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Biomedical subjects

D L Levin

Publications and source records attributed to D L Levin.

At least 55 records · Page 3Linked to original sources

Adult respiratory distress syndrome in pediatric patients. II. Management.

Adult respiratory distress syndrome, a clinical syndrome of respiratory failure that follows many kinds of insults, often in patients with no previous pulmonary disease, occurs in pediatric patients. This group of disorders has a typical clinical, pathologic, and pathophysiologic course, the hallmark of which is injury to the alveolar-capillary membrane with increased permeability of the pulmonary vasculature and pulmonary edema. Resolution may occur at any stage, but most patients die and many develop chronic lung disease requiring respiratory support for weeks or months. Multiple organ system failure, secondary infection, and irreversible respiratory dysfunction are responsible for the poor outcome. The underlying mechanisms that relate injury to the development of pulmonary disease are unclear. In some cases there may be direct injury to the lung, but in others, such as septic shock, there are mediators that link the initial insult to the subsequent lung injury. The leukocyte may have a central role in this process, although this is uncertain. Therapeutic measures needed to support the patient, especially increased inspired oxygen, are additional factors in the progression of lung disease. Current therapy, as summarized in Table II, is primarily supportive. Efforts to treat ARDS after it is clinically apparent have been disappointing. The pathogenic mechanisms that lead to ARDS are probably well advanced by the time the syndrome is diagnosed on the basis of the usual clinical signs. Therefore an emphasis on understanding the mechanisms of lung injury so that specific markers can be used to predict which patients will develop ARDS, allowing intervention in the early stages of the process, may prove rewarding.

Cardiac Output↗

Sporadic dysplastic nevus syndrome in a tyrosinase-positive oculocutaneous albino.

A case of dysplastic nevus syndrome in a 41-year-old tyrosinase-positive oculocutaneous albino man is presented. Clinically the patient exhibited multiple amelanotic lesions; histologic examination provided the diagnosis of dysplastic nevus syndrome. Fontana-Masson silver staining revealed the presence of melanin in the nevus cells. Hair bulbs incubated in tyrosine buffer produced melanin. This is the second reported case of dysplastic nevus syndrome in an oculocutaneous albino and the first case of dysplastic nevus syndrome in a tyrosinase-positive albino of which we are aware.

Adult↗

Dissociation of the stellate morphology from intracellular cyclic AMP levels in cultured rat brain astroglial cells: effects of ganglioside GM1 and lysophosphatidylserine.

Secondary microcultures of newborn rat cerebrum astroglial (AG) cells, maintained in a serum-free, chemically defined medium, were treated with various agents known to elevate intracellular cyclic AMP (cAMP) levels. Earlier studies had shown these drugs to induce a process-bearing (stellate) morphology in the AG cells, a response that was antagonized by the presence of gangliosides. One millimolar dibutyryl cyclic AMP (dBcAMP), 10 microM forskolin, 12 nM cholera toxin, and 30 microM isoproterenol all raised intracellular cAMP levels, from basal values of 3 pmol/10(6) cells to 30-30,000 pmol/10(6) cells, depending on the agent tested. dBcAMP caused the greatest elevation, and forskolin the least. The timing and/or the level of the AMP response did not precisely correlate with those of the stellation response. Values of ED50 with the four agents, as determined for the cAMP response, were always higher than stellation ED50 values in all treatments, and ED50 did not correlate with the maximal levels of cyclic AMP induced by the four agents. The capacity of ganglioside GM1 to block the stellation response to the four agents was not accompanied by a similar capacity to block the cAMP responses. Lysophosphatidylserine (lysoPS) had the capacity to induce AG cell stellation as well, without altering the basal level of cAMP. Both lysoPS and gangliosides, therefore, may act directly on the cellular machinery underlying the stellation response without involving changes in intracellular AMP.

Animals↗

Placental proteins as tumor markers in human monoclonal gammopathies: results in 109 patients.

Sera from 51 patients with multiple myeloma, 48 patients with monoclonal gammopathy of undetermined significance (MGUS), and 10 patients with Waldenstrom's macroglobulinemia (78 men and 31 women) were analyzed by radioimmunoassay for four placental proteins: the common alpha-subunit of glycoprotein hormones (alpha), chorionic gonadotropin and/or its free beta subunit (CG-beta), placental lactogen (PL), and "pregnancy-specific" beta 1-glycoprotein (SP1), to see if these would be useful tumor markers to distinguish benign from malignant monoclonal gammopathies. The 95th percentiles for serum alpha concentrations in our male patients and normal men were 7.0 and 2.0 ng/ml, respectively. When male patients with renal failure (known to be associated with elevated serum alpha) were excluded, the 95th percentile for serum alpha for the remaining 73 non-uremic men was 4.0 ng/ml. Of these, 7 with MGUS, 2 with macroglobulinemia, and 17 with myeloma had serum alpha concentrations above the 95th percentile for normal men, and analysis of covariance showed that both age and disease category were significantly related to serum alpha concentration. When the serum alpha concentrations from our 73 non-uremic men and 119 normal men were pooled, the 90th percentile was 2.7 ng/ml, and 16 of the 19 individuals in the top 10th percentile came from our non-uremic men (p less than 0.00002). For serum SP1, analysis of data combining our 109 patients with 93 controls again revealed a disproportionate number of the top 10% in our patient population. The 95th percentiles for serum alpha in our female patients, and for serum CG-beta in both sexes, were not significantly elevated above controls. Serum PL concentrations exceeded the 95th percentile of normal in only 5% of our patients, and were not further analyzed. Serum alpha and SP1 concentrations, but not those of CG-beta or PL, were significantly higher for our patients than for controls. These placental proteins are unlikely to be generally useful as tumor markers for monoclonal gammopathies, however, because of the overlap among "benign" and malignant groups, and because of a lack of correlation with stage of the disease as observed in our myeloma patients.

Adolescent↗

Prostaglandin synthesis inhibition in persistent pulmonary hypertension of the newborn.

The data implicating prostaglandin synthesis inhibitors as an etiology for PPHN are reviewed. Consideration is given to the pharmacology of prostaglandin synthesis inhibitors in the fetus and newborn, the role of prostaglandins in the fetal and neonatal circulation, and the effect of closure of the ductus arteriosus on the fetal pulmonary vasculature.

Animals↗

Pulmonary microthrombi syndrome in newborn infants with unresponsive persistent pulmonary hypertension.

Some newborn infants with either primary or secondary persistent pulmonary hypertension (PPHN) remain hypoxemic, hypercarbic, and acidotic despite therapeutic efforts. In autopsies of 23 infants who had PPHN, diffuse platelet-fibrin thrombi were present in the pulmonary microcirculation of eight (15.2 +/- 18.1 thrombi/cm2 lung tissue) and absent in 15 (0.2 +/- 0.3 thrombi/cm2 lung tissue), (P less than 0.004). Diagnoses in group A (thrombi) were pneumonia and sepsis (four patients), meconium inhalation (3), and primary PPHN (1); and in group B (no thrombi) pneumonia and sepsis (4), meconium inhalation (4), primary PPHN (4), hyaline membrane disease (2), and diaphragmatic hernia (1). The only significant differences between the two groups were the response to tolazoline infusion as assessed by changes in partial pressure of arterial oxygen (PaO2) and the platelet counts. Group A responded less favorably to tolazoline (14.8 mm Hg vs 83.6 mm Hg; P less than 0.05) and had lower platelet counts (51,000/microliter vs 128,000/microliter) (P less than 0.01) than group B. No significant differences could be detected in Apgar scores, duration or mode of mechanical ventilation, oxygen requirements, arterial blood gas tensions or pH, systemic arterial blood pressure, coagulation profile, amount of blood product transfusions, or intravascular catheter use. Pulmonary microthrombi should be added to the list of mechanisms for PPHN and may explain why some infants do not respond well to therapeutic efforts aimed at vasodilation. Thrombocytopenia and failure to respond to pulmonary vasodilators might suggest the diagnosis.

Blood Vessels↗

Breast cancer skin test antigens of increased sensitivity prepared from vesicular stomatitis virus-infected tumor cells.

Crude membrane (CM) extracts were prepared from five cultured breast tumor lines (MDA-MB-157, MDA-MB-231, ZR75-1, HS0578T, and MCF-7) which had been infected with vesicular stomatitis virus (VSV) to augment their antigenicity. In skin test trials, CM extracts of uninfected MCF-7 cells elicited positive response in 0 of 13 (0%) tests in breast cancer patients, while VSV-MCF-7 elicited positive responses in 11 of the same 13 patients (84.6%). CM extracts of VSV-ZR75-1 and VSV-MCF-7 elicited greater delayed hypersensitivity responses (mm induration at 48 hr) in breast cancer patients than in patients with lung carcinoma or melanoma. Although the sensitivity of VSV-ZR75-1 was too low (ten of 28, or 35.7% of tests positive) to be useful as a skin test antigen, VSV-MCF-7 elicited positive responses in 30 of 38 (78.9%) tests in breast cancer patients, as compared to two of 15 (13.3%) and two of 13 (15.4%) of tests in patients with lung carcinoma and melanoma, respectively. The "virus-augmented" CM extract of cultured MCF-7 cells exhibited markedly greater sensitivity as compared to control MCF-7 extracts (P less than .005), with a high degree of specificity for breast cancer patients as compared to patients with the other neoplasms (P less than .00001). The results of skin testing with VSV-MCF-7 CM extracts demonstrated antigenic cross-reactivity with a large number of breast cancer patients, a finding of great importance for any potential immunotherapy and/or immunodiagnosis.

Adult↗

Dobutamine: a hemodynamic evaluation in children with shock.

The hemodynamic effects of dobutamine were studied in 33 infants and children with cardiogenic or septic shock. Dobutamine was administered at doses of 2.5, 5.0, 7.5, and 10.0 micrograms/kg/minute. Significant increases above preinfusion values were observed in cardiac index, left ventricular stroke work index, and pulmonary wedge pressure. Significant decreases from preinfusion values were observed in systemic arteriolar resistance index. No significant differences occurred in heart rate, mean systemic arterial pressure, mean pulmonary arterial pressure, right atrial pressure, or pulmonary arteriolar resistance index. Analysis of the data also revealed significant effects of age and diagnosis on the hemodynamic responses. These data suggest that dobutamine is a useful drug in the pharmacologic management of children in shock, especially in children older than 12 months with cardiogenic shock not complicated by severe hypotension.

Adolescent↗

Histologic, immunofluorescent, and antinuclear antibody findings in PUVA-treated patients.

Twenty-two patients with psoriasis were treated with PUVA therapy for over two years. Skin biopsies from sun-exposed skin were evaluated before, during, and after PUVA therapy. No statistically significant epidermal changes were found when looking for hyperkeratosis, atrophy, melanin, or melanocyte numbers. No dyskeratosis was found. Dermal changes, including alterations in elastic tissue and collagen, were not statistically significant. Amyloid deposits were absent. The amount of mucin deposition was found to correlate with the length of PUVA therapy. In four patients, the mucin disappeared after withdrawal of PUVA, suggesting that this change is reversible.

Adult↗

Iatrogenic hyperadrenocorticism during topical steroid therapy: assessment of systemic effects by metabolic criteria.

Systemic absorption of topically applied glucocorticoids in quantities sufficient to replace endogenous production is not uncommon. However, iatrogenic Cushing's syndrome resulting from the use of topical corticosteroids is very rare. Thus the possibility that systemic absorption may cause hyperglucocorticism has been deemphasized and examined only sporadically. We have studied changes in carbohydrate metabolism induced by topical glucocorticoids in a psoriatic patient who had developed Cushing's syndrome from topical desoximetasone (Topicort). The results indicated that (1) fasting hyperglycemia and increased insulin-glucose ratios could be induced within 24 hours of administration of topical glucocorticoids, (2) insulin resistance accompanied abnormal carbohydrate tolerance, and (3) fluctuations in circulating leukocytes paralleled the changes in carbohydrate metabolism. The findings suggest that metabolic indexes of glucocorticoid action action may provide useful parameters for assessing systemic absorption of topical glucocorticoids. glucose relationship as one such index to assess the risk of treatment of extensive chronic skin disease with potent topical glucocorticoids.

Administration, Topical↗