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B O Howden

Publications and source records attributed to B O Howden.

34 records · Page 2Linked to original sources

Liver preservation with UW solution. I. Evidence that hydroxyethyl starch is not essential.

Preservation of rat livers by simple ice-storage has been demonstrated after 24 hr using the University of Wisconsin (UW) solution. Equally good preservation could be obtained by substituting hydroxyethyl starch (HES) from another source or by omission of HES from the UW formulation. Survival, early and late function, and morphology at the end of a 3-month follow-up period were essentially similar for all three test groups. It is concluded that HES is not required for optimum preservation of the rat liver in this treatment model.

Adenosine↗

Evaluation of UW solution in a rat kidney preservation model. I. Effect of hydroxyethyl starch and electrolyte composition.

Preservation of rat kidneys by simple ice-storage has been demonstrated after 48 hr using the University of Wisconsin (UW) solution; hypothermic preservation of the rat kidney was dramatically improved. A modified UW solution without hydroxyethyl starch (HES) also gave uniform survival after 48 hr of storage, and even better function and morphology. Substitution of HES from another source also improved renal function when compared with UW (Dupont) and it is suggested that prolonged storage of UW solution prior to use may reduce its effectiveness. Reversing the Na:K ratio of the solution still allowed successful preservation, but significantly worsened morphology of the surviving kidney.

Adenosine↗

Evaluation of UW solution in rat kidney preservation. II. The effect of pharmacological additives.

The present studies show clearly that both dexamethasone and insulin can be omitted without altering the efficacy of UW. Adenosine and glutathione are both helpful additives, as is allopurinol. These findings suggest an important role of reperfusion injury after preservation, and confirm the benefits of adding pharmacological agents likely to reduce this injury. Cold ischemic damage was significantly ameliorated by UW solution in this stringent model of rat kidney preservation for 48 hr. A substantially simplified modification of UW solution has been shown to give equally effective kidney preservation, after removal of hydroxyethyl starch, dexamethasone, and insulin. Adenosine, glutathione, and allopurinol have been confirmed as helpful pharmacological additives. These findings have defined some of the mechanisms of effectiveness of UW solution and suggest avenues of further exploration to improve simple hypothermic storage and to prevent reperfusion injury.

Adenosine↗

Papillary necrosis in experimental renal transplantation in the rat.

Renal papillary necrosis is a frequent complication of unsuccessful renal transplantation in rats, occurring in both isografts and allografts. Papillary necrosis does not occur alone, but only and inevitably in association with severe cortical damage. The pattern of the lesion is different from other forms of papillary necrosis in that the least severe lesions occur in the outer medulla and the more severe lesions involve both medulla and papilla. The incidence of papillary necrosis is increased in isografts, but not in allografts, by longer preservation times. It is suggested that the principal underlying cause may be damage to medullary capillaries, occurring either during preservation or as a consequence of rejection and leading to medullary ischemia.

Animals↗

An experimental model for assessment of renal recovery from warm ischemia.

A study was made of the acute and chronic (15 days) functional and morphologic effects on the rat kidney of warm ischemia and contralateral nephrectomy, in order to define a suitable animal model for testing renal transplant preservation techniques when warm ischemia is a contributing factor. Spontaneous recovery from 30-min warm ischemia was complete, and the model was consequently unsuitable; the high mortality from 90 min was unacceptable. Warm ischemia of 60 minutes produced severe renal tubular necrosis, an acceptable mortality, residual morphologic damage, and impairment of isolated kidney perfusion parameters at 15 days. Renal function in vivo was normal in many of these animals, despite appreciable residual morphologic changes, and it is evident that functional data alone are not sufficient for assessment of preservation regimens.

Animals↗

Apoptosis and the expression of genes of the Bcl-2 family and TGF-beta1 in rat renal allografts transplanted after donor-specific blood transfusion.

UNLABELLED: Factors involved in "operational" tolerance in animal models induced by recipient pre-treatment with donor-specific blood transfusion (DSBT) need elucidation. This study examined apoptosis, expression of genes of the Bcl-2 family and of TGF-beta(1) in isografts, rejecting and tolerant allografts. METHODS: Adult inbred Dark Agouti (DA) kidneys were transplanted, with immediate nephrectomy of recipient kidneys, to (1) ALLO, inbred Albino Surgery (AS) rats; (2) DSBT ALLO, AS rats who received two DA blood transfusions under cover of cyclosporine prior to transplantation; or (3) ISO, DA rats. Grafts were retrieved on day 1, 3, or 5. Apoptosis was assessed by TUNEL. RNA was extracted and reverse transcribed to cDNA for quantification by real-time PCR, relative to the 18s housekeeping gene. RESULTS: Apoptosis was negligible in ISO while it increased in allograft groups from day 1. On day 5, apoptosis in ALLO (114.0 +/- 30.6), involved renal tubular cells and leukocytes compared to DSBT ALLO (9.7 +/- 4.0) and ISO (0.9 +/- 0.3) involving leukocytes only. On day 1, DSBT ALLO had higher expression of Bax than ALLO or ISO. On day 3, DSBT ALLO and ALLO had higher TGF-beta(1) mRNA than ISO. On day 5, Bcl-2 expression was significantly decreased (P < .001) in ALLO compared to DSBT ALLO and ISO. Bad and Bid were higher in DSBT ALLO than in ALLO. TGF-beta(1) was higher in DSBT ALLO compared to ISO. CONCLUSIONS: Decreased expression of anti-apoptotic Bcl-2 gene may be implicated in increased apoptosis in rejecting allograft while expression of pro-apoptotic genes may be involved in the establishment of operational tolerance.

Animals↗