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Biomedical subjects

L Allen

Publications and source records attributed to L Allen.

At least 37 records · Page 2Linked to original sources

Does pH paper accurately reflect gastric pH?

The testing of gastric pH in the ICU has become the standard of care for most critically ill patients. It has been demonstrated that maintaining a gastric pH of greater than 3.5 confers protection from upper GI bleeding, while lesser pH values subject the patient to hemorrhagic risk. We compared nasogastric pH, as measured by pH electrode, to color-scaled pH paper in 16 critically ill patients hospitalized 3 to 10 days in the surgical ICU. Statistical analysis of 370 gastric specimens revealed a sensitivity of 66.7% and specificity of 94.5% when a paper pH (pH[p]) of greater than or equal to 4 was used as the therapeutic end-point. The sensitivity and specificity of the same pH(p) for clear buffered solutions were 100%. We conclude that the use of pH(p) lacks the clinical accuracy for determining the effects of therapy for the prophylaxis of stress gastritis and will lead to a significant degree of undertreatment. This lack of accuracy is not due to observer error or the quality or age of the testing paper. Our results suggest that if the measurement of gastric pH by pH(p) analysis is to be used as a guide for the prevention of stress-related hemorrhage, a more accurate method of monitoring may be warranted.

Critical Care

Congenital eyelid retraction.

Twenty two patients with primary congenital lid retraction affecting either the upper or lower eyelids or both are presented. The clinical features and management are discussed in the hope that recognition of this clinical entity will prevent unnecessary investigation.

Adolescent

A human D1 dopamine receptor gene is located on chromosome 5 at q35.1 and identifies an EcoRI RFLP.

Dopaminergic neurons have been shown to affect voluntary movement, hormone secretion, and emotional tone. Mediating these activities are two receptor subtypes, D1 and D2, which are biochemically and pharmacologically distinct. The D1 subtype, the most abundant form of dopamine receptor in the central nervous system, stimulates adenylate cyclase, modulates D2 receptor activity, regulates neuron growth and differentiation, and mediates several behavioral responses. Recently we reported the cloning of a human D1 dopamine receptor gene (DRD1). High-stringency hybridization of the DRD1 clone to human genomic blots suggests that DRD1 is single copy. When used to probe a Southern blot made with DNAs from a rodent-human somatic cell hybrid panel, DRD1 hybridized to a 6.5-kb EcoRI restriction fragment which was assigned to chromosome 5. Fluorescent in situ hybridization of this gene to human metaphase chromosomes refined the location of DRD1 to 5q35.1. A search for RFLPs associated with DRD1 identified a two-allele EcoRI RFLP, allowing confirmation of DRD1's localization by linkage analysis in Centre d'Etude du Polymorphisme Humain families.

Alleles

Molecular definition of a region of chromosome 21 that causes features of the Down syndrome phenotype.

Down syndrome (DS) is a major cause of mental retardation and heart disease. Although it is usually caused by the presence of an extra chromosome 21, a subset of the diagnostic features may be caused by the presence of only band 21q22. We now present evidence that significantly narrows the chromosomal region responsible for several of the phenotypic features of DS. We report a molecular and cytogenetic analysis of a three-generation family containing four individuals with clinical DS as manifested by the characteristic facial appearance, endocardial cushion defect, mental retardation, and probably dermatoglyphic changes. Autoradiograms of quantitative Southern blots of DNAs from two affected sisters, their carrier father, and a normal control were analyzed after hybridization with two to six unique DNA sequences regionally mapped on chromosome 21. These include cDNA probes for the genes for CuZn-superoxide dismutase (SOD1) mapping in 21q22.1 and for the amyloid precursor protein (APP) mapping in 21q11.2-21.05, in addition to six probes for single-copy sequences: D21S46 in 21q11.2-21.05, D21S47 and SF57 in 21q22.1-22.3, and D21S39, D21S42, and D21S43 in 21q22.3. All sequences located in 21q22.3 were present in three copies in the affected individuals, whereas those located proximal to this region were present in only two copies. In the carrier father, all DNA sequences were present in only two copies. Cytogenetic analysis of affected individuals employing R and G banding of prometaphase preparations combined with in situ hybridization revealed a translocation of the region from very distal 21q22.1 to 21qter to chromosome 4q. Except for a possible phenotypic contribution from the deletion of chromosome band 4q35, these data provide a molecular definition of the minimal region of chromosome 21 which, when duplicated, generates the facial features, heart defect, a component of the mental retardation, and probably several of the dermatoglyphic changes of DS. This region may include parts of bands 21q22.2 and 21q22.3, but it must exclude the genes S0D1 and APP and most of band 21q22.1, specifically the region defined by S0D1, SF57 and D21S47.

Adult

The universal orbital implant: indications and methods.

Major criticisms of quasi-integrated implants, such as the Iowa Implant, have been the time-consuming surgical technique needed to implant the prosthesis, and the high rate of extrusion. The Universal Implant (Oculo-Plastik, Montreal) is designed with these concerns in mind. In addition, those qualities that produce the motility advantages of a quasi-integrated implant and the ease of placement of a sphere have been incorporated into the design of the Universal Implant. The Universal Implant also (1) uses a faster implantation technique at surgery, (2) avoids cleaning the muscles, (3) has smaller mounds that are lower and more rounded, and should decrease the late extrusion rate, (4) can be used as an evisceration implant, enucleation implant, or secondary implant, and (5) has a larger girth and radius on the posterior surface that, in turn, helps support orbital fat and tissues and results in a more natural superior sulcus. It is recommended that the Universal Implant be used by surgeons who were pleased with the Iowa Implant, as the Universal implant represents an excellent alternative with major advantages over most other enucleation implants.

Humans

The role of tissue expanders in an anophthalmic animal model.

A study of orbital bony expansion using a custom tissue expander was performed in the anophthalmic cat model. Twelve 6-week-old kittens underwent right unilateral enucleations. Six kittens had immediate insertion of a tissue expander into the orbit. The remaining six served as controls. Every 2 weeks 0.5 cc saline was injected into the expander to a maximum of 5 cc. External horizontal and vertical orbital dimensions were obtained by palpation technique weekly. All animals had preoperative and study conclusion head CT scans with three-dimensional reconstructions performed. Dry skull preparations were done at the study conclusion at 24 weeks. Results demonstrated that tissue expanders were successful in maintaining normal orbital growth and size relative to the contralateral control orbit. The animals with enucleation only had an average difference in vertical and horizontal orbital measurements of -27 and -13 percent when compared with the contralateral normal orbit. In contrast, the enucleation and tissue-expansion animals had vertical and horizontal measurements of +4 and +2 percent (p less than 0.05) when compared with the contralateral orbit. Head CT scans with three-dimensional reconstructions demonstrated normal orbital geometry and volume for the animals with tissue expanders, whereas animals with enucleation only had small hypoplastic orbits. In conclusion, orbital tissue expanders offer a promising new technique in the treatment of anophthalmos.

Animals

Localization of a human brain sodium channel gene (SCN2A) to chromosome 2.

A DNA probe derived from a human genomic library has been used to localize on human chromosomes a gene coding for the alpha-subunit of the brain type II sodium channel (SCN2A). Hybridization of the probe to Southern blots made with DNAs from a rodent-human somatic cell hybrid panel indicates localization to the long arm of human chromosome 2. In situ hybridization to metaphase chromosomes confirms this assignment and indicates regional localization to 2q21-q33. The probe also reveals a frequent two-allele HaeIII RFLP.

Animals

Phosphorescence maxima and triplet state lifetimes of NAD+ and epsilon-NAD+ in ternary complexes with horse liver alcohol dehydrogenase.

This paper describes the phosphorescence emission and decay times of NAD+ and its fluorescent etheno derivative, epsilon-NAD+, in the pyrazole ternary complex with horse liver alcohol dehydrogenase (ADH). We show that the epsilon-NAD+ triplet state, as well as the tryptophan triplet state, can be utilized to monitor the coenzyme-enzyme interaction. The decays of NAD+ and AMP are single exponential, and the lifetimes are the same within experimental error. The phosphorescence lifetimes, evaluated as single exponentials, are slightly shorter in epsilon-NAD+ than they are in epsilon-AMP. Whereas the decay of epsilon-AMP was adequately fit by a single exponential with a time constant of very close to 0.5 s, it was necessary to fit the decay of epsilon-NAD+ to a double exponential. Ternary complexes with NAD+ excited at 297 nm exhibit decay kinetics nearly identical to those of ADH by itself. On the other hand, when excitation of the epsilon-NAD+ ternary complex is provided at 313 nm, where there is very little absorption by either tryptophan residue, the decay law of the ternary complex is similar to that of epsilon-NAD+ in solution. Our results demonstrate that NAD+ and epsilon-NAD+ quench tryptophan phosphorescence in ADH. Normalizing the phosphorescence intensity to the 0-0 vibronic band assigned to Trp-15 (blue-edge), we calculate a 21% decrease in the phosphorescence associated with Trp-314 at stoichiometric saturation of the coenzyme binding sites with NAD+ in the ternary complex. When the active sites are saturated with epsilon-NAD+, the relative phosphorescence due to Trp-314 decreases by 63%.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcohol Dehydrogenase

The human dopamine D2 receptor gene is located on chromosome 11 at q22-q23 and identifies a TaqI RFLP.

Human dopaminergic neurons are involved in the control of hormone secretion, voluntary movement, and emotional behavior. Mediating these effects are the dopamine D1 and D2 receptors. These macromolecules belong to a large family of related sequences known as the G protein-coupled receptors. The D2 receptors have been of special interest because they bind, with high affinity and specificity, many of the commonly prescribed antipsychotic drugs. We previously isolated a full-length cDNA clone of the rat D2 receptor. When a chromosome mapping panel was probed with the rat D2 receptor cDNA a 15-kb EcoRI restriction fragment was identified and localized to human chromosome 11. The rat cDNA was also used to clone a human genomic fragment, lambda hD2G1, which contains the last coding exon of the D2 receptor gene (DRD2) and 16.5 kb of 3' flanking sequence. Hybridization of lambda hD2G1 to a chromosome 11 regional mapping panel localized DRD2 to 11q. In situ hybridization of lambda hD2G1 to metaphase chromosomes refined this assignment to the q22-q23 junction of chromosome 11. A search for RFLPs associated with D2DR identified a frequent two-allele TaqI RFLP.

Chromosome Mapping

Plasma levels of highly sulphated glycosaminoglycans are raised in patients with chronic myeloid leukaemia.

A study of absolute basophil counts and plasma levels of highly sulphated glycosaminoglycans in 30 peripheral blood samples from 21 patients with different leukaemias was performed. This revealed significantly raised levels of both plasma highly sulphated glycosaminoglycans and basophils in those patients with chronic myeloid leukaemia, as compared to those with other types of leukaemia and 35 normal controls. A strong correlation (r = 0.83) was observed between the levels of highly sulphated glycosaminoglycans and basophil counts in the group as a whole, supporting a direct relationship between the two. The elevated plasma levels of highly sulphated glycosaminoglycans may contribute to the bleeding tendency reported in some patients with chronic myeloid leukaemia.

Adult

Diltiazem, nifedipine, and their combination in patients with stable angina pectoris: effects on angina, exercise tolerance, and the ambulatory electrocardiographic ST segment.

The efficacy and safety of oral nifedipine and diltiazem were compared in 20 patients with stable angina pectoris with use of a placebo run-in, randomized, double-blind titration to maximal effect crossover protocol. The effects of treatment withdrawal were also analyzed. All patients received placebo for 2 weeks and were then randomly assigned to receive either diltiazem or nifedipine. A 2 week drug titration phase in which patients received either diltiazem (180 to 360 mg/day) or nifedipine (30 to 120 mg/day) in three divided doses was followed by a 1 week maintenance phase. Patients then received placebo for 1 to 2 weeks, followed by crossover to the other treatment regimen and a second placebo washout period of 1 week. Patients (n = 13) who remained symptomatic on both diltiazem and nifedipine during the monotherapy periods entered a 3 week combination treatment phase, followed by a final 1 week placebo washout period. Frequency of angina, nitroglycerin consumption, exercise tolerance (Naughton protocol), and frequency of daily episodes of ST segment deviations on the electrocardiogram (1 mm of ST segment depression persisting for at least 1 min with and without chest pain) on an ambulatory electrocardiographic monitor were assessed during the baseline placebo, active monotherapy, placebo withdrawal, and combination treatment phases. Plasma drug levels were also measured. Compared with initial placebo values, the frequency of angina and the amount of nitroglycerin treatment were reduced by both diltiazem (p less than .001) and nifedipine (p less than .02). Diltiazem was more effective than nifedipine in reducing angina (p less than .02). Exercise duration increased with both drugs (p less than .0001). Diltiazem was significantly better than nifedipine in reducing the episodes of ST segment depression on the ambulatory monitor (p less than .01). Diltiazem reduced the resting heart rate (p less than .01); both drugs reduced the resting blood pressure and rate-pressure product. Overall, combination therapy was more effective in patients who did not maximally respond to diltiazem or nifedipine alone with respect to anginal and exercise variables and in reducing blood pressure at rest and during exercise. Plasma drug levels could not predict an individual patient's treatment response. Diltiazem may increase nifedipine drug levels when the drugs are combined. Fewer side effects were observed with diltiazem than nifedipine; the most side effects were seen with combination treatment. There were no apparent withdrawal effects observed with either treatment regimen.(ABSTRACT TRUNCATED AT 400 WORDS)

Angina Pectoris

A preliminary report on the Universal Implant.

Extrusion and time-consuming surgical techniques required of implantation have been the major criticisms of quasi-integrated implants such as the Iowa Implant. With these concerns in mind, the Universal Implant (Oculo-Plastik, Montreal) has been designed to offer the motility advantages seen with quasi-integrated implants and the ease of placement of a sphere. The Universal Implant incorporates most of the advantages seen in the Iowa Implant and other quasi-integrated implants. In addition, the Universal Implant (1) utilizes a faster surgical technique for implantation; (2) avoids cleaning the muscles; (3) has lower, more rounded, smaller mounds that should decrease the late extrusion rate; (4) can be used as an enucleation implant, evisceration implant, or secondary implant; and (5) has a greater girth and larger radius of the posterior surface that helps support orbital fat and tissues, resulting in a more natural superior sulcus. Considering that the Iowa Implant is presently not available, the Universal Implant should be used by those surgeons who were pleased with the former implant and should be considered as a reasonable alternative to other enucleation implants.

Equipment Design

Orchiectomy versus long-acting D-Trp-6-LHRH in advanced prostatic cancer.

One hundred and four patients were randomised for the study. Fifty-five were entered into the D-Trp-6-LHRH group and 49 into the orchiectomy group. All pre-treatment patient characteristics were similar and testosterone levels at 1 month or later were in the castrate range in both groups. Forty-six patients (83%) in the D-Trp-6-LHRH group and 40 (82%) in the orchiectomy group had a partial remission or stable disease at 3 months or later. There was no significant difference between the groups for response or survival. Three patients in the D-Trp-6-LHRH group had a disease "flare" in the first 10 days of treatment. The flare symptoms resolved by the end of 4 to 8 weeks. The incidence of flushing, decreased libido and impotence was similar in both groups. Although there was less psychological morbidity in the D-Trp-6-LHRH group the difference did not reach statistical significance. Our results indicate that long-acting D-Trp-6-LHRH offers a safe and highly effective alternative to orchiectomy.

Clinical Trials as Topic