Bile duct obstruction: radiologic evaluation of level, cause, and tumor resectability

In a prospective study of 65 patients with bile duct obstruction, various radiologic modalities were compared for their capability to demonstrate the level and cause of obstruction and to indicate accurately tumor resectability. Ultrasound (US) was performed in 65 patients, computed tomography (CT) in 51, direct cholangiography (DC) in 57, and angiography in 35. The level of obstruction was correctly indicated by US in 95% of patients and by CT in 90%, and the cause was correctly indicated by US in 88%, by CT in 63%, and by DC in 89%. In predicting tumor resectability, US was correct in 71% of patients, compared with 42% for CT, 58% for DC, and 25% for angiography. US therefore appears to be the single most useful modality in the evaluation bile duct obstruction.     

Diagnosis and treatment of simple acid-base disorders.

The ability to diagnose and treat acid-base disorders is an important component in the practice of the nutrition support clinician. A complete understanding of the basic principles of metabolic and respiratory disorders allows the practitioner to formulate educated decisions regarding fluids, parenteral nutrition salts, and the management of electrolytes. This review will discuss the diagnosis and treatment of common metabolic and respiratory disorders encountered in nutrition support practice.     

Hypocalcaemia in severe meningococcal infections

AIM: To determine the incidence of hypocalcaemia in critically ill children with meningococcal disease. METHODS: In a prospective cohort study, 70 of 80 patients admitted consecutively with a clinical diagnosis of meningococcal disease to intensive care had measurements of total and ionised calcium on admission. Parathormone and calcitonin were measured in a proportion of the children. RESULTS: Total and ionised calcium concentrations were low in 70% of the children. There was a weak relation of calcium concentration to the volume of blood derived colloid which had been given, but a good relation to disease severity, where sicker children had lower calcium concentrations. Although the parathormone concentration was higher in children with lower calcium concentrations, some children had low ionised calcium concentrations, without an increase of parathormone concentration. Serum calcitonin concentration was not related to calcium concentrations. CONCLUSION: Hypocalcaemia is common in meningococcal disease.     

Monoclonal antibody to human high-molecular-weight kininogen recognizes its prekallikrein binding site and inhibits its coagulant activity

We developed a mouse monoclonal antibody (MoAb 115-21) to human high- molecular-weight kininogen (HK) that recognizes its prekallikrein binding site (residues 565 through 595 of HK). The corresponding synthesized 31-amino acid peptide (peptide IV) was recently shown to retain native HK's prekallikrein binding property. The same peptide bound factor XI also, although less avidly. Our MoAb recognizes purified HK, peptide IV, and the light chain moiety of HK (where the peptide IV resides), as shown by enzyme-linked immunosorbent assay (ELISA) and Western blotting experiments. The apparent dissociation constant for the HK and MoAb 115-21 interaction was 2.2 nmol/L. It does not recognize low-molecular-weight kininogen (LK) with which HK shares its heavy chain moiety or any antigens in human plasma congenitally deficient in kininogens. The binding of MoAb 115-21 to purified light chain of HK was competitively inhibited by peptide IV. In addition, the antibody inhibits HK-dependent clotting activity of normal human plasma and dextran sulfate-mediated activation of prekallikrein in plasma and retards cleavage of HK in normal plasma after contact activation with dextran sulfate. Also, purified Fab fragments of MoAb 115-21 inhibited the HK-dependent coagulant activity and dextran sulfate-mediated prekallikrein activation in normal plasma. Since the kd for HK-MoAb 115- 21 interaction is ten times lower than that of HK-prekallikrein, our data suggest that binding of MoAb 115-21 to HK's peptide IV site increases the free prekallikrein concentration in plasma and thus results in the decreased efficiency of factor XIIa-mediated activation of prekallikrein. Decreased levels of kallikrein thus formed may be responsible for the inhibition of HK-dependent clotting activity and the decrease in rate and extent of HK cleavage in normal plasma on contact activation with dextran sulfate. MoAb 115-21 may thus prove very useful, especially with its high affinity for HK, in further delineation of the role of HK and prekallikrein in contact activation and kinin-related human pathology.     

A new test of object decision: 2D silhouettes featuring a minimal view.

A new test of object decision in which a minimal view 2D silhouette of an object is presented together with 3 nonsense shapes has been administered to a consecutive series of patients with right and left hemisphere lesions. There was a significant deficit in the right hemisphere lesion group as compared with the left hemisphere group. It is concluded that this object decision test provides a measure of the integrity of pre-semantic perceptual processing systems.     

Optimising antiemesis in cancer chemotherapy: efficacy of continuous versus intermittent infusion of high dose metoclopramide in emesis induced by cisplatin

Thirty three untreated patients being given cisplatin received metoclopramide (7 mg/kg) for antiemesis by either continuous or intermittent infusion in a random order. Each patient received intravenous dexamethasone in addition. High pressure liquid chromatography was used to measure plasma concentrations of metoclopramide. The two regimens were evaluated for antiemetic efficacy and the incidence of side effects. The intermittent metoclopramide regimen resulted in peak and trough plasma concentrations of metoclopramide with accumulation at eight hours, while the loading dose and continuous infusion resulted in mean plasma concentrations greater than 0.85 micrograms/ml (2.8 mumol/l) throughout the eight hour period. The continuous infusion was associated with a significant improvement in nausea and vomiting and reduction in diarrhoea. Major control of emesis (two episodes or fewer) was achieved in 27 patients receiving continuous metoclopramide compared with 18 receiving intermittent metoclopramide.     

Translational development of splice-modifying antisense oligomers

Introduction: Antisense nucleic acid analogues can interact with pre-mRNA motifs and influence exon or splice site selection and thereby alter gene expression. Design of antisense molecules to target specific motifs can result in either exon exclusion or exon inclusion during splicing. Novel drugs exploiting the antisense concept are targeting rare, life-limiting diseases; however, the potential exists to treat a wide range of conditions by antisense-mediated splice intervention.

Areas covered: In this review, the authors discuss the clinical translation of novel molecular therapeutics to address the fatal neuromuscular disorders Duchenne muscular dystrophy and spinal muscular atrophy. The review also highlights difficulties posed by issues pertaining to restricted participant numbers, variable phenotype and disease progression, and the identification and validation of study endpoints.

Expert opinion: Translation of novel therapeutics for Duchenne muscular dystrophy and spinal muscular atrophy has been greatly advanced by multidisciplinary research, academic-industry partnerships and in particular, the engagement and support of the patient community. Sponsors, supporters and regulators are cooperating to deliver new drugs and identify and define meaningful outcome measures. Non-conventional and adaptive trial design could be particularly suited to clinical evaluation of novel therapeutics and strategies to treat serious, rare diseases that may be problematic to study using more conventional clinical trial structures.     

Care related pain in hospitalized patients: A cross‐sectional study

Context: Care‐related pain includes pain occurring during transportation, movement, diagnostic imaging, physical examination, or treatment. Its prevalence has never been assessed in a large adult inpatient population. Objective: To identify the procedures likely to induce or increase pain in hospital patients, attempting to separate the most painful from those reported as most frequently inducing pain. Design: A single‐day cross‐sectional survey conducted in two large French teaching hospitals, including all hospitalized patients, free of communication problems. One third was randomly selected and interviewed about the painful episodes that had occurred or were associated with the procedures performed during the previous two weeks. Patients were interviewed using a structured questionnaire. Results: Six‐hundred‐eighty‐four patients were randomly selected. Six‐hundred‐seventy‐one painful events were reported in 55% of the patients, with an average of 1.8events/patient. Fifty‐two percent of the painful events were associated with procedures performed by non‐medical staff; 38% of the painful episodes occurred during procedures involving vascular puncture and 24% during patients’ mobilization. In 57% of painful procedures, pain was rated as severe or extremely severe. The most painful procedures were invasive procedures, other than vascular and non vascular punctures (74% of severe and extremely severe painful episodes). Maximum pain intensity was rated higher for procedures that were repeated than for those experienced only once (62% versus 53%, p=0.02). Conclusion: This survey gives new insight into our daily practice. Proper management of care‐related pain should be a major concern of all hospital staff to improve the quality of our health care.     

Sudden infant death syndrome and diphtheria-tetanus-pertussis-poliomyelitis vaccination status

Summary— Because diphtheria, tetanus, pertussis and poliomyelitis vaccine is routinely given during the period of highest incidence of sudden infant death syndrome (SIDS), we carried out a retrospective case-control study to assess whether such vaccination increased the risk of SIDS. The vaccination status of 118 SIDS and 332 control children, matched for sex, date of birth and age of the victims at death, was compared: the victims of SIDS were not significantly more often vaccinated than control children, the odds ratio was estimated at 1.9 with a 95% confidence interval from 0.9 to 3.9. There was a statistical difference between vaccination status of SIDS cases and controls aged less than three months. Nine percent of SIDS cases under 3 months had been vaccinated whereas the matched controls had not. In our study DTCP vaccination was not a risk factor for SIDS; although more of the SIDS infants less than 3 months of age had been vaccinated. This result however, concerns only one subgroup of the population studied and needs to be confirmed with another study of only SIDS infants less than 3 months of age, because DTCP vaccination was not a risk factor for SIDS when considering the total sample of the study.