Biomedical subjects
M M Lewis
Publications and source records attributed to M M Lewis.
Computed tomography--guided needle biopsy of head and neck lesions.
OBJECTIVE: To evaluate the diagnostic efficacy of computed tomography (CT)-guided needle biopsies of head and neck lesions. DESIGN: All CT-guided needle biopsies of head and neck lesions performed between September 1994 and February 1999 were included. Cytopathologic and histologic records, along with patient clinical records, were reviewed. SETTING: A tertiary care medical center. PATIENTS: Patients referred for evaluation of lesions inaccessible to routine methods of needle biopsy. RESULTS: Thirty-seven patients underwent 42 CT-guided biopsies. There were included 12 lesions in or adjacent to the skull base and 9 lesions around the pharyngoesophageal or laryngotracheal complex; the other lesions were located in the deep lobe of the parotid gland (n = 7), deep neck area (n = 12), and thyroid gland (n = 2). Diagnostic cytologic biopsy specimens were obtained in 38 (91%) of 42 needle biopsy procedures. The results were supported histologically and/or clinically in 36 cases (95%). Eighteen patients underwent open surgical procedures. Histologic confirmation was found in 86% of cases. Nineteen patients (51%) avoided an open surgical procedure: 11 with benign disease and 8 with recurrent malignancy. There were no false-positive or false-negative results, and no complications were identified. CONCLUSIONS: Computed tomography-guided needle biopsy is a safe and reliable minimally invasive technique for the diagnosis of poorly accessible or deep-seated lesions of the head and neck. Diagnostic needle biopsies allow improved preoperative planning and patient counseling in surgical patients and avoidance of open surgical procedures in patients with benign disease or recurrent malignant neoplasms.
Use of a novel marker, calponin, for myoepithelial cells in fine-needle aspirates of papillary breast lesions.
Benign and malignant papillary lesions of the breast (PBL) can be difficult to distinguish in fine-needle aspirates (FNA). This study evaluates the use of smooth muscle actin (SMA) and a new smooth muscle-specific protein, calponin, for identifying myoepithelial cells (MEC) by immunohistochemical methods in paraffin-embedded cell blocks of FNA of PBL. Formalin-fixed, paraffin-embedded cell blocks of 40 cases of PBL were stained using SMA and calponin, steam heat-induced epitope retrieval, and an avidin biotin-complex technique. Staining was evaluated in MEC, epithelial, and stromal cells. The diagnosis of benign vs. malignant papillary lesion was made by using cytomorphological criteria and the presence/absence of MEC in the cell block. These results were compared to the original cytologic and subsequent histologic diagnoses. Of 40 cases of FNA diagnosed as PBL, there were 27 intraductal papillomas (IP), 6 papillary lesions with atypical features (PLAF), and 7 papillary carcinomas (PC). In all of the IP, MEC stained both with SMA and calponin. None of the PC cases was positive for MEC with calponin, and 2 out of 7 cases were weakly positive by SMA. In 6 cases of PLAF, 2 were negative for MEC, both by SMA and calponin, and a malignant papillary lesion was confirmed by histology. The remaining 4 cases were positive for MEC with both markers and were confirmed to be benign by histology. SMA stained stromal cells strongly in all of the cases where stroma was present (18 of a total of 40 cases of PBL), while calponin stained stroma focally in only 7 cases. More than half of all cases had nuclear staining of epithelial cells with SMA; calponin did not show any nuclear staining.
A 66-year-old man with dyspnea, left lower lobe infiltrate, and abnormal imaging.
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Synthesis and dopaminergic properties of benzo-fused analogues of quinpirole and quinelorane.
In an analogy to the potent catechol dopamine D1 agonists dihydrexidine (1) and dinapsoline (2), benzo rings were fused onto the structures of the dopamine D2-selective agonists quinelorane (3) and quinpirole (4). Each of the phenyl ring-substituted derivatives had significant affinity for D2 receptors, albeit somewhat lower than the two parent compounds, 3 and 4. Compounds with N-propyl and N-allyl substituents (5b, 5c, 6c, and 6d) had higher affinity for the D2 dopamine receptor than did their corresponding secondary amines (5a and 6a). Slightly different effects on affinity of an n-propyl and an n-allyl group in the new analogues of 3 and 4 suggest that different binding orientations may be invoked at the receptor.
Interactions of the novel antipsychotic aripiprazole (OPC-14597) with dopamine and serotonin receptor subtypes.
OPC-14597 {aripiprazole; 7-(-4(4-(2,3-dichlorophenyl)-1-piperazinyl) butyloxy)-3,4-dihydro-2(1H)-quinolinone} is a novel candidate antipsychotic that has high affinity for striatal dopamine D2-like receptors, but causes few extrapyramidal effects. These studies characterized the molecular pharmacology of OPC-14597, DM-1451 (its major rodent metabolite), and the related quinolinone derivative OPC-4392 at each of the cloned dopamine receptors, and at serotonin 5HT6 and 5HT7 receptors. All three compounds exhibited highest affinity for D2L and D2S receptors relative to the other cloned receptors examined. Both OPC-4392 and OPC-14597 demonstrated dual agonist/antagonist actions at D2L receptors, although the metabolite DM-1451 behaved as a pure antagonist. These data suggest that clinical atypicality can occur with drugs that exhibit selectivity for D2L/D2S rather than D3 or D4 receptors, and raise the possibility that the unusual profile of OPC-14597 in vivo (presynaptic agonist and postsynaptic antagonist) may reflect different functional consequences of this compound interacting with a single dopamine receptor subtype (D2) in distinct cellular locales.
Substituted naphthofurans as hallucinogenic phenethylamine-ergoline hybrid molecules with unexpected muscarinic antagonist activity.
A series of substituted racemic naphthofurans were synthesized as "hybrid" molecules of the two major prototypical hallucinogenic drug classes, the phenethylamines and the tryptamines/ergolines. Although it was hypothesized that these new agents might possess high affinity for the serotonin 5-HT2A/2C receptor subtypes, unexpected affinity for muscarinic receptors was observed. The compounds initially synthesized for this study were (+/-)-anti- and syn-4-amino-6-methoxy-2a,3,4,5-tetrahydro-2H-naphtho[1,8-bc]furan (4a,b), respectively, and their 8-bromo derivatives 4c,d, respectively. The brominated primary amines 4c,d were assayed initially for activity in the two-lever drug discrimination (DD) paradigm in rats trained to discriminate saline from LSD tartrate (0. 08 mg/kg). Also, 4c,d were evaluated for their ability to compete against agonist and antagonist radioligands at cloned human 5-HT2A, 5-HT2B, and 5-HT2C receptors. After the syn diastereomers were found to have the highest activity in these preliminary assays, the N-alkylated analogues syn-N,N-dimethyl-4-amino-6-methoxy-2a,3,4, 5-tetrahydro-2H-naphtho[1,8-bc]furan (4e) and syn-N, N-dipropyl-4-amino-6-methoxy-2a,3,4,5-tetrahydro-2H-naphtho[1, 8-bc]furan (4f) were prepared and assayed for their affinities at [3H]ketanserin-labeled 5-HT2A and [3H]-8-OH-DPAT-labeled 5-HT1A sites. All of the molecules tested had relatively low affinity for serotonin receptors, yet a preliminary screen indicated that compound 4d had affinity for muscarinic receptors. Thus, 4b,d,e were evaluated for their affinity at muscarinic M1-M5 receptors and also assessed for their functional characteristics at the M1 and M2 isoforms. Compound 4d had affinities of 12-33 nM at all of the muscarinic sites, with 4b,e having much lower affinity. All three compounds fully antagonized the effects of carbachol at the M1 receptor, while only 4d completely antagonized carbachol at the M2 receptor. The fact that the naphthofurans lack LSD-like activity suggests that they do not bind to the serotonin receptor in a way such that the tricyclic naphthofuran nucleus is bioisosteric with, and directly superimposable upon, the A, B, and C rings of LSD. This also implies, therefore, that the hallucinogenic phenethylamines cannot be directly superimposed on LSD in a common binding orientation for these two chemical classes, contrary to previous hypotheses.
Homologous desensitization of the D1A dopamine receptor: efficacy in causing desensitization dissociates from both receptor occupancy and functional potency.
The role of drug efficacy in agonist-induced desensitization was studied in C-6 glioma cells transfected with the monkey dopamine D1A (mD1A) receptor. Dopamine pretreatment for 2 hr produced greater than 80% loss of responsiveness in the stimulation of cAMP accumulation that was blocked by the D1 antagonist SCH23390. A series of full and partial D1 agonists from structurally dissimilar classes were then examined. Three full agonists (dihydrexidine, SKF82958, A77636) desensitized the receptor to the same extent as dopamine, whereas two other full agonists (dinapsoline and A68930) and all the partial agonists tested (SKF38393, pergolide and d-lysergic acid diethylamide tartrate) produced only partial desensitization (i.e., 50% that of dopamine). Whereas partial agonists (i.e., SKF38393, pergolide and d-lysergic acid diethylamide tartrate) caused no alteration in ligand-accessible mD1A receptors, four of the full agonists (dopamine, dihydrexidine, dinapsoline, A68930) caused a 30 to 40% reduction in receptor number. One full agonist, A77636, caused nearly an 80% decrease in receptor number, despite the fact that the degree of functional desensitization was similar to the other full agonists. The desensitization of the D1 receptor was homologous, not affecting beta-2 adrenergic receptors endogenous to C-6 cells. Neither incubation with cAMP analogs, nor inhibition of protein kinase A, affected dopamine-induced desensitization, suggesting a cAMP-independent mechanism in this cell line. Together, these data suggest that functional desensitization of the mD1A receptor expressed in C-6 glioma cells is a cAMP-independent mechanism, cannot be predicted reliably from agonist efficacy for stimulating adenylate cyclase and can occur in the absence of changes in receptor number.
The radiographic stage of giant cell tumor related to stromal cells' proliferation. Tissue cultures in 13 cases.
The clinical behavior of giant cell tumor is related to the radiological appearance. To test the hypothesis that in vitro proliferation of the neoplastic stromal cell population of giant cell tumors is related to the radiological appearance, this study was undertaken. A prospective analysis of the cells migrating from 13 consecutive tumors was conducted. Growth curves and population doubling-times (PDT) for first and fifth passages were calculated and alkaline phosphatase levels were measured and compared to preoperative radiographic staging. A strong negative correlation was found between PDT and the radiographic stage. Tumors in stages I and II (low aggressiveness) were found to have an average cell population doubling-time of 11 (SD 2.2) days, while those in stage III (high aggressiveness) showed a doubling-time of 6 (SD 2.2) days. Low alkaline phosphatase activity was noted in all cultures, a finding consistent with the putative preosteoblastic potential of these stromal cells. This putative origin is also indicated by the differentiation response to retinoic acid. The findings suggest that the in vitro proliferation of the mononuclear stromal cell population of giant cell tumors is related to the radiographic stage and may predict the clinical behavior of these tumors.
Immediate breast reconstruction for stage III breast cancer using transverse rectus abdominis musculocutaneous (TRAM) flap.
BACKGROUND: The management of state III breast cancer is challenging; it often includes multimodal treatment with systemic therapy and/or radiation therapy and surgery. Immediate breast reconstruction has not traditionally been performed in these patients. We review the results of immediate transverse rectus abdominis musculocutaneous (TRAM) flap in 21 patients treated for stage III breast cancer. METHODS: Data have been collected retrospectively on 21 patients diagnosed with stage III breast cancer between 1987 and 1994. All patients had mastectomy and immediate TRAM reconstruction. Thirteen patients received primary systemic therapy, 10 patients received postoperative consolidation radiotherapy to the operative site, and 3 patients received preoperative radiation. RESULTS: Mean follow-up for the group was 26 months. Two patients died with disseminated disease: neither of them developed local disease recurrence in the operative site; 82% of the patients followed for at least two years are free of disease. Sixty-two percent of the patients received preoperative chemotherapy, the remaining patients received postoperative multiagent chemotherapy and/or radiation therapy. Two of the patients received autologous bone marrow transplants after their adjuvant therapy. Ten patients had postoperative radiotherapy for consolidation; three patients received preoperative radiation. CONCLUSIONS: Immediate TRAM reconstruction for stage III breast cancer is not associated with a delay in adjuvant therapy or an increased risk of local relapse. It facilitates wide resection of involved skin without skin grafting. Radiation therapy can be delivered to the reconstructed breast when indicated without difficulty. Breast reconstruction facilitates surgical resection of stage III breast cancer with primary closure and should be considered if the patient desires immediate breast reconstruction.
Preservation of the inframammary fold: what are we leaving behind?
Preservation of the inframammary fold (IMF) at the time of mastectomy facilitates immediate breast reconstruction. Twenty-four IMF specimens were removed separately after mastectomy for cancer, were serially sectioned, and were examined histologically. Computer image analysis was used to calculate the percentage of breast tissue in each specimen. The mean volume of IMF tissue removed was 99 cm3 (27.3-205.2 cm3), and the mean area examined histologically was 3,036.3 mm2 (294-11,755 mm2). Breast tissue was identified in 13 of the 24 specimens. All cases were negative for carcinoma, but one case had a focus of ductal hyperplasia, usual type. The mean percent breast tissue in those positive for breast tissue was 0.04 percent and 0.02 percent overall. Preservation of the IMF leaves a minimal amount of breast tissue and does not appreciably effect the completeness of a mastectomy.
Case report 863. Osteosarcoma associated with giant cell tumor.
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Radiation-induced leiomyosarcoma.
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Case report 819: Periosteal Ewing's sarcoma of the tibia.
An exceptionally rare case of periosteal Ewing's sarcoma involving the mid shaft of the right tibia was reported. In this case, MRI was the technique that confirmed the integrity of the bone marrow. The clinical, radiographic, and histopathologic features of Ewing's sarcoma have been discussed, as has the differential diagnosis of the periosteal type of this tumor.
Case report 839: Elastofibroma of the right shoulder causing brachial plexus impingement.
A case of an elastofibroma in the right scapular region in a 56-year-old woman was reported. The clinical and pathological findings were discussed. The location of this lesion was uncommon. The common sites were mentioned. The differential diagnosis and magnetic resonance findings were also described.
Case report 864. Elliptical, multicentric periosteal osteoid osteoma.
An extremely rare case of multicentric periosteal osteoid osteoma in a child was presented. The lesions were found to be embedded in a narrow elliptical strip, suggesting the possibility that lesional tissue was stretched in a longitudinal fashion as a result of the rapid skeletal growth. In young patients with stretched periosteal reaction who complain of pain, multicentric osteoid osteoma should be suspected. These nidi can be obscured by the exuberant periosteal reaction. Accurate evaluation of the radiographic findings is very important.
MRI of malignant fibrous histiocytoma of soft tissue: analysis of 13 cases with pathologic correlation.
We reviewed the magnetic resonance (MR) appearances of 13 malignant fibrous histiocytomas (MFH) of soft tissue and correlated each with the respective lesion's histopathology. The MR images were evaluated for signal intensity on T1- and T2-weighted spin echo sequences, homogeneity of the lesion, presence of internal low signal septations, and margin definition. Histologic subtypes of MFH included storiform-pleomorphic, giant cell, myxoid, and inflammatory. We could not establish a correlation between MR appearance and histopathology. Instead, our series exhibited general features suggestive of malignant soft tissue neoplasms, namely poor margin definition, internal low signal septation, and heterogeneous high signal intensity on T2-weighted images.
Case report 845. Fluid-filling giant cell tumor with an aneurysmal bone cyst component.
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