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Biomedical subjects

J L Fraser

Publications and source records attributed to J L Fraser.

16 recordsLinked to original sources

Morphologic predictors of papillary carcinoma on fine-needle aspiration of thyroid with ThinPrep preparations.

Although the cytologic features of papillary carcinoma of the thyroid are well-known, none is entirely specific. We conducted this study to determine the minimal criteria necessary to achieve 100% specificity for the diagnosis of papillary carcinoma on fine-needle aspiration (FNA). Forty patients with histologically confirmed papillary carcinoma and 17 patients with other thyroid lesions who underwent preoperative FNA at Beth Israel Deaconess Medical Center during a 4-yr period were included in the study. All cytology slides were prepared with the ThinPrep processing technique. Various architectural and nuclear features were evaluated, with a score assigned to each feature, and correlated with the histologic diagnosis of papillary carcinoma. Intranuclear inclusions, papillary and/or sheet arrangements, nuclear grooves, powdery chromatin, nuclear molding, high cellularity, and small nucleoli were significantly associated with papillary carcinoma (P < 0.05). The requirement of any intranuclear inclusions and many nuclear grooves, or a minimum of sum of scores (of the above eight features) of 10, yields 100% specificity and approximately 70% sensitivity. Cases with fewer features can be reported as suspicious or indeterminate for papillary carcinoma. A quantitative/probabilistic approach in the reporting of thyroid FNA provides a practical guide for management of patients with thyroid nodules.

Adult↗

Peritoneal washing cytology is unnecessary in gynecologic surgery for benign diseases.

BACKGROUND: The presence of tumor cells in peritoneal washing cytology specimens taken during surgery affects the staging of many gynecologic malignancies. Peritoneal washings are often collected routinely, even in cases of presumed benign disease. This study was designed to address whether evaluation of these specimens is justified. METHODS: We reviewed diagnostic reports from all peritoneal washings and the corresponding surgical pathology specimens from patients undergoing gynecologic surgery during a 1-year period in one institution and a 20-month period in the other. Cases were divided into benign and malignant categories based on the surgical pathology diagnosis. RESULTS: Three hundred forty-six patients had peritoneal washings collected during the study period. The proportion of cases with malignancy was 30% in one institution and 49% in the other. Of these, 119 had an endometrial or ovarian malignancy, including 16 ovarian tumors of low malignant potential. Malignant cells were detected in 19 cases. In 10 of these 19, grossly apparent peritoneal tumor implants were present at the time of surgery. The remaining 227 were found to have benign disease, and the peritoneal washing cytology diagnosis was negative in all cases. Potential savings of $13,000 to $17,000 based on current insurance reimbursement could have been realized for these 227 patients without compromising patient care. CONCLUSIONS: These data suggest that peritoneal washing cytology specimens collected at the time of gynecologic surgery for presumed benign disease can be held and processed later if an unsuspected malignancy is discovered. This practice can result in cost savings without compromising patient care. Cancer (Cancer Cytopathol)

Cytodiagnosis↗

A Uve1p-mediated mismatch repair pathway in Schizosaccharomyces pombe.

UV damage endonuclease (Uve1p) from Schizosaccharomyces pombe was initially described as a DNA repair enzyme specific for the repair of UV light-induced photoproducts and proposed as the initial step in an alternative excision repair pathway. Here we present biochemical and genetic evidence demonstrating that Uve1p is also a mismatch repair endonuclease which recognizes and cleaves DNA 5' to the mispaired base in a strand-specific manner. The biochemical properties of the Uve1p-mediated mismatch endonuclease activity are similar to those of the Uve1p-mediated UV photoproduct endonuclease. Mutants lacking Uve1p display a spontaneous mutator phenotype, further confirming the notion that Uve1p plays a role in mismatch repair. These results suggest that Uve1p has a surprisingly broad substrate specificity and may function as a general type of DNA repair protein with the capacity to initiate mismatch repair in certain organisms.

Base Pair Mismatch↗

Lowering the hemoglobin cutoff for female plateletpheresis donors.

BACKGROUND: The standards of the American Association of Blood Banks describe a minimum hemoglobin level of 12.5 g per dL for apheresis donors. Until 1995, the authors' institution accepted occasional platelet donors with a lower minimum hemoglobin (11.5 g/dL), if accompanied by medical director approval. STUDY DESIGN: All donation records from a 6-month period before 1995 were retrospectively reviewed to determine whether this lower hemoglobin cutoff adversely affected either the safety of the platelet donation process or donors' subsequent hemoglobin levels. RESULTS: Of 450 donations, 56 (12%, Group 1) were from donors with hemoglobin concentrations between 11.5 and 12.4 g per dL (2 donations from 1 man; 54 donations from 45 women). The remaining 394 donations (88%, Group 2) came from donors with hemoglobin concentrations > or = 12.5 g per dL (216 donations from 118 men; 178 donations from 119 women). The frequency of donor reactions was acceptable (Group 1, 11%; Group 2, 6%); 2 percent of donations by Group 1 donors and 1 percent by Group 2 donors were terminated because of these reactions. Of 46 donors in Group 1, 30 returned to donate platelets again at a later time; at least once, 23 (77%) had a hemoglobin > or = 12.5 g per dL. Ten donors in Group 1 returned for additional donations within 56 days; no meaningful decrease in hemoglobin levels occurred. A hemoglobin cutoff of 12.5 g per dL during the study period would have excluded 1 percent of platelet donations by men and 23 percent by women. CONCLUSION: The data demonstrate that the lower hemoglobin cutoff of 11.5 g per dL is a safe and relevant threshold for accepting female plateletpheresis donors and would allow more participation by women in blood donor programs.

Adult↗

Columnar alteration with prominent apical snouts and secretions: a spectrum of changes frequently present in breast biopsies performed for microcalcifications.

We have noted in breast biopsies performed for microcalcifications a spectrum of lesions in the terminal duct lobular unit (TDLU) characterized by columnar epithelial cells with prominent apical cytoplasmic snouts, intraluminal secretions, and varying degrees of nuclear atypia and architectural complexity. The appearance of some of these lesions is worrisome, but diagnostic difficulties arise because the histologic features do not fulfill established criteria for the diagnosis of atypical ductal hyperplasia or ductal carcinoma in situ (DCIS). We have termed such lesions columnar alteration with prominent apical snouts and secretions (CAPSS). The purpose of this study was to define the pathologic spectrum and mammographic features of these lesions. We reviewed histologic sections and mammograms from 100 consecutive breast biopsies performed for microcalcifications. The prevalence and histologic features of CAPSS and the association with other histologic findings were recorded. CAPSS was identified in 42% of cases. At the lower end of the spectrum were lesions similar to columnar alteration of lobules but in which apical cytoplasmic secretion and nuclear stratification were more pronounced and cells with a hobnail configuration were common. More advanced lesions showed columnar epithelial cell tufts, bridges, and micropapillations with prominent apical cytoplasmic snouts and with greater degrees of nuclear stratification and atypia. At the upper end of the spectrum were lesions that could arguably be considered DCIS. Calcifications were present within CAPSS in 74% of cases, were frequently psammomatous, and were typically nonbranching and often round on mammography. Columnar alteration of lobules was more common in biopsies with than without CAPSS (74 versus 36%, p < 0.001). Ductal carcinoma in situ was seen with similar frequency in biopsies with and without CAPSS (38 versus 41%). However, DCIS in cases with CAPSS was more often of the low-grade micropapillary-cribriform type than in cases without CAPSS (56 versus 17%, p < 0.01), and CAPSS and DCIS commonly coexisted in the same or adjacent TDLUs. In conclusion, 1) CAPSS encompasses a spectrum of lesions bounded at the lower end by columnar alteration of lobules and at the upper end by low-grade DCIS. Lesions recently described by Page as "hypersecretory hyperplasia with atypia" fall within this spectrum. 2) Some CAPSS lesions present architectural or cytologic features that create diagnostic difficulties and raise the possibility of atypical ductal hyperplasia or DCIS; however, the level of cancer risk associated with CAPSS lesions that do not fulfill established criteria for atypical ductal hyperplasia or DCIS is unknown and requires evaluation in follow-up studies.

Biopsy↗

Diagnostic yield of bronchoalveolar lavage and bronchoscopic lung biopsy for detection of Pneumocystis carinii.

OBJECTIVE: To assess the need to perform a bronchoscopic lung biopsy (BLB) in addition to bronchoalveolar lavage (BAL) to obtain a definitive diagnosis of Pneumocystis carinii pneumonia. DESIGN: We retrospectively reviewed the results of concurrently collected paired BAL and BLB specimens to determine the diagnostic yield of both methods for the detection of P. carinii organisms. MATERIAL AND METHODS: During a 3-year period, the BAL fluid specimens stained with a commercially available direct immunofluorescence monoclonal antibody (DFA) reagent and the BLB specimens stained with Grocott methenamine-silver nitrate (GMS) were assessed for the presence of P. carinii. BAL fluid was routinely collected from multiple sites and combined into a single specimen for testing. RESULTS: During the 3-year period of study, 119 patients were identified who had paired BAL fluid and BLB specimens tested for the presence of P. carinii. Of the 119 patients, 16 had either BAL fluid that could not be interpreted or BLB tissue that was inadequate. Of the other 103 patients, 21 had P. carinii pneumonia. The sensitivity of the DFA method on BAL fluid and of the GMS method on BLB was 95% and 43%, respectively. CONCLUSION: For detection of P. carinii, the diagnostic yield is significantly higher for DFA-stained BAL specimens than for GMS-stained BLB specimens.

Biopsy↗

Possible association between the Norplant contraceptive system and thrombotic thrombocytopenic purpura.

BACKGROUND: Thrombotic thrombocytopenic purpura (TTP) is a rare, potentially fatal disease of uncertain etiology. Early diagnosis and treatment are essential to patient survival. The ]purpose of this report is to describe three patients with levonorgestrel implants (Norplant system) who developed TTP. CASES: A 24-year-old woman with levonorgestrel implants in place for 7 months was admitted to our hospital for treatment of TTP. Clinical symptoms included easy bruising, menorrhagia, headaches, and fever; laboratory evaluation revealed thrombocytopenia (18 x 10(9)/L) and microangiopathic hemolytic anemia. She was treated with plasmapheresis, and the implants were removed. Through the Freedom of Information Act, we reviewed all adverse events associated with Norplant use reported to the Food and Drug Administration (FDA) as of the end of 1992. Two additional cases were identified. CONCLUSIONS: Although a causal relationship between progestogen-only contraceptives and TTP is not established by the data presented, these three cases may represent an increased incidence of TTP in women using levonorgestrel implants. Patients who receive Norplant should be advised to seek medical attention if symptoms appear. Physicians and other health care providers should be aware of the possible association between use of the Norplant system and TTP and are urged to report similar cases to the FDA.

Adult↗

Prevalence and nonspecificity of microvesicular fatty change in the liver.

Hepatic microvesicular fat (MVF) has been associated with clinical syndromes of liver failure (such as acute fatty liver of pregnancy and Reye's syndrome). We performed this pilot study to investigate the specificity and potential risk factors of MVF. Sections of the liver from 17 adult autopsies were snap-frozen, and Oil Red O (ORO)-stained sections were obtained. The presence of MVF in the ORO stains was analyzed in a semiquantitative manner: 3+ = > 90% liver parenchyma with MVF; 2+ = 25-90%; 1+ = 1-24%. H&E-stained liver sections were reviewed independently to determine the presence and extent of inflammation, fibrosis, and necrosis. Autopsy reports were reviewed for the gross findings; medical records were reviewed for demographic data, medical history, and, in particular, medication usage. The study consisted of 10 males and 7 females (15 white, 2 black), with a median age of 76 years (range: 50-88). MVF was identified in 16 patients (94%); it was infrequent (1+, 2+) in the majority, but 4 patients (24%) had 3+ MVF. MVF was not associated with the age or sex of the patients, liver weight, postmortem interval to examination, or other histologic features in the liver. None of the patients, including those with 3+ MVF, had a history of liver disease. All 4 patients with extensive MVF were using salicylates, as opposed to 2 of 5 with 2+ MVF and 1 of 8 with 0 to 1+ MVF (P = 0.015). In this autopsy study, the prevalence of MVF was high, with 24% of patients having extensive MVF.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Stereochemistry of 2,4-dimethyleicos-2-enoate from the pyruvylated glycolipid of Mycobacterium smegmatis.

The absolute stereochemistry of 2,4-dimethyleicos-2-enoic acid, isolated from the pyruvylated glycolipid of Mycobacterium smegmatis, has been determined. The two enantiomers of methyl 2,4-dimethyleicos-2-enoate were synthesised for the first time but could not be separated by gas chromatography on cyclodextrin phases. (E)-2-Methyloctadec-2-enoate, an intermediate in the synthesis, is a characteristic component of acyl trehalose glycolipids from Mycobacterium fortuitum. Ozonolysis of the fatty acid ester mixture, obtained from the pyruvylated glycolipid produced 2-methyloctadecanoate. It was identified as the (S)-enantiomer by comparison with (2R) and (2S)-2-methyloctadecanoic acid, intermediates in the synthesis of (4R)- and (4S)-2,4,-dimethyleicos-2-enoic acid, using enantioselective gas chromatography of the methyl esters with heptakis(2,6-di-O-methyl-3-O-pentyl)-beta-cyclodextrin as a chiral stationary phase. The natural acid was therefore determined to be 2E-(4S)-2,4-dimethyleicos-2-enoic acid.

Fatty Acids, Monounsaturated↗

The relative diagnostic sensitivity of different F-wave parameters in various polyneuropathies.

We studied F-wave minimum latency, persistence, and chronodispersion in the median and ulnar nerves of 70 controls and 75 patients with various polyneuropathies. Prolonged minimum latency was the most frequent F-wave abnormality in all groups of patients with polyneuropathy. The finding of decreased persistence or absence of F-responses was comparable in sensitivity to prolonged minimum latency in Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP), whereas chronodispersion had a comparable sensitivity only in CIDP. Decreased persistence of obtained F-responses, and the absence of F-responses in nerves with low compound muscle action potential amplitudes, were nonspecific findings. F-wave studies often provide useful additional information in the evaluation of patients suspected of having a polyneuropathy. In patients with axonal polyneuropathies, we found that F-wave studies are significantly more sensitive than standard motor conduction studies in identifying physiological abnormalities of motor axons. Furthermore, in a patient with an acquired polyneuropathy, the finding of markedly prolonged minimum latency, or the absence of F-responses in nerves with normal CMAP amplitude, is highly specific for the presence of demyelination.

Adult↗

Small cell carcinoma of the esophagus in a patient with longstanding primary achalasia.

Achalasia is believed to be a predisposing factor for the development of esophageal cancer. Small cell carcinoma of the esophagus is a rare neoplasm, with fewer than 150 cases having been reported in the world literature, and it has been described only once previously in a patient with longstanding achalasia. We describe a case of an 85-yr-old woman with long-term primary achalasia who developed primary small cell carcinoma of the esophagus. We hypothesize that this patient's recurrent, worsening dysphagia is related to a paraneoplastic phenomenon. We discuss this association and review the literature.

Aged↗