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Biomedical subjects

M Singer

Publications and source records attributed to M Singer.

At least 55 records · Page 3Linked to original sources

Effects of atrial natriuretic peptide on systemic haemodynamics and cardiac function in normal man.

Atrial natriuretic peptides (ANP) reduce blood pressure. Animal experiments suggest that this depressor action results from a reduction in cardiac output rather than peripheral vascular resistance but it is unresolved whether this is wholly due to their effect of reducing left ventricular filling or whether they have a negatively inotropic effect. We have therefore investigated the effects of ANP in normal man using Doppler measurements of ascending aortic blood flow. Six normal volunteers underwent infusions of placebo and incremental doses of ANP in the range 0.25 to 12 micrograms.min-1. Each infusion was given for 15 min and measurements made both in the supine and erect positions (passive tilt). In both positions ANP had dose dependent effects of increasing heart rate (HR) and maximal acceleration whilst lowering an index of systemic vascular resistance (ISVR). In the erect position ANP also lowered systolic blood pressure. In the 30 min after completion of the infusions there were significant decreases in peak velocity and cardiac output with increases in ISVR in both positions, but HR fell and diastolic pressure increased only when supine. During the course of the experiment mean haematocrit (SEM) increased from 43.9 (1.2) to 46.7 (1.0), indicating a mean reduction in plasma volume of 10.5%. This occurred despite a negative fluid balance of only 31(7) ml over the 2 h. These data suggest that ANP is not negatively inotropic and that, at pharmacological doses, it is an arteriolar dilator of rapid offset and reduces cardiac filling pressures by a mechanism of slower offset.

Adult

Continuous hemodynamic monitoring by esophageal Doppler.

A new 5.1-mHz continuous wave esophageal Doppler system is described for continuous hemodynamic monitoring in ventilated patients. Information is obtained from the size, shape, and changes in shape of the velocity waveforms of descending aortic blood flow. Minute distance, the product of waveform area (stroke distance) and heart rate, provides a measure of cardiac output. Good agreement between this technique and thermodilution was shown for cardiac output changes with 238 paired measurements made in 38 patients. The coefficient of variation was lower for Doppler (3.8%) than for simultaneous thermodilution measurements (6.2%). Seventy-eight changes in left ventricular filling, systemic vascular resistance, or inotropic state produced consistent alterations in waveform shape with a narrow-based waveform being indicative of hypovolemia. This development marks a significant advance in the technique and provides a useful alternative to invasive hemodynamic monitoring, both in the ICU and perioperatively.

Adult

A collection of strains containing genetically linked alternating antibiotic resistance elements for genetic mapping of Escherichia coli.

We present a collection of 182 isogenic strains containing genetically linked antibiotic resistance elements located at approximately 1-min intervals around the Escherichia coli chromosome. At most positions both Tn10 (Tetr) and TN10kan (Kanr) elements are available, so that the collection contains a linked set of alternating antibiotic resistance markers. The map position of each insertion has been aligned to the E. coli genetic map as well as to the Kohara ordered clone bank. These strains are designed to be used in a rapid two-step mapping system in E. coli. In the first step, the mutation is localized to a 5- to 15-min region of the chromosome by Hfr mapping with a set of Hfr strains containing either Tn10 or Tn10kan elements located 20 min from their respective origins of transfer. In the second step, the mutation is localized to a 1-min region by P1 transduction, with a collection of isogenic insertion strains as donors. We discuss the uses of this collection of strains to map and eventually to clone a variety of mutations in E. coli.

Chromosome Mapping

Freeze fracturing properties of native and heat-adapted Chinese hamster ovary (CHO) cells.

Chinese hamster ovary cells were either maintained at 37 degrees C (native cells) or heat adapted by exposure to a temperature of 40 degrees C for 2 h. Thereafter, native and heat-adapted cells were incubated at different temperatures for various times, harvested, fixed with glutaraldehyde and glycerol, and studied by freeze fracture microscopy. We observed that the fracture plane either passed through the cell, exposing cytoplasm, or stayed within the plasma membrane, and that the location of the fracture plane was strongly determined by the previous thermal history of the cell. We believe that these differences reflect changes in membrane lipid packing arrangements.

Animals

Invasive hemodynamic monitoring in the United Kingdom. Enough or too little?

In response to a questionnaire regarding use of invasive hemodynamic monitoring techniques in the United Kingdom, 211 replies were received from 276 hospitals (76.4 percent). Over one fifth of Intensive Care or combined Intensive/Coronary Care Units did not use pulmonary artery catheters (PAC); of those that did, two thirds used no more than two/month, and only two units used more than ten/month. Nearly a quarter did not possess a cardiac output computer. Only 18 complications occurring in the preceding year were reported, which suggests underrecognition. Clinical indications and lack of expertise were the main reasons proferred for limited use; however, cost (which was generally underestimated) and clinical value also were mentioned. The majority of CCUs did not use PACs, and only 10 percent used more than two/month. Only 10 percent of hospitals have used them perioperatively and most cardiothoracic units used no more than two PACs/month. In view of the large difference in numbers used between the United Kingdom and the United States, a large-scale study is warranted to determine the actual value of PACs in reducing mortality and morbidity.

Catheterization, Peripheral

Focused search of semantic cases: the effects of question form and case status.

The present study was designed to identify and examine some of the variables that influence the focused search of semantic cases in question answering. Singer, Parbery, and Jakobson (1988) have previously reported that people can focus on the case interrogated by a question and can largely disregard irrelevant cases. In the present study, people learned facts, such as the pilot painted the garage with the roller, the spraygun, and the brush. One day later, they answered questions that focused on a particular case. For example, the question did the pilot paint with a spraygun? focuses on the instrument case. Experiment 1 revealed that people can focus on a particular case in response both to complete questions and to comparable word probes, such as "pilot spraygun." Therefore, the given-new structure of questions is not essential to focused search. Experiment 2 revealed that people have a difficult time ignoring the agent case, even when it is irrelevant to the question. This corroborates proposals that agent and action information are closely interrelated in the representation of a fact. These results help to delineate the phenomenon of the focused search of semantic cases.

Cues

Early stages of spinal ganglion formation during tail regeneration in the newt, Notophthalmus viridescens.

Stages in the development of sensory ganglia in the regenerating newt tail after amputation are described by taking advantage of the rostrocaudal developmental gradient of the regenerating tail. A series of ganglia, beginning at the tip of the regenerate and progressing rostrally, were examined. Eight-week regenerates were used because they showed the most complete array of stages. The first recognizable ganglia appear as small clusters of cells sitting dorsally on the already established ventral roots. The cluster of ganglionic cells steadily expands with the addition of many new cells. Signs of cell differentiation within the ganglion precede the formation of the dorsal root rudiment, which assumes several different configurations but most commonly enters the cord close to the ventral root. Our material suggests that ganglion precursor cells originate in the ventral region of the developing spinal cord and migrate out of the cord by travelling along the ventral root until, at a suitable distance from the cord, they halt, proliferate, and eventually differentiate. In the regenerate, we saw no evidence of neural crest cells--such as those that give rise to ganglia in the trunk region during development--forming at the dorsal region of the regenerated neural tube. Nor was there any morphological evidence of mesenchymal contribution to the ganglion cell clusters.

Animals

Flexor tendon injuries: the results of primary repair.

This study is a critical analysis of results obtained following primary repair and post-operative controlled mobilisation of flexor tendon injuries which were treated by registrars with up to six months experience in hand surgery. 70 (55%) of 125 patients who underwent repair of a complete flexor digitorum profundus or flexor pollicis longus tendon injury during a 14-month period attended for review and these had a total of 140 injured digits. 93 (67%) were rated by Lister's standards as an "excellent" or "good" result. 39 (28%) occurred in "no man's land" (Zone 2) and only 19 (49%) in this area were rated "excellent" or "good". Isolated flexor digitorum superficialis tendon injuries have been excluded from this study, as have partial tendon injuries.

Adult

Use of exercise Doppler for non-invasive haemodynamic optimization of dose and identification of poor responders to an oral anti-anginal agent. A double-blind dose-finding study of nisoldipine.

Nisoldipine, a new dihydropyridine calcium antagonist, was examined for its dose-related haemodynamic effects using exercise-induced changes in aortic blood flow as measured by Doppler ultrasound. Following a two-week placebo run-in, 24 patients with stable angina pectoris were assigned double-blind to one of three groups receiving doses ranging from 2.5-20 mg/day over 8 weeks, given once or twice daily. Doppler studies identified the low dose group as responding less well at the placebo phase compared to the other two groups. There was an overall improvement in percentage change of peak velocity and stroke distance with exercise at all doses, with a dose of 5 mg/day giving optimal benefit in both variables (P less than 0.05) and no additional benefit being seen on twice-daily dosage. Six patients reporting increased chest pain exhibited a significantly worse rise in peak velocity and a fall in stroke distance to exercise (P less than 0.05) whilst on active drug compared to those who responded favourably. Doppler ultrasound can be of benefit in the haemodynamic assessment of new drugs, the recognition of non-responders and the optimization of therapeutic regimes.

Administration, Oral

Fantasy or structural defect? The borderline dilemma as viewed from analysis of an experience of nonhumanness.

The experience of nonhumanness, a crucial aspect of the phenomenal self of borderline states, is studied in two cases to test assumptions concerning the application of the classic ego-psychological or object-relations and self-psychological models. Are these experiences to be seen as fantasy and treated as manifest content, with dynamically active unconscious conflict and meaning, requiring interpretation, or as a developmental arrest in which structural disturbances are ameliorated through clarifying and empathic interventions? The first case is of a patient with a neurotic depression and hysterical and obsessional character traits, treated in a classic psychoanalysis. Even though dyadic oral and anal fantasies were strongly in evidence, the ego was well integrated. The second case is of a severe borderline patient who showed depressive panic and agoraphobia. Her major ego disturbances, poorly integrated and differentiated self- and object representations, and primitive defenses prevented effective psychoanalytically oriented treatment. Interventions were used to consolidate self-representations, internalize tension-regulating structures, promote adaptive ego functions and reality testing. These clarifications were necessary to move the patient to where she could tolerate facing unconscious dynamic conflicts. Only at that point could repression be lifted, memory emerge, and interpretation be utilized.

Adult

The LINE-1 DNA sequences in four mammalian orders predict proteins that conserve homologies to retrovirus proteins.

Recent work suggests that one or more members of the highly repeated LINE-1 (L1) DNA family found in all mammals may encode one or more proteins. Here we report the sequence of a portion of an L1 cloned from the domestic cat (Felis catus). These data permit comparison of the L1 sequences in four mammalian orders (Carnivore, Lagomorph, Rodent and Primate) and the comparison supports the suggested coding potential. In two separate, noncontiguous regions in the carboxy terminal half of the proteins predicted from the DNA sequences, there are several strongly conserved segments. In one region, these share homology with known or suspected reverse transcriptases, as described by others in rodents and primates. In the second region, closer to the carboxy terminus, the strongly conserved segments are over 90% homologous among the four orders. One of the latter segments is cysteine rich and resembles the putative metal binding domains of nucleic acid binding proteins, including those of TFIIIA and retroviruses.

Amino Acid Sequence

Thallium-201 myocardial scintigraphy in coronary triple-vessel disease: an attempt to increase sensitivity using quantitative methods.

In order to increase the sensitivity of thallium-201 exercise scintigraphy in patients with triple vessel coronary disease (TVD), we first examined retrospectively myocardial scintigrams of 179 patients with TVD, as documented subsequently by cardiac catheterization. Ischemia had been diagnosed visually in 141 (79%), scar without ischemia in 25 (14%) and no apparent perfusion defect in 13 (7%) cases. The subset of TVD patients without scintigraphic ischemia (i.e. those with scar or no perfusion defect) was then compared to a control group with normal coronary angiography using four quantitative criteria: (1) in preset-count analog images, a quotient of the exposure times rest image/stress image; (2) in preset-time digital images, a quotient of counts/pixel in stress image/rest image using two different myocardial regions of interest (ROI); (3) a similar quotient using paracardial lung ROIs of three different sizes; (4) the absolute values of stress lung uptake. Quotients (1) and (2) were expected to be lower in TVD patients than in normal controls due to exercise-induced global ischemia, quotient (3) and value (4) were expected to be higher due to exercise-induced left ventricular dysfunction with increased lung uptake of thallium-201. All results showed a tendency to confirm these hypotheses; significant differences (P less than 0.05) between patients and controls were obtained in all lung quotients and in 3 of 12 myocardial quotients. No significant differences were observed in the exposure time quotients of preset-count images and in the stress lung uptake. Due to overlapping values, it was not possible to fix normal and pathological ranges of any quotient.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary Disease