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Biomedical subjects

A J Watson

Publications and source records attributed to A J Watson.

At least 217 records · Page 12Linked to original sources
PubMed1986

Diuretic-induced hypokalemia and cardiac arrhythmias.

Premature ventricular contractions have long been recognized as a complication of severe diuretic-induced hypokalemia. Likewise, diuretic-induced mild hypokalemia is known to have an arrhythmogenic potential in patients who are concurrently being treated with digitalis compounds. Recent studies using exercise and ambulatory monitoring of the electrocardiogram suggest that diuretic-induced premature ventricular contractions may be a more common phenomenon than was previously recognized. The risk of this form of ventricular ectopic activity is controversial. However, the available data are substantial enough to warrant some precautions on the part of the clinician.

Arrhythmias, Cardiac↗
PubMed1986

Selective inhibition of thromboxane synthesis in glycerol-induced acute renal failure.

It has recently been postulated that thromboxane A2 may participate in the pathogenesis of acute myohemoglobinuric experimental acute renal failure. To investigate this further, the effect of selective inhibition of thromboxane synthesis on the course of glycerol-induced acute renal failure was determined. Despite significant inhibition of thromboxane synthesis by 4-imidazole-yl-acetophenone, the functional and morphologic disturbance induced by glycerol was unaltered. Moreover, pretreatment with 4-imidazole-yl-acetophenone failed to prevent the fall in renal blood flow seen following glycerol administration. These results argue against a major role for thromboxane A2 in the pathogenesis of this form of experimental acute renal failure.

6-Ketoprostaglandin F1 alpha↗
PubMed1986

Thiazide-induced hyponatremia.

We have described a case of severe acute hyponatremia developing in a patient who had been taking thiazides for the previous eight months without having any electrolyte abnormalities. The onset of the electrolyte disturbance coincided with a physician-recommended hydration regimen, which we believe unmasked a drug-related impairment of water excretion. Withdrawal of thiazide therapy promptly resulted in water diuresis and rapid correction of the hyponatremia.

Acute Disease↗
PubMed1986

A cytokinetic study of small-intestinal and colonic mucosa after resection of 70% of the small intestine.

Pulse-labelling with tritiated thymidine and a fraction of labelled mitoses experiments have been performed in order to investigate the proliferative changes induced at various sites in the hyperplastic small-intestinal mucosa of rats previously subjected to resection of 70% of the small intestine. Proliferative activity in the colon was also studied. In the distal ileum there is a significant reduction in cell cycle time (Tc) of cells at all levels within the crypt and the growth fraction falls. In the jejunum and proximal ileum the crypts contain an increased number of proliferating cells, but as the size of the maturation zone is also increased, there is no significant alteration in the relative number of proliferating cells per crypt. Nor does the distribution of proliferating cells in these crypts seem to alter. There is no general reduction in Tc at these sites, but there does appear to be a significant reduction in Tc on the part of the cells in the stem-cell zone at the crypt base. In neither proximal nor distal colon was there any significant proliferative change apparent after small-intestinal resection.

Animals↗
PubMed1986

De novo diabetic nephropathy with functional impairment in a renal allograft.

Recurrence of diabetic nephropathy in the allograft of diabetics with end-stage renal disease who undergo renal transplantation has been reported. We report a case of a patient who underwent cadaveric renal transplantation for end-stage renal disease secondary to chronic glomerulonephritis 13 years ago. He developed steroid-induced, insulin-dependent diabetes mellitus 9 months after transplantation and florid nephrotic syndrome with progressive functional impairment due to biopsy-proven diabetic nephropathy 11 years later. This is, to our knowledge, the first report of de novo diabetic nephropathy in a renal allograft of a patient who was not a diabetic at the time of transplantation. It is suggested that histopathologic changes of diabetes mellitus cannot only recur in a renal allograft, but also can develop de novo and lead to functional impairment and ultimately affect graft survival. In view of increasing patient and graft survival in transplanted diabetic and non-diabetic patients, it is reasonable to anticipate an increased incidence of this complication.

Biopsy↗
PubMed1986

Fetal wastage in women with anti-Ro(SSA) antibody.

Retrospective obstetric histories were obtained in 50 anti-Ro(SSA) antibody positive women (aged 15-50 years) and 47 anti-nRNP antibody positive women of similar age range. Twenty (40%) anti-Ro(SSA) positive women and 33 (70%) anti-nRNP positive women fulfilled the revised ARA criteria for systemic lupus erythematosus (SLE). Thirty-four anti-Ro(SSA) positive women had a total of 84 pregnancies with a fetal loss of 28%; 29 anti-nRNP positive women had a total of 63 pregnancies with a fetal loss of 19%. Although the overall frequency of fetal wastage between the 2 groups was not significantly different, analysis of the subgroup of SLE patients demonstrated a significantly greater fetal wastage in black anti-Ro(SSA) positive women (15 of 21, 71%) compared with black anti-nRNP positive women (5 of 28, 18% p less than .001). No significant difference in fetal wastage was noted between either the white SLE or the non-SLE women in either antibody group. These data suggest that black SLE patients with anti-Ro(SSA) antibody may be at increased risk of fetal wastage.

Abortion, Spontaneous↗
PubMed1986

A comparison of crypt-cell proliferation in rat colonic mucosa in vivo and in vitro.

The successful development of a long-term organ culture system has made it possible to perform experiments on rat colonic mucosa in vitro. However, the effect of trauma or the withdrawal of trophic influences in culture may result in the disturbance of proliferation within the tissue. In this paper we describe an investigation designed to characterise the culture system by a comparison of the proliferative parameters in vitro with those in vivo. Stathmokinetic experiments were performed in vivo and in vitro to estimate cell birth rate. Mitotic indices were also calculated. The in vivo birth rate (7.8 +/- 0.8 cells/1000 cells/hour) and the in vitro birth rate for the whole explant (7.7 +/- 0.5 cells/1000 cells/hour) were found to be similar. A study of crypts in the centre and at the edge of the cultured explants, however, indicated that proliferation at the two sites differed markedly, the birth rate at the edge (7.5 +/- 0.9 cells/1000 cells/hour) being approximately twice that at the centre (3.2 +/- 0.9 cells/1000 cells/hour). Provided that this topological difference in proliferation within the explant is recognised the in vitro model, in particular the basal level found at the centre, may still be regarded as a valid system for studying tissue responses to carcinogens and trophic factors.

Animals↗
PubMed1986

Acute renal failure following percutaneous transhepatic cholangiography. A retrospective study.

We analyzed retrospectively the incidence of potential nephrotoxic effects of radiographic contrast material associated with percutaneous transhepatic cholangiography and percutaneous biliary drainage. Of 72 consecutive patients who underwent these procedures, three developed acute renal insufficiency (defined as a rise in the serum creatinine concentration of greater than 2 mg/dL [greater than 180 mumol/L]) following administration of contrast medium. In two patients, abdominal roentgenograms taken after the procedure showed persistently opaque kidneys, indicating that contrast material had gained access to the circulation. Percutaneous transhepatic cholangiography and percutaneous biliary drainage may be associated with nephrotoxic effects of radiographic contrast material, and patients with recognized risk factors may benefit from prophylactic hydration regimens as recommended for other procedures.

Acute Kidney Injury↗
PubMed1985

Transient idiopathic hyperammonaemia in adults.

Transient severe hyperammonaemia developed in the absence of serious liver dysfunction in three patients being treated for acute leukaemia. The onset of the biochemical disturbance was abrupt and led rapidly to acute encephalopathy, fatal in two cases. In the third patient, prompt initiation of aggressive haemodialysis and intravenous sodium benzoate and sodium phenylacetate infusion successfully controlled plasma ammonium levels until they spontaneously resolved. The cause of the disorder remains to be determined, but urinary nitrogen partition studies suggest temporary impairment of ureagenesis in a catabolic setting as a major pathophysiological feature of this disorder. The absence of liver disease, the normal mitochondrial ultrastructure seen in two cases, and the plasma aminoacid profiles observed serve to distinguish this disorder from others such as Reye's syndrome.

Acute Disease↗
PubMed1985

Transplantation of a segment of ileum to the external abdominal wall: an animal model of intestinal mucosal hyperplasia.

When a segment of small intestine is transplanted to the external abdominal wall in rats adaptive changes occur in the exposed mucosa. These probably represent an extreme example of a physiological response to one type of trophic influence--the effect of mechanical trauma. The nature of the changes has been studied at 7 weeks after externalization using simple morphometry and a number of cytokinetic techniques (thymidine labelling, vincristine-induced metaphase arrest and the fraction-of-labelled-mitoses method), and comparisons drawn with the normal ileum. The exteriorized mucosa showed marked villus atrophy and hyperplasia of the crypts to three times normal size as a result of increases both in crypt length and crypt circumference. Neither metaplastic nor dysplastic epithelial abnormalities were observed. Crypt-cell production rate doubled in the hyperplastic crypts due to an increase in the size of the proliferation zone within the crypt, and the distribution of proliferating cells within the crypt changed. But cell cycle times were prolonged and more maturing cells were retained in the hyperplastic crypts. The potential usefulness of this model, particularly in carcinogenicity studies is considered.

Abdominal Muscles↗
PubMed1985

Demonstration of vincristine resistance in primary intestinal neoplasms in the rat by the 'post-metaphase index'.

A method is described enabling the direct measurement of vincristine resistance in intact tissues in vivo by morphological study. Using the metaphase arresting properties of the drug, counts were made of escaping anaphase and telophase mitotic figures at a range of doses. The proportion of post-metaphase mitotic figures is called the post-metaphase index (PMI). In 95 primary intestinal tumours induced by dimethylhydrazine (DMH) in rats, an increase in resistance to vincristine was shown over normal mucosa (P less than 0.001). The data were analysed by computer modelling and a linear relationship is demonstrated between the logit of the post-metaphase index, and log dose of vincristine. To achieve a PMI of 1% the fitted lines show an enhanced vincristine dose requirement over normal mucosa of 6 times in colonic tumours, and 8 times in small intestinal tumours. Non-neoplastic mucosa from the DMH-treated animals requires an enhanced dose of vincristine of 1.5 times, compared with normal mucosa, to achieve a PMI of 1%. Given current interest in the mechanism of vincristine resistance in cell lines this new approach provides a technique for assessing the resistance of solid tumours, both in vivo and in vitro, and for subsequent experimental manipulation.

Animals↗
PubMed1985

Baroreflex sensitivity and pressor responses in a rat model of uraemia.

Baroreflex sensitivity and pressor responsiveness to exogenous noradrenaline, angiotensin II and arginine vasopressin were determined in a rat model of uraemia. The slope of the regression line relating delta heart rate to delta blood pressure after phenylephrine administration was significantly less in the renal failure group than the normal control group, indicating a reduction of baroreflex sensitivity in the setting of uraemia. The pressor response to noradrenaline and angiotensin II was significantly less in the renal failure group whereas there was no difference in delta blood pressure on administration of arginine vasopressin. It is concluded that diminished baroreflex sensitivity does not contribute to the pathogenesis of hypertension in uraemia by the hypothesized mechanism of allowing the pressor effect of endogenous pressor substances to go unbuffered.

Angiotensin II↗
PubMed1985

Evaluation of the inhibition of glycolytic enzymes by the neurotoxicant dimethylaminopropionitrile.

The neurotoxic aminonitrile dimethylaminopropionitrile (DMAPN) inhibits the crystalline glycolytic enzymes glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and fructose-6-phosphate kinase (phosphofructokinase, PFK). Preincubation of GAPDH with the aminonitrile enhances the inhibition, indicating that the inhibition is irreversible. The overall bimolecular rate constant ki was determined to be 2.42 +/- 0.21 M-1 min-1. Dithiothreitol (DTT) partially protected the enzyme from inhibition. PFK is also inhibited by DMAPN, but the inhibition is reversible and noncompetitive with a Kl, of 2.79 X 10(-2) M. DMAPN does not inhibit lactate dehydrogenase (LDH), nor is GAPDH or PFK inhibited by 3,3'-iminodipropionitrile (IDPN).

Aminopropionitrile↗
PubMed1985

Vindesine as a stathmokinetic agent in human rectal tumours in organ culture.

Organ culture, using human colorectal mucosa and tumours, is a good system in which to test a new stathmokinetic agent such as vindesine. Using this system we have found that vindesine has similar metaphase-arresting properties to vincristine, including at least a 6-fold dose response difference in its ability to arrest mitosis in mucosa and tumour, mucosa being the more sensitive. Vindesine is a satisfactory stathmokinetic agent, but in view of its greater cost offers no particular advantages over vincristine.

Carcinoma↗
PubMed1985

Clinical utility of a monoclonal direct fluorescent reagent specific for Legionella pneumophila: comparative study with other reagents.

Twenty-four lower respiratory tract samples taken from patients with culture-confirmed Legionella pneumophila infection were examined with three different direct immunofluorescent antisera to L. pneumophila, as were 29 samples from similar sources taken from patients without Legionnaires disease. The reagents studied were Genetic Systems Corp. (GS) monoclonal L. pneumophila conjugate, which reacts with all known serogroups of L. pneumophila, BioDx polyvalent L. pneumophila serogroups 1 through 6 conjugate, and Centers for Disease Control polyvalent pool A L. pneumophila serogroups 1 through 4 conjugate. The specimens had been frozen at -70 degrees C for 0.5 to 5 years. Randomization was used in coding the samples, which were stained and read by an independent observer. All three conjugates correctly identified all positive and negative samples. No difference was noted among the conjugates in the absolute numbers of fluorescent L. pneumophila bacteria per sample. The GS conjugate had a much cleaner background than did the other two reagents. Mean staining intensity scores were 3.4, 3.9, and 3.7 for the GS, BioDx, and Centers for Disease Control conjugates, respectively. This study demonstrates that the diagnostic efficiency of all three conjugates is equivalent. Since the GS conjugate is easier to read, does not cross-react with non-L. pneumophila bacteria, and reacts with serogroups 1 through 10 of L. pneumophila, it appears to be preferable for use in diagnostic testing on nonhistopathologically processed specimens.

Antibodies, Bacterial↗
PubMed1985

Cure of cryptococcal infection during continued immunosuppressive therapy.

Cryptococcus neoformans is a significant pathogen in immunosuppressed patients. In renal transplant recipients receiving prednisone, the development of cryptococcosis is associated with a poor prognosis. When such patients develop cryptococcosis they pose a particularly difficult clinical dilemma since withdrawal of prednisone, to facilitate cure of their fungal infection, may predispose to loss of their transplanted kidney. We report our experience with cryptococcal infection in 13 renal transplant patients. In 11 of these patients maintenance immunosuppression was cautiously continued to preserve allograft function. The results of our study suggest that maintenance immunosuppressive therapy may be continued throughout the period of antifungal therapy and does not preclude eradication of the infecting organisms. Our experience indicates that the prognosis for the renal transplant patient who has cryptococcosis can be improved.

Amphotericin B↗