Search PubMed⌕ Search

Biomedical subjects

M Gutman

Publications and source records attributed to M Gutman.

At least 109 records · Page 6Linked to original sources

Are malignant melanoma patients at higher risk for a second cancer?

This study tests whether malignant melanoma (MM) patients are at higher risk of having an unrelated second cancer by comparing the observed incidence of a second cancer in a given population of MM patients with the expected number in an age-matched and sex-matched group of healthy people followed for a similar period. The analysis was based on the person-years method in which the main consideration is the follow-up period after the diagnosis of MM. Of 370 patients with histologically confirmed MM, 27 (7.3%) had a second noncutaneous invasive cancer, diagnosed either simultaneously (within 6 months, five patients) or after the diagnosis of MM (22 patients). The follow-up period for the entire MM group was 1253 person-years, a period during which the expected number of cancer cases in the normal population, according to the Israel Cancer Registry, was 6.6. The observed-expected ratio or the relative risk (RR) was 4.1 (P less than 0.01). After excluding the five patients with simultaneous diagnosis of MM and a second cancer, analysis of the remaining 22 patients in whom MM definitely preceded the second cancer showed an RR of 3.3 (P less than 0.01). For the entire group, there were nine patients with breast cancer, five with head and neck cancer (two with thyroid and three with oral cavity cancer), five with gynecologic cancer (one with uterine and four with ovarian cancer), five myeloproliferative malignancies (one with lymphoma, three with chronic lymphocytic leukemia, and one with myeloma), three gastrointestinal carcinomas (two with colon and one with stomach cancer), and two soft tissue sarcomas. When the differential analysis according to gender and age was done, it was found that the RR was higher for women (5.5, P less than 0.01) than for men where the RR was 2.2 (P less than 0.05). Differential analysis for various age groups showed that the trend for second cancer was consistent in all age groups, with a slight increase in the younger ones. None of the variables of MM, such as location of the primary tumor, level of invasion, or stage, were predictive for a second cancer. Furthermore, the RR for a second cancer did not relate significantly with the treatment given to the MM patient. Concerning the type of second cancer, it was found that the RR was especially high for breast cancer--6.6. These data indicate that MM patients may be at higher risk for having a noncutaneous invasive cancer compared with the general population.

Adolescent↗

Proton transfer dynamics in the nonhomogeneous electric field of a protein.

By adsorption of pyranine (8 hydroxypyrene 1, 3, 6 trisulfonate) to lysozyme we create on the positively charged protein a fluorophoric site with a total charge of -3. Photo dissociation of the dye's hydroxyl proton changes its absorption and fluorescence spectrum, permitting a continuous monitoring of the reprotonation dynamics. Absorbance measurements in the microsecond time scale monitor how the bulk protons penetrate the Coulomb cage of the bound dye. Time-resolved fluorescence monitors how the proton is escaping out of the Coulomb cage of the bound dye. These probe reactions were studied with a series of dye-enzyme complexes where the number of free carboxylate was reduced by amidation, increasing the total charge of the complex from +5 to +12.6. The time-resolved measurements demonstrate the complexity of the electric field in the immediate vicinity of the dye. It is consistent with a negative potential wall (of the anion) surrounded by a positive potential wall of proteinaceous moieties.

Adsorption↗

The management of acute cholecystitis in elderly patients.

Acute cholecystitis is a common cause of emergency room admissions in elderly patients, and may have an atypical course with serious complications and high mortality. The authors present 131 elderly patients (aged 70 and older) who were treated for acute cholecystitis. The most common complaint was right upper abdominal pain (73%), followed by fever (55%), vomiting (48%), palpable mass (22%) and jaundice (13%). Twelve per cent of the patients were in septic shock on admission. Most patients (74%) had severe concomitant disease, increasing their operative risk significantly. Patients were prepared for surgery by hydration, nasogastric drainage, and antibiotics, while imaging was performed. They were all operated on within 48 hours. The operation of choice was cholecystectomy, which was performed in 86 patients. In 45 older and high risk patients, cholecystostomy was performed. The decision to perform cholecystostomy was taken prior to the operation, and was based on the estimated operative risk. Five patients (3.8%) died postoperatively. The major cause of death was cardiovascular disorders. Major complications occurred in 14.5 per cent and minor in 23 per cent of the patients. The complication rate correlated with severe concomitant diseases and older age groups. Patients with fever and leukocytosis had a better outcome, possibly reflecting a better immunologic status. The authors conclude that aggressive preoperative preparation and judicious use of cholecystostomy as a life-saving drainage procedure can lower the mortality from acute cholecystitis in the elderly population.

Acute Disease↗

Proton dissociation dynamics in the aqueous layer of multilamellar phospholipid vesicles.

The water layers interspacing between the phospholipid membranes of a multilamellar vesicle are 3-10 water layers across and their width is adjusted by osmotic pressure (Parsegian, V.A., et al., 1986. Methods Enzymol. 127:400-416). In these thin water layers we dissolved pyranine (8 hydroxypyrene 1,3,6 trisulfonate), a compound which, upon photo excitation, ejects it hydroxy proton with time constant of 100 psec. (Gutman, M. 1986. Methods Enzymol. 127:522-538). In the present study we investigated how the width of the aqueous layer, the density of phosphomoieties on the membrane's surface and the activity of water in the layer affect the capacity of protons to diffuse out from the electrostatic cage of the excited anion before it decays to the ground state. Using a combination of steady-state and subnanosecond time-resolved fluorescence measurements we determined the average number of proton excited-anion recombinations before the proton escapes from the Coulomb cage. The probability of recombination in thin water layer is significantly higher than in bulk. The factor contributing most to enhancement of recombination is the diminished water activity of the thin aqueous layer. The time frame for proton escape from an electrostatic trap as big as a membrane-bound protein is 3 orders of magnitude shorter than turnover time of membrane-bound enzymes. Thus the effects of local forces on proton diffusion, at the time scale of physiological processes, is negligible.

Arylsulfonates↗

Amplification of c-myc and c-erbB-2 proto-oncogenes in human solid tumors: frequency and clinical significance.

Molecular probes for cellular proto-oncogenes have recently been extensively used in order to search for functional and structural alterations in tumor tissues. Variable, and sometimes contradictory, results have been obtained regarding the frequency and clinical significance of amplification of the c-myc and c-erbB-2 proto-oncogenes in different series of human solid tumors. We addressed this question by performing Southern blotting analysis on 131 primary adult solid tumors of various tissues and 5 metastases of unknown origin, using molecular probes for both genes. Amplification of c-myc was found in 5 of the primary tumors, and amplification of c-erbB-2 in 5 others. In 2 tumors of the latter group, the c-erbB-2 gene was also rearranged. The distribution of these 10 tumors with regard to clinical stage and course of the disease did not point to an association between the amplification events and specific stage or prognosis. We concluded that, in this series, the amplification of both proto-oncogenes was occasional and was not a prognostic marker.

Breast Neoplasms↗

Dynamics of proton diffusion within the hydration layer of phospholipid membrane.

The diffusion of protons at the immediate vicinity of (less than 10 A from) a phospholipid membrane is studied by the application of the laser-induced proton pulse. A light-sensitive proton emitter (8-hydroxypyrene-1,3,6-trisulfonate) was trapped exclusively in the hydration layers of multilamellar vesicles made of egg phosphatidylcholine, and the protons were dissociated by a synchronizing laser pulse. The recombination of the proton with pyranin anion was monitored by time-resolved spectroscopy and analyzed by a diffusion-controlled formalism. The measured diffusion coefficient is only slightly smaller than the diffusion coefficient of proton in bulk water. Modulating the width of the hydration layer by external pressure had a direct effect on the diffusibility of the proton: the narrower the hydration layer, the slower is the diffusion of protons.

Arylsulfonates↗

Role of cholecystostomy in the management of critically ill patients suffering from acute cholecystitis.

Between the years 1976 and 1985, 60 patients underwent cholecystostomy for acute cholecystitis in the surgical department of the Rokach hospital in Tel Aviv. The patients' average age was 73 years; 78 per cent were 70 years or older at the time of operation. The decision to perform cholecystostomy was taken before the operation which was performed as an emergency procedure for patients considered to be at high risk for cholecystectomy. Forty-six patients (77 per cent) had severe concomitant diseases, and 42 per cent of them had two or more associated diseases simultaneously. The cardiac risk index was high in most patients (90 per cent). Fifty-two patients recovered promptly after surgery. Five patients (8 per cent) developed significant postoperative complications. Three other patients (5 per cent) died of cardiovascular complications. Forty-two patients (70 per cent) underwent an elective cholecystectomy 6-8 weeks later with no further morbidity or mortality. Eleven patients who were at high risk had no further surgery. No residual stones were found in these patients and no relapse of the disease was recorded in the long term follow-up. Four patients were lost to follow-up. We conclude that cholecystostomy may still be used as an initial life saving procedure for critically ill patients with acute cholecystitis, and serves as a definitive procedure for patients considered to be at very high operative risk and who have no residual stones.

Acute Disease↗

Proximal colostomy: still an effective emergency measure in obstructing carcinoma of the large bowel.

Large bowel obstruction constitutes an emergency abdominal condition and necessitates prompt surgical treatment. The optimal approach is still controversial as to whether to perform a diverting colostomy only or a tumor resection with or without primary anastomosis. Seventy-one elderly and high-risk patients were treated by proximal diverting colostomy through a right upper abdominal incision. The operative mortality was 8.5%, with an additional morbidity of 20.5%. Stomal complications appeared in 6.1% of the survivors. Seventy-five percent of surviving patients underwent successful resection and closure of colostomy within 3 months without additional mortality. Others were not operated because of metastatic disease or severe concomitant disease. We conclude that although primary resection should be attempted in good risk patients, for those patients who are elderly and at high risk, a simple life-saving procedure, such as fecal diversion, could alleviate obstructions with relatively low morbidity and mortality and improve the patient's prospects for subsequent definitive surgery.

Aged↗

Late recurrence of stage I malignant melanoma.

Although the introduction of well-established risk factors has made the clinical course and prognosis of malignant melanoma disease much more predictable, in a considerable number of patients the disease's course is still not as expected. One group to which this applies are stage I melanoma patients who develop metastatic disease after 10 years or more of a disease-free interval. In our series of 94 such patients, 6 developed late relapse of their disease. The subsequent survival of these patients did not relate to any of the primary tumors' characteristics, but to the pattern of the late recurrence. Four patients with visceral metastases were dead within 1 to 5 years following relapse, one patient with lymph node involvement is alive with metastases, and another patient with skin metastases has no signs of disease following surgery and immunotherapy. Our conclusion is that malignant melanoma patients should be placed under close follow-up for the rest of their lives.

Abdominal Neoplasms↗

Sporadic amplification of the HER2/neu protooncogene in adenocarcinomas of various tissues.

The HER2/neu protooncogene was found to be amplified in 6 of 109 primary adenocarcinoma tumors. No HER2/neu amplification was found in 29 other primary nonadenocarcinomatous tumors. In two colon tumors, in addition to the amplification, DNA rearrangement of HER2/neu gene was also observed. The rearrangement was explored in detail in one tumor and it was shown to be confined to the 3' region of the gene. Moreover, this tumor expressed an aberrant HER2/neu polypeptide with a molecular weight of 190,000, which is larger by approximately 5,000 than the molecular weight of the normal HER2/neu protein. The aberrant HER2/neu protein was immunoprecipitated with site-specific antibodies against a synthetic peptide from the COOH-terminal end of the normal HER2/neu protein; it also displayed intrinsic protein tyrosine kinase activity leading to self-phosphorylation.

Adenocarcinoma↗

Prolonged fever as a presenting symptom in adrenal tumors.

Four patients with adrenal tumors in whom prolonged fever was the foremost symptom are presented. Two of the patients had nonfunctional adrenocortical carcinoma, one had a pheochromocytoma without adrenergic hyperactivity, and in the fourth, an aldosteronoma was found. Only in 1 case was the tumor (pheochromocytoma) resectable and this patient became afebrile post surgery. A review of the literature revealed that fever is encountered in 6-10% of cases with adrenal tumors, sometimes as the first manifestation of disease. However, a survey of the large series of fever of unknown origin revealed no mention of adrenal tumors in that group of solid tumors which many cause prolonged fever.

Adrenal Gland Neoplasms↗

Time-resolved protonation dynamics of a black lipid membrane monitored by capacitative currents.

The laser-induced proton pulse (Gutman, M. (1986) Methods Enzymol. 127, 522-538) was used for transient protonation of one side of a black lipid membrane. The charging of the membrane drives an electric (voltage or current) signal selectively representing the fast proton exchange at the membrane/electrolyte interface. The sensitivity of the electric signal to the presence of buffer indicates that proton transfer is measured, not some dyes or membrane photoelectric artifact. The same event can be visualized in an analogous system consisting of a pH indicator adsorbed to neutral detergent-phospholipid mixed micelles. The time-resolved light absorption transient is equivalent to the electrically determined transient charging of the membrane surface. The sensitivity of the current measurement exceeds the spectrophotometric method by 6-8 orders of magnitudes. As little as 10(-18) mol of H+ reacting with 0.75 mm2 of the membrane surface can be monitored in a time-resolved observation. Both types of observed transients were accurately reconstructed by the numerical solution of coupled, non-linear, differential equations describing the system. The rate constants of the various proton transfer reactions were calculated and found to be of diffusion controlled reactions. There is no evidence for any barrier at the interface which either prevents protons from reaching the membrane, or keeps proton on the interface. The electric measurements can be applied for monitoring proton transfer kinetics of complex biomembrane preparations.

Hydrogen-Ion Concentration↗