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Biomedical subjects

M P Joseph

Publications and source records attributed to M P Joseph.

At least 19 recordsLinked to original sources

Acquired QT interval changes and neck dissections.

STUDY OBJECTIVE: To determine if acquired long QT syndrome following right or left, radical or modified, neck dissections result in malignant arrhythmias or deaths. DESIGN: Prospective study. SETTING: Inpatient head and neck service of the Massachusetts Eye and Ear Infirmary. PATIENTS: 69 patients who underwent extensive neck surgery, without congenital long QT syndrome, medications known to prolong the QT interval, preoperative ventricular arrhythmias, or electrolyte abnormalities. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Preoperative and postoperative electrolytes were evaluated. Preoperative and postoperative electrocardiograms and QT intervals were evaluated. Continuous intraoperative and 10- to 12-hour postoperative monitoring of lead II or V5 were evaluated. Twenty-six patients (Group 1) underwent either right radical neck dissection or modified right radical neck dissection, 25 patients (Group 2) underwent either left radical neck dissection or modified left neck dissection, and 18 patients (Group 3) underwent extensive neck surgery without radical or modified neck dissection. Postoperatively, 38 patients (19 Group 1, 11 Group 2, and 8 Group 3 patients) developed a QT interval corrected for heart rate (QTc) of greater than 440 milliseconds. Repeated measures analysis of variance, comparing preoperative and postoperative QTc showed a statistically significant preoperative to postoperative change, but no significant difference among the three groups. No malignant arrhythmias or deaths were recorded in any of the three groups. CONCLUSIONS: Acquired long QT syndrome following radical neck dissection, without congenital, metabolic, or pharmacologic disturbance, is unlikely to trigger malignant arrhythmias, as previously reported for right radical neck dissection.

Analysis of Variance

Tyr292 in the seventh transmembrane domain of the AT1A angiotensin II receptor is essential for its coupling to phospholipase C.

An essential role of the conserved Asp74 in the coupling of the type 1 angiotensin II (AII) receptor (AT1) to phospholipase C has already been reported (Bihoreau, C., Monnot, C., Davies, E., Teutsch, B., Bernstein, K. B., Corvol, P., and Clauser, E. (1993) Proc. Natl. Acad. Sci. U. S. A. 90, 5133-5137). Moreover, preliminary modeling studies have shown that a spatial proximity exists between Asp74, located in transmembrane domain II, and Tyr292, located in transmembrane domain VII and conserved in many, but not all, G protein-coupled receptors. We mutated Tyr292 into Phe and evaluated the pharmacological and activation characteristics of the mutated receptor (Y292F) stably expressed in Chinese hamster ovary cells. This receptor possessed unchanged binding properties for agonist or antagonist peptide ligands compared to the wild-type receptor, while its coupling to phospholipase C was severely impaired. Interestingly, competition binding experiments, using 125I-[Sar1]AII as a tracer ligand, showed that the Y292F receptor displayed an increased Ki value for DuP 753, an AT1-specific nonpeptide antagonist and a greatly decreased Ki value for the AT2-specific ligand CGP 42112A. These pharmacological changes are similar to those observed for the previously reported mutation of Asp74 into Asn. This apparently symmetrical role of Asp74 and Tyr292 is consistent with the hypothesis that an interaction between these two amino acids could be a key event in the molecular processes linking AII recognition and AT1 receptor activation.

Animals

Optic canal decompression in indirect optic nerve trauma.

BACKGROUND: The proper management of neurogenic visual loss after blunt head trauma is controversial. Non-treatment, corticosteroids, and surgical decompression of the optic canal are all currently considered to be reasonable alternatives. The goal of this study was to identify factors affecting improvement in patients treated with canal decompression. METHODS: A retrospective analysis of 31 cases in which transethmoidal decompression of the optic canal had been performed for neurogenic visual loss after closed head trauma was conducted. Each patient was alert and free of injury to the globe when evaluated before surgery. Surgery was performed within 6 days of injury, and all were given perioperative steroids. RESULTS: Visual acuity improved in 22 (71%) patients, with 6 (19%) regaining visual acuity of 20/40 or better. The mean improvement from preoperative visual deficit was 42.0% +/- 6.6%, with a median improvement of 45.2%. Both univariate and multivariate analysis suggested that vision improved more in patients who were younger than 40 years of age than in patients who were 40 years of age or older. Interval between injury and surgery, preoperative visual acuity, and the presence of optic canal fracture did not affect outcome. CONCLUSION: Any future randomized trials of therapy should stratify patients based on age. Enrollment of patients with no light perception or who experienced delay between injury and treatment may be reasonably considered.

Adolescent

Transethmoidal transsphenoidal approach for embolization of a carotid-cavernous fistula. Case report.

The authors describe a case of carotid-cavernous fistula that was not treatable by the standard interventional neuroradiological techniques of transarterial or transvenous occlusion of the fistula because access was blocked by prior trapping procedures. Access to the venous side of the fistula was gained by means of a transethmoidal transsphenoidal exposure, making it possible to embolize the lesion with coils. The details of this approach are described.

Adult

A tetrapeptide within a receptor-binding region of human follicle-stimulating hormone beta-subunit, hFSH-beta-(34-37), regulates sodium-calcium exchange in Sertoli cells.

In a previous study, we showed that binding of FSH by cultured rat Sertoli cells significantly inhibited basal levels of Na+/Ca2+ exchange. Similar inhibition was observed when proteoliposomes enriched with bovine calf testis follicle-stimulating hormone (FSH) receptors were stimulated with FSH. In the present study, we screened a series of overlapping synthetic peptide amides, representing the entire primary structure of the beta-subunit of hFSH, for their effects on sodium-dependent calcium uptake (as 45Ca2+) by monolayer cultures of Sertoli cells from immature rats. hFSH-beta-(33-53), previously identified as a receptor binding region of hFSH-beta-subunit, significantly (P < 0.05) inhibited Na+/Ca2+ exchange. A tetrapeptide [TRDL, hFSH-beta-(34-37)] contained within this sequence, was observed to be equally as active as hFSH-beta-(33-53) at 200 microM, suggesting that the regulatory effect of hFSH-beta-(33-53) on sodium-dependent 45Ca2+ influx was due to residues 34-37. hFSH-beta-(81-95) also inhibited Na(+)-dependent calcium influx, although to a lesser extent than hFSH-beta-(33-53) or hFSH-beta-(34-37). Sodium-dependent 45Ca2+ entry into Sertoli cells was enhanced in a concentration-related manner when extracellular sodium was replaced by equimolar concentrations (up to 135 mM) of choline chloride. hFSH-beta-(34-37) significantly reduced basal uptake of 45Ca2+ in choline-containing buffer, but was without effect in buffer containing 135 mM NaCl.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence

A new role for follicle-stimulating hormone in the regulation of calcium flux in Sertoli cells: inhibition of Na+/Ca++ exchange.

Elucidation of mechanisms regulating intracellular calcium levels in steroidogenic tissues is important for understanding control of cellular function. We have previously described FSH receptor-mediated flux of 45Ca++ into cultured rat Sertoli cells and receptor-enriched proteoliposomes via voltage-sensitive and voltage-independent calcium channels. In the present study, we report heretofore unrecognized inhibitory effects of FSH on Na+/Ca++ exchange in these two systems. An outwardly directed Na+ gradient, developed by preincubating Sertoli cell monolayers in buffer made hypertonic with NaCl, resulted in uptake of 45Ca++ that was unaffected by calcium channel blocking agents, ruthenium red or methoxyverapamil, but was enhanced by ouabain, a specific inhibitor of Na+/K(+)-ATPase. Sodium-dependent 45Ca++ flux into Sertoli cells was inhibited in a concentration-related manner by increased extracellular Na+ (up to 135 mM). FSH consistently and reproducibly (28.9 +/- 3.8%, 10 separate assays) reduced sodium-dependent 45Ca++ influx in the absence or presence of ouabain. A lesser effect on Na+/Ca++ exchange was seen when Li+ replaced Na+ in the preincubation buffer, and a marked reduction occurred when Sertoli cells were incubated in buffer containing KCl, presumably due to membrane depolarization. FSH-sensitive Na+/45Ca++ exchange was also observed when using FSH receptor-enriched proteoliposomes. Our earlier calcium channel studies indicated that FSH affects Ca++ entry into Sertoli cells via a receptor-mediated process. The results reported here demonstrate that the interaction of FSH with its receptor is associated with changes in Na+/Ca++ exchange as well, and suggest that this activity may also be involved in regulating intracellular free Ca++ levels in the Sertoli cell.

Animals

Extracranial optic nerve decompression for traumatic optic neuropathy.

We examined 14 patients with acute, unilateral optic nerve injury after blunt head trauma. In each patient the optic canal was decompressed through an ipsilateral external ethmoidectomy. The patients also received treatment with dexamethasone during the perioperative period. There was no morbidity or mortality. Eleven of the 14 patients improved, including 3 of the 5 who could not perceive light preoperatively. Transethmoid-sphenoid optic canal decompression is a safe and effective treatment for indirect optic nerve trauma.

Adult

Brainstem facial-motor pathways from two distinct groups of stapedius motoneurons in the cat.

To determine the brainstem origins and axonal routes of stapedius motoneurons, we labeled motoneurons by injecting cat stapedius muscles with horseradish peroxidase. Some injections were made in normal cats and some in cats in which the middle segment of the internal facial genu had been cut. By tracing labeled axons and by comparing the locations of labeled cell bodies in normal and lesioned cats, we divided stapedius motoneurons into two groups: "perifacial" and "accessory." Perifacial stapedius motoneurons have cell bodies located around the motor nucleus of the facial nerve and axons which follow the classical course of facial motor axons through the internal genu of the facial nerve. Accessory stapedius motoneurons have cell bodies near the descending facial motor root and axons which ascend to the rostral tip of the internal facial genu, abruptly reverse direction, and then join the descending facial motor root. The sharply hooked course of axons of accessory stapedius motoneurons is similar to the course of axons from other accessory nuclei of cranial nerves V-VII. Our present results, with those of McCue and Guinan (J. Neurophysiol. 60:1160-1180, '88), demonstrate that cats have two groups of stapedius motoneurons which can be separated anatomically by the locations of their cell bodies or by the courses of their axons, and which, on the average, have different response properties.

Animals

Sebaceous carcinoma. Diuretic use, lacrimal system spread, and surgical margins.

Twenty cases of adnexal sebaceous carcinoma managed by contemporary methods, including monitoring of surgical margins, were reviewed. Eight of 20 patients were taking diuretic medications. The initial clinical diagnosis was incorrect in all cases, and 50% of cases were misdiagnosed by the pathologist interpreting the initial biopsy. The canaliculus was identified in 7 cases, and was involved by tumor in 3 cases. Tumor was identified in the lacrimal sac and inferior turbinate in an additional case. Thus, tumor spread into the lacrimal excretory system was documented by histologic findings in 4 cases.

Adenocarcinoma

Mucoepidermoid carcinoma involving the lacrimal sac.

Mucoepidermoid carcinoma of the lacrimal sac was diagnosed in a 62-year-old woman who presented with epiphora and a fixed painless mass in the area of the lacrimal sac. Histopathologic findings included nests and islands of neoplastic cells in a fibrotic stroma. The tumor nests contained both glandular spaces and solid epithelial areas. Treatment entailed dacryocystectomy with silastic intubation and subsequent medial maxillectomy and ethmoidectomy. The patient was tumor free on 1-year follow-up. Clinical features, histopathological findings, prognosis, and management of this rare tumor are reviewed in this article.

Carcinoma

Kartagener's syndrome. A blinded, controlled study of cilia ultrastructure.

We investigated respiratory mucosa cilia ultrastructure in patients homozygous for the gene for Kartagener's syndrome (KS) and patients apparently phenotypic for KS who had bronchiectasis and sinusitis but without situs inversus. Parents, as obligate carriers of the recessive KS gene, were also evaluated among other control groups. The four patients with KS had significantly fewer cilia outer dynein arms than normal subjects or parents of patients with KS. Two of five patients apparently phenotypic for KS demonstrated distinctive ultrastructural changes. No other subjects demonstrated explicit ultrastructural abnormalities. Internal control specimens showed that the number of outer dynein arms was consistent within a subject compared with variation between subjects. The outer dynein arm serves as a dependable ultrastructural marker. Carriers of KS do not demonstrate distinctive morphologic cilia abnormalities. Not every patient with chronic bronchiectasis and sinusitis demonstrates abnormal cilia ultrastructure.

Adolescent

Number and distribution of stapedius motoneurons in cats.

Cell bodies of stapedius motoneurons were identified by retrograde transport of horseradish peroxidase (HRP) following injections into the stapedius muscle. Large injections were made in an attempt to label all stapedius motoneurons. To control for labeling of non-stapedial neurons resulting from spread of HRP, we determined the locations of brainstem neurons labeled by HRP applied to the facial nerve, the chorda tympani nerve, the auricular branch of the vagus nerve, the tensor tympani muscle, and the cochlea. In three cats analyzed in detail, 1,133-1,178 neurons projecting to the stapedius muscle were identified. Arguments are given which suggest that in these three cats all stapedius motoneurons were labeled. The labeled stapedius neurons may all be motoneurons because they all stain positively for acetylcholinesterase and have medium-coarse Nissl bodies. Most stapedius motoneurons were located around the motor nucleus of the facial nerve. Staphedius motoneurons were also found near the descending limb of the facial-nerve root, in the peri-olivary neuropil, and in the reticular formation with the ascending fibers of the facial-nerve root.

Animals

An assessment of grafts in the posterior cricoid lamina.

Subglottic stenosis is a recognized complication of prolonged intubation. To date, there is no uniformly successful operative procedure for severe subglottic stenosis, fulfilling the criteria of decannulation and a serviceable voice. The surgical ideals for such a procedure should include the use of autogenous grafting material, avoidance of internal stenting, and limited manipulation of the mucosa. This study was intended to assess the fate of isolated hyoid and thyroid alar grafts interposed in the posterior cricoid lamina. Additionally, anterior/posterior splits with and without anterior grafting were evaluated. Seventeen dogs were used in the determinate animal model. Vocal cord mobility was evaluated by direct laryngoscopy prior to sacrifice. Graphic gross anatomical specimens depict the effects of anterior/posterior splitting on the cricoid cartilage. Clinical correlations are suggested.

Animals

Alternatives to anterior-posterior packs for epistaxis.

This paper describes two alternatives to a conventional anterior-posterior pack for control of posterior epistaxis. Both methods involve occluding the posterior choana with finger-cot packs introduced through the anterior nares. These have proved effective in controlling bleeding with significant reduced morbidity.

Epistaxis

Epidemiology of high-tension electrical injuries in children.

Twenty-seven acute high-tension electrical injuries were seen in seven years at the Shriners Burns Institute. All were in boys 7 to 16 years old; 13 suffered amputation(s) and 2 died. Most accidents occurred when boys climbed utility poles (9), trespassed, generally around transformer substations (9), or contacted power lines when tree climbing (5). All occurred in daylight, generally between 4 and 6 PM, on weekends in warm weather with boys in groups. Preventive education directed to this high-risk population should illustrate properties of high-voltage electricity, effects on the body, and how to cope with peer pressures in unstructured time.

Adolescent