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Biomedical subjects

O Cohen

Publications and source records attributed to O Cohen.

At least 55 records · Page 3Linked to original sources

Subacute painful lumbosacral polyradiculoneuropathy in immunocompromised patients.

The syndrome of inflammatory subacute lumbosacral polyradiculoneuropathy (SLP) has been reported in acquired immunodeficiency syndrome (AIDS) patients in association with cytomegalovirus infection and is only partially amenable to anti-viral therapy. We report three cases of relatively benign inflammatory painful SLP in two non-AIDS, immunosuppressed patients and one who HIV-seroconversed at the time of clinical presentation. SLP developed: (1) in association with HIV seroconversion; (2) during ECHO virus infection in a patient with common variable immune deficiency; and (3) after a severe systemic infection that induced transient immunosuppression due to Epstein-Barr virus reactivation. This report expands the spectrum of viruses associated with acute and subacute lumbosacral polyradiculoneuropathy and may shed light on its possible pathogenesis.

Adult↗

Seizures induced by frustration and despair due to unresolved moral and political issues: a rare case of reflex epilepsy.

We present a case of reflex-induced simple partial seizures, triggered by feelings of frustration, anger and despair. Such emotions were provoked by pondering over complex national and international, political and moral issues. The present case may suggest that activation of right temporal networks may mediate negative and adverse emotions induced by preoccupation with agitating, controversial issues.

Aged↗

Focal, steroid responsive myositis causing dropped head syndrome.

The dropped head syndrome, which occurs in a variety of neuromuscular disorders, is usually not due to an inflammatory process and generally either self-limited or nonresponsive to therapy. We present an 80-year-old woman who developed progressive neck weakness over a few months due to a focal and restricted inflammatory process involving the neck extensor muscles. She responded dramatically to treatment with immunosuppressive therapy.

Aged↗

Myocardial protection in operations requiring more than 2 h of aortic cross-clamping.

OBJECTIVE: Long periods of aortic cross-clamping time during cardiac surgery are associated with high rates of morbidity and mortality because of damage to the myocardium. Recently, we have used a method of myocardial protection based on the principles of hyperkalemic cardioplegic arrest. We use antegrade administration of warm, undiluted blood followed by continuous retrograde infusion of tepid, undiluted blood supplemented with potassium and magnesium. In this study, we have retrospectively reviewed our experience with this method of cardioprotection in operations requiring more than 2 h of cross-clamp time. METHODS: We retrospectively reviewed the medical records of 1280 patients who underwent myocardial revascularization, valve repair or replacement, or a combination of both operations between January 1, 1994 and December 31, 1997. Patients were divided into two groups: the short cross-clamp group (SXC) (n = 1144) had cross-clamp times < 120 min (mean, 78 +/- 20 min; range, 35-119 min) and the long cross-clamp group (LXC) (n = 136) had cross-clamp times > 120 min (mean, 154 +/- 31 min; range, 120-277 min). We compared preoperative, operative, and postoperative variables between the two groups. RESULTS: Significantly more patients in the long cross-clamp group (43.4%) underwent the combined operation than in the short cross-clamp group (2.3%), and the rate of reoperation was significantly higher in the long cross-clamp group (12%) than in the short cross-clamp group (5%). Despite these differences in operative complexity, we found no difference in hospital mortality rates between the two groups. The only significant postoperative differences were that the long cross-clamp group had a greater need for inotropic agents (43 vs. 29%), higher serum levels of creatine kinase (880 +/- 583 vs. 613 +/- 418) and CK-MB (10.9 +/- 6.4 vs. 5.9 +/- 5.2), and a longer hospital stay (9.6 vs. 6.1 days). CONCLUSION: Long, complex operations requiring more than 2 h of cross-clamping can be performed safely with our method of cardioprotection based on continuous retrograde infusion of tepid, hyperkalemic, undiluted blood.

Aged↗

The value of histomorphometric nuclear parameters in the diagnosis of well differentiated follicular carcinomas and follicular adenomas of the thyroid gland.

AIMS: To explore the potential of histomorphometric analysis in distinction between follicular adenomas and well differentiated follicular carcinomas of the thyroid gland. Their differentiation on routine histological study may be a challenging exercise, being contingent upon the absence or presence of vascular invasion and penetration of neoplastic follicles through the capsule of the tumour. METHODS AND RESULTS: Computer-assisted image analysis was performed to gauge the nuclear area, nuclear Ferret diameter, nuclear regularity factor, nuclear elongation factor, number of nuclear vesicles and total area of all nuclear vesicles in the follicles of 37 adenomas and 36 well differentiated carcinomas. By univariate analysis, these nuclear descriptors (with the exception of the elongation factor) were found to correlate with the benign or malignant nature of the tumours. By multivariate analysis, only the nuclear area, Ferret diameter and regularity factor were ascertained to be significant predictors of malignancy. A fitted logit model correctly predicted 91% of the cancers and 87% of the adenomas. CONCLUSIONS: Histomorphometrically gauged nuclear parameters of the tumour cells may reinforce pathologists' decision-making by adding objective and unbiased criteria to their subjective assessment of follicular neoplasms in cases in which vascular or capsular invasion are not detected.

Adenocarcinoma, Follicular↗

Medical investigations requested by patients: how do primary care physicians react?

BACKGROUND AND OBJECTIVES: We investigated the characteristics of patients who request medical investigations and the type of tests requested to study the manner in which primary care physicians react to these requests. METHODS: The study was conducted within the framework of a national health insurance system. Twelve primary care practices from three randomly chosen clinics with different population characteristics participated in the study. The attending physicians were instructed to ask all patients who presented to the clinics within a 7-month period and requested a medical test to complete a questionnaire, indicating the type of test(s) requested and the reason. The physicians were asked to rate the manner in which the patient made the request, their own reaction to the request, and whether they ordered the tests that were requested. RESULTS: During the survey period, 12,322 patients visited the clinics, of whom 295 (2.4%) were reported by a physician to have requested a medical investigation. More-educated patients were more likely to request tests for disease prevention. The types of tests requested were imaging scans, laboratory (blood) tests, and others. The main reason for the request was symptoms (60%), followed by disease prevention (25%). More than 30% of the requests generated self-reported negative feelings in the physician. Physician compliance with patient requests was not significantly correlated with the reason for the request. Laboratory tests were ordered significantly more often than other types. There was a strong correlation between physicians' compliance with the request and physicians' feelings about the request. CONCLUSION: Our findings raise questions about the frequency with which physicians order tests solely in response to patients' requests and provide information about circumstances in which patients make requests for medical investigations.

Adult↗

Complication-free duration and the risk of development of retinopathy in elderly diabetic patients.

BACKGROUND: Determining which diabetic patients are at risk for complications and targeting these patients for intensive therapy may avoid the unwanted consequences of hypoglycemia in low-risk patients. Since aging is associated with a decrease in the incidence of diabetic retinopathy, we assessed whether long complication-free duration can define elderly patients at lower risk for future development of diabetic retinopathy. METHODS: In a 10-year clinic-based study, we studied 833 type 2 diabetic patients who were free of diabetic retinopathy and older than 50 years, followed up for more than 4 years. Data included demographic and clinical information on arrival, updated every 3 to 6 months, and yearly direct ophthalmoscopic examination after pupillary dilation by experienced ophthalmologists. All the data were prospectively compiled on relational databases. End points studied were presence of retinopathy, nephropathy, peripheral neuropathy, peripheral vascular disease, hyperlipidemia, and hypertension. RESULTS: Of the patients without retinopathy at the age of 50 years, 10% developed retinopathy during 4 years of follow-up. These patients had longer duration and younger onset of diabetes than the group without retinopathy at the 4-year follow-up. Clustering of microvascular and macrovascular complications was noted. Discriminant analysis showed the following factors to be significant and independent predictors of the development of retinopathy in the elderly: duration of diabetes, body mass index, age, and glucose control. CONCLUSIONS: A long complication-free period does not define elderly patients with type 2 diabetes who are at lower risk for future development of retinopathy. On the contrary, the increase in disease duration is significantly associated with the development of retinopathy in this age group, as described in younger patients.

Aged↗

Cerebrospinal fluid and plasma concentrations of dipyrone metabolites after a single oral dose of dipyrone.

OBJECTIVE: Dipyrone is a veteran analgesic and antipyretic drug. After oral administration it is rapidly converted by hydrolysis to 4-methylaminoantipyrine (MAA), which is further metabolized to 4-formylaminoantipyrine (FAA), 4-aminoantipyrine (AA) and 4-acetylaminoantipyrine (AAA). It is still debated whether the site of dipyrone action is in the central nervous system or in the periphery. The purpose of this study was to assess whether dipyrone metabolites cross the blood-brain barrier (BBB) when administered systemically. METHODS: Twenty-eight patients undergoing diagnostic lumbar puncture (LP) were randomly assigned to receive two 0.5-g dipyrone tablets either 30 min, 1, 1.5, 2, 4, 6, 8 h or 12 h before the lumbar tap. A 5-ml blood sample was drawn concomitantly. RESULTS: All four metabolites were found in the cerebrospinal fluid (CSF). Their appearance in the CSF lagged but followed that found in the plasma. Mean CSF/plasma ratios were 0.40 (for samples taken between 0.5-2 h) and 0.83 (for samples taken between 4-12 h) for MAA, 0.62 for AA, 0.55 for FAA and 0.40 for AAA (for all samples). Significant correlation was found between plasma and CSF concentrations for MAA, AA, FAA and AAA. CONCLUSION: The concentration-time course of dipyrone metabolite CSF concentrations are in agreement with that of their plasma concentrations and the analgesic effect of dipyrone.

Administration, Oral↗

Cerebrospinal fluid prostaglandins after systemic dipyrone intake.

OBJECTIVE: The object of this study was to evaluate the time course of thromboxane B2 and prostaglandin E2 concentrations in cerebrospinal fluid after oral administration of dipyrone (INN, metamizole). METHODS: A single 1.0 gm oral dose of dipyrone was given to consenting patients undergoing elective diagnostic lumbar puncture 0.5, 1, 1.5, 2, 4, 6, 8, or 12 hours before the tap. RESULTS: For thromboxane B2 a time decrease in cerebrospinal fluid concentration was apparent. In contrast, for prostaglandin E2 cerebrospinal fluid levels no consistent trend was observed. CONCLUSIONS: A time-related decrease in cerebrospinal fluid thromboxane B2 level was noted in patients receiving dipyrone. Thirty minutes after dipyrone intake cerebrospinal fluid thromboxane B2 levels already tended to be lower than those seen in patients with neurologic diseases who were not receiving dipyrone. These results are consistent with the hypothesis that dipyrone acts in the central nervous system by inhibition of particular prostanoids.

Administration, Oral↗

Self-representation of suicidal adolescents.

This study focused on the self-representations of suicidal adolescent. Twenty-six Israeli suicidal inpatients, 24 nonsuicidal inpatients, and 24 control participants completed scales on suicidal tendencies, the hedonic value of self-representations, the complexity (differentiation, integration) of these self-representations, and the discrepancies among self domains (actual, ideal, ought). Suicidal adolescents showed more negative self-representations, a less differentiated and less integrated organization of self-attributes, and more discrepancies between the 3 assessed domains of the self than did control participants. In addition, compared with psychiatric nonsuicidal participants, suicidal adolescents showed a less complex organization of self-attributes and a higher discrepancy between ideal self and ought self. Results were discussed in terms of the vulnerable self of suicidal adolescents, characterized by uneven processing of positive and negative information, confusion, and simplicity.

Adolescent↗

Lithium carbonate therapy is not a risk factor for osteoporosis.

Lithium carbonate is a widely used drug for affective disorders. It may effect calcium metabolism and alter parathyroid physiology by causing hypersecretion of parathyroid hormone. Patients treated with this medication might therefore be predisposed to osteoporosis. The purpose of this study was to evaluate the effect of either short- or long-term lithium carbonate therapy on parameters of bone metabolism. Parathyroid function and indices of bone metabolism were assessed in 23 patients treated for affective disorders. 10 patients were treated for 0.4-1.0 year (Group 1), and 13 patients were treated for more than 3 years (Group 2). In all subjects, bone mineral density measurements in the hip and lumbar spine regions were performed using dual energy X-ray absorptiometry. Serum thyroid hormone, PTH, LH, testosterone and urine OH-proline, free cortisol, calcium and phosphate excretion were measured. The two groups were well matched for sex, weight, calcium intake, lithium levels and smoking habits, although Group 2 was slightly older. No differences between the two groups were noted in either bone mineral density or other parameters that were assessed. Urinary OH-proline was elevated similarly in both groups. Our results did not detect any effect on bone density after short- or long-term lithium carbonate therapy, although the data does suggest an increase in bone turnover associated with this treatment. Thus, short- or long-term treatment with lithium is not associated with increased risk for osteoporosis.

Absorptiometry, Photon↗

Uterine leiomyomata--a feature of acromegaly.

In order to assess the prevalence of leiomyomata in patients diagnosed with acromegaly, files of all women so diagnosed were obtained (n = 25). Eight of these patients had undergone hysterectomy. In eight of the remaining patients, assessment of the uterus was performed by gynaecological examination and transvaginal ultrasound. The prevalence of leiomyomata was 81% (13/16) in patients who had undergone hysterectomy (8/8) or who underwent gynaecological examination (5/8). In conclusion, the very high prevalence of leiomyomata in patients diagnosed with acromegaly warrants the inclusion of growth hormone excess as a cause of leiomyomata. Leiomyomata are a feature of the organomegalic syndrome associated with acromegaly.

Acromegaly↗

Herpes simplex virus type 1 latency-associated transcripts suppress viral replication and reduce immediate-early gene mRNA levels in a neuronal cell line.

During herpes simplex virus type 1 (HSV-1) latent infection in human dorsal root ganglia, limited viral transcription, which has been linked to HSV-1 reactivation ability, takes place. To study the involvement of this transcription in HSV-1 replication in neuronal cells and consequently in viral latency, we constructed stably transfected neuronal cell lines containing (i) the entire HSV-1 latency transcriptionally active DNA fragment, (ii) the same DNA sequence with deletions of the latency-associated transcript (LAT) promoters, or (iii) the DNA coding sequence of the LAT domain. Replication of HSV-1 or a LAT-negative mutant was markedly repressed in the LAT-expressing cells, a phenomenon mediated by the LATs. To study the mechanism responsible for this effect, we examined LAT influence upon expression of HSV-1 immediate-early (IE) genes ICP0, ICP4, and ICP27, by Northern blot analysis. Following infection of a LAT-expressing neuronal cell line with a LAT-negative mutant, the steady-state levels of all three IE mRNAs were reduced compared to those for control cells. Transient transfections into a neuronal cell line indicated that the LAT suppressive effect upon ICP0 mRNA was mediated directly and was not due to the LAT effect upon the ICP0 promoter. We therefore propose that the LATs may repress viral replication in neuronal cells by reducing IE gene mRNA levels and thus facilitate the establishment of HSV-1 latency in nervous tissue.

Animals↗

Immunohistochemical analysis of p27/kip1 expression in thyroid carcinoma.

Cyclin-dependent kinase inhibitors, including the protein product of the p27/kip1 gene, play an important role in cell-cycle regulation. Loss of p27 expression was reported in a number of neoplasms and shown to be an independent prognostic factor in colorectal, lung, and breast carcinoma By immunohistochemical analysis, we investigated p27/kip1 expression, using a polyclonal antibody, in a series of 87 benign and malignant thyroid neoplasms. We correlated its expression with the Ki-67 labeling index and other prognostic factors. All of the thyroid neoplasms examined exhibited significantly lower p27 expression than did normal thyroid tissue (P < .001). Poorly differentiated carcinomas had the lowest p27 staining frequency of all carcinomas examined. p27 staining frequency of the papillary carcinomas was significantly lower than that of the follicular carcinomas (P < .001). This difference could not be attributed solely to the inverse correlation between the staining patterns of p27 and Ki-67, which was reported for other neoplasms, because there was no significant difference between the Ki-67 labeling indices of these two groups. The follicular variant of papillary carcinoma had a significantly higher p27 staining frequency (P = .05) than did classical papillary carcinoma. We saw no significant difference in the p27 staining frequencies between minimally and widely invasive follicular carcinomas nor between localized and nonlocalized papillary carcinoma. In summary, the p27 immunostaining pattern of thyroid neoplasms is related to neoplastic transformation and varies according to tumor phenotype. It seems, however, to have limited routine diagnostic or prognostic significance in thyroid neoplasia.

Adenocarcinoma, Follicular↗

DAP kinase links the control of apoptosis to metastasis.

DAP kinase is a new type of calcium/calmodulin-dependent enzyme that phosphorylates serine/threonine residues on proteins. Its structure contains ankyrin repeats and the 'death' domain, and it is associated with the cell cytoskeleton. The gene encoding DAP kinase was initially isolated as a positive mediator of apoptosis induced by interferon-gamma, by using a strategy of functional cloning. We have now tested whether this gene has tumour-suppressive activity. We found that lung carcinoma clones, characterized by their highly aggressive metastatic behaviour and originating from two independent murine lung tumours, did not express DAP kinase, in contrast to their low-metastatic counterparts. Restoration of DAP kinase to physiological levels in high-metastatic Lewis carcinoma cells suppressed their ability to form lung metastases after intravenous injection into syngeneic mice, and delayed local tumour growth in a foreign 'microenvironment' Conversely, in vivo selection of rare lung lesions following injection into syngeneic mice of low-metastatic Lewis carcinoma cells or of DAP kinase transfectants, was associated with loss of DAP kinase expression. In situ TUNEL staining of tumour sections revealed that DAP kinase expression from the transgene raised the incidence of apoptosis in vivo. DAP-kinase transfectants also showed increased sensitivity in vitro to apoptotic stimuli, of the sort encountered by metastasizing cells at different stages of malignancy. We propose that loss of DAP kinase expression provides a unique mechanism that links suppression of apoptosis to metastasis.

Animals↗

DAP-kinase loss of expression in various carcinoma and B-cell lymphoma cell lines: possible implications for role as tumor suppressor gene.

DAP-kinase is a novel calmodulin dependent serine/threonine kinase that carries ankyrin repeats and the death domain. It was recently isolated, by a functional selection approach of gene cloning, as a positive mediator of programmed cell death. In this study the expression of DAP-kinase was examined in the cell lines derived from various human neoplasms. DAP-kinase mRNA and protein expression were below the limit of detection in eight out of ten neoplastic derived B-cell lines. In six out of 14 examined bladder carcinoma, in three out of five renal cell carcinoma, and in four out of ten tested breast carcinoma cell lines, the DAP-kinase protein levels were below detection limits or lower than 1% compared to the positive cell lines. Interestingly, DAP-kinase expression could be restored in some of the negative bladder carcinoma and B-cell lines by treatment of cells with 5'-azadeoxycytidine that causes DNA demethylation. The high frequency of loss of DAP-kinase expression in human tumor cell lines, and the occasional involvement of methylation in this process raise the possibility that this novel mediator of cell death may function as a tumor suppressor gene.

Apoptosis Regulatory Proteins↗