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Biomedical subjects

J Rehder

Publications and source records attributed to J Rehder.

11 recordsLinked to original sources

Hypopituitarism following severe traumatic brain injury.

Although hypopituitarism is a known complication of traumatic head injury, it may be under-recognized due to its subtle clinical manifestations. To address this issue, we determine the prevalence of neuroendocrine abnormalities in patients rehabilitating from severe traumatic brain injury (Glasgow Coma Scale < or = 8). 76 patients (mean age 39 +/- 14 yr; range 18-65; 53 males and 23 females; BMI 25.8 +/- 4.2 kg/m2; mean +/- SD) with a severe traumatic brain injury, an average of 22 +/- 10 months before this study (median, 20 months), underwent a series of standard endocrine tests, including TSH, free T4, T4, T3, prolactin, testosterone (males), estradiol (females), cortisol, ACTH, GH, and IGF-I. All subjects also underwent GH response to GHRH + arginine. Growth hormone deficiency (GHD) was defined as a GH response < 9 microg/L to GHRH + arginine and was confirmed by ITT (< 3 microg/L). Pituitary deficiency was shown in 24% of the patients (18/76). 8% (n = 6) had GHD (GH-peak range [GHRH + arginine]: 2.8-6.3 microg/L; GH-peak range [ITT]: 1.5-2.2 microg/L; IGF-I range: 62-174 microg/L). 17% (n = 13) had hypogonadism (total testosterone < 9.5 nmol/L and low gonadotropins in 12 males; low estradiol, and low gonadotropins in 1 female). Total testosterone levels did not correlate with BMI or age. 2 males with hypogonadism also showed a mild hyperprolactinemia (33 and 41 ng/ml). 3% (n = 2) patients had partial ACTH-deficiency (cortisol-peak [ITT] 392 and 417 nmol/L) and 3% (n = 2) had TSH-deficiency. In summary, we have found hypopituitarism in one-fourth of patients with predominantly secondary hypogonadism and GHD. These findings strongly suggest that patients who suffer head trauma must routinely include neuroendocrine evaluations.

Adolescent↗

Superoxide release and cellular gluthatione peroxidase activity in leukocytes from children with persistent asthma.

Asthma is an inflammatory condition characterized by the involvement of several mediators, including reactive oxygen species. The aim of the present study was to investigate the superoxide release and cellular glutathione peroxidase (cGPx) activity in peripheral blood granulocytes and monocytes from children and adolescents with atopic asthma. Forty-four patients were selected and classified as having intermittent or persistent asthma (mild, moderate or severe). The spontaneous or phorbol myristate acetate (PMA, 30 nM)-induced superoxide release by granulocytes and monocytes was determined at 0, 5, 15, and 25 min. cGPx activity was assayed spectrophotometrically. The spontaneous superoxide release by granulocytes from patients with mild (N = 15), moderate (N = 12) or severe (N = 6) asthma was higher at 25 min compared to healthy individuals (N = 28, P < 0.05, Duncan test). The PMA-induced superoxide release by granulocytes from patients with moderate (N = 12) or severe (N = 6) asthma was higher at 15 and 25 min compared to healthy individuals (N = 28, P < 0.05 in both times of incubation, Duncan test). The spontaneous or PMA-induced superoxide release by monocytes from asthmatic patients was similar to healthy individuals (P > 0.05 in all times of incubation, Duncan test). cGPx activity of granulocytes and monocytes from patients with persistent asthma (N = 20) was also similar to healthy individuals (N = 10, P > 0.05, Kruskal-Wallis test). We conclude that, under specific circumstances, granulocytes from children with persistent asthma present a higher respiratory burst activity compared to healthy individuals. These findings indicate a risk of oxidative stress, phagocyte auto-oxidation, and the subsequent release of intracellular toxic oxidants and enzymes, leading to additional inflammation and lung damage in asthmatic children.

Adolescent↗

Scintigraphic studies of rectal emptying in patients with constipation and defecatory difficulty.

We prospectively evaluated 38 adult patients with chronic constipation with and without defecatory difficulties using a newly described scintigraphic test to measure rectal emptying and compared them to 20 healthy controls. All patients underwent anorectal manometry, and 30 who complained of infrequent defecation underwent a colonic transit study using radiopaque markers. Control subjects promptly evacuated both 100 ml and 200 ml artificial stool in a characteristic fashion, but three evacuated none of the 100-ml volume and two had no evacuation of the 200-ml stool (inhibited controls). Constipated patients exhibited three patterns of emptying: (1) normal emptying of both volumes (47%); (2) poor emptying of both volumes or inhibited defecation (29%); and (3) normal emptying of the 200-ml but abnormal evacuation of the 100-ml volume (24%). An abnormal expulsion pattern during manometry occurred in 21% of patients and was strongly associated with the inhibited defecation pattern. However, defecation patterns could not be predicted on the basis of age, gender, symptoms, duration of complaints, colonic transit, or other rectal manometric parameters. Although rectal scintigraphy has potential advantages as a diagnostic test in terms of quantitation and decreased radiation exposure, the inability of the test to distinguish patients with slow transit constipation and defecatory complaints makes the potential utility of this test of uncertain value in clinical and investigative settings.

Adult↗

Incidence and natural history of phrenic neuropathy occurring during open heart surgery.

OBJECTIVE: To study the incidence of phrenic neuropathy following coronary artery bypass grafting and determine long-term outcome. DESIGN: Prospective observational. SETTING: Surgical ICU in a university hospital, out-patient follow-up. PATIENTS: Ninety-two consecutive patients undergoing open heart surgery. INTERVENTIONS: None. MEASUREMENTS: Chest radiographs (CXR) 48 to 72 h post-operatively, ultrasonography of diaphragm, phrenic nerve conduction studies, diaphragmatic electromyogram, each repeated every 1 to 3 months until normal. MAIN RESULTS: Seventy-eight of 92 (78 percent) patients had abnormal radiographs, 42 of 78 (54 percent) with abnormal CXRs had abnormal diaphragm motion, 24 of 42 (57 percent) with abnormal motion had phrenic neuropathy. Patients with normal diaphragm motion improved faster than those without; patients with normal nerve conduction (and abnormal motion) improved faster than those with abnormal nerve conduction. CONCLUSIONS: Phrenic neuropathy is relatively common if sensitive tests are utilized for diagnosis. Nerve conduction studies can predict duration of morbidity. Most patients have low morbidity and recover fully. Abnormal diaphragm motion alone is not diagnostic of phrenic nerve injury.

Aged↗

[Pharmacokinetics and pharmacodynamics of prednisolone following extremely high dosage as prednisolone hemisuccinate].

Plasma levels of prednisolone and prednisolone hemisuccinate of volunteers were measured with HPLC following i.v. injections of 1200 and 75 mg of prednisolone, given as the water-soluble hemisuccinate ester. The hemisuccinate ester is hydrolyzed relatively quickly with a plasma half-life between 18 and 25 min, and the resulting prednisolone has a plasma half-life of 3.5-3.7 h. The dose dependency of the pharmacokinetic parameters indicates a partial saturation of the metabolizing enzymes as consequence of the application of the high dose of prednisolone. In saliva no hemisuccinate could be detected. The prednisolone saliva concentration corresponds with those of non-protein-bound prednisolone in plasma measured at the same time. Only minor quantities of intact ester (1-8%) or intact prednisolone (2-4%) are excreted in urine. Following the application of 1200 mg prednisolone the endogenous cortisol level is partially suppressed only 24 h after the i.v. injection; 48 h later the difference from the basis value is not statistically significant. Leukocytosis and granulocytosis are at maximum 24 h after the injection of the high dose, and after 48 h normal values are observed. Lymphocytes and monocytes fall below normal levels for a longer time after 1200 mg compared to 75 mg, the minimum is between 4 and 8 h. Glucose levels are enhanced dose-dependently. They are normalized even after the extremely high dose at 24 h. Sodium, potassium, calcium, plasma proteins, urea, creatinine, hematocrit and hemoglobin showed no significant differences within 48 h following the injections.

Adult↗

Simultaneous determination of glucocorticoid alcohols, their succinates and hydrocortisone in plasma.

A reversed-phase high-performance liquid chromatographic (HPLC) assay is described for the simultaneous determination of methylprednisolone, methylprednisolone-21-hemisuccinate and endogenous hydrocortisone in biological fluids. This assay is also applicable to the determination of prednisolone-21-hemisuccinate in the presence of prednisolone and hydrocortisone in biological fluids. Prednisolone and hydrocortisone are determined by normal-phase HPLC. The stability of hemisuccinate esters in ampoules, in saline and in plasma has been studied. Whereas the esters were stable in saline at 37 degrees C, they were considerably hydrolysed in plasma at the same temperature. Comparison of hydrocortisone levels obtained by HPLC and radioimmunoassay (RIA) showed the large influence of the cross-reactivity of methylprednisolone and hydrocortisone in the presence of high serum concentrations of methylprednisolone.

Journal Article↗

Kinetics of methylprednisolone and its hemisuccinate ester.

Methylprednisolone in the form of its hemisuccinate ester was injected intravenously in doses of 10 mg/kg and 63.1 mg. Plasma levels of methylprednisolone and of the ester were measured and their kinetics were calculated. Results indicate dose dependency in the kinetics of both. About 10% of the dose was excreted unchanged as hemisuccinate in the urine, indicating incomplete conversion of the prodrug. When methylprednisolone (80 mg) was also taken by mouth, the relative bioavailability of the tablets was 99%. Saliva levels of methylprednisolone were low but paralleled plasma levels in the postdistribution phase. No methylprednisolone hemisuccinate was found in saliva.

Absorption↗

Pharmacokinetics of prednisolone after high doses of prednisolone hemisuccinate.

Prednisolone in the form of its hemisuccinate was given intravenously in two different doses (1200 mg and 75 mg). Plasma levels of the ester and prednisolone were measured and pharmacokinetic parameters were calculated. The results indicate a dose-dependency in the pharmacokinetics of both hemisuccinate and the free alcohol. For the high dose 8 per cent of the administered ester was found unchanged in the urine indicating incomplete conversion of the pro-drug. Comparison with previous studies leads to the conclusion that prednisolone shows doubled non-linear pharmacokinetics with higher total body clearance in the medium dose range than in the low and high dose range. Volume of distribution changes accordingly, but overall elimination rate remains remarkably constant. Saliva levels of prednisolone were low and agree reasonably well with calculated plasma concentrations of free, non-protein-bound prednisolone. No prednisolone hemisuccinate was found in saliva.

Adult↗

Pharmacokinetics of dexamethasone and its phosphate ester.

Dexamethasone in form of its phosphate was given intravenously in two different doses (1.5 mg kg-1 and 15 mg). Plasma levels of the ester and dexamethasone were measured and pharmacokinetic parameters were calculated. The results indicate no dose-dependency of the pharmacokinetic parameters in the investigated range for dexamethasone. Conversion from the prodrug to the active form was rapid; maximum dexamethasone plasma concentrations were reached after 10 min. The results were verified by dexamethasone level monitoring in patients after chronic dosing. Predicted and achieved steady state levels agreed well.

Adult↗

[Glucose-6-phosphate dehydrogenase deficiency with recurrent infections: case report]

OBJECTIVE: To report a case of rare neutrophil functional disorder with clinical and laboratory findings similar to those of chronic granulomatous disease. METHODS: Patient with extremely reduced level of glucose-6-phosphate dehydrogenase and recurrent infections that improved after continuous use of cotrimoxazole. The patient presented leukocytes with defective respiratory burst, similar to what occurs in chronic granulomatous disease. COMMENTS: The diagnosis of glucose-6-phosphate dehydrogenase deficiency in neutrophils should be considered in any patient with hemolytic anemia whose level of G6PD is extremely low or in any patient that presents recurrent infections as differential diagnosis of chronic granulomatous disease.

Journal Article↗