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Biomedical subjects

C Mathias

Publications and source records attributed to C Mathias.

15 recordsLinked to original sources

Chronic myelogenous leukemia: extending the prospects for cure.

Advances in our understanding of the molecular defects underlying this leukemia have led to novel therapeutic approaches that have not only altered the natural history of the disease but also apparently effected cures in some patients. The next step may be to offer the possibility of a cure to all patients. Allogeneic bone marrow and T cell transplantation shows promise in this regard.

Bone Marrow Transplantation

Role of sodium in contrast medium-induced polymorphic ventricular tachycardia: results in a rabbit model of lengthened QT interval.

RATIONALE AND OBJECTIVES: The authors (a) compared the proarrhythmic effects of ioxaglate (152 mmol/L sodium) and iohexol (no sodium) in a rabbit model and (b) assessed the effect of adding 150 mmol/L sodium to isotonic iohexol. MATERIALS AND METHODS: Either ioxaglate (320 mg of iodine per milliliter) or iohexol (350 mg of iodine per milliliter) was selectively injected into the right coronary artery (1.5 mL over 30 seconds) of 10 rabbits, some of which also received the alpha 1-adrenergic receptor agonist methoxamine. To validate the model, the class III antiarrhythmic agent clofilium was injected intravenously during methoxamine infusion. Frontal electrocardiography was performed continuously to detect polymorphic ventricular tachycardia (PVT). In a second study, the authors assessed the frequency of arrhythmias after injection of isotonic iohexol solution (145 mg of iodine per milliliter), either alone or with 150 mmol/L sodium. RESULTS: Methoxamine significantly lengthened the QT, QTc, and RR intervals (P < .05). The use of clofilium alone induced no PVT, whereas five of eight methoxamine-infused rabbits developed PVT after clofilium injection (P = .03). Both contrast media prolonged the repolarization period. Iohexol alone induced a higher frequency of PVT than did ioxaglate alone (P = .0006). Methoxamine infusion did not potentiate the frequency of PVT in the ioxaglate-injected rabbits. The addition of sodium to isotonic iohexol prevented the occurrence of PVT (P = .0006). CONCLUSION: Although ioxaglate prolonged the repolarization period, it did not cause a higher frequency of arrhythmia when injected in association with methoxamine. Iohexol, which contains no sodium, induced a high frequency of arrhythmia. The addition of a physiologic concentration of sodium to isotonic iohexol can prevent ventricular arrhythmias.

Adrenergic alpha-Agonists

"Minimal change" multiple system atrophy.

We describe the pathological findings in two patients who developed atypical parkinsonism and autonomic failure, leading to a diagnosis of multiple system atrophy (MSA). Postmortem examination of the brain showed cell loss restricted to substantia nigra and locus coeruleus. However, glial cytoplasmic inclusions (GCIs) were present in both cases. We propose that GCIs are highly suggestive of a pathological diagnosis of MSA in the absence of detectable cell loss outside pigmented brain stem nuclei and that brains from cases of atypical parkinsonism should routinely be examined for their presence.

Adult

Small bowel myoelectric activity in peritonitis.

Peritonitis is associated clinically with paralytic ileus, but the physiologic mechanisms of the effects of peritonitis on bowel myoelectric activity have not been explored. Bipolar electrodes were inserted into the rats, and myoelectric control recordings were obtained for 4 h/d for 5 consecutive days. Peritonitis was then induced, and myoelectric recordings were again obtained. Each animal served as its own control. Prior to induction of peritonitis (control), phase I, II, and III myoelectric activity was present in all recordings. The cycle duration of the migrating myoelectric complex was 17.17 +/- 0.39 minutes, and the migration velocity of phase III was 0.61 +/- 0.02 cm/min. The most striking feature during peritonitis was the complete inhibition of phase II activity. Phase III activity, however, was present with a cycle duration of 16.69 +/- 0.42 minutes. This study shows that some features of intestinal myoelectric activity (phase III) are preserved during episodes of peritonitis, and others are changed (phase I) or lost (phase II). Disappearance of phase II activity in this type of ileus emphasizes its importance in normal small bowel motility.

Animals

Left external iliac artery dissection and bilateral renal artery aneurysms secondary to fibromuscular dysplasia: a case report.

A case of acute lower limb ischaemia due to spontaneous dissection of the left external iliac artery and coincidental bilateral renal artery aneurysms is reported. Histopathological examination of the resected iliac artery showed features of fibromuscular dysplasia. Dissection of the external iliac artery without involvement of the aorta is extremely rare with only two previously reported cases. The aetiology and management of fibromuscular dysplasia is discussed.

Acute Disease

Expression of intron-containing C. elegans heat shock genes in mouse cells demonstrates divergence of 3' splice site recognition sequences between nematodes and vertebrates, and an inhibitory effect of heat shock on the mammalian splicing apparatus.

Splicing of a pair of intron-containing heat shock genes from Caenorhabditis elegans has been studied in transfected mouse cells. The hsp16-1 and hsp16-48 genes of C. elegans encode 16,000 Da heat shock polypeptides. Each gene contains a short intron of 52 (hsp16-1) or 55 (hsp16-48) base pairs. When these genes were introduced into mouse cells, they were efficiently induced following heat shock, but splicing of the introns was abnormal. In mouse cells, cleavage of the hsp16 transcripts occurred at the correct 5' splice sites, but the 3' splice sites were located at AG dinucleotides downstream of the correct sites. This aberrant splicing was not solely due to the small size of the C. elegans introns, since a hsp16-1 gene containing an intron enlarged by tandem duplication showed exactly the same splicing pattern. The mouse cells thus seem to be unable to recognize the natural 3' splice sites of the C. elegans transcripts. The efficiency of splicing was greatly reduced under heat shock conditions, and unspliced transcripts accumulated in the nucleus. During a subsequent recovery period at 37 degrees C, these transcripts were spliced and transported to the cytoplasm.

Animals

Unusual cranial and abdominal computed tomographic (CT) scan appearances in a case of systemic lupus erythematosus (SLE).

A 35 year old woman presented with headache and fever. Computed brain tomography showed diffuse low attenuation in the cerebral white matter. Several months later, serological tests for systemic lupus erythematosus (SLE) became positive. In spite of immunosuppressive therapy she relapsed after six months of treatment, presenting with abdominal symptoms and signs. On this occasion an abdominal CT scan showed distended and oedematous loops of bowel attributed to an underlying vasculitis. This case illustrates novel CT scan appearances in two systems involved in SLE.

Adult

Effect of betablockade on dynamic exercise in human heart transplant recipients.

We evaluated the tolerance of heart transplant recipients to acute betablockade during maximal dynamic exercise. Although the increase in rate and systolic blood pressure were attenuated, exercise tolerance was reduced by only about 15%, which is similar to that previously reported in normal individuals. Betablockade attenuated the increases in heart rate of the denervated donor hearts to a greater extent compared to the increases in the innervated recipient hearts in patients with heterotopic heart transplantation. Therefore, betablockers may be safely used in heart transplantation for appropriate indications such as hypertension.

Blood Pressure

Increased numbers of alpha receptors in sympathetic denervation supersensitivity in man.

Cardiovascular responses to intravenous administration of norepinephrine and the properties of alpha receptors on platelets were compared in normal human subjects and subjects with multiple system atrophy (MSA) and sympathetic degeneration. All the subjects with MSA had low plasma norepinephrine concentrations (in the supine position) (0.42 +/- 0.09 nM, normal 3.47 +/- 0.58 nM), which did not increase on tilt. The pressor sensitivity of subjects with MSA to norepinephrine infusion was increased 10- to 20-fold, demonstrating denervation supersensitivity to adrenergic agonists. Analysis of alpha receptors was by binding of [3H]dihydroergocryptine to platelets. Results are shown as mean +/- standard error of the mean. In the MSA subjects, the number of alpha receptors (1,712 +/- 699 fmol/10(8) platelets) was about sevenfold greater than in normal subjects (224 +/- 21 fmol/10(8) platelets), and the affinity, as measured by the equilibrium dissociation constant (Kd), was similar in both groups (MSA subjects, 9.6 +/- 4.3 nM; normal subjects, 4 +/- 0.5 nM). These observations suggest that an increase in alphaadrenergic receptor numbers may account for the denervation supersensitivity to infused norepinephrine in patients with sympathetic degeneration. All the subjects with MSA had low levels of the endogenous adrenergic transmitter norepinephrine: the simultaneous increase in alpha adrenergic receptors supports the theory of agonist regulation of receptor numbers.

Adult

T-cell depletion of spleen in patients with longstanding lepromatous leprosy.

In 8 autopsied lepromatous patients the spleen was examined histopathologically and their differential cell population was counted in subcapsular area, red pulp and white pulp. There was considerable reduction of lymphocytes and well marked increase in macrophages and plasma cells in the thymus dependent white pulp. In the subcapsular area and the red pulp, although there was an increase in plasma cells and macrophages no significant reduction of lymphocytes was recorded. Therefore, it is suggested that in lepromatous leprosy there is a selective reduction in the number of T lymphocytes.

Adult