Perioperative complications of lumbar instrumentation and fusion in patients with diabetes mellitus.

BACKGROUND CONTEXT: Prior studies have documented an increased complication rate in diabetics treated by lumbar decompression. Despite the assumption that this risk would be exacerbated in larger fusion procedures, a recent study found no such increased risk. PURPOSE: To clarify the perioperative risk for patients with diabetes mellitus undergoing instrumented lumbar fusion as compared with controls. To identify differences, if any exist, between patients with insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes (NIDDM). STUDY DESIGN/SETTING: This is a retrospective case-control study designed to examine the risk of perioperative complications in patients with diabetes mellitus treated by lumbar instrumentation and fusion. This study analyzed 94 diabetic patients and 43 controls treated by posterior lumbar instrumentation and fusion. Outcome was assessed based on the occurrence of perioperative complications. Complications were classified as major or minor. METHODS: Hospital and office records were reviewed for 94 diabetics (51 NIDDM, 43 IDDM) and 43 controls matched for age, sex and procedure with the IDDM group. The groups were compared for demographic characteristics, surgical data, perioperative complications and fusion rate. RESULTS: The NIDDM, IDDM and control groups were equivalent with regard to age, gender, nicotine use, fusion levels, operative time and estimated blood loss. There was a significant difference in complication rate between the NIDDM (53%) and IDDM (56%) groups versus controls (21%). There was a significant increase in complications with multilevel fusion in all groups and with increased operative time in the IDDM group. There was a significantly greater nonunion rate in the NIDDM (22%) and IDDM (26%) groups as compared with controls (5%). CONCLUSIONS: Patients with both IDDM and NIDDM have a significantly increased risk of perioperative complications as compared with controls when treated by lumbar instrumentation and fusion.     

Moderate alcohol intake and renal function decline in women: a prospective study.

BACKGROUND: The impact of moderate alcohol consumption on renal function has important public health implications given the high prevalence of alcohol use. Experimentally, alcohol may adversely affect renal function, but clinical data are limited and no large, prospective studies have examined this issue. METHODS: In a prospective study of 1658 nurses enrolled in the Nurses' Health Study, we sought to determine if there was an association between moderate alcohol consumption and rate of decline in renal function. Daily alcohol intake was measured in 1990, 1994 and 1998 using a detailed questionnaire. Maximum daily alcohol intake was measured in 1988. Creatinine, measured from blood samples provided in 1989 and 2000, was used to estimate glomerular filtration rate (GFR) and creatinine clearance (CCr). RESULTS: Compared to individuals with no alcohol intake, the odds ratios (ORs) for developing a >or=25% estimated GFR decline were: 0.98 (95% CI: 0.72-1.32) for 0.1-4.9 g/day, 0.83 (95% CI: 0.56-1.21) for 5-14.9 g/day and 0.81 (95% CI: 0.50-1.31) for 15-59.9 g/day. For women with hypertension (n = 726), the ORs for a >or=25% estimated GFR decline were: 0.98 (95% CI: 0.53-1.21) for 0.1-4.9 g/day, 0.62 (95% CI: 0.34-1.12) for 5-14.9 g/day and 0.53 (95% CI: 0.25-1.12) for 15-59.9 g/day. CONCLUSIONS: Moderate alcohol consumption had no substantial adverse effect on renal function in women over an 11 year follow-up period.     

Analgesic efficacy of inhaled morphine in patients after bunionectomy surgery

BACKGROUND: The AERx Pain Management System (Aradigm Corporation, Hayward, CA) is a novel pulmonary delivery system for the systemic administration of morphine. The authors compared the relative analgesic efficacy and safety of the AERx Pain Management System with those of placebo and intravenous morphine in an orthopedic postsurgical pain model. METHODS: Eighty-nine male and female PS-1 to PS-3 patients underwent standardized bunionectomy surgery and received multiple doses of inhaled or intravenous placebo, inhaled morphine (one inhalation [2.2 mg] or three inhalations [6.6 mg]), or intravenous morphine (4 mg) in a blinded fashion. Open-label rescue morphine (2 mg) was also available as needed. Pain intensity, pain relief, and time to pain relief were measured after the first dose. Global evaluation, morphine consumption, vital signs, and adverse events were monitored for 8 h after treatment. Blinded study personnel performed all treatment administrations and pain assessments. RESULTS: Three inhalations of morphine and 4 mg intravenous morphine provided comparable single- and multiple-dose analgesia. One inhalation of morphine was statistically indistinguishable from placebo. Three inhalations of morphine and 4 mg intravenous morphine both consistently demonstrated significantly greater analgesic efficacy than did placebo and one inhalation of morphine. CONCLUSIONS: Comparable analgesic efficacy was demonstrated between a carefully matched dose of inhaled and intravenous morphine in a postsurgical pain model.     

Metastatic cutaneous squamous cell carcinoma to the parotid: the role of surgery and adjuvant radiotherapy to achieve best outcome

Background: Australia has the highest incidence of cutaneous squamous cell carcinoma in the world. The majority of lesions occur in the head and neck with metastases to the parotid gland lymph nodes reflecting an uncommon, but aggressive, manifestation. Parotidectomy ± neck dissection followed by adjuvant radiotherapy should be considered as best practice. Methods: Between 1983 and 2000, seventy-four patients were treated for metastatic cutaneous squamous cell carcinoma to the parotid with surgery and adjuvant radiotherapy at Westmead Hospital, Sydney. Relevant data were extracted from patient files and a prospectively maintained database. Patterns of relapse and outcome were analysed. Results: Median age at diagnosis was 65 years (34−93 years) in 63 men and 11 women. Median follow-up duration was 41 months (12−188 months). All patients underwent parotidectomy with 52 undergoing a simultaneous neck dissection. Twelve patients required sacrifice of the facial nerve (4) or one or more branches (8). All received adjuvant radiotherapy to the parotid region with 56 also receiving radiotherapy to the ipsilateral neck. Despite treatment, 24% developed locoregional recurrence, with a median time to relapse of 7.5 months. The most common site for recurrence was the treated parotid region and upper neck. Most relapsed patients died. No variable independently predicted for locoregional recurrence on multivariate analysis. The 5-year absolute and cause-specific survival rates were 58% and 72%, respectively. Conclusion: Parotid gland lymph node metastases from cutaneous squamous cell carcinoma are associated with a high rate of recurrence and cause-specific mortality despite current best practice (surgery and high dose adjuvant radiotherapy). The role of more aggressive surgery, altered fractionation or chemotherapy to enhance locoregional control remains unclear.     

Surgical revision of biliary strictures following adult live donor liver transplantation: patient selection, morbidity, and outcomes

Biliary strictures after live donor liver transplantation (LDLT) are frequent and difficult to manage. The outcomes of surgical correction of biliary anastomotic complications remain unclear. Clinical outcomes of patients requiring surgical revision of their biliary anastomosis following LDLT were analyzed. Of 296 consecutive right lobe LDLTs, approximately 21% of patients developed biliary strictures. Of these patients, twelve required surgical revision of a biliary anastomotic stricture. For patients who had operative repair, the average time from transplantation to stricture diagnosis was 7.6 months. Mean time to surgical correction was 8.2 months from the time of stricture diagnosis. Eight of 12 (67%) patients no longer require any intervention with a mean follow-up of 43.7 months. Two of 12 patients require intermittent medical treatment for presumed cholangitis, but have not required biliary interventions. Two patients have required chronic PTC catheter drainage. The 30-day postoperative morbidity was 58%, with four serious (Grade 3) complications occurring in three patients. Early stricture repair (<6 months from diagnosis of stricture) and younger donor grafts were associated with better surgical outcomes. Timely surgical correction of biliary strictures is successful and durable in appropriately selected patients. However, operative repair is associated with significant postoperative morbidity.     

Synthesis of carbon-11-labeled tricyclic necroptosis inhibitors as new potential PET agents for imaging of tumor necrosis factor α (TNF-α)

Carbon-11-labeled tricyclic necroptosis inhibitors were first designed and synthesized as new potential PET agents for imaging of tumor necrosis factor α (TNF-α). The target tracers were prepared by O-[¹¹C]methylation of their corresponding precursors using [¹¹C]CH₃OTf under basic conditions and isolated by a simplified SPE method in 50–60% radiochemical yields based on [¹¹C]CO₂ and decay corrected to end of bombardment (EOB). The overall synthesis time from EOB was 15–20 min, the radiochemical purity was >99%, and the specific activity at end of synthesis (EOS) was 111–185 GBq/μmol.     

Pharmacokinetic characterization in xenografted mice of a series of first-generation mimics for HLA-DR antibody, Lym-1, as carrier molecules to image and treat lymphoma.

Despite their large size, antibodies (Abs) are suitable carriers to deliver systemic radiotherapy, often molecular image-based, for lymphoma and leukemia. Lym-1 Ab has proven to be an effective radioisotope carrier, even in small amounts, for targeting human leukocyte antigen DR (HLA-DR), a surface membrane protein overexpressed on B-cell lymphoma. Pairs of molecules (referred to as ligands), shown by computational and experimental methods to bind to each of 2 sites within the Lym-1 epitopic region, have been linked to generate small (<2 kDa) molecules (referred to as selective high-affinity ligands [SHALs]) to mimic the targeting properties of Lym-1 Ab. METHODS: A lysine-polyethylene glycol (PEG) backbone was used to synthetically link 2 of the following ligands: deoxycholate, 5-leuenkephalin, triiodothyronine, thyronine, dabsyl-L-valine, and N-benzoyl-L-arginyl-4-amino-benzoic acid to generate a series of 13 bidentate SHALs with a biotin or 1,4,7,10-tetraazacyclododecane-N,N',N',N'-tetraacetic acid (DOTA) chelate attached to the linker. These SHALs have been assessed for their selectivity in binding to HLA-DR10-expressing cells and for their pharmacokinetics and tissue biodistribution in mice. Biotinylated versions of these SHALs discriminated cell lines positive for HLA-DR10 expression with near-nanomolar affinity. The DOTA versions of 4 SHALs were labeled with (111)In for pharmacokinetic studies in mice with HLA-DR10-expressing malignant Raji xenografts. RESULTS: The bidentate, biotinylated, and DOTA-SHALs were synthesized in high-purity, multimilligram amounts. Mean radiochemical and product yields and purities were 90%, 75%, and 90% at mean specific activities of 3.9 MBq/microg (105 microCi/microg) for the (111)In-labeled SHALs. As expected, rapid blood clearance and tumor targeting were observed. The pharmacokinetics of the SHALs was influenced by the component ligands. Biliary clearance, kidney localization, and serum receptor binding contributed to less favorable tumor targeting. CONCLUSION: A series of SHALs was readily synthesized in multimilligram amounts and showed the expected selective binding in vitro. Better selection of the SHAL components should provide second-generation SHALs with improved properties to fulfill the substantial potential of these novel molecular carriers for targeting.     

3He MRI in mouse models of asthma.

In the study of asthma, a vital role is played by mouse models, because knockout or transgenic methods can be used to alter disease pathways and identify therapeutic targets that affect lung function. Assessment of lung function in rodents by available methods is insensitive because these techniques lack regional specificity. A more sensitive method for evaluating lung function in human asthma patients uses hyperpolarized (HP) (3)He MRI before and after bronchoconstriction induced by methacholine (MCh). We now report the ability to perform such (3)He imaging of MCh response in mice, where voxels must be approximately 3000 times smaller than in humans and (3)He diffusion becomes an impediment to resolving the airways. We show three-dimensional (3D) images that reveal airway structure down to the fifth branching and visualize ventilation at a resolution of 125 x 125 x 1000 microm(3). Images of ovalbumin (OVA)-sensitized mice acquired after MCh show both airway closure and ventilation loss. To also observe the MCh response in naive mice, we developed a non-slice-selective 2D protocol with 187 x 187 microm(2) resolution that was fast enough to record the MCh response and recovery with 12-s temporal resolution. The extension of (3)He MRI to mouse models should make it a valuable translational tool in asthma research.