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Biomedical subjects

M Steele

Publications and source records attributed to M Steele.

At least 19 recordsLinked to original sources

Kawasaki disease manifesting with acute cholangitis. A case report.

A 3-year-old boy, who developed the signs and symptoms characteristic of Kawasaki disease, is described. The child also had an 8 cm tender hepatomegaly. Hydrops of the gallbladder could not be shown. Liver biopsy showed marked infiltration of inflammatory cells, including neutrophil and eosinophil leucocytes in the portal tracts involving the periphery of the portal arteries and veins, and acute inflammation of the bile ducts with neutrophil and eosinophil infiltration of the walls. Overt cholangitis has been described only once before in Kawasaki disease, when a viral agent was suggested as being important in the pathogenesis. Although the clinical and laboratory findings in cases of Kawasaki disease clearly suggest an acute infection--as they did in this case--no aetiological agent has yet been incriminated. The possibility of a drug-induced auto-allergic or hypersensitivity state is considered. Evidence for such a state includes a history of drug administration, pathological findings similar to peri-arteritis nodosa--a condition often associated with a hypersensitivity state--the presence of eosinophils in the lesions and a response to treatment with aspirin, a drug known to ameliorate hypersensitivity states.

Acute Disease

Maternal representations of attachment during pregnancy predict the organization of infant-mother attachment at one year of age.

While strong retrospective and concurrent associations between maternal and infant patterns of attachment have been noted, this is one of the first reports of a prospective investigation of such associations. The Adult Attachment Interview was administered to 100 mothers expecting their first child, and, at 1-year follow-up, 96 of these were seen with their infants at 12 months in the Strange Situation. Maternal representations of attachment (autonomous vs. dismissing or preoccupied) predicted subsequent infant-mother attachment patterns (secure vs. insecure) 75% of the time. These observed concordances, as well as the discordances, are discussed in terms of the uniquely powerful contribution the Adult Attachment Interview makes to the study of representational and intergenerational influences on the development of the infant-mother attachment.

Adult

Growth-related gene expression in type 2 alveolar epithelial cells.

Our laboratory is studying mechanisms of growth control in alveolar type 2 cells. This highly differentiated cell is induced to proliferate in lungs of animals of all ages during various forms of growth and during the repair process after lung injury. Using type 2 (T2) cells isolated from adult and neonatal rat lungs and an SV40-T transfected T2 cell line, we have shown tha growth-arrested T2 cells constitutively express genes associated with G1 and S phase of the cell cycle, yet they do not efficiently translate the proteins encoded by these genes. This block of growth-related gene expression is post-transcriptional and appears to involve mechanisms that control translation, perhaps at the level of initiation. Furthermore, growth-arrested T2 cells initiate DNA synthesis; however, the cells do not complete the cell cycle, suggesting that they are arrested in a late stage, perhaps the G1/S border. Differential screening of a cDNA library of growth-arrested T2 cells with DNA from growing and growth-arrested T2 cells has identified four families of genes preferentially expressed in the growth-arrested cells. These genes, which are in the process of being characterized, may be responsible for the unusual type of growth arrest demonstrated by T2 cells.

Animals

The clinical utility of visual-evoked potential acuity testing.

We assessed the clinical utility of objectively measured acuity using visual-evoked potentials. The technique was first standardized in normal emmetropic subjects and then applied to uncorrected myopic subjects. We found that visual-evoked potential acuity could accurately indicate Snellen acuity in emmetropia and corrected myopia; however, the two measures were highly correlated only in those uncorrected myopic subjects with visual acuities of 20/100 or better. In subjects with poorer than 20/200 uncorrected visual acuity caused by myopia, estimates of visual-evoked potential acuity could not be obtained. The correlation between these two measures of visual acuity was also lower in patients with decreased Snellen acuity attributable to retinal or ocular disease. We found that patients with unexplainable claims of decreased visual acuity could be diagnosed as having functional visual loss based on objective visual-evoked potential acuities.

Adolescent

Abnormalities of one-carbon metabolism in psychiatric disorders: study of methionine adenosyltransferase kinetics and lipid composition of erythrocyte membranes.

Two independent lines of inquiry have implicated some disturbance of one-carbon cycle metabolism in affective disorders. Folic acid deficiency commonly leads to depression, and S-adenosylmethionine has been reported to have antidepressant properties. Methionine adenosyltransferase has been reported to be underactive in depression and schizophrenia and overactive in mania. This study reports the effects on erythrocyte methionine adenosyltransferase (MAT) kinetics (Vmax) of a 2-week treatment in a population of patients housed on a psychiatric research ward. The drug-free schizophrenic patients and depressives had, upon admission, low Vmax values, and the drug-free manic patients had high Vmax values on admission. After 2 weeks of appropriate treatment, the values for all three patient samples showed significant normalization (i.e., the levels rose in schizophrenics and depressives and fell in manics). We have further shown that pretreatment low levels of erythrocyte membrane phosphatidylcholine in depressives and high levels in manics show statistically significant normalization following 2 weeks of pharmacotherapy. The significance of these results is discussed.

Bipolar Disorder

Evaluation of management of the emergency right hemicolectomy.

To evaluate the morbidity and mortality attending emergency resection of the right colon, we studied retrospectively 119 consecutive patients from two major centers, particularly examining the role of delayed anastomosis (initial ileostomy with subsequent ileocolic anastomosis). Emergency right colectomy was defined as an operative procedure in which partial resection of the terminal ileum and total or partial resection of the cecum and/or ascending colon were necessary before the colon could be evacuated and prepared as might be the case in elective resection. Ninety patients underwent primary anastomosis; hospital mortality and morbidity were 26 and 11%, respectively. Among 29 patients who underwent ileostomy, hospital mortality was 38%; hospital morbidity was 10%. In general, the patients selected for ileostomy were somewhat more ill or had more severe injury. only 17% of all deaths and 8% of all serious complications could be attributed to the anastomosis, leaving little statistical opportunity for improvement by deleting it. The data indicate that a very high mortality (29%) attends emergency right hemicolectomy. Our study indicates that ileostomy in lieu of anastomosis does not reduce this high mortality.

Adolescent

Serotonergic mediation of the suckling-induced release of prolactin in the lactating rat.

Lactating female rats were infused with the serotonergic neurotoxin, p-chloramphetamine (PCA), via stainless steel cannulae implanted into either the 3rd or the lateral ventricle. Those mothers receiving the drug in the 3rd ventricle sustained a more severe depletion of hypothalmic serotonin (43% vs 23%) and a significantly greater incidence of pup mortality (98% vs 48%) than those receiving the drug in the lateral ventricle. Coincident with the depletion of hypothalmic serotonin was a reduction in serum prolactin (Prl). Subcutaneous (s.c.) infections of Prl into each group of females sharply reduced the number of pup deaths. It was concluded that hypothalmic serotonergic neurons mediate the suckling-induced release of Prl necessary for the maintenance of lactation.

Animals

Management of acute lower extremity arterial ischemia due to embolism and thrombosis.

Despite a general impression to the contrary, a recent survey showed that the current mortality rate for acute arterial ischemia approximates 25%. Much of this apparently relates to toxins and procoagulants released from the dying limb, a tendency which may be enhanced further by attempts at revascularization. Based on these observations, we have utilized selective management of acute arterial ischemia in an attempt to minimize deaths and to salvage the maximum number of limbs. If the patient presents within 6 to 8 hours of the onset of acute arterial occlusion and if paralysis or anesthesia is present, then ultimate limb loss is likely. The therapeutic choices are high-dose heparin therapy, operative removal of the clot, or amputation of the limb--the ultimate choice being dependent upon the particular status of the patient. But if sensation and motor function are present, viability of the limb is not threatened, and good results can be obtained by utilizing anticoagulation and delayed elective revascularization, if the latter is indicated. But revascularization attempts after 10 to 12 hours of severe ischemia often are unsuccessful, and ischemia is followed by either recurrent thrombosis and ultimate limb loss, or by death from the systemic effects of reperfusion of ischemic tissue. This type of limb is managed best by using high-dose heparin therapy if viable, or by amputation if it is not. Employing the above criteria, 54 patients with acute arterial ischemia averaging 59 years of age, were treated. Seventeen had immediate thrombectomy, yielding two deaths and four subsequent amputations. Twenty-nine received anticoagulation treatment, resulting in one death and five amputations, and six had immediate amputation, yielding one death. Three had no specific treatment, with one poor result. There were four deaths in the entire series--a mortality rate of 7.5%--and two thirds of the limbs were salvaged. We have concluded that selective management, as prescribed above, was responsible for a significant decrease in mortality rate with no corresponding increase in limb loss, and that high-dose heparin therapy ultimately may prove the initial treatment of choice in all cases of acute arterial ischemia.

Acute Disease

Prevention of complications after liver trauma.

Treatment of 681 cases of liver trauma during the past ten years at the San Francisco General Hospital was reviewed. The mortality was 14.7 per cent and the morbidity rate 18.9 per cent. The complications relating specifically to liver injury were bleeding subphrenic or subhepatic abscesses, intrahepatic abscess, biliary fistula, and liver failure. These complications and the recommended management of the liver injury are discussed.

Adolescent

Pharyngoesophageal caustic stricture. Treatment by pharyngogastrostomy compared to colon interposition combined with free bowel graft.

Four cases of combined hypopharyngeal and cervical esophageal stricture secondary to caustic ingestion are presented. Although gastropharyngostomy has rarely been used for treatment of patients with caustic stricture of the pharynx and cervical esophagus, we believe that it is a useful procedure and has several advantages over use of the colon. We prefer total esophagectomy and posterior mediastinal transposition of the stomach to the neck followed by gastropharyngostomy in those patients who have minimal stomach involvement.

Adolescent

Cellular pharmocodynamics of several anthrocycline antibiotics.

Alterations in the C-9 side chain of the anthracycline antibiotics, adriamycin and daunorubicin, have a profound effect on antibiotic uptake and accumulation by cultured L1210 cells. The degree of inhibition of DNA and RNA biosynthesis in the L1210 cells is directly related to the cellular uptake and accumulation of the drug analogues. Polar drug metabolites, daunorubicinol and adriamycinol, retain inhibitory activity against nucleic acid metabolism but have a decreased membrane binding and permeability. Cellular uptake and accumulation of the C-9 analogues are inversely related to drug polarity. We propose that the polarity of the anthracycline analogues contributes heavily to the differences in therapeutic index and in vivo activity through fundamental effects on membrane permeability, metabolism, and macromolecular binding.

Animals

Advances in management of splenic injuries.

Because there is no such thing as "minor splenic injury", the diagnosis of splenic rupture is a major problem after abdominal trauma. Since it is our policy to explore all penetrating abdominal injuries, the problem of early recognition arises in patients with blunt trauma. When abdominal evaluation is difficult because of associated injuries, we increasingly use peritoneal dialysis. This has been particularly helpful in patients with head injury or drug intoxication and has also contributed to earlier operation in patients with signs of hypovolemia but minimal abdominal findings. Angiography has been useful in doubtful cases. Review of our experience in the last five years with splenectomy (298 cases) has revealed complications, particularly thromboembolic, that have changed our management of these patients. The incidence of clinical pulmonary embolism was 4 per cent in patients having splenectomy for trauma as contrasted with 0.5 per cent in patients having laparotomy for trauma without splenectomy. Postoperative platelet evaluations in patients after splenectomy for trauma revealed thrombocytosis. Detailed follow-up platelet studies showed a peak thrombocytosis at about two weeks, averaging 976,000/mm3. In contrast, similar studies in other patients having laparotomy for trauma showed counts of about 200,000/mm3. Because of the high incidence of thromboembolic complications, a low-dose heparin regimen was initiated. There was a 30 per cent incidence of infection postoperatively.

Abdominal Injuries

Hypothalamic norepinephrine: concentration and metabolism during pregnancy and lactation in the rat.

Both norepinephrine (NE) and its major metabolite, 3-methoxy-4-hydroxyphenylglycol (MHPG), were assayed in rat hypothalamus during selected stages of pregnancy and lactation. No changes were observed in the concentration of either NE or MHPG at 5, 15 or 21 days' gestation. However, with 8-15 h after parturition, the concentration of NE decreased sharply while that of MHPG showed a correspondingly sharp increase. The possible significance of such change in hypothalamic catecholamine activity was considered in relation to parturition, postpartum estrus and onset of maternal behavior.

Animals