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Biomedical subjects

R Levy

Publications and source records attributed to R Levy.

At least 325 records · Page 18Linked to original sources
PubMed1994

The role and value of pharmaceutical marketing.

Pharmaceutical marketing is the last element of an information continuum, where research concepts are transformed into practical therapeutic tools and where information is progressively layered and made more useful to the health care system. Thus, transfer of information to physicians through marketing is a crucial element of pharmaceutical innovation. By providing an informed choice of carefully characterized agents, marketing assists physicians in matching drug therapy to individual patient needs. Pharmaceutical marketing is presently the most organized and comprehensive information system for updating physicians about the availability, safety, efficacy, hazards, and techniques of using medicines. The costs of pharmaceutical marketing are substantial, but they are typical of high-technology industries that must communicate important and complex information to sophisticated users. These costs are offset by savings resulting from proper use of medicines and from lower drug costs owing to price competition.

Advertising↗
PubMed1994

A monoclonal anti-idiotypic antibody to opioid receptors labels desipramine-induced opioid binding sites on rat C6 glioma cells and attenuates thymidine incorporation into DNA.

Treatment of rat C6 glioma cells with the tricyclic antidepressant desipramine induces opioid binding. Here the distribution of these opioid-binding sites on C6 cell membranes and a functional property were investigated. Immunohistochemical examination of C6 cells was performed using a monoclonal anti-idiotypic antibody to opioid receptors (Ab2AOR). Ab2AOR uniformly labeled > 97% of the cells exposed to desipramine over their entire surface. The opioid-receptor antagonist naltrexone completely blocked Ab2AOR binding. Ab2AOR, which has opioid agonist properties, also inhibited DNA synthesis in desipramine-treated but not in naive C6 cells. Similarly, morphine blocked C6 cell proliferation only after desipramine treatment. The antineurotrophic action of Ab2AOR was reversed by naltrexone and was insensitive to pertussis toxin. These findings demonstrate that Ab2AOR suppresses the proliferation of C6 glioma cells by binding to desipramine-induced opioid receptors.

Animals↗
PubMed1994

The influence of midtrimester termination of pregnancy on subsequent fertility: four to five years follow-up.

A four to five years follow-up upon subsequent fertility was performed on 46 women who underwent a midtrimester termination of pregnancy. Thirty out of 31 (96.8%) women who wanted to conceive became pregnant. Of those, term delivery rate was 73.3%. Only one woman who desired to conceive could not become pregnant. Her infertility workup revealed bilateral occlusion of tubes. We conclude that termination of pregnancy in midtrimester possibly has little, if any, impact upon subsequent fertility.

Abortion, Induced↗
PubMed1994

Single fetal demise in twin gestation resulting in the resolution of severe pre-eclampsia.

A primigravida presenting with a twin pregnancy and severe pre-eclampsia which developed during early pregnancy is described. Complete resolution of symptoms and signs of pre-eclampsia were evident following the death of a growth-retarded single fetus. Pregnancy continued successfully until 35 weeks of gestation, when a single healthy infant was delivered. Few such cases of complete resolution of pre-eclampsia following the death of a single fetus are reported in the literature. The possibility that genetic susceptibility to pre-eclampsia is conferred by homozygosity for the same single recessive gene expressed by both mother and fetus is discussed.

Adult↗
PubMed1994

Development of proliferative retinopathy in a gestational diabetes patient following rapid metabolic control.

Rapid glucose control was achieved by insulin therapy in a patient diagnosed to have gestational diabetes at 8 weeks of pregnancy. A decrease of the initially high hemoglobin A1c level (16.2%) to normal values (5.9%) was achieved within 12 weeks. At 31 weeks severe bilateral proliferative diabetic retinopathy developed. To our knowledge this case is the first report of a patient with gestational diabetes who developed de novo proliferative diabetic retinopathy.

Adult↗
PubMed1994

Phenomenology, demography and diagnosis in late paraphrenia.

One hundred and one patients with late paraphrenia were examined using the Present State Examination. The established high prevalence rates of female gender, the unmarried state and sensory impairment were confirmed. All of the symptoms of schizophrenia, with the exception of formal thought disorder, were found in the subjects with approximately the same prevalence as reported in schizophrenics with a symptom onset in younger life. The presence of visual hallucinosis was significantly associated with visual impairment, but the same association was not found between auditory hallucinations and deafness. Mean age at onset of symptoms was high at 74.1 years. Using ICD-10 diagnostic criteria the patients were categorized as schizophrenia (61.4%), delusional disorder (30.7%) and schizoaffective disorder (7.9%). Patients in these diagnostic categories differed in their pre-morbid IQ estimations, current cognitive state measured by the Mini-Mental State Examination and in the number of scored positive psychotic PSE symptoms and their systematization of and preoccupation with delusions and hallucinations. There were no significant differences between the patients in the ICD-10 schizophrenia and delusional disorder groups in terms of age at symptom onset, sex ratio, response to treatment, being unmarried, the presence of insight or sensory impairment. The high degree of clinical similarity between patients with late paraphrenia combined with the inability of ICD-10 to define diagnostic subgroups that correspond to patient clusters derived from clinical symptoms or which are meaningfully different from each other in terms of demographic and prognostic factors provide a strong argument for the retention of late paraphrenia as the most appropriate diagnosis for such patients.

Aged↗
PubMed1994

Disproportionate loss of noradrenergic and cholinergic neurons as cause of depression in Alzheimer's disease--a hypothesis.

Forty-two patients with neuropathologically confirmed Alzheimer's disease, who had been examined prospectively, had a significant decrease of neuron numbers in the locus coeruleus, substantia nigra, and basal nucleus of Meynert compared to 10 age-matched, non-demented controls. A subgroup of 12 demented patients with a history of depression had significantly lower neuron numbers in the locus coeruleus and slightly higher neuronal density in the basal nucleus of Meynert. We hypothesize that a noradrenergic/cholinergic imbalance may promote the development of depressive features in patients with Alzheimer's disease.

Aged↗
PubMed1994

Killing of meningococci by neutrophils: effect of vaccination on patients with complement deficiency.

To evaluate the in vitro effect of meningococcal vaccination, 3 C7-deficient (C7-D) siblings and 2 normal controls were studied before and 6 weeks after vaccination with treatment meningococcal vaccine (serogroups A, C, Y, and W). Serobactericidal activity was not detected in the C7-D subjects and was low in the controls. Neither group was affected by vaccination. However, opsonized phagocytic killing increased significantly following vaccination in C7-D subjects and normal controls, despite only a modest increase in antimeningococcal titers. Heat inactivation of sera added to neutrophils resulted in low killing activity, which did not increase after vaccination. Thus, tetravalent meningococcal vaccine appears to enhance the phagocytic killing of meningococci in both normal and C7-deficient persons and should be given to all persons with C7 deficiencies.

Adult↗
PubMed1994

Epithelial markers in malignant melanoma. A study of primary lesions and their metastases.

In order to determine epithelial markers in malignant melanoma in routinely processed paraffin sections and to compare the staining of primary (cutaneous) malignant melanomas and their metastases, we stained formalin-fixed paraffin sections of 13 primary and 18 metastatic malignant melanomas using the streptavidin-biotin peroxidase method by antibodies to S-100, vimentin, HMB-45, polyclonal carcinoembryonic antigen (CEA), monoclonal CEA, cytokeratins (CAM 5.2 and broad-spectrum CKKES), and epithelial membrane antigen (EMA). All primary and most metastatic malignant melanomas showed positive staining with anti-S-100, HMB-45, and anti-vimentin. Reactivity with polyclonal CEA was observed in 15 (48%) of the 31 lesions; 14 of them were metastatic. No lesion was reactive with monoclonal CEA. Significant cytokeratin (CK) staining was evident in only three (9.7%) lesions (all metastatic), which also stained specifically with anti-CK 18. EMA was observed only focally in two (6.5%) lesions. There was no correlation between epithelial markers staining of the primary tumours and their metastases. All lesions with CK or EMA staining showed concomitant extensive staining for S-100, HMB-45, and vimentin. We conclude that (a) polyclonal CEA staining in malignant melanoma is not rare and is probably due to CEA-related molecules; (b) significant CK reactivity is rare and related to simple CK, such as CK 18; (c) epithelial marker reactivity is more common in metastases of malignant melanomas and is not correlated to the reactivity in their primary tumors. Considering our results and reports of positive S-100, vimentin, and HMB-45 in epithelial tumors, a wide panel of antibodies is recommended for the study of undifferentiated tumors.

Adult↗
PubMed1994

Superoxide production by neutrophils from trauma patients: regulation of NADPH oxidase activity.

The production of free oxygen radicals by polymorphonuclear cells (PMNs) was studied in 25 patients after blunt trauma. Superoxide generation significantly increased immediately after trauma and returned to normal soon after the event. Patients were subsequently divided into two groups: those who developed sepsis and those who did not develop infectious complications. Superoxide production by intact PMNs following stimulation by three different stimulants was initially not different in trauma patients who developed sepsis. Follow-up showed an increase in superoxide production when infection complicated the course of trauma patients. Further studies were performed in a cell-free system containing cell membranes and cytosol from patients or healthy controls. No difference in the production of superoxide was found when membranes from trauma patients or controls were mixed with cytosols from controls. When cytosols from patients were mixed with membranes from controls, a significant increase in superoxide production was observed in the group that developed sepsis. Immunoblotting analysis of two protein components of the cytosolic portion of the NADPH oxidase, p47 and p67, were done. The increase in quantity of p47 correlated with the increase in superoxide production during sepsis, and thus may be the major contributor to the high activity.

Adolescent↗
PubMed1994

Early glottic carcinoma involving the anterior commissure.

Between 1958 and 1990 67 patients with an early glottic carcinoma involving the anterior commissure were treated by radiotherapy. Excluding three with carcinoma in situ, 64 had a T1N0M0 squamous cell carcinoma; in eight of these (12.5%) the tumour was only located in the anterior commissure, in 45 (70.3%) it also involved one vocal cord and in 11 (17.2%) both vocal cords. The overall 5-year survival rate was 85%. For those with only anterior commissure involvement it was 60%, with involvement of one vocal cord and the anterior commissure it was 89% and with involvement of both vocal cords 82%. The 3-year recurrence rate was 58% for patients with involvement of only the anterior commissure, 24% with involvement also of one vocal cord, and 45% for those with involvement of both vocal cords. It was found that in cases of early glottic carcinoma, involving the anterior commissure and treated by radiotherapy, the prognosis for recurrence and survival was poorest when the carcinoma was only located in the anterior commissure, and it was concluded that this group of patients deserves special consideration.

Carcinoma, Squamous Cell↗
PubMed1994

The direct cost of type 1 diabetes mellitus in Israel.

Estimates of the cost of Type 1 (insulin-dependent) diabetes mellitus should take into account the development of various complications. In this study, we calculated separately the basic direct costs of a Type 1 diabetic patient over a span of 35 years of living with the disease, and on average, the cost of complications which developed during this period of time. Assessment of costs showed that there is a difference between the cost of treating the disease itself, which decreases over the years, and the cost of treating its complications, which increases. The cost of treating one patient over the 35-year period amounted to about 247,000 pounds in 1993 prices, and in terms of discount value, to about 104,000 pounds. These costs are significant in planning the health expenditure and the investment of resources for prevention of the disease, and in selecting proper methods of treatment of complications.

Blood Glucose Self-Monitoring↗
PubMed1994

Diagnosis of accessory mitral valve tissue by transesophageal echocardiography.

Accessory mitral valve tissue is a rare cause of intracardiac mass and subvalvular left ventricular outflow tract obstruction. The preoperative diagnosis of this congenital anomaly has been facilitated by transthoracic two-dimensional and Doppler echocardiography. However, transthoracic two-dimensional echocardiography cannot identify or correctly diagnose all cases of accessory mitral valve tissue. We report a patient in whom an intracardiac mass detected by transthoracic echocardiography was definitively diagnosed as accessory mitral valve tissue by transesophageal echocardiography.

Adult↗
PubMed1994

Genetic differences between blood- and brain-derived viral sequences from human immunodeficiency virus type 1-infected patients: evidence of conserved elements in the V3 region of the envelope protein of brain-derived sequences.

Human immunodeficiency virus type 1 (HIV-1) sequences were generated from blood and from brain tissue obtained by stereotactic biopsy from six patients undergoing a diagnostic neurosurgical procedure. Proviral DNA was directly amplified by nested PCR, and 8 to 36 clones from each sample were sequenced. Phylogenetic analysis of intrapatient envelope V3-V5 region HIV-1 DNA sequence sets revealed that brain viral sequences were clustered relative to the blood viral sequences, suggestive of tissue-specific compartmentalization of the virus in four of the six cases. In the other two cases, the blood and brain virus sequences were intermingled in the phylogenetic analyses, suggesting trafficking of virus between the two tissues. Slide-based PCR-driven in situ hybridization of two of the patients' brain biopsy samples confirmed our interpretation of the intrapatient phylogenetic analyses. Interpatient V3 region brain-derived sequence distances were significantly less than blood-derived sequence distances. Relative to the tip of the loop, the set of brain-derived viral sequences had a tendency towards negative or neutral charge compared with the set of blood-derived viral sequences. Entropy calculations were used as a measure of the variability at each position in alignments of blood and brain viral sequences. A relatively conserved set of positions were found, with a significantly lower entropy in the brain-than in the blood-derived viral sequences. These sites constitute a brain "signature pattern," or a noncontiguous set of amino acids in the V3 region conserved in viral sequences derived from brain tissue. This brain-derived signature pattern was also well preserved among isolates previously characterized in vitro as macrophage tropic. Macrophage-monocyte tropism may be the biological constraint that results in the conservation of the viral brain signature pattern.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Analgesic action of acute and chronic intraspinally administered opiate and alpha 2-adrenergic agonists in chronic neuropathic pain.

Intrathecal (IT) administration of opiate analgesics has become a popular method of pain control in patients with pain of both malignant and nonmalignant origin. Therapeutic efficacy for nonmalignant pain states might be improved by having a broader range of available pharmacologic agents for intrathecal administration. Toward this aim, we have applied a new model of neuropathic pain in the rat to evaluate the relative analgesic efficacy and potential cross tolerance of both acutely and chronically administered IT morphine (MS) and tizanidine (TZ), an alpha 2-adrenergic agonist. Under anesthesia, 225 Sprague-Dawley male rats underwent unilateral multiple partial suture ligation of the sciatic nerve. This produces a syndrome similar to human neuropathic pain. Chronic lumbar IT cannulae were placed via the cisterna magna. Seven days after surgery, animals were tested for spontaneous ambulation and paw pinch tolerance. These tests correlate with human clinical observations of chronic pain and hyperpathia. For the acute drug administration, animals were then given saline, 10, 20, or 30 micrograms IT MS or 10, 25 or 50 micrograms IT TZ and testing was repeated. Preliminary results suggest that MS, in a dose-dependent manner, significantly decreased abnormal limb withdrawal from the floor while ambulating and increased paw pinch withdrawal latency to cutoff values (p < or = 0.01 in all tests). IT MS had significant effects on pain sensation in the operated and unoperated limbs, increasing latencies to cutoff and nonspecifically inhibiting pain transmission. IT TZ had a similar effect on decreasing limb withdrawal from the floor, but paw pinch withdrawal latency was increased only to the normal range, not to cutoff values. These effects were also dose-dependent. For chronic drug administration, after baseline testing, osmotic minipumps (Alza, Palo Alto, Calif.) delivering either saline, 60 or 120 micrograms/day MS, or 75 or 150 micrograms/day TZ were attached to the IT catheter. Testing was done on days 1, 4, 7 and 14 after pump attachment. On day 14, the animals were given an IT bolus of the noninfused drug (50 micrograms tizanidine or 30 micrograms morphine) and the tests were repeated to determine degree of cross tolerance. Initially, chronic MS and TZ administration produced a similar degree of analgesia seen with results obtained with acute administration. The animals rapidly became tolerant to these agents so that by day 4, neither drug had an analgesic effect. No significant cross tolerance between MS and TZ was observed. Thus, both IT MS and TZ are analgesic in experimental chronic neuropathic pain.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenergic alpha-Agonists↗
PubMed1994

Delusional misidentification in Alzheimer's disease: a summary of clinical and biological aspects.

Delusional misidentification symptoms (DMS) are common in Alzheimer's disease (AD) and they are frequent sources of serious distress for patients and particularly caregivers. We observed DMS in around 30% of the patients with moderate to severe AD in two independent prospective studies; the Capgras type, phantom boarder, mirror and TV DMS were found most frequently. Patients with DMS showed increased EEG delta-power over the right hemisphere, their CT scans showed more severe right frontal lobe atrophy, and the number of their pyramidal cells in area CA1 was lower than in the patients without DMS. This may indicate that the development of DMS in AD can be promoted by certain patterns of brain degeneration which affect systems relevant to the recognition and updating of memories, while verbal skills may initially be left largely intact.

Aged↗
PubMed1994

Cellular mechanism of the conduction abnormalities induced by serum from anti-Ro/SSA-positive patients in rabbit hearts.

In this study, IgG fractions from sera of SLE patients with anti-Ro/SSA or anti-Ro/SSA and anti-La/SSB activity were tested in Langendorff preparations of adult rabbit hearts, aiming to reproduce the cardiac manifestations observed in neonatal lupus in an experimental model. The hearts were perfused with normal Tyrode's solution for 30 min, followed by perfusion with Tyrode's containing 0.3 mg/ml of anti-Ro/SSA- (or anti-Ro/La-) positive IgG (nine sera), anti-ribonucleoprotein (RNP)-positive IgG (five sera), or IgG fractions from normal donors (five sera). In one third of the experiments done with anti-Ro/La-positive IgG, heart block was observed. With the remaining fractions, a decrease in heart rate of 17.1% was observed, but normal sinus rhythm was maintained. The IgG fractions with anti-RNP activity (five experiments) and from normal sera (six experiments) reduced heart rates by 12.9 and 3.3%, respectively, but heart block was not observed. To further characterize the cellular mechanisms involved in the conduction disturbances observed in the whole rabbit hearts, we conducted experiments with ventricular myocytes isolated from young rabbit hearts, studied by whole cell patch-clamp technique. In these experiments, the slow inward currents were analyzed during the superfusion of the cell with normal Tyrode's solution and 5 min after superfusion with Tyrode's solution containing 0.3 mg/ml of anti-Ro/SSA- (or anti-Ro/La-) positive IgG (five sera), anti-RNP-positive IgG (three sera), or IgG from normal donors (four sera). Resting and action potential amplitudes were not affected by any of the sera used. The anti-Ro/SSA IgG fraction induced a mean reduction in the peak slow inward current of 31.6%. IgG fractions with anti-RNP activity reduced slow inward current by 4.4%, whereas IgG fractions from normal donors increased this current by 3.3%. IgG-free fractions from sera of patients with anti-Ro/SSA activity did not alter the peak slow inward current. These results show, for the first time, that the presence of anti-Ro/SSA or anti-Ro/SSA and anti-La/SSB antibody activity in IgG fractions from lupus patients' sera can induce cardiac conduction disorders similar to those observed in neonatal lupus.

Animals↗