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Biomedical subjects

J Douglas

Publications and source records attributed to J Douglas.

At least 91 records · Page 5Linked to original sources

Coagulation disturbances in cancer of the breast and colon measured with specific monoclonal antibody enzyme immunoassay for fibrin-fibrinogen degradation products.

Disturbances of coagulation were measured in breast cancer, colon cancer and benign breast disease using an enzyme immunoassay against total plasma fibrinogen and fibrin degradation products (TDP). Results were compared with measurements of fibrinopeptide A (FPA) and of serum fibrinogen-related antigen (FRA). Plasma TDP before surgery was significantly higher in colon cancer than in breast cancer patients (p = 0.0009) or in benign breast disease (p = 0.0292). A post-operative rise in TDP at 4 months (colon cancer) or 9 months (breast cancer) was associated with early recurrent disease (p less than 0.0173 for colon cancer, p less than 0.1835 for breast cancer). No such association was noted with FPA or FRA measurements. TDP may prove to be of value in detecting activation of coagulation by malignant disease.

Antibodies, Monoclonal↗

Effect of angiotensin II infusion in rats on Na,K-ATPase activity in renal cortical microsomal preparations.

Direct dose-dependent effects of angiotensin II on renal tubular sodium reabsorption have been demonstrated. Alterations in tubular sodium reabsorption may occur via modulation of renal Na,K-ATPase activity. Thus, these experiments were undertaken to ascertain whether angiotensin II could influence renal cortical Na,K-ATPase activity. Angiotensin II, 495 ng/microliters/h, or vehicle (controls) was infused for 24 h via miniosmotic pumps 48 h after rats were adrenalectomized and implanted with osmotic pumps containing 12.5 micrograms/microliters corticosterone (Treatment I) or both corticosterone and 0.2 microgram/microliter aldosterone (Treatment II), and in rats receiving 3% NaCl in their food (sodium loaded, Treatment III). Rats receiving Treatments I and III received saline to drink. Renal cortical microsomal membranes were prepared, and the effects of angiotensin II infusion on the K1/2 and Vmax for Na, K, and ATP determined. Angiotensin II infusions were associated with (i) a decrease (P less than 0.001) in the K1/2 for Na activation of Na,K-ATPase from 14 +/- 3 to 6 +/- 1 (n = 4 experiments), 16 +/- 1 to 12 +/- 1 (n = 5), and 12 +/- 3 to 7 +/- 1 (n = 5) mM (means +/- SE) for treatments I, II, and III, respectively; (ii) no changes in the K1/2 for K activation or the Km for ATP; (iii) no changes in the Vmax for Na, K, or ATP; and (iv) no change in Mg-ATPase activity. We conclude that angiotensin II infusion is associated with a decrease in the K1/2 of renal cortical Na,K-ATPase activity for sodium. This action of angiotensin II on the enzyme activity may contribute to the regulation of tubular sodium transport.

Adrenalectomy↗

In vivo measurements of fibrin formation and fibrinolysis in operable breast cancer.

Fibrin formation and fibrinolysis were estimated in 89 breast cancer patients by measurement in plasma of Fibrin Fragment B beta 15-42 and Fibrinopeptide A (FPA), serum Fibrin(ogen) Degradation Products (FDPs) and plasminogen activator by Fibrin Plate Lysis Assay. Results were compared with (a) 26 patients with benign breast diseases; and (b) 45 healthy factory workers. FPA, FDP and B beta 15-42 levels were elevated in both breast cancer patients and benign disease patients, but there were no significant differences between these two groups. Cancer stage, patient age and smoking habits did not affect these results, but Oestrogen Receptor (ER) positive patients had higher B beta 15-42 values than ER negative patients (p = 0.017). These results show that fibrin formation is enhanced preoperatively in patients with either benign or malignant breast disease. The fibrinolytic response to activated coagulation may be relatively deficient in breast cancer. The roles of malignancy, stress and other factors in the causation of these abnormalities require further assessment.

Breast Neoplasms↗

Frequency and extent of allelic loss in the short arm of chromosome 3 in nonsmall-cell lung cancer.

DNA was prepared from tumour and normal tissue from 48 patients representing all common histological types of nonsmall-cell lung cancer. Using eight DNA probes, which detect nine restriction enzyme fragment length polymorphisms (RFLP) on chromosome 3, we established that among the 44 informative patients 32 had lost alleles on the short arm of one of their copies of chromosome 3. Of these 32, at least 13 had also lost alleles on the long arm of chromosome 3, suggesting that the whole chromosome might be lost. For one patient, cytogenetic analysis indicated that the mechanism of allelic loss was reciprocal translocation followed by chromosomal loss of one of the reciprocal products. Two patients with allelic loss distal to the D3S3 locus (which maps to 3p13-14) retained heterozygosity at that locus. These results indicate that loss of alleles on the short arm of chromosome 3 is a common event in lung tumours of the nonsmall-cell type, that this loss occurs by a variety of chromosomal mechanisms, and that the minimally deleted region is 3p13-14----3pter.

Alleles↗

The presumptive role of fantasy in serial sexual homicide.

The authors examined the role of fantasy as an internal drive mechanism for repetitive acts of sexual violence. A sample of 25 serial sexual murderers with three or more known victims each was compared with a sample of 17 single sexual murderers, with only one known victim each. The drive mechanism was hypothesized to be an intrusive fantasy life manifested in higher prevalences of paraphilias, documented or self-reported violent fantasies, and organized crime scenes in the serial murderers. All three hypotheses were supported.

Adult↗

The effect of dietary protein on the efficacy of L-dopa: a double-blind study.

We randomly placed 10 parkinsonian patients on high- and low-protein diets that tasted and looked alike, each for 1 week. All patients were taking L-dopa and carbidopa with or without other antiparkinson medications; medications remained unchanged. A "blind" physician recorded the modified Columbia scores, objective measurements of rigidity, movement velocity, and pegboard tests three times a day for 5 days during each week. The patients recorded fluctuations hour to hour. We measured serial blood L-dopa levels on day 4 of each week. Performance was significantly better while the patients were on low-protein diets. These results did not correlate with blood L-dopa levels, which had higher peaks in three patients while they were on high-protein diets despite inferior performance and increased number of "off" hours. Thus, high dietary protein probably affects the efficacy of L-dopa at a central level.

Antiparkinson Agents↗

DNA probe technology for rapid detection of Haemophilus influenzae in clinical specimens.

In a previous study, we reported that a 5-kilobase Haemophilus influenzae DNA fragment involved in penicillin-binding protein expression could be used as a probe for specific detection of H. influenzae strains (F. Malouin and L. E. Bryan, Mol. Cell. Probes 1:221-232, 1987). Here, we report the ability of this probe to detect H. influenzae in clinical specimens. In a bacterial dot experiment, there was strong hybridization of the 32P-labeled probe to nonencapsulated and serotype a through f H. influenzae strains. The detection of H. influenzae in body fluids was then evaluated by using pooled human serum, urine, cerebrospinal fluid, and sputum as dilution media for H. influenzae, Haemophilus aegyptius, Haemophilus parainfluenzae, and Escherichia coli cells. At 65 degrees C, the probe hybridized to H. influenzae and H. aegyptius (greater than or equal to 10(5) cells) in all fluids. There was no hybridization with the E. coli negative control, and H. parainfluenzae hybridized when greater than or equal to 10(7) cells were used. Experiments performed at 73 and 80 degrees C permitted elimination of H. parainfluenzae hybridization. The detection of H. influenzae in 232 sputa from patients with respiratory tract infections was very specific (96 to 97%) and sensitive (74 to 100%) when the total time of the procedure was sufficient (6 to 24 h) and when the experiments were performed at 80 degrees C. In addition, the probe detected three of three and four of four H. influenzae-infected cerebrospinal fluids and blood cultures, respectively, and did not react with pneumococcus- or streptococcus-infected cerebrospinal fluids. Finally, by using a small-scale procedure, the probe rapidly detected H. influenzae in cerebrospinal fluid and sputum specimens (4 and 8 h, respectively). These results imply prompt diagnosis of H. influenzae infections caused by nonencapsulated and serotype a through f strains.

Body Fluids↗

Differential expression of preproenkephalin and preprodynorphin mRNAs in striatal neurons: high levels of preproenkephalin expression depend on cerebral cortical afferents.

Preproenkephalin and preprodynorphin mRNAs can be detected by in situ hybridization in medium-sized striatal neurons in normal rats and in rats with unilateral cerebral cortical lesions. Hybridization of 35S-labeled oligonucleotide cDNAs complementary to specific regions of each mRNA reveals that preproenkephalin-expressing neurons are more numerous than cells expressing preprodynorphin. Hybridization densities above enkephalin-positive neurons are also more than twice those noted above preprodynorphin-expressing cells. Northern analyses of mRNA extracted from the striatum are consistent with these relationships. The striatal preproenkephalin hybridization densities are decreased ipsilateral to cerebral cortical lesions; this change evolves largely between 1 and 5 d following the lesion. Striatal preproenkephalin mRNA is thus more prominent than preprodynorphin mRNA and depends on cerebral cortical inputs for its full expression.

Animals↗

Arrhythmia and late mortality after Mustard and Senning operation for transposition of the great arteries. An eight-year prospective study.

Arrhythmia and late sudden death are recognized complications of intraatrial repair of transposition of the great arteries. We performed a prospective study over 8 years in 100 consecutive hospital survivors who underwent Mustard (46 patients) or Senning (54 patients) operations between 1978 and 1982. Arrhythmia was analyzed by preoperative, postoperative, and serial follow-up Holter monitoring and standard electrocardiograms and was related to clinical outcome. Before repair, all patients were in sinus rhythm with a low incidence of arrhythmia. After repair, there was a gradual decrease in stable sinus rhythm during follow-up so that at a mean of 7 years after operation only 56% of patients having the Senning operation and 66% having the Mustard, with simple transposition, were in stable sinus rhythm on Holter monitoring. There was no significant difference between the two operations. Eleven patients (five after Senning [two simple, three complex], six after Mustard [five simple, one complex]) died during follow-up, four suddenly (two after Senning, two after Mustard). However, loss of sinus rhythm or the presence of arrhythmia on standard electrocardiograms or Holter recordings did not identify patients at risk for increased morbidity or mortality. Thus, even with current surgical techniques, gradual loss of sinus rhythm occurred after both Mustard and Senning operations. Because late death could not be predicted by electrocardiographic analysis, an alternative approach involving detailed hemodynamic and electrophysiologic measurements may be required to identify high-risk patients.

Arrhythmias, Cardiac↗

Meperidine-induced delirium.

Despite the widespread use of meperidine as an analgesic, its potential for producing delirium has been overlooked. Six cases demonstrating meperidine-induced behavioral toxicity are reported. Toxicity was more likely when meperidine was combined with cimetidine or drugs having anticholinergic activity. Discontinuation of meperidine and substitution of morphine for analgesia were usually successful in treating the delirium. Physostigmine reversed the delirium in one patient. The authors suggest that the delirium results from the excessive anticholinergic activity of meperidine or its only active metabolite, normeperidine.

Adult↗

Evaluation of long-term results of homograft and heterograft valves in extracardiac conduits.

Between 1971 and 1982, 249 patients received right heart extracardiac conduits. The 173 patients who survived 30 days were reviewed retrospectively; 72 had antibiotic-sterilized aortic homografts, 97 had xenografts of various types, and four had valveless tubes. Reoperation for conduit obstruction was required as early as 13 months after the original operation, but actuarial analysis showed no differences in overall performance of homograft and heterograft conduit groups with respect to late death or survival free of conduit obstruction. More important risk factors for late death or the need for reoperation were the severity of the underlying cardiac lesions and the influence of early postoperative complications. When analyzed statistically, the performance of conduits bearing homografts was disappointing, influenced sometimes by complications in the Dacron extension tubes. Repairs dispensing with conduits entirely should be evaluated.

Actuarial Analysis↗