ABSTRACT
Emphysematous pyelonephritis (EPN) is a rare condition which can rapidly progress to sepsis and multiple organ failure with high mortality. We experienced a rare case of EPN in a renal allograft related to antibody-mediated rejection (AMR). The patient received a deceased donor kidney transplant due to end-stage renal disease secondary to diabetes mellitus. Cross-match test was negative but she had remote history of anti-HLA-A2 antibody corresponding with the donor HLA. Surgery concluded without any major events. Anti-thymoglobulin was given perioperatively for induction. She was compliant with her immunosuppressive medications making urine of 2 L/d with serum creatinine of 1.9 mg/dL at discharge on post-operative day (POD) 6. She did well until POD 14 when she presented to the clinic with features of sepsis, pain over the transplanted kidney area and decline in urine volume with elevated serum creatinine. CT revealed extensive gas throughout the transplanted kidney. Renal scan revealed non-functional transplant kidney with no arterial flow. Based on these findings, a decision to perform transplant nephrectomy was made. At laparotomy, the kidney was completely necrotic. Pathology showed non-viable kidney parenchyma with the tubules lacking neutrophilic casts suggestive of ischemic necrosis. Donor-specific antibody (DSA) returned positive with high intensity anti-HLA-A2 antibody. This is the first case of early EPN in allograft considered to have occurred as a result of thrombotic ischemia secondary to AMR. This case suggests consideration of perioperative anti-B-cell and/or anti-plasma cell therapies for historical DSA and strict post-operative follow-up in immunologically high-risk recipients to detect early signs of rejection and avoid deleterious outcomes.
Subject(s)
Emphysema/immunology , Graft Rejection/immunology , Isoantibodies/immunology , Kidney Transplantation/adverse effects , Pyelonephritis/immunology , Allografts/blood supply , Allografts/diagnostic imaging , Allografts/immunology , Allografts/pathology , Biopsy , Emphysema/diagnosis , Emphysema/pathology , Emphysema/therapy , Female , Graft Rejection/diagnosis , Graft Rejection/pathology , Graft Rejection/therapy , Graft Survival/immunology , Humans , Ischemia/diagnosis , Ischemia/immunology , Ischemia/pathology , Ischemia/therapy , Kidney/blood supply , Kidney/diagnostic imaging , Kidney/immunology , Kidney/pathology , Kidney Failure, Chronic/surgery , Middle Aged , Pyelonephritis/diagnosis , Pyelonephritis/pathology , Pyelonephritis/therapy , Radioisotope Renography , Renal Dialysis , Thromboembolism/diagnosis , Thromboembolism/immunology , Thromboembolism/pathology , Thromboembolism/therapyABSTRACT
BACKGROUND: 1-year data from this trial showed the noninferiority of a novel once-daily extended-release tacrolimus (LCPT; Envarsus XR) to immediate-release tacrolimus (IR-Tac) twice daily after kidney transplantation. STUDY DESIGN: Final 24-month analysis of a 2-armed, parallel-group, randomized, double-blind, double-dummy, multicenter, phase 3 trial. SETTING & PARTICIPANTS: 543 de novo kidney recipients randomly assigned to LCPT (n=268) or IR-Tac (n=275); 507 (93.4%) completed the 24-month study. INTERVENTION: LCPT tablets once daily at 0.17 mg/kg/d or IR-Tac twice daily at 0.1 mg/kg/d; subsequent doses were adjusted to maintain target trough ranges (first 30 days, 6-11 ng/mL; thereafter, 4-11 ng/mL). The intervention was 24 months; the study was double blinded for the entirety. OUTCOMES & MEASUREMENTS: Treatment failure (death, transplant failure, biopsy-proven acute rejection, or loss to follow up) within 24 months. Safety end points included adverse events, serious adverse events, new-onset diabetes, kidney function, opportunistic infections, and malignancies. Pharmacokinetic measures included total daily dose (TDD) of study drugs and tacrolimus trough levels. RESULTS: 24-month treatment failure was LCPT, 23.1%; IR-Tac, 27.3% (treatment difference, -4.14% [95% CI, -11.38% to +3.17%], well below the +10% noninferiority criterion defined for the primary 12-month end point). Subgroup analyses showed fewer treatment failures for LCPT versus IR-Tac among black, older, and female recipients. Safety was similar between groups. From month 1, TDD was lower for LCPT; the difference increased over time. At month 24, mean TDD for LCPT was 24% lower than for the IR-Tac group (P<0.001), but troughs were similar (means at 24 months: LCPT, 5.47 ± 0.17 ng/mL; IR-Tac, 5.8 ± 0.30 ng/mL; P=0.4). LIMITATIONS: Trial participant eligibility criteria may limit the generalizability of results to the global population of de novo kidney transplant recipients. CONCLUSIONS: Results suggest that once-daily LCPT in de novo kidney transplantation has comparable efficacy and safety profile to that of IR-Tac. Lower TDD reflects LCPT's improved bioavailability and absorption.
Subject(s)
Immunosuppressive Agents/administration & dosage , Kidney Transplantation , Tacrolimus/administration & dosage , Adult , Aged , Double-Blind Method , Drug Administration Schedule , Female , Humans , Male , Middle Aged , Prospective Studies , Time FactorsABSTRACT
African-American and elderly kidney transplant recipients (KTR) have increased risk for poor clinical outcomes post-transplant. Management of immunosuppression may be challenging in these patients and contribute to worse outcomes. A novel once-daily formulation of tacrolimus (LCPT) has demonstrated noninferiority, similar safety, improved bioavailability, a consistent concentration time profile, and less peak and peak-trough fluctuations vs. tacrolimus twice-daily (Tac BID). This pooled analysis of two phase 3 randomized, controlled trials, including 861 (LCPT N = 428; Tac BID N = 433; 38% of patients were stable KTR, and 62% were de novo KTR) patients, examined the efficacy of LCPT in KTR subgroups (blacks, females, and age ≥65). Overall, treatment failure [death, graft failure, centrally read biopsy-proven acute rejection (BPAR), or lost to follow-up] at 12 months was as follows: LCPT: 11.9%, BID Tac: 13.4% [-1.48% (-5.95%, 2.99%)]. BPAR rates were as follows: LCPT: 8.2%, Tac BID: 9.5% [-1.29% (-5.14%, 2.55%)]. Numerically, fewer treatment failure events with LCPT were found in the majority of subgroups, with significantly less treatment failure associated with LCPT among black KTR [-13.82% (-27.22%, -0.31%)] and KTR ≥65 [-13.46% (-25.27%, -0.78%)]. This pooled analysis suggests numerically lower efficacy failure rates associated with LCPT among high-risk subgroups, in particular black KTR and KTR ≥65 years old.
Subject(s)
Immunosuppressive Agents/administration & dosage , Kidney Transplantation , Tacrolimus/administration & dosage , Aged , Biopsy , Data Interpretation, Statistical , Delayed-Action Preparations , Drug Administration Schedule , Female , Graft Rejection/etiology , Graft Survival , Humans , Kidney/surgery , Male , Middle Aged , Prospective Studies , Tablets , Treatment OutcomeABSTRACT
The discovery of a diiron organometallic site in nature within the diiron hydrogenase, [FeFe]-H2ase, active site has prompted revisits of the classic organometallic chemistry involving the Fe-Fe bond and bridging ligands, particularly of the (µ-SCH2XCH2S)[Fe(CO)3]2 and (µ-SCH2XCH2S)[Fe(CO)2L]2 (X = CH2, NH; L = PMe3, CN(-), and NHC's (NHC = N-heterocyclic carbene)), derived from CO/L exchange reactions. Through the synergy of synthetic chemistry and density functional theory computations, the regioselectivity of nucleophilic (PMe3 or CN(-)) and electrophilic (nitrosonium, NO(+)) ligand substitution on the diiron dithiolate framework of the (µ-pdt)[Fe(CO)2NHC][Fe(CO)3] complex (pdt = propanedithiolate) reveals the electron density shifts in the diiron core of such complexes that mimic the [FeFe]-H2ase active site. While CO substitution by PMe3, followed by reaction with NO(+), produces (µ-pdt)(µ-CO)[Fe(NHC)(NO)][Fe(CO)2PMe3](+), the alternate order of reagent addition produces the structural isomer (µ-pdt)[Fe(NHC)(NO)PMe3][Fe(CO)3](+), illustrating how the nucleophile and electrophile choose the electron-poor metal and the electron-rich metal, respectively. Theoretical explorations of simpler analogues, (µ-pdt)[Fe(CO)2CN][Fe(CO)3](-), (µ-pdt)[Fe(CO)3]2, and (µ-pdt)[Fe(CO)2NO][Fe(CO)3](+), provide an explanation for the role that the electron-rich iron moiety plays in inducing the rotation of the electron-poor iron moiety to produce a bridging CO ligand, a key factor in stabilizing the electron-rich iron moiety and for support of the rotated structure as found in the enzyme active site.
ABSTRACT
The Ph3 PAu(+) cation, renowned as an isolobal analogue of H(+) , was found to serve as a proton surrogate and form a stable Au2 Fe2 complex, [(µ-SAuPPh3 )2 {Fe(CO)3 }2 ], analogous to the highly reactive dihydrosulfide [(µ-SH)2 {Fe(CO)3 }2 ]. Solid-state X-ray diffraction analysis found the two SAuPPh3 and SH bridges in anti configurations. VT NMR studies, supported by DFT computations, confirmed substantial barriers of approximately 25â kcal mol(-1) to intramolecular interconversion between the three stereoisomers of [(µ-SH)2 {Fe(CO)3 }2 ]. In contrast, the largely dative SAu bond in µ-SAuPPh3 facilitates inversion at S and accounts for the facile equilibration of the SAuPPh3 units, with an energy barrier half that of the SH analogue. The reactivity of the gold-protected sulfur atoms of [(µ-SAuPPh3 )2 {Fe(CO)3 }2 ] was accessed by release of the gold ligand with a strong acid to generate the [(µ-SH)2 {Fe(CO)3 }2 ] precursor of the [FeFe]H2 ase-active-site biomimetic [(µ2 -SCH2 (NR)CH2 S){Fe(CO)3 }2 ].
Subject(s)
Intestinal Fistula/etiology , Kidney Transplantation/adverse effects , Renal Artery/transplantation , Vascular Fistula/etiology , Embolization, Therapeutic , Female , Gastrointestinal Hemorrhage/etiology , Humans , Intestinal Fistula/diagnostic imaging , Intestinal Fistula/therapy , Middle Aged , Renal Artery/diagnostic imaging , Time Factors , Tomography, X-Ray Computed , Vascular Fistula/diagnostic imaging , Vascular Fistula/therapyABSTRACT
OBJECTIVE: To describe the use of robotic-assisted transplant ureteral repair (RATUR) for treating transplant ureteral stricture (TUS) in 3 patients who had undergone robot assisted kidney transplant (RAKT). METHOD: We reviewed the medical records of 3 patients who experienced TUS after RAKT and who underwent RATUR between 2017 and 2020. The patients' RAKT, post-transplant clinical course, endourological interventions, reoperation, and recovery were assessed. RESULTS: All patients diagnosed with TUS presented with deterioration of kidney function after RAKT. Method of diagnosis included ultrasound, antegrade ureterogram, and CT scan. All 3 patients had a short (<1 cm) area of TUS and underwent RATUR. For 2 patients, distal strictures were bypassed with modified Lich-Gregoir ureteroneocystostomy reimplantation. One patient was treated with pyelo-ureterostomy to the contralateral native ureter. No intraoperative complications, conversions to open surgery, or significant operative blood loss requiring blood transfusion for any patient were observed. Also, no patients had urine leaks in the immediate or late postoperative period. After RATUR, 2 patients developed Clavien grade II complications with rectus hematoma or urinary tract infection. CONCLUSION: RATUR is a technically feasible operation for kidney transplant patients with TUS after RAKT. This procedure may provide the same benefits of open operation without promoting certain comorbidities that may occur from open surgical procedures.
Subject(s)
Kidney Transplantation/adverse effects , Postoperative Complications , Reoperation/methods , Robotic Surgical Procedures/methods , Ureteral Obstruction , Aged , Constriction, Pathologic/diagnosis , Constriction, Pathologic/etiology , Constriction, Pathologic/surgery , Female , Humans , Kidney Function Tests/methods , Kidney Transplantation/methods , Male , Middle Aged , Postoperative Complications/diagnosis , Postoperative Complications/surgery , Replantation/methods , Treatment Outcome , Ureteral Obstruction/diagnosis , Ureteral Obstruction/etiology , Ureteral Obstruction/surgery , Ureterostomy/methodsABSTRACT
The synthesis and isolation of mono- and dithiolate-bridged Zn(mu-SR)(n)W(CO)(m) (where n = 1, m = 5; n = 2, m = 4) species from the dimeric N,N'-bis(2-mercaptoethyl)-1,4-diazacycloheptanezinc(II), [Zn-1'](2), and the monomeric [N-(3-thiabutyl)-N'-(3-thiapentaneoate)-1,5-diazacycloheptane]zinc(II), Zn-1'-Ac, are described. Upon cleavage of the dimeric [Zn-1'](2) with Na(+)[ICH(2)CO(2)](-), the resulting Zn-1'-Ac product is isolated as a monomeric, five-coordinate Zn(N(2)SS'O) complex equipped with one available Zn-bound thiolate for further reactivity. Cleavage of [Zn-1'](2) with [Et(4)N](+)Cl(-) afforded a monomeric intermediate, [Zn-1'-Cl](-), containing two Zn-bound thiolates. The zinc mono- and dithiolato complexes demonstrated reactivity toward labile-ligand tungsten carbonyl species, (THF)W(CO)(5) and (pip)(2)W(CO)(4), to yield respectively [(Zn-1'-Ac)W(CO)(5)](x) and [(Zn-1'-Cl)W(CO)(4)](-) complexes that were isolated and characterized spectroscopically and via X-ray diffraction. Upon binding to W(CO)(5), the five-coordinate Zn(N(2)SS'O) complex becomes six-coordinate within the coordination polymer [(Zn-1'-Ac)W(CO)(5)](x), in which the acetate tether of each molecule provides an O donor to occupy the octahedral axial position of a neighboring moiety. The [(Zn-1'-Cl)W(CO)(4)](-) dithiolate-bridged complex maintains a five-coordinate, square-pyramidal [Zn(N(2)S(2)Cl)](-) center, utilizing a chloride as the apical donor and resulting in an overall anionic complex. The addition of CO(g) to the [(Zn-1'-Cl)W(CO)(4)](-) complex was monitored by IR spectroscopy, which showed the emergence of [(Zn-1'-Cl)W(CO)(5)](-).
Subject(s)
Organometallic Compounds/chemical synthesis , Polymers/chemistry , Sulfur/chemistry , Tungsten/chemistry , Zinc/chemistry , Ligands , Models, Molecular , Molecular Conformation , Organometallic Compounds/chemistry , Spectrophotometry, InfraredABSTRACT
INTRODUCTION: Postcraniotomy pain protocols use opioids, which are considered suboptimal analgesia following this procedure. Multimodal analgesia components are sparse. Our null hypothesis states that sumatriptan is not different to placebo in addition to usual intravenous opioids, for the treatment of acute postcraniotomy pain. METHODS AND ANALYSIS: This is a prospective single-centre randomised double-blinded placebo-controlled phase III clinical trial comparing subcutaneous sumatriptan injection in the recovery area with placebo for the treatment of postcraniotomy pain. Eligible adult patients (18 years and older) undergoing craniotomy will be identified preoperatively. Both patient groups will receive a subcutaneous injection at a point where recovery-nursing staff would initiate the usual intravenous opioid analgesia as per standardised pain management protocol. In both groups, further pain management will be followed by the usual intravenous opioid administration. Primary outcome will consist of the difference in pain experienced by the two groups of patients in recovery area 60 min after the study drug administration. Postcraniotomy pain will be measured at regular intervals using the Visual Analogue Scale (VAS) in recovery area. The minimal clinically important difference of 10 mm on the VAS between the two groups will be considered as statistically significant. We will include selected clinical and patient-reported outcomes as secondary endpoints. Univariate regression will be conducted on each one of the clinically plausible potential confounders. We will enrol a total 136 patients, with the study duration of 2 years. This trial will commence recruitment on the 1 July 2019. ETHICS AND DISSEMINATION: This trial protocol has achieved approval by the Austin Health Research Committee, HREC/17/Austin/596. This trial was prospectively registered with Australian New Zealand Clinical Trials Registry on the 10/05/2018 with a unique trial identifier U1111-1209-9072 and registration Number ACTRN12618000793213P. Findings of this study will be disseminated in peer-reviewed academic journals. TRIAL REGISTRATION NUMBER: U1111-1209-9072, ACTRN12618000793213P.
Subject(s)
Analgesics, Opioid/administration & dosage , Craniotomy/adverse effects , Pain Management/methods , Pain, Postoperative/drug therapy , Sumatriptan/administration & dosage , Administration, Intravenous , Australia , Clinical Trials, Phase III as Topic , Double-Blind Method , Humans , Injections, Subcutaneous , Pain Measurement , Prospective Studies , Randomized Controlled Trials as Topic , Visual Analog ScaleABSTRACT
BACKGROUND: Patients with end-stage renal disease are at increased risk for psychiatric and cognitive pathologies. Despite this, there is little standardization of the psychosocial and/or psychiatric evaluation of renal transplant candidates. The purpose of this study is to report the frequency of psychiatric and cognitive pathologies and corresponding psychiatric recommendations in a sample of patients actively listed for kidney transplant. METHODS: We performed a retrospective chart review of 104 patients listed for kidney transplant who underwent semistructured psychiatric assessments as part of a novel clinical protocol. Transplant psychiatry routinely administers brief screeners of cognitive functioning and health literacy, also collected from patients' charts. RESULTS: There were a number of primary psychiatric disorders, including active substance abuse. Even using a conservative cutoff, 52.4% of patients' charts indicated evidence of cognitive impairment, and 28.9% indicated limited health literacy. In addition, there were numerous additional recommendations made within every category (educational, psychotherapeutic/psychiatric, cognitive, cessation of substance use, substance abuse treatment, and mobilizing support for transplant). With the exclusion of the recommendation for more education regarding the transplant process, most patients had at least 1 to 3 recommendations (n = 72, 69.2%). CONCLUSIONS: We have identified a number of concerning psychosocial and psychiatric factors in patients who were evaluated and listed for kidney transplantation that can adversely impact transplant outcomes. The findings provide support for more in-depth and ongoing psychiatric assessments as standard clinical protocol for kidney transplant candidates.
Subject(s)
Kidney Failure, Chronic/psychology , Mental Disorders/complications , Psychological Tests , Adult , Female , Health Literacy , Humans , Kidney Failure, Chronic/complications , Kidney Transplantation/psychology , Male , Mental Disorders/diagnosis , Middle Aged , Retrospective Studies , Substance-Related Disorders/complicationsABSTRACT
We report a rare case of allograft loss from acute Page kidney secondary to trauma that occurred 12 years after kidney transplantation. A 67-year-old Caucasian male with a past surgical history of kidney transplant presented to the emergency department at a local hospital with left lower abdominal tenderness. He recalled that his cat, which weighs 15 lbs, jumped on his abdomen 7 d prior. On physical examination, a small tender mass was noticed at the incisional site of the kidney transplant. He was producing a normal amount of urine without hematuria. His serum creatinine level was slightly elevated from his baseline. Computer tomography revealed a large subscapular hematoma around the transplant kidney. The patient was observed to have renal trauma grade II at the hospital over a period of three days, and he was finally transferred to a transplant center after his urine output significantly decreased. Doppler ultrasound demonstrated an extensive peri-allograft hypoechoic area and abnormal waveforms with absent arterial diastolic flow and a patent renal vein. Despite surgical decompression, the allograft failed to respond appropriately due to the delay in surgical intervention. This is the third reported case of allograft loss from acute Page kidney following kidney transplantation. This case reinforces that kidney care differs if the kidney is solitary or a transplant. Early recognition and aggressive treatments are mandatory, especially in a case with Doppler signs that are suggestive of compression.
ABSTRACT
BACKGROUND Ketorolac is a nonsteroidal anti-inflammatory drug indicated for pain control after surgeries in many fields. The aim of this study was to evaluate the impact of ketorolac use after live-donor nephrectomy (LDN). MATERIAL AND METHODS We reviewed data on 251 patients who underwent laparoscopic LDN from April 2008 to March 2016. Ketorolac was given to 167 patients intraoperatively or postoperatively within 24 h after LDN. Glomerular filtration rate (GFR) percentage was defined as postoperative GFR/preoperative GFR. GFR and GFR percentage at 2 weeks, 6 months, and 1 year after LDN were compared between patients with and without ketorolac administration. Multivariate analysis was performed to identify risk factors for low GFR percentage 1 year after LDN. RESULTS GFR at 1 year was significantly lower in patients who received ketorolac than in those who did not (62 ml/min/1.73 m² vs. 73 ml/min/1.73 m², P<0.01). The differences in GFR and GFR percentage between 2 weeks and 1 year after LDN was significantly lower in the ketorolac group (GFR; 3.0 ml/min/1.73 m² vs. 14.0 ml/min/1.73 m², P<0.01; GFR percentage; 2.0% vs. 12.0%, P<0.01). Urinary albumin/creatinine ratio 1 year after LDN was significantly higher in the ketorolac group compared to the non-ketorolac group (8.6 mg/g vs. 12.6 mg/g, P=0.02). Multivariate analysis revealed that ketorolac use was an independent risk factor for low GFR percentage 1 year after LDN (odds ratio 1.38). CONCLUSIONS Ketorolac appears to be a risk factor for renal dysfunction in the long term after LDN. Prospective clinical trials are needed to reassess its safety.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Glomerular Filtration Rate/drug effects , Ketorolac/adverse effects , Kidney/drug effects , Living Donors , Nephrectomy/methods , Renal Insufficiency/chemically induced , Adult , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Female , Humans , Ketorolac/administration & dosage , Ketorolac/therapeutic use , Kidney/physiopathology , Kidney Function Tests , Kidney Transplantation/methods , Laparoscopy/methods , Male , Middle Aged , Pain, Postoperative/drug therapy , Renal Insufficiency/physiopathology , Risk FactorsABSTRACT
A CCC-NHC pincer Ni(ii)Cl complex was prepared according to the metallation/transmetallation methodology. It was fully characterized by electrochemical, NMR spectroscopic, theoretical, and X-ray crystallographic methods. The complex and its cation were evaluated for electrocatalytic reduction of CO2 under a variety of conditions and found to provide some of the fastest catalytic rates and highest substrate selectivities (CO2vs. H+) reported. Rates improved in the presence of water and, significantly, catalysis occurred at the first reduction potential, presumably at the Ni(i) state. Controlled potential electrolysis (CPE) was found to yield CO at 34% and formate at 47% Faradaic efficiency (FE).
ABSTRACT
The bipyridine ligand is renowned as a photo- and redox-active ligand in catalysis; the latter has been particularly explored in the complex Re(bipy)(CO)3Cl for CO2 reduction. We ask whether a bidentate, redox-active MN2S2 metallodithiolate ligand in heterobimetallic complexes of Mn and Re might similarly serve as a receptor and conduit of electrons. In order to assess the electrochemical features of such designed bimetallics, a series of complexes featuring redox active MN2S2 metallodithiolates, with M = Ni2+, {Fe(NO)}2+, and {Co(NO)}2+, bound to M'(CO)3X, where M' = Mn and Re, were synthesized and characterized using IR and EPR spectroscopies, X-ray diffraction, cyclic voltammetry, and density functional theory (DFT) computations. Butterfly type structures resulted from binding of the convergent lone pairs of the cis-sulfur atoms to the M'(CO)3X unit. Bond distances and angles are similar across the M' metal series regardless of the ligand attached. Electrochemical characterizations of [MN2S2·Re(CO)3Cl] showed the redox potential of the Re is significantly altered by the identity of the metal in the N2S2 pocket. DFT calculations proved useful to identify the roles played by the MN2S2 ligands, upon reduction of the bimetallics, in altering the lability of the Re-Cl bond and the ensuing effect on the reduction of ReI to Re0.
ABSTRACT
BACKGROUND Mycophenolate mofetil (MMF) induced lung disease has been described in only a few isolated reports. We report a case of fatal respiratory failure associated with MMF after kidney transplantation. CASE REPORT A 50-year-old Hispanic male with a history of end-stage renal disease secondary to hypertension underwent deceased donor kidney transplantation. His preoperative evaluations were normal except for a chest x-ray which showed bilateral interstitial opacities. Tacrolimus and MMF were started on the day of surgery. His postoperative course was uneventful and he was discharged on postoperative day 5. One month later, he presented with shortness of breath and a cough with blood-tinged sputum. His respiratory condition deteriorated rapidly, requiring intubation. Chest computer tomography (CT) demonstrated patchy ground-glass opacities with interlobular septal thickening. Comprehensive pulmonary, cardiac, infectious, and immunological evaluations were all negative. Open lung biopsy revealed extensive pulmonary fibrosis with no evidence of infection. He temporarily improved after discontinuation of tacrolimus and MMF, however, on resuming MMF his respiratory status deteriorated again and he subsequently died from hypoxic respiratory failure. CONCLUSIONS An awareness of pulmonary lung disease due to MMF is important to prevent adverse outcomes after organ transplantation. MMF must be used with utmost care in recipients with underlying lung disease as their pulmonary condition might make them more susceptible to any harmful effects of MMF.
Subject(s)
Immunosuppressive Agents/adverse effects , Kidney Transplantation/adverse effects , Mycophenolic Acid/adverse effects , Pulmonary Fibrosis/chemically induced , Fatal Outcome , Humans , Male , Middle AgedABSTRACT
The synthesis and characterization of bis-mercaptoethanediazaheptane cadmium(II) is reported and compared to the analogous zinc complex. Of significance is the dimeric form of the [Zn(N(2)S(2))](2) complex achieves penta-coordination about zinc through a bridging thiolate whereas cadmium engages two thiolate as S-bridges resulting in hexa-coordination about cadmium within a coordination polymer whose X-ray crystal structure is reported here. In the presence of W(CO)(5), this polymer breaks up, generating dimeric [Cd(N(2)S(2))](2) with two W(CO)(5) units appended to the terminal thiolates, a feat that is not observed for the zinc dimer analogue. The greater thiophilicity of cadmium over zinc is noted in several features of these complexes.
Subject(s)
Cadmium Compounds/chemistry , Cadmium/chemistry , Coordination Complexes/chemistry , Ketones/chemistry , Tungsten/chemistry , Zinc/chemistry , Coordination Complexes/chemical synthesis , Coordination Complexes/isolation & purification , Ligands , Molecular ConformationABSTRACT
To explore the displacement of Zn(2+) by Ni(2+) from within N-, S-, and O-chelate ligands, (N-(3-thiabutyl)-N'-(3-thiapentaneoate)-1,4-diazacycloheptane)zinc(II), Zn-1'-Ac, and 1,4-diazacycloheptane-1,4-diylbis(3-thiapentanoato) zinc(II), Zn-1'-Ac(2), were reacted with Ni(BF(4))(2) in a methanol solution and were found to yield, in both cases, the bright blue, hexa-coordinate Ni-1'-Ac(2) metal-exchanged product. The latter conditions imply an intact-ligand unwrapping process as the hexadentate N(2)S(2)O(2) ligand is transferred from zinc to nickel. The former involves transfer of the pentadentate N(2)S(2)O ligand generating a green, penta-coordinate nickel intermediate which engages in CH(2)CO(2) fragment scavenging from a second zinc unit. This conclusion is supported by the observed analogous reformulation of the stable Zn-1'-Ac complex into Zn-1'-Ac(2) and the dithiolato [Zn-1'](2) dimer. To our knowledge, this is a rare (possibly the first) example of cannibalism reported in such ligand systems. The M-1'-Ac(2) complexes were characterized by X-ray diffraction and compared to the directly synthesized products.
Subject(s)
Chelating Agents/chemistry , Nickel/chemistry , Nitrogen/chemistry , Oxygen/chemistry , Sulfur/chemistry , Zinc/chemistry , Crystallography, X-Ray , Ligands , Models, Molecular , Molecular ConformationABSTRACT
The reaction between the complexes [MCl(L)]Cl(x) (L = 2,2',2''-terpyridine, terpy and dien, diethylenetriamine; M = Pd, x = 1; M = Au, x = 2) and [Zn(bme-dach)](2), an N(2)S(2)-Zn-thiolate bridged dimer used to mimic zinc finger protein sites, was studied by Electrospray Ionisation Mass Spectrometry and the structures of some of the products confirmed by X-ray crystallography. All reactions investigated in this work gave heteronuclear (Zn-thiolate)-metal products, the predominant species being the trinuclear dithiolate-bridged aggregate {[Zn(bme-dach)](2)M}(n+) (M = Pd, Au). X-Ray diffraction studies verified the molecular structure of [{ZnCl(bme-dach)}(2)Pd], and further confirmed that the zinc within the [Zn(bme-dach)](2) unit was retained within the N(2)S(2) binding site. The Zn-bound thiolates form stable thiolate bridges to Pd(2+) in a stair-step shape, held together by a planar PdS(4) center. In addition, both zinc atoms maintained penta-coordinate coordination with apical chloride ligands rather than the more commonly observed tetrahedral geometry. Further, [Pd(bme-dach)] was directly synthesized for X-ray structural characterization of the metal exchanged product observed in mass spectrometry experiments. In the case of Au compounds, the reactions were very fast and the products were similar for both [AuCl(L)]Cl(2) (L = terpy and dien) starting materials. In addition to the multimetallic Zn,Au,Zn aggregate formation, the predominant species from the reaction between [Zn(bme-dach)](2) and both Au compounds was the [Au(bme-dach](+) cation observable via ESI-MS, suggesting Zn/Au metal exchange immediately after mixing the compounds. The direct synthesis of [Au(bme-dach)]BPh(4) confirmed the molecular structure of this species through X-ray crystallography. The reactivity profile of Pd(2+) and Au(3+) species is compared with previous studies using the isostructural Pt compounds and the biological relevance of the results discussed.