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Biomedical subjects

J M Morgan

Publications and source records attributed to J M Morgan.

At least 145 records · Page 8Linked to original sources

Rigid analogues of dopamine: synthesis and interaction of 6-exo- and 6-endo-(3',4'-dihydroxyphenyl)-2-azabicyclo[2.2.2]octanes with dopamine uptake sites and receptors.

Two isomeric 6-endo- and 6-exo-(3',4'-dihydroxyphenyl) derivatives (1 and 2) of 2-azabicyclo[2.2.2]octane were synthesized as semirigid analogues of dopamine (DA) to help evaluate the preferred conformation of dopamine at the uptake site of the presynaptic nerve terminal and at the DA receptor. Against the uptake of 0.1 microM [3H]DA by a synaptosomal preparation of corpus striatum from the reserpine-pretreated rat, 2 was found to have a weak inhibitory effect that was three times greater than that of 1 (IC50 = 32 vs. 110 microM). Interactions with DA receptors were assessed with competition for binding of [3H]apomorphine (APO) and on the effect on DA-sensitive adenylate cyclase. Compounds 1 and 2 were both virtually inactive against the binding of 0.5 nM [3H]APO at a screening concentration of 100 microM. The experimental compounds also exhibited only slight adenylate cyclase stimulation in rat striatal homogenates, with 1 appearing to be somewhat more active (at 50 or 400 microM). The weak activities of 1 and 2 and their relatively small differences in activity in these test systems suggest that the DA analogues interact only weakly with the DA transport and receptor sites, possibly as a result of the steric interference caused by the bulky bicyclic ring.

Adenylyl Cyclases↗

Angiotensin injected into the neostriatum after learning disrupts retention performance.

Angiotensin II, injected into the dorsal neostriatum of rats 5 minutes after they had learned a passive avoidance task, disrupted the retention of the task 24 hours later. Identical neostriatal injections given 22 hours after learning (2 hours before retention) were without effect on retention performance. Ventral neostriatum or posterior thalamus were ineffective sites for injection of angiotensin. Injection of thyrotropin releasing hormone or lysine-8-vasopressin into the dorsal neostriatum was ineffective. These findings indicate a possible role for endogenous angiotensin in the neostriatum on retention performance and suggest potential involvement in mnemonic processes.

Angiotensin II↗

Alternate-day prednisone therapy in recipients of renal allografts. Risk and benefits.

Forty-five patients receiving renal allografts were gradually converted from daily to alternate-day prednisone therapy. Indications for conversion included aseptic necrosis, growth retardation in children and adolescents, obesity, diabetes, cataract formation, and cosmetic appearance. Eight of the 45 patients developed acute or chronic rejection during or just after completion of alternate-day steroid therapy. The remaining 37 patients had a notable decrease in the degree of hypercorticism, with return of growth in children and adolescents. However, there was no improvement once aseptic necrosis or cataract formation had occurred. Although the use of alternate-day prednisone therapy is of benefit in reducing the untoward side effects of corticosteroids, the risk of precipitating allograft rejection is a significant threat and must be carefully considered whenever this form of treatment is undertaken.

Adolescent↗

Gastrointestinal hemorrhage secondary to cytomegalovirus after renal transplantation. A case report and review of the problem.

Generalized cytomegalovirus infection was associated with massive and ultimately fatal upper gastrointestinal bleeding in a renal allograft recepient and persisted even after subtotal gastric resection. The surgical specimen and the remaining stomach at autopsy revealed multiple superficial ulcerations with cytomegalic inclusion bodies within the gastric mucosa. Renal failure in the terminal stages of the patient's illness required hemodialysis but did not seem to be the sole result of allograft rejection, suggesting that the renal dysfunction may be caused by the systemic viral infection.

Blood Urea Nitrogen↗

Retrospective analysis of 100 consecutive patients undergoing related living donor renal transplantation.

One hundred consecutive patients receiving related donor kidneys were analyzed in regards to graft and patient survival, morbidity, mortality, histocompatibility and rehabilitation. The average followup was 3 years and 2 months with a minimum post transplant evaluation of one year. Donor morbidity was minimal and the mortality nil. Recipient mortality was 17%, all of which occurred after the first two post transplant months. The most serious life threatening complications after transplantation were due to infection. The greatest morbidity was secondary to aseptic necrosis. The overall graft survival at one year was 94%, 2 years--87%, 3 years--81% and 4 and 5 years--72%. Separation of patients according to tissue typing revealed 95% of recipients with A and B matched kidneys to be alive 5 years later compared to 55% of patients receiving C and D matched kidneys. Rehabilitation was good to excellent in 76% of the living patients and poor in only 4%. These results suggest related donor renal transplantation to be the treatment of choice for patients with chronic renal failure excluding only those individuals who are exceptionally high risks in terms of morbidity and mortality.

Acute Kidney Injury↗

Hyperkalemia and acidosis in lead nephropathy.

Defective potassium excretion with clinical acidosis, associated with fixed moderate sodium wasting, has been found to be a common abnormality in lead nephropathy. Lead poisoning has been shown by others to be associated with depression of the renin-aldosterone system and of sodium and potassium activated adenosinetriphosphatase (ATPase). Since these hormonal defects may contribute to the hyperkalemia and are reversible, lead poisoning should be treated aggressively. Management also requires proper regulation of dietary sodium, correction of acidosis, limitation of dietary potassium, and minimal use of antihypertensive agents, as well as the administration of allopurinal for urate control.

Acidosis↗

Etiologic factors in lead nephropathy.

The rare occurrence of lead nephropathy in widely differing circumstances has suggested that additional causative factors might be required for its production. Seventeen cases of interstitial nephritis associated with severe chronic lead poisoning were reviewed in an attempt to identify these. Data suggested that alcoholism and preexistent hypertension, and also previous or minor urinary tract disease, may potentiate the injurious effects of lead. We recommend that the diagnosis of lead nephropathy should be a positive one, not one of exclusion, and that stored lead should be removed, particularly in persons with hypertension or previous urinary tract diseases.

Adult↗

Two antimicrobial alkaloids from heartwood of Liriodendron tulipifera L.

Alcoholic extracts of the heartwood of Liriodendron tulipifera have demonstrated antimicrobial activity against Staphylococcus aureus, Mycobacterium smegmatis, Candida albicans, and Aspergillus niger. The antimicrobial activity was associated only with the alkaloidal fraction. Separation of the active alkaloidal fraction by chromatography led to the isolation and identification of dehydroglaucine and liriodenine as the active components. Several other alkaloidal derivatives were prepared and tested. In addition to the active alkaloids, michelabine was also identified in the tertiary nonphenolic base fraction along with the lignan, lirioresinol-B-dimethyl ether, and two N-acetylnoraporphine alkaloids from the nonbasic fraction.

Alkaloids↗

Gastrointestinal and hepatic complications affecting patients with renal allografts.

Of 126 renal allograft recipients, 34 were found to have gastrointestinal and hepatic complications. In order of frequency, these included: mild liver dysfunction, severe hepatitis usually associated with cytomegalovirus infection, peptic ulceration complicated by bleeding, intestinal obstruction, and pancreatitis. These complications did not appear to influence the long-term survival or function of the renal allograft, but proved to be fatal when massive infection of cytomegalovirus affected the gastrointestinal tract and especially the liver. Gastrointestinal and pancreatic complications occurring in renal allograft recipients can be managed in the same manner as in patients who are not receiving immunosuppression. When surgical intervention is required, it should be performed promptly. The fact that these patients are receiving immunosuppressive therapy should not be a contraindication to early surgical intervention. When the presence of ulcerative lesions of the gastrointestinal mucosa, pancreatitis, or hepatitis is confirmed, the possibility of these lesions being caused by viral agents, especially cytomegalovirus, should be considered and attempts to confirm this diagnosis should be made. If cytomegalovirus infection is confirmed and the patient is experiencing rejection of the allograft, careful consideration should be given to immediate discontinuation of immunosuppressive therapy followed by removal of the renal allograft. In this way the relentless and fatal course of the cytomegalovirus infection seen in some of the patients reported in this study may be avoided.

Adult↗

Kidney transplantation in patients with end stage congenital renal disease. Report of eighteen cases and review of the Organ Transplant Registry.

Eighteen patients with end stage congenital renal disease requiring kidney transplantation constituted 12 per cent of the transplantation recipients at this institution over the past six years. The post-transplantation course in this group was remarkably satisfactory, with a 94 per cent graft survival at three years. In addition, we analyzed survival data from over 9,900 patients in the Organ Transplant Registry and demonstrated that transplant recipients with end stage congenital renal disease have equal or better five year patient survival compared with those with acquired end stage renal disease. Only those patients with adult polycystic disease had a less satisfactory prognosis, probably because of age-related factors. In contrast, there were few statistical correlations between renal allograft survival, age, and original disease.

Adolescent↗

Chelation therapy in lead nephropathy.

Although treatment has been well defined for childhood lead poisoning and for industrial lead exposure, the treatment of lead nephropathy has been poorly studied. The available chelating agents are reviewed and the results of treatment in 17 cases of lead nephropathy are shown. It is concluded that lead nephropathy should be recognized early and treated energetically, as this may stabilize or improve renal function. Since EDTA is excreted much like creatinine, the dosage must be reduced proportionately in response to elevated serum creatinine levels in the patient with renal failure.

Acute Kidney Injury↗

Treatment of accelerated hypertension and end stage renal failure by bilateral nephrectomy and renal transplantation.

Accelerated hypertension with end stage renal failure not responsive to hemodialysis and ultrafiltration was an indication for bilateral nephrectomy in 22 patients, five of whom required the procedure as an emergency. Normotension occurred in every patient after removal of the kidneys, but hypertension returned in 12 persons after renal transplantation. Five of these required long term antihypertensive medication, and in an additional seven, some form of diuretic was necessary. There were no distinguishing features among those patients in whom post-transplant hypertension developed from those in whom it did not. In spite of severe accelerated hypertension in the patient with well documented chronic renal disease, prompt nephrectomy and renal transplantation were compatible, with an 86 per cent patient survival rate. Seventy-seven per cent of the kidneys functioned for an average of 29 months.

Acute Kidney Injury↗

Erythrocyte delta-aminolevulinic acid dehydratase activity as a measure of lead exposure.

The measurement of erythrocyte delta-aminolevulinic acid dehydratase (ALA-D) activity has been found to be a useful guide to lead exposure for screening purposes. The pH of the test should be well-controlled for adequate clinical interpretation. False-normal tests are rare even with iron-deficiency anemia or macrocytosis. Recent transfusion and recent bleeding or hemolysis with reticulocytosis tend to invalidate the test. ALA-D activity above 600 International Units effectively excludes significant lead exposure and eliminates the need for further testing. ALA-D activity is maximally depressed at a red cell lead concentration of 200 mug per 100 ml. When activity is moderately depressed, interpretation is difficult and the urinary excretion of lead after the administration of a chelating agent is usually required to differentiate the degree and significance of lead exposure.

Aged↗