Testosterone and resistance training effects on muscle nitric oxide synthase isoforms in COPD men

SummaryBackgroundSkeletal muscle dysfunction contributes to exercise limitation in COPD. The role of the nitric oxide synthase (NOS) system in muscle dysfunction is ill defined. Reduced levels of endothelial NOS (eNOS) and elevated levels of inducible NOS (iNOS) in the skeletal muscle of COPD patients have been recently reported. We hypothesized that resistance exercise training (R) and/or testosterone supplementation (T) would alter the transcription and expression of the NOS isoenzymes in COPD skeletal muscle.MethodsVastus lateralis biopsies were obtained before and after a 10-week intervention in 40 men with severe COPD(age 67.7 ± 8.3, FEV1 41.4 ± 12.6% predicted): placebo + no training (P) (n = 11), placebo + resistance training (PR) (n = 8), testosterone + no training (T) (n = 11) and testosterone + resistance training (TR) (n = 10) groups. eNOS, nNOS and iNOS mRNA and protein levels were measured in each sample. mRNA and protein levels were measured using real-time PCR and enzyme-linked immunosorbant assay, respectively.ResultseNOS mRNA increased in the TR group compared to P and T groups (P < 0.001). eNOS protein was increased in TR and T groups after intervention (P < 0.05) but not in the PR group. nNOS protein increased in the PR, T, and TR groups (P < 0.05). iNOS protein decreased only in the TR group (P = 0.01).ConclusionResistance training and testosterone supplementation increased eNOS and nNOS proteins and decreased iNOS protein in the skeletal muscles of men with COPD. These changes in NO system might explain some of the favorable effects of these therapies

A Controlled Investigation of Optimal Internal Medicine Ward Team Structure at a Teaching Hospital

BACKGROUND: The optimal structure of an internal medicine ward team at a teaching hospital is unknown. We hypothesized that increasing the ratio of attendings to housestaff would result in an enhanced perceived educational experience for residents. METHODS: Harbor-UCLA Medical Center (HUMC) is a tertiary care, public hospital in Los Angeles County. Standard ward teams at HUMC, with a housestaff∶attending ratio of 5:1, were split by adding one attending and then dividing the teams into two experimental teams containing ratios of 3:1 and 2:1. Web-based Likert satisfaction surveys were completed by housestaff and attending physicians on the experimental and control teams at the end of their rotations, and objective healthcare outcomes (e.g., length of stay, hospital readmission, mortality) were compared. RESULTS: Nine hundred and ninety patients were admitted to the standard control teams and 184 were admitted to the experimental teams (81 to the one-intern team and 103 to the two-intern team). Patients admitted to the experimental and control teams had similar age and disease severity. Residents and attending physicians consistently indicated that the quality of the educational experience, time spent teaching, time devoted to patient care, and quality of life were superior on the experimental teams. Objective healthcare outcomes did not differ between experimental and control teams. CONCLUSIONS: Altering internal medicine ward team structure to reduce the ratio of housestaff to attending physicians improved the perceived educational experience without altering objective healthcare outcomes

Intrahepatic Cholangiocarcinoma Skin Metastasis in a Patient with Hidradenitis Suppurativa: A Rare Entity

We present a challenging diagnosis of disseminated intrahepatic cholangiocarcinoma presenting with perineal cutaneous masses in a young African American male with known hidradenitis suppurativa. The patient was a 39-year-old male who presented to the emergency department with difficulty walking due to severe gluteal swelling and pain. The patient had an 18-month history of biopsy-proven hidradenitis suppurativa. Examination under anesthesia disclosed a 9×6 cm left perianal mass and right 5×3 cm right peri-scrotal mass; both masses were excised and revealed adenocarcinoma with signet ring cell differentiation. The patient was diagnosed with widely metastatic adenocarcinoma of unknown primary. Initiation of palliative capecitabine was planned however the patient decompensated and expired one month from the time of his diagnosis due to septic shock. Autopsy with histologic staining revealed innumerable liver lesions consistent with rare variant Intrahepatic Cholangiocarcinoma (ICC) with signet-ring cell differentiation. Multiple red papules were noted on the aortic valve with histology similarly demonstrating signet-ring cell adenocarcinoma. Cutaneous metastasis of cholangiocarcinoma has been reported but is rare, and to our knowledge this is the first reported case of cholangiocarcinoma cutaneous metastasis in a patient with hidradenitis suppurativa. This case re-emphasizes the protean presentation and aggressive metastatic potential of ICC. It also highlights the importance of maintaining a wide differential for dermatologic lesions in patients with hidradenitis suppurativa and postulates a mechanism for metastatic seeding of areas affected by this disease.</p

Hematuria in a Patient with Non-malignant Bladder Nodules

Introduction: Gross hematuria in adults with resultant anemia is highly concerning for genitourinary malignancy.&nbsp; However, in rare instances, malakoplakia can mimic such malignancy. Malakoplakia is a benign granulomatous condition with malfunction of the phagolysosomal activity of macrophages and monocytes. This leads to formation of foamy histocytes with intracytoplasmic basophilic inclusions known as Michaelis-Gutmann bodies.&nbsp; These inclusion bodies are pathognomonic for the condition.&nbsp; &nbsp;Case presentation:&nbsp; A 41-year-old female presented with spontaneous gingival bleed and painless gross hematuria for 2 days. Two weeks prior to the current admission she had been hospitalized with gastrointestinal bleed and gross hematuria with symptomatic anemia. The hematuria diminished during treatment with ceftriaxone. She was discharged with a course of cephalexin to treat complicated cystitis. On the subsequent admission, she denied taking any medications. Labs on admission showed Hgb 8.6g/dL, WBC 4.9×109/L (4900/μL, platelets 307×109/L (307×103/μL), INR 1.09, creatinine 61.88μmol/L (0.7mg/dL), calcium 2.17mmol/L (8.7mg/dL). Cystoscopy showed several very abnormal appearing nodules present all over the bladder in a very unusual and abnormal fashion. Frozen section from the biopsy showed no evidence of malignancy but possible fungal infection. Final biopsy result showed malakoplakia, negative stains for acid fast bacilli and fungal organisms, and no evidence of tumor. Urine cultures for bacteria, fungus, acid fast bacilli were negative. Tissue culture grew light Enterococcus faecium, vancomycin resistant (VRE), sensitive to linezolid and quinopristin/dalfopristin, and light Candida glabrata. She was treated presumptively with ceftriaxone but switched to linezolid based on results from tissue cultures. Discussion: The German scientists and physicians Michaelis and Gutmann first described Malakoplakia in 1902. Malakoplakia is a rare condition that most commonly affects the urinary tract and can mimic tumors. It is a benign condition characterized by a granulomatous process consisting of foamy histiocytes with basophilic Michaelis-Gutmann bodies. These basophilic inclusions consist of partially digested bacteria and calcium and iron deposits that result from a defective phagolysosomal activity in the macrophages. It is more commonly reported in patients with immunodeficiencies like HIV or in transplant patients. It is important to obtain a correct pathologic diagnosis in these cases given that it is a benign condition that mimics carcinoma. Treatment consists of a prolonged course of antibiotics. Bethanechol and ascorbic acid appear to improve cure rates.</p

A controlled investigation of optimal internal medicine ward team structure at a teaching hospital.

BackgroundThe optimal structure of an internal medicine ward team at a teaching hospital is unknown. We hypothesized that increasing the ratio of attendings to housestaff would result in an enhanced perceived educational experience for residents.MethodsHarbor-UCLA Medical Center (HUMC) is a tertiary care, public hospital in Los Angeles County. Standard ward teams at HUMC, with a housestaff∶attending ratio of 5:1, were split by adding one attending and then dividing the teams into two experimental teams containing ratios of 3:1 and 2:1. Web-based Likert satisfaction surveys were completed by housestaff and attending physicians on the experimental and control teams at the end of their rotations, and objective healthcare outcomes (e.g., length of stay, hospital readmission, mortality) were compared.ResultsNine hundred and ninety patients were admitted to the standard control teams and 184 were admitted to the experimental teams (81 to the one-intern team and 103 to the two-intern team). Patients admitted to the experimental and control teams had similar age and disease severity. Residents and attending physicians consistently indicated that the quality of the educational experience, time spent teaching, time devoted to patient care, and quality of life were superior on the experimental teams. Objective healthcare outcomes did not differ between experimental and control teams.ConclusionsAltering internal medicine ward team structure to reduce the ratio of housestaff to attending physicians improved the perceived educational experience without altering objective healthcare outcomes

Nitric oxide-dependent modulation of sympathetic neural control of oxygenation in exercising human skeletal muscle

Nitric oxide (NO) attenuates α-adrenergic vasoconstriction in contracting rodent skeletal muscle, but it is unclear if NO plays a similar role in human muscle. We therefore hypothesized that in humans, NO produced in exercising skeletal muscle blunts the vasoconstrictor response to sympathetic activation. We assessed vasoconstrictor responses in the microcirculation of human forearm muscle using near-infrared spectroscopy to measure decreases in muscle oxygenation during reflex sympathetic activation evoked by lower body negative pressure (LBNP). Experiments were performed before and after NO synthase inhibition produced by systemic infusion of NG-nitro-l-arginine methyl ester (l-NAME). Before l-NAME, LBNP at −20 mmHg decreased muscle oxygenation by 20 ± 2 % in resting forearm and by 2 ± 3 % in exercising forearm (n = 20), demonstrating metabolic modulation of sympathetic vasoconstriction. As expected, l-NAME increased mean arterial pressure by 17 ± 3 mmHg, leading to baroreflex-mediated supression of baseline muscle sympathetic nerve activity (SNA). The increment in muscle SNA in response to LBNP at −20 mmHg also was attenuated after l-NAME (before, +14 ± 2; after, +8 ± 1 bursts min−1; n = 6), but this effect of l-NAME was counteracted by increasing LBNP to −40 mmHg (+19 ± 2 bursts min−1). After l-NAME, LBNP at −20 mmHg decreased muscle oxygenation similarly in resting (−11 ± 3 %) and exercising (−10 ± 2 %) forearm (n = 12). Likewise, LBNP at −40 mmHg decreased muscle oxygenation both in resting (−19 ± 4 %) and exercising (−21 ± 5 %) forearm (n = 8). These data advance the hypothesis that NO plays an important role in modulating sympathetic vasoconstriction in the microcirculation of exercising muscle, because such modulation is abrogated by NO synthase inhibition with l-NAME