Biomedical subjects
Publications and source records attributed to R Levy.
We report a patient who developed tension pneumopericardium following penetrating trauma to the chest. Lung adhering to the pleura due to previous infection prevented the lung from collapsing and resulted in diversion of the air leak into the anterior mediastinum and from there through a breach into the pericardium.
Lipoteichoic acid isolated from Streptococcus faecalis or Streptococcus pyogenes caused direct activation of the respiratory burst in human peripheral blood monocytes. This activity appears to be related to the ability of lipoteichoic acid to bind to the monocyte membrane and trigger the polarization of receptors (capping).
A murine monoclonal antibody was identified by its ability to induce a reversible antiproliferative effect on a human lymphoma cell line. Immunoprecipitation studies revealed that the antibody reacted with a 26-kilodalton cell surface protein (TAPA-1). A diverse group of human cell lines, including hematolymphoid, neuroectodermal, and mesenchymal cells, expressed the TAPA-1 protein. Many of the lymphoid cell lines, in particular those derived from large cell lymphomas, were susceptible to the antiproliferative effects of the antibody. TAPA-1 may therefore play an important role in the regulation of lymphoma cell growth. A cDNA clone coding for TAPA-1 was isolated by using the monoclonal antibody to screen an expression library in COS cells. Analysis of the deduced amino acid sequence indicated that the protein is highly hydrophobic and that it contains four putative transmembrane domains and a potential N-myristoylation site. TAPA-1 showed strong homology with the CD37 leukocyte antigen and with the ME491 melanoma-associated antigen, both of which have been implicated in the regulation of cell growth.
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In a sample of 178 subjects with Alzheimer's disease, diagnosed by clinical criteria (NINCDS/ADRDA), delusions had occurred in 16% of the sample since the onset of the illness and been present within the last 12 months in 11%. Simple delusions of theft and suspicion were the most common types and a greater proportion of men suffered delusions of theft. Subjects with other types of delusion had relatively well preserved lateral ventricular size and basal ganglia calcification. Twenty per cent of the group had experienced persecutory ideation short of delusions since the onset of the illness. Cognitive function at entry to the study and cognitive deterioration over the succeeding 12 months was not influenced by the presence of disorders of thought content.
In a sample of 178 patients with AD, visual hallucinations had been experienced by 13% and auditory hallucinations by 10%. Thirty per cent had misidentification syndromes; these were associated with a younger age and younger age at onset of illness, and proportionally more men than women were affected. There was a reduced 30-month mortality rate in this group. Subjects with hallucinations had a greater deterioration in cognitive function at 12-month follow-up, which could not be accounted for by neuroleptic medication.
Of 178 patients with AD, at least one depressive symptom was reported by 63%, 24% were rated as being depressed by a trained observer, and 43% were considered depressed by their relatives. Ten per cent had a previous history of depression. Elevated mood was rare, occurring in only six patients (3.5%). Subjects with depressive symptoms had less cognitive impairment and less ventricular enlargement on CT compared with those without symptoms. Widening of the interhemispheric fissure was associated with symptoms of mania but was inversely related to presence of depressive symptoms.
Out of a sample of 178 patients with AD, aggression was present in 20%, wandering in 19%, binge-eating in 10%, hyperorality in 6%, urinary incontinence in 48%, and sexual disinhibition in 7%. Behavioural abnormalities were greater in those with more severe dementia. Temporallobe atrophy correlated with aggression, and widening of the third ventricle with hyperorality. Features of the Kluver-Bucy syndrome were commonly seen, but the full syndrome occurred in only one subject. Patients with at least one feature of the Kluver-Bucy syndrome had greater temporal-lobe atropy than those without any of the features.
Seventeen patients with malignant external otitis were treated with oral ofloxacin. Their mean age was 69 years. Seven of the patients were diabetic. Pseudomonas aeruginosa, sensitive to ofloxacin (Kirby-Bauer method, inhibition zone greater than or equal to 22 mm), was isolated from the external auditory canal in all patients. Ofloxacin (200 mg b.i.d.) was given to the patients for 12 to 39 days. Two patients also received additional parenteral antibiotic therapy. Subjective and objective improvement occurred in all patients during treatment, and complete resolution was documented in all patients, with one exception. Only one patient suffered recurrence 2 weeks after discontinuation of antimicrobial therapy. The results of our study suggest that oral ofloxacin is an effective treatment for malignant external otitis caused by Pseudomonas aeruginosa.
Fifty of the 810 patients who underwent stapedotomy for otosclerosis from 1969 through 1988 were randomly chosen for follow-up of at least 5 years. Most of the patients (65%) had follow-up of 10 years after stapedotomy, but another 50 patients who underwent stapedectomy had follow-ups of longer than 10 years. In 50 patients, stapedectomy under local anesthesia was performed by removal of the footplate of the stapes, using an endaural incision, and covering the oval window with Gelfoam. In the other 50 patients, stapedotomy was performed under general anesthesia, using an endopreauricular incision, making a small hole in the footplate, and covering the hole only with blood from the surgical area. Although both groups showed improvement in hearing after the operation, the air-bone gap in the stapedotomy group was significantly better than that in the stapedectomy group. The use of the endopreauricular incision under general anesthesia was preferable to endaural incision under local anesthesia because the operative field was wider, more convenient for the surgeon, and conducive to patient safety. There were no significant complications in either group.
Anti-idiotype monoclonal antibodies are now available for up to one-third of all patients with B-cell cancer. This is because some antibodies made in the past for individual patients cross-react with the idiotype expressed by other patients' tumor cells. Clinical trials with anti-idiotype antibodies have demonstrated reproducible antitumor effects in patients who have failed conventional treatments. The anti-idiotype antibody treatments are not associated with any significant toxicity and rarely induce immune responses in patients with B-cell lymphoma. They can therefore be used repetitively. Future developments will include the combination of anti-idiotype antibodies with other biologic therapies and with chemotherapy. In addition, one may be able to induce the patient to make an active immune response against the idiotype expressed by his or her tumor cells.
1,25-Dihydroxyvitamin D3 (1,25[OH]2D3) caused a rise in the concentration of intracellular free calcium ions ([Ca2+]i) in HL-60 cells. This effect of 1,25(OH)2D3 parallels its suppression of cell proliferation and its induction of cell differentiation into monocyte-like cells. The changes in [Ca2+]i are dose and time dependent. The concentration of 1,25(OH)2D3 (10(-7) M) that induced maximal differentiation also caused the maximal increase in intracellular Ca2+. The rise in cytoplasmic free Ca2+ concentration was not immediate and reached statistical significance only after 24 h. The [Ca2+]i reached its peak at 48 h (134 +/- 4 nM vs 101 +/- 3 nM in controls) and remained stable at this level. The increase in intracellular Ca2+ was found to be related to new protein synthesis, because it was inhibited in the presence of specific RNA and protein synthesis inhibitors. The rise in [Ca2+]i was not observed during incubation of HL-60 cells with 24,25-dihydroxyvitamin D3 (24,25[OH]2D3), a vitamin D metabolite that does not induce the differentiation of HL-60 cells. In contrast, 25-hydroxyvitamin D3 (25-OH-D3) and phorbol 12-myristate 13-acetate (TPA), both of which induce differentiation in this cell line, also increase [Ca2+]i. In conclusion, the present study emphasizes that a significant increase in intracellular free Ca2+ occurs in the effect of 1,25(OH)2D3 on HL-60 cells.
Chronic oral administration of oxodipine, a new calcium channel blocker, resulted in a reduction in the blood enzyme activity of alanine and aspartate aminotransferase. The reductions were both time and dose related. The decline in enzyme activities was accompanied by microscopic hepatic changes, which in the opinion of the authors should have been associated with an increase in the enzyme activities of alanine aminotransferase and aspartate aminotransferase. The effect was only partially reversed one month after the cessation of oxodipine treatment.
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Pregnant women are more susceptible to candida infections than nonpregnant women. Since monocytes play a major role in host defense against candida, their association with radiolabeled candida and their capacity for killing candida were compared in sera of pregnant and nonpregnant women. While the basal rate of these monocyte functions was similar in both groups of women, candida opsonized with serum from pregnant women was less effective in enhancing these monocyte activities. Serum from nonpregnant women increased the association about twofold, whereas serum from pregnant women increased it only by about one and a half times in the two groups of women. Pretreatment of candida with serum from pregnant women increased the killing to 28%, whereas the serum from nonpregnant women was more effective, increasing the killing to 40%. The difference between the effect of the sera could not be attributed to the level of serum complement or IgG.
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The question whether chronic membrane depolarization regulates selectively the expression of different muscarinic cholinergic receptors has been studied in primary neuronal cultures prepared from two regions of embryonic rat brain. Chronic (3 or 6 days) but not acute (3 or 24 h) membrane depolarization of cultured septal neurons with 40 mM potassium chloride have increased the number of muscarinic receptors by 168 +/- 28%, but no such effect has been observed with hippocampal cultures. Displacement experiments with the M1 selective antagonist pirenzepine have shown that muscarinic receptors in the septum of adult rat have 3-5 times lower affinity to this compound than hippocampus receptors. The results suggest that chronic membrane depolarization selectively increases the number of presynaptic muscarinic receptors, expressed by septal neurons, whereas hippocampal neurons expressing postsynaptic receptors have no such response.
Each B-cell lymphoma expresses a surface immunoglobulin that contains unique antigenic determinants (idiotypes). We have produced 199 murine monoclonal antibodies reactive with the idiotypes isolated from 67 patients with follicular small-cleaved-cell lymphoma. These antiidiotype antibodies were analyzed for their ability to react with lymphoma cells from patients other than the one against which each antibody was made. Twenty of the 199 antiidiotype antibodies were reactive with lymphoma cells from more than one patient. Depending on the antibody, the frequency of idiotype sharing ranged from 0.6 to 6.2 percent of B-cell lymphoma tumors evaluated. Tumors could be grouped into distinct families on the basis of their reactivity with these antibodies. In the aggregate, the 20 antibodies reacted with a total of 49 of 150 B-cell lymphomas (33 percent), including 30 of 110 follicular small-cleaved-cell lymphomas (27 percent). Many of these shared idiotypes were expressed by more than one histopathological subtype of lymphoma. We conclude that a panel of antibodies reactive with shared idiotypes can be produced for patients with B-cell lymphoma, obviating the need to produce an antiidiotype antibody for each patient.