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Biomedical subjects

A Awada

Publications and source records attributed to A Awada.

At least 73 records · Page 4Linked to original sources
PubMed1999

[Residual cerebellar ataxia following acute phenytoin intoxication].

A 30-year-old man was given high doses of phenytoin together with 4 antituberculous drugs for a seizure associated with a probable brain tuberculoma. He developed hepatic toxicity and his serum phenytoin reached the high level of 298 mumol/l (therapeutic range 40-79 mumol/l). All drugs were stopped and the biological parameters returned progressively to normal over the next 15 days. However, he remained with a cerebellar axial syndrome and was still severely ataxic 2 months later. Brain CT and MRI showed mild cerebellar atrophy. This case and the few other published ones, together with some recent experimental data, show that high doses of phenytoin can be toxic to the cerebellar cortical cells. The rarity of similar cases, while millions of epileptics are under phenytoin treatment, would however suggest that individual susceptibility may play a role in this toxicity.

Adult↗
PubMed1999

The Saudi Stroke Data Bank. Analysis of the first 1000 cases.

OBJECTIVES: To determine the types of stroke, their risk factors and their most likely causes in Saudi patients. METHODS: Data on stroke cases admitted to 2 major hospitals in Saudi Arabia since 1982 were collected retrospectively up to 1991 then prospectively since then. By January 1995, the number of cases with first-ever-stroke stored in our Saudi Stroke Data Bank reached 1280. This article describes the findings in the first 1000 Saudi patients investigated by brain computed tomography. RESULTS: Males (68%) outnumbered females. There was no significant difference between the retrospective cases and the prospective ones in relation to the types of stroke or the risk factors. Ischemic strokes accounted for 76% of the cases and one third of them were lacunar infarcts. Most of the hemorrhagic strokes were intracerebral hemorrhages (ICHs) and only 2% of all strokes were subarachnoid hemorrhages (SAHs). Hypertension (52%), diabetes mellitus (41%) and cardiac disorders were common risk factors. The commonest causes of cerebral infarcts were atherosclerosis 36%, hypertensive and/or diabetic arteriolopathy 24% and cardiac embolisms 19%. Hypertensive arteriolopathy accounted for two-thirds of the cerebral hemorrhages. Strokes related to small artery disease, i.e. lacunar infarcts and ICHs accounted for 47% of the cases. CONCLUSION: The overall distribution of stroke types in Saudis is not very different from that reported in western studies, except for the low frequency of SAH. However, the important role of small artery disease in stroke pathogenesis and the high number of diabetic patients are quite distinctive.

Adolescent↗
PubMed1999

Application of DNA-based tests for diagnosis of spinal muscular atrophy in Saudi Arabia.

We examined the deletion of the survival motor neuron (SMN) and neuronal apoptosis inhibitory protein (NAIP) genes in patients with spinal muscular atrophy (SMA) using polymerase chain reaction followed by restriction site assay methods. The study included 16 Saudi patients (9 SMA type I and 7 SMA type II) and 6 healthy Saudi volunteers. The homozygous deletions of exons 7 and 8 of the telomeric SMN gene, and exon 5 of the NAIP gene were found in all SMA type I patients. Exons 7 and 8 of telomeric SMN were deleted in all SMA type II patients. However, exon 5 of NAIP was deleted in three of the seven cases. All control volunteers and all family members of the patients had normal SMN and NAIP. The incidence of NAIP deletion was higher in the more severe SMA cases and the dual deletion of the SMN and NAIP genes was more common in Saudi SMA type I patients compared with patients of other ethnic groups.

Case-Control Studies↗
PubMed1998

Molecular analysis of the SMN and NAIP genes in Saudi spinal muscular atrophy patients.

In this study we examined the deletion of the SMN and NAIP genes in 14 Saudi families (16 patients and 38 relatives of the patients, including parents and siblings) and six healthy Saudi volunteers. The homozygous deletions of exons 7 and 8 of the telomeric SMN gene and exon 5 of the NAIP gene were found in seven out of eight spinal muscular atrophy (SMA) type-I patients. In seven SMA type-II patients, exons 7 and 8 of telomeric SMN were deleted in six cases and exon 5 of NAIP was deleted in three cases. Three patients with SMA diagnosis did not show either of the above deletions. All control Saudi volunteers and all but two family members of the patients had both normal SMN and NAIP genes. Our results show that the incidence of NAIP deletion is higher in the more severe SMA cases and the dual deletions of the SMN and NAIP genes are more common in Saudi SMA type-I patients compared to patients of other ethnic groups.

Arabs↗
PubMed1998

A clinical pharmacokinetics study of carzelesin given by short-term intravenous infusion in a phase I study.

We investigated the pharmacokinetic behavior of carzelesin in 31 patients receiving this drug by 10-min intravenous infusion in a Phase I clinical trial, which was conducted at institutions in Nijmegen (institution 1) and Brussels (institution 2). The dose steps were 24, 48, 96, 130, 150, 170, 210, 250, and 300 microg/m2. Carzelesin is a cyclopropylpyrroloindole prodrug that requires metabolic activation via U-76,073 to U-76,074. The lower limit of quantitation (LLQ) of the high-performance liquid chromatography (HPLC) method used in this study was 1 ng/ml for the parent drug and its metabolic products. Carzelesin was rapidly eliminated from plasma (elimination half-life 23 +/- 9 min; mean value +/- SD). At all dose levels, U-76,073 was found as early as in the first samples taken after the start of the infusion. However, the concentration of U-76,074 exceeded the LLQ for only short periods and only at the higher dose levels. Although the plasma levels of all three compounds were well above the respective IC50 values obtained by in vitro clonogenic assays, they were much lower than those observed in a preclinical study in mice. There was a substantial discrepancy in the mean plasma clearance observed between patients from institution 1 (7.9 +/- 2.1 l h[-1] m[-2]) and those from institution 2 (18.4 +/- 13.6 l h[-1] m[-2]; P = 0.038), probably reflecting problems with drug administration in the latter institution. The results recorded for patients in institution 1 indicated that the AUC increased proportionately with increasing doses. There was a good correlation between the maximal plasma concentration and the AUC, enabling future monitoring of drug exposure from one timed blood sample. Urinary excretion of carzelesin was below 1% of the delivered dose.

Antineoplastic Agents↗
PubMed1998

Evolution of brain tuberculomas under standard antituberculous treatment.

The treatment of brain tuberculomas is primarily medical. Surgery, excision or biopsy, is generally performed when the diagnosis is in doubt or there is no response to medical therapy. The aim of this study was to determine the radiological evolution of intracranial tuberculomas under standard anti-tuberculous drug therapy and to establish guidelines for better management of these patients. Eighteen patients were studied retrospectively. None of them had surgical intervention and all were treated by standard antituberculous drugs and had serial computed tomography (CT) scans until disappearance or stabilization of brain lesions. The regression of lesions' size and number was slow in the first month (mean -7.3%) then became rapid after this (-15% to -20% per month). A paradoxical increase in size was noted in three patients in the first month. All three had associated meningitis. All tuberculomas disappeared on CT scan after 12 months of therapy. Most of the edema images disappeared by 6 months. This study would suggest that a long treatment regimen of 15-18 months may not be necessary in most intracranial tuberculomas occurring in non-immunocompromised patients. It also demonstrates that medical trial in well tolerated suspected cases should last for at least 2 months before considering other etiologies or surgical exploration.

Adolescent↗
PubMed1998

Pharmacokinetic and phase I studies of brequinar (DUP 785; NSC 368390) in combination with cisplatin in patients with advanced malignancies.

Brequinar (DUP 785; NSC 368390) is a quinoline carboxylic acid derivative that inhibits pyrimidine synthesis at the level of dihydro-orotate dehydrogenase and revealed synergy with cisplatin in preclinical models. In this study investigating the pharmacokinetic and toxicity of brequinar in combination with cisplatin, patients were initially treated with weekly brequinar, in combination with an every-three-week administration of cisplatin. Due to toxicity, the schedule was modified to a 28-day cycle with brequinar given on days 1, 8, 15, and cisplatin on day 1. A total of 24 patients (16 male, 8 female; median age 57; median performance status 1) received 69 courses of therapy. Six dose levels were explored, with cisplatin/ brequinar doses, respectively, of 50/500, 50/650, 50/860, 60/860, 75/650, and 75/860 mg/m2. The serum concentration versus time curves for brequinar were biphasic. A comparison of the pharmacokinetic results after the first and third doses of brequinar indicate that the presence of 50, 60, and 75 mg/m2cisplatin did not change the protein binding and the pharmacokinetics of brequinar in any of the three brequinar-dose groups. Total cisplatin plasma pharmacokinetic followed a triphasic-shape curve and unbound cisplatin decayed at a very rapid rate. Since pharmacokinetic parameters for total cisplatin in this study were similar to those reported in the literature, the presence of brequinar is unlikely to alter the pharmacokinetics of cisplatin. Main dose-limiting toxicities included myelosuppression (including neutropenia and thrombocytopenia) and mucositis. Cisplatin/brequinar doses of 50/500, 50/650, 50/860, 60/860, 75/650, and 75/860 mg/m2, were associated with dose limiting toxicity in 0/3, 1/3, 1/3, 1/3, 2/4, 2/5, and 4/6 patients, respectively. This study shows that co-administration of brequinar and cisplatin does not affect the pharmacokinetic properties of either drug and that the MTDs of cisplatin/brequinar combinations are 60/860 mg/m2 or 75/650 mg/m2. From this study, we conclude that full dose of 75 mg/m2 cisplatin (day 1) can be administered with 650 mg/m2 brequinar (days 1, 8 and 15) without significant modifications of individual drug pharmacokinetic parameters.

Adolescent↗
PubMed1998

Spontaneous cervical epidural hematoma: case report.

Spontaneous spinal epidural hematoma (SSEH) is an uncommon cause of acute nontraumatic myelopathy. We report a 14 year-old boy who had tetraplegia on awakening. Diagnosis of spinal epidural hematoma was made by magnetic resonance imaging. Despite spinal cord decompression within 9 h from onset, he remained tetraplegic. No cause for the bleeding was found. The pathogenic hypotheses of SSEH are discussed and the importance of rapid diagnosis and treatment is emphasized.

Adolescent↗
PubMed1998

Pattern of presentation of multiple sclerosis in Saudi Arabia: analysis based on clinical and paraclinical features.

We studied 89 MS patients comprising 38 males and 51 females seen over a 10-year period. The hospital frequency was 25/100,000 patients. The diagnosis was mainly clinical and was supported by neuroimaging, cerebrospinal fluid analysis and neurophysiological tests. Sixty-five patients (73%) were Saudis and the peak age of onset was in the third decade. Fifty-two patients (58.4%) had clinically definite MS, 17 (19.1%) had laboratory-supported definite MS, 15 (16.9%) were clinically probable MS cases and the remaining 5 (5.6%) had laboratory-supported probable MS. The mean age at onset of Saudi patients (25.9 years) was lower than that of the non-Saudis (29.4 years; p < 0.001). Involvement of the pyramidal system was the commonest mode of presentation. The clinical course was relapsing-remitting in 60.7%, progressive-relapsing in 20.2% and primary progressive in 19.1%. The number of systems involved was significantly associated with the duration of disease (p < 0.001). The demographic features and the variability of clinical presentation of Saudi MS patients is similar to the results from neighbouring countries. Combination of clinical features and paraclinical tests is essential for accurate determination of extent of dissemination and for unmasking clinically silent lesions.

Adult↗
PubMed1997

Mitomycin C and vinblastine in combination with amifostine in metastatic breast cancer. A feasibility study of the EORTC--Investigational Drug Branch for Breast Cancer (IDBBC).

Mitomycin C (MMC)-vinblastine (VBL) is a regimen that has commonly been used as salvage therapy for advanced breast cancer for many years. The hematologic toxicity of this combination is one aspect that limits its usefulness. Amifostine, an organic thiophosphate, has been developed as a selective chemoprotective agent. In this pilot study, we tested the feasibility of MMC/VBL administration in combination with amifostine and we monitored the hematologic toxicity closely. Patients having failed one or two chemotherapy regimens for advanced breast cancer, with a good performance status scored at 2 or better and measurable or evaluable lesion(s), were eligible. They were treated according to the following schedule: mitomycin C 10 mg/m2 i.v. day 1, vinblastine 5 mg/m2 i.v. day 1 and 15, amifostine 910 mg/m2 in short i.v. infusion prior to MMC. Premedication consisted of dexamethasone 3 x 20 mg, haloperidol 2 x 0.5 mg p.o., hydration with 11 of normal saline, metoclopramide 1.5 mg/kg in short infusion and procyclide HCl 10 mg i.v. Cycles were repeated every 4 weeks. In all, 14 cycles were administrated to six heavily pretreated patients. Following the first cycle, five of the six patients experienced grade 3 or 4 neutropenia on day 15, and consequently did not receive the second vinblastine administration as planned. Three out of four patients receiving two or more cycles had moderate thrombocytopenia. There were no patients with neutropenic fever or major bleeding problems. The MMC/VBL+amifostine regimen was well tolerated regarding other toxicities. Neither amifostine-related acute vomiting nor any significant decrease in blood pressure was observed. Administration of amifostine in combination with MMC/VBL was feasible but in this group of heavily pretreated patients there were no hints of a protective effect of amifostine on the hematologic toxicity profile of this chemotherapy regimen.

Adult↗
PubMed1997

Cystic meningiomas, a diagnostic and pathogenic challenge.

A 55-year-old woman presented with focal seizures, then rapidly evolving hemiplegia. Brain CT and MRI showed a large cystic lesion of the right frontal lobe with a small enhancing nodule adjacent to the dura. The nodule corresponded to a meningioma on pathological examination, and the operative findings suggested that the cyst was due to local entrapment of CSF by the tumor and its arachnoid adhesions. The rapid clinical deterioration was probably due to the rapid expansion of the cyst volume. Pathogenesis and unusual radiological appearances of cystic meningiomas are discussed.

Arachnoid Cysts↗
PubMed1997

Centro-temporal benign epilepsy in Saudi children.

A review of 36 interictal EEGs compatible with the diagnosis of benign childhood epilepsy with centro-temporal spikes (BECTS) was made in this study. These children constituted 31% of the children with focal epileptic EEG activity observed in the same period. The dipolic spikes occurred either as a single focus (78%) or as two independent foci with a greater preponderance to the right (22%). The onset of seizures before the age of 5 years (Group I) is 53% and between 6 and 10 years (Group II) is 47%. Clinical evaluation showed that 60% of the patients in Group I and 75% in Group II had lateralized seizures, although all of them were initially diagnosed as nocturnal generalized tonic-clonic seizures. A follow-up study showed 31% complete recovery, 47% seizure-free under medications, 8% occasional seizures, 8% frequent seizures, and the rest 6% had a single seizure without medication. It is therefore concluded that the syndrome is common in Saudi Arabia and is usually unrecognized by the general physicians. The follow-up of our patients so far confirms the excellent prognosis.

Adolescent↗
PubMed1997

Cavernous angioma presenting as pregnancy-related seizures.

PURPOSE: To determine the reason that one-quarter to one-third of epileptic women experienced an increased number of seizures during pregnancy. The cause of this increase is not always clearly understood and the principle emphasis of the literature is on the pregnancy-associated changes of anticonvulsant pharmacokinetics. METHODS: Two patients presented with recurrent seizures occurring only during pregnancy. Both had MRI findings typical of cavernous angiomas of the temporal lobe. RESULTS: In addition to changes in anticonvulsant pharmacokinetics, potential mechanisms underlying the exacerbation of seizures from a vascular malformation during pregnancy include effects of estrogen on temporal structures critically involved in epileptogenesis and changes within the malformation itself secondary to direct actions of estrogen and the hemodynamic changes of pregnancy. CONCLUSIONS: The possibility of an occult lesion such as cavernous angioma should be considered for seizures occurring during pregnancy. Even in the presence of a normal CT scan, an MRI investigation should be pursued, despite the ill-defined fears of MRI in pregnancy.

Adult↗
PubMed1997

Corticosteroids significantly delay the onset of docetaxel-induced fluid retention: final results of a randomized study of the European Organization for Research and Treatment of Cancer Investigational Drug Branch for Breast Cancer.

PURPOSE: To confirm the efficacy of docetaxel in patients with breast cancer previously treated with one chemotherapy regimen for advanced or metastatic disease and to compare the incidence of fluid retention (FR) and skin toxicity when docetaxel is administered with and without prophylactic corticosteroids. PATIENTS AND METHODS: Eighty-three patients, pretreated with one chemotherapy regimen for metastatic breast cancer (MBC) with bidimensionally measurable and progressive disease, were eligible for this randomized trial. Docetaxel with prophylactic oral antihistamine was administered at a dose of 50 mg/m2 as a 1-hour infusion on days 1 and 8 every 21 days and patients were randomized to receive methylprednisolone (40 mg days -1, 0, 1, 7, 8, and 9 of each cycle) (arm A) or no methylprednisolone (arm B). RESULTS: Twenty-eight patients (34%, 95% confidence interval [CI], 23% to 45%) achieved on objective response. The median time to disease progression and median overall survival time were 5 and 13.5 months, respectively. In total, 415 cycles of docetaxel were administered (arm A: N = 219, median = six; arm B: N = 196, median = five). The most common toxicity observed was grade 3 or 4 neutropenia, which occurred in 79% of patients. Clinically significant nonhematologic side effects included skin reactions and asthenia. In an intent-to-treat analysis, patients who received methylprednisolone premedication had a delayed onset of FR (median time to onset of FR: arm A, 84 days; arm B, 62 days; P = .01) and received a higher median cumulative dose of docetaxel before the onset of FR (arm A, 333 mg/m2; arm B, 215 mg/m2; P = .001). There was no statistically significant difference in the incidence of skin toxicity between the two arms. CONCLUSION: Docetaxel, at this dose and schedule, has definite antitumor activity in pretreated MBC patients. Moreover, this is the first randomized trial to show that corticosteroids have a favorable impact on docetaxel-induced FR.

Adult↗
PubMed1997

Breast cancer therapies in development. A review of their pharmacology and clinical potential.

Although the management of breast cancer has improved over the past few decades, it remains an important challenge for the clinician. Cytotoxic chemotherapy and hormonotherapy, when given in the adjuvant setting, have a definitive though modest impact on the outcome of early-stage breast cancer. In metastatic disease, these therapies help to provide substantial palliation of symptoms but have a limited impact on survival. The discovery of vinorelbine and the taxanes, paclitaxel and docetaxel, certainly represented the most encouraging clinical development of the 1980s in breast cancer therapy. Several other new cytotoxic agents have been recognised for their potential in the treatment of this disorder. Many of them are only in a very early phase of their clinical development and it remains to be proven that they will have a major role in daily practice in the near future.

Antineoplastic Agents↗
PubMed1997

[Blepharospasm caused by bilateral paramedian thalamic infarction].

A 67 year-old woman developed a small infarct in the superficial anterior territory of the left middle cerebral artery, then 2 other successive infarcts in the left then right thalamic paramedian territories. Left thalamic infarct was associated with right hemiparesis and speech disorders of the subcortical type. The occurrence of the additional right thalamic infarct was associated with stupor, left hemiparesis and oppositional behavior. A severe blepharospasm and paralysis of convergence and vertical eye movements were also noted. Blepharospasm has been rarely reported with structural central nervous system lesions. An extensive literature review disclosed 2 other cases associated with thalamic paramedian infarcts and 2 additional cases described with other thalamic lesions. In all these cases, blepharospasm seems to have been due to lesions of the intralaminar and dorsomedian nuclei.

Aged↗