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A Soliman

Publications and source records attributed to A Soliman.

At least 19 recordsLinked to original sources

Dopamine D(2) receptor occupancy is a common mechanism underlying animal models of antipsychotics and their clinical effects.

Conditioned avoidance response (CAR) behavior and catalepsy (CAT) are the standard preclinical tests used to predict antipsychotic activity and motor side-effect liability, respectively. Recent data in patients show that striatal dopamine D(2) occupancy predicts antipsychotic response (at 65% D(2) occupancy) and motor side-effects (at greater than 80%). To relate preclinical and clinical findings, this study examined the relationship between striatal D(2) occupancy, CAT and CAR in rats receiving typical and atypical antipsychotics. CAT was observed in animals receiving haloperidol, risperidone and olanzapine, but only at doses that produced a D(2) receptor occupancy > or =85%. The D(2) occupancy of quetiapine did not cross the 85% threshold (up to 100 mg/kg) and it did not show catalepsy. All drugs were effective in the CAR model at a lower level of D(2) occupancy than was required for catalepsy. We suggest that the CAR and CAT models may have displayed high predictive accuracy because they share with the clinical condition a common underlying mechanism: dopamine D(2) occupancy. The implications of this finding for understanding antipsychotic action as well as the continued use of these models in drug discovery is discussed.

Animals↗

Early manifestations of "sick euthyroid" syndrome in patients with compensated chronic heart failure.

BACKGROUND: A "sick euthyroid" syndrome occurs in patients with severe decompensated chronic heart failure (CHF) and other chronic illnesses and is related to adverse prognosis, but it has not been described in patients with compensated CHF. The aim of this study was to determine whether manifestations of the sick euthyroid syndrome occur in patients with compensated CHF caused by ischemic heart disease. METHODS AND RESULTS: Thyroid hormonal responses to thyrotropin-releasing hormone (TRH) stimulation were compared in 8 patients with New York Heart Association class I/II CHF considered secondary to ischemic heart disease and 7 control patients after serial 10-minute blood sampling over 3-hour periods. Secretory dynamics of TRH-induced thyroid-stimulating hormone (TSH) release were compared by using deconvolution analysis. Changes in serum thyroxine (T4), triiodothyronine (T3), reverse T3 (rT3), and rT3/T4 concentration ratios were compared. Patients with CHF had lower baseline serum T3 concentrations (P <.001), with lower maximum serum T(3) (P <.01) and higher maximum serum rT(3) (P <.05) concentrations after TRH stimulation but similar estimated TRH-induced TSH secretory burst amplitude, mass, and 3-hour production rates, compared with control patients. CONCLUSIONS: Patients with compensated CHF display the derangements in thyroid hormone metabolism of impaired peripheral conversion of T4 and T3 and increased production of rT(3) in the presence of normal dynamic function of the hypothalamic-pituitary-thyroid axis, which are consistent with early manifestations of a sick euthyroid state.

Aged↗

Dopamine D2 receptor occupancy predicts catalepsy and the suppression of conditioned avoidance response behavior in rats.

RATIONALE: Human positron emission tomography (PET) shows that striatal dopamine D2 receptor occupancy predicts extrapyramidal side effects (EPS). Patients showed a clinical response with > or = 65% D2 occupancy, but EPS only when D2 occupancy >78%. Catalepsy and the selective suppression of conditioned avoidance response (CAR) are often used as animal models to predict EPS and antipsychotic effect, respectively. However, the quantitative relationship between striatal D2 occupancy and effects in these models is not known. OBJECTIVES: The present study intended to investigate the relationship between animal catalepsy, suppression of CAR, and D2 receptor blockade using a method of evaluating D2 receptor occupancy similar in principle to that used in patients. METHODS: In vivo binding of [11C]-raclopride and [3H]-raclopride was compared. Doses of cold raclopride were chosen to provide a D2 occupancy from 0 to 95%. The relationship between dose/time course of catalepsy and D2 occupancy was assessed. Effects of raclopride on conditioned avoidance response (CAR) behavior were tested. RESULTS: In vivo binding of [11C]-raclopride compared to [3H]-raclopride was virtually the same. Using [3H]-raclopride, cold raclopride (0.01-0.2 mg/kg) produced 16-77% D2 receptor occupancy and no catalepsy. Raclopride (0.5-2 mg/kg) produced 83-95% D2 occupancy and significant catalepsy. Raclopride (2 mg/kg) produced on average 95% and 87% D2 receptor occupancy 1 and 2 h after administration, respectively, and maximum catalepsy. D2 occupancy at 4, 8 and 24 h was on average 58%, 46%, and 4%, respectively. No catalepsy was observed. Raclopride (0.2 mg/kg), estimated at 70-75% D2 occupancy, produced suppression of CAR. CONCLUSIONS: In vivo D2 occupancy measurements in rats using [3H]-raclopride is analogous to using [11C]-raclopride in human PET scanning. Suppression of CAR occurred at a D2 occupancy of around 70-75%, and catalepsy at D2 occupancy >80%. Results closely resembled human studies where 65-70% D2 occupancy was required for antipsychotic response, while > or = 80% D2 occupancy led to EPS. Brain mechanisms involved in mediation of catalepsy in rats and EPS in humans might indeed be similar. Both suppression of CAR in rats and antipsychotic response in humans might share an underlying construct, i.e. the need for around 70% D2 receptor blockade.

Animals↗

Telomerase activity as a potential marker in preneoplastic bladder lesions.

OBJECTIVE: To assess telomerase activity (involved in cell immortalization and detectable in most malignant tumours but not in normal somatic tissues) as a marker in cancer diagnosis. PATIENTS AND METHODS: Tissue telomerase activity was assayed by two different techniques, the telomeric repeat amplification protocol-polymerase chain reaction (TRAP-PCR) and a telomerase PCR-enzyme linked immunosorbent assay. Malignant and inflammatory bladder lesions and their adjacent normal tissues were assessed for telomerase activity in a group of 18 patients, 14 of whom had urothelial carcinoma and four a nonspecific inflammatory lesion of the bladder. RESULTS: Eleven of the 14 tumour samples analysed were telomerase-positive and two of the three telomerase-negative tumour samples had a detectable 'telomerase inhibitor'. In the apparently normal tissues next to bladder tumours, four of the 14 specimens were telomerase-positive. Interestingly, these lesions were always next to high-grade muscle-invasive bladder tumours (pT2G3). Two of the four nonspecific inflammatory lesions (one of cystitis glandularis and one of severe dysplasia), known to be preneoplastic lesions, were also telomerase-positive. CONCLUSION: These results strongly suggest that the reactivation of telomerase may be an early event in bladder carcinogenesis, preceding morphological changes related to malignant transformation. Telomerase activity may therefore be useful both as an indicator of malignant potential in preneoplastic lesions, e.g. cystitis glandularis and severe dysplasia, and as a prognostic marker of bladder tumour relapse or progression.

Adult↗

Increased prevalence of patent foramen ovale in patients with severe chronic obstructive pulmonary disease.

This study was designed to assess the prevalence of patent foramen ovale (PFO) in patients with severe chronic obstructive pulmonary disease (COPD) and the magnitude of any effects of right-to-left interatrial PFO shunting on systemic arterial oxygen desaturation after the Valsalva maneuver. The prevalence of PFO was compared between a group of 20 patients with severe chronic obstructive pulmonary disease (FEV1% <50%; FEV1/FVC <50%) and 20 control subjects (FEV1% >70%; FEV1/FVC >70%) by contrast transesophageal echocardiography during the Valsalva maneuver with simultaneous measurement of systemic arterial oxygen saturation (SaO2) by pulse oximetry. Patients with severe COPD (FEV1 = 27.2% +/- 8.4%; FEV1 /FVC = 44.3% +/- 11.0%) had a significantly higher pulmonary artery systolic pressure (38.3 +/- 7.3 vs 21.0 +/- 2.4 mm Hg; P <.005), higher prevalence of PFO (14/20 = 70% vs 7/20 = 35%; P <.05), and greater systemic arterial desaturation after Valsalva (Sao2 change: -2.6% +/- 1.4% vs -1.1% +/- 0.9%; P <.005) than control subjects. In the severe COPD group, the degree of systemic arterial desaturation after Valsalva in patients with PFO was significantly greater than in patients without PFO (Sao2 change: -3.1% +/- 1.4% vs -1.5% +/- 0. 5%; P <.05). Significant systemic arterial oxygen desaturation was observed after Valsalva in 45% of patients with interatrial PFO shunting and severe COPD. This significantly correlated with the degree of pulmonary hypertension (r = 0.6; P <.05). We conclude (1) that patients with severe COPD have an increased prevalence of PFO and (2) that approximately one half of subjects with severe COPD and PFO demonstrate statistically significant systemic arterial oxygen desaturation after the Valsalva maneuver.

Aged↗

Pulmonary alveolar proteinosis in Israel: ethnic clustering.

BACKGROUND: Pulmonary alveolar proteinosis is a rare disease in which a surfactant-like phospholipid-rich protein accumulates in the lungs. The disease is amenable to effective therapy by total lung lavage. OBJECTIVES: To investigate the prevalence, ethnic distribution and course of PAP in Israel. METHODS: A countrywide survey was conducted during which pulmonologists were questioned about patients with PAP. The patients were examined and their charts, radiological images, pathological slides and physiological data were reviewed. RESULTS: The survey yielded 15 patients (8 females) during the period 1976-98 (14 in the last decade), giving a prevalence of 3.7 x 10(6) and an incidence of 0.36 x 10(6)/year. Mean age of the patients was 33 +/- 13 years (range 0.5-46 years). Seven patients were North African (two were siblings), four were from Iraq and two were Arabs; there was only one Ashkenazi Jew (a child). Symptoms at the onset were dyspnea and chest pain. Spontaneous remission occurred in at least 3 patients, and 10 patients required 1-4 bronchoalveolar lavage treatments. The subjective and physiological response was favorable, but there was less consistent radiological improvement. CONCLUSION: The prevalence of PAP in Israel is approximately 3.7 x 10(6). Most cases occurred in Jews who had immigrated from North Africa or Iraq, and two were siblings. The prevalence among the Arab population appears to be similar. This clustering suggests the existence of a genetic predisposition. The course of the disease appears to be similar to that reported elsewhere.

Adolescent↗

Detection of coronary vasospasm by posthyperventilation technetium-99m sestamibi single-photon emission computed tomography imaging in patients with coronary artery disease.

Forced hyperventilation is simple, safe to perform, and can be used as a provocative test for coronary vasospasm. This study assesses whether a vasospastic component of angina might be detected in patients with angiographically "nonobstructive" coronary artery disease by posthyperventilation technetium-99m (Tc-99m) sestamibi single-photon emission computed tomography (SPECT) cardiac imaging. Eleven patients with angiographically nonobstructive coronary artery disease underwent Tc-99m sestamibi SPECT imaging at rest and after forced hyperventilation. Vessel diameters were measured by quantitative angiography before and after forced hyperventilation, and posthyperventilation SPECT images were compared with dipyridamole Tc-99m sestamibi stress images. Forced hyperventilation resulted in a 15% reduction in coronary artery diameter in stenotic segments (p <0.01), and a 17% reduction in adjacent nonstenotic segments (p <0.001). Myocardial uptake of Tc-99m sestamibi in segments perfused by vessels with angiographically nonobstructive stenoses was reduced by 24% following forced hyperventilation (p <0.001) compared with only 4% following dipyridamole (p <0.02). These findings suggest that posthyperventilation Tc-99m sestamibi SPECT imaging in patients with angina pectoris and nonobstructive coronary artery disease may be useful in identifying a vasospastic component of angina.

Angina Pectoris↗

Comparison of technetium-99m tetrofosmin and thallium-201 single-photon emission computed tomographic imaging for detection of myocardial perfusion defects in patients with coronary artery disease.

OBJECTIVES: We compared dipyridamole technetium-99m (Tc-99m) tetrofosmin and thallium-201 (Tl-201) single-photon emission computed tomographic (SPECT) imaging with respect to the detection rate of perfusion abnormalities in 26 patients with angiographic coronary artery disease (CAD). BACKGROUND: Experimental studies have shown that myocardial extraction of Tc-99m tetrofosmin is lower than that of Tl-201 at high flow rates, resulting in less severe defects with vasodilator stress. It is uncertain whether this results in a lower sensitivity than Tl-201 for detecting coronary stenoses with vasodilator stress in patients. METHODS: Twenty-six patients with CAD underwent both dipyridamole Tl-201 and Tc-99m tetrofosmin SPECT. Tomographic images were scored for initial defects and the presence of reversibility. Defect magnitude was computer quantitated. RESULTS: Of the 26 patients, 25 had defects on both Tl-201 and Tc-99m tetrofosmin SPECT images. Of 340 segments analyzed, 102 had defects by Tl-201 and 92 by Tc-99m tetrofosmin (p = NS). Whereas Tl-201 detected 27 fixed defects in 12 patients, Tc-99m tetrofosmin identified 37 fixed defects in 14 patients (p = NS). In contrast, Tl-201 identified more reversible and partially reversible defects than did Tc-99m tetrofosmin (89 vs. 55, p = 0.002). The average defect magnitude (percent normal) was similar for defects concordantly graded as fixed (38 +/- 3.0% for Tl-201 vs. 42 +/- 4% [mean +/- SEM] for Tc-99m tetrofosmin, p = NS). The average defect magnitude for defects concordantly graded as completely reversible was significantly more severe on Tl-201 than on Tc-99m tetrofosmin (49 +/- 3% vs. 58 +/- 3%) SPECT images. A significantly greater defect magnitude for Tl-201 was also found for defects concordantly classified as partly reversible (30 +/- 4% for Tl-201 vs. 45 +/- 5% for Tc-99m tetrofosmin). CONCLUSIONS: With dipyridamole stress, 1) at least one defect was seen on both Tl-201 and Tc-99m tetrofosmin SPECT images; 2) Tc-99m tetrofosmin SPECT identified fewer reversible defects than did Tl-201, but showed a similar number of fixed defects; 3) the magnitude of reversible defects seen on Tc-99m tetrofosmin images was less, whereas fixed defects were similar for both tracers; 4) reversible defects seen on Tl-201 and not on Tc-99m tetrofosmin SPECT images were predominantly regions perfused by mild coronary stenoses.

Adult↗

Conservative management of colonoscopic perforation can be misleading.

The management of colonoscopic perforations is still evolving. Many now agree to the selective management strategy: Perforations during diagnostic colonoscopy being treated surgically and therapeutic ones treated conservatively. However, patients with diagnostic perforation, if they have clean bowel and no signs of peritonitis, are still treated conservatively. We report here the case of a woman who had a perforation during diagnostic colonoscopy who was treated medically with good progress and no signs of peritonitis during her hospital stay for five days, but collapsed and died at home two days later.

Aged↗

Intrasplenic venous flow patterns demonstrated by Doppler ultrasound in patients with portal hypertension.

The flow pattern in the splenic vein has been previously reported in patients with portal hypertension, but with no reference to the flow within the intrasplenic venous radicles. Using Doppler ultrasound, this study describes the intrasplenic venous flow direction in 176 adult patients with intrahepatic portal hypertension. In our series, a normal flow pattern was maintained in all except four patients (2.3%) who had either reversed or dual venous drainage patterns resulting in trans-splenic portosystemic shunts. These abnormal patterns are Doppler signs of portal hypertension which might be associated with a higher risk of oesophageal variceal bleeding. It is recommended that the intrasplenic venous flow pattern should be assessed before surgical intervention involving the spleen in patients with portal hypertension.

Adolescent↗

Prevalence of patent foramen ovale and its contribution to hypoxemia in patients with obstructive sleep apnea.

STUDY OBJECTIVES: The objectives of this study were (1) to assess the prevalence of patent foramen ovale (PFO) by means of contrast transesophageal echocardiography (TEE) in patients with obstructive sleep apnea, and (2) to determine the potential contribution of right to left interatrial shunting to systemic oxygen desaturation following the performance of Valsalva maneuver. DESIGN: Performance of contrast TEE during Valsalva maneuver with simultaneous measurement of systemic arterial oxygen saturation (SaO2) by means of pulse oximetry in patients with obstructive sleep apnea and a control group. SETTING: Government teaching hospital, university hospital affiliate. PATIENTS: Study group comprised 48 patients with documented obstructive sleep apnea and 24 control subjects. INTERVENTIONS: Sleep studies, contrast TEE, Valsalva maneuver, pulse oximetry. MEASUREMENTS AND RESULTS: Thirty-three of 48 patients with obstructive sleep apnea compared with 4 of 24 control patients had a detectable PFO (69% vs 17%; p < 0.0001). All sleep apnea patients had comparable baseline SaO2 regardless of the presence of a PFO (93.9+/-1.7% vs 95+/-1.2%; p=not significant). After performance of a Valsalva maneuver, however, a significantly greater fall in SaO2 was observed in patients with obstructive sleep apnea and PFO compared with patients with obstructive sleep apnea without PFO (-2.4 +/- 1.5% vs -1.3 +/- 0.6%; p=0.007). A statistically significant fall in SaO2 (defined as > 4 SD of recorded SaO2 values after Valsalva maneuver in patients without PFO) was found in one third of patients with sleep apnea and PFO. CONCLUSION: We conclude that there is an increased prevalence of PFO in patients with obstructive sleep apnea that could contribute to significant hypoxemia after a Valsalva maneuver in approximately one third of these patients.

Aged↗

The role of NAD+ as a signal during nitrogenase switch-off in Rhodospirillum rubrum.

The role of NAD+ in the metabolic regulation of nitrogenase, the 'switch-off' effect, in Rhodospirillum rubrum has been studied. We now show that the decrease in nitrogenase activity upon addition of NAD+ to R. rubrum is due to modification of dinitrogenase reductase. There was no effect when NAD+ was added to a mutant of R. rubrum devoid of dinitrogenase reductase ADP-ribosyltransferase, indicating that NAD+ 'switch-off' is an effect of the same regulatory system as ammonium 'switch-off'. We also show that oxaloacetate and alpha-ketoglutarate function as 'switch-off' effectors. On the other hand beta-hydroxybutyrate has the opposite effect by shortening the 'switch-off' period. Furthermore, by using an inhibitor of glutamate synthase the role of this enzyme in 'switch-off' was investigated. The results are discussed in relation to our proposal that changes in the concentration of NAD+ are involved in initiating 'switch-off'.

Dinitrogenase Reductase↗

Prevalence of anti-Rift-Valley-fever IgM antibody in abattoir workers in the Nile delta during the 1993 outbreak in Egypt.

In the early summer of 1993, an outbreak of Rift Valley fever (RVF) was reported among both humans and animals in Aswan Governorate, Upper Egypt. To determine whether RVF infection had spread to the Nile delta region of the country, we carried out a cross-sectional survey of 1181 occupationally exposed abattoir workers (97% male; age 10-72 years) in 15 governorates of Egypt in November 1993. The overall prevalence of anti-RVF virus IgM antibody was 2% (range: 0% (7 governorates) to 10%). The highest prevalences were in Ismailia (10%) and Sharqîya (8%) Governorates. None of the seropositive subjects reported having experienced an episode of fever in the 2 months prior to the study. The prevalence of antibody was significantly higher (P < 0.05) among workers employed in high-risk jobs such as cutting animals' throats (relative risk (RR = 2.24)) and handling animal parts (RR = 2.37). The findings suggest that abattoir workers represent a useful sentinel population for surveillance of RVF.

Abattoirs↗

High prevalence of diabetes mellitus and impaired glucose tolerance in the Sultanate of Oman: results of the 1991 national survey.

A national survey of glucose intolerance and cardiovascular disease risk factors in Oman has demonstrated a high prevalence of diabetes (10%) and impaired glucose tolerance (IGT, 13% in females and 8% in males). Prevalence of diabetes rose with age to a maximum of over 30% in both sexes. Prevalence of total glucose intolerance (diabetes and IGT combined) exceeded 50% in the seventh (females) and eighth (males) decade of life.

Adult↗

Serious renal disease in Egypt.

We studied serious renal disease in Egypt by registering all 155 patients coming to the nephrology service at the University of Cairo during a period of 62 days in 1993. The patients presented with severe uremic symptoms. Admission creatinine and urea levels were high, 804 mumol/l and 64 mmol/l. Fifteen percent of the patients died; 115 underwent dialysis. Sixty patients presented with chronic renal failure; 53 with acute renal failure, but 24 of these were later found to have end-stage renal failure. Of 29 patients with true acute renal failure, 11 (38%) had pre-renal failure and 7 (24%) post-renal failure. Twenty-one patients were followed up after transplantation and chronic dialysis, another 17 had nephrotic syndrome, 3 hypertension, and one had asymptomatic urinary abnormalities. The most common specific etiology for chronic end-stage renal failure was diabetes mellitus type II in the older patients; second most common was Schistosoma in the younger ones. Most diabetic patients came from the city. All but one Schistosoma patient came from rural Egypt. In the 22 patients who underwent renal biopsy the most common diagnosis was mesangio capillary glomerulonephritis. The prevalence of acute renal failure, particularly iatrogenic-toxic, is increasing.

Adolescent↗

Plasma fibronectin and serum complement C3 levels in chronic active hepatitis following virus "B" versus virus "C" infection.

Plasma fibronectin and serum complement C3 levels were estimated in 30 patients with chronic active hepatitis (CAH) post virus "B" and another 30 patients with CAH post virus "C" as well as 20 normal healthy subjects. Fibronectin level was significantly increased in CAH when compared to normal controls. Moreover, fibronectin level was significantly increased in CAH following virus "C" when compared to CAH following virus "B" hepatitis. Concerning complement C3 there was no significant changes in the different groups studied. We may conclude that CAH following virus "C" may lead to vigorous inflammatory damage than CAH following virus "B" infection.

Adult↗