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Biomedical subjects

R Levy

Publications and source records attributed to R Levy.

At least 289 records · Page 16Linked to original sources

Multicenter trial of octreotide in patients with refractory acquired immunodeficiency syndrome-associated diarrhea.

BACKGROUND/AIMS: Diarrhea is a significant problem in patients with acquired immunodeficiency syndrome (AIDS). The aim of this study was to determine octreotide effectiveness in refractory AIDS-associated diarrhea. METHODS: In a 3-week protocol, 129 patients with a stool weight of > 500 g/day despite standard antidiarrheal therapy were randomized to receive octreotide or placebo (3:2 ratio). Octreotide dose was increased 100 micrograms weekly to a maximum of 300 micrograms three times a day based on weekly 72-hour stool collections. Subsequently, patients received open-label octreotide at doses of up to 500 micrograms three times a day. RESULTS: A 30% decrease in stool weight defined response. After 3 weeks, 48% of octreotide- and 39% of placebo-treated patients had responded (P = 0.43). At 300 micrograms three times a day, 50% of octreotide- and 30.1% of placebo-treated patients responded (P = 0.12). At a baseline stool weight of 1000-2000 g/day, 57% of octreotide- and 25% of placebo-treated patients responded (P = 0.06). Response rates based on CD4 counts, diarrhea duration, body weight, human immunodeficiency virus risk factor, and presence or absence of pathogens showed no benefit of octreotide. Adverse events were more frequent in the octreotide-treated group. CONCLUSION: In the doses studied, octreotide was not more effective than placebo in patients with refractory AIDS-associated diarrhea. This lack of effectiveness may be attributable to inadequate sample size, doses, and duration of study treatment.

Acquired Immunodeficiency Syndrome↗

Magnetic resonance imaging volumetric measurements of the superior temporal gyrus, hippocampus, parahippocampal gyrus, frontal and temporal lobes in late paraphrenia.

Quantified magnetic resonance measurements were made of superior temporal gyrus, parahippocampal gyrus, hippocampal, frontal and temporal lobe volumes and of the planar area of the thalamus and basal ganglia structures in 47 late paraphrenic patients and 33 healthy elderly controls. The late paraphrenics were divided into 31 schizophrenics and 16 patients with delusional disorder according to ICD-10 guidelines. Patients with delusional disorder tended to have smaller left temporal volumes compared with control subjects and patients with schizophrenia, but this difference failed to reach accepted levels of statistical significance after correction for the effects of multiple statistical comparisons, age and total brain size. Physiological right-left asymmetry, reported for temporal and frontal lobe volumes, was present in control, schizophrenic and delusional disorder subjects but delusional disorder patients had a significantly greater degree of temporal lobe asymmetry. The results add to the evidence for heterogeneity among late-onset psychoses and emphasize the subtle nature of any structural brain abnormalities in these patients.

Aged↗

Cognitive features of psychotic states arising in late life (late paraphrenia).

The cognitive performance of 47 elderly psychotic patients with onset of symptoms in late life (late paraphrenia) was compared to that of 33 controls matched for age, sex, ethnic origin, number of years of education, and pre-morbid IQ as measured by the NART. Neuropsychological indices of general cognitive functioning (MMSE, CAMCOG, WAIS-R verbal and performance scores) showed that patients were performing the tasks at a significantly lower level than controls. Patients also showed a trend to have a lower span capacity than controls, particularly at the spatial span subtest. There was no obvious impairment of learning as measured by the digit and spatial recurring span tasks nor of simultaneous matching-to-sample ability. However, patients' performance on a delayed-matching-to-sample procedure was significantly worse than that of controls. In addition, patients performed worse than controls on the Recognition Memory Test for Faces, but not for Words. Finally, the performance of patients on tests assessing executive functioning (Verbal Fluency Test, Computerized Extra and Intra-Dimensional Shift Task, Computerized Spatial Working Memory Task, and Computerized Tower of London Task) was consistently worse than that of controls. These results suggest that psychotic states arising in late life are predominantly associated with a decline on measures of general cognitive ability and executive functioning. The neuropsychological meaning of these findings is discussed in the light of cognitive models of psychotic symptoms, as well as of schizophrenia and dementia research. We concluded that the lack of a clear pattern of impairment among these patients may be the result of their clinical and cognitive diversity.

Aged↗

Clinical and cognitive diversity of psychotic states arising in late life (late paraphrenia).

This study aimed to explore the heterogeneity of paranoid psychosis with onset in late life by using cognitive factors in a centroid method of cluster analysis. Forty-seven subjects were allocated to two different clusters, the first with 24 (51.1%) and the second with 23 (48.9%) patients. Their cognitive attainment was evaluated against the performance of 33 elderly controls, all groups being matched for age, sex, and the numbers of years of education. Patients in cluster 2 showed a pattern of widespread cognitive impairment, which involved general measures of cognitive performance (MMSE, CAMCOG, WAIS-R verbal and performance scores), memory (digit and spatial span, delayed matching-to-sample, recognition memory for words and faces), and executive functions (verbal fluency, extra and intra-dimensional shift ability, spatial working memory, and planning). In contrast, patients in cluster 1 were only impaired on their extra-dimensional set shift and planning abilities, suggesting a more specific and restricted executive functioning deficit. We also analysed the impact that the use of antipsychotic medication could have had on patients' cognitive performance, which was shown to be negligible. In addition, there was no difference between the clusters with regard to the number of patients using neuroleptics, suggesting that the medication was unlikely to have introduced a performance bias in the two patient clusters. The validity of the subdivision of these patients into two separate groups was further supported by other clinical findings. Patients in cluster 1 exhibited more severe psychotic symptoms, as measured by the SAPS, than their counterparts in cluster 2, and were also more likely to display first-rank symptoms of Schneider. Conversely, cluster 2 membership was strongly associated with the presence of neurological signs and negative symptoms. We suggest that psychotic states arising in late life are a heterogeneous condition that may be best divided in two: 'type A', including patients with a wide range of psychotic symptoms, mild increase in the frequency of neurological signs, and cognitive deficits restricted to executive functions, and 'type B', which includes patients with less complex psychotic symptoms associated with a marked increase in the frequency of neurological signs and generalized cognitive impairment. The basis for this subdivision and the prospect for future studies are discussed.

Aged↗

Dynorphins modulate DNA synthesis in fetal brain cell aggregates.

Previously, opioid peptide analogues, beta-endorphin, and synthetic opiates were found to inhibit DNA synthesis in 7-day fetal rat brain cell aggregates via kappa- and mu-opioid receptors. Here dynorphins and other endogenous opioid peptides were investigated for their effect on DNA synthesis in rat and guinea pig brain cell aggregates. At 1 microM, all dynorphins tested and beta-endorphin inhibited [3H]thymidine incorporation into DNA by 20-38% in 7-day rat brain cell aggregates. The putative epsilon-antagonist beta-endorphin (1-27) did not prevent the effect of beta-endorphin, suggesting that the epsilon-receptor is not involved in opioid inhibition of DNA synthesis. The kappa-selective antagonist norbinaltorphimine blocked dynorphin A or B inhibition of DNA synthesis, implicating a kappa-opioid receptor. In dose-dependency studies, dynorphin B was three orders of magnitude more potent than dynorphin A in the attenuation of thymidine incorporation, indicative of the mediation of its action by a discrete kappa-receptor subtype. The IC50 value of 0.1 nM estimated for dynorphin B is in the physiological range for dynorphins in developing brain. In guinea pig brain cell aggregates, the kappa-receptor agonists U50488, U69593, and dynorphin B reduced thymidine incorporation by 40%. When 21-day aggregates were treated with dynorphins, a 33-86% enhancement of thymidine incorporation was observed. Because both 7- and 21-day aggregates correspond to stages in development when glial cell proliferation is prevalent and glia preferentially express kappa-receptors in rat brain, these findings support the hypothesis that dynorphins modulate glial DNA synthesis during brain ontogeny.

Animals↗

Shoulder dystocia: could it be deduced from the labor partogram?

The study was undertaken to test the hypothesis that shoulder dystocia might be suspected and reliably identified from the labor partogram. A retrospective analysis of 52 consecutive patients with shoulder dystocia was performed. The 52 controls were the next consecutive parturient matched for maternal age, gestational age at delivery, parity, presentation, and infants weight at delivery. The mean dilation rate was 2.1 +/- 1.9 cm/hr in shoulder dystocia group compared to 2.4 +/- 1.5 cm/hr in the control group. The incidence of protracted rate of less than 1 cm/hr was 14.3% in shoulder dystocia group and 13.5% in the control group. The mean duration of second stage was 38.3 +/- 30.7 minutes in the shoulder dystocia group compared to 35.5 +/- 32.5 minutes in the control group. Only 1.9% have had a prolonged second stage (more than 2 hours) in the shoulder dystocia group compared to 1.9% in the control group. The difference between the groups regarding the length of labor was not statistically significant. We conclude that protracted labor does not seem to be a risk factor for shoulder dystocia.

Adult↗

Sustained increases in CD4 cell counts in asymptomatic human immunodeficiency virus type 1-seropositive patients treated with prednisolone for 1 year.

Forty-four asymptomatic patients infected with human immunodeficiency virus type 1 (HIV-1), who had 200-799 CD4 cells/microL, received oral prednisolone (0.5 mg/kg for 6 months; 0.3 mg/kg thereafter). After 1 year of treatment, no major side effect or AIDS events had occurred. The percentage of DR+ and CD25+ phenotypes in CD4 T cells decreased significantly as did levels of serum IgG, IgA, and beta 2-microglobulin. Serum p24 antigen and HIV RNA levels remained stable. CD4 cell counts increased significantly at all time points (median increase at 1 year, 119 cells/microL). Peripheral blood mononuclear cell apoptosis after overnight stimulation with anti-CD3 monoclonal antibodies was strongly inhibited at all times. In asymptomatic seropositive patients, immunotherapy for 1 year with glucocorticoids was safe and led to sustained increases in CD4 cell counts and to improvement or stabilization of other biologic markers of disease activity.

Adult↗

Immunohistochemical study of p53 protein expression in Spitz nevus as compared with other melanocytic lesions.

The accumulation of p53 protein was studied immunohistochemically on paraffin-embedded sections of 26 Spitz nevi (SNs), 26 primary invasive cutaneous malignant melanomas (MMs), 20 metastases of MM, and 17 ordinary compound nevi (CNs), using monoclonal antibody BP53-12. Positive reactivity was detected in some of the tumor cells in seven (35%) metastatic MMs, all exhibiting strong nuclear staining; eight (31%) primary MMs, of which seven showed strong nuclear staining; two (7%) SNs, of which only one showed strong nuclear staining; and none of the CNs. The frequencies of the positively stained lesions in general, and the strongly positively stained lesions in particular, in the MM and metastatic MM groups were each statistically significantly higher than the respective frequencies in the SN and CN groups. We believe that the immunohistochemical detection of p53 protein with the use of monoclonal antibodies such as BP53-12 on paraffin sections, especially when strong nuclear reactivity is demonstrated, may prove to be an adjunctive tool in the histopathologic differentiation of MM from SN.

Adolescent↗

Inhibition of superoxide production in human neutrophils by combinations of heparin and thrombolytic agents.

OBJECTIVE: To investigate the effect of heparin and thrombolytic agents on superoxide generation by human neutrophils, as inhibition of superoxide production may have a role in reducing ischaemia and reperfusion injury. METHODS: Neutrophil superoxide production stimulated by phorbol myristate acetate (PMA), opsonised zymosan, or formyl methionyl leucyl phenylalanine (FMLP) was measured as the superoxide dismutase inhibitable reduction of acetyl ferricytochrome c by a microtitre plate technique. RESULTS: Heparin, at concentrations of 0.5-500 U/ml, caused a gradual inhibition of superoxide production stimulated by PMA, opsonised zymosan, or FMLP. Tissue plasminogen activator was more potent than heparin in inhibiting superoxide production induced by opsonised zymosan or FMLP, but it did not affect the activity stimulated by PMA. Streptokinase or urokinase had no effect on superoxide production. When heparin was used in combination with tissue plasminogen activator, streptokinase, or urokinase at their therapeutic concentrations there was a significant inhibition of superoxide generation (70%, 30%, and 25%, respectively). The therapeutic concentrations of tissue plasminogen activator alone caused a reduction of 40% of neutrophil superoxide production. When tissue plasminogen activator and streptokinase were both added to neutrophils, however, a synergistic inhibition of 80% was achieved. CONCLUSIONS: The inhibition of super oxide generation by these drug combinations may explain the limited inflammatory response and reduction of reperfusion injury observed in patients receiving thrombolytic treatment.

Depression, Chemical↗

Intraoperative diagnostic techniques for stereotactic brain biopsy: cytology versus frozen-section histopathology.

Stereotactic brain biopsy has gained widespread acceptance as a primary diagnostic tool for the evaluation of intracranial lesions. Intraoperative evaluation of such specimens has included the use of both cytological and frozen section histologic techniques. The current study seeks to compare the diagnostic utility of frozen section histopathology and cytology in the intraoperative evaluation of stereotactic brain biopsies in HIV-seropositive patients. Seventy-five HIV-seropositive patients undergoing stereotactic brain biopsy for the evaluation of intracranial lesions were evaluated; intracranial diseases were predominantly infectious or hematologic malignancies. Comparison of frozen section and cytology as a means of intraoperative evaluation showed cytology to have a greater sensitivity (86 vs. 78%), positive (95 vs. 90%) and negative (50 vs. 39%) predictive values and a greater overall diagnostic efficiency (84 vs. 75%) than frozen section. Thus, cytology is a highly effective tool equaling and in some cases surpassing frozen section in terms of sensitivity, predictive value, and overall accuracy. Cytologic examination may often be used as the sole means of intraoperative diagnosis, obviating the need for the freezing and sectioning of fresh tissue and potentially reducing specimen turn around time as well. In other cases, cytology can be used in conjunction with other methodologies for arriving at both intraoperative and final diagnoses in these often difficult cases.

Biopsy↗

Positive serology for chlamydia: is it always for Chlamydia trachomatis?

In this study we tried to determine the factual prevalence of Chlamydia trachomatis seropositive women. Sera of 174 sexually active women of reproductive age who attended the emergency room in our gynecology department were tested by both a species-specific solid-phase enzyme immunoassay (SPEIA, ImmunoComb, Orgenics, Israel) and by an immunoperoxidase assay (IPA). One-hundred and twenty-two of 174 women (70.1%) tested were found positive for C. trachomatis by the IPA test. The SPEIA test identified 41 (33.6%) of those as positive for C. trachomatis and 81 (66.4%) positive for C. pneumoniae. We conclude that the currently used IPA method for chlamydia diagnosis overestimates C. trachomatis infection and its specificity for the diagnosis of C. trachomatis is limited. By using the SPEIA test, it is possible to distinguish between C. trachomatis and C. pneumoniae seropositivity.

Antibodies, Bacterial↗

Massive infarcts involving the territory of the anterior choroidal artery and cardioembolism.

BACKGROUND AND PURPOSE: At neuropathological examination, the territory of the anterior choroidal artery is frequently found to be involved in massive infarcts of the internal carotid artery territory. The aim of our study was to analyze the clinical spectrum, the course, and the mechanism of these massive infarcts compared with the rare infarcts involving only the anterior choroidal artery territory. METHODS: Retrospective clinical examination and pathological study were performed in 35 patients with cerebral infarcts affecting at least the territory of the anterior choroidal artery. RESULTS: In no patient had the involvement of the anterior choroidal territory infarcts been recognized clinically, nor had the triad of clinical signs (hemiplegia, hemianesthesia, and hemianopsia) classically seen in infarcts restricted to this territory been found alone. Impairment of consciousness, cognitive disorders, or oculomotor palsies had been found in addition to one or more signs of the triad. This was probably related to the involvement of other territories (94%), especially the middle cerebral artery territory (68%) and the posterior cerebral artery territory (20%). The concomitant involvement of several territories was due most frequently to an occlusion of the internal carotid artery, which was found at autopsy in 74% of the patients. These occlusions were often associated with cardioembolism (54%). In contrast, artery-to-artery embolism (17%) and small-artery disease (6%) were seldom found. Only two cases of infarcts restricted to the anterior choroidal artery territory were observed. CONCLUSIONS: The involvement of the territory of the anterior choroidal artery in massive infarcts was due mainly to a cardioembolic occlusion of the internal carotid artery.

Aged↗

Psychotic states arising in late life (late paraphrenia) psychopathology and nosology.

BACKGROUND: This study explored the psychopathological state of a sample of 'late paraphrenic' patients and the reliability of their diagnosis according to the most widely used systems of classification of mental disorders. METHOD: The presence and severity of psychiatric symptoms were assessed with the Present State Examination (PSE), the Scale for the Assessment of Positive Symptoms (SAPS), and the High Royds Evaluation of Negativity (HEN) scale. Patient signs and symptoms were classified according to the PSE9-CATEGO4, DSM-III-R, DSM-IV, and ICD-10 diagnostic systems. Agreement among the 11 most widely used criteria for the diagnosis of schizophrenia was assessed for these patients. These included DSM-III-R, DSM-IV, ICD-10, Schneider, Langfeldt, New Haven Schizophrenia Index, Carpenter, Research Diagnostic Criteria (RDC), Feighner, Taylor & Abrams, and PSE9-CATEGO4. The study assessed 47 patients, including in-patients, out-patients, day-patients, and those in the community. Thirty-three elderly controls were recruited from luncheon clubs in Southwark and Lambeth (London, UK). RESULTS: Patients showed a wide range of delusional ideas, most frequently involving persecution (83.0%) and reference (31.9%). Eighty-three per cent of patients reported some sort of hallucination, most frequently auditory (78.7%). Formal thought disorder was very rare, only one patient showing mild signs of circumstantial speech. No patients exhibited catatonic symptoms or inappropriate affect. Shallow, withdrawn, or constricted affect was found in only 8.5% of patients. The various systems of classification indicated that most patients displayed typical schizophrenic symptoms, although up to one-third of them did not meet criteria for the diagnosis of schizophrenia. There was poor agreement among the different diagnostic schedules as to whether to classify patients as schizophrenic (0.02 < k < 0.45). CONCLUSION: Psychotic states arising in late life are accompanied by various psychiatric symptoms that are not entirely typical of early-onset schizophrenia. The current trend to include 'late paraphrenia' into the diagnosis of schizophrenia or delusional disorder has poor empirical and theoretical bases.

Age of Onset↗

Psychotic states arising in late life (late paraphrenia). The role of risk factors.

BACKGROUND: This study explored the association between 'late paraphrenia' and various risk factors such as female gender, sensory impairment, marital status, positive family history of psychoses, and the presence of abnormal neurological signs. It was hypothesised that patients would show significantly more abnormal neurological signs than controls. METHOD: Inclusion criteria for the diagnosis of late paraphrenia were fulfilled by 47 patients, including in-patients, out-patients, day-patients, and those living in the community. Thirty-three age-, sex-, education-, and premorbid IQ-matched elderly controls were recruited from luncheon clubs in Southwark and Lambeth (London, UK). A scale for the assessment of neurological soft and hard signs was developed for this study. The Abnormal Involuntary Movement Scale (AIMS) and the Tardive Dyskinesia Rating Scale (TDRS) were also used. RESULTS: There was a high female-to-male ratio (42:5), and a fourfold increase in the risk of patients having hearing impairment (odds ratio = 4.15, Clodds = 1.36 to 12.63). There was no difference between the two groups in visual difficulties nor in marital status. Patients were approximately ten times more likely to be living on their own (odds ratio = 10.61; Clodds = 3.59 to 31.33) and 16 times more likely to be considered socially isolated (odds ratio = 16.65; Clodds = 5.39 to 51.40). There was no difference between patients and controls in frequency of schizophrenia-like family history. Patients were more likely than controls to exhibit neurological soft signs (z = 4.70; P < 0.001; Cld = 4.61 to 9.63). The presence of abnormal involuntary and tardive dyskinesia movements was associated with the use of antipsychotic medication. CONCLUSION: Women appear to run a greater risk of developing late paraphrenia, especially those who are socially isolated and present with associated hearing impairment. The increased presence of neurological soft signs among patients indicates that brain disease may be a critical factor in the development of psychotic symptoms in late life.

Aged↗

Safety and efficacy of long-term octreotide therapy of acromegaly: results of a multicenter trial in 103 patients--a clinical research center study.

One hundred and three acromegalic patients from 14 medical centers were enrolled in this study to determine the efficacy and safety of the somatostatin analog, octreotide acetate, during long term treatment. Seventy percent of the patients had undergone previous surgery or radiation treatment. Octreotide was initiated at a dose of 100 micrograms, sc, every 8 h and gradually increased to a maximum of 1500 micrograms daily depending upon the individual patient's clinical and biochemical response [GH and insulin-like growth factor I (IGF-I) reduction]. The mean duration of treatment was 24 months (range, 3-30 months). However, most patients were treated for a mean of 30 months, because this study took place after an initial 6-month study previously reported. Mean serum GH fell from 30.9 micrograms/L (range, 2.7-350) to 5.7 micrograms/L (range, 0.6-59) at the 3 months visit and remained suppressed (P < 0.001). Plasma IGF-I concentrations were also significantly reduced and remained in the normal range for at least half of the treatment visits in 56 of 87 patients (64%) treated for 12-30 months. Patients with higher initial GH concentrations were less likely to normalize IGF-I concentrations during treatment (P < 0.001). There was no evidence of drug tachyphylaxis in those patients who continued taking stable doses of medication. With some exceptions, dose increments above 800 micrograms daily in 31 patients did not provide additional benefit in terms of GH and IGF-I reduction. Headache, excessive perspiration, fatigue, and joint pain were ameliorated in 83-95% of patients. Mean finger circumference was decreased significantly at the 12 month visit (P < 0.05). The most common adverse events reported were diarrhea, abdominal discomfort, loose stools, and nausea; these symptoms usually disappeared within 3 months of treatment. Five patients discontinued octreotide because of adverse events. Of 102 patients with normal baseline ultrasound examinations of the gallbladder, 24 patients (23.5%) developed gallstones (usually during the first year of treatment), and 21 patients developed sludge alone. Gallstone formation was not related to the dose of octreotide. Most patients with cholelithiasis were asymptomatic, and none developed cholecystitis. These observations suggest that octreotide is a valuable long term medical treatment for acromegaly.

Acromegaly↗

Alterations of GABAergic neurons in the basal ganglia of patients with progressive supranuclear palsy: an in situ hybridization study of GAD67 messenger RNA.

We analyzed postmortem GABAergic neurons in the basal ganglia of three patients with progressive supranuclear palsy (PSP) and four matched controls by means of glutamic acid decarboxylase (M(r) 67,000 [GAD67]) mRNA in situ hybridization. In PSP, we found a 50 to 60% decrease in the number of neurons expressing GAD67 mRNA in the caudate nucleus, ventral striatum, and the external and internal pallidum. The expression of GAD67 mRNA per neuron was reduced in the caudate nucleus and putamen (-43%), the ventral striatum (-55%), and the external and internal pallidum (-59% and -68%). Our data indicate that striatal and pallidal GABAergic neurotransmission is markedly reduced in PSP and we suggest that this alteration may account for the motor and cognitive symptoms observed in PSP. Furthermore, the destruction of the basal ganglia output systems may explain the lack of responsiveness to L-dopa therapy of PSP patients.

Aged↗