involved in the regulation of gonadotropin secretion. Insulin-like growth factor I (IGF-I) has an augmenting effect on gonodotropin-releasing hormone (GnRH)-induced luteinizing hormone (LH) release from female rat gonadotrophs that is facilitated by estradiol. To identify the underlying mechanisms, we investigated whether IGF-I influences total LH pool and the production of intracellular inositol phosphate. In another series of experiments we tested whether IGF-II and estradiol affect LH release of gonadotrophs. Pituitary cells were incubated with 100 pM IGF-I and/or 100 pM estradiol for 24 h. They were stimulated, partially in the presence of Wortmannin, an inhibitor of phosphoinositide 3-kinase, with 330 pM GnRH for 3 h. Subsequently, total LH pool (released and remaining hormone content in lysed cells) in cultures was measured. Intracellular inositol trisphosphate of alphaT3-1 cells, a gonadotrope cell line, treated with estradiol and IGF-I as described before and stimulated with 100 nM GnRH for 15 min was analyzed by ion exchange chromatography. To determine the interaction of IGF-II and estradiol on GnRH-stimulated LH secretion, cells were treated with increasing concentrations of IGF-II (0.05 pM-10 nM) and 100 pM estradiol. IGF-I significantly increased the accumulation of inositol trisphosphate in basal and GnRH-stimulated cells. IGF-I, estradiol, or their combinations did not change total LH pool, although they enhanced LH secretion. Wortmannin abolished the positive effects of IGF-I and estradiol on LH secretion. IGF-II alone increased basal, but not GnRH-induced LH secretion at low concentrations (0.05 pM). Additional estradiol treatment further increased basal, but not GnRH-induced LH secretion. In conclusion, our results suggest that increased LH secretion from female anterior pituitary cells after IGF treatment is due to the amplification of early signal transduction steps rather than changes in LH pool. The inositol trisphosphate signaling pathway is involved in the regulation of LH secretion from gonadotrophs treated with IGF-I. It is not likely that IGF-II plays an important role in the regulation of gonadotropin secretion.

Actions of GnRH antagonists on IGF-II, IGF-binding protein-2 and pregnancy-associated plasma protein-A in human granulosa-lutein cells.

OBJECTIVE: Recently, GnRH antagonists (GnRHants) have been introduced for the prevention of premature LH surges during controlled ovarian hyperstimulation (COH). Here we investigated whether the GnRHants cetrorelix and ganirelix exert effects on the human ovarian IGF system. Since controversy exists on the action of GnRH agonists in the human ovary, we also tested the effect of triptorelin on IGF-II, IGF-binding protein-2 (IGFBP-2) and pregnancy-associated plasma protein-A (PAPP-A) in cultured human granulosa-lutein cells. DESIGN: In vitro cell culture study in a research laboratory of a university hospital. PATIENTS: Cells were obtained from patients treated with different protocols of COH. In addition to gonadotropins they received triptorelin or cetrorelix. Cells were treated with triptorelin, cetrorelix or ganirelix, 1 nmol/l each, for 48 h. IGF-II, IGFBP-2 and PAPP-A were measured by RIA and enzyme immunoassay respectively. RESULTS: GnRHants and triptorelin did not affect IGF-II, IGFBP-2 or PAPP-A. CONCLUSIONS: We conclude that GnRHants do not exert any significant effects on the IGF system of granulosa-lutein cells and therefore their introduction into protocols of COH is unlikely to impair ovarian function.

Effects of insulin on luteinizing hormone and prolactin secretion and calcium signaling in female rat pituitary cells.

INTRODUCTION: Polycystic ovary syndrome (PCOS) is associated with insulin resistance and hyperinsulinemia, which might contribute to the hypersecretion of luteinizing hormone (LH). Hyperprolactinemia is another finding in a subgroup of patients with PCOS, whereas its relation to hyperinsulinemia is not fully understood yet. METHODS: In the present study we tested the hypothesis that insulin might affect LH or prolactin secretion of cultured female rat pituitary cells. To address the mechanisms by which insulin could act at the intracellular level we examined the GnRH- and TRH-induced Ca(2+) signals in single gonadotrophs and lactotrophs, because Ca(2+) is an important component of GnRH signal transduction that is closely related to exocytosis. RESULTS: Cells treated for 24 h with insulin (10(-9) M) showed an enhancement of basal and agonist-induced LH and prolactin secretion. Insulin did not affect GnRH- and TRH-induced Ca(2+) signals compared to controls. There were no differences neither in the frequency nor in the amplitude of the Ca signal. CONCLUSION: Our findings suggest that insulin might contribute to LH hypersecretion. Insulin might be partially responsible for hyperprolactinemia. Since insulin did not affect Ca signaling, other components of the GnRH signal transduction pathway might be involved in LH hypersecretion.

Actions of gonadotropin-releasing hormone antagonists on steroidogenesis in human granulosa lutein cells.

OBJECTIVE: GnRH antagonists have recently been introduced for the prevention of premature LH surges during controlled ovarian hyperstimulation (COH). We have here investigated whether the GnRH antagonists cetrorelix and ganirelix exert effects on ovarian steroidogenesis. Since there is some controversy about the action of GnRH agonists in the human ovary we also tested the effect of triptorelin on steroid production in cultured human granulosa lutein cells. METHODS: Cells were obtained from patients treated with different protocols of COH. In addition to gonadotropins they received triptorelin, cetrorelix, ganirelix or no GnRH analogue. RESULTS: Such in vivo treatment did not result in significant effects of triptorelin or the two GnRH antagonists on spontaneous or human chorionic gonadotropin (hCG)-stimulated steroidogenesis. To exclude the possibility that the in vivo treatment might not affect in vitro steroid production because of low or absent peptide activity, we performed in vitro treatments with triptorelin, cetrorelix and ganirelix for up to 96 h. However, these treatment paradigms did not influence basal or hCG-stimulated steroid production. CONCLUSIONS: We conclude that GnRH antagonists do not exert any significant effects on ovarian steroidogenesis in vitro and therefore their introduction into protocols of COH is unlikely to impair ovarian function.

Interactions of insulin-like growth factor-I, insulin and estradiol with GnRH-stimulated luteinizing hormone release from female rat gonadotrophs.

BACKGROUND: It is well established that ovarian steroids modulate gonadotropin secretion from anterior pituitary cells. It has been speculated that insulin and IGF-I might influence gonadotropin secretion. OBJECTIVE: To investigate the effects of IGF-I and estradiol alone, or combinations of IGF-I with insulin and estradiol on GnRH-stimulated LH release from female rat pituitary cells in serum-supplemented and serum-free culture conditions. METHODS: Pituitary cells were incubated for 24 h or 48 h with a series of increasing concentrations of IGF-I or estradiol and stimulated with 1 nmol/l GnRH for 3 h. To determine the interaction of IGF-I and estradiol on GnRH-stimulated LH secretion, cells were exposed to increasing concentrations of IGF-I and 100 pmol/l estradiol for 24 h. We also investigated the effects of combined treatment with IGF-I and insulin on GnRH-stimulated LH secretion. RESULTS: Our findings indicate that long-term IGF-I treatment (24 h) alone has a significant augmenting effect on GnRH-stimulated LH release in serum-free medium only, with a maximum at low concentrations (10 and 100 pmol/l). Estradiol significantly increased GnRH-induced LH release in a dose-dependent manner. The extent of GnRH-stimulated LH secretion by long-term estradiol treatment (24 h) was significantly greater in serum-supplemented (+42%) medium than in serum-free medium. Estradiol facilitated IGF-I-primed LH responses to GnRH in serum-free medium. In contrast, in serum-supplemented medium, the facilitating potential of estradiol was lower. We also found that, in GnRH-stimulated cells, LH release was augmented by insulin treatment, in contrast to quiescent cells that had been pretreated with 100 pmol/l IGF-I alone and 1 nmol/l insulin alone. CONCLUSIONS: IGF-I and to a lesser extent insulin stimulate GnRH-induced LH secretion from pituitary gonadotrophs. This action is enhanced by estradiol treatment of the cells. However, the well known stimulatory action of estradiol on LH secretion is dependent on the presence of growth factors.

Effect of the gonadotropin-releasing hormone antagonist ganirelix on cyclic adenosine monophosphate accumulation of human granulosa-lutein cells.

OBJECTIVE: To evaluate whether the GnRH antagonist ganirelix exerts an effect on cyclic adenosine monophosphate (cAMP) production of human granulosa-lutein (GL) cells in vitro. DESIGN: In vitro cell culture study. SETTING: Research laboratory of a university hospital. PATIENT(S): Mural GL and cumulus cells were obtained from 15 patients on whom controlled ovarian hyperstimulation was being performed for intracytoplasmic sperm injection treatment. INTERVENTION(S): Mural GL and cumulus cells were cultured for 48 hours with and without 1 nM ganirelix or triptorelin. For the last 6 hours, the cells were either exposed to 1-5 IU hCG or left unstimulated. MAIN OUTCOME MEASURE(S): At the end of the culturing period, the intracellular and extracellular cAMP accumulations were measured by an (125)I-scintillation proximity assay. RESULT(S): hCG induced dose-dependent increases in total cAMP accumulation. Stimulation with 1 IU/mL hCG resulted in 9-fold and 13-fold increases, and 5 IU/mL hCG resulted in 19-fold and 14-fold increases in total cAMP release from cumulus and mural GL cells, respectively. On the other hand, treatments with 1 nM GnRH antagonist ganirelix and 1 nM GnRH agonist triptorelin did not exert any significant changes on the basal and hCG-stimulated cAMP accumulation of mural GL cells and cumulus cells as compared with controls. CONCLUSION(S): Ganirelix does not influence basal and hCG-stimulated cAMP accumulation of human GL cells in vitro. cAMP is apparently not involved in the mechanism of action of GnRH analogs in human ovary.

Engraftment of human kidney tissue in rat radiation chimera: I. A new model of human kidney allograft rejection.

BACKGROUND: We have recently shown that lethally irradiated normal strains of mice and rats, reconstituted with bone marrow from severe combined immune deficiency (SCID) mice, can be engrafted with human peripheral blood mononuclear cells (PBMC). METHODS: The feasibility of transplanting human renal tissue under the kidney capsule of the SCID/Lewis and SCID/nude radiation chimera and the effects of intraperitoneal infusion of allogeneic human PBMC on the human renal implants were investigated by histology, electron microscopy, immunohistochemistry, and fluorescence-activated cell sorter analysis. RESULTS: Sequential evaluation of the human renal implants from 10 days to 2 months after transplantation showed that human parenchymal elements survive in the implants up to 2 months after transplantation. The overall architecture of the transplanted kidney tissue and the normal structure of individual cells in the glomeruli and tubuli were preserved. Infusion of allogeneic human PBMC after kidney implantation resulted in patchy cellular infiltrates, composed mainly of activated human T cells, and led to prompt rejection of the human renal tissue, whereas no signs of inflammation were observed in human renal implants of chimeric rats that did not receive human PBMC. Treatment with OKT3 antibody, anti-human CD25 antibody, or CTLA4Ig fusion protein in vivo ameliorated the rejection process. CONCLUSIONS: Human adult kidney fragments transplanted into SCID-like rats transiently retain competent parenchymal structures. When these grafts are combined with allogeneic human PBMC, acute cellular rejection develops. We suggest that this chimeric model might be useful for the investigation of the effects of experimental manipulation on the kinetics of the inflammatory response during human renal allograft rejection.