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2.
Ann Plast Surg ; 92(4): 412-417, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38527348

ABSTRACT

BACKGROUND: Free flap selection in extremity reconstruction can be challenging. The ideal flap has to be thin and pliable to achieve optimal contour and function. We explore the role of the fascia-only anterolateral thigh (fALT) flap in extremity reconstruction. METHODS: We conducted a retrospective review of our experience using fALT-free flap for extremity reconstruction over a 2-year period. Patient demographics, mechanism of injury, flap characteristics, complications- and follow-up were recorded. Descriptive statistics were calculated. RESULTS: Twelve patients were included. The median (interquartile range [IQR]) age was 34 (28-52) years. One fALT flap was used for upper extremity reconstruction, while 11 flaps were used for lower extremity reconstruction (4 for lower third of the leg, 4 for dorsum of foot, and 3 for heel). The median (IQR) flap surface area was 90 (63-120) cm2 and time from injury to reconstruction was 10 (6-16) days. The postoperative course was uneventful for all flaps except for 1 flap failure and 1 delayed healing. The median (IQR) follow-up was 2 (1-4) months. In all cases, durable soft tissue reconstruction was achieved with no need for revisions. CONCLUSIONS: The fALT-free flap can be successfully used in extremity reconstruction. The ALT fascia has robust perfusion that allows for the harvest of a large flap that can be surfaced with a split thickness skin graft. Its thin pliable tissue provides excellent contour for the hand, distal leg, and foot that does not require future thinning, optimizing the cosmetic and functional result.


Subject(s)
Free Tissue Flaps , Plastic Surgery Procedures , Soft Tissue Injuries , Humans , Adult , Middle Aged , Thigh/surgery , Lower Extremity/surgery , Fascia/transplantation , Soft Tissue Injuries/surgery , Treatment Outcome
5.
Article in English | MEDLINE | ID: mdl-38084992

ABSTRACT

BACKGROUND AND IMPORTANCE: Severe cases of cervical vertebral osteomyelitis can pose a challenge regarding reconstruction, stability/alignment, and infection eradication. Here we describe the application of vascularized free fibula (FF) flaps to reconstruct the cervical spine without instrumentation in the setting of severe osteomyelitis. CLINICAL PRESENTATION: Two patients presented with symptomatic multilevel cervical osteomyelitis. Both patients were treated with corpectomy and FF flap without instrumentation using a novel wedging and distraction technique to secure the flap into position. Clinical outcomes were based on neurological recovery and infection management. Computed tomography (CT) and CT angiography with 3-dimensional reconstruction were used to measure fusion status and patency of the anastomoses. CT of the cervical spine completed 8 weeks postoperatively demonstrated robust fusion of the fibula flaps to adjacent cervical vertebrae. In both patients, CT angiography demonstrated patency of the arterial anastomoses. Both flaps maintained persistent deformity correction. Both patients made full neurological recovery. DISCUSSION: This reconstructive approach represents a salvage technique that offers advantages in cases of prior hardware failure or unfavorable host factors with rapid fusion and definitive treatment with a single surgery. CONCLUSION: The use of FF flap without instrumentation seems to be a safe and effective option for cervical spine reconstruction in the setting of severe osteomyelitis.

6.
Plast Reconstr Surg ; 145(2): 412e-420e, 2020 Feb.
Article in English | MEDLINE | ID: mdl-31985659

ABSTRACT

BACKGROUND: The muscle-sparing descending branch latissimus dorsi muscle (MSLD) flap is a versatile flap with numerous benefits. It is an often overlooked but useful option when considering free flap donors. In this article, the authors present the largest experience with the MSLD flap, with focus on its use in lower extremity reconstruction. METHODS: Patients undergoing lower extremity reconstruction with the MSLD flap at a single institution from 2012 to 2017 were identified. Patient and wound characteristics, surgical details, complications, and outcomes were examined. Outcomes were compared to a cohort who underwent lower extremity reconstruction with other free muscle flaps during the same period. RESULTS: Thirty-six consecutive patients who underwent MSLD flap surgery were identified. Mean follow-up was 18.8 months. Mean body mass index was 29.2 kg/m and 56 percent were smokers. The most common wound causes were motor vehicle collision (46 percent) and fall (22 percent). The most common anatomical location was the distal third of the tibia (33 percent). Mean operative time was 380 minutes. Complications included three total losses (8 percent) and one partial loss (3 percent). No donor-site seromas were reported. Four patients required subsequent amputation for orthopedic issues (nonunion/pain). Patients receiving MSLD and other flaps had similar rates of amputation, donor- and recipient-site complications, and ambulation status (p > 0.05). CONCLUSIONS: The MSLD flap is a useful and reliable option for free flap reconstruction of the lower extremity. Advantages include an easily contourable flap, low revision rate, low complication rate, and the ability to harvest in supine position. In addition, the MSLD flap preserves donor function useful for rehabilitation and minimizes seroma risk. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.


Subject(s)
Lower Extremity , Muscle, Skeletal/transplantation , Plastic Surgery Procedures/methods , Surgical Flaps/blood supply , Wounds and Injuries/surgery , Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Lower Extremity/injuries , Lower Extremity/surgery , Male , Middle Aged , Muscle, Skeletal/blood supply , Skin Transplantation/methods , Young Adult
7.
Plast Reconstr Surg ; 143(3S A Review of Breast Implant-Associated Anaplastic Large Cell Lymphoma): 51S-58S, 2019 03.
Article in English | MEDLINE | ID: mdl-30817556

ABSTRACT

BACKGROUND: Standard of care treatment of breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) involves surgical resection with implant removal and complete capsulectomy. We report a case series of BIA-ALCL reconstruction with proposals for timing and technique selection. METHODS: We retrospectively reviewed and prospectively enrolled all BIA-ALCL patients at 2 tertiary care centers and 1 private plastic surgery practice from 1998 to 2017. Demographics, treatment, reconstruction, pathology staging, patient satisfaction, and oncologic outcomes were reviewed. RESULTS: We treated 66 consecutive BIA-ALCL patients and 18 (27%) received reconstruction. Seven patients (39%) received immediate reconstruction, and 11 (61%) received delayed reconstruction. Disease stage at presentation was IA (T1N0M0 disease confined to effusion or a layer on luminal side of capsule with no lymph node involvement and no distant spread) in 56%, IB in 17%, IC (T3N0M0 cell aggregates or sheets infiltrating the capsule, no lymph node involvement and no distant spread) in 6%, IIA (T4N0M0 lymphoma infiltrating beyond the capsule, no lymph node involvement and no distant spread) in 11%, and III in 11%. Types of reconstruction included smooth implants (72%), immediate mastopexy (11%), autologous flaps (11%), and fat grafting (6%). Outcomes included no surgical complications, but 1 patient progressed to widespread bone metastasis (6%); ultimately, all patients achieved complete remission. Ninety-four percent were satisfied/highly satisfied with reconstructions, whereas 6% were highly unsatisfied with immediate smooth implants. CONCLUSIONS: Breast reconstruction following BIA-ALCL management can be performed with acceptable complications if complete surgical ablation is possible. Immediate reconstruction is reserved for disease confined to capsule on preoperative positive emission tomography/computed tomography scan. Genetic predisposition and bilateral cases suggest that BIA-ALCL patients should not receive textured implants. Autologous options are preferable for implant adverse BIA-ALCL patients. Patients with extensive disease at presentation should be considered for 6- to 12-month delayed reconstruction with interval positive emission tomography/computed tomography evaluation.


Subject(s)
Breast Implants/adverse effects , Breast Neoplasms/etiology , Lymphoma, Large-Cell, Anaplastic/etiology , Lymphoma, Large-Cell, Anaplastic/surgery , Mammaplasty/methods , Adult , Aged , Breast Implantation/adverse effects , Breast Implantation/methods , Breast Neoplasms/pathology , Breast Neoplasms/surgery , Cohort Studies , Device Removal/methods , Female , Humans , Lymphoma, Large-Cell, Anaplastic/pathology , Mastectomy/methods , Middle Aged , Prognosis , Retrospective Studies , Risk Assessment , Tertiary Care Centers , Treatment Outcome
8.
Ann Plast Surg ; 80(1): 54-58, 2018 Jan.
Article in English | MEDLINE | ID: mdl-28930782

ABSTRACT

INTRODUCTION: Despite the advances in cutaneous melanoma management, the false-negative rates (FNRs) of sentinel lymph node biopsy (SLNB) are still high. These rates are dependent not only on the technique but also on definitional terms and percentage of head/neck melanoma (highest false-negative SLNB). Fluorescence imaging technology is well acquainted in plastic surgery and other specialties. Having demonstrated that fluorescence-assisted SLNB is effective in melanoma, we are interested in determining its FNR. METHODS: We obtained institutional review board approval to follow up prospectively all patients with cutaneous melanoma who underwent radioisotope/fluorescence-assisted SLNB with the intent to capture 100 negative SLNB patients. Inclusion criteria were as follows: (1) National Comprehensive Cancer Network criteria; (2) an SLNB report; (3) at least 24 months of follow-up in the negative SLNB group. The outcome variables were FNR and adjusted FNR of SLNB, considering the criterion standard of assessing the accuracy of SNLB. The FNR was defined as the proportion of patients with false-negative SLNB to patients with true-positive and false-negative SLNB [false negative/(false negative + true positive)]. Adjusted FNR refers to the previously described false-negative SLNB, but in the absence of local/in-transit recurrence or distant metastases. Furthermore, false-negative incidence (false-negative/negative SLNB patients) was also calculated. Length of follow-up was date of surgery to the date of last follow-up/death. RESULTS: A total of 125 participants, with 52.0% being male and 48.0% being female, were included. One hundred patients had an SLNB negative for metastases, whereas the rest had positive SLNB results. Median follow-up time of the cohort and that of the negative SLNB group were 36.7 (2.6-58.5) and 37.9 (24.0-58.5) months, respectively. A relatively high number (24.8%) of head/neck melanoma were included. We identified 2 cases of false-negative SLNB, with one having in-transit metastases. Thus, the FNR and adjusted FNR were 7.4% and 3.7%, respectively. The false-negative incidence and adjusted false-negative incidence were 2.0% and 1.0%, respectively. CONCLUSIONS: This is the first prospective study examining the FNR of fluorescence-assisted SLNB for patients with cutaneous melanoma. Our study reveals that this technique has one of the lowest FNRs published, especially considering the large percentage of participants with head/neck melanoma involved.


Subject(s)
Melanoma/pathology , Optical Imaging , Sentinel Lymph Node Biopsy/methods , Skin Neoplasms/pathology , Adult , Aged , False Negative Reactions , Female , Follow-Up Studies , Humans , Male , Melanoma/diagnostic imaging , Melanoma/surgery , Middle Aged , Prospective Studies , Skin Neoplasms/diagnostic imaging , Skin Neoplasms/surgery
9.
Hand (N Y) ; 12(3): 223-228, 2017 05.
Article in English | MEDLINE | ID: mdl-28453357

ABSTRACT

BACKGROUND: Mallet finger is a common injury of the extensor tendon insertion causing an extension lag of the distal interphalangeal joint. METHODS: We reviewed the most current literature on the epidemiology, diagnosis, and management of mallet finger injuries focusing on the indications and outcomes of surgical intervention. RESULTS: Nonoperative management has been advocated for almost all mallet finger injuries; however, complex injuries are usually treated surgically. There is still controversy regarding the absolute indications for surgical intervention. CONCLUSIONS: Although surgery is generally indicated in the case of mallet fractures involving more than one-third of the articular surface as well as in all patients who develop volar subluxation of the distal phalanx, a significant advantage of surgical management even in those complicated cases has yet to be clearly proven.


Subject(s)
Finger Injuries/diagnosis , Tendon Injuries/diagnosis , Finger Injuries/epidemiology , Finger Injuries/surgery , Finger Joint/diagnostic imaging , Finger Joint/surgery , Humans , Radiography , Soccer/injuries , Tendon Injuries/epidemiology , Tendon Injuries/surgery
10.
Aesthet Surg J ; 37(5): 550-556, 2017 05 01.
Article in English | MEDLINE | ID: mdl-28333178

ABSTRACT

Background: Recent studies reviewing large patient databases suggested that age may be an independent risk factor for abdominoplasty. However, these investigations by design considered only short-term major complications. Objectives: The purpose of this investigation was: (1) to compare the safety of abdominoplasty in an elderly and younger patient population; (2) to determine the complication rates across all spectrums: major, minor, local, and systemic; and (3) to evaluate complications occurring both short and long term. Methods: Abdominoplasty procedures performed from 2010 to 2015 were retrospectively reviewed. Subjects were divided into two groups: ≤59 years old and ≥60 years old. Major, minor, local, and systemic complications were analyzed. Patient demographics, comorbidities, perioperative details, adjunctive procedures were also assessed. Results: A total of 129 patients were included in the study: 43 in the older and 86 in the younger age group. The median age of The elderly and young groups was 65.0 and 41.5 years, respectively (P < .001). No statistically significant differences in major, minor, local, or systemic complications were found when both age groups were compared. Major local, major systemic, minor local, and minor systemic in the elderly were 6.9%, 2.3%, 18.6%, and 2.3%, while in the younger patients were 9.3%, 4.7%, 10.5%, and 0.0%, respectively (P > .05). Median follow-up time of the elderly (4.0 months) was no different than the younger (5.0 months) patients (P > .07). Median procedure time in the elderly (4.5 hours) was no different than the younger group (5.0 hours) (P = .4). The elderly exhibited a greater American Society of Anesthesiologist score, median body mass index (28.7 vs 25.1 kg/m2), and number of comorbidities (2.7 vs 0.9) (P < .001). Conclusions: There was no significant difference in either major or minor complications between the two groups. This suggests that with proper patient selection, abdominoplasty can be safely performed in the older age patient population. Level of Evidence: 2.


Subject(s)
Abdominoplasty/adverse effects , Postoperative Complications/epidemiology , Adult , Age Factors , Aged , Female , Humans , Male , Middle Aged , Retrospective Studies , Risk Factors , Treatment Outcome
12.
J Craniofac Surg ; 28(2): 472-476, 2017 Mar.
Article in English | MEDLINE | ID: mdl-28114212

ABSTRACT

INTRODUCTION: Large scalp soft tissue defects can present difficulties with reconstruction. The ideal flap for scalp reconstruction has yet to be described although the latissimus dorsi flap is frequently referred to as the first choice in this setting. PATIENTS AND METHODS: Following institutional review board approval, the authors reviewed their experience in scalp reconstruction for the past 4 years. Patient demographics, reconstruction indication, flap choice, complications, and outcomes were recorded. RESULTS: Thirteen patients underwent scalp reconstruction with an anterolateral thigh (ALT) free flap. In most patients, the indication was resection of a cutaneous malignancy. In all but 1 patient the facial or more proximal vessels were used for anastomosis. None of the patients required vein grafts to increase pedicle length. The median flap surface area was 156 cm. One flap had vascular compromise. All donor sites healed without complications. DISCUSSION: The ALT flap can emerge as the flap of choice for scalp reconstruction, even when proximal neck vessels are used as the recipient targets. Using a suprafascial dissection and extending the vascular pedicle to the profunda femoris artery can optimize its role in this setting. The ALT flap provides excellent cosmesis and durable scalp coverage with minimal donor site morbidity.


Subject(s)
Free Tissue Flaps , Scalp/surgery , Femoral Artery , Free Tissue Flaps/blood supply , Head and Neck Neoplasms/surgery , Humans , Neck/blood supply , Plastic Surgery Procedures/methods , Skin Neoplasms/surgery , Thigh/surgery
13.
Ann Plast Surg ; 78(3): 342-346, 2017 Mar.
Article in English | MEDLINE | ID: mdl-26954747

ABSTRACT

BACKGROUND: The medial gastrocnemius muscle flap is commonly used for the reconstruction of defects around the knee and proximal leg. The flap can be raised using either a medial or a posterior midline incision, although no studies have been done comparing the 2 different surgical approaches. METHODS: We compared the reach of the medial gastrocnemius muscle flap using either of the 2 incisions in a series of 25 fresh cadavers. All muscle flaps were elevated without division of the muscle origin. Muscle reach was calculated using the distance from a fixed bony point with the leg fully extended and the muscle under no tension. Muscle width measurements were used to calculate surface area of coverage. RESULTS: Muscle flaps elevated through the posterior midline incision group reached 2.02 cm farther than flaps through the medial incision (P < 0.05). This resulted in 20.3 cm increase in surface area for the posterior midline incision group over the medial incision group (P < 0.05). The posterior midline incision allowed for better visualization of the vascular pedicle and dissection of fascial attachments around the pes anserinus. CONCLUSIONS: The posterior midline incision for the elevation of the medial gastrocnemius pedicled muscle flap allows for a safe, thorough mobilization of the muscle resulting in increased muscle reach and increased surface area when compared with the medial incision. Furthermore, the posterior midline incision provides better access to the gastrocnemius muscle origin and the lateral muscle head.


Subject(s)
Leg/surgery , Muscle, Skeletal/surgery , Plastic Surgery Procedures/methods , Surgical Flaps/surgery , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged
14.
Med Mycol ; 48(2): 310-7, 2010 Mar.
Article in English | MEDLINE | ID: mdl-19642052

ABSTRACT

Members of the genus Aspergillus are opportunistic fungal pathogens characterized by their genomic diversity. However, whether variations among Aspergillus strains and species at the genome level translate into significant differences in virulence is unclear. Therefore, we studied the interstrain and interspecies variations in virulence for a collection of Aspergillus fumigatus and Aspergillus terreus isolates using a previously described model of invasive aspergillosis in Toll-deficient fruit flies. We then looked for associations between survival in the fly model and strain relatedness as defined by repetitive-sequence polymerase chain reaction (rep-PCR). We observed no significant differences in the survival of flies infected with A. fumigatus vs. A. terreus or flies infected with colonizing vs. invasive isolates of either species. However, in both Aspergillus species we observed significant interstrain variability in fly survival (P<0.001 by the log-rank test). Using rep-PCR, we identified two dominant A. fumigatus clades that were associated with significantly different survival rates in Toll-deficient flies (P=0.007). We conclude that the fly model of invasive aspergillosis enables high-throughput screening of Aspergillus species for variations in virulence and may uncover distinct A. fumigatus clades that differ in their pathogenicity.


Subject(s)
Aspergillosis/microbiology , Aspergillus fumigatus/pathogenicity , Aspergillus/pathogenicity , Drosophila Proteins/deficiency , Drosophila melanogaster/microbiology , Toll-Like Receptors/deficiency , Animals , Animals, Genetically Modified/genetics , Animals, Genetically Modified/microbiology , Aspergillus/genetics , Aspergillus/growth & development , Aspergillus fumigatus/genetics , Aspergillus fumigatus/growth & development , Cluster Analysis , DNA Fingerprinting , Drosophila Proteins/genetics , Drosophila melanogaster/genetics , Female , Kaplan-Meier Estimate , Toll-Like Receptors/genetics
15.
J Infect Dis ; 199(9): 1399-406, 2009 May 01.
Article in English | MEDLINE | ID: mdl-19358672

ABSTRACT

BACKGROUND: Breakthrough zygomycosis is increasingly observed among patients at high risk for fungal infection who are receiving voriconazole, reflecting either selective pressure or voriconazole-associated alterations in Zygomycetes virulence. We tested the latter hypothesis, using 2 phylogenetically disparate zygomycosis models. METHODS: Three Zygomycetes strains were exposed to voriconazole by serial passages on voriconazole-containing medium. The virulence of voriconazole-exposed Zygomycetes strains was compared with that of voriconazole-nonexposed strains in Drosophila and murine models of zygomycosis by assessment of survival curves, pulmonary fungal burdens, and expression of inflammation-associated genes. RESULTS: Among Toll-deficient (Tl(-/-)) and wild-type fruit flies, infection with Zygomycetes isolates that had been exposed to voriconazole yielded significantly lower survival rates than infection with Zygomycetes strains grown in drug-free media. In contrast, exposure of Rhizopus oryzae to itraconazole, amphotericin B, or caspofungin and exposure of Aspergillus fumigatus to voriconazole did not alter the virulence of these isolates in fruit flies. In the murine model, infection with a R. oryzae strain preexposed to voriconazole was associated with decreased survival rates and increased pulmonary fungal burdens, compared with infection with a voriconazole-nonexposed R. oryzae strain. In addition, enhanced angioinvasion, inflammation, and expression of genes involved in stress response and tissue repair were found in mouse lungs infected with voriconazole-exposed R. oryzae. CONCLUSIONS: Exposure of Zygomycetes organisms to voriconazole selectively enhanced their virulence. The mechanisms underlying these phenotypic changes should be studied further.


Subject(s)
Antifungal Agents/pharmacology , Drosophila/drug effects , Fungi/drug effects , Pyrimidines/pharmacology , Triazoles/pharmacology , Zygomycosis/physiopathology , Amphotericin B/therapeutic use , Animals , Antifungal Agents/therapeutic use , Aspergillus fumigatus/drug effects , Aspergillus fumigatus/isolation & purification , Disease Models, Animal , Fungi/isolation & purification , Humans , Itraconazole/therapeutic use , Mice , Mucor/pathogenicity , Rhizopus/pathogenicity , Virulence/drug effects , Voriconazole , Zygomycosis/drug therapy , Zygomycosis/pathology
16.
J Infect Dis ; 198(2): 186-92, 2008 Jul 15.
Article in English | MEDLINE | ID: mdl-18500936

ABSTRACT

BACKGROUND: We investigated whether caspofungin and other echinocandins have immune-enhancing properties that influence human polymorphonuclear neutrophil (PMN)-mediated mold hyphal damage. MATERIALS AND METHODS: Using aniline blue staining, we compared patterns of beta-glucan exposure in Aspergillus fumigatus, Aspergillus terreus, Rhizopus oryzae, Fusarium solani, Fusarium oxysporum, Scedosporium prolificans, and Scedosporium apiospermum hyphae after caspofungin exposure. We also determined PMN-mediated hyphal damage occurring with or without preexposure to caspofungin or with preexposure to the combination of caspofungin and anti-beta-glucan monoclonal antibody, using 2,3-bis (2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino) carbonyl]-sH-tetrazolium hydroxide (XTT) assay. RESULTS: Preincubation with caspofungin (32 microg/mL for R. oryzae; 0.0625 microg/mL for other isolates) increased exposure to beta-glucan. PMN-induced damage increased after caspofungin exposure and was further augmented by the addition of anti-beta-glucan antibody. Preincubation with micafungin or anidulafungin had similar effects on PMN-induced damage of A. fumigatus hyphae. Finally, preexposure of A. fumigatus, but not S. prolificans, to caspofungin induced expression of Dectin-1 by PMN. CONCLUSIONS: The results of the present study suggest inducement of beta-glucan unmasking by echinocandins and enhancement of PMN activity against mold hyphae, thereby supporting the immunopharmacologic mode of action of echinocandins.


Subject(s)
Aspergillus fumigatus/drug effects , Aspergillus/drug effects , Echinocandins/pharmacology , Hyphae/physiology , Neutrophils/drug effects , Neutrophils/microbiology , beta-Glucans/metabolism , Aspergillus/growth & development , Aspergillus fumigatus/growth & development , Caspofungin , Cell Wall/drug effects , Cell Wall/metabolism , Fusarium/drug effects , Humans , Hyphae/drug effects , Lectins, C-Type , Lipopeptides , Membrane Proteins/genetics , Mycetoma/drug therapy , Nerve Tissue Proteins/genetics , Reverse Transcriptase Polymerase Chain Reaction , Rhizopus/drug effects , Scedosporium/drug effects , Toll-Like Receptor 2/drug effects , Toll-Like Receptor 4/genetics
17.
Antimicrob Agents Chemother ; 52(4): 1325-9, 2008 Apr.
Article in English | MEDLINE | ID: mdl-18212113

ABSTRACT

Gliotoxin (GT) is a secondary fungal metabolite with pleiotropic immunosuppressive properties that have been implicated in Aspergillus virulence. However, the mechanisms of GT cytotoxicity and its molecular targets in eukaryotic cells have not been fully characterized. We screened a haploid library of Saccharomyces cerevisiae single-gene deletion mutants (4,787 strains in EUROSCARF) to identify nonessential genes associated with GT increased resistance (GT-IR) and increased sensitivity (GT-IS). The susceptibility of the wild-type parental strain BY4741 to GT was initially assessed by broth microdilution methods using different media. GT-IR and GT-IS were defined as a fourfold increase and decrease, respectively, in MIC, and this was additionally confirmed by susceptibility testing on agar yeast extract-peptone-glucose plates. The specificity of GT-IR and GT-IS mutants exhibiting normal growth compared with the wild-type strain was further tested in studies of their susceptibility to conventional antifungal agents, cycloheximide, and H2O2. GT-IR was associated with the disruption of genes acting in general metabolism (OPI1, SNF1, IFA38), mitochondrial function (RTG2), DNA damage repair (RAD18), and vesicular transport (APL2) and genes of unknown function (YGL235W, YOR345C, YLR456W, YGL072C). The disruption of three genes encoding transsulfuration (CYS3), mitochondrial function (MEF2), and an unknown function (YKL037W) led to GT-IS. Specificity for GT-IR and GT-IS was observed in all mutants. Importantly, the majority (69%) of genes implicated in GT-IR (6/10) and GT-IS (2/3) have human homologs. We identified novel Saccharomyces genes specifically implicated in GT-IR or GT-IS. Because most of these genes are evolutionarily conserved, further characterization of their function could improve our understanding of GT cytotoxicity mechanisms in humans.


Subject(s)
Antifungal Agents/pharmacology , Drug Resistance, Fungal/genetics , Gliotoxin/pharmacology , Saccharomyces cerevisiae Proteins/genetics , Saccharomyces cerevisiae/drug effects , Gene Deletion , Gene Library , Genome, Fungal , Microbial Sensitivity Tests/standards , Saccharomyces cerevisiae/genetics
18.
J Infect Dis ; 196(12): 1860-4, 2007 Dec 15.
Article in English | MEDLINE | ID: mdl-18190268

ABSTRACT

We developed a model of infection, using 1 Fusarium species (F. moniliforme) and 2 Scedosporium species (S. apiospermum and S. prolificans), in wild-type and Toll-deficient Drosophila melanogaster flies by injecting them with a standardized conidia inoculum. Wild-type flies were resistant to infection with both S. apiospermum and S. prolificans but were susceptible to infection with F. moniliforme. When Toll-deficient flies were infected with any of the 3 pathogens, the result was acute infection and high mortality rates. Voriconazole mixed in fly food significantly protected flies infected with F. moniliforme or S. apiospermum but not those infected with S. prolificans.


Subject(s)
Drosophila melanogaster/microbiology , Fusarium/pathogenicity , Mycetoma/microbiology , Mycoses/microbiology , Scedosporium/pathogenicity , Animals , Drosophila Proteins/deficiency , Drosophila Proteins/metabolism , Drosophila melanogaster/metabolism , Female , Fusarium/isolation & purification , Fusarium/physiology , Humans , Pyrimidines/pharmacology , Scedosporium/isolation & purification , Scedosporium/physiology , Spores, Fungal/pathogenicity , Spores, Fungal/physiology , Toll-Like Receptors/deficiency , Toll-Like Receptors/metabolism , Triazoles/pharmacology , Virulence , Voriconazole
19.
Clin Infect Dis ; 43(12): 1580-4, 2006 Dec 15.
Article in English | MEDLINE | ID: mdl-17109292

ABSTRACT

We reviewed the records of patients with cancer who had Scedosporium infection (due to Scedosporium apiospermum and Scedosporium prolificans in 21 and 4 patients, respectively). The incidence of Scedosporium infection increased from 0.82 cases per 100,000 patient-inpatient days (in 1993-1998) to 1.33 cases per 100,000 patient-inpatient days (in 1999-2005). Cases of S. prolificans infection occurred only after 2000. Dissemination occurred in 16 patients (64%). The 12-week mortality rates were 70% and 100% for S. apiospermum and S. prolificans infection, respectively.


Subject(s)
Immunocompromised Host , Mycetoma/epidemiology , Neoplasms/complications , Adult , Aged , Cancer Care Facilities , Female , Humans , Incidence , Male , Middle Aged , Mycetoma/etiology , Mycetoma/mortality , Scedosporium
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