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Biomedical subjects

E Davis

Publications and source records attributed to E Davis.

At least 19 recordsLinked to original sources

Autism and developmental abnormalities in children with perinatal cocaine exposure.

Cocaine in all forms is the number one illicit drug of choice among pregnant women. Records of 70 children with cocaine exposure in utero who were referred for developmental evaluation at a large inner-city hospital were reviewed in an effort to determine whether a specific pattern of abnormalities could be discerned. Patients received physical examinations, neurological screenings, and behavioral and developmental assessments based on the Gesell Developmental Inventory, and the Denver Developmental Screening Test. Documentation of specified drug use was obtained by history. Mean age (SEM) at referral was 19.2 (1.7) months. All mothers used cocaine in one of its forms, although polydrug use was common. Growth parameters were low (median = 15th percentile). Significant neurodevelopmental abnormalities were observed, including language delay in 94% of the children and an extremely high frequency of autism (11.4%). The high rate of autistic disorders not known to occur in children exposed to alcohol or opiates alone suggests specific cocaine effects.

Adolescent

Histologic studies of splenic megakaryocytes after bone marrow ablation with strontium 90.

We previously showed that purified strontium 90 produced sustained bone marrow ablation in mice, lowering platelet levels to less than 10% of normal 11 days after administration. Platelet levels later rose exclusively from splenic production and were maintained at a stable level (58% of normal) from 20 to 115 days after injection. However, there was no change in the total number or ploidy distribution of splenic megakaryocytes, as immunologically detected by flow cytometry. To further study the characteristics of splenic thrombopoiesis after bone marrow ablation by 90Sr, we measured the frequency, cross-sectional area, and endomitotic figures of histologically recognizable megakaryocytes (as well as bare megakaryocyte nuclei) in mouse spleen sections. During the hematopoietic nadir 9 days after injection of yttrium 90-free 90Sr, the size (area) of megakaryocyte cross-sections (mean +/- SD, 1079.3 +/- 661.6 microns 2; normal, 398.7 +/- 192.8 microns 2) was greater than for any other time studied, but megakaryocyte frequency (corrected for size) did not increase until day 16. Overall, splenic megakaryocytes in marrow-ablated mice 16 or more days after 90Sr injection showed substantial increases (p = 0.001 for both comparisons) in mean area (707.5 +/- 386.2 microns 2) and sectional frequency (mean +/- SEM, 4.52 +/- 0.20 per 1.83 mm2; normal, 0.78 +/- 0.06 per 1.83 mm2). Megakaryocyte bare nuclei and endomitotic figures were also more numerous after 90Sr, injection, suggesting acceleration of megakaryocyte maturation and platelet production. The induction of splenic platelet production after bone marrow ablation is associated with increased size of recognizable megakaryocytes, despite lack of change in overall splenic megakaryocyte ploidy.

Animals

Oscillometry of radial artery in acrocyanosis and cold sensitivity.

Acrocyanosis is reassessed on the basis of 34 new patients with diagnostic clinical features. The most useful tests are the skin temperature differences (STD) between wrist and end of fingers (or ankle and end of toes) and oscillometry over the radial and dorsalis pedis and posterior tibial arteries. Capillaroscopy of the conjunctival and nailfold vessels is useful in half the patients. Capillary resistance was not helpful. STD of 1.5 degrees C or more between skin of wrist or ankle and fingertip or toetip, is usually associated with more severe disease and capillary abnormalities on microscopy, and with reduced oscillometry (to 1 or less) over the radial arteries and dorsalis pedis and posterior tibial arteries. Reduced oscillometry is more associated with abnormalities than the other tests, and more than STD. The work of Mulvany and his colleagues suggests an explanation for the low oscillometry. Larger vessels than the arterioles and digital vessels can become resistance vessels in various circumstances. It is likely that the radial artery and vessels of similar diameter can temporarily act as resistance vessels in patients with acrocyanosis in a low temperature environment.

Adolescent

Raynaud's features in childhood. Clinical, immunological and capillaroscopic study.

Raynaud's phenomenon, uncommon in childhood, often heralds connective tissue disorder. Since microvascular abnormalities can be detected at an early stage of the connective tissue disease, especially in scleroderma, a specific diagnosis can be made in patients presenting with Raynaud's phenomenon alone or Raynaud's phenomenon associated with symptoms suggestive of connective tissue disease. Raynaud's phenomenon was studied in 11 consecutive children, 10 girls and 1 boy, ages 6 to 15. One child had a definite diagnosis of cutaneous polyarteritis nodosa. In 6 others connective tissue disease was suspected: 4 had arthritis, 2 has telangiectasia, leg ulcers and antinuclear antibodies. Of the remaining 4, one had hemiplegia and 3 Raynaud's phenomenon only. Oscillometry of the radial artery was reduced in 7 of 9. Decreased capillary resistance was found in 2 of 6, while abrupt thinning in conjunctival vessels was seen in 3 of 7. On nailfold capillaroscopy, reduced vascularity was noted in 5 of 11, dilated capillaries in 4 of 11, tortuousity in 2 of 11, capillary thinning in 1 of 11, capillary spasm in 1 of 11 and normal pattern in 3 of 11. Two patients presenting with Raynaud's phenomenon were found to have "scleroderma-like pattern" on nailfold capillaroscopy. One of them died 2 years later of cardiopulmonary sclerosis, and another developed esophageal stricture and Barrett's esophagus. Neither has sclerodermatous skin. In childhood Raynaud's phenomenon, nailfold capillaroscopy is a non-invasive examination enabling early diagnosis of "systemic scleroderma sine scleroderma".

Adolescent

Transesophageal color flow Doppler imaging for aortic insufficiency in patients having cardiac operations.

Transesophageal color flow Doppler findings were studied in 30 patients with aortic insufficiency who had cardiac operations. Measurements were expressed as ratios of corresponding left ventricular outflow tract dimensions. Regurgitant jet proximal width ratio was significantly related to jet area ratio (r = 0.92) and correlated poorly with the degree of jet penetration into the left ventricular cavity (r = 0.32). The vectors of the regurgitant jets were variable. Nine patients had undergone aortography. Regurgitant jet proximal width and area ratios were significantly related to angiographic grade (r = 0.88 and 0.87, respectively) in these patients. We concluded that the esophagus offers a satisfactory transducer orientation for color flow Doppler assessment of aortic insufficiency.

Adult

Purification and structural study of two albumin variants in an Irish population.

Two types of variant albumins were detected during routine electrophoresis on cellulose acetate on 34,000 sera from patients in a relatively stable Irish population. The fast type (IRE1) (relative mobility 1.05) had a heterozygote frequency of 1/3,780, and the slow type (IRE2) (relative mobility of 0.94) had a heterozygote frequency of 1/8,500. A method for purification of the two types of variants is described. Structural study of the fast variant established a single amino acid substitution 313 lysine----asparagine (313 Lys----Asn); this variant has been reported in several European populations and also in New Guinea indigenes. However, the slow variant has a new substitution, 479 glutamic acid----lysine (479 Glu----Lys). Because it appears to be uniquely Irish, the slow variant (formerly called IRE2) has been renamed albumin Dublin. Three other albumin variants most often reported in European populations (cumulative frequency only about 1/3,500) were not detected in this study. Because of the significance of albumin genetic variants for the study of protein evolution and as an aid in identification of drug-binding sites, clinical chemists are asked to be on the alert for cases of bisalbuminemia.

Adult

Genetic variants of serum albumin in Americans and Japanese.

A collaborative search for albumin genetic variants (alloalbumins) was undertaken by cellulose acetate and agarose electrophoresis at pH 8.6 of the sera of patients at two major medical centers in the United States and of nearly 20,000 blood donors in Japan. Seventeen instances of alloalbuminemia were ascertained, and seven different alloalbumin types were characterized by structural study. Two previously unreported alloalbumin types were identified. In one type, which was present in a Caucasian family and designated Iowa City-1, aspartic acid at position 365 was replaced by valine (365 Asp----Val); this is the second reported mutation at this position. The other type present in a Japanese blood donor had the mutation 128 His----Arg. An unexpected finding was the presence in a single Japanese of a Naskapi-type alloalbumin (372 Lys----Glu), a variant that had previously been described only for certain Amerindian tribes in whom it occurs with a polymorphic frequency (greater than 1%) and in Eti Turks. An arginyl-albumin (-1 Arg, 1 Asp----Val) occurred in an American family. The other alloalbumin types identified were proalbumins Lille and Christchurch and albumin B that have a cumulative frequency of about 1:3500 in Caucasians probably because of the hypermutability of CpG dinucleotides at the mutated sites. All of the variants characterized in this study are point mutants, and the sites are spread throughout the albumin gene. However, about one-fourth of all known albumin mutations are clustered in the sequence segment from position 354 through 382.

Amino Acid Sequence

A donor splice mutation and a single-base deletion produce two carboxyl-terminal variants of human serum albumin.

At least 35 allelic variants of human serum albumin have been sequenced at the protein level. All except two COOH-terminal variants, Catania and Venezia, are readily explainable as single-point substitutions. The two chain-termination variants are clustered in certain locations in Italy and are found in numerous unrelated individuals. In order to correlate the protein change in these variants with the corresponding DNA mutation, the two variant albumin genes have been cloned, sequenced, and compared to normal albumin genomic DNA. In the Catania variant, a single base deletion and subsequent frameshift leads to a shortened and altered COOH terminus. Albumin Venezia is caused by a mutation that alters the first consensus nucleotide of the 5' donor splice junction of intron 14 and the 3' end of exon 14, which is shortened from 68 to 43 base pairs. This change leads to an exon skipping event resulting in direct splicing of exon 13 to exon 15. The predicted Venezia albumin product has a truncated amino acid sequence (580 residues instead of 585), and the COOH-terminal sequence is altered after Glu-571. The variant COOH terminus ends with the dibasic sequence Arg-Lys that is apparently removed through stepwise cleavage by serum carboxypeptidase B to yield several forms of circulating albumin.

Amino Acid Sequence

Cognitive and behavioral dimensions of dysfunction in alcohol and polydrug abusers.

Development of a measure of parallel dimensions of cognitive and behavioral dysfunction related to substance abuse is described. Dimensions were assessed in alcohol and polydrug abusers entering treatment and social drinkers. Dimensions included quantity/frequency of use, physiological symptoms, situational stressors, antisocial behaviors, interpersonal problems, affective dysfunction, attitude toward treatment, degree of life impact, and three use expectancies. Principal component analysis of the dimensions and expectancies yielded three factors; behavioral/physiological, social, and cognitive. Although the groups could be discriminated statistically, alcohol and polydrug abusers exhibited relatively similar patterns of dysfunction across the dimensions and expectancies, with alcohol abusers demonstrating greater intensity or degree of dysfunction in several areas on admission to treatment. Implications of the findings with respect to multidimensional models of substance abuse and use of the dimensions in treatment matching and outcome research are discussed.

Adult

A hamartoma of the colon with unusual features.

An unusual case of colonic hamartoma in a 67-year-old man is reported. Colonoscopy polyp surveillance revealed a polypoid lesion of the sigmoid colon which had the characteristics of a hamartoma on microscopic examination. The lesion, which was classified as a colonic hamartoma, is described. Review of the literature revealed no previous report of such a colonic poylp.

Aged

Interstitial deletion of chromosome 2q associated with ovarian dysgenesis.

In the present report we describe a girl with mental retardation, Dandy-Walker malformation, craniofacial anomalies, cardiac defect, and ovarian dysgenesis associated with an interstitial deletion of chromosome 2. The interstitial deletion in the proband was associated with an apparently balanced translocation involving chromosomes 2 and 7 in the father.

Abnormalities, Multiple

Homebound aged: the dilemma of psychiatric intervention.

This study reports the 12 month experience of a hospital-based, multidisciplinary psychogeriatric community team. The patients evaluated were unable to come to the hospital clinics because of a psychiatric and/or physical disability. The group included some patients rarely seen in psychiatric office practice and outpatient facilities, but who posed problems for their families and the community. Some required referral to a clinic, crisis management or emergency hospitalization. Others however, required only minimal intervention. A total of 151 patients (119 females and 32 males) whose average age was 78.2, were seen. Seventy percent were widowed, single, divorced or separated; 43% lived alone. The patients were grouped according to the method of intervention used: psychiatric and social intervention--55%; social and nursing intervention--28%; no follow-up--11% and; emergency hospitalization--6%. Seventeen patients were left "untreated". These patients usually had more adequate family or community support than was initially apparent. They were referred for a crisis which was resolved quickly. An attempt is made to explain our approach, and several case examples are given.

Activities of Daily Living

Preliminary study of the protective effect of the calcium channel blocker, nifedipine, on adriamycin-induced tissue injury.

The effect of nifedipine, an oral calcium-channel blocker, on adriamycin-induced wound healing was studied. Nifedipine was administered to animals prior to treating with adriamycin. The healing strengths of cecal, fascial, and skin anatomoses were measured. Animals treated with adriamycin alone had significant decreases in healing strength compared to controls: for cecum at postoperative days (POD) 7 and 14; for skin at PODs 14, 21, and 28; for fascia at POD 28. Overall, nifedipine reduced the impact of adriamycin injury on the strength of healing incisional anastomoses. Nifedipine also appeared to protect collagen synthesis at anastomotic sites from adriamycin-induced impairment.

Animals

Effect of allopurinol on adriamycin-induced impairment of wound healing.

Use of antineoplastic drugs perioperatively requires an understanding of their potential effects on healing wounds. Adriamycin is an antineoplastic drug with a wide range of antitumor activity. Prior studies have demonstrated that adriamycin impairs skin wound healing but these studies have offered limited explanations for the mechanism of action of the drug vis á vis impairment of healing wounds. In this study we investigated the effect of a xanthine oxidase inhibitor, allopurinol, on adriamycin-induced tissue injury to determine the role oxyradicals might play in reducing wound-breaking strength. Sixty-four Buffalo rats were studied. Eight animals were used to establish drug tolerances. Fifty-six animals were divided into four experimental groups; saline control (2 mL IP), allopurinol control (4.3 mg/kg po), allopurinol-adriamycin (4.3 mg/kg po + 6 mg/kg IV, respectively), and adriamycin (6 mg/kg IV). Animals treated with adriamycin alone had significantly reduced weight at postoperative day (POD) 7 compared to control groups (p less than .025). Bowel-bursting strength (BBS) of the animals treated with adriamycin alone was also significantly decreased at POD 7, compared to controls (p less than .025), and by POD 14 the animals treated with adriamycin alone had a significantly decreased fascial tensile strength, compared to the saline control (p less than .05). At no point did the animals treated with both allopurinol and adriamycin show a significantly decreased weight, BBS, or fascial tensile strength compared to control animals. Allopurinol appeared to protect against adriamycin toxicity on healing wounds. These results suggest that xanthine oxidase and possibly superoxide radicals play an important role in mediating adriamycin toxicity on healing wounds.

Allopurinol

The effect of smoking and menopause on the small blood vessels.

The small blood vessels were examined in 31 premenopausal and 31 postmenopausal women. In each group there were 14 non-smokers and 17 smokers of age groups 35-45 and 45-59. The women underwent full gynecological examination. Blood pressure was normal in each. The small blood vessels were examined by capillaroscopy of conjunctivae and nailfolds, by oscillometry of the radial artery, skin thermometry of the wrist and terminal phalanx, and by capillary fragility. When all abnormalities in non-smokers were compared with those in smokers in the menopausal groups, a significant difference was found, (Table 4), to the disadvantage of the smokers.

Adult