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Biomedical subjects

D H Adams

Publications and source records attributed to D H Adams.

At least 199 records · Page 11Linked to original sources

Liver transplantation.

The 1-year survival rates of around 70% that are now being achieved have resulted in the acceptance of liver transplantation as a treatment for end-stage liver disease. The number of patients undergoing transplantation is increasing rapidly and the indications are widening. More patients are being transplanted for acute liver failure following the recent encouraging reports of successful grafting in this condition. The proportion of patients transplanted for liver cancer is falling as it becomes apparent that 80% of patients will die from recurrent disease. The selection of candidates and timing of transplantation continue to pose difficult clinical problems. Although the surgical and anaesthetic aspects of liver transplantation have been greatly improved, the 30-day mortality remains high at around 30% and postoperative complications, especially infection and rejection, continue to be major problems. However, rehabilitation is excellent for most patients and liver transplantation should no longer be considered an experimental procedure.

Humans↗

Hepatic endothelial cells. Targets in liver allograft rejection?

Hepatic endothelial cell damage was evaluated in patients following liver transplantation using 2 serum markers: hyaluronic acid (HA), which measures hepatic endothelial cell function, and factor VIII related antigen (VIIIRAg), an indicator of generalized endothelial damage. HA was elevated in rejection (median 22.3 x control) when compared with stable patients (3.7 x control; P less than 0.00001) and those with posttransplant complications not related to rejection (6.8 x control; P less than 0.0005). The highest levels were seen in patients with chronic rejection (28.7 x control). Levels were also elevated in acute rejection (21.3 x control), and the highest levels in this group were seen in patients who subsequently developed chronic rejection (25.2 x control). Serial studies demonstrated that HA increased 24 hr before serum bilirubin in patients developing acute rejection. VIIIRAg was elevated in all posttransplant patients with no significant difference between rejection and other complications. These results show that hepatic endothelial dysfunction occurs during acute and particularly chronic rejection of liver allografts suggesting that VECs may be an important target of the immune response. Measurement of HA may allow for the early diagnosis of acute rejection and the identification of patients at risk of developing chronic rejection.

Adolescent↗

Massive haemorrhagic necrosis of the liver after liver transplantation.

Six of the first 85 patients who received the first 100 liver transplantations carried out in Birmingham developed a syndrome of fulminant liver failure with distinctive clinical and pathological features. The typical clinical presentation was of an uneventual initial postoperative period, followed by a sudden deterioration in graft function, progressing rapidly to graft failure. All six patients died. The characteristic pathological changes were those of massive haemorrhage and hepatocyte necrosis with only mild inflammation and without occlusive lesions in large arteries or veins. These distinctive features differed from other recognised patterns of graft damage and seemed to comprise a specific post-transplant syndrome. The pathogenesis was not clear and in the absence of any definite aetiology it is suggested that the term "massive haemorrhagic necrosis" be used to describe these cases. Additional findings seen in five of the six cases were venoocclusive lesions (n = 4) and a combination of ductopenia and foam cell arteriopathy (n = 2). The presence of these associated lesions suggests that there may be an overlap with other types of graft damage.

Adult↗

The chick embryo fibroblast cytosolic DNA complex--a possible cell-cell messenger.

1. The uptake of [3H]thymidine and [3H]uridine labelled DNA-RNA cytosol complex has been studied in chick embryo fibroblast cells. 2. The complex appears to be cleaved into DNA and RNA containing fragments in the recipient cell nucleus: both then enter the cell cytosol fraction, but the RNA fragment in particular is rapidly degraded. 3. Although [3H]thymidine labelled material present in the nucleus co-extracts with bulk nuclear DNA, caesium gradienting shows little or no evidence that integration of host and imported DNA has occurred. 4. It is suggested that the cytosolic/extruded DNA complex may be a "messenger" DNA, capable of the transfer of regulatory information between cells on a transient basis.

Animals↗

The search for the DNA of the chick embryo fibroblast cytosolic complex.

1. Conventional DNA extraction procedures have failed to release free DNA from the chick embryo fibroblast cytosolic DNA-RNA complexes. 2. Free DNA has been released only from the smallest cell cytosol DNA fraction, which is not in the native state associated with RNA: it is very small (of the order of 100 bases) and single stranded. 3. However, phenol extraction does separate complex DNA-associated material from the RNA which has invariably been found to accompany it in all but the smallest fraction (see 2 above). 4. The principal factor preventing DNA release appears to be a massive aggregation of partially purified DNA-associated material.

Animals↗

High-resolution real-time ultrasonography. A new tool in the diagnosis of acute appendicitis.

A prospective study was performed to assess the sensitivity and specificity of ultrasonographic evaluation in 44 patients with suspected appendicitis. We found ultrasonographic evaluation to have a sensitivity rate of 89 percent, a specificity rate of 86 percent, and an overall accuracy rate of 87 percent. These results are very similar to those in other recently reported studies. We also identified certain patients in whom nondiagnostic studies are likely. Our results suggest that ultrasonographic evaluation may be of particular use in selected patients who do not demonstrate the classical signs and symptoms of acute appendicitis.

Acute Disease↗

Beta-2-microglobulin expression in the liver after liver transplantation.

The distribution of major histocompatibility complex (MHC) class 1 antigens was studied in the liver after transplantation by immunoperoxidase staining for beta-2-microglobulin (beta 2m), a subunit of the class 1 antigen system. Paraffin wax sections were examined from 25 "time zero" biopsy specimens, taken immediately after insertion of the graft, and 87 biopsy specimens taken after transplantation in seven diagnostic categories: acute cellular rejection (n = 22); resolving acute rejection (n = 8); chronic rejection (n = 22); pure cholestasis (n = 14); ischaemia/infarction (n = 5); biliary obstruction (n = 8); massive haemorrhagic necrosis (n = 8). Staining was graded semiquantitatively on a scale of 0-3+ in bile ducts, hepatocytes, sinusoidal lining cells and vascular endothelium. Using the "time zero" biopsy specimens as a baseline for comparison, increased expression of beta 2m was seen in bile ducts, hepatocytes, and endothelial cells after transplantation. These changes were most pronounced in cases of rejection but also occurred in other graft conditions. The degree of hepatocyte and endothelial staining was significantly higher in cases of rejection and massive haemorrhagic necrosis than in the other categories. These findings may have implications for the pathogenesis and diagnosis of rejection of the transplanted liver.

Graft Rejection↗

Neurological complications following liver transplantation.

17 (33%) of 52 patients who underwent 56 consecutive orthotopic liver transplants had serious neurological complications postoperatively. The commonest complication was fits, which occurred in 13 (25%) patients. 50% of patients had their onset of fits within the first week. In 3 patients the fits were associated with postoperative metabolic encephalopathy and fatal progressive neurological deterioration. In some patients the evidence implicating cyclosporin in the development of fits is strong. In others factors such as electrolyte disturbances, steroid treatment for graft rejection, and cerebral infarction may have contributed to the development of the fits. Phenytoin controlled the fits in 10 out of 13 patients. Other neurological complications included 1 case of central pontine myelinolysis, 1 of cerebral abscess, and 4 of non-encephalopathic psychosis.

Adolescent↗

Orthotopic liver transplantation: postoperative complications and their management.

The Birmingham liver transplant programme started in 1982. Forty-six patients have been transplanted with a follow-up of 3 months or longer. Twenty-seven patients are still alive, of whom sixteen have lived for more than one year. The 30 day hospital mortality was 30.4 per cent and the actuarial predicted one year survival 55.5 per cent. Four patients have been regrafted for chronic rejection and graft failure. Thirteen patients have required surgery in the postoperative period for: bleeding (two), removal of abdominal packs (four), biliary leaks and obstruction (five), duodenal perforation (one) and small bowel obstruction (one). Acute rejection was common, occurring in 30 patients and progressing to chronic rejection in 4. Ten patients developed renal failure with an 80 per cent mortality and eleven patients developed grand mal fits. Severe bleeding (greater than 70 units) was associated with previous abdominal surgery and a high mortality (88.9 per cent). Opportunistic fungal infection carried a 100 per cent mortality. Although more than half of all transplanted patients will survive for more than one year, the postoperative period is still one of high morbidity and mortality.

Acute Kidney Injury↗

The assembly of the DNA complex present in chick embryo cell cytosol.

Chromatography of chick embryo fibroblast cytosol labelled with [3H]thymidine or [3H]uridine precursors has shown the presence of early labelled DNA and RNA eluting at a position corresponding to a relative molecular mass of approximately 1.5-10(5). The early DNA-RNA (heteroduplex?) then moves progressively to a higher molecular weight peak, relative molecular mass approximately 10(6). The process appears similar in cytosol from cultured cells and from whole amniotically labelled chick embryos: consequently the cytosolic DNA complex is not an artefact of cell culturing. The relative contribution of artefactual and specific cytosol-associated DNA material is discussed: it is concluded that while both are present in cytosol as prepared, it is possible to discriminate between specific and artefactual DNA material.

Animals↗

The triplet code: is it enough?

It is suggested that the triplet code dogma that the role of DNA as an information carrier can only be defined in terms of a code for amino acids embodied in the sequence of nucleotides, is inadequate to encompass the totality of information/instruction/organisation necessary for the maintenance of living systems. It is proposed that, as a minimum, a second independent but complementary mechanism is necessary involving direct DNA--DNA intercommunication. Further, that this mechanism may operate on the basis of a chemically switched microprocessor network system with individual DNA sequences able to act as individual microprocessors.

Cell Communication↗

Granulomatous mastitis--a rare cause of erythema nodosum.

Granulomatous mastitis is a recently described, rare condition of unknown aetiology. It occurs in young, parous women as a tender extra-areolar breast lump and therefore needs to be differentiated from carcinoma. Histologically, a discrete granulomatous lobulitis is seen and because of morphological similarities to granulomatous thyroiditis it has been suggested it may be immunologically mediated. We present a patient in whom granulomatous mastitis presented with periarthritis and erythema nodosum, an association not previously described.

Adult↗

Non-steroidal anti-inflammatory drugs and renal failure.

In 3 years seventeen patients presented to one unit with renal failure associated with the use of non-steroidal anti-inflammatory drugs (NSAID). Seven patients presented with acute renal failure, in four due to acute tubular necrosis and in three to acute interstitial nephritis; all recovered when NSAID treatment was stopped. Four patients presented with symptomless renal impairment discovered during routine follow-up in a rheumatology clinic; again all improved on withdrawal of NSAID. The remaining six patients presented with chronic renal failure, a disorder not previously associated with NSAID treatment. The pattern of renal disease associated with NSAID may be more extensive than has previously been recognised. A history of NSAID use should be sought in all patients presenting with unexplained renal failure.

Acute Kidney Injury↗