Warfarin or Low-Molecular-Weight Heparin Therapy does not Prolong Pig-To-Primate Cardiac Xenograft Function

Microvascular thrombosis is a prominent feature in cardiac delayed xenograft rejection (DXR). We investigated the impact of warfarin or low-molecular-weight heparin (LMWH) anti-coagulation on xenograft function using a heterotopic pig-to-primate model. Donor hearts were from CD46 transgenic pigs and baboon immunosuppression included tacrolimus, sirolimus, anti-CD20 and TPC, an alpha-galactosyl-polyethylene glycol conjugate. Three groups of animals were studied. Group 1 (n = 9) was treated with warfarin, Group 2 (n = 13) with LMWH and Group 3, received no anti-coagulant drugs. The median duration of xenograft function was 20 days (range 3-62 days), 18 days (range 5-109 days) and 15 days (range 4-53 days) in Groups 1 to 3 respectively. Anti-coagulation achieved the targeted international normalized prothrombin ratio (INR) and anti-factor Xa levels consistent with effective in vivo therapy yet, no significant impact on median xenograft function was observed. At rejection, a similar histology of thrombosis and ischemia was apparent in each group and the levels of fibrin deposition and platelet thrombi in rejected tissue was the same. Anti-coagulation with warfarin or LMWH did not have a significant impact on the onset of DXR and microvascular thrombosis. However, a role for specific anti-coagulant strategies to achieve long-term xenograft function cannot be excluded.     

Use of pressure-hold test for sterilizing filter membrane integrity in radiopharmaceutical manufacturing

The bubble point test is the de facto standard for postproduction filter membrane integrity test in the radiopharmaceutical community. However, the bubble point test depends on a subjective visual assessment of bubbling rate that can be obscured by significant diffusive gas flows below the manufacturer's prescribed bubble point. To provide a more objective means to assess filter membrane integrity, this study evaluates the pressure-hold test as an alternative to the bubble point test. In our application of the pressure-hold test, the nonsterile side of the sterilizing filter is pressurized to 85% of the predetermined bubble point with nitrogen, the filter system is closed off from the pressurizing gas and the pressure is monitored over a prescribed time interval. The drop in pressure, which has a known relationship with diffusive gas flow, is used as a quantitative measure of membrane integrity. Characterization of the gas flow vs. pressure relationship of each filter/solution combination provides an objective and quantitative means for defining a critical value of pressure drop over which the membrane is indicated to be nonintegral. The method is applied to sterilizing filter integrity testing associated with the commonly produced radiopharmaceuticals, [¹⁸F]FDG and [¹¹C]PIB. The method is shown to be robust, practical and amenable to automation in radiopharmaceutical manufacturing environments (e.g., hot cells).     

A preliminary statistical model for identifying repeaters of parasuicide

This paper presents a statistical model constructed using logisticregression to identify those at high-risk of repeating parasuicide. Thesubjects in the study are Cork city residents who exhibited parasuicidalbehaviour between 1 January and 30 June 1995. Repetition of the behaviourwithin six months of the index episode distinguishes repeaters fromnon-repeaters. The model was designed so that it could be used bynon-clinicians and hence does not require information relating topsychiatric diagnosis or use of psychiatric services. The proportion ofsubjects correctly classified remained stable across a range of cut-pointprobabilities (mean = 86%, range: 83.9–87.5%). Using acut-point of 0.2, 96% of repeaters and 81% of non-repeaters were correctly classified. Using 0.45 led to the correct identification of81% of repeaters and 90% of non-repeaters. If these highlevels of sensitivity and specificity are maintained in validation tests onfuture cohorts in Cork city then the model could form the basis of anintervention programme designed to prevent the repetition of parasuicide.     

Embolisation of recently ruptured intracranial aneurysms.

Patients with subarachnoid haemorrhage due to the rupture of aneurysms unsuitable for craniotomy and clipping have been treated by coil embolisation within three weeks. Sixty nine of 75 consecutive patients were successfully treated. Procedure related complications occurred in 10 patients, resulting in permanent neurological deficits in three and one death (4.8%). The Glasgow outcome scores at six weeks were 53 grade 1, seven grade 2, four grade 3, and five grade 5. These results are comparable with surgical series despite a high proportion of aneurysms in the posterior cerebral circulation.     

Benign intracranial hypertension and recombinant growth hormone therapy in Australia and New Zealand

Benign intracranial hypertension (BIH) is reported in three children from Australia and one from New Zealand, who were being treated with recombinant human growth hormone (rhGH). Three males and one female, aged between 10.5 and 14.2 y, developed intracranial hypertension within 2 weeks to 3 months of starting treatment. A national database, OZGROW, has been prospectively collecting data on all 3332 children treated with rhGH in Australia and New Zealand from January 1986 to 1996. The incidence of BIH in children treated with growth hormone (GH) is small, 1.2 per 1000 cases overall, but appears to be greater with biochemical GHD (<10IUml ^-1), i.e. 6.5/1000 (3 in 465 cases), relative risk 18.4, 95% confidence interval 1.9-176.1, than in all other children on the database. The incidence in patients with Turner's syndrome was 2.3/1000 (1 in 428 cases). No cases in patients with partial GHD (10–20 IUml ^-1) or chronic renal failure were identified. Possible causative mechanisms are discussed. The authors'practice is now to start GH replacement at less than the usual recommended dose of 14IUm-² week^-1 in those children considered to be at high risk of developing BIH. Ophthalmological evaluation is recommended for children before and during the first few months following commencement of rhGH therapy and is mandatory in the event of peripheral or facial oedema, persistent headaches, vomiting or visual symptoms. The absence of papilledema does not exclude the diagnosis.     

The fit of fixed partial dentures joined by infrared soldering.

This study determined the accuracy of fit of three-unit fixed partial dentures joined by an infrared soldering technique compared with one-piece fixed partial denture castings and individually cast crowns. Wax patterns of prepared Ivorine teeth, maxillary left central incisor and maxillary left canine, were injection molded; a plastic rod was used as a pontic. One group of patterns was cast as one-piece dentures; the other group was sectioned in the connector area, cast individually and then joined by infrared soldering. Castings were seated on their respective dies, embedded in epoxy resin, and sectioned. Gap distances between the casting and the die were measured at specified marginal sites with a profile projector. Results showed that the fit of infrared-soldered fixed partial dentures was significantly better than that of one-piece castings and was comparable with the fit of single crowns. The gap openings measured in all castings were within the range of clinical acceptability.     

Acute psychoses: A proposed diagnosis for ICD-11 and DSM-V

This paper concerns the diagnostic classification of nonaffective acute remitting psychosis (NARP), which we also term acute brief psychosis. We argue that NARP can be delineated from both schizophrenia and the affective psychoses and considered as a single diagnosis. As indicated by the term NARP, four criteria would be central to the diagnosis: 1. nonaffective, 2. acute onset (over less than two weeks), 3. recovery within a brief duration (less than six months), and 4. psychosis broadly defined. We review the rationale and the empirical evidence for this proposed classification.     

Infantile free sialuria without lysosomal storage

Except for two reported patients, increased free sialic acid excretion has been associated with lysosomal storage. This is a report of a child with progressive neurologic deterioration and increased excretion of free sialic acid. Although lysosomal storage was absent, nuclear invagination or inclusions were present.