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Biomedical subjects

S Thomas

Publications and source records attributed to S Thomas.

At least 163 records · Page 9Linked to original sources

Thalidomide for the treatment of AIDS-associated wasting.

A double-blind, placebo-controlled trial of efficacy and safety of thalidomide in AIDS-associated wasting was carried out. Ninety-nine of 103 male patients had at least one on-study measurement (intent-to-treat [ITT] cohort). Patients were randomized to thalidomide at 100 mg/day (T100) or 200 mg/day (T200), or placebo for 8 weeks. By ITT analysis, the mean change in body weight of the placebo, T100, and T200 treatment groups was 0.3 kg (0.4%), 2.0 kg (3.0%), and 0.9 kg (1.4%), respectively (p = 0.021 for T100 versus placebo; p = 0.53 for T200 versus placebo). Of the 64 patients who completed the 8 weeks of study treatment, significant weight gain was observed in both the T100 group (2.2 kg, [33%]; p = 0.008 versus placebo) and the T200 group (1.5 kg [2.5%]; p = 0.019 versus placebo). Approximately half the weight gain was fat-free mass (bioimpedance analysis). Patients in the T100 or T200 groups had no significant change in CD4+ cell counts, neutrophil counts, or TNF-alpha levels, compared with placebo. HIV viral load measured as log10 copies/ml decreased by a median of 0.07 in the placebo group, and increased by a median of 0.29 (T100 group) and 0.23 (T200 group) (p = 0.024 andp = 0.018 versus placebo, respectively). Thalidomide therapy was associated with mild to moderate rashes and fevers, but not peripheral neuropathy. Although the anabolic benefits of high-dose thalidomide are limited by drug intolerance, 8 weeks of low-dose thalidomide results in significant weight gain in patients with AIDS-associated wasting.

Adult↗

Neighboring group participation of the indole nucleus: An unusual DAST-mediated rearrangement reaction

A rearrangement reaction involving the indole nucleus was investigated using stereochemical markers and low-temperature NMR experiments. Treatment of (3S, 4S)-3-hydroxy-4-(2-phenyl-1H-indol-3-yl)-piperidine-1-carboxylic acid benzyl ester (>90% ee) with diethylaminosulfur trifluoride gave stereospecifically (3S, 4S)-4-fluoro-3-(2-phenyl-1H-indol-3-yl)-piperidine-1-carboxylic acid benzyl ester (>90% ee) with complete regioselectivity. The initial formation of a reactive spirocyclopropyl-3H-indole intermediate is believed to be responsible for the stereo- and regiochemical outcome of the reaction.

Journal Article↗

Human alpha 1,3/4 fucosyltransferases. Characterization of highly conserved cysteine residues and N-linked glycosylation sites.

Human alpha1,3 fucosyltransferases (FucTs) contain four highly conserved cysteine (Cys) residues, in addition to a free Cys residue that lies near the binding site for GDP-fucose (Holmes, E. H., Xu, Z. , Sherwood, A. L., and Macher, B. A. (1995) J. Biol. Chem. 270, 8145-8151). The participation of the highly conserved Cys residues in disulfide bonds and their functional significance were characterized by mass spectrometry (MS) analyses and site-directed mutagenesis, respectively. Among the human FucTs is a subset of enzymes (FucT III, V, and VI) having highly homologous sequences, especially in the catalytic domain, and Cys residues in FucT III and V were characterized. The amino acid sequence of FucT III was characterized. Peptides containing the four conserved Cys residues were detected after reduction and alkylation, and found to be involved in disulfide bonds. The disulfide bond pattern was characterized by multiple stage MS analysis and the use of Glu-C protease and MS/MS analysis. Disulfide bonds in FucT III occur between Cys residues (Cys(81) to Cys(338) and Cys(91) to Cys(341)) at the N and C termini of the catalytic domain, bringing these ends close together in space. Mutagenesis of highly conserved Cys residues to Ser in FucT V resulted in proteins lacking enzymatic activity. Three of the four mutants have molecular weights similar to wild type enzyme and maintained an ability to bind GDP, whereas the other (Cys(104)) produced a series of lower molecular weight bands when characterized by Western blot analysis, and did not bind GDP. FucTs have highly conserved, potential N-linked sites, and our mass spectrometry analyses demonstrated that both N-linked sites are modified with oligosaccharides.

Amino Acid Sequence↗

Strategies for maintaining the particle size of peptide DNA condensates following freeze-drying.

The particle size of peptide DNA condensates were studied after freeze-drying and rehydration as a function of sugar excipient, concentration, pH, DNA concentration, and peptide condensing agent. In the absence of an excipient, freeze-dried 50 microg/ml AlkCWK(18) (iodoacetic acid alkylated Cys-Typ-Lys(18)) DNA condensates formed large fibrous flocculates on rehydration. Of the sugars tested as lyoprotectants, sucrose proved most effective at preserving particle size during rehydration. The addition of 5 wt/vol% sucrose preserved a mean particle diameter of less than 50 nm during rehydration of AlkCWK(18) DNA condensates prepared at DNA concentrations up to 200 microg/ml; however, higher DNA concentrations led to the formation of insoluble fibrous flocculates. Substitution of polyethylene glycol (PEG)-CWK(18) as a DNA condensing peptide eliminated the need for sucrose, resulting in peptide DNA condensates that retained particle size when rehydrated in water or normal saline at concentrations up to 5 mg/ml. The results suggest that sucrose functions primarily as a bulking agent during freeze-drying that only preserves the particle size of AlkCWK(18) DNA condensates up to a maximum concentration of 200 microg/ml. Alternatively, the steric layer created on the surface of PEG-CWK(18) DNA condensates provides far more efficient lyoprotection, preserving their particle size at a concentration of 5 mg/ml without a bulking agent.

DNA↗

Mesino-antimesino oscillations

The phenomenology of supersymmetric theories with low scale supersymmetry breaking and a squark as the lightest standard model superpartner are investigated. Such squarks hadronize with light quarks, forming sbaryons and mesinos before decaying. Production of these supersymmetric bound states at a high energy collider can lead to displaced jets with large negative impact parameters. Neutral mesino-antimesino oscillations are not forbidden by any symmetry and can occur at observable rates. Stop mesino-antimesino oscillations would give a sensitive probe of up-type sflavor violation, and can provide a discovery channel for supersymmetry through events with a same-sign top-top topology.

Journal Article↗

A novel B lymphocyte-associated adaptor protein, Bam32, regulates antigen receptor signaling downstream of phosphatidylinositol 3-kinase.

We have identified and characterized a novel src homology 2 (SH2) and pleckstrin homology (PH) domain-containing adaptor protein, designated Bam32 (for B cell adaptor molecule of 32 kD). cDNAs encoding the human and mouse Bam32 coding sequences were isolated and the human bam32 gene was mapped to chromosome 4q25-q27. Bam32 is expressed by B lymphocytes, but not T lymphocytes or nonhematopoietic cells. Human germinal center B cells show increased Bam32 expression, and resting B cells rapidly upregulate expression of Bam32 after ligation of CD40, but not immunoglobulin M. Bam32 is tyrosine-phosphorylated upon B cell antigen receptor (BCR) ligation or pervanadate stimulation and associates with phospholipase Cgamma2. After BCR ligation, Bam32 is recruited to the plasma membrane through its PH domain. Membrane recruitment requires phosphatidylinositol 3-kinase (PI3K) activity and an intact PI(3,4, 5)P(3)-binding motif, suggesting that membrane association occurs through binding to 3-phosphoinositides. Expression of Bam32 in B cells leads to a dose-dependent inhibition of BCR-induced activation of nuclear factor of activated T cells (NF-AT), which is blocked by deletion of the PH domain or mutation of the PI(3,4,5)P(3)-binding motif. Thus, Bam32 represents a novel B cell-associated adaptor that regulates BCR signaling downstream of PI3K.

Adaptor Proteins, Signal Transducing↗

[Summary of 'Cholesterol' guideline (first revision) of the Dutch Society of Family Physicians].

The revised guidelines on cholesterol of the Dutch College of General Practitioners (DCGP), which closely follow the consensus of the Dutch Institute for Health Care Improvement, provide thresholds for treatment with statins in patients with elevated risks for coronary heart disease (CHD): patients with a history of cardiovascular disease, with an annual CHD risk larger than 2.5-3%, or with a (suspected) hereditary lipid disorder. Unlike the consensus the DCGP guideline advises only to determine a total cholesterol/HDL cholesterol ratio if the accompanying risk table indicates that the patient might fall in the range where drug treatment is indicated. For this purpose an extra column has been added to the table. In patients with a possible hereditary lipid disorder a higher threshold for referral to a specialist is used because moderately raised levels are common in the population and indicate a familial lipid disorder in only part of the cases.

Anticholesteremic Agents↗

RLR1 (THO2), required for expressing lacZ fusions in yeast, is conserved from yeast to humans and is a suppressor of SIN4.

We isolated a mutation (rlr1-1; required for lacZ RNA) in the Saccharomyces cerevisiae (Sc) RLR1 gene as a suppressor of sin4, a component of the Mediator subcomplex of the RNA polymerase II holoenzyme and a determinant of chromatin structure. RLR1 encodes a deduced protein found also in fission yeast, nematode worms, and humans. The presence of these orthologs suggests that Rlr1 family members comprise a class of putative KEKE motif-containing proteins, characteristic of certain chaperones as well as regulators and subunits of the mammalian 20S proteasome. A role for RLR1 (THO2) in transcription appears to occur at a step subsequent to transcription initiation (see also Piruat, J.I. and Aguilera, A., 1998. EMBO J. 17, 4859-4872); Sc genes fused to the reporter gene lacZ were expressed at a very low level, while the corresponding native chromosomal genes were expressed at approximately normal levels in rlr1 mutants. Our studies show that rlr1 mutations cause a wide range of growth defects in addition to their novel affect on lacZ.

Amino Acid Sequence↗

Does leukoaraiosis predict morbidity and mortality?

OBJECTIVE: To determine whether leukoaraiosis predicts morbidity and mortality. BACKGROUND: Gait disturbance and leukoaraiosis both are common in the elderly. Gait disturbance predicts mortality. Leukoaraiosis may be a unifying factor to both gait disturbance and mortality. METHODS: We followed 221 patients prospectively evaluated for severity of neurologic deficits by the National Institutes of Health (NIH) stroke scale and for leukoaraiosis in seven brain regions by CT, graded as absent (n = 119, 54%), mild (in at least one of seven brain regions; n = 54, 24%), or severe (present in all seven brain regions; n = 48, 22%). Pneumonia (n = 27, 12%), falls resulting in fracture requiring hospitalization (n = 7, 3%), and death (n = 38, 17%) were end points. RESULTS: Severe leukoaraiosis predicted death (Cox hazard ratio [HR] = 2.91; 95% CI = 1.5 - 5.6), pneumonia (HR = 5.1; 95% CI = 2.4 - 10.9), death from pneumonia (HR = 8.3; 95% CI = 1.5 - 46), and falls (HR = 6.8; 95% CI = 1.5 - 30). Severe leukoaraiosis predicted a combined end point of death, pneumonia, and falls (HR = 3.5; 95% CI = 2 - 6). Other predictors were NIH stroke scale score, age, smoking, diabetes, gait score, and referral diagnosis of either dementia or Parkinsonism. Severe leukoaraiosis remained a predictor after adjustment for these other factors (HR = 2.2; 95% CI = 1.2 - 3.9), but was borderline after adjusting for gait (HR = 1.96; 95% CI = 0.97 - 3.94; p = 0.061). The combination of severe leukoaraiosis and gait disturbance had the highest risk (HR = 4.4; 95% CI = 2.4 - 7.9). CONCLUSION: Severe leukoaraiosis predicts morbidity and mortality independently of preexisting neurologic deficits. The combination of leukoaraiosis and gait disturbance carries a poor prognosis.

Accidental Falls↗

Assessment of the in vitro and in vivo genotoxicity of Thalomid (thalidomide).

Thalomid is the FDA-approved commercial formulation of thalidomide currently used in the US to treat erythema nodosum leprosum, a complication of leprosy. The genotoxicity of Thalomid thalidomide was assessed in the Ames reverse mutation, AS52/XPRT mammalian cell forward gene mutation, and mouse bone marrow micronucleus assays. The Ames and AS52 assays were performed with and without S9. In the Ames, Salmonella typhimurium strains TA1535, 1537, 98, 100, and 102 and Escherichia coli strain WP2 uvrA were used. Assays were performed by using plate incorporation and liquid pre-incubation systems at thalidomide doses of 50-10,000 microg/plate. In the AS52 assay, Chinese hamster ovary cells were plated with fortified Ham's F12 medium and incubated overnight. The medium was then incubated with 1-1000 microg/ml thalidomide. After a series of aspirations, washings, reconstitutions, and incubations, mutant AS52 cells were fixed and stained. Colonies were then counted and the relative survival frequencies compared to negative controls. In the mouse micronucleus assay, Crl:CD-1 albino mice were dosed with 500, 2,500, and 5,000 mg/kg thalidomide and sacrificed over 72 h. Femurs were flushed with fetal bovine serum and the suspensions centrifuged. The supernatant was aspirated and the cell pellet resuspended and stained. Polychromatic erythrocytes were scored for micronucleated polychromatic and normochromatic erythrocytes. Thalidomide did not increase revertant frequencies in all bacterial strains. It also did not produce any significant increase in the average mutant frequencies of AS52 cells and mouse micronucleated polychromatic erythrocytes. We conclude that Celgene's Thalomid thalidomide is non-genotoxic.

Animals↗

1H-MR spectroscopic monitoring of posttraumatic metabolism following controlled cortical impact injury: pilot study.

Proton magnetic resonance spectroscopy (1H-MRS) has been increasingly utilised in experimental traumatic brain injury for characterisation of posttraumatic metabolic dysfunction. Following human brain injury pathological findings correlated with outcome measures. Combined with conventional T2-weighted MR imaging MRS is a sensitive tool to evaluate metabolic changes in brain tissue following trauma. Studies have been restricted so far to diffuse axonal injury models and fluid percussion injury. Using a high resolution scanner at 4.7 T, MRI combined with 1H-MRS was applied in a pilot study to the controlled cortical impact injury model of experimental brain contusion (CCII). Eight Sprague-Dawley rats were investigated, of which two served as controls. Four animals were injured 24 h after craniotomy, two investigated at 72 h post craniotomy. MRS/MRI indicated a transient brain oedema development and metabolic changes induced by the craniotomy itself. Following CCII MRI demonstrated that the area of contusion as well as the surrounding brain oedema increased twofold in size within 24 h (p < 0.05). MRS showed an immediate increase of N-acetylaspartate (NAA) and glutamate ipsilateral to the contusion and a drop of NAA on the contralateral side. MRS/MRI investigations in the CCII model demonstrated a potential to further elucidate the pathophysiology following traumatic brain contusion.

Animals↗

ICP and MABP following traumatic subarachnoid hemorrhage in the rat.

Traumatic subarachnoidal hemorrhage (t-SAH) is a common finding in head-injured patients occurring with a frequency of 39% according to data of the Traumatic Coma Data Bank. The present study is the first description of a t-SAH-model with particular emphasis on patterns of intracranial pressure (ICP) changes and mean arterial blood pressure (MABP) response. Diffuse brain injury was produced in intubated and ventilated adult Sprague-Dawley rats (N = 24) using a brass weight (500 gm) free falling from a predetermined height (1.5 m) on a steel disc glued to the skull of the rat. Before induction of the injury, heparin was administered intra-arterially (i.a.) and antagonised after injury by protamine. MABP-recordings and ICP-recordings were performed continuously. Histopathology was undertaken. Following injury MABP decreased from 138 +/- 14 mmHg to 89 +/- 22 mmHg. During 5 to 15 min ICP increased up to 89.4 +/- 50.4 mmHg, decreasing slowly within 60 min in surviving animals. The mortality rate was 41.6%. All brains showed a severe subarachnoid hemorrhage in the basal cisterns and cell-loss within the brainstem. Experimental t-SAH is possible. Following t-SAH there is a subacute increase of ICP due to the actual bleeding. The model may provide deeper understanding in the basic physiological patterns of t-SAH.

Animals↗

Influences of secondary injury following traumatic brain injury in developing versus adult rats.

Hypoxia and hypotension are both common findings following traumatic brain injury occurring with a frequency of up to 46% according to data of the Traumatic Coma Data Bank. In the present study the influence of secondary injury on intracranial pressure and the cardiovascular response is investigated in developing rats. Differences from adult rats are determined. Diffuse brain injury was produced in intubated and ventilated 17-20 days old Sprague-Dawley rats (N = 16) using a modification of the Marmarou-model. Hypoxia was induced by reducing O2-concentration to 8% lasting for 15/30 min. Mean arterial blood pressure recordings and intracranial pressure recordings were performed continuously. Animals were divided into two groups, sustaining hypoxia alone (N = 9) and trauma/hypoxia (N = 7). The results were compared to readings in adult animals subjected to hypoxia (N = 5) and trauma/hypoxia (N = 5) (450 gm/150 cm). Immediately following the onset of hypoxia in the developing rat, MABP decreased from 76.5 +/- 13 mm Hg to 35.8 +/- 7 mm Hg. In the adult rat the decrease was more marked (from 93.3 +/- 8 mm Hg to 33.5 +/- 5.7 mm Hg) (p < 0.05). Mortality rate in developing rats with trauma/hypoxia was 43% with no significant change of ICP (from 13 +/- 5.2 to 22.3 +/- 11). All adult animals recovered following trauma/hypoxia with no relevant ICP-increase within one hour post-trauma. Hypoxia induces hypotension in adult and developing rats. However, developing rats appear to be more vulnerable to hypoxia associated with trauma.

Age Factors↗

Visualization of gap junction mobility in living cells.

In order to study the dynamics of gap junctions in living cells, a cDNA was expressed in hepatocellular carcinoma-derived PLC cells coding for chimerical polypeptide Cx.EGFP-1, which consists of rat connexin32 and enhanced green fluorescent protein (EGFP). Cx.EGFP-1 was integrated into gap junctions, and the emitted epifluorescence reliably reported the distribution of the chimera. Therefore, stably transfected PLC clone PCx-9 was used to examine the dynamic behavior of gap junctions by time-lapse fluorescence microscopy. The pleomorphic fluorescent junctional plaques were highly motile within the plasma membrane. They often fused with each other or segregated into smaller patches, and fluctuation of fluorescence was detected within individual gap junctions. Furthermore, the uptake of junctional fragments into the cytoplasm of live cells was documented as originating from dynamic invaginations that form long tubulovesicular structures that pinch off. Endocytosis and subsequent lysosomal degradation, however, appeared to contribute only a little to the rapid gap junction turnover (determined half-life of 3.3 h for Cx.EGFP-1), since most cytoplasmic Cx.EGFP-1 fluorescence did not colocalize with the endocytosed fluid phase marker horseradish peroxidase or the receptor-specific endocytotic ligand transferrin and since it was distinct from lysosomes. Disassembly of gap junctions was monitored in the presence of the translation-inhibitor cycloheximide and showed increased endocytosis and continuous reduction of junctional plaques. Highly motile cytoplasmic microvesicles, which were detectable as multiple, weakly fluorescent puncta in all movies, are proposed to contribute significantly to gap junction morphogenesis by the transport of small subunits between biosynthetic, degradative, and recycling compartments.

Animals↗

Minimal access approach for surgical management of cardiac tumors.

BACKGROUND: Following our experience with minimally invasive valve replacement operation, we utilized this technique for surgical management of cardiac tumors. METHODS: Between April 1997 and September 1999, 5 consecutive patients with cardiac tumors underwent minimally invasive excision of the tumors. The patients were 4 women and 1 man with an age range of 32 to 50 years. The tumor was located in the left atrium in 4 patients and the right atrium in 1 patient. The common presenting symptoms were dyspnea on exertion (100%), chest pain (60%), palpitation (60%), and transient ischemic attack (20%). Diagnosis was established preoperatively by echocardiography only. RESULTS: In 2 patients the approach was right parasternal and the subsequent 3 patients had direct-access partial sternotomy. The myxoma was resected transseptally in all patients. There was no hospital mortality. One patient had postoperative embolic episode leading to left hemiparesis. Follow-up did not reveal any complication related to this technique and all were in New York Heart Association (NYHA) functional class I. CONCLUSIONS: Minimal access partial sternotomy is an effective approach that adheres to all the identified surgical principles in successful removal of these tumors. The smaller incision does not compromise the efficacy or safety of the operation, reduces hospital stay, and has a good cosmetic result.

Adult↗

Developmental compensation of imposed astigmatism is not initiated by astigmatic accommodation in chickens.

PURPOSE: It is not clear whether emmetropization is confined to spherical refractive errors, or whether astiqmatic errors are also corrected via visual feedback. Experimental results from the animal model of the chicken are equivocal since compensation of imposed astimatic defocus was found in some but not all studies. Astigmatism could only be compensated by changes in the geometry of the cornea or lens. One has tested whether astigmatic spectacle lenses induce astigmatic accommodation as a possible first step of long-lasting compensation. METHODS: Thirty-five chickens were treated with cylinder lenses (+3/0D or -3/0D) for 5 h. Refractions were determined at 1.38 m distance without cycloplegia in hand-held chicks before attaching the lenses, with the lenses on (0 h), and after 3 and 5 h, and after removal of the lenses. Spheres (S), cylinders (C) and axes (A) were determined using infrared photoretinocopy in three axes (the 'PowerRefractor', equipped with a 135 mm lens). RESULTS: (1) The performance of the 'PowerRefractor' was tested in the chickens with trial lenses and gave correct refractions. (2) Astigmatic trial lenses induced refractive errors as expected from their powers in the case of +3/0D lenses: (S) +3.26 +/- 0.93D, (C) -3.45 +/- 0.87D). In the case of -3/0D lenses, slightly more hyperopic spheres were induced (refractions (S) +4.5 +/- 0.48D) but the cylinders were still as expected (-3.25 +/- 0.49D). The axes of astigmatism were correctly reproduced, since rotating the lenses changed the axes of the induced cylinders as expected. (3) Neither after 3 nor after 5 h of lens wear were there significant changes in the axes or the magnitude of astigmatism. Directly after removal of the lens, the refractions did not differ from their start-up values (with +3/0D lenses: (S) +3.31 +/- 1.05D vs. +3.22 +/- 0.76D, (C) -1.19 +/- 1.77D vs. -0.65 +/- 0.94D, (A) 96 +/- 49 vs. 113 +/- 45 deg; with -3/0D lenses: (S) 2.63 +/- 1.12D vs. 2.97 +/- 0.94D, (C) -1.11 +/- 1.15D vs. -0.53 +/- 0.56D, (A) 78 +/- 24 vs. 131 +/- 35 deg). CONCLUSIONS: The most intuitive mechanism for compensation of astigmatic refractive errors, astigmatic accommodation, could not be demonstrated in chickens. In light of this finding, it seems unlikely that a visually controlled mechanism is operating during development to reduced astigmatism by changing corneal or lenticular growth.

Accommodation, Ocular↗

Large-diameter lamellar keratoplasty in severe ocular alkali burns: A technique of stem cell transplantation.

PURPOSE: To evaluate the efficacy of large-diameter lamellar keratoplasty in cases of severe ocular alkali burns. DESIGN: Prospective, noncomparative, interventional case series. PARTICIPANTS: Nine eyes of nine patients with severe ocular alkali burns (grade III/IV) exhibiting corneal vascularization, conjunctivalization, and chronic inflammation were recruited from the Cornea Clinic of Dr. Rajendra Prasad Centre for Ophthalmic Sciences, New Delhi, a tertiary eye care center. INTERVENTION: Large-diameter lamellar keratoplasty was performed using McCarey-Kaufman media-preserved donor corneas. The patients were followed up for a minimum of 6 months. MAIN OUTCOME MEASURES: Symptomatic relief, time to epithelialization, best-corrected visual acuity, Schirmer I, tear film break-up time, and central corneal clarity were the parameters evaluated. RESULTS: The mean duration between the injury and surgery was 29.5 +/- 19.4 months. No intraoperative complications were seen. Successful epithelialization of the ocular surface was achieved in all but one eye, and the mean time to epithelialization was 5.2 +/- 4.9 days. One eye had a persistent epithelial defect which was managed with a bandage soft contact lens. All patients achieved symptomatic relief. The preoperative best-corrected visual acuity was </=1/60 in all the patients. There was a significant improvement in vision in six eyes postoperatively (P = 0.013). The corneal clarity was grade 2+ or better in five eyes and 1+ in four eyes. No recurrence of corneal vascularization or signs of rejection were seen in any eye during the mean follow-up of 7.4 +/- 3.2 months. Causes of no improvement of vision included the presence of subepithelial nebulomacular haze in one eye caused by persistent epithelial defect and residual stromal haze. CONCLUSIONS: Large-diameter lamellar keratoplasty is a useful therapeutic modality in cases of severe alkali burns. It is a single-stage procedure that provides a stable ocular surface because of stem cell supplementation and may visually rehabilitate the patient.

Adolescent↗