The addition of insulin to home parenteral nutrition for the control of hyperglycaemia: A case series.

There is little data on the safety or efficacy of insulin added to parenteral nutrition in the homecare setting. We report the use of this route of insulin administration in a series of 4 patients spanning 39 patient years in which it appeared effective, safe and well tolerated.

Cytomegalovirus Infection and Rates of Antiviral Resistance Following Intestinal and Multivisceral Transplantation.

BACKGROUND: Cytomegalovirus (CMV) disease is a common and clinically significant complication following intestinal or multivisceral transplantation. CMV disease is more common in cases of serologic mismatch between donor and recipient. Though in some cases it may be asymptomatic, in the immunosuppressed population it often manifests with evidence of systemic infection or end-organ disease. METHODS: We conducted a retrospective review of all patients undergoing intestinal or multivisceral transplantation over 8 years at our institution. RESULTS: Forty-eight transplantations were performed, with 40% of the patients (19/48) having ≥1 episode of CMV viremia, which rose to 90% in the "donor-positive, recipient-negative" (DPRN) serologic mismatch group. The median time to 1st episode following transplantation was 22.3 weeks (range, 1-78) and median duration of each episode was 4.9 weeks (range, 1.6-37.4). Six of the 19 viremic patients (31.6%) developed virologic resistance with 4 of these occurring in the DPRN group. Four of the 6 patients with drug-resistant CMV died with CMV viremia. All patients with drug resistance acquired ganciclovir resistance; these patients were more challenging to manage with second-line toxicity-limited treatments, including foscarnet, cidofovir, and leflunomide. CMV immunoglobulin has been used and we briefly discuss the use of CMV-specific adoptive T-lymphocyte transfer in the management of 1 case. CONCLUSIONS: Post-transplantation CMV disease continues to be challenging to manage, and there is little consensus on optimal management strategies in this patient group, with a significant requirement for novel therapies; these may be pharmacologic or cell based. Extensive multidisciplinary discussion is important for most cases, but particularly for those patients who acquire virologic resistance.

Optimising delivery of care in coeliac disease - comparison of the benefits of repeat biopsy and serological follow-up.

BACKGROUND: The majority of deleterious health consequences of coeliac disease (CD) are most likely to be secondary to intestinal inflammation; hence, mucosal recovery is a desirable goal of therapy. Follow-up in CD is controversial and serological response is often used as a surrogate for histological recovery. AIMS: To inform the clinical management of CD using comparative serological and histological data from a biopsy-driven pathway of care. METHODS: A retrospective analysis of the Cambridge Coeliac Clinic database of 595 patients routinely followed up by biopsy and serology. RESULTS: Paired biopsy results were available for 391 patients (15% seronegative). Persisting villous atrophy (VA) occurred in 182 patients (47%). The sensitivity of anti-tissue transglutaminase (TTG) antibody for ongoing VA was only 43.6%. Information on dietetic management and further biopsy to assess response was available for 94 initially unresponsive patients, in whom targeted dietetic intervention by removal of identified gluten sources or avoidance of trace amounts of gluten led to resolution of persistent VA in 50%. The effects of institution of a formal care pathway are analysed in 298 patients. Discharge to primary care and clinical management was facilitated by the information derived from repeat biopsy. CONCLUSIONS: Serology appears to be a poor surrogate marker for mucosal recovery on a gluten-free diet; dietary assessment fails to identify a potential gluten source in many patients with ongoing villous atrophy. The benefits of re-biopsy on diet include stratification of patients with coeliac disease suitable for early discharge from secondary care or those requiring more intensive clinical management.

Cambridge-Miami score for intestinal transplantation preoperative risk assessment: initial development and validation.

INTRODUCTION: Preoperative quantification of survival after transplantation would assist in assessing patients. We have developed a preliminary preoperative scoring system, called the Cambridge-Miami (CaMi) score, for transplantation of the small intestine either alone or as a composite graft. METHODS: The score combines putative risk factors for early-, medium-, and long-term survival. Factors included were loss of venous access and impairment of organs or systems not corrected by transplantation. Each factor was scored 0-3. A score of 3 indicated comorbidity approaching a contraindication for transplantation, that which might lead to but was not currently an adverse risk factor scored 1, and that presenting a definite but moderate increase in risk scored 2. The preoperative scores of 20 patients who had received intestinal transplants either isolated or as part of a cluster graft, who had either been followed up postoperatively for at least 10 years, or died within 10 years were compared with their survivals. RESULTS: Postoperative survival and CaMi score inversely correlated when analysed using Spearman test (r(s) = -0.82; P = .0001). A score of <3 associated with survival > or =3 years (12/12 patients) and >3 with survival of <6 months (4/4). Patient Kaplan-Meier (KM) survival curves for patients grouped according to CaMi score became significantly different from group 0 to group 3. Using this as a threshold score patients grouped as either >2 or <3 had significantly different survival rates (log-rank; P = .0001), KM median survival hazard ratio (HR) = 6, and rate of death KM HR = 5. Receiver-operator characteristics indicate a high degree of accuracy for prediction of death with an area under the curve (C statistic) at 3 years of 0.98, at 5 years of 0.82, and at 10 years of 0.65. CONCLUSION: This initial validation suggested that the preoperative CaMi score predicted postoperative survival.

Ischaemic enterocolitis complicating idiopathic dysautonomia.

A previously fit 23 year old adult male who presented with a sudden onset of profound autonomic neuropathy, for which no cause could be found, is described. The patient subsequently developed ischaemic enterocolitis that ultimately necessitated colectomy and subtotal enterectomy. Potential neural and humoral mechanisms are discussed.

The unique challenge of small intestinal transplantation.

The past decade has seen major organ transplantation become routine. Although the small intestine can now be successfully transplanted alone or with other organs, the operation presents unique challenges which are reflected in lower survival rates compared with transplantation of other organs. This review presents the development of clinical small intestinal transplantation and its current status.

Effect of "mood that day" on pharmacists' job and career satisfaction.

We speculated that mood would affect responses to global measures of job and career satisfaction. We randomly selected 692 pharmacists from the Iowa Board of Pharmacy Examiners' mailing list. After two follow-up mailings, 389 questionnaires were received for a usable rate of 56.9%. "Good day" pharmacists were more satisfied with their jobs and careers than "typical day" pharmacists, supporting the contention that global satisfaction indicators reflect affective satisfaction.

Genetic analysis of Escherichia coli from porcine postweaning diarrhoea.

A total of 79 Australian isolates of beta-haemolytic Escherichia coli from cases of porcine postweaning diarrhoea (PWD), and 18 isolates of serotype O 149:K91:K88 (F4) from unweaned pigs from Australia, Indonesia and Denmark, were examined by multilocus enzyme electrophoresis. These were divided into 57 electrophoretic types (ETs), with an overall mean genetic diversity per enzyme locus of 0.466. This value closely resembled that previously recorded for the whole species. Not only was the collection diverse, but there was considerable genetic heterogeneity amongst PWD isolates of the same serogroup. Isolates from serogroups O 8 and O 138 were most varied, whilst many from serogroups O 141 and O 149 were more closely related. In contrast, the isolates from the unweaned pigs all belonged to only one ET.

Genetic analysis of Actinobacillus pleuropneumoniae, and comparison with Haemophilus spp. Taxon "minor group" and Taxon C.

The genetic diversity among 52 field isolates, mainly from Australia, and 15 reference strains of Actinobacillus pleuropneumoniae was examined using multilocus enzyme electrophoresis. Thirty three electrophoretic types (ETs) were recognised, with a mean genetic diversity per locus of 0.312. Australian strains of serovars 1, 2, 5 and 7 belonged to the same clonal lines as strains of these serovars in other countries, but distinct clones of serovars 3, 7, 11 and 12 were also identified. The type strains of serovars 1, 9 and 11 were placed in the same ET. Strains of A. pleuropneumoniae biovar 2 were closely related to biovar 1 strains. Twenty three isolates which did not react with the typing sera or could not be assigned to a single serovar were divided into seven clonal groups. Five strains of Haemophilus sp. Taxon "minor group" which were included in the study were distinct from A. pleuropneumoniae, and were diverse, being divided into at least two major genetic groupings. Two strains of Haemophilus sp. Taxon C were placed in another distinct ET.

Clonal analysis of Escherichia coli of serogroups O9, O20, and O101 isolated from Australian pigs with neonatal diarrhea.

The genetic diversity of 87 isolates of Escherichia coli recovered from Australian pigs with neonatal diarrhea was examined by multilocus enzyme electrophoresis. The isolates were of serogroups O9, O20, and O101, and although most isolates lacked K88(F4), K99(F5), 987P(F6), and F41 fimbriae, they were considered to be involved in the etiology of the diarrhea. The isolates were extremely diverse, considering their origin from a single pathological condition in one country. There were estimated to be 18, 16, and 12 clones of the three respective serogroups in the collection, with serogroup diversities of 0.387, 0.448, and 0.275, respectively. Comparison with the results previously obtained for isolates from piglets with postweaning diarrhea suggested that bacteria from piglets with these two conditions did not come from any particular common genetic background. The overall genetic diversity for the combined collection was the same as that reported by others for representative isolates selected from throughout the species (0.47). The current results indicate that if isolates of these O groups are involved in porcine diarrhea, their pathogenicity is directly linked to their O somatic antigen type and is not simply due to the wide distribution of a small number of virulent clones.

Physiologic response of stress and aminoglycoside clearance in critically ill patients.

OBJECTIVE: To examine the relationships between aminoglycoside clearance and physiologic parameters associated with the physiologic response to injury. DESIGN: Cross-sectional study of surgical patients receiving aminoglycoside pharmacokinetic monitoring and parenteral nutritional support. SETTING: An adult surgical ICU. PATIENTS: Fifty-four surgical/trauma patients who had Gram-negative sepsis. INTERVENTIONS: Measurements of the physiologic stress response to injury were associated with aminoglycoside clearance in 54 surgical/trauma patients who had Gram-negative sepsis. Measurements used to estimate the magnitude of the stress response included a 24-hr urinary urea nitrogen excretion, blood urea nitrogen, peak temperature, serum albumin, bilirubin, and transferrin concentrations. MEASUREMENTS AND MAIN RESULTS: Mean drug clearance rate (4.4 +/- 2.5 [SD] L/hr) was related to the physiologic measurements using correlation and regression techniques. Collectively, all physiologic indices (utilized) explained 59% of the variance in drug clearance (p < .001), an amount similar to the variance explained by creatinine clearance alone (53%). When all six physiologic measurements were included into a multiple regression model that included creatinine clearance, the total variance explained increased to 73%. CONCLUSIONS: Along with renal function estimates, the physiologic response to stress should be considered when treating critically ill patients with aminoglycosides and other, similar, renally eliminated drugs.

Specific heart granules and natriuretic peptide in the developing myocardium of fetal and neonatal rats and hamsters.

The ontogenesis of specific heart granules and of the related natriuretic peptide activity in heart muscle was studied in fetal and neonatal rats and golden hamsters by ultrastructural analysis including immunogold labelling for ANP-28 and by radioimmunoassay. In both species, immunoreactive granules first appear in the myocardial sleeve of the embryonic heart tube during the looping stages which precede chamber formation and the peptide becomes detectable by radioimmunoassay two or three days later by which time the chambers are identifiable. Granule density and ANP concentration in the rat are higher than in the hamster at all stages of development. Almost all atrial myocytes express ANP in fetal hearts whereas, in the ventricular wall, cells containing immunoreactive granules are scattered. The density of granules in atrial myocytes increases during further stages of fetal and neonatal development, while it decreases markedly even in those ventricular myocytes which are immunoreactive. Changes in the ultrastructural appearance of ventricular SHG suggest that the mode of production of ANP changes in ventricular myocytes after birth but does not change in atrial cells. There is no correlation between the distribution of immunoreactive ventricular myocytes and that of the conducting system. In both species, the concentration of ANP in the atrial well is higher than ventricular levels from the outset and the disparity becomes exaggerated with development till, in six months old adult animals, the atrial to ventricular concentration ratio is about 3 x 10(3):1 in the rat and 1.5 x 10(3): 1 in the hamster. In the hamster, a distinct gradient of ANP concentration between the right and left atria is already established in the early fetal period and it becomes enhanced in the neonatal period. In the rat, however, a slight difference becomes discernible only after birth.

Immunocytochemical localization of natriuretic peptide sequences in the human right auricle.

Samples of the right auricle from ten patients undergoing surgery were processed for the immunocytochemical localization of atrial natriuretic peptide sequences (ANP-28 and the 26-92, 26-55 and 56-92 segments of the prohormone) using commercially available antisera and labelled with protein-A gold. Single antigen and double antigen (ANP-28 and one other) detection procedures were employed. The results show that there is no correlation between the ultrastructural appearance of specific heart granules and the molecular form of their ANP content. All specific granule types contain the full range of prohormone sequences. D granules are few and appear to be recently budded from the Golgi apparatus, whereas A and B profiles comprise the majority of specific granules and are more widely distributed in the cytoplasm. In the Golgi elements, peptide immunoreactivity is principally associated with the membrane but a proportion lies within the of vesicles and becomes concentrated within the core of developing granules. The density of ANP-immunoreactivity is higher in A profiles than in the other types. Multivesicular bodies are not intrinsically immunoreactive for ANP, nor are the numerous synaptic nerve profiles which are present in atrial muscle. In two elderly patients the basal lamina of myocytes was heavily labelled for ANP.

The diagnosis and management of post traumatic syringomyelia.

We have reviewed 21 cases with the clinical diagnosis of Post Traumatic Syringomyelia (P.T.S.). Fifteen of these cases had proven syrinx formation on Contrast Computed Tomography (C.C.T.) and the other 6 had obviously abnormal cords. A much earlier onset of P.T.C.M. was found in complete spinal injuries than in incomplete ones. We have discussed the technique of contrast computed tomography used at this hospital, its value in the diagnosis of this condition and its ability to define actual spinal cord structure. Most cases (91%) benefitted from surgery and several had marked sensory improvement, which previously has been described as unusual. Syringo-cisternal shunting, a new technique for the drainage of cervical and upper thoracic syrinxes is described. A theory is proposed to explain why, in some patients with classical presentations of P.T.S., no syrinx was found on C.C.T., although abnormal cords were found in all cases. It is felt that these abnormal areas of spinal cord are responsible for the presenting symptomatology and may be precursors of syrinxes.