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Biomedical subjects

M Rothman

Publications and source records attributed to M Rothman.

At least 19 recordsLinked to original sources
PubMed1995

Structural model of the phospholamban ion channel complex in phospholipid membranes.

Phospholamban is a 52 amino acid residue membrane protein involved with the regulation of calcium levels across sarcoplasmic reticulum membranes in cardiac muscle cells. The N-terminal 30 amino acid residues of the protein are largely hydrophilic and include two sites whose phosphorylation is thought to dissociate an inhibitory complex between phospholamban and Ca2+ ATPase. The C-terminal 22 amino acid residues are largely hydrophobic, anchor the protein in the membrane and are responsible for Ca2+ selective ion conductance. Specific interactions between the transmembrane domains stabilize a pentameric protein complex. We have obtained circular dichroism (CD), transmission Fourier transform infrared (FTIR) and attenuated total reflection Fourier transform infrared (ATR-FTIR) spectra of the full-length protein and have compared these results to those from a 28 residue peptide that includes the transmembrane domain. Both proteins reconstituted into phospholipid membranes are largely alpha-helical by CD and FTIR. Polarized ATR-FTIR measurements show that both the cytosolic and transmembrane helices are oriented perpendicular to the membrane plane with a tilt of 28 (+/- 6) degrees with respect to the membrane normal. This tilt angle is in close agreement to that calculated from a model for the transmembrane domain of phospholamban suggested by mutagenesis and molecular modeling. Phosphorylation does not significantly change the secondary structure or orientation of the protein. The pentameric complex is modeled as a left-handed coiled-coil of five long helices (40 (+/- 3) residues) that extend across the membrane from the lumenal carboxy terminus to the phosphorylation site in the cytoplasm. The helix bundle forms a perpendicular ion pore that may begin at a distance (17 to 29 A) from the membrane surface. Based on the above, we propose a mechanism by which phospholamban regulates Ca2+ levels across membranes that takes into account both its selective ion conductance and inhibitory association with the Ca2+ pump.

Amino Acid Sequence↗
PubMed1995

Localization of a misplaced coronary artery stent by magnetic resonance imaging.

Coronary artery stents have been developed to overcome arterial abrupt closure and restenosis following balloon angioplasty. Complications of stent insertion include loss of the device from its delivery system into the peripheral circulation. Certain types of stents are almost radiolucent, making localization of the lost devices difficult. Nonferromagnetic metallic biomedical implants induce alteration of the local magnetic field and this leads to loss of signal from the surrounding tissues. We have used this property to localize a misplaced coronary artery stent in a 53-year-old man who underwent unsuccessful stent insertion. A 0.5 Tesla magnetic resonance scanner was used to acquire gradient-echo and spin-echo images. An in vitro experiment was first carried out on a stent similar to that used in our patient to establish that it was nonferromagnetic and to determine the optimum imaging technique. Gradient-echo images with a relatively long echo time (22 ms) gave the largest area of signal loss around the stent, and this sequence was used for localization of the stent found in the patient's left profunda femoris artery. This was subsequently confirmed by digital radiography. We have demonstrated the convenience and practicality of using magnetic resonance imaging for the localization of a misplaced coronary artery stent in a patient. The technique is safe, noninvasive, and uses no ionizing radiation.

Angioplasty, Balloon, Coronary↗
PubMed1995

MRI of silicone vitreous ocular implants with phantom correlation.

We imaged two patients who had silicone oil injected their vitreous cavities. The images demonstrated an increased chemical shift artifact. We developed and tested an in vitro silicone oil model in an attempt to explain this. To our knowledge, this artifact has not been previously described. We constructed a phantom using medication cups containing water, lard and two types of silicone. Background control baths of water and lard were used to simulate different local environments. The phantoms were imaged with T1-and T2-weighted and T1-weighted fat suppression sequences. The artifacts were due to the pronounced chemical shift of silicone in relation to intraconal fat. Our model accurately reproduced our clinical images. Spectral analysis of the silicone model revealed different resonating frequencies for fat/silicone, thereby explaining the pronounced chemical shift artifact.

Artifacts↗
PubMed1995

Including deaths when measuring health status over time.

Measuring health status over time is problematic when some subjects die, because death does not have a defined value on most health status measures. This situation is different from the usual missing data problem because the health status of the dead is, in a sense, known. We examined eight strategies for incorporating deaths into such analyses using three health status measures taken from two data sets, after which we used computer simulation to explore more fully the effect of deaths. The strategies differed in the amount of influence given to the deaths, varying from none (deaths were discarded) to complete (mortality itself was the health measure). The strategies that gave less influence to deaths tended to show more favorable changes in health over time, and therefore, tended to favor the group that had more deaths. The strategies that were more influenced by death showed more negative changes over time and favored the group with fewer deaths. The choice of strategy should depend on the goals of an intervention. For health promotion studies, we recommend recoding the health variables to estimate the probability that a person will be healthy in 2 years (or in some other period that can be estimated from the data).

Aged↗
PubMed1994

Accuracy of clinical examination versus computed tomography in detecting occult lymph node involvement in patients with oral epidermoid carcinoma.

PURPOSE: To determine the accuracy of clinical examination versus computed tomography (CT) scanning in detecting positive cervical lymph nodes (N) in patients with epidermoid carcinomas of the oral cavity, 27 patients with epidermoid carcinomas were reviewed. PATIENTS AND METHODS: The patients underwent 40 neck dissections, 20 with N- and 20 with N+ necks histologically. All patients were examined by the same clinician, and all CT scans were read by the same radiologist. Patients with clinical and CT N- necks underwent neck dissection only if the neck had to be entered to resect the primary tumor or if the primary tumor was T3 or T4 with a high probability of microscopic metastasis. RESULTS: Of the 20 necks that were histologically N-, 16 (80%) were clinically diagnosed as N- and 4 (20%) N+ versus 18 (90%) N- and 2 (10%) N+ diagnosed by CT scan. Of the 20 histologically N+ necks, 12 (60%) were clinically diagnosed as N+ and 8 (40%) N- versus 11 (55%) N+ and 9 (45%) N- diagnosed by CT scan. All lymph nodes diagnosed as N- by both clinical examination and CT scan were less than 1 cm in diameter. Overall, clinical examination of the neck was correct in 28 patients (70%) and the CT scan was correct in 29 patients (73%). Both clinical examination and CT scan were more accurate in diagnosis of N- necks. In 31 necks (78%), the CT and clinical examination were in agreement. Of these, 10 of 10 (100%) were correctly positive. Of the 21 in which both were negative, 14 were histologically N-, and 14 (67%) were correct. Overall, in those cases in which both CT and clinical examination were in agreement, the diagnosis was correct in 24 of 31 (77%). CONCLUSION: These results suggest that there is no significant difference in the accuracy of clinical examination versus CT scanning in detecting both positive and negative cervical nodes. When both CT and clinical examination agree, positive cervical nodes are almost always correctly diagnosed. However, one third of the negative cervical nodes were incorrectly diagnosed. Improved methods for detecting occult disease are still needed.

Carcinoma, Squamous Cell↗
PubMed1994

Cerebral mucormycosis associated with intravenous drug use: three case reports and review.

We describe three cases of cerebral mucormycosis in intravenous drug users and review 22 previously reported cases. Involvement of the basal ganglia was demonstrated in all but two cases. Seven of the 10 patients tested for antibodies to the human immunodeficiency virus (HIV) were seronegative. Eight of the 25 patients survived and were discharged from the hospital; for 7 of 10 patients, cultures of brain lesions yielded Rhizopus arrhizus. The radiographic findings varied, and in most cases, no or minimal contrast enhancement was seen in the initial computed tomography scans. Although uncommon, the diagnosis of cerebral mucormycosis should be considered when basal ganglia lesions are present in an intravenous drug user, regardless of previous exposure to HIV.

AIDS-Related Opportunistic Infections↗
PubMed1992

[Initial treatment of urinary tract infection with augmentin].

Urinary tract infections have been treated empirically according to the development of bacterial resistance, and semisynthetic penicillins have been out of favor. Only 12% (4/34) of our patients treated with augmentin failed to respond, compared with 20% of those on a combination of gentamicin and ampicillin.

Amoxicillin↗
PubMed1990

Identification of a high risk subgroup of patients with silent ischaemia after myocardial infarction: a group for early therapeutic revascularisation?

Asymptomatic ("silent") ischaemia has been shown to be of prognostic significance in patients with stable and unstable angina and more recently in patients recovering after myocardial infarction. No therapeutic regimen has yet been shown to improve the prognosis of patients with silent ischaemia after infarction, which can be found in as many as a third of these patients. Attempts to achieve therapeutic revascularisation in all these patients may be undesirable, but early revascularisation could be especially beneficial in some selected high risk patients. Two hundred and fifty consecutive clinically stable survivors of myocardial infarction who had predischarge submaximal exercise tests were followed up for a year. Silent ischaemia was found in 27% of these patients; 15% had symptomatic ischaemia. Patients with a positive exercise test were prescribed a beta blocker before discharge. Mortality in patients with silent (9.4%) and symptomatic (5.4%) ischaemia in the first year after infarction was not significantly different. Patients with symptomatic ischaemia were more likely to have undergone coronary artery bypass grafting in the first year. Patients with silent ischaemia were, however, significantly more likely to die than patients with a negative exercise test (relative odds 12:1). Patients with silent ischaemia and an abnormal blood pressure response or who could not complete a submaximal exercise protocol were at particularly high risk, being 32 times more likely to die than those with a negative test (95% confidence interval from 3.3 to 307 times more likely). First year mortality in this group was 22%. The benefits of therapeutic revascularisation in this high risk group need to be studied.

Coronary Angiography↗
PubMed1988

A survey of extubation practices following orthognathic surgery.

The incidence of respiratory complications following orthognathic surgery was investigated by a survey of 234 private oral and maxillofacial surgeons and residency programs to determine if prolonged postoperative intubation is warranted. The results showed no significant increase in such complications when patients were extubated within 8 hours following surgery compared to longer intubation times.

Humans↗
PubMed1988

Relative power of clinical, exercise test, and angiographic variables in predicting clinical outcome after myocardial infarction: the Newham and Tower Hamlets study.

The interrelations of clinical, exercise test, and angiographic variables and their relative values in predicting specific clinical outcomes after myocardial infarction have not been fully established. Of 302 consecutive stable survivors of infarction, 262 performed a predischarge submaximal exercise test. In the first year after infarction patients with a "positive" exercise test were 13 times more likely to die, 2.8 times more likely to have an ischaemic event, and 2.3 times more likely to develop left ventricular failure than patients with negative tests. Patients with positive exercise tests underwent cardiac catheterization. Features of the history, 12 lead electrocardiogram, in-hospital clinical course, exercise test, and left ventricular and coronary angiograms that predicted these clinical end points were identified by univariate analysis. Then multivariable analysis was used to assess the relative powers of all variables in predicting end points. Certain features of the exercise test remained independent predictors of future ischaemic events and the development of overt left ventricular failure, but clinical and angiographic variables were more powerful predictors of mortality. Because the exercise test is also used to select patients for angiography, however, the results of this study strongly support the use of early submaximal exercise testing after infarction.

Adult↗
PubMed1984

DNA repair and induction of plasminogen activator in human fetal cells treated with ultraviolet light.

We have tested human fetal fibroblasts for development associated changes in DNA repair by utilizing nucleoid sedimentation as an assay for excision repair. Among skin fibroblasts the rate of excision repair was significantly higher in non-fetal cells than in fibroblasts derived from an 8 week fetus; this was evident by a delay in both the relaxation and the restoration of DNA supercoiling in nucleoids after irradiation. Skin fibroblasts derived at 12 week gestation were more repair proficient than those derived at 8 week gestation. However, they exhibited a somewhat lower rate of repair than non-fetal cells. The same fetal and non-fetal cells were also tested for induction of the protease plasminogen activator (PA) after u.v. irradiation. Enhancement of PA was higher in skin fibroblasts derived at 8 week than in those derived at 12 week gestation and was absent in non-fetal skin fibroblasts. These results are consistent with our previous findings that in human cells u.v. light-induced PA synthesis is correlated with reduced DNA repair capacity. Excision repair and PA inducibility were found to depend on tissue of origin in addition to gestational stage, as shown for skin and lung fibroblasts from the same 12 week fetus. Lung compared to skin fibroblasts exhibited lower repair rates and produced higher levels of PA after irradiation. The sedimentation velocity of nucleoids, prepared from unirradiated fibroblasts, in neutral sucrose gradients with or without ethidium bromide, indicated the presence of DNA strand breaks in fetal cells. It is proposed that reduced DNA repair in fetal cells may result from alterations in DNA supercoiling, and that persistent DNA strand breaks enhance transcription of PA gene(s).

Cell Line↗
PubMed1983

Immunocytochemical localization of carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP), and human chorionic gonadotropin (HCG) in cervical neoplasia.

Sixty-one cases of invasive cervical carcinoma and 40 cases of dysplasia and carcinoma in situ were studied by peroxidase-antiperoxidase method (PAP) for the presence of carcinoembryonic antigen (CEA). Forty-two cases (13 carcinomas in situ and 29 invasive carcinomas) also were tested for alpha-fetoprotein (AFP) and human chorionic gonadotropin hCG. CEA was not detected in normal cervical epithelium but was present in 90% of the neoplastic lesions. Not mere presence, but a pattern of CEA tissue distribution emerged as the main differential point between noninvasive and invasive lesions. Twenty-nine of 51 invasive squamous carcinomas (57%) contained CEA-positive cells at the stromal edge of epithelium, while this feature was not found in dysplasia and carcinoma in situ. Adenocarcinomas and adenosquamous carcinomas all were positive for CEA, while clear-cell carcinomas were negative. AFP was present only in a case of poorly differentiated adenosquamous ("glassy cell") carcinoma. hCG has not been revealed in any of the tumors.

Adenocarcinoma↗
PubMed1982

Patients released after psychiatric commitment evaluation: comparison with the committed.

The authors retrospectively analyzed two groups of patients who were evaluated for involuntary commitment. Based on the psychiatrist's evaluation, one group (N = 39) was committed and the other group (N = 39) was released. The committed patients were significantly younger and diagnosed psychotic. No significant differences between groups were found in sex, race, petitioner, treatment history and presenting behavior. Psychiatrists regardless of experience tended not to commit the non-psychotic patient, with the released patients constituting a unique subgroup of the outpatient population.

Adolescent↗
PubMed1981

Prostacyclin: haemodynamic and metabolic effects in patients with coronary artery disease.

The therapeutic potential of prostacyclin was evaluated in 10 patients with angina pectoris and angiographically proved coronary artery disease. Platelet aggregation and coronary and systemic haemodynamic effects were examined before and after intravenous infusions of 2, 4, 6, and 8 ng/kg/min of prostacyclin and were dose related. At 8 ng/kg/min the ADP concentration required to induce 50% of maximum platelet aggregation increased from 1.8 to 4.5 mumol/l (p less than 0.001). Heart rate and cardiac index rose from 77 to 93 beats/min and 2.47 to 3.48 l/min/m2, respectively (p less than 0.01). Mean blood pressure and systemic and pulmonary resistances fell from 107 to 92 mm Hg and 1704 to 1048 and 80 to 45 dyn s cm-5, respectively (p less than 0.01). Coronary vascular resistance also fell from 0.95 to 0.73 units (p less than 0.01). Mean atrial pacing time to angina rose from 142 to 241 s (p less than 0.05), while lactate production during rapid atrial pacing was decreased, lactate extraction ratio rising from -25 to -9% (p less than 0.05). These coronary and systemic vasodilator effects and the prolongation of pacing time to angina indicate an acute beneficial effect of prostacyclin on angina. Since prostacyclin has been shown to prevent platelet accumulation and progression to total occlusion in animals with experimental coronary stenoses, the observed inhibition of platelet aggregation suggests that prostacyclin should be further evaluated in unstable angina.

Angina Pectoris↗