Tryptophan and its metabolites in patients on continuous ambulatory peritoneal dialysis and following renal transplantation

Plasma tryptophan (Trp) concentration in its total (TTrp) andnon-protein-bound free form (FTrp) and its metabolite 5-hydroxyindole-3-aceticacid (5-HIAA) as well as muscle Trp contents (MTrp) were studiedin 12 uraemic patients undergoing continuous ambulatory peritonealdialysis (CAPD), 10 renal transplant patients, and 10 healthycontrol subjects. The CAPD patients exhibited signs of muscleweakness, as assessed by dynamometry, and signs of protein malnutritionwith a decreased ratio of alkalisoluble protein relative toDNA in muscle as well as low serum albumin concentration. Inthe uraemic patients TTrp was markedly reduced, whereas in thetransplant patients it did not differ from the controls. TheFTrp, which was separated by the process of equilibrium dialysis,was less in the uraemic (P<0.01) as well as transplant patients(P<0.0l) than in the controls. The plasma FTrp/TTrp ratiowas increased in the uraemic patients (40±8%) but lessin the transplant patients (16±4%), as compared to thecontrols (25±5%). The uraemic patients had increasedplasma concentrations of 5-HIAA, whereas this metabolite couldnot be found in the plasma of renal transplant patients andhealthy controls. MTrp was increased by an average of 33% inthe uraemic patients whereas it did not differ between the transplantpatients and the controls. The results indicate that the abnormalTrp metabolism in uraemic patients is to a large extentcorrectedby a successful renal transplantation. The increased MTrp inCAPD patients would suggest thatthe marked reduction in theplasma Trp, TTrp, and FTrp reflects a shift from the extra-to the intracellularspace rather than a depletion of Trp.     

Pathophysiology of ketoacidosis in Type 2 diabetes mellitus.

AIMS: Despite an increasing number of reports of ketoacidosis in populations with Type 2 diabetes mellitus, the pathophysiology of the ketoacidosis in these patients is unclear. We therefore tested the roles of three possible mechanisms: elevated stress hormones, increased free fatty acids (FFA), and suppressed insulin secretion. METHODS: Forty-six patients who presented to the Emergency Department with decompensated diabetes (serum glucose > 22.2 mmol/l and/or ketoacid concentrations > or = 5 mmol/l), had blood sampled prior to insulin therapy. Three groups of subjects were studied: ketosis-prone Type 2 diabetes (KPDM2, n = 13) with ketoacidosis, non-ketosis-prone subjects with Type 2 diabetes (DM2, n = 15), and ketotic Type 1 diabetes (n = 18). RESULTS: All three groups had similar mean plasma glucose concentrations. The degree of ketoacidosis (plasma ketoacids, bicarbonate and anion gap) in Type 1 and 2 subjects was similar. Mean levels of counterregulatory hormones (glucagon, growth hormone, cortisol, epinephrine, norepinephrine), and FFA were not significantly different in DM2 and KPDM2 patients. In contrast, plasma C-peptide concentrations were approximately three-fold lower in KPDM2 vs. non-ketotic DM2 subjects (P = 0.0001). Type 1 ketotic subjects had significantly higher growth hormone (P = 0.024) and FFA (P < 0.002) and lower glucagon levels (P < 0.02) than DM2. CONCLUSIONS: At the time of hospital presentation, the predominant mechanism for ketosis in KPDM2 is likely to be greater insulinopenia.     

Invalid use of pain drawings in psychological screening of back pain patients

Drawings by low back pain patients depicting the severity, type, and location of their pain have been suggested as a brief screening technique for psychological involvement in the pain complaints. A study of 212 back pain patients showed that pain drawings cannot validly be used in this way, since over half of the patients meeting MMPI criteria for psychological involvement in their pain were incorrectly identified as normal on the Pain Drawing test.     

Premedication and high-dose fentanyl anesthesia for myocardial revascularization: a comparison of lorazepam versus morphine-scopolamine

Using a randomized double-blind placebo-controlled experimental protocol, the authors compared two premedication regimens in 42 patients undergoing elective myocardial revascularization. Group L patients (n = 23) received lorazepam 0.06 mg/kg po 90 min preoperatively, while group M patients (n = 19) received morphine 0.1 mg/kg im, plus scopolamine 0.006 mg/kg im 60 min preoperatively. Anesthesia was induced with fentanyl 100 micrograms/kg and atracurium 0.50 mg/kg administered over 10 min. The treatment groups did not differ significantly with respect to the degree of sedation or anxiolysis achieved, or the rapidity of induction with fentanyl. Premedication significantly influenced the hemodynamic response to anesthetic induction. Hemodynamics were stable post-induction in group M, but cardiovascular depression was noted in group L. Control heart rate (HR) was lower in group L. The HR, arterial pressure, and cardiac index were significantly lower, following both induction and intubation, in group L. Following sternotomy hemodynamics were identical in both groups. Serum fentanyl concentration was significantly higher during intubation in group L, probably secondary to the pharmacokinetic consequences of a decreased CI. New electrocardiographic evidence of myocardial ischemia did not occur in either group. Based on their findings with fentanyl-at-racurium, and their review of the literature, the authors speculate that premedication exerts a significant hemodynamic effect during induction with other narcotic-relaxant combinations.     

Extraocular muscle involvement in Wegener's granulomatosis

A 44-year-old man with Wegener's granulomatosis involving the upper and lower respiratory tracts developed a diplopia with involvement of three extraocular muscles of one eye and one extraocular muscle of the other eye. The ocular and orbital examinations were otherwise normal, as were computerized tomography (CT) scans of the brain and orbits. The patient was treated with systemic Cytoxan and Prednisone and the respiratory and extraocular muscle abnormalities cleared within 1 month. Because of the bilateral extraocular muscle involvement, the absence of central nervous system or orbital findings, and the rapid and complete resolution after Cytoxan and Prednisone therapy, a diffuse vasculitis affecting the extraocular muscles was implicated as the etiology of the diplopia.     

External auditory atresia and the deleted chromosome

Four patients presented with suspected hearing loss and growth and motor retardation. Hearing loss was confirmed, and in three patients was conductive in nature, associated with bilateral atresia or hypoplasia of the bony external auditory canal and essentially normal pinnae. One patient had normal ear canals and mixed hearing loss. The patients had a variety of somewhat subtle associated defects. These included epicanthic folds, strabismus, microcephaly, hypertelorism, hypoplasia of the mid-face, carpshaped mouth, short stature, foot anomalies, congenital heart disease and absent IgA. Chromosome analysis showed deletion of the long arm or a ring formation of chromosome 18, which defects are potentially transmissible to the next generation. Petrous pyramid polytomography showed atresia plates in the region of the tympanic membrane in the three patients with abnormal external auditory canals. The middle ears appeared normal. Polytomography was entirely normal in the fourth patient with patent canals and a mixed hearing loss. The patient with “isolated” auditory atresia, retardation, relatively minor facial abnormalities and either previously surgically corrected or previously undetected other abnormalities (e.g., congenital heart disease, club foot), should be suspect for this disorder. The diagnosis is confirmed by karyotype. Complete workup also includes audiometry and petrous pyramid polytomography. Karyotypes should be performed on the parents to rule out a balanced translocation. Otologic management is basically the same as that in other children with external auditory atresia, but may be contingent on the control of other health problems.     

Quantitative microradiographic study of simultaneous demineralization/remineralization of dental enamel in weak acid buffers

The remineralization behavior of weak acid-treated bovine tooth enamel has been investigated using a recently developed quantitative microradiographic method. Acetate buffer solutions at pH 4.5 containing calcium, phosphate, and 10 ppm fluoride were used in this study. When the solution ion activity product ( KFAP = a10CA a6PO4 a2F ) was 1 X 10(-108), the remineralization of the demineralized region was relatively uniform and complete. On the other hand, when the KFAP was approximately less than or equal to 1 X 10(-112), remineralization of the outer 10-20 micron was incomplete. In addition, for the smaller KFAP solutions there was significant demineralization in the deeper recesses of the originally demineralized region. These results agree with a recent chemical kinetics study in which it was proposed that KFAP = 1 X 10(-112) demarcated the region of solution conditions in which remineralization only occurs from that in which simultaneous demineralization/remineralization takes place. A model consistent with all of the data is proposed.     

On the mechanisms of inhibition of insulin action by small-molecular-weight trypsin inhibitors

Evidence from a number of laboratories has suggested that the mechanism of insulin action involves the release of an intracellular mediator polypeptide from the plasma membrane. It has been proposed that activation of a protease with trypsin-like specificity is involved in release of the putative mediator. In an effort to assess the potential role of such a protease in intact cells, the present study tested the effects of a variety of low-mol-wt protease inhibitors on insulin's metabolic action in isolated rat epididymal fat cells. The protease inhibitors studied included p-aminobenzamidine, benzamidine, phenylguanidine, diisopropylfluorophosphate, leupeptin, and the competitive substrate N-alpha-tosyl-L-arginine methylester. Leupeptin was devoid of activity. Most of the other inhibitors used were able to interfere with insulin-stimulated metabolism if used in sufficiently high concentrations, concentrations considerably higher than those required for inhibition of known proteases or inhibition of intracellular processes in a previously described system which involves a trypsin-like enzyme. Moreover, they displayed various activities unrelated to protease inhibition that could explain their effects on insulin action better than protease inhibition. While none of the data on individual inhibitors were by themselves convincing enough to either confirm or reject the hypothesis concerning the involvement of a protease with trypsin-like specificity in insulin action, taken together our results do weaken the hypothesis considerably and in particular render the involvement of an extracellular trypsin-like enzyme improbable.