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1.
Eur J Haematol ; 112(3): 350-359, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37823328

ABSTRACT

Organ dysfunction, including pulmonary function impairment, plays a key role in the choice of conditioning chemotherapy before autologous hematopoietic stem cell transplantation (auto-HSCT). Replacement of BCNU/carmustine as part of BEAM (BCNU/carmustine, etoposide, cytarabine, and melphalan) conditioning protocol by thiotepa (TEAM) reduces pulmonary toxicity while maintaining efficacy. We retrospectively analyzed the association of clinical characteristics, comorbidities, and organ function with outcomes after conditioning with BEAM or TEAM. Three hundred ninety-six patients undergoing auto-HSCT (n = 333 with BEAM; n = 63 with TEAM) at our institution between 2008 and 2021 were included in this study. In the multivariate analysis, CO-diffusion capacity corrected for hemoglobin (DLCOcSB) ≤ 60% of predicted, progressive disease (PD) before auto-HSCT, Karnofsky performance score (KPS) ≤ 80%, HCT-CI score ≥ 4, and cardiac disease before auto-HSCT were associated with decreased overall survival (OS) in patients treated with BEAM. In contrast, only PD before auto-HSCT was identified in patients treated with TEAM. Patients conditioned with BEAM and DLCOcSB ≤ 60% had higher non-relapse mortality, including pulmonary cause of death. In summary, we have identified clinical and pulmonary risk factors associated with worse outcomes in patients conditioned with BEAM compared to TEAM. Our data suggest TEAM conditioning as a valid alternative for patients with comorbidities, including pulmonary dysfunction and/or poorer performance scores, before auto-HSCT.


Subject(s)
Carmustine , Hematopoietic Stem Cell Transplantation , Humans , Carmustine/adverse effects , Thiotepa , Retrospective Studies , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Hematopoietic Stem Cell Transplantation/adverse effects , Hematopoietic Stem Cell Transplantation/methods , Transplantation, Autologous , Cytarabine/adverse effects , Etoposide/therapeutic use , Transplantation Conditioning/adverse effects , Transplantation Conditioning/methods , Melphalan/adverse effects
2.
Wounds ; 30(3): E32-E35, 2018 Mar.
Article in English | MEDLINE | ID: mdl-29584607

ABSTRACT

Calcinosis cutis (CC), or calcium deposition in soft tissue, can cause significant morbidity associated with arthralgias and ulceration. This condition has an elusive pathophysiology and is often associated with autoimmune disorders, significantly impacting the disease burden. The clinical presentation of CC varies, and there is no gold standard treatment modality. The case of a 50-year-old woman with scleroderma and a rare presentation of milky drainage of a left hip ulcer secondary to underlying CC that was treated successfully with surgery and negative pressure wound therapy is reported herein. Also included is a review of the literature of the medical and surgical modalities used in the management of this debilitating condition.


Subject(s)
Calcinosis/surgery , Negative-Pressure Wound Therapy , Skin Ulcer/surgery , Calcinosis/complications , Female , Humans , Middle Aged , Scleroderma, Systemic/complications , Skin Ulcer/etiology
3.
Mol Cell Biochem ; 355(1-2): 65-73, 2011 Sep.
Article in English | MEDLINE | ID: mdl-21541678

ABSTRACT

To evaluate the protective effects of two naturally occurring antioxidants, α-Lipoic acid and coenzyme Q10 on the response to in vitro ischemia of the rabbit urinary bladder. We measured free fatty acid (FFA) content, phospholipid (PL) content, malondialdehyde (MDA) levels, and phospholipase A(2) activity (PLA) of subcellular compartments. Twenty New Zealand White male rabbits were separated into four groups of five rabbits each. The in vitro whole bladders from Groups 1 and 2 received a 3 h incubation under normal oxygenated physiological conditions. The bladders were stimulated by field stimulation at 1 and 3 h. The bladders from groups 3 and 4 underwent 1 h incubation time under normal oxygenated physiological conditions. After 1 h, the bladders were stimulated with field stimulation. After a maximal pressure response was recorded, the stimulation was turned off and the bath medium changed to one equilibrated with 95% nitrogen, 5% oxygen without glucose (ischemic medium) and incubated for 1 h with field stimulations occurring at 5 min intervals during this time. At the end of this hour of ischemia with repetitive stimulation, the bath was changed to an oxygenated medium with glucose for a 1-h reperfusion period after which the stimulation was repeated. The rabbits from groups 2 and 4 received α-Lipoic acid (10 mg/kg/day) + Coenzyme Q10 (3 mg/kg/day) by gavage for 4 weeks before the experiment. At the end of the experimental period, each bladder was opened longitudinally, and the muscle and mucosa separated by blunt dissection, frozen under liquid nitrogen, and stored at -80°C for biochemical analyses. Each tissue was fractionated by differential centrifugation into nuclear, mitochondrial, synaptosomal, and cytosol (supernatant) components. PL, FFA, MDA, and PLA were analyzed using standard biochemical techniques. Post-ischemic contractility only returned to 30% of control of the untreated group. However, post-ischemic contractility of the treated group returned to approximately 70% of control. PL loss in the muscle mitochondria and synaptosomes was prevented by antioxidant treatment, while the mucosal layer showed a significant drop in PL with antioxidants treatment. Administration of CoQ + LA significantly decreased MDA levels in both control and ischemic tissues in both the muscle and mucosal bladder layers, especially substantial in the microsomal and mitochondrial components. Treatment had variable effects on PLA(2) activity. Treatment of bladder dysfunction with antioxidants daily can be beneficial in man to prevent or delay the onset of progressive loss of bladder function especially that due to ischemic damage to mitochondrial and microsomal lipids. CoQ10 + LA can provide similar protection of the bladder muscle and mucosa against lipid oxidative stress as they have been shown to protect against protein oxidative damage.


Subject(s)
Antioxidants/pharmacology , Ischemia/prevention & control , Reperfusion Injury/prevention & control , Thioctic Acid/pharmacology , Ubiquinone/analogs & derivatives , Urinary Bladder/drug effects , Animals , Fatty Acids, Nonesterified/metabolism , Ischemia/metabolism , Lipid Peroxidation , Male , Malondialdehyde/metabolism , Mucous Membrane/metabolism , Mucous Membrane/pathology , Muscle, Smooth/metabolism , Muscle, Smooth/pathology , Organ Size , Phospholipases A2/metabolism , Phospholipids/metabolism , Rabbits , Reperfusion Injury/metabolism , Ubiquinone/pharmacology , Urinary Bladder/blood supply , Urinary Bladder/metabolism , Urinary Bladder/pathology
4.
Mol Cell Biochem ; 346(1-2): 179-86, 2011 Jan.
Article in English | MEDLINE | ID: mdl-20882398

ABSTRACT

To evaluate the effects of in vitro ischemia/reperfusion on contractile response to field stimulation (FS), free fatty acid (FFA) content, phospholipid (PL) content, and malondialdehyde (MDA) levels of the rabbit urinary bladder. There is significant evidence that ischemia/reperfusion injury is linked to obstructive bladder dysfunction secondary to men with benign prostatic hyperplasia (BPH). Twelve New Zealand White male rabbits were separated into two groups of six rabbits each. Each rabbit was euthanized, and the bladder was surgically removed intact for whole bladder incubation. The bladders in Group 1 received a 3-h incubation under normal oxygenated physiological conditions. These bladders received electrical field stimulation (32 Hz) after 1 and 3 h. The bladders associated with Group 2 received a 1-h incubation under normal oxygenated physiological conditions. At the end of this 1-h period, the bladders were subjected to FS. After a maximal pressure response was recorded, the stimulation was turned off and the bath medium was changed to one equilibrated with 95% nitrogen, 5% oxygen without glucose (ischemic medium) and incubated for 1 h with field stimulations (32 Hz) occurring at 5-min intervals to represent overactive bladder dysfunction. At the end of this hour of ischemia with repetitive stimulation, the bath was changed to an oxygenated medium with glucose for a 1-h period after which the stimulation was repeated. At the end of the experimental period, each bladder was opened longitudinally and the muscle and mucosa separated by blunt dissection, frozen under liquid nitrogen, and stored at -80°C for biochemical analyses. Each tissue was fractionated by differential centrifugation into nuclear, mitochondrial, synaptosomal, and supernatant (cytosol) components. PL, FFA, and MDA content were analyzed for each fraction using standard biochemical techniques. The bladder contractile responses decreased during the period of in vitro ischemia and returned to only 30% of control after reperfusion. In vitro ischemia/reperfusion showed the following: (1) There was a modest but significant decrease in the FFA content of the microsomes of the muscle and significant increases in the FFA content of the nuclei and mitochondria of the mucosa. (2) There were decreases in the PL content of the homogenate and microsomes of the muscle and decreases in the PL content of the homogenate, microsomes, and supernatant of the mucosa. (3) Significant increases were observed in the MDA levels of the homogenate, mitochondria, and microsomes of both the muscle and mucosa. The significant increases in the lipid peroxidation of the bladder smooth muscle are consistent with the marked decrease in the contractile ability of the bladder following ischemia/reperfusion. The specific increased lipid peroxidation of the mitochondrial and microsomal components is consistent with the specific dysfunctions of the mitochondria and innervations observed following I/R in earlier published studies. The marked increases in lipid peroxidation in the mucosa associated with the loss of PL and FFA from this component are consistent with the significant dysfunction in both the antiadherence and antipermeability properties of the mucosa and may play a major role in the symptomatic nature of I/R-linked diseases of the bladder.


Subject(s)
Fatty Acids, Nonesterified/metabolism , Malondialdehyde/metabolism , Phospholipids/metabolism , Reperfusion Injury/physiopathology , Urinary Bladder/metabolism , Animals , Male , Rabbits , Reperfusion Injury/metabolism
5.
Mol Cell Biochem ; 323(1-2): 139-42, 2009 Mar.
Article in English | MEDLINE | ID: mdl-19043779

ABSTRACT

Partial urinary bladder outlet obstruction mediates cyclic ischemia and reperfusion resulting in the generation of both reactive oxygen species and reactive nitrogen species. It is theorized that with an increase in the level of free radicals, the level of protective antioxidants should decrease. To test this hypothesis, two electron transfer assays, the FRAP method and the CUPRAC method, were used to determine the level of antioxidant reactivity of obstructed and control bladder tissue. The results showed that the CUPRAC assay detected a significant decrease in the reactivity of antioxidants found within the obstructed bladder tissue as compared to the control bladder tissue in both the muscle and mucosa. The FRAP assay did not detect any difference between the muscle and mucosa of the obstructed and control bladder tissue.


Subject(s)
Antioxidants/metabolism , Biological Assay/methods , Fluorescence Recovery After Photobleaching , Urinary Bladder Neck Obstruction/metabolism , Urinary Bladder/metabolism , Animals , Male , Muscle, Smooth/chemistry , Muscle, Smooth/metabolism , Rabbits , Reactive Nitrogen Species/metabolism , Reactive Oxygen Species/metabolism , Urinary Bladder/anatomy & histology , Urinary Bladder/chemistry , Urinary Bladder Neck Obstruction/pathology
6.
BJU Int ; 102(7): 885-9, 2008 Sep.
Article in English | MEDLINE | ID: mdl-18485034

ABSTRACT

OBJECTIVE: To evaluate the effects of ovariectomy (Ovx) and oestrogen therapy on the free fatty acid (FFA) content, endogenous lipase activity, and the phospholipid (PL) content of the urinary bladder, as reduced circulating oestrogen during and after the menopause has been linked to various bladder dysfunctions including incontinence and recurrent urinary tract infections. MATERIALS AND METHODS: In all, 12 New Zealand White female rabbits were separated into three groups; the Ovx + oestrogen group received Ovx and treatment with conjugated beta-oestradiol (3 weeks), the Ovx group received Ovx and vehicle (3 weeks), and the control group received sham operation and vehicle. Cystometry was used to evaluate compliance and in vitro muscle strip studies quantified contractility. For the bulk of the bladder, the muscle and mucosa were separated; FFA and PL concentrations were analysed using standard biochemical techniques. RESULTS: The bladder contractile responses and compliance decreased after Ovx and returned to or above normal after oestrogen administration. Both FFA and PL concentrations of the mucosa were about three times greater than that of the smooth muscle. Ovx significantly reduced the FFA and PL concentrations of both muscle and mucosa, while oestrogen therapy restored them to normal. CONCLUSIONS: Reduced FFA and PL content of the smooth muscle membranes would decrease their fluidity and contribute to decreased compliance and contractility. Reduced FFA and PL content of the mucosa would be consistent with mucosal damage and may contribute to the increased incidences of incontinence and bladder infection.


Subject(s)
Estrogens/therapeutic use , Fatty Acids, Nonesterified/metabolism , Muscle, Smooth/physiopathology , Ovariectomy , Urinary Bladder/physiopathology , Animals , Female , Lipase/metabolism , Muscle Contraction/physiology , Phospholipids/metabolism , Rabbits , Urinary Incontinence/etiology , Urinary Tract Infections/etiology
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