Normal insulin-receptor cDNA sequence in Pima Indians with NIDDM

Pima Indians have served as a model of non-insulin-dependent diabetes mellitus (NIDDM). Within this population, inherited insulin resistance is a primary determinant of abnormal glucose metabolism. The insulin receptor is regarded as a "candidate gene" that could potentially be defective in Pima Indians or other populations with NIDDM. To directly address the question of potential insulin-receptor genetic defects in Pima Indians, we isolated and sequenced insulin-receptor cDNA from two Pima Indians with NIDDM. Small amounts of lymphoblast RNA were used to generate first-strand cDNA, which was then amplified via the polymerase chain reaction (PCR). In this way, seven overlapping segments of insulin-receptor cDNA were obtained. With the exception of the alternatively spliced 36-base pair exon 11, which is not expressed in lymphoblasts, the complete coding region of the mature proreceptor was examined with a combination of direct sequencing and sequencing of subcloned PCR segments. The nucleotide sequence in both subjects was identical to previously published insulin-receptor cDNA sequences obtained from healthy subjects. These data indicate that abnormalities of insulin binding and receptor function that have been previously observed in vitro with fresh and cultured cells from Pima Indians may be consequences of the diabetic milieu and/or genetic abnormalities in molecules that interact with the insulin receptor.     

Clinical evaluation of esophageal Doppler cardiac output measurement during general anesthesia

We evaluate the accuracy of cardiac output measurement with esophageal Doppler ultrasonography (ECO). A total of 71 simultaneous measurement of esophageal Doppler and thermodilution cardiac output were compared in 16 patients undergoing general anesthesia in the supine position. ECO was determined easily with minimal experience, and significantly correlated with thermodilution cardiac output (TDCO) measurement (P < 0.001). The regression equation obtained was Y = 0.983X + 0.019, and the correlation coefficient was 0.935. Furthermore, ECO was more reproducible than TDCO. However, ECO is not able to assess CO accurately in either lateral or prone position and after cardiopulmonary bypass in open heart surgery. Our results suggest that the esophageal Doppler technique allows a noninvasive and continuous cardiac output monitoring in patients during general anesthesia, and that it is more useful in patients for whom invasive monitoring is considered inappropriate. However, further improvement in this technique will be necessary for its routine use in clinical anesthesia.(Ueda M, Yokota S, Nakata F et al.: Clinical evaluation of esophageal doppler cardiac output measurement during general anesthesia. J Anesth 3: 178–182, 1989)     

Cutaneous signs (Raynaud's phenomenon,sclerodactylia, and efladema of the hands) and hand-arm vibration exposure

Summary Dermatological tests and examinations of the hand(s) were carried out in vibration-exposed and un exposed males. The subjects were 179 chain-saw workers in private forestry companies and 205 local inhabitants who had never used vibrating tools. The prevalences of Raynaud's phenomenon (RP), sclerodactylia, and edema of the hands were estimated in both groups, and associations between these cutaneous signs and vibration exposure were evaluated. The prevalences of RP and edema in the exposed group were 9.5% and 1.7%, respectively, and in the unexposed group, 2.9% and 1.5%, respectively. Sclerodactylia was seen in 31.8% of the chain-saw workers but in only 6.4% of the unexposed individuals. In statistical analyses based on unconditional logistic regression models with adjustment for age, RP was associated with long-term ( 20 years) vibration exposure [odds ratio (OR) = 7.06; 95% confidence interval (CI) = 2.51–19.87]. Sclerodactylia was associated with both short- and long-term vibration exposure (OR = 6.54, Cl = 3.30-13.36; OR = 7.05; CI = 3.41-14.60, respectively). There were significant dose-response relationships between RP and duration of exposure and between sclerodactylia and duration of exposure. Results of function tests indicated a longer recovery time and a higher vibration threshold for the workers with RP. The presence of sclerodactylia, however, did not have any significant influence on function test results. It is possible to conclude that not only RP but also sclerodactylia could be induced by vibration exposure. However, most cases of sclerodactylia were not so serious as to involve disturbances of peripheral circulatory and nerve function.     

Effects of halothane and calcium entry blockers on atrioventricular conduction

The effects of halothane on AV nodal function were evaluated in dogs with verapamil, diltiazem, or nifedipine during atrial pacing using the technique of Hisbundle electrocardiography. Fifty-one mongrel dogs were divided into six groups. Anesthesia was induced with ketamine 100mg im. and thiamylal 25mg/kg iv. The animals were intubated and mechanically ventilated at normocapneic levels. Anesthesia was maintained with 50% nitrous-oxide in oxygen with pancuronium 2mg im. Dogs in groups I, III, and V were anesthetized with 0.8% halothane and 50% nitrous-oxide in oxygen. We observed interactions between halothane and intravenous administration of either verapamil 0.1mg/kg, diltiazem 0.15mg/kg, or nifedipine 0.01mg/kg respectively. Dogs in groups II, IV, and VI were administered either verapamil, diltiazem, or nifedipine iv without halothane. There were prolongations of sinus cycle length (SCL) (414 ± 10 to 542 ± 19msec.), atrium-His (AH) interval (73 ± 3 to 97 ± 5msec.), and functional refractory period (FRP) of the AV-node (227 ± 5 to 260 ± 5msec.) in halothane anesthesia in groups I, III, and V. There were more prolongations of these variables after iv administration of verapamil (SCL; 617 ± 35, AH; 118 ± 7, FRP of the AV node; 311 ± 4) and diltiazem (SCL; 554 ± 19, AH; 118 ± 12, FRP of the AV node; 283 ± 12) but no prolongations after nifedipine (SCL; 533 ± 19, AH; 99 ± 8, FRP of the AV node; 272 ± 9). Comparing effects of calcium entry blockers with and without halothane in groups I and II, III and IV, or V and VI, there were additive depressing effects of halothane with either verapamil or diltiazem on AV nodal function. And there is a difference between the effects of nifedipine on SCL with and without halothane.(Yokota S, Harada K, Takigawa C et al.: Effects of halothane and calcium entry blockers on atrioventricular conduction; A comparative study of verapamil, diltiazem, and nifedipine. J Anesth 2: 219–226, 1998)     

“Sporadic” prealbumin-related amyloid polyneuropathy: report of two cases

Summary Two sporadic cases of amyloid polyneuropathy are reported. There was no family history or plasma cell dyscrasia. Both showed sensorimotor and autonomic polyneuropathy with onset in the seventh decade. Amyloid deposits in both cases reacted with anti-human prealbumin sera but not with antisera to human AA and anti-human immunoglobulin light-chain amyloids, including A and A. One patient had the abnormal serum prealbumin and abnormal DNA sequence found in type I familial amyloid polyneuropathy (FAP) (Japanese type). Investigations in sporadic amyloid polyneuropathy should include immunohistochemistry, using antisera to the different amyloid proteins, and the radioimmunoassay and recombinant DNA techniques for diagnosis of FAP.     

Immediate reconstruction using a scalp-forehead flap for the entire upper lip defect with the application of lyophilized porcine skin to surgical wounds. A case report of a malignant melanoma in the upper lip and oral mucosa

A rare extensive malignant melanoma involving the upper lip and maxillary alveolar mucosa was removed by en bloc resection after chemotherapy and radiotherapy. Simultaneous immediate reconstruction of the entire upper lip defect was carried out with a bitemporal pedicle flap which included the scalp and forehead after applying lyophilized porcine skin to the wound where the alveolar bone had been resected, and the bilateral scalp-forehead and thigh donor sites. A partial denture was inserted six months postoperatively. Now, one and a half years after operation, the patient is quite satisfied with his cosmetic appearance and masticatory recovery.     

The detection of residual acute lymphoblastic leukemia cells with immunologic methods and polymerase chain reaction: a comparative study

In this study we applied double color immunofluorescence analysis and polymerase chain reaction (PCR) amplification of rearranged TCR delta genes for detecting residual leukemia in the posttreatment bone marrow (BM) samples taken from four patients in morphological remission. In three of these patients (nos. 1-3; T-ALL) a combination of CD3 and anti-TdT antibodies (Abs) was used to identify residual blasts while in patient 4 (B lineage ALL) the combination CD13/TdT served to detect residual disease. Two rounds of PCR primed by nested amplimers were carried out to prepare clonospecific probes from presentation DNA and to investigate the follow-up samples. In patients 1 and 2 no cCD3+/TdT+ cells were seen posttreatment, but PCR amplification of the TCR V delta 1-D-J delta 1 region revealed residual disease in both patients. Patient 1 underwent allogeneic BM transplant (BMT) 8 months after diagnosis and is well 3 months post-BMT while patient 2 relapsed 12 months after presentation. In patient 3 the remission samples investigated 2 and 3 months after diagnosis did not contain cCD3+/TdT+ cells, but in the sample collected at 4 months a few such cells (0.0001-0.001%) could be detected. In the same sample, PCR amplification of the TCR V delta 2-D-J delta 1 region indicated the presence of 10(-4)-10(-3) residual leukemic cells. These findings predicted full morphological relapse which occurred 2 months later. In patient 4 CD13/TdT double positive cells were clearly seen 2 and 3 months after presentation. PCR amplification of the V delta 2-D delta 3 recombination also revealed residual blasts when applied to one of such "remission" samples. After further remission induction treatment, no immunologic evidence of residual disease was detected. This patient received an allogeneic BMT 8 months after diagnosis and is disease free 4 months after BMT. Our data indicate that both double color immunofluorescence and PCR analysis offer powerful tools to study residual leukemia and highlight the advantages as well as the potential limitations of each technique.     

Alterations of endothelin-converting enzyme expression in early and advanced stages of human coronary atherosclerosis

Endothelin-1 is a potent vasoconstrictor and exhibits a mitogenic activity on vascular smooth muscle cells (SMCs). Endothelin-converting enzyme (ECE) is the final key enzyme of endothelin-1 processing. We studied the immunolocalization of ECE in human coronary atherosclerotic lesions with different disease stages. Frozen sections of normal coronary arteries with diffuse intimal thickening (n=13) and those of coronary arteries with early (n=10) or advanced atherosclerotic plaques (n=13) were studied. Monoclonal antibodies used were directed against SMCs, macrophages, endothelial cells, and ECE. For the identification of cell types that express ECE, double immunostaining analysis was also used. In normal coronary arteries, ECE immunoreactivity was observed in luminal endothelial cells and medial SMCs. Early atherosclerotic plaques, which consisted predominantly of SMCs, showed enhanced ECE expression in luminal endothelial cells and intimal SMCs. In advanced atherosclerotic plaques, distinct ECE expression was found in accumulated macrophages and in endothelial cells of intraplaque microvessels, while luminal endothelial cells showed relatively weak immunoreactivity for ECE. In conclusion, the present study demonstrates that the major cell types expressing ECE within the plaques are different between early and advanced stages of human coronary atherosclerosis. Enhanced ECE expression and possible endothelin-1 generation may contribute to SMC proliferation and vasoconstriction in early atherosclerotic stages, and may promote plaque destabilization in advanced atherosclerotic stages.