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Biomedical subjects

D Blake

Publications and source records attributed to D Blake.

At least 73 records · Page 4Linked to original sources

Clathrate hydrate formation in amorphous cometary ice analogs in vacuo.

The presence of clathrate hydrates in cometary ice has been suggested to account for anomalous gas release at large radial distances from the sun as well as the retention of volatiles in comets to elevated temperatures. However, how clathrate hydrates can form in low-pressure environments, such as in cold interstellar molecular clouds, in the outer reaches of the early solar nebula, or in cometary ices, has been poorly understood. Experiments performed with the use of a modified electron microscope demonstrate that during the warming of vapor-deposited amorphous ices in vacuo, clathrate hydrates can form by rearrangements in the solid state. Phase separations and microporous textures that are the result of these rearrangements may account for a variety of anomalous cometary phenomena.

Chemical Phenomena↗

Adult Reye's syndrome: a review with new evidence for a generalized defect in intramitochondrial enzyme processing.

A 42-year-old woman developed a flu-like illness and died 8 days later with Reye's syndrome (RS). There are 26 other cases of adult-onset RS reported. Biochemical, immunologic, and molecular studies of liver, brain, and skeletal muscle revealed a non-uniform decrease in several mitochondrial residual enzyme activities in liver and brain. Pyruvate carboxylase activity was negligible. Cross-reacting material was present in normal abundance in isolated liver mitochondria for several enzymes that had reduced catalytic activity including pyruvate carboxylase. Subunit II (encoded by mitochondrial DNA) and subunit IV (encoded by nuclear DNA) of cytochrome c oxidase also were present in normal abundance with normal electrophoretic mobility. These observations, combined with pertinent findings of other investigators, allow us to speculate that the intramitochondrial matrix chemical environment is disturbed by preceding pathophysiologic events resulting in a lowered ATP/ADP ratio. The lowered intramitochondrial energetic state interferes with the refolding and assembly of imported mitochondrial proteins, causing a loss of the catalytic efficiency of these enzymes. This explains the selective vulnerability of mitochondria in RS and the non-uniform, disproportionate loss of enzyme activity.

Adult↗

A comparative study of the cerebrovascular complications of cocaine: alkaloidal versus hydrochloride--a review.

Cocaine, especially in its alkaloidal or "crack" form, has been increasingly associated with cerebrovascular disease. Before the crack epidemic, cocaine hydrochloride (HCl) was also implicated as a cause of stroke. However, less is known about the differences in stroke subtypes, age at stroke onset, or presence of underlying structural cerebrovascular disease with different forms of cocaine use. We compared 26 patients (previously reported) from our four institutions plus 16 cases reported in the literature of stroke associated with alkaloidal cocaine to 63 (57 reported in the literature and six not previously reported from our four institutions) cases of stroke associated with cocaine HCl. Ischemic and hemorrhagic strokes are equally likely after alkaloidal cocaine use, whereas cocaine HCl is more likely (approximately 80% of the time) to cause hemorrhagic stroke, with approximately half the intracranial hemorrhages occurring from ruptured cerebral saccular aneurysms or vascular malformations. The presence of an underlying cerebral aneurysm was more common among patients with cocaine HCl-associated strokes than alkaloidal cocaine-associated strokes. Cerebral infarction was significantly more common among the alkaloidal cocaine users than in all the cocaine HCl users, and this was also true when alkaloidal cocaine users were compared with parenteral cocaine HCl (intravenous and intramuscular) users. Only hemorrhagic stroke has been reported with intravenous cocaine HCl use. We conclude that the pathogenesis of cocaine-related stroke is heterogeneous, and depends, in part, on the form of cocaine used.

Administration, Intranasal↗

Cerebrovascular complications of the use of the "crack" form of alkaloidal cocaine.

BACKGROUND AND METHODS: The use of cocaine, especially one of its alkaloidal forms ("crack"), has been increasingly associated with cerebrovascular disease. To clarify the clinical, radiologic, and pathological features of the events associated with cocaine use, we identified 28 patients at four medical centers who had stroke temporally related to the use of alkaloidal cocaine (during or within 72 hours of use). RESULTS: The 28 patients had the following types of cerebrovascular event: cerebral infarction (n = 18 [2 hemorrhagic; 1 fatal]) in the areas supplied by the middle cerebral artery (n = 10), anterior cerebral artery (n = 3), posterior cerebral artery (n = 1), and vertebrobasilar arteries (n = 4); subarachnoid hemorrhage (n = 5); intraparenchymal hemorrhage (n = 4); and primary intraventricular hemorrhage (n = 1). Eighteen patients (64 percent) had acute neurologic symptoms immediately or within one hour of using cocaine. Fifteen patients (45 percent) with either occlusive or hemorrhagic strokes had sever headache as an early symptom. Vasculitis was not suggested by radiography in any patient, nor was it identified on pathological examination in one patient who died. All the patients were young (mean age, 34 years; range, 23 to 49) and had no other apparent, direct cause of stroke. Other risk factors for stroke among the patients included mild mitral-valve prolapse (n = 4), hypertension (n = 4), cigarette smoking (n = 8), and regular alcohol use (n = 6). CONCLUSIONS: There is a strong temporal association of the use of alkaloidal cocaine with both ischemic and hemorrhagic cerebrovascular events. Cocaine-related stroke probably has many causes. A thorough history focusing on the use of cocaine and toxicologic screening of urine and serum should be part of the evaluation of any young patient with a stroke.

Adult↗

Vasoconstriction in the renal vascular bed during exercise: studies in control and heart failure rabbits.

1. The effects of graded treadmill exercise on renal blood flow (RBF) were examined in seven rabbits, in which congestive heart failure (CHF) was produced by the administration of doxorubicin, 1 mg/kg, twice weekly for 8 weeks, and in seven controls. A third group of five rabbits underwent doxorubicin treatment with the addition of surgical section of the left renal sympathetic nerve. 2. During submaximal exercise, there was a small reduction in RBF in controls, which was greatly exaggerated in CHF. 3. In both control and heart failure rabbits, there was a precipitous fall in RBF as exercise fatigue developed. 4. Renal sympathectomy ablated these changes in RBF during exercise. 5. It is concluded that in heart failure there is an exaggerated, sympathetically mediated, diversion of blood flow away from the kidney. The onset of exercise fatigue in both normal and heart failure rabbits is accompanied by a marked intensification of this process.

Animals↗

An unusual case of variegate porphyria with possible homozygous inheritance.

We report an unusual case of variegate porphyria in a young girl with epilepsy, mental retardation and premature adrenarche. Symptoms of porphyria commenced about the age of 12 years and death occurred about 18 months later. The patient had very low protoporphyrinogen oxidase activity in her cultured fibroblasts. Both parents had half the normal activity of this enzyme in lymphocytes and are heterozygous for the abnormal gene for variegate porphyria. Therefore, it is possible that the patient was a homozygous variant. Anticonvulsant therapy and low hepatic 5 alpha reductase activity were probably other contributing factors to the severity of the condition in this patient.

Animals↗

Role of immunity to mycobacterial stress proteins in rheumatoid arthritis.

'Stress Proteins in Inflammation' provided a forum for the discussion of topical issues in this rapidly moving field. The mycobacterial 65 kDa stress proteins play a key role in certain animal models of inflammatory arthritis. However, the impression emerging is that the mechanism probably involves more than a simple cross-reaction between mycobacterial SP65 and either the host SP65 or a cartilage antigen, and that evidence for a primary role in human rheumatoid arthritis is lacking. A realistic role for immune responses against stress proteins might be the amplification or perpetuation of inflammation. If so, this is unlikely to be limited to arthritis.

Animals↗

Effect of ingestion of hemoproteins on fecal excretion of hemes and porphyrins.

Stools from asymptomatic volunteers on diets containing red meat, whole blood, or high fiber were analyzed for their content of hemes and dicarboxylic (heme-derived) porphyrins by the "HemoQuant" assay, the "Hemoccult" test, and "high-performance" liquid chromatography (HPLC). In 49 subjects, ingestion of red meat increased HemoQuant-determined combined fecal heme plus dicarboxylic porphyrins by an average 375%; the contribution of heme-derived porphyrins to total fecal porphyrins increased from 37% to 78%. Of subjects on a red-meat diet, 27% passed stools with a porphyrin content suggestive of a porphyria, compared with only 4% on a red-meat-free diet. These increases were due largely to protoporphyrin and its derivatives pemptoporphyrin and deuteroporphyrin, all of which were present in feces as iron-free porphyrins and iron-ligated (heme) forms. Ingestion of blood had an effect similar to that of red meat, but ingestion of fiber had no effect. These effects of dietary and endogenous hemoproteins must be considered when such methods are used to test feces for occult blood or to test for excess fecal porphyrins as an indicator of a porphyria.

Adolescent↗

An assay of uroporphyrinogen decarboxylase in erythrocytes.

Measurement of uroporphyrinogen decarboxylase (UROD; EC 4.1.1.37) activity in erythrocytes is useful in distinguishing between familial porphyria cutanea tarda (PCT), in which UROD activities are low, and acquired PCT, in which UROD activity is normal. In this method for measuring UROD, pentacarboxylic acid porphyrinogen I (PPI) is used as substrate. A sample of the patient's whole blood is incubated with PPI at 37 degrees C for 30 min at pH 6.0. The reaction is stopped by adding trichloroacetic acid/dimethyl sulfoxide containing mesoporphyrin (internal standard). The coproporphyrin so produced is measured directly by high-performance liquid chromatography, with fluorescence detection. Our values by this method for healthy subjects and non-PCT patients ranged from 1.8 to 4.0 U/L. The CV for the assay was 10% at 1.1 U/L and 9% at 2.4 U/L. Twelve of 42 patients with PCT had low erythrocyte UROD activities. In each of six families of patients with low UROD activity we found at least one other family member with a low UROD activity in erythrocytes.

Adult↗

Pregnancy among obstetricians: a comparison of births before, during, and after residency.

Questionnaires were sent to 1025 female board-certified obstetricians, and information was retrieved about pregnancy outcome. A total of 454 pregnancies, one third of which occurred during residency, were evaluated, and the relationship between pregnancy outcome and residency was assessed. Children of primiparous women who were delivered during or after residency had significantly lower mean birth weights than those who were delivered before residency (p less than 0.001 and p less than 0.005, respectively), whereas birth weights of infants born to multiparous women were not significantly different. The low birth weight rate (less than 2500 gm) was significantly increased during residency (p less than 0.002), and infants born during residency were 7.5 times more likely to be growth retarded than those born outside residency (p less than 0.002). The incidence of other pregnancy complications was not found to be increased during residency. Our data suggest a potentially negative impact of residency on the birth weights of infants born to female obstetricians in training.

Birth Weight↗

Speed of injection and spread of bupivacaine in the epidural space.

Speed of injection of bupivacaine was assessed in 73 women who received epidural analgesia in labour. Rapid injection was shown to produce quicker onset of epidural block and more reliable perineal anaesthesia than slow injection, but there was no difference in the final extent of the block.

Anesthesia, Epidural↗