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Biomedical subjects

John J Kelly

Publications and source records attributed to John J Kelly.

At least 19 recordsLinked to original sources

Up-regulation of adiponectin, its isoforms and receptors in end-stage kidney disease.

BACKGROUND: Despite the favourable effects of adiponectin on the vasculature and insulin resistance (IR), levels are increased in patients with end-stage kidney disease (ESKD), in whom both IR and atherosclerosis are prevalent. METHODS: To investigate this paradox, we examined the distribution of adiponectin isoforms, the expression of adiponectin receptor (AdipoR) mRNA on peripheral blood mononuclear cells (PBMC) in 41 patients with ESKD on haemodialysis and 41 matched controls, and its function by adenosine monophosphate-activated protein kinase (AMPK) phosphorylation of AdipoR on PBMC. We also compared the expression of AdipoR on PBMC with that on muscle and subcutaneous and visceral fat in 10 patients undergoing elective cholecystectomy. RESULTS: The proportion of the high molecular weight (HMW) isoform of adiponectin was increased in the dialysis group (P = 0.001), even though these patients were significantly insulin resistant compared with controls (P = 0.006). AdipoR1 and AdipoR2 on PBMC were also increased in patients with ESKD (P < 0.05 and P = 0.007, respectively), but levels did not correlate with IR, the HMW isoform or other anthropometric measurements. There was a strong correlation between AdipoR1 and AdipoR2 on PBMC in ESKD and in subcutaneous and visceral fat in controls. However, there was no relationship between AdipoR in PBMC, muscle or visceral fat. Phosphorylation of AMPK by recombinant adiponectin showed that AdipoR on PBMC, from controls and ESKD patients, were equally functional. CONCLUSIONS: IR in ESKD is not explained by the change in isoformic distribution, or by AdipoR down-regulation or dysfunction. Rather, this receptor-ligand axis is up-regulated and may be a beneficial response to the inflammatory milieu of ESKD.

AMP-Activated Protein Kinases↗

Effect of synthetic corticosteroids on vascular reactivity in the human forearm.

Exogenous cortisol raises blood pressure (BP) and suppresses acetylcholine (ACh)-induced vasodilatation in healthy male volunteers. This study tests the hypothesis that the activation of either classical type I or II corticosteroid receptors by synthetic corticosteroids induces endothelial dysfunction. In two separate studies, dexamethasone or fludrocortisone was administered to healthy male subjects over five days. BP, metabolic parameters, and forearm blood flow (FBF) responses to intra-arterial ACh and nitroprusside (SNP) were measured on day 5 of treatment. Fludrocortisone (800 microg/day) and dexamethasone (3 mg/day) increased BP from control measurements, but not when compared with placebo. Metabolic effects of the steroids were consistent with their known actions. Endothelium-dependent vasodilatation was enhanced by fludrocortisone, most obviously in the presence of nitric oxide (NO) synthase inhibition with NG-mono-methyl-L-arginine (LNMMA). Dexamethasone did not suppress endothelium dependent or independent vasodilatation. Non-NO-mediated endothelium-dependent vasodilatation was increased by systemic mineralocorticoid excess but unaffected by glucocorticoid excess. These results do not support the notion that cortisol-induced vascular effects are mediated through classical corticosteroid receptors.

Acetylcholine↗

Benefits of laparoscopic adrenalectomy: a 10-year single institution experience.

INTRODUCTION: We aimed to compare the outcomes of laparoscopic and open adrenalectomies and to assess the impact of the availability of advanced laparoscopy on adrenal surgery at our institution. MATERIALS AND METHODS: A retrospective analysis of data of all patients who underwent adrenalectomy at the University of Massachusetts Medical Center over a 10-year period. RESULTS: Sixty-four consecutive patients underwent adrenalectomy during the study periods. There were 19 open (OA) and 45 laparoscopic (LA) adrenalectomies performed. There was no significant difference between the average size of adrenal masses removed for the LA and the OA groups [4.3 vs. 5.5 cm, respectively (P=0.23)]. LA proved superior to OA, resulting in shorter operative times (171 vs. 229 min, P=0.02), less blood loss (96 vs. 371 mL, P<0.01), shorter time to regular diet (1.9 vs. 4.4 d, P<0.001), and shorter hospital stay (2.5 vs. 5.8 d, P=0.02). In addition, the average annual number of adrenalectomies increased significantly since the establishment of our advanced laparoscopic program (10.0 vs. 2.0, P=0.02). CONCLUSIONS: LA offers superior results when compared to OA in terms of operative time, blood loss, return of bowel function, duration of hospital stay, and functional recovery. The availability of advanced laparoscopy has resulted in a significant increase in the number of adrenalectomies performed at our institution without a shift in surgical indications.

Adrenal Gland Neoplasms↗

Species variability in cardiovascular research: the example of adrenocorticotrophin-induced hypertension.

1. Lawrie Beilin has contributed greatly to international hypertension research through both animal and human studies. 2. Animals are used in biomedical research to gain insights that can be extrapolated ultimately to humans. 3. A simple experimental manipulation, adrenocorticotrophin (ACTH) administration, has a range of different cardiovascular effects in different species. 4. Caution should be exercised in extrapolating data from animals to humans.

Adrenocorticotropic Hormone↗

Impact of prehybridization PCR amplification on microarray detection of nitrifying bacteria in wastewater treatment plant samples.

A gel-based microarray that included a set of 26 oligonucleotide probes targeting all nitrifying bacteria at varying levels of specificity suggested the presence of targeted microorganisms when hybridized to RNA isolated from a wastewater treatment plant, but could not discriminate between perfectly matched and mismatched sequences due in part to low signal intensity. To enhance sensitivity and improve discrimination, polymerase chain reaction was used to selectively amplify the 16S rRNA genes of specific nitrifier groups. RNA transcribed from these DNA templates was hybridized to the microarray and thermal dissociation analysis was used to characterize the specificity of hybridization. Amplification with Nitrospira-specific primers resulted in the selective amplification of this target group, confirmed by both a significant increase in signal intensity and a melting profile identical to the reference RNA. In contrast, Nitrobacter was not detected in the environmental samples with probe Nbac1000 despite pre-amplification with Nitrobacter-specific primers, indicating the absence of strains containing this Nitrobacter-specific sequence. Pre-amplification using primers specific for beta-Proteobacterial ammonia-oxidizing bacteria resulted in a significant increase in signal intensity for probe Nso190, but melting profiles for probe Nso190 showed a slight deviation between amplified RNA and the reference microorganism, suggesting that the amplification products contained some sequences that varied by a single nucleotide difference in the probe target region.

Bacteria↗

Effects of an invasive cattail species (Typha x glauca) on sediment nitrogen and microbial community composition in a freshwater wetland.

Sediments from Cheboygan Marsh, a coastal freshwater wetland on Lake Huron that has been invaded by an emergent exotic plant, Typhaxglauca, were examined to assess the effects of invasion on wetland nutrient levels and sediment microbial communities. Comparison of invaded and uninvaded zones of the marsh indicated that the invaded zone showed significantly lower plant diversity, as well as significantly higher aboveground plant biomass and soil organic matter. The sediments in the invaded zone also showed dramatically higher concentrations of soluble nutrients, including greater than 10-fold higher soluble ammonium, nitrate, and phosphate, which suggests that Typhaxglauca invasion may be impacting the wetland's ability to remove nutrients. Terminal restriction fragment length polymorphism analyses revealed significant differences in the composition of total bacterial communities (based on 16S-rRNA genes) and denitrifier communities (based on nirS genes) between invaded and uninvaded zones. This shift in denitrifiers in the sediments may be ecologically significant due to the critical role that denitrifying bacteria play in removal of nitrogen by wetlands.

Bacteria↗

Predictors of weight status following laparoscopic gastric bypass.

BACKGROUND: Weight loss after bariatric surgery varies and depends on many factors, such as time elapsed since surgery, baseline weight, and co-morbidities. METHODS: We analyzed weight data from 494 patients who underwent laparoscopic Roux-en-Y gastric bypass (RYGBP) by one surgeon at an academic institution between June 1999 and December 2004. Linear regression was used to identify factors in predicting % excess weight loss (%EWL) at 1 year. RESULTS: Mean patient age at time of surgery was 44 +/- 9.6 (SD), and the majority were female (83.8%). The baseline prevalence of co-morbidities included 24% for diabetes, 42% for hypertension, and 15% for hypercholesterolemia. Baseline BMI was 51.5 +/- 8.5 kg/m(2). Mean length of hospital stay was 3.8 +/- 4.6 days. Mortality rate was 0.6%. Follow-up weight data were available for 90% of patients at 6 months after RYGBP, 90% at 1 year, and 51% at 2 years. Mean %EWL at 1 year was 65 +/- 15.2%. The success rate (> or = 50 %EWL) at 1 year was 85%. Younger age and lower baseline weight predicted greater weight loss. Males lost more weight than females. Diabetes was associated with a lower %EWL. Depression did not significantly predict %EWL. CONCLUSION: The study demonstrated a 65 %EWL and 85% success rate at 1 year in our bariatric surgery program. Our finding that most pre-surgery co-morbidities and depression did not predict weight loss may have implications for pre-surgery screening.

Adult↗

Chronic peripheral neuropathy responsive to rituximab.

A 73-year-old man was referred for evaluation of unsteady gait and numbness of the feet. His symptoms had progressed over the previous 3 years from numbness and tingling in his left lateral thigh to a gait imbalance severe enough to necessitate crutches for ambulation. After a thorough neurological work-up, including an electromyogram that was markedly abnormal, and extensive testing for anti-nerve antibodies, a diagnosis of neuropathy, secondary to monoclonal IgM antibodies against myelin-associated glycoprotein, was made. Aggressive treatment was deemed necessary; however, none of the standard options, including intravenous immunoglobulin, prednisone, and cytotoxic drugs, seemed suitable given his underlying health and the severity of his deficit. A course of rituximab 375 mg/m2 weekly for 4 weeks was recommended for the patient. Shortly after the treatment was completed, he began to notice a slow and steady improvement. Within 3 months his gait had improved to the point where he no longer required crutches or a cane and he was able to return to work.

Aged↗

Neurologic complications of primary systemic amyloidosis.

Amyloid is a botanical term that denotes a waxy, amorphous, eosinophilic material and is used to describe similar pathological findings in humans. The deposits in primary systemic amyloidosis are derived from monoclonal serum proteins in plasma cell dyscrasia, which are degraded locally in tissues and deposited in insoluble sheets that damage organs. The cause of organ damage in amyloidosis is unclear but most likely due to the direct toxic effects of amyloid. Symptoms of the disorder include neuropathy, myopathy, and cardiac or renal insufficiency; there is often multiple-organ involvement. Congestive heart failure and nephrotic syndrome are predominant causes of death. Differential difficulties exist in diagnosing the disorder, and familial amyloid polyneuropathy directly mimics the disease. Diagnostic tools include electromyography, laboratory testing for abnormalities in serum and urine, and histological investigation of appropriate tissue. The median survival of patients is 2 years. However, melphalan and prednisone treatment for at least 1 year has resulted in increased survival rates. There have also been reports of benefit from high-dose chemotherapy followed by peripheral blood stem cell transplantation. Without early therapy, however, the disease has a dismal prognosis, and peripheral neuropathy usually persists or worsens despite therapy and improvement in other organs.

Amyloidosis↗

Anisotropy in the anodic oxidation of silicon in KOH solution.

The electrochemical oxidation and passivation of Si(100) and Si(111) electrodes in KOH solution was studied by potentiodynamic and potential-step measurements. Striking differences were observed between the surfaces. A comparison of the results for n- and p-type electrodes led us to conclude that electrochemical oxidation of silicon in alkaline solution must be triggered by a chemical reaction. The strong influence of temperature on the current-potential and current-time results of (111) surfaces supports the importance of chemical activation. Photocurrent experiments on n-type (111) electrodes show that oxide nucleation is important for growth of the passive layer. A mechanism combining surface chemistry and electrochemistry is proposed to account for the pronounced anisotropy in anodic oxidation.

Journal Article↗

Elevated atmospheric CO2 alters soil microbial communities associated with trembling aspen (Populus tremuloides) roots.

Global atmospheric CO(2) levels are expected to double within the next 50 years. To assess the effects of increased atmospheric CO(2) on soil ecosystems, cloned trembling aspen (Populus tremuloides) seedlings were grown individually in 1 m(3) open bottom root boxes under either elevated (720 ppm, ELEV) or ambient CO(2) (360 ppm, AMB). After 5 years, soil cores (40 cm depth) were collected from the root boxes and divided into 0-20 cm and 20-40 cm fractions. ELEV treatment resulted in significant decreases in both soil nitrate and total soil nitrogen in both the 0-20 cm and 20-40 cm soil fractions, with a 47% decrease in soil nitrate and a 50% decrease in total soil nitrogen occurring in the 0-20 cm fraction. ELEV treatment did not result in a significant change in the amount of soil microbial biomass. However, analysis of indicator phospholipid fatty acids (PLFA) indicated that ELEV treatment did result in significant increases in PLFA indicators for fungi and Gram-negative bacteria in the 0-20 cm fraction. Terminal restriction fragment length polymorphism (T-RFLP) analysis was used to analyze the composition of the soil bacterial communities (using primers targeting the 16SrRNA gene) and the soil fungal communities (using primers targeting the intergenic transcribed spacer region). T-RFLP analysis revealed shifts in both bacterial and fungal community structure, as well as increases in both bacterial and fungal species richness with ELEV treatment. These results indicated that increased atmospheric CO(2) had significant effects on both soil nutrient availability and the community composition of soil microbes associated with aspen roots.

Carbon Dioxide↗

Advantages of mini-laparoscopic vs conventional laparoscopic cholecystectomy: results of a prospective randomized trial.

HYPOTHESIS: The use of smaller instruments during laparoscopic cholecystectomy (LC) has been proposed to reduce postoperative pain and improve cosmesis. However, despite several recent trials, the effects of the use of miniaturized instruments for LC are not well established. We hypothesized that LC using miniports (M-LC) is safe and produces less incisional pain and better cosmetic results than LC performed conventionally (C-LC). DESIGN: A patient- and observer-blinded, randomized, prospective clinical trial. SETTING: A tertiary care, university-based hospital. PATIENTS: Seventy-nine patients scheduled for an elective LC who agreed to participate in this trial were randomized to undergo surgery using 1 of the 2 instrument sets. The criteria for exclusion were American Society of Anesthesiologists class III or IV, age older than 70 years, liver or coagulation disorders, previous major abdominal surgical procedures, and acute cholecystitis or acute choledocholithiasis. INTERVENTION: Laparoscopic cholecystectomy performed with either conventional or miniaturized instruments. MAIN OUTCOME MEASURES: Patients' age, sex, operative time, operative blood loss, intraoperative complications, early and late postoperative incisional pain, and cosmetic results. RESULTS: Thirty-three C-LCs and 34 M-LCs were performed and analyzed. There were 8 conversions (24%) to the standard technique in the M-LC group. No intraoperative or major postoperative complications occurred in either group. The average incisional pain score on the first postoperative day was significantly less in the M-LC group (3.9 vs 4.9; P = .04). No significant differences occurred in the mean scores for pain on postoperative days 3, 7, and 28. However, 90% of patients in the M-LC group and only 74% of patients in the C-LC group had no pain (visual analog scale score of 0) at 28 days postoperatively (P = .05). Cosmetic results were superior in the M-LC group according to both the study nurse's and the patients' assessments (38.9 vs 28.9; P<.001, and 38.8 vs 33.4; P = .001, respectively). CONCLUSIONS: Laparoscopic cholecystectomy can be safely performed using 10-mm umbilical, 5-mm epigastric, 2-mm subcostal, and 2-mm lateral ports. The use of mini-laparoscopic techniques resulted in decreased early postoperative incisional pain, avoided late incisional discomfort, and produced superior cosmetic results. Although improved instrument durability and better optics are needed for widespread use of miniport techniques, this approach can be routinely offered to many properly selected patients undergoing elective LC.

Analgesia↗

Lymphoma and peripheral neuropathy: a clinical review.

Lymphoma occasionally affects the peripheral nervous system. When it does, the diagnosis can be elusive since many patients present without known lymphoma. Most peripheral nerve complications are due to non-Hodgkin's lymphoma (NHL), which infiltrates nerves causing axonal damage. This disorder can affect nerve roots and cranial nerves, often associated with lymphomatous meningitis. NHL may also infiltrate peripheral nerves and cause plexopathy, mononeuropathy, or generalized neuropathy. These neuropathies may resemble an asymmetric mononeuropathy multiplex or a generalized disorder such as chronic inflammatory demyelinating polyradiculoneuropathy. When NHL infiltrates diffusely, the term neurolymphomatosis is used. Hodgkin's lymphoma (HL), by contrast, rarely infiltrates nerves. More often, HL causes immunological disorders of the peripheral nervous system such as inflammatory plexopathy or Guillain-Barré syndrome. Other rare lymphomas such as intravascular lymphoma and Waldenstrom's macroglobulinemia can also affect peripheral nerves in specific ways. In addition, other malignant and nonmalignant lymphoproliferative disorders enter into the differential diagnosis of lymphomatous neuropathy. This review discusses the multiple peripheral nerve presentations of lymphoma from the clinician's point of view and provides a guide to the evaluation and diagnosis of these uncommon, challenging disorders.

Humans↗

Left ventricular pseudoaneurysm causing myocardial infarction and cerebrovascular accident.

Although post-infarction mortality is most often due to ventricular dysrhythmias, the non-dysrhythmic causes of post-myocardial infarction death present a potential dilemma to the clinician. Non-dysrhythmic hemodynamic complications include cardiogenic shock, left ventricular free wall rupture, rupture of the interventricular septum, papillary muscle rupture, left ventricular pseudoaneurysm, and acute stroke. We present a rare case of a left ventricular pseudoaneurysm presenting with altered mental status, ultimately suspected to have caused the thromboembolic complications of acute myocardial infarction and cerebrovascular accident.

Aged↗

Epilepsy surgery with intraoperative MRI at 1.5 T.

Despite the infancy of iMRI in epilepsy surgery and the paucity of literature on this topic, some conclusions may be reached. Although iMRI is a useful adjunct during epilepsy procedures, a randomized control trial is necessary to determine its true impact.

Adolescent↗

DNA microarray detection of nitrifying bacterial 16S rRNA in wastewater treatment plant samples.

A small scale DNA microarray containing a set of oligonucleotide probes targeting the 16S rRNAs of several groups of nitrifying bacteria was developed for the monitoring of wastewater treatment plant samples. The microarray was tested using reference rRNAs from pure cultures of nitrifying bacteria. Characterization of samples collected from an industrial wastewater treatment facility demonstrated that nitrifying bacteria could be detected directly by microarray hybridization without the need for PCR amplification. Specifically, the microarray detected Nitrosomonas spp. but did not detect Nitrobacter. The specificity and sensitivity of direct detection was evaluated using on-chip dissociation analysis, and by two independent analyses--an established membrane hybridization format and terminal restriction fragment length polymorphism fingerprinting (T-RFLP). The latter two analyses also revealed Nitrospira and Nitrobacter to be contributing populations in the treatment plant samples. The application of DNA microarrays to wastewater treatment systems, which has been demonstrated in the current work, should offer improved monitoring capabilities and process control for treatment systems, which are susceptible to periodic failures.

DNA Fingerprinting↗

Acute effects of hydrocortisone on plasma nitrate/nitrite activity and forearm vasodilator responsiveness in normal human subjects.

1. The aim of the present study was to examine the acute effects of cortisol infusion on plasma nitrate/nitrite (NO) activity and forearm vascular responsiveness to acetylcholine. 2. We performed two randomized, placebo-controlled, cross-over studies. Study A examined the effects of intravenous hydrocortisone (200 mg over a 3 h period) on blood pressure (BP) and plasma NO activity in six healthy male volunteers. Study B examined the effects of intra-arterial hydrocortisone on cholinergic vasodilator responsiveness in six healthy male volunteers. Vasodilator responsiveness was measured by bilateral strain gauge plethysmography. 3. In study A, there was no significant change in BP during the hydrocortisone infusion. Comparing values obtained following 180 min infusion of hydrocortisone and control, there were significant increases in plasma cortisol (3441 +/- 342 vs 209 +/- 29 nmol/L, respectively; P < 0.001) and glucose (5.7 +/- 0.2 vs 4.6 +/- 0.2 mmol/L, respectively; P < 0.05) and a reduction in plasma renin concentration (PRC) (8.1 +/- 1.2 vs 11.0 +/- 1.8 pg/mL, respectively; P < 0.05) following hydrocortisone infusion. However, there were no significant changes in either plasma NO or in the endogenous NO synthase inhibitors asymmetrical and symmetrical dimethylarginine. 4. In study B, there was no significant change in BP or in cholinergic vasodilator responsiveness during the hydrocortisone infusion. 5. Short-term cortisol infusions do not alter biochemical or physiological markers of NO activity. If cortisol-induced hypertension is mediated by suppression of NO activity in humans, it seems likely that these changes take more than 3 h to become detectable.

Acetylcholine↗