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Biomedical subjects

S M Lippman

Publications and source records attributed to S M Lippman.

At least 235 records · Page 13Linked to original sources

Cranial metastases from prostate cancer simulating meningioma: report of two cases and review of the literature.

Two cases of prostatic carcinoma metastatic to the cranium that presented with clinical and radiographic features simulating meningioma are described. The literature was reviewed, and 13 similar cases were identified. From the data gathered, we conclude that metastatic prostate cancer should be considered in the differential diagnosis of elderly males who present with characteristic clinical and radiological features of meningioma and that the classical description of meningioma is not specific.

Adenocarcinoma↗

Mitral valve prolapse in sickle cell disease: manifestation of a generalized connective tissue disorder.

Previous studies have shown an association of sickle cell disease with generalized connective tissue disorders such as pseudoxanthoma elasticum. We recently documented an unexpectedly high prevalence of mitral valve prolapse, a connective tissue disorder, in sickle cell disease. To investigate this association, skin biopsies were analyzed from 32 sickle cell disease patients, 11 of whom had mitral prolapse. Total and type III collagen, collagen solubility, and uronic acid were not different between the patients with or without mitral prolapse (p greater than 0.05). Computerized morphometric quantitation of the volume fraction of elastic fibers was greater in sickle cell disease patients than in 10 normals (3.1 +/- 0.1 mean +/- SEM vs 2.0 +/- 0.3%; p less than 0.01) but less than in three patients with pseudoxanthoma elasticum (9.7 +/- 0.6%; p less than 0.001). Desmosine radioimmunoassay (an index of elastic fibers) was greater in sickle cell disease patients with mitral prolapse than those without (239.3 +/- 9.3 vs 171.7 +/- 25.4 ng/mg wet weight; p less than 0.02). Histopathologic grading showed a similar trend (p = 0.07). The combined probabilities of these three independent tests of elastic fiber quantity showed an increased elastic fiber concentration in mitral prolapse patients compared to those without mitral prolapse (p less than 0.02). Thus, there is no evidence for a specific collagen defect; rather, sickle cell disease appears to be associated with a spectrum of elastic tissue disorders, a feature that could predispose to mitral valve prolapse.

Adolescent↗

Abnormal septal Q waves in sickle cell disease. Prevalence and causative factors.

Electrocardiograms and M-mode echocardiograms were obtained prospectively from 72 patients with hemoglobin SS (n = 55) or SC (n = 17) disease to assess the prevalence of abnormal Q waves in sickle cell disease and to determine if such Q waves could be explained by, or related to, echocardiographically determined anatomic or functional abnormalities. The mean age (+/- SD) of the population under study was 28 +/- 9 years, and the mean hematocrit reading was 28 +/- 5 percent; 43 male and 29 female patients were evaluated. No patient had a history of systemic arterial hypertension, valvular heart disease, or congestive heart failure. Abnormal septal Q waves (amplitude greater than or equal to 0.30 mV; duration less than or equal to 29 msec) were noted in leads V4, V5, or V6 in 15 of 72 patients, and 50 percent (36) of the population under study demonstrated electrocardiographic voltage changes consistent with left ventricular hypertrophy. M-mode echocardiography showed that 29 of 72 patients had a thickened interventricular septum (greater than or equal to 1.2 cm), 16 of 72 had an abnormally thickened left ventricular posterior wall (greater than or equal to 1.2 cm), and 31 of 72 had increased left ventricular mass (greater than 215 g). The prevalence of electrocardiographic and echocardiographic abnormalities was not significantly different between patients with hemoglobin SS and SC disease. Septal excursion was decreased in 11 of the patients, and global left ventricular function (percent fractional shortening) was slightly decreased in three patients. Regional wall motion was normal in all 72 patients. Six percent (four) of the patients met echocardiographic criteria for asymmetric septal hypertrophy. Linear regression analysis yielded significant positive correlations between septal dimension (r = 0.38; p less than 0.001) and left ventricular mass (r = 0.37; p less than 0.005) when each was compared with Q-wave amplitude. A significant negative correlation (r = 0.40; p less than 0.001) was noted between hematocrit reading and Q-wave amplitude. We conclude that abnormal septal Q waves are common in sickle cell disease and are related, in part, to septal thickness, as well as left ventricular mass and degree of anemia.

Adolescent↗

Mitral valve prolapse in sickle cell disease. Presumptive evidence for a linked connective tissue disorder.

To determine the prevalence of mitral valve prolapse in sickle cell disease, M-mode echocardiography was performed on 57 patients with sickle cell disease and 35 patients with chronic anemia of end-stage renal disease (anemic control group). In 25% (14/57) of patients with sickle cell disease, unequivocal mitral valve prolapse was diagnosed by echocardiography; all these patients had a mobile systolic click and/or late systolic murmur. This figure was significantly greater than the reported 5% to 6% prevalence in the general adult population, the 1% to 3% prevalence in the black population, and the 3.0% prevalence (1/35) in the anemic control group. The association of mitral valve prolapse and sickle cell disease cannot be explained on the basis of left ventricular size, systolic function, ischemic left ventricular or papillary muscle dysfunction, or chronic anemia. Therefore, a linked connective tissue defect in these two diseases is a hypothesis worthy of further investigation.

Adolescent↗

Genetic factors predisposing to autoimmune diseases. Autoimmune hemolytic anemia, chronic thrombocytopenic purpura, and systemic lupus erythematosus.

Genetic factors predisposing to autoimmune diseases were investigated in 10 families having more than one affected member. Seventy relatives and 23 spouses from two large kindreds (one in whom the proband had autoimmune hemolytic anemia and the other immune thrombocytopenic purpura) were examined for immunologically mediated disorders, autoantibodies, immunoglobulin abnormalities, and HLA genotypes. Significant differences between relatives and spouses were found for immune diseases (21 percent versus 0 percent; p = 0.02), antinuclear antibody titer of 1:80 or more (18 percent versus 0 percent; p = 0.04), single-strand DNA antibodies (18 percent versus 0 percent; p = 0.04), high-titer antinuclear antibody or antibodies to single-strand DNA or both (33 percent versus 0 percent; p = 0.001), and the combined frequencies of immune diseases and serologic abnormalities (44 percent versus 4 percent; p = 0.0004). Similar frequencies were found in 41 relatives from eight families in whom the proband had SLE. Segregation analyses using these abnormalities as genetic traits were most compatible with a Mendelian dominant model. Impressive odds (100:1) against linkage to HLA were calculated.

Adolescent↗

The prognostic and biological significance of cellular heterogeneity in medullary thyroid carcinoma: a study of calcitonin, L-dopa decarboxylase, and histaminase.

We evaluated the cellular distribution of calcitonin (CT), L-dopa decarboxylase (DDC), and histaminase [diamine oxidase (DAO)] in 33 patients with medullary thyroid carcinoma (MTC). CT immunostaining was uniform (greater than 90% of the cells) and intense (4+) in lesions from 7 patients with C-cell hyperplasia and 6 with microscopic MTC: conversely, patchy CT staining (less than 40% of the cells) and diminished intensity (1+) were found in metastases from 8 patients who died of virulent disease. In 17 patients who underwent thyroidectomy for macroscopic cervical MTC with no evidence distant metastases, CT staining was intense (3-4+) and homogeneous (greater than 90%) in 11 subjects who were well 0.5-16 yr postoperatively. Six patients with similar clinical presentations had heterogeneous staining for CT in primary tumor (less than 40% of the cells; 1-2+ intensity); 5 died of disseminated MTC 0.5-5 yr postoperatively (P less than 0.001). Biochemical studies of distant metastases revealed an inverse relationship between the distribution of CT and that of both relationship between the distribution of CT and that of both DDC (r = 0.71; P less than 0.01) and DAO (r = 0.81; P less than 0.001). We conclude that cellular heterogeneity in MTC tissue is associated with a distinct biochemical pattern, and its presence, whether in a primary or metastatic lesion, indicates a virulent neoplasm associated with a grave prognosis.

Adult↗

Autoimmune hemolytic anemia with reticulocytopenia. A medical emergency.

In four cases of autoimmune hemolytic disease, rapidly developing anemia was associated with reticulocytopenia despite intensely erythroid bone marrow. Transfusions had been withheld because compatible blood could not be obtained, and each patient was virtually moribund on admission. Type-specific RBCs were administered promptly without reaction. From 2 to 84 carefully selected units were required to sustain life during the reticulocytopenic episodes, which lasted from a few days to more than six months. Transfusion in patients with autoimmune hemolytic anemia generally is unwise, because the autoantibody in the serum usually reacts with the RBCs of all potential donors, making a satisfactory cross match impossible. However, reticulocytopenia with profound anemia may present as a medical emergency in which prompt, careful transfusion is lifesaving.

Aged↗

Chemoprevention of upper aerodigestive tract cancers: a report of the third Upper Aerodigestive Cancer Task Force workshop.

The National Cancer Institute Organ Systems Program-sponsored Upper Aerodigestive Cancer Task Force workshops are specifically designed to enhance interactions between basic science and clinical investigators and between academic institutions and the community, and ultimately will contribute to more expeditious clinical advances. The third workshop in this series focused on the rapidly expanding area of chemoprevention of upper aerodigestive epithelial cancers. The first two sessions were devoted to discussion of in vitro and animal-model data documenting the multistep process of squamous differentiation and carcinogenesis, associated molecular and biochemical alterations, and modulation by chemopreventive agents. Animal-model studies have identified several promising chemopreventive agents and synergistic combinations for clinical trial. The last two sessions reviewed nutritional epidemiology, major methodologic issues of large intervention studies, and the novel concept of biologic markers as intermediate endpoints for chemoprevention trials.

Animals↗

Laryngeal preservation by induction chemotherapy plus radiotherapy in locally advanced head and neck cancer: the M. D. Anderson Cancer Center experience.

Standard treatment of locally advanced laryngeal, hypopharyngeal, and some oropharyngeal cancers includes total laryngectomy. In an attempt to preserve the larynx through induction chemotherapy, we conducted two consecutive phase II studies. From March 1986 to February 1991, 64 patients with advanced untreated but resectable head and neck cancer who would require total laryngectomy were enrolled on one of two cisplatin-based induction regimens: cisplatin-bleomycin-5-fluorouracil (PBF) in 31 patients and cisplatin-5-fluorouracil (PF) in 33; all received definitive radiotherapy. Surgery was reserved for patients who achieved less than a partial response to chemotherapy and patients with residual or recurrent disease after sequential chemotherapy plus radiotherapy. Overall complete plus partial response rates to both cisplatin-based regimens were comparable. The combined PF and PBF overall response rates were 75% for laryngeal cancer, 78% for hypopharyngeal cancer, and 75% for oropharyngeal cancer. Complete response rates after radiotherapy were 88%, 83%, and 50%, respectively. Neutropenia (< 1,000 cells/mm3) was the most common hematologic toxic effect: it occurred in 44% of patients who received PF and 16% of those who received PBF. Grade > or = 3 mucositis occurred in 50% of patients who received PF and 4% who received PBF. The data suggest that laryngeal preservation was feasible in all three primary-site subgroups. With follow-up of 15+ to 54+ months, 44% of patients with laryngeal cancer, 28% with hypopharyngeal cancer, and 22% with oropharyngeal cancer are alive with laryngeal preservation. The overall 2-year survival rates for patients with cancer of the larynx, hypopharynx, and oropharynx were 71%, 46%, and 38%, respectively.

Adult↗

Non-steroidal anti-inflammatory drugs and the risk of oral cancer: a nested case-control study.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) seem to prevent several types of cancer, but could increase the risk of cardiovascular complications. We investigated whether use of NSAIDs was associated with a change in the incidence of oral cancer or overall or cardiovascular mortality. METHODS: We undertook a nested case-control study to analyse data from a population-based database (Cohort of Norway; CONOR), which consisted of prospectively obtained health data from all regions of Norway. People with oral cancer were identified from the 9241 individuals in CONOR who were at increased risk of oral cancer because of heavy smoking (15 pack-years), and matched controls were selected from the remaining heavy smokers (who did not have cancer). FINDINGS: We identified and analysed 454 (5%) people with oral cancer (279 men, 175 women, mean [SD] age at diagnosis 63.3 [13.2] years) and 454 matched controls (n=908); 263 (29%) had used NSAIDs, 83 (9%) had used paracetamol (for a minimum of 6 months), and 562 (62%) had used neither drug. NSAID use (but not paracetamol use) was associated with a reduced risk of oral cancer (including in active smokers; hazard ratio 0.47, 95% CI 0.37-0.60, p<0.0001). Smoking cessation also lowered the risk of oral cancer (0.41, 0.32-0.52, p<0.0001). Additionally, long-term use of NSAIDs (but not paracetamol) was associated with an increased risk of cardiovascular-disease-related death (2.06, 1.34-3.18, p=0.001). NSAID use did not significantly reduce overall mortality (p=0.17). INTERPRETATION: Long-term use of NSAIDs is associated with a reduced incidence of oral cancer (including in active smokers), but also with an increased risk of death due to cardiovascular disease. These findings highlight the need for a careful risk-benefit analysis when the long-term use of NSAIDs is considered.

Acetaminophen↗

The evaluation of patients with Eales' disease.

Thirty-two patients with documented Eales' disease who have been followed-up at Johns Hopkins Hospital for periods of as long as 37 years were investigated. The previously reported association of Eales' disease with tuberculoprotein hypersensitivity was confirmed in 10 of 21 patients tested. For the first time, associated vestibuloauditory dysfunction is described. The previously reported association with multiple sclerosis was not confirmed. Eales' disease is a specific vasculopathy that can affect both the retinal and vestibuloauditory circulations. Patients with suspected Eales' disease should also be examined to rule out other diseases such as diabetes, sarcoidosis, and connective tissue diseases including systemic lupus erythematosus. This can be done by obtaining such tests as fasting blood glucose, chest radiograph, erythrocyte sedimentation rate, antinuclear antibody, rheumatoid factor, and LE cell preparation. Tuberculoprotein sensitivity status should be ascertained and active tuberculosis should be ruled out. The patient should be questioned regarding hearing or balance problems, and if a history suggestive of abnormalities is elicited, referral for vestibuloauditory function testing should be made.

Adult↗

Expression of E-cadherin is associated with squamous differentiation in squamous cell carcinomas.

E-cadherin is a cell surface molecule that mediates cell-cell adhesion in normal epithelium. Disabled or aberrant E-cadherin expression increases cell motility and promotes the transition of well-differentiated adenoma to invasive carcinoma. To evaluate whether E-cadherin could serve as a biomarker of squamous cell differentiation, we analyzed its expression by immunohistochemistry in formalin-fixed, paraffin-embedded tissue sections of 7 head and neck cancer patients, 19 lung cancer patients, 73 esophageal cancer patients, 19 skin cancer patients, and 18 cervical cancer patients. E-cadherin was expressed at very high levels (93%-100%) in adjacent or distant normal squamous epithelia. Likewise, most (75-100%) well-differentiated squamous cell carcinomas (SCCs) also expressed E-cadherin. In contrast, poorly differentiated SCCs expressed less than 40% of E-cadherin. Furthermore, immunohistochemical analysis showed that the differentiation-inducing agent, all-trans retinoic acid, can up-regulate E-cadherin expression in esophageal SCC cells in vitro. Our data demonstrated that E-cadherin expression is associated with SCC differentiation and that may serve as a squamous cell differentiation marker.

Biomarkers, Tumor↗

Cancer risk reduction counseling: a computer-assisted curriculum.

Significant progress has been made in the identification of factors associated with an increased risk of developing cancer. Cancer is increasingly viewed as a preventable disease. Its prevention involves risk reduction counseling. This counseling is an important skill for the family physician but can be difficult to learn and to teach. We used a prototype, computer-assisted cancer risk reduction counseling curriculum with first-year medical students. We found a statistically significant change in both knowledge-based and attitudinal questions and answers after the use of this curriculum.

Adult↗

[Treatment of 32 cervico-uterine cancer patients with 13-cis-retinoic acid and interferon alpha].

BACKGROUND: The use of chemotherapy for cervical squamous cell carcinoma has shown some positive results. Total percentage of complete plus partial responses are near 30% with the use of single cytotoxic agents. Higher percentages are achievable with combined chemotherapy including platinum but the lack of evidence that current chemotherapy can increase survival, coupled with a devastating worldwide mortality, indicates the urgent need for more effective therapies. OBJECTIVE: To further assess the role of 13-cis-Retinoic acid (13-cRA) plus interferon alfa (IFN-alfa) in a prospective phase II trial in advanced cervical cancer. METHODS: Thirty two women with untreated cervical carcinoma, with median age of 42 years (24 to 60 years) and median Zubrod performance of 1 (range 0-2) were treated for at least two months with oral 13-cRA (1 mg/kg/day) and IFN-alfa 2a (subcutaneously, 6 million units daily). RESULTS: Sixteen patients (50%) had major responses, including four complete clinical responses. Major response rate in regard to disease stage were 100% in the four patients with stage IVA, 36% (4/11) in stage IIIB, 50% (4/8) in stage IIB, 50% (1/2) in stage IIA, and 43% (3/7) in stage IB. Remission of the cancer in 15 patients was reached after only two months of treatment and in one patient within one month. Dose escalations after two months of therapy in nonresponding patients had no effect. Toxicity to treatment was manageable. Twenty one patients had poorly differentiated tumors. CONCLUSIONS: These preliminary results indicate that systemic 13-cRA plus IFN-alfa 2a is a highly active, well tolerated therapy for locally advanced squamous cell carcinoma of the cervix, with potential to be used in the primary, adjuvant and salvage therapy of cervical cancer. This therapy warrants further study.

Adult↗

Reduction in oral mucosa micronuclei frequency following alpha-tocopherol treatment of oral leukoplakia.

Micronuclei frequency, a marker of genotoxicity, was studied within a trial of alpha-tocopherol for chemoprevention of oral leukoplakia. Oral swabs were obtained from two sites, the leukoplakia lesion and normal-appearing mucosa, at baseline and following 24 weeks of therapy with 400 international units of alpha-tocopherol twice daily. These specimens were analyzed for micronuclei frequency. The major risk factors for oral carcinogenesis in the group studied were cigarette smoking and alcohol consumption. alpha-tocopherol therapy produced a significant reduction in micronuclei frequencies in specimens from both the visible lesions (P < 0.01) and the normal-appearing mucosa (P < 0.01). The micronuclei frequencies, both at baseline and following therapy, were greater in specimens taken from the lesion than in those from the normal-appearing mucosa. Although these results indicate that alpha-tocopherol has a beneficial effect in oral carcinogenesis, there was no significant clinical or histological response associated with the change in micronuclei frequency. Micronuclei frequency has not yet been validated as a biomarker for cancer incidence, and consequently, its utility as an intermediate end point for chemoprevention trials is not known. Determining clinical significance of micronuclei frequency patterns in oral carcinogenesis and chemoprevention will require further study.

Adult↗