Analysis of a large pedigree with elliptocytosis, multiple lipomatosis, and biological false-positive serological test for syphilis

Elliptocytosis, multiple lipomatosis, and biological false-postive serological test for syphilis (BFPSTS) were found in a single individual. One hundred eighty relatives were tested for the three diseases: 74 were typed for seven blood group antigens, and 58 were typed for four electrophoretic enzyme markers. Likelihood analysis of the pedigree data confirmed independent dominant inheritance for elliptocytosis and lipomatosis. BFPSTS appears dominant, but the analysis was inconclusive. No linkages were found between any disease gene and any marker gene. Two female pedigree members with BFPSTS developed systemic lupus erythematosus, a finding in agreement with the previously described association. The analysis did not lead to any conclusions about the causal relationship between the two traits.     

Prednisolone disposition in steroid-dependent asthmatics

A 40-mg intravenous dose of prednisolone was given as prednisolone phosphate to seven severe steroid-dependent asthmatics and to 13 healthy volunteers to determine if the large prednisone requirements of these patients were a function of the disease, cellular response, or rapid clearance of prednisolone. Plasma concentrations of prednisolone, prednisone, and cortisol were determined by high-performance liquid chromatography over an 8-hr test period. Circulating eosinophil concentrations were monitored concurrently. The apparent half-lifes of prednisolone in the asthmatics and normals were 3.33 +/- 0.71 and 3.25 +/- 0.58 hr (mean +/- SD). The apparent plasma clearances of prednisolone were 201 +/- 54 and 198 +/- 38 ml/min/1.73 m2 and the apparent volumes of distribution were 50.8 +/- 11.7 and 53.5 +/- 13.5 L/1.73 m2 for the asthmatic and normal groups, respectively. When the concentration-dependent binding of prednisolone to plasma protein was examined, no differences in the apparent clearances of unbound drug were found between the two groups. The eosinopenic response to prednisolone was similar in the steroid-dependent asthmatics and healthy normal volunteers. These studies indicate that binding, distribution, and clearance of prednisolone are not responsible for the large prednisone requirement of some steroid-dependent asthmatics. Differences in steroid-receptor sensitivity or in severity or pathophysiology of the disease state more likely account for the need for large prednisone dosages in these patients.     

An evaluation of procedures used in staging carcinoma of the cervix

A review of 227 cases of invasive carcinoma of the cervix was undertaken to determine the efficacy of procedures using in the staging of this disease. All patients had a pretreatment chest radiography and intravenous pyelogram. 96.5% had pretreatment cystoscopy, 98.6% had pretreatment proctoscopy, and 92% had a pretreatment barium enema. These patients were retrospectively staged on the findings of physical examination only. Each additional procedure was then evaluated by comparison with the initial staging. Cystoscopy and chest film findings each would have changed the clinical stage in fewer than 1% of cases, barium enema in 1.4%, and proctoscopy in 2.2%. No patient had a positive barium enema without a positive proctoscopy, while two patients had positive proctoscopies with negative barium enemas. The overall yield of positive findings by pretreatment intravenous pyelography was 7.3%. Lymphangiography, although inconsistently done, yielded positive findings in all stages. Chest radiographs, intravenous pyelography, proctoscopy, and lymphangiography are recommended as part of the pretreatment workup of patients with carcinoma of the cervix. Routine barium enema is no longer recommended, and cystoscopy is only recommended in patients with clinical stage IIB disease or greater.     

A new quinoline-carbamate aphicide

We found that it was nearly impossible to apply the quinoline-carbamate aphicide per os by means of synthetic diets, owing to its high feeding-deterrent-effect. After application via the roots of the host plant, this systemic compound is deposited on the leaf surface. The results suggest that the toxic effect is not the result of the oral uptake of phloem sap, but of the tarsal contact with the toxicant. Sensitivity of aphids to this compound and LD50-values were determined after topical applications.     

Tetrahydroisoquinolinecarboxylic acids and catecholamine metabolism in adrenal medulla explants

In a study of the relationship of the tetrahydroisoquinolinecarboxylic acids (TIQCAs) to catecholamine metabolism, we have investigated their effects on cultured rat adrenal medulla explants. Medullae were incubated in medium containing norlaudanosolinecarboxylic acid (NLCA) or 3',4'-deoxynorlaudanosolinecarboxylic acid (DNLCA) (0.5 mM) in the presence and absence of [3H]tyrosine. By paired-ion reverse-phase high pressure liquid chromatography, tissue epinephrine (EPI), norepinephrine (NE), dopamine (DA) and TIQCA were resolved. Endogenous concentrations were measured with electrochemical detection, and radioactivity was assayed by collecting appropriate effluents. Tissue levels of the TIQCAs reached saturating levels of 0.36 mM by about 20 hr. DNLCA elicited a significant decrease (60%) in endogenous DA, NE and EPI at 40 hr, whereas only DA was depressed at 30 hr. NLCA had little effect after 30 or 40 hr. When tissues were maintained in the presence of alpha-methyltyrosine (0.5 mM) for 40 hr, catecholamine levels were depressed to an extent similar to that observed with DNLCA. Incubation with [3H]tyrosine in the presence of TIQCAs revealed inhibition of tyrosine uptake and suggested a reduction in the rate of catecholamine synthesis. These results are consistent with previous data on the inhibition of tyrosine 3-monooxygenase by DNLCA in vitro.     

Suppression of tumorigenicity of rat liver epithelial tumor cell lines by a putative human 11p11.2-p12 liver tumor suppressor locus

We have previously identified and mapped a locus within human chromosome 11p11.2-p12 that suppresses the tumorigenic potential of a rat liver tumor cell line (termed GN6TF) which contains well defined chromosomal aberrations involving rat chromosomes 1, 4, 7, and 10. In the present study, we investigated the potential of this human 11p11.2-p12 liver tumor suppressor locus to suppress the tumorigenic potential of two other rat liver tumor cell lines (GN3TG and GP10TA) following microcell-mediated introduction of human chromosome 11. These tumor cell lines are aneuploid and contain chromosomal abnormalities that are similar to the GN6TF tumor line. The tumorigenic potential and other phenotypic characteristics of GN3TG-11neo and GP10TA-11neo microcell hybrid (MCH) cell lines were variable, and dependent upon the status of the introduced human chromosome 11. MCH cell lines that retained the region of 11p11. 2-p12 delineated by microsatellite markers D11S1385 and D11S903 exhibited suppression of tumorigenicity in vivo (decrease in tumorigenicity and/or elongation of latency), whereas, the tumorigenic potential of one MCH line that lacked markers in this region of human 11p11.2-p12, but retained flanking markers, was not changed from that of the parental tumor cell line. The chromosomal interval between microsatellite markers D11S1385 and D11S903 encompasses the previously localized minimal liver tumor suppressor region, suggesting that a common locus is responsible for tumor suppression among the rat liver tumor cell lines examined. The results of the present study have verified the presence of a liver tumor suppressor locus within human 11p11.2-p12, and have identified a substantial number of microsatellite markers that are closely linked to this tumor suppressor region. These chromosomal markers will facilitate positional cloning of candidate genes from this region, and may prove useful for determining the involvement of this locus in the pathogenesis of human liver cancer.     

Carotid artery repair for radiation-associated atherosclerosis is a safe and durable procedure

OBJECTIVE: The development of carotid atherosclerosis after neck irradiation is well documented. There has been concern about the safety and durability of carotid artery repair through a radiated field. The objective of this report is to describe the immediate and long-term results of a series of cases collected in a 13-year interval. METHODS: From 1984 to 1997, 24 patients underwent 26 carotid artery operations. All the patients had undergone prior radiation therapy at a mean interval of 17 years, with an average radiation dose of 6300 rad. Severe scarring of the skin or radiation fibrosis were present in two thirds of the patients, with 4 patients having permanent tracheostomies. The indications for carotid surgery included cerebral or monocular transient ischemic attack (58%), asymptomatic high-grade stenosis (27%), prior stroke (12%), and tumor invasion of the carotid artery (4%). General anesthesia was used with selective shunting on the basis of carotid artery back pressure or electroencephalography monitoring. Patch angioplasty closure was used in 79% of the patients. The operations included standard carotid endarterectomy (n = 20), external carotid endarterectomy (n = 2), carotid patch angioplasty alone (n = 2), aortocarotid bypass grafting (n = 1), and carotid interposition grafting (n = 1). Four patients required skin grafting or myocutaneous flaps. RESULTS: No deaths or strokes occurred within 30 days of the operations. Six patients had transient cranial nerve palsy, and two had wound infections. The patients were followed from 1 to 156 months, with six patients being followed for longer than 18 months. No strokes were seen at late follow-up examination. Duplex scan examination documented one occlusion, in a patient with primary closure, and two restenoses, one of which necessitated reoperation. The remainder of the grafts were widely patent. CONCLUSIONS: Carotid surgery after neck irradiation is safe and durable. The long-term patency rates and the protection against subsequent neurologic events are similar to the results obtained in the absence of radiation therapy. Problems of wound healing were not found in this series.