Evaluation of the impact of pharmacist-led therapeutic tutorials on third-year medical students' knowledge and understanding of drugs used in clinical practice.

Three cohorts of third-year medical students on clinical placements were compared (n = 48). One cohort (study group, n = 18) attended a series of therapeutic tutorials led by the pharmacist. The other two cohorts (control group A and control group B) did not.

Factor XIII deficiency causing mutation, Ser295Arg, in exon 7 of the factor XIIIA gene.

Inherited factor XIII (FXIII) deficiency is an autosomal recessive disorder which results in a serious bleeding diathesis, problems with wound healing and a very high risk of recurrent miscarriage in deficient females. We have analysed the molecular basis of factor XIII deficiency in two patients and their parents, who originate from the North of Pakistan. Four sequence changes were identified: an AGC-->AGG (Ser-->Arg) FXIII deficiency-causing mutation in codon 295; G-->A at position -246 upstream of exon 1; T-->C and C-->T at positions -23 and -24, respectively, in intron 9.

Splicing and missense mutations in the human FXIIIA gene causing FXIII deficiency: effects of these mutations on FXIIIA RNA processing and protein structure.

We have investigated the molecular basis of factor XIII (FXIII) deficiency in a family from the north-west region of the U.K. and identified two sequence changes in the FXIII subunit A (FXIIIA) gene.

New splicing mutations in the human factor XIIIA gene, each producing multiple mutant transcripts of varying abundance.

Coagulation factor XIII, a transglutaminase which stabilises blood clots by covalently cross-linking fibrin, is essential for normal haemostasis. FXIII deficiency results in a life-long bleeding disorder with added complications in wound healing and tissue repair. Sequence changes in the human FXIIIA gene, largely missense mutations, are primarily responsible for inherited FXIII deficiency.

Identification of a large deletion, spanning exons 4 to 11 of the human factor XIIIA gene, in a factor XIII-deficient family.

Inherited deficiency of factor XIIIA subunit (FXIIIA) is an autosomal recessive disorder that is characterized by a life-long bleeding tendency and complications in wound healing. Molecular genetic studies have shown the deficiency can be due to small sequence changes within the FXIIIA gene, such as point mutations or microdeletions. On molecular analysis of the FXIIIA gene in an FXIII-deficient patient, of United Kingdom origin, we identified a putative homozygous missense mutation, Arg408Gln.

Molecular basis of inherited factor XIII deficiency: identification of multiple mutations provides insights into protein function.

Factor XIII (FXIII) is a zymogen essential for normal haemostasis. In inherited FXIII deficiency the majority of cases show absence of the FXIIIa subunit. Molecular analysis of PCR-amplified FXIIIa subunit exonic regions, and of RT-PCR amplified cDNA from six patients with FXIIIa subunit deficiency, from five unrelated families, has revealed 10 sequence changes: three mutations resulting in abnormal splicing of pre-mRNA, one nonsense mutation, one deletion/insertion change, three point mutations producing Val34Leu, Asn60Lys and Arg408Gln changes, and two silent mutations.

Pharmacokinetics and tolerability of factor XIII concentrates prepared from human placenta or plasma: a crossover randomised study.

The pharmacokinetics and tolerability of factor XIII (FXIII) from plasma were compared with those of FXIII from placenta in a randomised, double-blind, crossover study involving 13 patients with congenital FXIII deficiency. Both FXIII activity and FXIII antigen were monitored. No difference was seen in the mean half-lives of the two preparations (9.

Mutations causing coagulation factor XIII subunit A deficiency: characterization of the mutant proteins after expression in yeast.

We identified the mutations causing factor XIII A subunit deficiency in two families. Two distinct mutations were identified in the S family: the nonsense mutation Tyr 441-->stop in exon 11, inherited through the paternal line, and the missense mutation Asn 60-->Lys in exon 3, inherited through the maternal line. Two members of the J family were heterozygous for the previously described type 3 A subunit.

Factor XIII: inherited and acquired deficiency.

Factor XIII (XIII), an enzyme found in plasma (present as a pro-enzyme), platelets and monocytes, is essential for normal haemostasis. It may also have a role to play in the processes of wound healing and tissue repair. Inherited XIII deficiency results in a life-long, severe bleeding diathesis which, if untreated, carries a very high risk of death in early life from intracranial bleeding.

Identification of a point mutation in factor XIII A subunit deficiency.

Oligonucleotide primers have been designed for the amplification of all 15 exons of the human coagulation factor XIII A subunit gene. Each exon and its intron flanking regions has been amplified and sequenced from a patient with severe A subunit deficiency. A single G to A transition in the last base of exon 14 has been identified in the homozygous proband and in his heterozygous parents.

Palliative removal of a giant polypoid 'carcinosarcoma' of the oesophagus by YAG laser photocoagulation of the tumour stalk.

Dysphagia in a 79 year old lady was caused by a giant polypoid tumour in mid-oesophagus. Surgery was not appropriate. Shrinkage of the tumour and its eventual detachment were achieved by stopping its blood supply by YAG laser photocoagulation of the tumour stalk.

Changes in intracranial pressure during machine and continuous haemofiltration.

Nine consecutive patients with both fulminant hepatic failure and acute oliguric renal failure were treated either by daily machine haemofiltration (MHF), or by continuous arterio-venous haemofiltration (CAVHF). Six patients received a total of twenty treatments by MHF and four CAVHF, mean duration of treatment 56 hours, range 24-160. Intracranial pressure (ICP) was measured using a subdural catheter.

Changes in intracranial pressure during haemofiltration in oliguric patients with grade IV hepatic encephalopathy.

Seven consecutive patients with grade IV hepatic encephalopathy, due to fulminant hepatic failure complicated by oliguric renal failure were allocated at random to treatment with daily machine haemofiltration (MHF) or continuous arteriovenous haemofiltration (CAVHF). Intracranial pressure (ICP) was continuously monitored using a subdural catheter. Four patients received 17 treatments by MHF, and ICP increased from 8.

The prognosis of elderly subjects with oesophageal varices.

Discharge survival following variceal bleeding was similar in 27 elderly subjects, aged 65-93 years, and 125 younger subjects, aged under 65 (63% versus 70%, p greater than 0.05). Of 39 elderly subjects with varices which were not bleeding on admission, 82% were discharged alive but subsequent mortality was higher and long-term survival was similar (median 1 year) on life-table analysis.

Comparison of the effectiveness of midazolam and diazepam in lipid emulsion as sedation during upper gastrointestinal endoscopy.

In a study of 101 patients undergoing upper gastrointestinal endoscopy, 90% of patients had complete amnesia for the procedure after intravenous midazolam (average dose 10 mg), but only 61% had complete amnesia after intravenous diazepam in lipid emulsion (average dose 18.4 mg) (P = 0.0006).

Raised parathyroid hormone levels in the milk alkali syndrome: an appropriate response?

A case of the 'milk alkali syndrome' associated with grossly elevated levels of amino terminal parathyroid hormone is described. The hypercalcaemia (calcium 4.09 mmol/l) and hyperparathyroidism settled on conservative measures.

Localisation of factor XIII in human tissues using an immunoperoxidase technique.

An immunoperoxidase technique has been used to localise clotting factor XIII subunits A and S in human tissues. The presence of factor XIII in placenta and megakaryocytes was confirmed. Factor XIII was also found in fibroblasts, a hitherto unreported finding.

An acquired inhibitor of factor XIII with a qualitative abnormality of fibrin cross-linking.

A patient with an acquired inhibitor to factor XIII is reported. The patient's plasma produced a profound inhibition of factor XIII activity in normal plasma measured by a dansylcadaverine casein assay and stimulated a very abnormal pattern of fibrin cross-linking, not normally seen with factor XIII. Partial characterisation of the inhibitor suggests that it is heat stable and not an immunoglobulin.

Factor XIII levels in five families of patients with inherited factor XIII deficiency: support for an autosomal recessive inheritance.

Using quantitative methods, f.XIII activity and levels of subunits a and b have been measured in 5 families of 6 patients with inherited XIII deficiency, including 2 children of a XIII deficient male. The parents, as a group, and the children, individually, have low XIII activity and low levels of subunit A when compared to controls.

The half life of factor XIII in the management of inherited deficiency.

Following the injection of a large dose of factor XIII concentrate the in vivo half life of factor XIII was estimated in a patient with inherited deficiency. Factor XIII activity and enzyme concentration were measured quantitatively, and a qualitative assessment of the crosslinking of fibrin was also made for upto 6 weeks after the injection. The half life was found to be about 9--10 days.