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M Luke

Publications and source records attributed to M Luke.

At least 19 recordsLinked to original sources

Digitoxinlike and digoxinlike immunoreactivitis in sera of patients with uremia and liver disease as measured by fluorescence polarization immunoassays: poor correlation between digitoxinlike and digoxinlike immunoreactivities.

Digoxinlike immunoreactive substances (DLIS) cross-react with antidigoxin antibodies and falsely elevante total digoxin levels. Cross-reactivity of DLIS with various immunoassays for digoxin has been extensively studied in the past. The digitoxin molecule differs from digoxin by having one extra hydroxyl group in the aglycone ring. Therefore, DLIS may also falsely elevate total digitoxin concentrations. However, in the past, limited studies have shown the presence of digitoxinlike immunoreactive substances (DTLIS) in cord blood and sera of neonates. We compared DLIS and DTLIS concentrations in sera of patients with uremia, liver disease, and hypoalbuminemia. We found measurable DLIS concentrations in 11 of 45 patients by the fluorescence polarization immunoassay (FPIA) for digoxin (range, 0.20-0.89 ng/ml digoxin equivalent). These patients did not receive any digoxin or digitoxin. Using the FPIA, we also found elevated DTLIS concentrations in 10 of these 45 patients (range, 2.88-21.24 ng/ml digitoxin equivalent). Given the narrow therapeutic range of digitoxin (15-30 ng/ml), this cross-reactivity is significant. Elevated concentrations of DTLIS in sera falsely elevated the measured concentrations of digitoxin (positive interference) when known amounts of digitoxin were added to such sera. Interestingly, we found a poor correlation between DLIS and DTLIS concentrations in sera of patients with liver disease and uremia (r = 0.58), with some patients having no measurable DLIS activity but measurable DTLIS activity and vice versa. Digoxin showed only 4-8% cross-reactivity against digitoxin antibody with a wide range of concentration. Some proposed DLIS compounds (nonesterified fatty acids, cholic acid, lysophospholipid, and DHEA-sulfate) did not show any cross-reactivity with the digitoxin assay at a concentrations much higher than the physiologic range. We conclude that DTLIS activity is present in patients with liver disease and uremia, and the correlation between DLIS activity and DTLIS activity is poor. Moreover, some proposed DLIS do not explain the DTLIS activity detected in serum.

Digitoxin↗

Valproic acid-ketoconazole interaction in normal, hypoalbuminemic, and uremic sera: lack of interaction in uremic serum caused by the presence of inhibitor.

Ketoconazole is an antifungal agent widely used in the management of patients with fungal infection, especially in patients with acute acquired immuno-deficiency syndrome (AIDS). Ketoconazole is 99% bound to serum albumin and may interact with valproic acid, an anticonvulsant with 90% to 95% binding to serum albumin. The interaction may be more significant in hypoalbuminemia, a common finding in patients with AIDS. However, valproic acid-ketoconazole interaction has not been reported. The authors prepared two serum pools from patients receiving valproic acid with normal serum albumin and another pool from patients with hypoalbuminemia. Another serum pool was prepared from uremic patients not receiving valproic acid. The aliquots of serum pool were supplemented with various concentrations of ketoconazole, representing therapeutic and slightly higher therapeutic concentrations. The concentrations of free valproic acid were determined in protein-free ultrafiltrates (prepared by centrifuging specimens at 25 degrees C with the Centrifree Micropartition System at 1500 g for 20 minutes) using fluorescence polarization immunoassay. In the serum pool with normal albumin concentration, the authors observed statistically significant displacement of valproic acid only at higher ketoconazole concentrations (10 and 20 micrograms/ml) whereas, in the serum pool with hypoalbuminemia, they observed statistically significant displacement of valproic acid by ketoconazole with lower and higher concentrations of ketoconazole. The magnitude of displacement was more significant at high valproic acid concentrations (95 and 150 mg/ml, respectively) probably because of the concentration-dependent binding of valproic acid to serum albumin. The authors observed no displacement of valproic acid by ketoconazole in the uremic serum pool. On the other hand, the free valproic acid concentrations were decreased in the presence of ketoconazole in the uremic serum pool.

Anticonvulsants↗

Cimetidine as an adjuvant treatment in colorectal cancer. A double-blind, randomized pilot study.

PURPOSE: To evaluate the influence of a H2 receptor antagonist (cimetidine) on survival in patients with colorectal carcinoma, a randomized, controlled pilot study was performed in three university hospitals in Copenhagen, Denmark. METHODS: A total of 192 patients, who had undergone a resection or an exploratory operation for adenocarcinoma of the colon or rectum between May 1988 and May 1991, were enrolled in the study. After a median observation time of 40 months, outcome was noted for each patient concerning cancer-specific mortality rate. RESULTS: In patients operated with curative intent (n = 148), no difference was found in cancer-specific mortality between the two treatments. However, a tendency toward reduction in mortality rate was found in patients with curatively operated Dukes Stage C carcinoma (P = 0.11, log-rank test; difference, 29 percent; 90 percent confidence interval, 2 to 57 percent) in the cimetidine-treated group. In patients with disseminated disease no total difference was found between the two treatment groups. CONCLUSIONS: Cimetidine does not seem to reduce mortality in patients with colorectal cancer, but there seems to be a tendency toward a survival benefit in patients undergoing surgery for Dukes Stage C carcinoma. Results seem to justify trials in this patient category to reveal a benefit of H2 receptor antagonists in adjuvant therapy of colorectal carcinoma.

Adenocarcinoma↗

Is the sleep apnoea/hypopnoea syndrome inherited?

BACKGROUND--The aetiology of the sleep apnoea/hypopnoea syndrome (SAHS) is unclear in many patients. Snoring, a prerequisite for SAHS, runs in families. A study was carried out to determine whether there is an increased frequency of irregular breathing during sleep in relatives of patients with SAHS. METHODS--A prospective study was performed of first degree relatives of 20 consecutive non-obese (BMI < 30 kg/m2) patients with SAHS. Questionnaires on SAHS symptoms were sent to all first order relatives and those living within 150 miles of Edinburgh were invited for overnight monitoring of their breathing, sleep, and oxygenation patterns in the sleep laboratory. RESULTS--Ten of the 40 relatives had more than 15 apnoeas + hypopnoeas/hour of sleep, and eight had more than five 4% desaturations/hour. These frequencies of irregular breathing and desaturation are significantly higher than in the British population. Cephalometric studies showed no skeletal abnormality but an increased uvular width was found in the affected relatives. CONCLUSIONS--There is an increased frequency of abnormal breathing during sleep in relatives of non-obese patients with SAHS.

Adult↗

Chromosome assembly in vitro: topoisomerase II is required for condensation.

The role of topoisomerase II (topo II) in chromosome condensation was studied in a mitotic extract derived from Xenopus eggs by specific immunodepletion. HeLa nuclei, which have a high complement of endogenous topo II, are converted to mitotic chromosomes in the topo II-depleted extract equally well as in the control. Chicken erythrocyte nuclei, however, which have a very low content of topo II, do not convert to condensed chromosomes in the depleted extract, although their condensation is normal upon addition of purified topo II. Dosage experiments support the possible notion of a structural involvement of topo II in chromosome condensation. In the topo II-depleted extract the erythrocyte nuclei progress to precondensation chromosomes, which lack the nuclear membrane-lamina complex and consist of a cluster of swollen chromatids.

Animals↗

Ceftriaxone vs. ampicillin + metronidazole as prophylaxis against infections after clean-contaminated abdominal surgery.

In a prospective, controlled, double-blind study, 496 patients undergoing abdominal surgery were given antibiotic prophylaxis with a single dose of either ceftriaxone or ampicillin + metronidazole. No significant intergroup difference was found between the respective overall rates of infectious complications (3.2% and 4.9%). Analysis of the microbiologic findings showed incisional wound infections, mainly caused by gram-negative rods, to be more common in the ampicillin-metronidazole group, whereas deep wound infections were more frequent in the ceftriaxone group. It is concluded that ceftriaxone seems to be more efficient than ampicillin-metronidazole as prophylaxis against incisional wound infection, but should preferably be supplemented with an antianaerobic agent to prevent deep wound infections.

Abdomen↗

Immune thrombocytopenia and May-Hegglin anomaly during pregnancy.

A 22-year-old pregnant woman presented with presumed immune thrombocytopenia. Postpartum, the persistence of Dohle bodies and macrothrombocytopenia led to the diagnosis of the May-Hegglin anomaly. Clinical management is described. The May-Hegglin anomaly may be mimicked by immune thrombocytopenia in pregnancy unless suspected and carefully excluded.

Adult↗

The potential difference response of the human gastric mucosa to cimetidine.

The effect of cimetidine on the dynamic transmucosal potential difference (PD) of the normal human gastric fundus was studied, to quantitate the influence of the hydrogen ion on measurements. PD was measured between an intravenous flowing bridge of isotonic NaCl and a perfused intragastric probe by means of two calomel half-cells. The probe was used for luminal infusion of different electrolyte solutions, which at the same time functioned as the mucosal measuring electrode. Cimetidine increased PD -12 mV during NaCl infusion. When gastric acidity was neutralized with isotonic NaHCO3, this change of PD decreased to -5 mV. We conclude that 60% of the PD increase seen after H2 blockade may be explained by the mere disappearance of H+ from the gastric juice, and the other 40% by changes in the gastric mucous membrane. PD decreased progressively as luminal NaCl content was lowered, but this reaction was reversed after cimetidine. These findings may be explained by a twofold decrease of transmucosal permeability to Na+ during H2 blockade.

Adolescent↗

[Endoscopic treatment of acute colonic pseudo-obstruction].

Four patients admitted on account of various extracolonic conditions developed acute pseudo-obstruction of the colon during hospitalisation. All of these were successfully treated with colonoscopic decompression. The technique is described.

Acute Disease↗

Quantitation of type II topoisomerase in oocytes and eggs of Xenopus laevis.

We have generated a monoclonal antibody and a polyclonal antiserum specific for Xenopus laevis topoisomerase II. Using quantitative immunoprecipitation and Western blotting techniques, we have determined the content of topoisomerase II in X. laevis oocytes during oogenesis and in unfertilized eggs. An average stage I oocyte contains 6 pg of topoisomerase II. The content of topoisomerase II per oocyte increases throughout oogenesis to 1.5 ng per stage VI oocyte. The topoisomerase II protein in stage VI oocytes is stored in the germinal vesicles. The cellular content of type II topoisomerase increases significantly when stage VI oocytes are hormonally stimulated to mature into unfertilized eggs.

Animals↗

Randomized trial of fibrin adhesive for reduction of drained secretion after elective cholecystectomy.

Eighty patients scheduled for elective cholecystectomy were randomly allocated to application of fibrin adhesive (Beriplast) to the gallbladder bed or to a control group. No significant difference was found between the two groups in regard to amount of postoperatively drained secretion or in drainage time. Fibrin adhesive thus had no effect on secretion of peritoneal fluid after simple cholecystectomy.

Adult↗