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Biomedical subjects

M H Nathan

Publications and source records attributed to M H Nathan.

At least 19 recordsLinked to original sources

The ectopic parathyroid adenoma: a cost justification for routine preoperative localization with technetium Tc 99m sestamibi scan.

OBJECTIVES: To evaluate the cumulative costs of failure to identify the ectopic parathyroid adenoma when exploration without preoperative localization is performed and to compare these costs with the expenses of routine preoperative localization in every patient. DESIGN: A consecutive series of 59 patients with primary hyperparathyroidism studied with preoperative scans using technetium Tc 99m sestamibi and ultrasound was submitted to a cost analysis. A subset of 5 cases of ectopic adenomas, presumed to be unidentifiable on routine surgery, was similarly analyzed. SETTING: Academic tertiary referral center. METHODS: The operative, anesthesia, hospitalization, imaging, and physician reimbursement costs of a failed exploration are compared with the costs of preoperative technetium Tc 99m sestamibi and ultrasound scans in every patient. RESULTS: Two cases of mediastinal parathyroid adenomas in this consecutive series of 59 patients were given a theoretical cost, including hospitalization, physician reimbursement, and anesthesia fees. These costs were based on a failed cervical exploration and extracted from the record of an actual patient who underwent such a process at the University of Vermont, Burlington, in 1995. In addition, the records of 2 patients with intrathyroidal adenomas were submitted to the same theoretical cost analysis with the exception that these patients were assumed to have adenomas that could be discovered after prolonged cervical exploration and thyroid lobectomy. The net management and imaging costs for 4 cases of ectopic parathyroid adenomas undergoing theoretical failed exploration are compared with the cost of obtaining routine technetium Tc 99m sestamibi and ultrasound scans for each of the 59 patients. CONCLUSION: The added cost of protracted or failed cervical exploration nearly neutralized the costs of a routine preoperative localization with technetium Tc 99m sestamibi and ultrasound scans.

Adenoma↗

Preoperative technetium Tc 99m sestamibi imaging. Paving the way to minimal-access parathyroid surgery.

OBJECTIVE: To examine the reliability of technetium Tc 99m sestamibi scanning as a new adjunct to the surgical management of hyperparathyroidism. DESIGN: Preoperative localization of parathyroid adenoma by technetium Tc 99m sestamibi delayed washing-out scanning and high-resolution ultrasound was compared with a historical institutional experience of surgical intervention without preliminary localization studies. A 10-year retrospective review from 1985 to 1995 of patients with surgical hyperparathyroidism was performed. SETTING: Academic tertiary referral medical center. PATIENTS: Thirty-three technetium Tc 99m sestamibi scans in patients with primary hyperparathyroidism were correlated with eventual surgical and pathologic findings. The last 10 patients were also studied with 10-MHz linear transducer ultrasound, and the results were compared with those of the radionuclide scan and eventual surgical and pathologic findings. From 1985 to 1995, 142 patients underwent surgical exploration for primary hyperparathyroidism, and 125 records were available for review. RESULTS: The technetium Tc 99m sestamibi parathyroid scan correctly identified the site and presence of 31 adenomas among 34 confirmed tumors, a sensitivity of 91% and positive predictive value of 97%. The scan detected three anterior mediastinal adenomas that could not be removed through cervical exploration. In each instance median sternotomy was included in the primary surgery and allowed efficient, successful management of these ectopic adenomas. High-resolution ultrasound correctly identified nine of 10 cervical parathyroid adenomas and predicted the volume of each tumor to a statistically significant level. CONCLUSIONS: Hyperthyroidism has traditionally been treated surgically without preliminary localization studies. We found both technetium Tc 99m sestamibi scanning and high-resolution ultrasound to be highly sensitive at detecting parathyroid adenomas at the 90% level. Furthermore, preoperative localization allowed efficient surgical intervention for our group of patients who had high frequency of mediastinal adenomas that required transmediastinal surgery.

Adenoma↗

EGF induces increased ligand binding affinity and dimerization of soluble epidermal growth factor (EGF) receptor extracellular domain.

The binding of epidermal growth factor (EGF) to its cell surface receptor (EGF-R) results in a number of intracellular responses including the activation of the receptor intracellular tyrosine kinase. Receptor oligomerization induced by ligand binding has been suggested to play an important role in signal transduction. However, the mechanisms involved in oligomerization and signal transduction are poorly understood. We have produced and purified several milligrams of recombinant extracellular domain of the EGF receptor (EGF-Rx) using the baculovirus/insect cell expression system. The baculovirus-generated EGF-Rx is glycosylated, has had its signal peptide correctly cleaved, and exhibits a dissociation constant for EGF similar to that for solubilized full-length receptor, of about 100 nM. The binding of EGF to EGF-Rx leads to the formation of receptor dimers and higher oligomerization states which are irreversibly captured using the covalent cross-linking agent disuccinimidyl suberate. Interestingly, purified receptor monomers and dimers, stabilized by the cross-linker in the presence of EGF, exhibit increased binding affinity toward EGF as compared with receptor monomers which have not been exposed to EGF. It appears that the high affinity state of receptor can be maintained by the covalent cross-linking agent. These results indicate that in addition to ligand binding, the extracellular domain of EGF receptor possesses the inherent ability to undergo ligand-induced dimerization and that the low affinity state is converted to a high affinity state by EGF.

Animals↗

Lipoxygenase-generated icosanoids inhibit glucose-induced insulin release from rat islets.

Lipoxygenase-pathway metabolites of arachidonic acid are produced in pancreatic islets. They are are implicated in insulin release, since nonselective inhibitors of lipoxygenases inhibit glucose-induced insulin release. We studied the interplay in insulin release between glucose and selected icosanoids formed in 5-, 12- and 15-lipoxygenase pathways. Effects on immunoreactive insulin release of 10(7) to 10(6)-12-(R)-HETE, 12-(S)-HETE, hepoxilin A3, lipoxin B4, LTB4 or LTC4 were tested individually in 30-min incubations of freshly isolated young adult Wistar rat pancreatic islets, in the presence of 5.6 mM or 23 mM glucose. Basal insulin release (at 5.6 mM glucose) was stimulated by LTC4 and hepoxilin A3 (304% and 234% of controls at 5.6 mM glucose alone, respectively), inhibited by 12-(S)-HPETE (56%), and was not affected by 12-(R)-HETE, 12-(S)-HETE, lipoxin B4 or LTB4 (111%, 105%, 106% and 136%, respectively). Insulin release evoked by 23 mM glucose (190-320%) was inhibited (50-145%) by all icosanoids tested, except LTC4 (162%). We conclude that, among the lipoxygenase products tested, only leukotrienes and hepoxilin are candidates for a tonic-stimulatory influence on basal insulin release. Since glucose promotes icosanoid formation in islets, the observed inhibition of glucose-induced insulin release by lipoxygenase products suggests the existence of a negative-feedback system.

Animals↗

The pathological, ultrasonographic and computerized tomographic characteristics of chronic hematocele.

We report a case of a chronic hematocele and describe its characteristics. The specific pathological lesion of a chronic hematocele consists of several neovascular formations covered by layers of fibrin. These lesions give characteristic ultrasonic and computerized tomographic images, consisting of several sharply circumscribed small spherical areas of soft tissue. When correctly interpreted before the initiation of surgical treatment, these images will obviate an orchiectomy, which is not always necessary.

Aged↗

Familial double testicular tumors: identical chromosome changes in seminoma and embryonal carcinoma of the same testis.

An identical abnormal chromosome, i(12p), and a marker chromosome of unknown origin were seen in 2 tumors of different histology (seminoma and embryonal carcinoma) in the same testis. A younger brother of the patient also had undergone orchiectomy for 2 seminomas in the left testis 2 years previously. These findings are discussed in relation to the possible cellular background of testicular tumors and their genetic parameters.

Adult↗

Stable expression of recombinant factor VIII molecules using a bovine papillomavirus vector.

The bleeding disorder in hemophilia A results from a deficiency or abnormality of Factor VIII (FVIII), a member of the coagulation cascade. FVIII is a large glycoprotein (approximately 350,000 daltons) that is activated by a series of proteolytic cleavages. During activation, a large internal domain (B domain) is removed, resulting in an active complex comprised of the amino and carboxyl subunits of the parental molecule. Using a bovine papillomavirus expression vector system, we have established stable, genetically engineered cell lines harboring either full-length FVIII cDNA or variant FVIII cDNA (delta FVIII), the latter containing an extensive deletion in the region encoding the B domain. We demonstrate that the two recombinant FVIII molecules manifest the biological attributes of native FVIII. Relative to full-length FVIII transformants, cells harboring delta FVIII cDNA are five to eight times more efficient in expressing coagulant activity. This difference is due to a post-transcriptional event.

Bovine papillomavirus 1↗

The projection from the olfactory epithelium to the olfactory bulb in the salamander, Ambystoma tigrinum.

Odor quality may be represented as a "topographic" code of responses of receptor cells throughout the olfactory epithelium, with this code conveyed to the central nervous system by a topographic projection from the olfactory epithelium to the olfactory bulb. There is good evidence for topographic differences in odor-induced receptor cell activity in the tiger salamander but there is no evidence for a topographic epithelium-to-bulb projection in this species. In the present study 3H-leucine autoradiography was used to trace the projections of olfactory receptor neurons in the tiger salamander. Thirteen animals received small injections of tritiated leucine into different regions of the dorsal or the ventral olfactory epithelium, or into the ventrolateral, "vomeronasal organ". The results show that the anterior-to-posterior axes in the dorsal and ventral epithelia are represented along the ventral-to-dorsal axis in the rostral end of the olfactory bulb. The "vomeronasal organ" projects to the caudal end of the bulb. We conclude that the central projection of the olfactory epithelium in the tiger salamander is topographically organised only along the antero-posterior axis and not the medio-lateral axis. Thus epithelial receptor cell activity along the anteroposterior axis would be represented in the glomerular layer of the bulb by activity along its ventro-dorsal axis.

Ambystoma↗

Pressure-infusion venography.

A new, simple pressurizing technique using air injection into an infusion bottle, makes rapid intravenous infusion of radiopaque contrast medium possible. This method permits the use of 30% solutions in a large volume to obtain excellent venograms while eliminating the complications of pain and thrombophlebitis which often occur with more concentrated solutions.

Contrast Media↗

Conventional oral cholecystography versus single-visit oral cholecystography.

The conventional manner of preparing ambulatory patients for oral cholecystography with six tablets of iopanoic acid yields results which are essentially equal to those obtained by single-visit oral cholecystography (two-day preparation with 12 tablets of iopanoic acid). Also, it is more convenient for patients and referring physicians. The conventional method of preparation is recommended for hospitalized patients as well.

Administration, Oral↗

Normal findings in oral and cholecystokinin cholecystography.

Normal findings in oral cholecystography and normal response of the gallbladder to cholecystokinin are established in 200 normal controls. These include absence of right upper quadrant pain in 98.5%, absence of spasm of the body of the gallbladder and of severe spasm in the fundus, a common bile duct diameter of 6 mm or less in those 182 that were visualized, and gallbladder size of less than 11 cm in length in about 97% and less than 4 cm in width in about 97%. If normal contraction occurs after cholecystokinin (or sincalide), an unusually large gallbladder is of no importance. Little or no gallbladder contraction in the presence of normal concentration is probably of no importance.

Administration, Oral↗