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Biomedical subjects

C P Johnson

Publications and source records attributed to C P Johnson.

At least 37 records · Page 2Linked to original sources

Inflammatory modulation of calcium-activated potassium channels in canine colonic circular smooth muscle cells.

BACKGROUND & AIMS: The characteristics of colonic circular smooth muscle slow waves are altered during inflammation. The aim of this study was to examine whether inflammation modulates the open-state probability of Ca2+-activated K+ (KCa) channels in these cells to contribute to these alterations. METHODS: The experiments were performed on freshly dissociated single smooth muscle cells from the canine colon using standard patch clamp methods. Inflammation was induced by mucosal exposure to ethanol and acetic acid. RESULTS: Inflammation decreased the open-state probability of large-conductance KCa (BK) channels in the cell-attached and excised inside-out configurations. The voltage sensitivity of the channels was also reduced during inflammation. Inflammation had no significant effect on the large, medium, and small conductances or the unitary current levels of channel openings. However, it decreased the maximum number of simultaneous channel openings. The channels were Ca2+-dependent and were blocked by tetraethylammonium and charybdotoxin in normal and inflamed cells. CONCLUSIONS: Inflammation decreases the open-state probability of BK channels. This may partially reverse the decrease in duration and amplitude of slow waves and depolarization of membrane potential seen in inflammation.

Animals↗

The screening and diagnosis of autistic spectrum disorders.

The Child Neurology Society and American Academy of Neurology recently proposed to formulate Practice Parameters for the Diagnosis and Evaluation of Autism for their memberships. This endeavor was expanded to include representatives from nine professional organizations and four parent organizations, with liaisons from the National Institutes of Health. This document was written by this multidisciplinary Consensus Panel after systematic analysis of over 2,500 relevant scientific articles in the literature. The Panel concluded that appropriate diagnosis of autism requires a dual-level approach: (a) routine developmental surveillance, and (b) diagnosis and evaluation of autism. Specific detailed recommendations for each level have been established in this document, which are intended to improve the rate of early suspicion and diagnosis of, and therefore early intervention for, autism.

Asperger Syndrome↗

Pre-transplant identification of risk factors that adversely affect length of stay and charges for renal transplantation.

BACKGROUND: In the current era of renal transplantation, increasing attention is being focused on resource utilization. The purpose of this study was to identify demographic, medical and immunologic risk factors that are associated with changes in length of stay (LOS) and charges for renal transplantation. METHOD: The study was a retrospective analysis of 311 consecutive renal transplants performed at a single institution. Univariate and multivariate analyses were used to examine relationships between risk factors, LOS, charges and post-operative complications. RESULTS: The following pre-transplant variables were found to be independently significant in predicting increased LOS and/or charges: African-American race, obesity for women, chronic obstructive pulmonary disease (COPD), presence of cardiac disease or previous stroke, pre-transplant dialysis time > or = 1 yr, a 10% increase in panel reactive antibody (PRA), cadaver donor and retransplantation. The analyses were performed with and without adjustment for key outcome variables such as delayed graft function (DGF) and use of induction antibody therapy. Increased LOS or charges for specific risk factors could be attributed to increased complication rates, including delayed graft function seen with various co-morbidities, or increased immunologic risk and more frequent use of induction antibody therapy. CONCLUSION: Analysis of linked financial and clinical databases can reveal demographic, medical and immunologic risk factors that correlate with LOS, charges and complications for renal transplantation. Efforts to establish quantitative relationships for various risk factors relative to resource utilization will become important in managed care and/or capitated healthcare delivery systems.

Adult↗

Renal transplantation for end-stage renal disease following bone marrow transplantation: a report of six cases, with and without immunosuppression.

UNLABELLED: BACKGROUND. Over 12000 bone marrow transplantations (BMT) are performed in the USA each year. This procedure is associated with significant morbidity including acute and chronic renal failure (CRF). CRF after BMT is usually secondary to radiation nephropathy and,or cyclosporine (CsA) toxicity. Survival on dialysis therapy for patients with radiation nephropathy is poor and renal transplantation may be a preferable form of renal-replacement therapy. METHODS: We report our experience with renal transplantation in 6 patients with end-stage renal disease (ESRD) following BMT: 4 as a result of radiation nephropathy; one secondary to hemolytic uremic syndrome; and 1 as a result of antitubular basement membrane nephritis. Ages at the time of BMT ranged from 26 to 40 yr. ESRD developed after a mean period of 94 months (range 42-140 months) after BMT. The kidney source was from a living donor in 5 patients, and a cadaveric donor (CAD) in 1 patient. In 3 recipients, the bone marrow and kidney were from the same donor. They are managed without any immunosuppressive therapy. The other 3 were initiated on triple therapy (prednisone, mycophenolate mofetil/azathioprine and cyclosporine/tacrolimus). RESULTS: These patients have been followed for up to 31 months (range 3-30 months) after kidney transplant, and 5 out of 6 are alive with functioning bone marrow and renal transplants. Their plasma creatinines range from 70 to 160 micromol/L (mean 97 micromol/L). One patient died following metastatic squamous cell cancer of the genital tract. CONCLUSIONS: 1) Renal transplant is a feasible alternative for patients with ESRD following BMT: 2) if bone marrow and kidney are from the same donor, the recipient requires little or no maintenance immunosuppression; 3) short-term results show good survival, but long-term follow-up is needed: 4) infections and malignancy post-renal transplantation were seen in recipients who needed immunosuppression; and 5) reduction in immunosuppression may be needed in such post-BMT patients who undergo kidney transplants.

Adult↗

American Academy of Pediatrics. Committee on Children With Disabilities. Care coordination: integrating health and related systems of care for children with special health care needs.

Care coordination is a process that links children with special health care needs and their families to services and resources in a coordinated effort to maximize the potential of the children and provide them with optimal health care. Care coordination often is complicated because there is no single entry point to multiple systems of care, and complex criteria determine the availability of funding and services among public and private payers. Economic and sociocultural barriers to coordination of care exist and affect families and health care professionals. In their important role of providing a medical home for all children, primary care pediatricians have a vital role in the process of care coordination, in concert with the family.

Case Management↗

Recurrent and de novo renal diseases after renal transplantation: a report from the renal allograft disease registry.

Recurrent or de novo glomerular disease is an important cause of graft dysfunction and eventual loss. Cyclosporine A (CyA) has improved short-term renal allograft outcome but has not altered long-term graft survival. The purpose of the current study is to determine the prevalence of such disease and its impact on graft function in the CyA era. From 1984 to 1994, 1,557 renal allografts were performed at the Medical College of Wisconsin and the University of Cincinnati. Patients were followed up for an average of 7.2 years (minimum, 1 year). Recurrent disease was diagnosed by renal biopsy in 98 (6.3%) patients after an average of 36 months. Demographic characteristics of patients with and without recurrent disease were similar. Glomerulonephritis was the most common finding, occurring in 73 patients, and included focal segmental glomerulosclerosis (FSGS), 25; IgA nephropathy (IgAN), 11; membranous (MN), 11; proliferative, 11; membranoproliferative glomerulonephritis (MPGN), 10; glomerular basement membrane (anti-GBM), 3; and systemic lupus erythematosus (SLE), two. Diabetic nephropathy was present in 22, hemolytic uremic syndrome (HUS) in two, and oxalosis in one. Graft loss occurred in 60 of 98 (61%) recipients. Half-life of the allograft was diminished in patients with recurrent disease, 2,038 +/- 225 versus 3,135 +/- 385 days, P = 0.002. The actuarial allograft survival at 1, 3, 5, and 8 years posttransplantation with recurrence was 88%, 74%, 57%, and 34%, respectively; and the corresponding graft survival for patients without recurrent disease was 80%, 70%, 64%, and 53%, respectively (P = 0.003). The risk of recurrent disease increased with length of graft survival from 2.8% at 2 years to 9.8% and 18.5% at 5 and 8 years, respectively. We conclude that recurrent disease is a significant problem after renal transplantation and is associated with decreased graft survival.

Actuarial Analysis↗

Prognostic value of intraoperative blood flow measurements in vascular access surgery.

BACKGROUND: The purpose of this study was to correlate intraoperative blood flow measurements with outcome in vascular access surgery. METHODS: In 303 patients, 389 vascular access operations were performed. Intraoperative blood flow measurements were made immediately following construction of 227 autogenous and 162 prosthetic arteriovenous fistulas (AVFs) using a handheld flowprobe. Blood flow measurements were stratified by demographic variables such as age, race, sex, and presence of diabetes and were correlated with primary and secondary (assisted) patency. Statistical methods included life-table analysis and Cox proportional hazards model. RESULTS: Blood flow increased progressively from distal to proximal access sites and was not significantly affected by age, race, sex, or presence of diabetes. Autogenous AVFs with flow rates at or below 320 mL/min and polytetrafluoroethylene (PTFE) grafts with flow rates at or below 400 mL/min had significantly worse primary and secondary patency rates compared to their higher flow counterparts at all sites. Using hazard analysis flow rate was the single most important determinant of primary and secondary patency. PTFE grafts with flow rates at or below 400 mL/min also required more interventions (1.58 per patient-year) and failed sooner (median time, 0.5 +/- 4.7 months) than grafts with flow rates above 400 mL/min (1.08 interventions per patient-year; P = .03; median time, 1.6 +/- 5.0 months; P = .003). CONCLUSIONS: Intraoperative measurements of access blood flow provide objective, reliable data that correlate with outcome. Routine use of this technology might lead to more efficient management of patients undergoing hemodialysis access surgery.

Adult↗

Experimental inoculation of mice with trypsin-resistant and trypsin-sensitive avian reoviruses.

Groups of sucking Swiss albino mice were inoculated by the intracerebral (i.c.), intraperitoneal (i.p.) or oral route with a trypsin-sensitive avian reovirus (TR1) or a trypsin-resistant (R2) reovirus. The viruses caused a number of effects, the most severe occurring after i.c. inoculation and the least after oral inoculation. They included incoordination and tremors, oiliness of the hair, and retarded growth. Patterns of viral persistence in tissues were similar for the two viruses, with high titres in the brain on days 3 and 6 after i.c. or i.p. injection. Both viruses were still present in the brain 21 days after i.c. injection. No virus was found in any tissue when TR1 was given orally. All groups "seroconverted" except the one infected orally with TR1, but neutralization titres were low. The effects resembled those described for mammalian reoviruses in mice. The results indicate that, for short periods, wild mice may be capable of transmitting avian reoviruses between poultry flocks. Furthermore, in the production of monoclonal antibodies to avian reoviruses in mice, it is possible that pathological changes will occur.

Administration, Oral↗

Postprandial motor activity and its relationship to transit in the canine ileum.

BACKGROUND: The purpose of this study was to elucidate the mechanism of reduced intestinal transit rate in the ileum as compared with the jejunum. METHODS: Twenty-one dogs were each instrumented with 12 strain gauge transducers, 2 collection cannulas, and an infusion catheter defining a 100 cm study in the midjejunum (n = 11) and midileum (n = 10). Postprandial motor activity and intestinal transit were measured 1 hour after ingestion of a 650 kcal solid meal. Contractile activity was analyzed by means of computer programs that determine frequency, amplitude, and propagation behavior of circular smooth muscle contractions. RESULTS: Postprandial ileal contractions occurred with greater frequency (13.7 +/- 2.5 versus 11.5 +/- 0.4; p = 0.04) and displayed a higher incidence of propagation (61% +/- 2% versus 44% +/- 3%; p = 0.0001) than jejunal contractions, but traveled at significantly slower rates (1.0 +/- 0.7 cm/sec vs 3.7 +/- 0.9 cm/sec; p = 0.0001). The net result was significantly slower transit in the ileum compared with the jejunum (4.7 +/- 0.7 cm/min versus 13.1 +/- 1.5 cm/min; p = 0.0006). Within each region, transit correlated with parameters of propagating contractions. Stepwise regression of the combined data revealed that contraction velocity was the most important variable determining intestinal transit rate (r = 0.64; p < 0.001). CONCLUSIONS: Contrary to previous thinking, postprandial ileal contractions display a high degree of temporal and spatial organization. Slow ileal transit is mainly due to reduced propagation velocity, which is intrinsic to the circular smooth muscle.

Animals↗

Management of severe pancreatitis in renal transplant recipients.

OBJECTIVE: The authors determine if any aspects of the treatment of renal transplant patients with pancreatitis were of particular benefit with regard to graft and patient survival. BACKGROUND: The incidence of pancreatitis in renal transplant patients is low (1%-2%), but the mortality of the disease approaches 100%. Although several descriptive reports have been published, there is no consensus-regarding management. METHODS: The authors conduct a retrospective chart review. RESULTS: Twenty-one patients were identified with posttransplant pancreatitis (1.3% incidence). The cause of pancreatitis was presumed to be maintenance immunosuppression in all cases. Patients were classified by dynamic computed tomography (CT) scans having 1) mild/edematous disease (4 patients), 2) localized abscess or pseudocyst (6 patients), or 3) severe disease (11 patients). Patients with mild/edematous pancreatitis did well with medical management. The six patients with localized abscess or pseudocyst were successfully treated with standard operative intervention. Of the 11 patients with severe disease, 6 had several days of intensive medical management before operation, and all died. The other five patients underwent early operative intervention based principally on CT scan findings, and all survived. The latter group had multiple operations and four of five had functioning renal allografts at discharge. CONCLUSION: The severity of pancreatitis in the posttranplant patients may be difficult to assess by clinical criteria. Dynamic CT scanning is, therefore, essential in defining the extent of disease. Early, and perhaps repeated, operations may be lifesaving in those patients having CT scan findings of severe pancreatitis.

Adult↗

Myoelectric activity and absorptive capacity of rat small intestinal isografts.

The effect of transplantation on small intestinal absorption, digestive capacity, myoelectric activity, and morphology was assessed in inbred Lewis rats. Electrodes were sutured to the duodenum and isografted jejunoileum or to the native jejunoileum in controls. The frequency of migrating myoelectric complexes (MMCs) in the duodenum was 3.3 +/- 0.3/hr in controls and 1.8 +/- 0.4/hr in transplants (P < 0.05). MMC frequency in the jejunoileum was 5.1 +/- 1.3/hr in controls and 3.2 +/- 0.9/hr in transplants (P > 0.05). MMCs appeared to migrate from the duodenum to the jejunoileum 80 +/- 3% of the time in controls and 59 +/- 7% of the time in transplant rats (P < 0.05). Absorption in the transplanted jejunoileum demonstrated a 35-40% decrease in glucose and electrolytes absorption. Villus height and number of nuclei per villus was reduced. Intestinal length (dry) was 103 +/- 6 cm for controls and 51 +/- 3 cm for transplant rats (P < 0.05). Brush border sucrase activity was unchanged. We conclude that small intestinal isografts display similar myoelectric activity as controls, but the decreased absorptive capacity and villus height may require longer segments of intestine to be transplanted in order to support normal nutrition.

Animals↗

Delayed gastroduodenal emptying is an important mechanism for control of intestinal transit in short-gut syndrome.

PURPOSE: To understand the relative importance of changes in ileal smooth muscle contractility versus alteration of intestinal flow rate as control mechanisms for regulating intestinal transit in a surgical model of short-gut syndrome. METHODS: A model of short-gut syndrome was created by performing a 70% proximal small-bowel resection in dogs. Ten control and 6 animals with short-gut syndrome were instrumented with strain gauge transducers, steel collection cannulas, and a Silastic intraluminal infusion catheter in the midileum. Motor activity was analyzed by computer programs that determine frequency, amplitude, and propagation behavior of postprandial contractions. Perfusions of 14C-polyethylene glycol and bolus injection of 3H-polyethylene glycol were used to determine intestinal flow and transit rates. Total gastroduodenal emptying was determined using a 14C-polyethylene glycol-labelled meal. RESULTS: Postprandial contraction frequency was decreased in animals with short-gut syndrome, but other significant changes in amplitude, mean area, and propagation behavior of postprandial ileal contractions were not seen. Gastroduodenal emptying and mean intestinal flow rates were markedly slower in animals with short-gut syndrome, as were intestinal transit rates. CONCLUSIONS: In this model of short-gut syndrome, the major adaptive change is decreased intestinal flow rate, related to delayed gastroduodenal emptying. The spatial organization of ileal contractions does not change substantially aside from a change in frequency which can be accounted for by transection of the intestinal wall.

Animals↗

The differential contribution of spinopetal projections to increases in vocalization and motor reflex thresholds generated by the microinjection of morphine into the periaqueductal gray.

The capacity of morphine microinjected into the ventrolateral periaqueductal gray (vPAG) to elevate the thresholds of spinal motor reflexes (SMRs), vocalizations during shock (VDSs) and vocalization afterdischarges (VADs) was challenged by the intrathecal administration of receptor antagonists to serotonin (methysergide), norepinephrine (phentolamine) and mu-opiates (naloxone). Methysergide and phentolamine were equipotent in reversing increases in SMR thresholds. The efficacy of these antagonists to reduce increases in VDS and VAD thresholds was dependent on the dose of morphine administered into the vPAG. These results indicate that the dose of morphine administered into the vPAG determines the contribution of spinopetal projections in inhibiting dorsal horn neurons involved in reflex generation versus the rostral transmission of pain information. A hypothesis is offered regarding the mechanisms by which vPAG administered morphine suppresses nociceptive transmission through different levels of the neuraxis.

Animals↗

Increases in vocalization and motor reflex thresholds generated by the intrathecal administration of serotonin or norepinephrine.

The capacity of serotonin and norepinephrine to elevate the thresholds of spinal motor reflexes (SMRs), vocalizations during shock (VDSs), and vocalization afterdischarges (VADs) when administered into the spinal subarachnoid space was evaluated. Both monoamines generated dose-dependent increases in the thresholds of all 3 responses. The minimum effective doses of serotonin and norepinephrine that elevated all 3 response thresholds were 40 micrograms and 1 microgram respectively. Monoamine-induced increases in response thresholds were reversed by the intrathecal administration of their corresponding receptor antagonists (phentolamine or methysergide). Threshold increases generated by serotonin were also partially reduced by phentolamine. These results indicate that dorsal horn neurons that underlie flexion reflex generation (SMR) and the rostral transmission of pain information (VDS and VAD) have similar thresholds of inhibition to spinopetal monoaminergic projections.

Afferent Pathways↗