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Biomedical subjects

M S Allen

Publications and source records attributed to M S Allen.

At least 145 records · Page 8Linked to original sources
PubMed1991

Management of vocal nodules: a regional survey of otolaryngologists and speech-language pathologists.

This study surveyed 21 otolaryngologists (70% return) and 32 speech-language pathologists (46% return) in Maine about the treatment of vocal nodules in children and adults, referral patterns, effectiveness of therapy, and adequacy of speech-language pathologists' training. Differences in opinions between the two professional groups were found in treatment of children and referral patterns.

Adult↗
PubMed1990

Synthetic and computer-assisted analyses of the pharmacophore for the benzodiazepine receptor inverse agonist site.

The structural requirements for ligand binding to the benzodiazepine receptor (BzR) inverse agonist site were probed through the synthesis and in vitro evaluation of 3-substituted beta-carbolines 6, 7, 11, 12, gamma-carboline 13, and diindoles 18-21, 23-25, 27, 28, and 34. On the basis of the apparent binding affinities of these and other analogues, a hydrogen bond acceptor site (A2) on the receptor is proposed to interact with the N(9) hydrogen atom of the beta-carbolines or the N(7) hydrogen nuclei of the diindoles. Likewise, a proposed hydrogen bond donating site (H1) interacts with the N(2) nitrogen atom of the beta-carbolines or the N(5) nitrogen atom of the diindoles. It appears that interaction with both sites is a prerequisite for high affinity since analogues which have either one or both of these positions blocked exhibit substantial reduction in affinity. Moreover, H1 appears to be capable of engaging in a three-centered hydrogen bond with appropriately functionalized ligands, which explains the increase in potency observed in the following series of 3-substituted beta-carbolines: the n-butyl (12, IC50 = 245 nM), n-propoxy (9, IC50 = 11 nM), and propyl ketone (11, IC50 = 2.8 nM) congeners. In addition to H1 and A2, there appears to be a relatively narrow hydrophobic pocket in the binding cleft that can accommodate substituents at the 3-position of the beta-carbolines which have chain lengths less than or equal to C5. There is a 1 order of magnitude decrease in affinity between n-propoxy analogue 9 (IC50 = 11 nM, chain length = 4) and n-butoxy derivative 7 (IC50 = 98 nM, chain length = 5). Furthermore, alpha- and gamma-branching [e.g. ethoxycarbonyl (2), IC50 = 5 nM and tert-butoxycarbonyl (31) IC50 = 10 nM] but not beta- and delta-branching [e.g. isopropoxy (6), IC50 = 500 nM and (neopentyloxy) carbonyl (48), IC50 = 750 nM] at position 3 are tolerated. Occupation of this hydrophobic pocket is clearly important for high affinity as evidenced by the relatively low affinity of 30, a beta-carboline which possesses a hydrogen atom at the 3-position. This same hydrophobic pocket is partially filled by the D and E rings of the diindoles, which accounts for the high affinity of several members of this series. An excluded volume analysis using selected 3-substituted beta-carbolines and ring-E substituted pyridodiindoles is consistent with the presence of this hydrophobic pocket (see Figure 1).(ABSTRACT TRUNCATED AT 400 WORDS)

Binding Sites↗
PubMed1989

Vascular adrenal cysts. A clinicopathologic and immunohistochemical study of endothelial and hemorrhagic (pseudocystic) variants.

Three endothelial cysts and five hemorrhagic cysts (pseudocysts) arose in the adrenal glands of seven patients aged 23-73 years. Four patients were male and three were female. Five were symptomatic and gave abdominal pain as their chief complaint. Endothelial cysts were collapsed or filled with serous fluid, multiloculated, had an endothelial lining, and often contained adrenal cortex in their outer walls. The endothelial lining reacted only weakly for Factor VIII-related antigen (FVII-RAg), but it stained strongly for collagen type IV (C-IV). The lack of hemorrhage and the FVIII-RAg/C-IV staining pattern in endothelial cysts suggest lymphatic differentiation. Hemorrhagic cysts were spherical, firm masses containing clotted blood and hyalinized thrombus with attenuated adrenal cortex in the outer fibrous wall. Islands of intact cortical cells were present deep within the thrombi of four hemorrhagic cysts. Three of five hemorrhagic cysts stained strongly for FVIII-RAg and C-IV in irregular vascular channels of the attenuated cortex and within the cyst contents. These channels suggest that at least some hemorrhagic cysts arise when hemorrhage occurs in a preexisting blood vascular anomaly. Entrapment of cortical islands by extravasated blood in hemorrhagic cysts may be misdiagnosed as necrotic cortical neoplasm. To avoid confusion, one must recognize the normality of the entrapped cortical cells, identify an intrinsic vascular anomaly, and distinguish thrombus from necrotic tumor.

Adrenal Gland Diseases↗
PubMed1988

3-Ethoxy-beta-carboline: a high affinity benzodiazepine receptor ligand with partial inverse agonist properties.

3-Ethoxy-beta-carboline binds with high affinity to benzodiazepine receptors in the central nervous system (Ki approximately equal to 10.1, 15.3, and 25.3 nM in rat cerebellum, cerebral cortex, and hippocampus, respectively). This compound has pharmacological actions reminiscent of benzodiazepine receptor partial inverse agonists such as FG 7142 and 3-carboethoxy-beta-carboline. Thus, while not a convulsant, 3-ethoxy-beta-carboline potentiated the convulsant actions of pentylenetetrazole in mice. Furthermore, this compound reduced both the time spent and the total entries in the open arms of an elevated plus maze and also inhibited stress-induced ulcer formation, effects that are also observed with benzodiazepine receptor inverse agonists. These findings suggest that 3-ethoxy-beta-carboline is a partial inverse agonist at benzodiazepine receptors which may prove useful for in vivo studies since it has a higher affinity for benzodiazepine receptors and better solubility than the commonly used partial inverse agonist FG 7142. Furthermore, 3-ethoxy-beta-carboline appears to be less vulnerable to metabolic degradation than ester analogs with a similar pharmacological profile such as 3-carboethoxy-beta-carboline.

Animals↗
PubMed1988

Synthesis of novel 3-substituted beta-carbolines as benzodiazepine receptor ligands: probing the benzodiazepine receptor pharmacophore.

The 3-substituted beta-carbolines 2-4 and 5-7 were prepared from 3-amino-beta-carboline (8) in one step via diazotization, followed by reaction with the appropriate nucleophile in order to determine their binding affinity for benzodiazepine receptors (BzR). All three of the 3-alkoxy-beta-carbolines 2 (IC50 = 124 nM), 3 (IC50 = 24 nM), and 4 (IC50 = 11 nM) have high affinities for BzR. The beta-carbolines substituted with electron-withdrawing groups including 5 (Cl; IC50 = 45 nM), 6 (NO2; IC50 = 125 nM), and 7 (N = C = S; IC50 = 8 nM) also had high affinities for BzR. The affinities of 5-8 clearly indicate that a carbonyl moiety at position 3 of a beta-carboline is not required for high-affinity binding to BzR. These findings have led to the development of a model for the binding of ligands to an inverse agonist domain at BzR. This model is supported by the recent synthesis of 3-ethoxy-beta-carboline (3), a potent, long-lived partial inverse agonist, and 7, an irreversible BzR ligand.

Animals↗
PubMed1988

Evaluating constraints on fiber digestion by rumen microbes.

Factors affecting fiber digestion in ruminants were evaluated with the use of simple mathematical models. These models were constructed to define the dynamic processes involved so that constraints on fiber digestion may be elucidated. The fraction of fiber that is resistant to digestion and the rate of digestion and passage of potentially fermentable fiber were identified as constraints on fiber digestion in the rumen. Fermentation lag was shown to have no direct effect on fiber digestibility. Fiber that is resistant to fermentation by rumen microbes represents a significant fraction of forage fiber and accumulates in the rumen relative to potentially fermentable fiber. The digestibility of fiber that is potentially fermentable is a function of the rate at which the fiber is digested and its retention time in the rumen. Selective retention of potentially fermentable fiber in the rumen is necessary for the maximization of fiber digestion.

Animals↗
PubMed1986

Congenital occult papillary carcinoma of the thyroid gland.

A male infant born at 34 weeks of gestation had a 3-mm occult papillary thyroid carcinoma of the follicular variant type that was discovered fortuitously at autopsy. Although clinically overt papillary thyroid carcinoma has been described in neonates in whom nodules were present at birth, this is apparently the first description of an occult congenital thyroid carcinoma. The reasons for this discrepancy and the potential value of further documentation of occult thyroid carcinoma in neonates are briefly discussed.

Carcinoma, Papillary↗
PubMed1984

Low-grade papillary adenocarcinoma of palatal salivary gland origin.

The clinicopathologic features of five low-grade papillary adenocarcinomas of palatal salivary gland origin are presented and seven well-documented cases from the literature are reviewed. Patients in our series ranged in age from 30 to 77 years (median 48). Symptoms were nonspecific and related to a mass present for a long duration. Histologically, these were complex cystic, papillary, focally solid tumors that were partially encapsulated. Cytologically, they were composed of bland, predominantly cuboidal cells with eosinophilic or clear cytoplasm. Four tumors were initially considered to be benign mixed tumors, but long-term follow-up indicates that these are slowly growing, malignant neoplasms. Three patients developed solitary cervical lymph node metastases from 2 to 21 years after initial presentation. One tumor underwent an anaplastic transformation to solid adenocarcinoma, and this was from the only patient in our series who died with tumor. Low-grade papillary adenocarcinoma is a clinicopathologically distinctive salivary gland neoplasm, with histologic features unlike those of other papillary salivary gland tumors.

Adenocarcinoma↗
PubMed1984

Retrorectal cystic hamartoma. Report of three cases, including one with a perirenal component.

Retrorectal cystic hamartomas (RCHs) are uncommon lesions of controversial pathogenesis that arise in the presacrococcygeal space. We describe the clinicopathologic features of RCHs from three adult patients. Two were asymptomatic women; the third was a man who had a pelvic abscess. All three specimens were multiloculated cysts lined by squamous, transitional, and glandular epithelium. Poorly organized collections of smooth muscle were present in the surrounding connective tissue, but no well-formed smooth-muscle coat was seen. Although RCHs possess elements of three germ-cell layers, their histologic features are similar to those of the embryonic tailgut. The male patient also had a perirenal mass that was grossly and histologically identical to the RCH. The associated kidney was malrotated. A portion of the embryonic tailgut may have been pulled cephalad by the developing kidney, inhibiting its rotation. Clinicopathologic features distinguish RCH from other retrorectal cystic lesions, including teratoma, dermoid, epidermal cyst, rectal duplication, anal duplication, and anal gland cyst.

Adolescent↗
PubMed1983

Small-cell undifferentiated carcinoma of the colon. A clinicopathological study of five cases and their association with colonic adenomas.

Colonic small-cell undifferentiated carcinoma (SCUC) is an extremely aggressive neoplasm. We describe five patients with colonic SCUC and review five additional, well-documented cases. The longest known duration of survival is 14 months and all patients with follow-up of this duration have died of disease. Regional lymph nodes are invariably involved at the time of diagnosis and when distant metastases were present, the liver was always affected. Four of our cases of SCUC arose in association with colonic adenomas and in two of these the SCUC component was confined to the superficial submucosa. Yet, both produced regional metastases and one had massive hepatic involvement. Ultrastructurally, colonic SCUC exhibits divergent, predominantly neuroendocrine differentiation. The ultrastructural features and association with colonic adenomas suggest an endodermal rather than neuroectodermal derivation.

Adenoma↗
PubMed1982

Malignant melanoma of the anus: report of 12 patients and analysis of 255 additional cases.

The authors present a report of 12 patients with anal melanoma (AM) and review 255 cases reported since 1947. Combining these patients with those from the literature, the authors analyze several aspects of AM that are controversial or have not been studied in a systematic manner. The mean clinical tumor size was 4.1 cm. Seventy per cent were grossly pigmented, 63 per cent were polypoid, and 44 per cent were prolapsed. Two-thirds of AM were located in the proximal pecten, at or near the level of the anal valves. Microscopically, the most useful diagnostic criteria were melanin production, junctional change, and a nesting growth pattern. In four of the authors' cases, atypical junctional change extended laterally from the overt invasive neoplasm for distances up to 1 cm. Approximately 60 per cent of patients had metastases at the time of diagnosis. There was no statistical difference in determinate survivals of patients treated for cure by local excision and abdominoperineal resection. Neither tumor size nor configuration affected survival. The choice of therapy was not influenced by tumor size.

Adult↗
PubMed1979

Adenoid cystic carcinoma: biologic behavior in 38 patients.

This study presents the clinical and pathologic data on 38 patients with adenoid cystic carcinoma. Most of the tumors arose from the major salivary glands or the mucus glands of the upper respiratory tract and oral cavity. The typical biological behavior of these tumors was slow but aggressive local growth despite all therapy, followed by eventual death from local disease and/or metastases. Twenty-eight of the patients have died, 22 from adenoic cystic carcinoma, 3 from postoperative complications, and 3 from intercurrent disease. Of the 10 living patients, 4 have active disease, 2 have no evidence of disease 14 years after diagnosis, and 4 have no evidence of disease but follow-up is less than 5 years. We compared various microscopic features of the tumors, including histologic grading, with prognosis but did not demonstrate a correlation in this small series.

Adult↗
PubMed1979

Colorectal carcinoma in the first three decades of life.

Sixteen cases of colorectal adenocarcinoma in patients 30 years of age and younger were treated at the University of Virginia Medical Center between 1957 and 1977. Ten patients (63%) were black, and seven patients (44%) were black females. The high incidence of this tumor in young blacks in our patient population appears to be a recent development, becoming clinically manifested since 1965. Pain was the major presenting symptom, and bleeding was a constant finding in the patients with rectosigmoid lesions. Eighty-six percent had metastases at the time of diagnosis despite a short duration of symptoms. Five-year survival in 11 patients with mucinous adenocarcinoma was 18%, while the three patients with well-differentiated glandular carcinoma had a 5-year survival of 33%. Material was unavailable for histologic review in two cases. Fourteen of 16 patients eventually died of their carcinoma, and one patient died of malignant lymphoma. Additional factors which correlated with length of survival were resectability, extent of bowel wall invasion, and the presence of lymph node capsular invasion. Nodal capsular invasion is an especially sensitive marker for short-term survival and has not been previously reported in colonic tumors.

Adenocarcinoma↗
PubMed1978

Emergency Department treatment, triage and transfer protocols for the burn patient.

Emergency department treatment, triage and transfer protocols for patients with major thermal injury have been devised by the three burn centers in Virginia. A burn nurse educator has presented these guidelines to the emergency departments of Virginia. The development of these protocols has considerably improved the immediate care of the victims of thermal injury who are transferred to the burn centers in the Commonwealth of Virginia.

Adolescent↗
PubMed1978

Methylmethacrylate: A study of teratogenicity and fetal toxocity of the vapor in the mouse.

To determine possible deleterious effects of methylmethacrylate vapor on mouse gestation, pregnant mice were exposed to average vapor concentrations of 1330 parts per million for two hours twice daily during Day 6 through Day 15 of pregnancy. A slight increase in the average weight of the fetuses of the exposed mothers were demonstrated but no other evidence of fetal toxicity or teratologic effects was found. During three total hip replacements, the concentration of methylmethacrylate in operating-room air never rose above 280 parts per million.

Abnormalities, Drug-Induced↗