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Biomedical subjects

S A Mayer

Publications and source records attributed to S A Mayer.

54 records · Page 3Linked to original sources
PubMed1996

Spontaneous multivessel cervical artery dissection in a patient with a substitution of alanine for glycine (G13A) in the alpha 1 (I) chain of type I collagen.

Cervical artery dissection occurs spontaneously and in multiple vessels with surprising frequency. An underlying arteriopathy is frequently suspected, but specific causes of vascular fragility are rarely identified. We describe a 35-year-old woman who developed multiple cervical artery dissections after scuba diving. She had no stigmata of connective tissue disease apart from bluish sclerae, and no family history of arterial dissection or congenital musculoskeletal disease. Analysis of the COL1A1 gene that encodes the pro alpha 1(I) chains of type I procollagen revealed a point mutation in one allele, resulting in substitution of alanine for glycine (G13A) in about half the alpha 1(I) chains of type I collagen. Genetic disorders of collagen, such as the mild phenotypic variant of osteogenesis imperfecta identified in our patient, should be considered in the differential diagnosis of unexplained cervical artery dissection.

Adult↗
PubMed1995

Noninvasive monitoring of cardiac output by Doppler echocardiography in patients treated with volume expansion after subarachnoid hemorrhage.

OBJECTIVE: To assess the validity and potential clinical utility of cardiac output monitoring using Doppler echocardiography in patients treated with volume expansion after subarachnoid hemorrhage. DESIGN: Observational study of patients in a randomized, clinical trial. SETTING: Neurologic intensive care unit. PATIENTS: Simultaneous, blinded measurements of cardiac output by thermodilution and Doppler echocardiography were performed in 48 patients 1 or 2 days after aneurysmal clipping. Follow-up Doppler echocardiography was performed an average of 3.9 days later (range 3 to 6) in 15 patients assigned to normovolemia and 24 patients assigned to hypervolemia. INTERVENTION: Patients received supplemental 5% albumin in order to maintain increased (hypervolemia) or normal (normovolemia) cardiac filling pressures. MEASUREMENTS AND MAIN RESULTS: The overall degree of correlation between the two measures was moderate (r = .67, r2 = .45, p < .0001). Bias and precision calculations (-0.75 +/- 1.34 L/min) showed a tendency for Doppler echocardiography to underestimate thermodilution, particularly when cardiac output was very high. Although hypervolemia patients received more 5% albumin than normovolemia patients, mean percent change in Doppler echocardiography cardiac output did not differ between the two groups. Multiple regression analysis showed that the percent change in Doppler echocardiography cardiac output correlated strongly with changes in heart rate (p < .0001), but not with daily net fluid balance or 5% albumin administration. CONCLUSIONS: Agreement was poor between Doppler echocardiography and thermodilution measurements of cardiac output, and trends reflected variations in heart rate rather than fluid status. Monitoring of cardiac output by this technique cannot be recommended in patients treated with volume expansion after subarachnoid hemorrhage.

Adult↗
PubMed1995

Electrocardiographic markers of abnormal left ventricular wall motion in acute subarachnoid hemorrhage.

A reversible and presumably neurogenic form of myocardial dysfunction may occur following subarachnoid hemorrhage (SAH), but the relationship of this finding to electrocardiographic abnormalities remains unclear. To clarify this issue, serial electrocardiograms (ECGs, mean 6.2 per patient) and echocardiograms (mean 3.4 days after SAH) were obtained in 57 SAH patients without preexisting cardiac disease. The goal was to determine which specific electrocardiographic changes, if any, reflect abnormal left ventricular wall motion in acute SAH. Wall motion abnormalities were identified in five (8%) of 57 patients. Four of these affected patients experienced hypotension (systolic blood pressure < 100 mm Hg) and three exhibited pulmonary edema within 6 hours of SAH, compared to none of the 52 patients with normal wall motion (p < 0.0001). Patients with abnormal wall motion were more likely than patients with normal echocardiograms to have symmetrical T wave inversion (five of five vs. seven of 52, p < 0.001) and severe (> or = 500 msec) QTc segment prolongation (five of five vs. three of 52, p < 0.001) on serial ECGs. These associations maintained their significance with analysis limited to single ECGs performed on or near the day of echocardiography. Abnormal wall motion was also associated with borderline (2% to 5%) creatine kinase MB elevation (five of five vs. three of 52, p < 0.001) and poor neurological grade (p < 0.0001). Although no combination of findings on a single ECG resulted in 100% sensitivity for abnormal wall motion, the presence of either inverted T waves or severe QTc segment prolongation on serial ECGs was associated with 100% sensitivity and 81% specificity. These results demonstrate an association between reduced left ventricular systolic function, mild creatine kinase MB elevation, and electrocardiographic repolarization abnormalities in acute SAH. Symmetrical T wave inversion and severe QTc segment prolongation best identified patients at risk for myocardial dysfunction and may serve as useful criteria for echocardiographic screening following SAH.

Acute Disease↗
PubMed1994

Cardiac injury associated with neurogenic pulmonary edema following subarachnoid hemorrhage.

OBJECTIVE: To describe the clinical features of cardiac injury associated with neurogenic pulmonary edema (NPE) in patients with acute subarachnoid hemorrhage (SAH). BACKGROUND: NPE is generally viewed as a form of noncardiogenic pulmonary edema related to massive sympathetic discharge. METHODS: Case series. RESULTS: We found echocardiographic evidence of reduced global and segmental left ventricular (LV) systolic function in five women (mean age, 44; range, 36 to 57) with SAH and NPE. None had a history of heart disease. Four patients were Hunt/Hess grade III and one was grade IV. All five patients experienced (1) sudden hypotension (systolic blood pressure < 110 mm Hg) following initially elevated blood pressures, (2) transient lactic acidosis, (3) borderline (2 to 4%) creatine kinase MB elevations, and (4) varied acute (< 24 hours) electrocardiographic changes followed by widespread and persistent T wave inversions. Pulmonary artery wedge pressures were normal in 3/3 patients at the onset of pulmonary edema but reached high levels (> 16 mm Hg) in all four patients studied beyond this period. Reduced cardiac output and LV stroke volume were identified in three patients; the fourth patient demonstrated normal values on high doses of intravenous pressors. Cerebral infarction due to vasospasm occurred in four patients and resulted in two deaths. Follow-up echocardiography performed 2 to 6 weeks after SAH revealed normal LV function in all three survivors. CONCLUSIONS: A reversible form of cardiac injury may occur in patients with NPE following SAH and is associated with characteristic clinical findings. Impaired LV hemodynamic performance in this setting may contribute to cardiovascular instability, pulmonary edema formation, and complications from cerebral ischemia.

Adult↗
PubMed1994

Neurologic deterioration in noncomatose patients with supratentorial intracerebral hemorrhage.

OBJECTIVE: To determine the frequency, time course, and predictors of neurologic deterioration (ND) in noncomatose patients with supratentorial intracerebral hemorrhage (ICH). BACKGROUND: Patients with worsening ICH may benefit from therapy aimed at reducing mass effect due to active bleeding or cerebral edema. METHODS: We analyzed 46 noncomatose (Glasgow Coma Scale [GCS] score > or = 8) patients with ICH in the Stroke Data Bank (SDB). All subjects were examined within 24 hours of onset (mean, 13.6 hours) and were prospectively followed with serial examinations during hospitalization. ND was defined as (1) a > or = 2-point decrease in the GCS score, (2) a > or = 1-point increase in the SDB weakness score, or (3) a new deficit, unrelated to medical or surgical complications. RESULTS: ND occurred in 15 of 46 patients (33%). The frequency of ND was greatest on the first hospital day (eight of 15 patients) and decreased progressively thereafter. Patients with ND had larger hemorrhages (mean volume, 45 ml versus 16 ml, p < 0.01) and more frequently demonstrated marked mass effect (60% versus 19%, p < 0.01) on initial CT than those with stable deficits, but did not differ with regard to mean GCS score, mean blood pressure, or other clinical variables on admission. Hematoma enlargement was judged to be the cause of worsening in four of 15 (27%) patients. Thirty-day case fatality was 47% in those with ND compared with 3% in those with stable deficits (p = 0.001). CONCLUSIONS: ND occurs in one-third of noncomatose patients with supratentorial ICH and carries a poor prognosis. Large hematoma volume on CT, rather than clinical predictors, identifies patients at high risk for subsequent worsening.

Adult↗
PubMed1993

Hemineglect and seizures in Binswanger's disease: clinical-pathological report.

The range of clinical effects from ischaemic damage to white matter in Binswanger's disease has not been fully characterised. Although focal deficits and seizures occur frequently, superficial infarcts often coexist, making the cause of these symptoms unclear. The case of a 69 year old woman is described who presented with acute left sided weakness and hemispatial neglect, followed a year later by electrographically documented seizures originating from the right hemisphere. Interim examinations showed bilateral pyramidal signs and mild intellectual decline. Serial CT and MRI studies showed bilateral diffuse ischaemic lesions of the cerebral white matter and old left sided lacunar infarcts but no evidence of acute infarction. Post-mortem examination showed gliosis and demyelination of the deep white matter which spared the subcortical arcuate fibres; this is consistent with Binswanger's disease. The neocortex was normal. This case and previous reports indicate that focal symptoms typically referable to the grey matter, including hemineglect and seizures, may occur as a manifestation of subcortical ischaemic injury to white matter in Binswanger's disease.

Aged↗
PubMed1993

Free protein S deficiency in acute ischemic stroke. A case-control study.

BACKGROUND AND PURPOSE: Deficiency of free protein S, a naturally occurring anticoagulant, may be acquired in the setting of acute illness and increasingly has become recognized as a possible stroke risk factor. We sought to determine whether free protein S deficiency is associated with acute cerebral infarction among older individuals at risk for stroke. METHODS: Free protein S was measured by Laurell rocket immunoelectrophoresis in 94 adults admitted for acute cerebral infarction and in 94 hospitalized control subjects of similar age, sex, and race. Patients with a history of cerebrovascular disease, acute thrombotic or hematologic diseases, or medical conditions known to cause free protein S deficiency were excluded from the control group. RESULTS: The percentage of patients with free protein S deficiency (< 20% normal total protein S) was similar in the case and control groups (21% versus 20%, respectively). Among all subjects, free protein S deficiency was more common in blacks than nonblacks (34% versus 13%, p = 0.001). A very low free protein S (< 15% normal total protein S) was more frequent among case patients than control subjects (11% versus 5%), but this trend failed to reach statistical significance. CONCLUSIONS: Free protein S deficiency is common among hospitalized patients, even in the absence of a recognized predisposing condition. Our findings indicate that acquired deficiency of free protein S is not a major risk factor for ischemic stroke.

Acute Disease↗
PubMed1993

Biopsy-proven isolated sarcoid meningitis. Case report.

Neurosarcoidosis without systemic involvement is rare and difficult to diagnose. The case of a 27-year-old man with a 6-week history of headache, mental status changes, and polyradiculopathy attributable to hypoglycorrheic lymphocytic meningitis is presented. Extensive testing for occult systemic sarcoidosis was negative. The presence of noncaseating granulomatous inflammation was established by open brain biopsy, and the patient improved clinically with oral steroid therapy. In individuals with undiagnosed chronic meningitis, brain biopsy may be necessary to rule out isolated neurosarcoidosis.

Adult↗
PubMed1992

Failure of GM1 ganglioside to influence outcome in experimental focal ischemia.

BACKGROUND AND PURPOSE: Reports of improved short-term (less than 72 hours) outcome in experimental models of mechanical and ischemic central nervous system injury suggest that exogenous ganglioside administration may confer a protective effect on neural tissue. We studied the effect of the monosialoganglioside GM1 on cerebral infarction and edema in spontaneously hypertensive rats subjected to permanent focal cerebral ischemia. METHODS: GM1 or normal saline was injected intramuscularly once a day for 3 days before and 30 and 120 minutes after occlusion of the right middle and common carotid arteries. Following a 24-hour survival period, the volume of infarction was measured by computer-assisted image analysis, and the extent of edema was assessed by measurements of tissue water content and hemispheric volume. RESULTS: Infarct volume was similar among the GM1-treated (n = 10) and saline-treated (n = 10) rats (212 +/- 10 versus 220 +/- 13 microliters, respectively). In a second series of experiments, the brain water content and edema volume of the ischemic right hemisphere in GM1-treated rats (n = 10) did not differ from saline-treated controls (n = 10). CONCLUSIONS: GM1 ganglioside does not effectively reduce cerebral infarction caused by permanent focal ischemia.

Animals↗
PubMed1991

Characterization and molecular cloning of polypyrimidine tract-binding protein: a component of a complex necessary for pre-mRNA splicing.

alpha-Tropomyosin exons 2 and 3 are spliced in a mutually exclusive manner. Exon 3 is included as the default exon in the mRNA of most cell types, whereas exon 2 is only included in the mRNA of smooth muscle cells. The primary determinant for the default selection of exon 3 is the branchpoint/polypyrimidine tract. This element upstream of exon 3 clearly and effectively outcompetes the corresponding element upstream of exon 2. To identify trans-acting factors that bind to this important cis element, we used UV cross-linking to identify a 57-kD protein whose binding characteristics directly correlate with 3'-splice-site selection in cis-competition splicing assays. This protein appears to be identical to polypyrimidine tract-binding protein. In this report we have used oligonucleotides derived from peptide sequences to isolate and sequence cDNA clones encoding this 57.2-kD protein. The primary sequence reveals a novel protein with significant homology to other RNA-binding proteins. Expression of the mRNA is detected in all tissues and cells examined, although its levels exhibit tissue-specific and developmental regulation. Using a biochemical complementation assay, we have found that this protein, along with a 100-kD protein, exists as part of a large complex that is required to rescue splicing from depleted nuclear extracts.

Amino Acid Sequence↗
PubMed1991

Yeast CBP1 mRNA 3' end formation is regulated during the induction of mitochondrial function.

Alternative mRNA processing is one mechanism for generating two or more polypeptides from a single gene. While many mammalian genes contain multiple mRNA 3' cleavage and polyadenylation signals that change the coding sequence of the mature mRNA when used at different developmental stages or in different tissues, only one yeast gene has been identified with this capacity. The Saccharomyces cerevisiae nuclear gene CPB1 encodes a mitochondrial protein that is required for cytochrome b mRNA stability. This 66-kDa protein is encoded by a 2.2-kb mRNA transcribed from CPB1. Previously we showed that a second 1.2-kb transcript is initiated at the CBP1 promoter but has a 3' end near the middle of the coding sequence. Furthermore, it was shown that the ratio of the steady-state level of 2.2-kb CBP1 message to 1.2-kb message decreases 10-fold during the induction of mitochondrial function, while the combined levels of both messages remain constant. Having proposed that regulation of 3' end formation dictates the amount of each CBP1 transcript, we now show that a 146-bp fragment from the middle of CBP1 is sufficient to direct carbon source-regulated production of two transcripts when inserted into the yeast URA3 gene. This fragment contains seven polyadenylation sites for the wild-type 1.2-kb mRNA, as mapped by sequence analysis of CBP1 cDNA clones. Deletion mutations upstream of the polyadenylation sites abolished formation of the 1.2-kb transcript, whereas deletion of three of the sites only led to a reduction in abundance of the 1.2-kb mRNA. Our results indicate that regulation of the abundance of both CBP1 transcripts is controlled by elements in a short segment of the gene that directs 3' end formation of the 1.2-kb transcript, a unique case in yeast cells.

Base Sequence↗
PubMed1989

The yeast CBP1 gene produces two differentially regulated transcripts by alternative 3'-end formation.

CBP1 is a yeast nuclear gene encoding a mitochondrial protein that stabilizes the 5' end of cytochrome b (cob) pre-mRNA. Cytochrome b is the only mitochondrially synthesized component of the respiratory chain complex III. Since the nuclearly encoded subunits of this complex are regulated at the transcriptional level by catabolite repression, we hypothesized that CBP1 might be similarly regulated. To test the idea that transcriptional regulation of CBP1 could coordinate an increase in cytochrome b mRNA stability with an increase in nuclearly encoded complex III subunit production, we characterized the change in abundance of CBP1 mRNA during derepression on a nonfermentable carbon source. Poly(A)+ RNA from derepressed yeast cells was examined by Northern (RNA) analyses with cRNA probes from CBP1. Both 2.2- and 1.3-kilobase (kb) transcripts were detected. The 1.3-kb mRNA lacked approximately 900 nucleotides of the 3' end of the 2.2-kb mRNA, which encodes the carboxyl-terminal 250 amino acid residues of the CBP1 coding sequence. Northern analyses of RNA isolated from deletion-insertion mutants of CBP1 and from strains that overexpress CBP1 mRNA demonstrated that both mRNAs were transcribed from the CBP1 gene. Furthermore, we demonstrated that the levels of the two CBP1 mRNAs were reciprocally regulated by the carbon source in the growth medium. This is the first description of a yeast gene from which two transcripts that can encode proteins with distinctly different coding properties are generated by alternative 3'-end formation.

Blotting, Northern↗