Serum leptin and pathological findings at the time of radical prostatectomy

PURPOSE: Obesity has been associated with a higher risk of progression following radical prostatectomy (RP). Obese men have higher serum leptin, a hormone produced by adipocytes, which has also been shown to be an in vitro prostate cancer growth factor. We examined whether serum leptin correlates with advanced pathological findings at RP. MATERIALS AND METHODS: Preoperative serum from 225 men treated with RP between 1998 and 1999 was examined for serum leptin. Multivariate logistic regression analysis was used to determine whether serum leptin was predictive of extraprostatic extension (pT3a). RESULTS: Serum leptin highly correlated with body mass index (Spearman r = 0.602, p <0.001). Serum leptin was not associated with total or percent free prostate specific antigen (PSA), biopsy or prostatectomy Gleason score, age or height. On multivariate analysis with total and percent free PSA, clinical stage, age, biopsy Gleason score, body mass index, serum leptin, and height as variables considered for entry into the model, serum PSA (p = 0.009), clinical stage (p = 0.019) and serum percent free PSA (p = 0.041) were the only variables predictive of extraprostatic extension. Serum leptin was not significantly associated with pathological stage (pT3a). CONCLUSIONS: In the current study of predominantly white men with mainly low risk disease there was no statistically significant association between serum leptin and pathological stage (pT3a) at RP. In this cohort serum leptin was not a good biomarker for predicting advanced stage at RP.     

Obesity and capsular incision at the time of open retropubic radical prostatectomy

PURPOSE: The goal of radical prostatectomy (RP) is complete removal of the intact prostate. Obese men can represent a technical challenge. However, to our knowledge objective data linking obesity with technically inferior surgery are lacking. Therefore, we examined the association between body mass index (BMI) and capsular incision at RP as a surrogate of a poor technical operation in men treated for prostate cancer by several high volume surgeons at a center of excellence. MATERIALS AND METHODS: The study population consisted of 7,027 men treated with anatomical retropubic RP between 1996 and 2004 by 7 high volume surgeons. We evaluated the association between BMI and capsular incision using logistic regression, adjusting for clinical and pathological variables, and for the surgeon. RESULTS: Overall capsular incision was noted in 4.6% of all RP specimens. After adjustment for preoperative prostate specific antigen, patient race, height, year of surgery, clinical stage, pathological Gleason sum, prostate weight, extraprostatic extension and seminal vesicle invasion increased BMI was associated with increased odds of capsular incision (p trend = 0.005). After further adjustment for surgeon mild obesity was associated with 30% increased odds of capsular incision (OR 1.30, 95% CI 0.92 to 1.83), while moderate and severe obesity was associated with 57% increased odds of capsular incision (OR 1.57, 95% CI 0.82 to 3.00) relative to normal weight men (p trend = 0.06). CONCLUSIONS: In a study of more than 7,000 men treated by 7 experienced surgeons BMI was positively related to capsular incision. This suggests that open retropubic RP is technically more difficult in obese men, which results in a greater likelihood of a less than technically ideal operation. Although this may be predicted to have a negative impact on disease-free survival outcomes in obese men, it is unlikely to alone explain the worse outcomes in obese men noted in previous RP series.     

Peripheral arterial disease: comparison of color duplex US and contrast-enhanced MR angiography for diagnosis

PURPOSE: To prospectively compare the diagnostic accuracies of color duplex ultrasonography (US) and contrast material-enhanced magnetic resonance (MR) angiography and to assess interobserver agreement regarding contrast-enhanced MR angiographic findings in patients suspected of having peripheral arterial disease (PAD). MATERIALS AND METHODS: The institutional review board approved the study, and all patients provided signed informed consent. Two hundred ninety-five patients referred for diagnostic and preinterventional work-up of PAD with duplex US also underwent gadolinium-enhanced MR angiography. Data sets were reviewed for presence or absence of 50% or greater luminal reduction, which indicated hemodynamically significant stenosis, and to determine interobserver agreement. At duplex US, a peak systolic velocity ratio of 2.5 or greater indicated significant stenosis. Primary outcome measures were differences between duplex US and contrast-enhanced MR angiography in sensitivity and specificity for detection of significant stenosis, as assessed with the McNemar test, and interobserver agreement between the two contrast-enhanced MR angiogram readings, expressed as quadratic weighted kappa values. Intraarterial digital subtraction angiography (DSA) was the reference standard. RESULTS: Two hundred forty-nine patients had at least one hemodynamically significant stenotic lesion at contrast-enhanced MR angiography, duplex US, or both examinations. One hundred fifty-two patients underwent intraarterial DSA. The quadratic weighted kappa for agreement regarding the presence of 50% or greater stenosis at contrast-enhanced MR angiography was 0.89 (95% confidence interval [CI]: 0.87, 0.91). Sensitivity of duplex US was 76% (95% CI: 69%, 82%); specificity, 93% (95% CI: 91%, 95%); and accuracy, 89%. Sensitivity and specificity of contrast-enhanced MR angiography were 84% (95% CI: 78%, 89%) and 97% (95% CI: 95%, 98%), respectively; accuracy was 94%. Sensitivity (P = .002) and specificity (P = .03) of contrast-enhanced MR angiography were significantly higher. CONCLUSION: Results of this prospective comparison between contrast-enhanced MR angiography and duplex US provide evidence that contrast-enhanced MR angiography is more sensitive and specific for diagnosis and preinterventional work-up of PAD.     

Continuous pulse oximeter monitoring for inapparent hypoxemia after long bone fractures

BACKGROUND: Continuous pulse oximeter monitoring (CPOM) and daily intermittent arterial blood gas (ABG) were used to define the incidence, pattern, and severity of inapparent hypoxemia after long bone fractures. METHOD: Twenty long bone fracture patients and 19 normal control patients were studied. CPOM, daily ABG, hypoxic symptoms, and features of fat embolism syndrome were monitored for 72 hours after fractures and after surgical interventions. RESULTS: CPOM trend curves showed that all fracture patients except one had recurrent desaturations below 90% Sao2 of varying duration and depth. The lowest Sao2 was down to 60% and the longest episode lasted for 1.47 hours. ABG analysis could not show the recurrent phenomena and never detected the corresponding desaturation episodes. Long bone fracture patients had more desaturation episodes, longer total desaturation duration, and larger total area under desaturation curves in both the postfracture and postoperative periods (p < 0.05). The mean Sao2 was significantly lower in the postfracture period. Although most patients remained asymptomatic and recovered spontaneously, two required transient oxygen therapy and one progressed to fat embolism syndrome. CONCLUSION: Inapparent hypoxia with profound desaturation is common after long bone fractures. CPOM of all patients admitted with long bone fractures is recommended for early detection. In patients who develop inapparent hypoxia, additional pulmonary insult should be avoided or undertaken with care and well timed.     

Tacrolimus therapy in pediatric patients with treatment-resistant nephrotic syndrome

This is a retrospective analysis of 16 children started on tacrolimus with various types of treatment-resistant nephrotic syndrome. There are 13 patients with focal glomerulosclerosis, 1 minimal change disease, and 2 IgA nephropathy with nephrosis. The mean age of the children was 11.4 years (range 3.5–18.1 years) with a mean age at diagnosis of 5.6 years (range 1.6–13.3 years). All patients initially received prednisone 2 mg/kg per day. Other therapies for 15 of 16 included cyclosporine (n=15), chlorambucil (n=5), mycophenolate mofetil (n=5), levamisole (n=3), i.v. methylprednisolone (n=3), and cyclophosphamide (n=2). The major indication for the initiation of tacrolimus included treatment resistance/dependence (n=15) and intolerable side effects from other therapies (n=1). The average time from the diagnosis to initiation of tacrolimus was 5.3 years (range 0.3–13.3 years, median 6 years). The initial dosage of tacrolimus utilized was 0.1 mg/kg per day divided into two doses. The mean follow-up period was 6.5 months (range 2.5–18 months). Thirteen patients (81%) went into a complete remission within an average of 2 months (range 0.5–5.5 months), with 3 patients relapsing while on treatment. Three patients did not respond. Of these, 2 had partial remissions (13%) and 1 failed to respond. Adverse events included anemia (n=1), seizure (n=1), worsening or new-onset hypertension (n=5), and sepsis (n=1). All patients remain on tacrolimus. Tacrolimus is an effective, well-tolerated medication for treatment-resistant forms of nephrotic syndrome in children, with a complete remission rate of 81% and a partial remission rate of 13% (totaling 94%).     

Bacteremia due to Clostridium hathewayi in a patient with acute appendicitis

Clostridium hathewayi is a newly described Clostridium species isolated from the feces of healthy human individuals, but its clinical significance is not known. We describe a case of human infection associated with C. hathewayi. The bacterium (strain HKU18) was isolated from the blood culture of a 39-year-old patient with acute gangrenous appendicitis complicated by septic shock. The cells were strictly anaerobic, nonmotile rods that stained gram negative. Conventional phenotypic tests and commercial identification systems failed to identify HKU18 to the species level. 16S rRNA gene analysis showed 1.4% nucleotide difference between the sequence of HKU18 and that of C. hathewayi, indicating that HKU18 was a strain of C. hathewayi. The patient responded to appendectomy and antibiotic treatment. 16S rRNA gene sequencing would be useful in further characterizing the clinical disease spectrum of C. hathewayi.     

Magnetic resonance imaging in 122 children with spastic cerebral palsy

The interrelationship between magnetic resonance imaging findings, types of cerebral palsy, and gestation was studied. We analyzed the magnetic resonance imaging of brain in 122 children with spastic cerebral palsy. Forty-three patients had spastic hemiplegia, 61 had spastic diplegia, and 18 had spastic tetraplegia. Magnetic resonance imaging abnormalities were observed in 75% of patients. Periventricular leukomalacia accounted for 66% of abnormalities observed in patients with spastic diplegia; other types of brain lesions were uncommon. In patients with spastic tetraplegia, two types of magnetic resonance imaging abnormalities predominated: congenital brain anomalies and term-type brain injuries, 42% and 33% respectively. Types of magnetic resonance imaging abnormalities were more heterogeneous in patients with spastic hemiplegia. Preterm brain injuries (periventricular leukomalacia and posthemorrhagic porencephaly) were observed often in patients born at preterm but were also observed in patients born at term. Term-type brain injuries (term-type border-zone infarct, basal ganglia-thalamic lesion, subcortical leukomalacia, and multicystic encephalomalacia) were observed only in patients born at or near term. We conclude that magnetic resonance imaging findings for patients with spastic cerebral palsy were closely related to types of cerebral palsy and gestation at birth. Magnetic resonance imaging in patients with perinatal brain injury may reflect pathologic changes and is useful in understanding and evaluating cerebral palsy.     

Role of echocardiography in the detection and prognosis of ischemic mitral regurgitation

Ischemic mitral regurgitation (IMR) is mitral regurgitation (MR) due to complications of coronary artery disease and not fortuitously associated with it. Acute MR secondary to ruptured papillary muscle after myocardial infarction is rare and often fatal. We focus on functional MR, much more common, which occurs without any intrinsic valve disease. It was often underrated because of low murmur intensity but with the use of echocardiography this complication is observed between 15%-20% after a myocardial infarction. Recent advances in noninvasive Doppler echocardiography allow accurate assessment of regurgitant volume and effective regurgitant orifice and thus provide the tools to reliably evaluate the prognosis and mechanisms of IMR. IMR presence is associated with excess mortality. The mortality risk is directly related to the degree of regurgitation and a regurgitant volume > or = 30 ml or an effective regurgitant orifice > or = 20 mm2; define a high-risk group. Presence and degree of the regurgitation are related to local left ventricular remodeling. The apical and posterior displacement of papillary muscles leads to excess valvular tenting which in turn, in association with loss of systolic annular contraction, determines the severity of the regurgitation. In current clinical practice, IMR is mainly corrected by ring annuloplasty. However, this technique does not correct local alterations of left ventricular remodeling and its benefits on long-term outcome remains to be demonstrated.     

Severe acute respiratory syndrome: radiographic evaluation and clinical outcome measures

PURPOSE: To evaluate the relationship among chest radiographs, oxygen supplementation requirement, and treatment response in severe acute respiratory syndrome (SARS). MATERIALS AND METHODS: Forty patients (20 women, 20 men; mean age, 42.90 years +/- 14.01 [SD]; median age, 41.5 years; age range, 25-82 years) with SARS were evaluated. Daily chest radiographs were graded according to percentage of lung involvement during 20.15 days +/- 5.56 (median, 20 days; range, 14-38 days). Times between symptoms and treatment and time to reach maximal radiographic score from admission and treatment day were determined. Daily oxygen saturation (Sao2) and oxygen supplementation including mechanically assisted ventilation were recorded. Treatment response was defined as good, fair, and poor. Patterns of radiographic opacity at admission and at maximal radiographic score were noted. Differences in radiographic and clinical parameters with respect to oxygen supplementation and treatment response were respectively evaluated with Mann-Whitney and Kruskal-Wallis tests. RESULTS: Larger maximal radiographic scores, lower Sao2 at maximal radiographic change, longer time from treatment to maximal radiographic score (P <.01), and diffuse consolidation at maximal radiographic score were associated with oxygen supplementation. Parameters that influenced treatment response were time from symptom onset to treatment day (P =.003), time from admission to treatment day (P <.001), time to maximal radiographic score from treatment day (P =.001), maximal radiographic score (P =.009), Sao2 at maximal radiographic score (P =.13), and treatment radiographic score (P =.03). Fair responders had shorter time between admission and treatment than did either good (P <.001) or poor responders (P =.002) and shorter time between symptoms and treatment (P <.001) and lower treatment radiographic score (P =.012) than did good responders. Good (82%), poor (36%), and fair (33%) responders developed maximal chest radiographic scores within 4 days of treatment (P =.008). Radiographic patterns at both admission and maximal radiographic score did not influence treatment response. CONCLUSION: There are significant relationships among radiographic parameters, oxygen supplementation, and treatment response, and these relationships appear to be clinically useful in the treatment of SARS.