A novel treatment for chronic pancreatitis

Background Hereditary pancreatitis is an important cause of chronic pancreatitis, which may result in endocrine and exocrine failure. This may necessitate simultaneous pancreas and kidney transplant (SPK). Bladder drainage of the exocrine secretions may cause problems. Aim To report one such case and its surgical correction. Methods A 20-year-old male with insulin-dependent diabetes mellitus secondary to idiopathic chronic pancreatitis had a SPK with bladder drainage. Urological and metabolic complications secondary to the drainage of pancreatic secretions, rich in proteolytic enzymes required convertion from bladder to enteric drainage. Results He was able to discontinue his pancreatic enzyme supplements, ceased to have steatorrhoea and gained weight. He was referred to the €pean Registry of Hereditary Pancreatitis and Familial Pancreatic Cancer (€PAC), hereditary pancreatitis was confirmed by genetic analysis. Conclusion Enteric-drained pancreas transplantation is a successful treatment for exocrine as well as endocrine pancreatic failure and should be considered as a treatment option in patients with chronic pancreatitis.     

Adhesion of Pseudomonas aeruginosa ocular isolates to mucin

The purpose of this study was to compare the adhesion of Pseudomonas aeruginosa ocular isolates to mucin. An adhesion assay was developed using biotin‐labelled P. aeruginosa strains (two corneal ulcer, two acute red eye, one asymptomatic and one standard strains) incubated with porcine gastric mucin immobilized on a nitrocellulose membrane. The adhesion was semiquantified using densitometry. The results showed that all P. aeruginosa strains tested were able to adhere to mucin to various extents with three strains (one corneal ulcer, one acute red eye, one asymptomatic) binding significantly greater than the negative control (P < 0.1). Results suggest that ocular strains of P. aeruginosa strains differ in their adhesion to mucin but this did not correlate with the pathogenic origin of the strain. It is concluded that the adhesion of P. aeruginosa strains to mucin alone may not be a principal determinant of pathogenesis but may be a contributing factor along with other bacterial virulence traits.     

Rapid mobilization of hematopoietic progenitor cells in rhesus monkeys by a single intravenous injection of interleukin-8

Interleukin-8 (IL-8) is a chemoattractant cytokine involved in chemotaxis and activation of neutrophils. Because in vivo administration of IL-8 induces mobilization of hematopoietic stem cells in mice, we assessed the mobilizing properties of IL-8 in rhesus monkeys. Recombinant human IL-8 was administered as a single intravenous injection at doses of 10, 30, and 100 micrograms/kg to rhesus monkeys (age, 2 to 3 years; weight, 2.5 to 4.5 kg). Venous blood samples were obtained at time intervals ranging from 1 to 480 minutes after IL-8 administration. Cell counts, colony-forming unit-Mix assays, and fluorescence-activated cell sorter analysis were performed. Plasma was harvested to assess IL-8 levels. A time-controlled bolus intravenous injection of 100 micrograms IL-8 per kilogram of body weight resulted in peak IL-8 plasma levels up to 5 micrograms/mL. The calculated half-time life of free IL-8 was 9.9 +/- 2.2 minutes. IL-8 injection resulted in instant neutropenia that was due to pulmonary sequestration, as shown using 99mTc-labeled leukocytes. Within 30 minutes after IL-8 injection, neutrophilia developed with counts up to 10-fold greater than baseline levels. The numbers of hematopoietic progenitor cells (HPCs) increased from 45 +/- 48/mL to 1,382 +/- 599/mL of blood at 30 minutes after injection of 100 micrograms IL-8 per kilogram of bodyweight (mean +/- SD, n = 8). Individual animals showed 10- to 100-fold increase in numbers of circulating HPCs that returned to almost pretreatment values (92 +/- 52 CFU/mL) at 240 minutes after the injection of IL-8. Immunophenotyping showed no significant changes in lymphocyte (sub)populations. A second bolus injection of IL-8 with an interval of 72 hours resulted in similar numbers of mobilized stem cells as observed after the first injection, showing that no tachyphylaxis had occurred. We conclude that IL-8 induces mobilization of HPCs from the bone marrow of rhesus monkeys in a rapid and reproducible fashion. Therefore, IL-8 may be a potentially useful cytokine in the setting of blood stem cell transplantation.     

Platelet glycoproteins IIb and IIIa as a calcium channel in liposomes

Human platelet membrane glycoproteins IIb and IIIa (GPIIb and IIIa) were incorporated into phospholipid vesicles by the reverse-phase technique to assess the ability of GPIIb and IIIa to function as a Ca2+ channel. Movement of Ca2+ across the lipid bilayer was quantitated by injection of proteoliposomes with encapsulated Fura-2 into Ca2+ buffers and measurement of Fura-2 fluorescence as an indicator of Ca2+ influx. Reciprocally, to assess the function of proteins in an inside-out orientation, Ca2+-loaded vesicles were injected into Ca2+-free buffer and Ca2+ efflux monitored by a calcium electrode. Incorporation of the IIb-IIIa complex produced significant facilitation of Ca2+ movement across the lipid bilayer. No net transmembrane Ca2+ movement was seen with dissociated IIb and IIIa. Movement of Ca2+ was proportional to the transmembrane Ca2+ gradient. Ca2+ movement into the vesicles was inversely proportional to extravesicular NaCl from 25 to 150 mmol/L, analogous to several studies in the intact platelet. Adenosine triphosphate had no effect on Ca2+ movement into or out of the vesicles. Specific inhibition of a Ca2+ shift into the vesicles was seen with M148, a monoclonal antibody to IIb/IIIa, while no inhibition was observed with a panel of other anti-IIb/IIIa monoclonal antibodies. This suggests that a specific site on the complex or orientation of the complex is essential for calcium channel function. These data demonstrate that the GPIIb/IIIa complex can serve as a passive Ca2+ channel across a phospholipid bilayer and has the potential to play a role in Ca2+ flux across the platelet plasma membrane.     

Implementation of a Standardized Discharge Time-out Process to Reduce Prescribing Errors at Discharge

Background:

To reduce prescribing errors occurring on discharge from the hospital, a standardized discharge time-out process was implemented on a general medicine service at Wake Forest Baptist Medical Center. In the time-out process, the multidisciplinary care team reviewed the patient’s medical records together to determine the optimal discharge medication regimen. This regimen was recorded on a time-out form and then was used to develop the patient’s discharge documents.

Objective:

To evaluate the impact of a standardized discharge time-out process on prescribing errors that occur as patients are discharged from a general medicine service.

Methods:

The medical records of all patients discharged from a general medicine service during 60-day periods before (“pre-group”) and after (“post-group”) implementation of a standardized discharge time-out process were retrospectively reviewed by an internal medicine physician to determine the presence of discharge prescribing errors.

Results:

There were 142 and 124 evaluable patients in the pre- and post-groups, respectively. Compliance with the time-out process was 93% in the post-group. At least 1 prescribing error was detected in 49 (34.5%) of the discharges in the pre-group and 17 (13%) of the discharges in the post-group (P < .0001). All of the errors noted in the post-group occurred in discharges in which a clinical pharmacist was not involved.

Conclusions:

A multidisciplinary, standardized discharge time-out process was associated with a dramatic reduction in prescribing errors when patients were discharged from a general medicine service. The time-out process is one strategy to improve patient safety at hospital discharge.     

Cat-301 immunoreactivity in the lateral geniculate nucleus and visual cortex of the strabismic amblyopic cat

Purpose: It was investigated whether alterations in neuronal structure and function occasioned by strabismic amblyopia also may be reflected in alterations in the expression on Y type neurons of a Cat-301 antibody sensitive antigen in the lateral geniculate nucleus (LGN) and cortex of our cat model of strabismic amblyopia. Methods/Results: The percentage of positively labelled cells was reduced in LGN laminae that received input from the deviated eye in strabismic amblyopic cats compared with normal cats. In the strabismic cortex, the density of immunopositive neurons was significantly reduced compared with normal, the effect being most pronounced in layer IV Conclusions: Despite previous physiological recordings indicating a decrease in X-cell associated acuity in strabismic amblyopia, the present findings imply that the changes in the early visual experience occasioned by strabismus also produce specific molecular changes in theY neuronal class.     

A reversible monoamine oxidase inhibitor, toloxatone: Structural and electronic properties

Toloxatone is a reversible MAO_A-inhibitor, marketed as antidepressant (Humoryl^®), with an original chemical structure. It differs from first generation irreversible MAOIs, known to induce covalent bonds with the enzyme active site. In order to understand the mechanism of the reversible inactivation of the MAO, as a first step, a detailed structural and electronic analysis was undertaken. An X-ray diffraction-crystallographic study showed that toloxatone is a planar molecule and brought to light hydrogen bonds and π-π interactions. MO calculations confirmed the planar structure as energetically favoured. Electronic analysis demonstrated a delocalization of both ring systems. The combined results give evidence for the potential of toloxatone to participate in reversible, long distance interactions with an appropriate partner.     

Occupational stress in migraine is weekend headache a myth or reality?

To determine whether or not the frequency of migraine attacks increased at weekends in employed patients and if so, whether or not this was related to the type of migraine, 35 female patients prospectively recorded the presence or absence of migraine attacks daily over a six-week period. They were also asked to estimate the frequency with which emotional factors predisposed to their migraine attacks and to provide details of their occupation. A diagnosis of common (migraine without aura) or classical migraine (migraine with aura) was made according to both the criteria of the Ad Hoc Committee on the Classification of Headache and those of the International Headache Society. Eleven percent and 6% of patients, respectively, felt that emotional factors "usually" or "always" predisposed to migraine attacks. There was no significant increase in the frequency of migraine attacks at weekends in either the total group or in the employed patients. Similarly, the type of migraine made no difference to the results. There was therefore no evidence for a delayed onset of migraine at weekends related to the weekday stress of employment.