Impact of Microsurgical Reconstruction Timing on the Risk of Free Flap Loss in Acute Burns: Systematic Review and Meta-Analysis.

Background: Free tissue transfer is usually considered as a last resort in severe burn cases, when skin substitutes and local flaps are not viable options. Prior studies have demonstrated a free flap loss rate ranging from 0% to 44%. The aim of this study is to identify the ideal timing to perform free flap reconstruction in acute burn-related injuries to minimize free flap loss. Methods: A systematic review and meta-analysis was performed and reported according to PRISMA guidelines. PubMed, Embase, Web of Science, and Cochrane Library databases were queried. The review protocol was registered on PROSPERO database (CRD42023404478). Three time intervals from day of injury were identified: (1) 0-4 days, (2) 5-21 days, and (3) 22 days-6 weeks. The primary outcome was total free flap loss. Results: A total of 17 articles met inclusion criteria. The analysis included 275 free flaps performed in 260 patients (88% men, 12% women) affected by acute burn injuries. The pooled prevalence of free flap failure in the three time intervals (0-4 days, 5-21 days, and 22 days-6 weeks) were 7.32% [95% confidence interval (CI): 2.38%-20.37%], 16.55% (95% CI: 11.35%-23.51%), and 6.74% (95% CI: 3.06%-14.20%), respectively. Conclusions: Free flap reconstruction carries a high risk of failure in patients with acute burn. However, timing of the reconstruction appears to influence surgical outcomes. Free flap reconstruction performed between 5 and 21 days from burn injury had a trend toward higher flap loss rates and should be discouraged.

Free Flap Failure and Contracture Recurrence in Delayed Burn Reconstruction: A Systematic Review and Meta-analysis.

Background: Free tissue transfer is often considered a last resort in burn reconstruction due to its complexity and associated risks. A comprehensive review on free flap outcomes in delayed burn reconstruction is currently lacking. The study aimed to evaluate the available evidence on the failure and contracture recurrence rates in free flap delayed burn reconstruction. Methods: A systematic review and meta-analysis was conducted and reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. The protocol was registered on PROSPERO (CRD42023404478). The following databases were accessed: Embase, PubMed, Web of Science, and Cochrane Library. The measured outcomes were free flap loss and contracture recurrence rate. Results: Of the 1262 retrieved articles, 40 qualified for inclusion, reporting on 1026 free flaps performed in 928 patients. The mean age was 29.25 years [95% confidence interval (CI), 24.63-33.88]. Delayed burn reconstruction was performed at an average of 94.68 months [95% CI, - 9.34 to 198.70] after initial injury, with a follow-up period of 23.02 months [95% CI, 4.46-41.58]. Total flap loss rate was 3.80% [95% CI, 2.79-5.16] and partial flap loss rate was 5.95% [95% CI, 4.65-7.57]. Interestingly, burn contracture recurrence rate was 0.62% [95% CI, 0.20-1.90]. Conclusions: This systematic review provides a comprehensive evaluation of the free flap outcomes in delayed burn reconstruction. The flap loss rate was relatively low, given the complexity of the procedure and potential risks. Furthermore, burn contracture rate was found to be extremely low. This study demonstrates that free flaps are a safe and effective option for delayed burn reconstruction.

The Development and Management of Neck Burn Scar Contracture Recurrence: A Single-Center Retrospective Cohort Study.

INTRODUCTION: Burn neck contractures pose a great challenge for reconstructive surgeons. A paucity of literature exist regarding long-term outcomes based on different surgical management strategies. The aim of this study was to evaluate the long-term outcomes of the treatment of neck burn scar contractures and evaluate surgical strategies according to their long-term effectiveness and associated complications. METHODS: A retrospective cohort study was conducted to review outcomes of neck contractures release after burn injury. All patients operated on between January 2009 and February 2023 at a single institution were included. RESULTS: A total of 20 patients developed neck burn scar contracture and were included in this study. The mean age was 32.9 ± 20.3 years. The burn injuries were most commonly thermal (n = 19, 95%). All burn injuries were full-thickness burns, with an average neck defect size of 130.5 ± 106.0 cm2. Overall, 45 surgical scar release procedures were performed on the 20 patients who developed a neck contracture. Patients underwent 1.65 ± 1.04 surgeries on average to address neck contracture. Although 25% of patients only received 1 surgery to treat neck contracture, some patients underwent as many as 8 surgeries. Contracture recurrence (CR) was the most common complication and occurred in 28.9% of the cases. The mean percentage total body surface area did not significantly differ in CR patients (26.7% ± 14.9%) and no-CR patients (44.5% ± 30.2%). However, there was a significant difference (P = 0.01) in the average neck defect size between CR patients (198.5 ± 108.3 cm2) and no-CR patients (81.1 ± 75.1 cm2). CONCLUSIONS: This study showed that risk factors for initial burn scar contractures may differ from those associated with CR, highlighting the importance of neck defect size as a predictor. The study also examines various surgical approaches, with Z-plasty showing promise for managing CR. However, the absence of data on neck range of motion is a limitation. This research underscores the complexity of managing CR and emphasizes the need for ongoing postoperative monitoring.

Free Flap Failure and Complications in Acute Burns: A Systematic Review and Meta-analysis.

Background: Severe acute burn injuries represent a challenge to the reconstructive surgeon. Free flap reconstruction might be required in cases of significant critical structure exposure and soft tissue deficits, when local options are unavailable. This study aimed to determine the free flap complication rate in acute burn patients. Methods: A systematic review and meta-analysis were conducted and reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines and registered on the International Prospective Register of Systematic Reviews database (CRD42023404478). The following databases were accessed: Embase, PubMed, Web of Science, and Cochrane Library. The primary outcome was the free flap failure rate. Results: The study identified 31 articles for inclusion. A total of 427 patients (83.3% men, 16.7% women) accounting for 454 free flaps were included. The mean patient age was 36.21 [95% confidence interval (CI), 31.25-41.16]. Total free flap loss rate was 9.91% [95% CI, 7.48%-13.02%], and partial flap loss was 4.76% [95% CI, 2.66%-8.39%]. The rate of venous thrombosis was 6.41% [95% CI, 3.90%-10.36%] and arterial thrombosis was 5.08% [95% CI, 3.09%-8.26%]. Acute return to the operating room occurred in 20.63% [16.33%-25.71%] of cases. Stratified by body region, free flaps in the lower extremity had a failure rate of 8.33% [95% CI, 4.39%-15.24%], whereas in the upper extremity, the failure rate was 6.74% [95% CI, 3.95%-11.25%]. Conclusion: This study highlights the high risk of free flap complications and failure in acute burn patients.

The adoption of climate-smart agriculture to address wildfires in the Maya Golden Landscape of Belize: Smallholder farmers' perceptions.

Ecosystems around the globe are enduring wildfires with greater frequency, intensity, and severity and this trend is projected to continue as a result of climate change. Climate-smart agriculture (CSA) has been proposed as a strategy to prevent wildfires and mitigate climate change impacts; however, it remains poorly understood as a strategy to prevent wildfires. Therefore, the authors propose a multimethod approach that combines mapping of wildfire susceptibility and social surveys to identify priority areas, main factors influencing the adoption of CSA practices, barriers to their implementation, and the best CSA practices that can be implemented to mitigate wildfires in Belize's Maya Golden Landscape (MGL). Farmers ranked slash and mulch, crop diversification, and agroforestry as the main CSA practices that can be implemented to address wildfires caused by agriculture in the MGL. In order to reduce wildfire risk, these practices should, be implemented in agricultural areas near wildlands with high wildfire susceptibility and during the fire season (February-May), in the case of slash and mulch. However, socio-demographic and economic characteristics, together with a lack of training and extension services support, inadequate consultation by agencies, and limited financial resources, hinder the broader adoption of CSA practices in the MGL. Our research produced actionable and valuable information that can be used to design policies and programs to mitigate the impacts of climate change and wildfire risk in the MGL. This approach can also be used in other regions where wildfires are caused by agricultural practices to identify priority areas, barriers and suitable CSA practices that can be implemented to mitigate wildfires.

Is Eriocnemis luciani meridae (Aves: Trochilidae) a diagnosable taxon and does it come from Venezuela, with remarks on the collectors Salomn Briceo and Walther Frederick Henninger.

Eriocnemis luciani meridae was originally described from a single specimen collected in the late 19th century in western Venezuela. Subsequently a second specimen of E. luciani, also labelled Venezuela, has been taken as additional proof for a highly disjunct population of this hummingbird, which otherwise ranges from southwest Colombia to southern Peru (taxonomy-dependent). Eriocnemis l. meridae has been accepted by all of the global checklists of birds, but has been routinely ignored by Venezuelan sources. In an effort to resolve this dichotomy of treatment, we re-examined the specimens plumage in comparison with relevant material in two major European bird collections. We found that the characters used to erect E. l. meridae are only doubtfully or weakly expressed in the holotype and appear invisible in the Ohio specimen, but both are clearly referrable to the species E. luciani. Evidence that the second specimen was definitely collected in Venezuela is weak and its overall provenance is unclear. In contrast, an extensive historical investigation of the relevant collectors indicates that the holotype does appear to have been taken in Venezuela, although perhaps not in the precise locality indicated for it. This leaves an unusual situation whereby we consider the case for a separate Venezuelan endemic taxon to be unproven, but there is no incontrovertible reason to exclude the species from the countrys avifauna; according to recent niche modelling data it is best searched for in the Sierra Nevada of Mrida state. In contrast, a second subspecies of E. luciani, E. l. baptistae, described by the same authors as endemic to part of western Ecuador is, according to our reappraisal, clearly diagnosable and is upheld.

The Use of a Hartmann's Pouch for Bowel Vaginoplasty: A Case Report.

Bowel vaginoplasty is a well-described procedure utilizing a pedicled segment of large or small bowel. It has most commonly been used for vaginal agenesis, male-to-female gender affirmation surgery when the phallus skin is not sufficient, or a revision after failure of the primary reconstruction. Our case report describes the usage of a pedicled segment of large bowel to reconstruct the vagina after severe stricture of the original reconstruction. We were able to provide relief of the symptomatic Hartmann's pouch mucocele, urethral stricture, and provide a functional introitus and vaginal canal. This technique can provide a framework that can be used as a salvage plan in patients with previously irritated and inhospitable defects.

Gender Disparities Among Burn Surgery Leadership.

Gender disparities have been described in the plastic surgery and general surgery literature, but no data have been reported in burn surgery. The aim of this study is to determine gender disparities among burn surgery leadership. A cross-sectional study was performed. Burn surgeons included were directors of American Burn Association (ABA)-verified burn centers, past presidents of the ABA, and International Society for Burn Injuries (ISBI), and editors of the Journal of Burn Care & Research, Burns, Burns & Trauma, Annals of Burns & Fire Disasters, and the International Journal of Burns and Trauma. Training, age, H-index, and academic level and leadership position were compared among surgeons identified. Among the 69 ABA and ISBI past presidents, 203 burn journals' editorial board members, and 71 burn unit directors, females represented only 2.9%, 10.5%, and 17%, respectively. Among burn unit directors, females completed fellowship training more recently than males (female = 2006, male = 1999, P < .02), have lower H-indexes (female = 8.6, male = 17.3, P = .03), and are less represented as full professors (female = 8.3%, male = 42.4%, P = .026). There were no differences in age, residency, research fellowship, or number of fellowships. Gender disparities exist in burn surgery and are highlighted at the leadership level, even though female surgeons have a similar age, residency training, and other background factors. However, gender diversity in burn surgery may improve as females in junior faculty positions advance in their careers.

Delayed Hypersensitivity Reaction after Nipple Tattooing: A Novel Case Report.

We present a patient who underwent bilateral 3-dimensional (3D) nipple tattooing for nipple areolar reconstruction after implant-based breast reconstruction for breast cancer. Several weeks after nipple tattooing, the patient developed a delayed hypersensitivity reaction around both of her tattooed nipple areolar complexes. This is the first case reported in the literature of a hypersensitivity reaction from 3D nipple tattooing.

Synonymization of the genus nomen Dendroplex Swainson, 1827 and description of a new genus of woodcreeper (Aves: Passeriformes: Dendrocolaptidae) with remarks on Articles 67.5 and 70.3 of the Code.

The polytypic Straight-billed Woodcreeper Dendroplex picus (J. F. Gmelin, 1788) is one of the most complex species-groups of Dendrocolaptidae (Aves: Passeriformes), from both the nomenclatural and morphological standpoints. Firstly, its alpha taxonomy is debatable. Virtually all recent works (e.g. Aleixo 2002; Marantz et al. 2003; del Hoyo Collar 2016) have recognized just two species in the group-Dendroplex picus and Zimmer's Woodcreeper Dendroplex kienerii (Des Murs, 1856)-although some of the other described taxa possess singular morphological characters and well-defined ranges somewhat isolated from their geographically closest relatives (e.g. Plain-throated Woodcreeper Dendroplex picirostris Lafresnaye, 1847). Secondly, the correct genus to which to allocate taxa presently included in this group (vide Aleixo 2002) has been controversial. There is a considerable confusion as to which nominal species should be regarded as the type of Dendroplex Swainson, 1827b. Three species are involved in the dispute (Cory Hellmayr 1925; Peters 1951; Aleixo et al. 2002; Marantz et al. 2003; Aleixo et al. 2007): Oriolus picus J. F. Gmelin, 1788; Dendrocolaptes guttatus M. H. C. Lichtenstein, 1818; and Dendrocolaptes ocellatus Spix, 1824. Here, we re-examine the nomenclatural issue and show that application of the nomen Dendroplex to the clade comprising the species-group D. picus (Aleixo et al. 2007) is based on a misunderstanding of the application of Article 70.3 of the Code (Anon. 1999) and that Dendrocolaptes ocellatus Spix, 1824, is its real type species. Consequently, the genus Dendroplex Swainson, 1827b, must be considered a junior synonym of Xiphorhynchus Swainson, 1827a. Because no generic nomen is currently available for them, we propose a new genus nomen to encompass the species originally described as Oriolus picus J. F. Gmelin, 1788, Dendroplex picirostris Lafresnaye, 1847, and Dendrornis kienerii Des Murs, 1856.

The 'foremost ornithological mystery of Costa Rica': Amazilia alfaroana Underwood, 1896.

The hummingbird Amazilia alfaroana is known from a single specimen, collected on the Volcán de Miravalles, in north-west Costa Rica, in September 1895. Since the early 20th century, the taxon has been almost always been treated as a subspecies of Indigo-capped Hummingbird A. cyanifrons, which is otherwise endemic to Colombia, although it has also been tentatively suggested that the holotype might represent a hybrid between two unnamed species of trochilids. Our detailed analysis of the specimen reveals species-level differences between A. alfaroana and A. cyanifrons, and no evidence of characters that might suggest a hybrid between two species known to occur in the relevant region. Until molecular techniques have been brought to bear, we believe that A. alfaroana is best treated as a possibly now extinct species.

Tiny Bird, Huge Mystery-The Possibly Extinct Hooded Seedeater (Sporophila melanops) Is a Capuchino with a Melanistic Cap.

Known with certainty solely from a unique male specimen collected in central Brazil in the first quarter of the 19th century, the Critically Endangered (Possibly Extinct) Hooded Seedeater Sporophila melanops has been one of the great enigmas of Neotropical ornithology, arguably the only one of a host of long-lost species from Brazil to remain obstinately undiscovered. We reanalysed the morphology of the type specimen, as well as a female specimen postulated to represent the same taxon, and sequenced mitochondrial DNA (COI and Cyt-b) from both individuals. Furthermore, we visited the type locality, at the border between Goiás and Mato Grosso, and its environs on multiple occasions at different seasons, searching for birds with similar morphology to the type, without success. Novel genetic and morphological evidence clearly demonstrates that the type of S. melanops is not closely related to Yellow-bellied Seedeater S. nigricollis, as has been frequently postulated in the literature, but is in fact a representative of one of the so-called capuchinos, a clade of attractively plumaged seedeaters that breed mostly in the Southern Cone of South America. Our morphological analysis indicates that S. melanops has a hitherto unreported dark-coffee throat and that it is probably a Dark-throated Seedeater S. ruficollis collected within its wintering range, acquiring breeding plumage and showing melanism on the cap feathers. Alternatively, it may be a melanistic-capped individual of a local population of seedeaters known to breed in the Esteros del Iberá, Corrientes, Argentina, to which the name S. ruficollis might be applicable, whilst the name S. plumbeiceps might be available for what is currently known as S. ruficollis. A hybrid origin for S. melanops cannot be ruled out from the available data, but seems unlikely. The purported female specimen of S. melanops pertains either to S. nigricollis or to Double-collared Seedeater S. caerulescens based on genetic and morphological data, and thus cannot be a female of S. melanops. We conclude that Sporophila melanops is not typical of any natural population of seedeaters, appears to have been collected far from its breeding grounds while overwintering in central Brazil, and should not be afforded any conservation status.

Agomelatine or placebo as adjunctive therapy to a mood stabiliser in bipolar I depression: randomised double-blind placebo-controlled trial.

BACKGROUND: Adjunctive antidepressant therapy is commonly used to treat acute bipolar depression but few studies have examined this strategy. AIMS: To examine the efficacy of agomelatine v. placebo as adjuncts to lithium or valproate in bipolar depression. METHOD: Patients who were currently depressed despite taking lithium or valproate for at least 6 weeks were randomised to treatment with agomelatine (n = 172) or placebo (n = 172) for 8 weeks of acute therapy and 44 weeks of continuation therapy (trial registration: ISRCTN28588282). RESULTS: No significant differences in improvement of depressive symptoms were observed between the two groups either at 8 weeks or 52 weeks on the primary efficacy measure of change in Montgomery-Åsberg Depression Rating Scale scores from baseline to end-point. Adverse events including switches into mania/hypomania were low and similar in both groups. CONCLUSIONS: Agomelatine adjunctive therapy was not superior to placebo adjunctive therapy for acute bipolar depression.

Supplemental feeding for ecotourism reverses diel activity and alters movement patterns and spatial distribution of the southern stingray, Dasyatis americana.

Southern stingrays, Dasyatis americana, have been provided supplemental food in ecotourism operations at Stingray City Sandbar (SCS), Grand Cayman since 1986, with this site becoming one of the world's most famous and heavily visited marine wildlife interaction venues. Given expansion of marine wildlife interactive tourism worldwide, there are questions about the effects of such activities on the focal species and their ecosystems. We used a combination of acoustic telemetry and tag-recapture efforts to test the hypothesis that human-sourced supplemental feeding has altered stingray activity patterns and habitat use at SCS relative to wild animals at control sites. Secondarily, we also qualitatively estimated the population size of stingrays supporting this major ecotourism venue. Tag-recapture data indicated that a population of at least 164 stingrays, over 80% female, utilized the small area at SCS for prolonged periods of time. Examination of comparative movements of mature female stingrays at SCS and control sites revealed strong differences between the two groups: The fed animals demonstrated a notable inversion of diel activity, being constantly active during the day with little movement at night compared to the nocturnally active wild stingrays; The fed stingrays utilized significantly (p<0.05) smaller 24 hour activity spaces compared to wild conspecifics, staying in close proximity to the ecotourism site; Fed stingrays showed a high degree of overlap in their core activity spaces compared to wild stingrays which were largely solitary in the spaces utilized (72% vs. 3% overlap respectively). Supplemental feeding has strikingly altered movement behavior and spatial distribution of the stingrays, and generated an atypically high density of animals at SCS which could have downstream fitness costs for individuals and potentially broader ecosystem effects. These findings should help environmental managers plan mitigating measures for existing operations, and develop precautionary policies regarding proposed feeding sites.

Prevention of hyponatremia during maintenance intravenous fluid administration: a prospective randomized study of fluid type versus fluid rate.

OBJECTIVES: To determine the importance of sodium content versus administration rate of intravenous fluids in the development of hyponatremia in postoperative children. STUDY DESIGN: In this prospective, randomized, nonblinded study, 124 children admitted for surgery received 0.9% (NS) or 0.45% (N/2) saline solution at 100% or 50% maintenance rates. Plasma electrolytes, osmolality, and ADH at induction of anesthesia were compared with values 8 hours (T(8)), and 24 hours (T(24); n = 67) after surgery. Blood glucose and ketones were measured every 4 hours. Electrolytes and osmolality were measured in urine samples. RESULTS: Plasma sodium concentrations fell in both N/2 groups at T(8) (100%: -1.5 +/- 2.3 mmol/L 50%: -1.9 +/- 2.0 mmol/L; P < .01) with hyponatremia more common than in the NS groups at T(8) (30% vs 10%; P = .02) but not T(24). Median plasma antidiuretic hormone concentrations increased 2- to 4-fold during surgery (P < or = .001) and only reattained levels at induction of anesthesia by T(24) in the N/2 100% group. On multiple linear regression analysis, fluid type, not rate determined risk of hyponatremia (P < .04). Two children on 100% developed SIADH (1NS). Fourteen (23%; 7NS) on 50% maintenance were assessed as dehydrated. Dextrose content was increased in 18 for hypoglycemia or ketosis. CONCLUSIONS: The risk of hyponatremia was decreased by isotonic saline solution but not fluid restriction.

Candidate-gene association study of mothers with pre-eclampsia, and their infants, analyzing 775 SNPs in 190 genes.

Pre-eclampsia (PE) affects 5-7% of pregnancies in the US, and is a leading cause of maternal death and perinatal morbidity and mortality worldwide. To identify genes with a role in PE, we conducted a large-scale association study evaluating 775 SNPs in 190 candidate genes selected for a potential role in obstetrical complications. SNP discovery was performed by DNA sequencing, and genotyping was carried out in a high-throughput facility using the MassARRAY(TM) System. Women with PE (n = 394) and their offspring (n = 324) were compared with control women (n = 602) and their offspring (n = 631) from the same hospital-based population. Haplotypes were estimated for each gene using the EM algorithm, and empirical p values were obtained for a logistic regression-based score test, adjusted for significant covariates. An interaction model between maternal and offspring genotypes was also evaluated. The most significant findings for association with PE were COL1A1 (p = 0.0011) and IL1A (p = 0.0014) for the maternal genotype, and PLAUR (p = 0.0008) for the offspring genotype. Common candidate genes for PE, including MTHFR and NOS3, were not significantly associated with PE. For the interaction model, SNPs within IGF1 (p = 0.0035) and IL4R (p = 0.0036) gave the most significant results. This study is one of the most comprehensive genetic association studies of PE to date, including an evaluation of offspring genotypes that have rarely been considered in previous studies. Although we did not identify statistically significant evidence of association for any of the candidate loci evaluated here after adjusting for multiple testing using the false discovery rate, additional compelling evidence exists, including multiple SNPs with nominally significant p values in COL1A1 and the IL1A region, and previous reports of association for IL1A, to support continued interest in these genes as candidates for PE. Identification of the genetic regulators of PE may have broader implications, since women with PE are at increased risk of death from cardiovascular diseases later in life.

[Epidemiology of certain endemic parasitic diseases in the town of Guadalupe (Republic of Sao Tome and Principe). II. Other endemic parasitic diseases]. / Epidémiologie de certaines endémies parasitaires dans la ville de Guadalupe (République de Saõ Tomé et Príncipe). II. Autres endémies parasitaires.

Stool, blood and urine specimens have been collected from 380 inhabitants of all age groups living in the small town of Guadalupe in May 1992. The seroprevalence of Falciparum malaria (96%), toxoplasmosis (73.3%), have been measured.

[Epidemiology of certain endemic parasitic diseases in the town of Guadalupe (Republic of Sao Tome and Principe) I. Schistosomiasis intercalatum and intestinal worms]. / Epidémiologie de certaines endémies parasitaires dans la ville de Guadalupe (République de Saõ Tomé et Príncipe). I. Schistosomose à S. intercalatum et verminoses intestinales.

Schistosomiasis intercalatum in known to exist in Saõ Tomé since 1988, (Corachan et al.). It is transmitted by Bulinus forskalii, (Brown et al., 1989). Stool, blood and urine specimens have been collected from 380 inhabitants of all age groups living in the small town of Guadalupe close to the Agua Traz river and Agua Polino. The prevalence of schistosomiasis by detection of S. intercalatum eggs in a 10 mg stool thick smear (Kato technique) is 25.5%. An excreted Schistosoma polysaccharide antigen, detected by means of a monoclonal antibody (Ripert et al., 1992), is found in 49.1% of the urine samples. Patients voiding S. intercalatum eggs in stools have been treated with praziquantel (40 mg/kg body weight), as recommended by WHO Expert Committee on Schistosomiasis, but it might be wise to also treat persons excreting antigen in urine. The prevalence of intestinal helminthiasis, ascariasis (73.7%), trichuriasis (73.7%) and necatoriasis have been measured.

Isolation and characterization of human T-Cell lymphotropic virus type-1 from patients with tropical spastic paraparesis

Endemic tropical spastic paraparesis/HTLV-I associated myelopathy (TSP/HAM) is a slowly progressive chronic neurological disorder that is manifested clinically by spastic paraperesis frequently in association with bowel and bladder dysfunction. It is one of the most common chronic neurologic disorders in many endemic foci around the world. Human T-lymphotropic virus type-1 (HTVL-I) has been etiologically associated with TSP/HAM based primarily on the high prevalence of antibodies to HTLV-I in the serum and CSF of affected patients. We report here the isolation of HTLV-I from peripheral blood lymphocytes and cerebrospinal fluid derived mononuclear cells of TSP/HAM patients by stimulation with interleukin-2 and cocultivation with umbilical cord blood mononuclear cells. Established cell lines contained HTLV-I antigen as demonstrated by immunoflourescence and cell-associated virus particles as observed by electron microscopy; low level reverse transcriptase activity was detected in cultures expressing viral antigens. Virus infected cultures were transformed in vitro as determined by their loss of contact inhibition and their continuous growth in the absence of exogenous IL-2. Of particular significance was our location of HTLV-I from three family members with TSP/HAM of varying duration and clinical severity. This study resulted in the first isolation of virus from a cluster of TSP/HAM patients within the same family, the first isolation of virus from a childhood case of TSP/HAM, and the first in vitro transformed HTLV-I infected cells from TSP/HAM patients. In addition, the methodology applied in this investigation subsequently has been used to consistently isolate virus from HTLV-I infected persons from widely separated geographic locations. This work supports a causative role for HTLV-I in the pathogenesis of TSP/HAM and helps to extend the spectrum of disease that may result from HTLV-I infection. (AU)