Biomedical subjects
Publications and source records attributed to S Farah.
The clinical, electrophysiological, and radiological features of a patient with a typical Miller Fisher Syndrome are reported. The patient has shown a unique affection of the ophthalmic division of the trigeminal nerve. The significance of serial electrophysiological testing particularly blink reflex study is discussed.
Human T-lymphotropic virus, type 1 (HTLV-1) infection was detected in two unrelated Kuwaiti patients with tropical spastic paraparesis (HAM/TSP) and in the asymptomatic mother of one of them. The family roots of these patients were traced to the Najaf region of Iraq. The DNA sequence of three PCR-amplified fragments (env, 512 bp; pol, 140 bp; LTR, 704 bp) was determined for each of Kuwaiti HTLV-1 isolates (KUW-1,2,3). All three Kuwaiti HTLV-1 were identical in env and pol fragments and virtually identical in LTR. Two rare substitutions were found in the env and pol fragments. They were shared only with two isolates from Reunion Island (substitution in env), and two isolates from India and the Caribbean (substitution in pol). The sequences of env and pol fragments of the Middle Eastern HTLV-1 isolates were not available. However, the comparison of Kuwaiti isolates with representative Middle Eastern HTLV-1 was possible for the LTR fragment. The phylogenetic analysis of LTR sequences of KUW and 34 other HTLV-1 isolates has shown that Kuwaiti HTLV-1 belongs to a cosmopolitan "a" subtype of HTLV-1 and tends to cluster together with HTLV-1 originating from the Mashhad region of Iran. These results suggest that common origin of Mashhadi and Kuwaiti (Najafi) HTLV-1 and the possibility of another pocket of HTLV-1 infection in the Middle East, located in the Najaf region of Iraq.
In addition to their ability to radiosensitize, nitroimidazoles are selectively toxic toward hypoxic cells. Reduction of the nitro group is required to observe cytotoxicity. One of the reduction products believed to play a role in this cytotoxicity is the nitroso-derivative. One-methyl-2-nitrosoimidazole (INO), chemically synthesized from one-methyl-2-nitroimidazole (INO2), has been used as a model to study the reactivity of 2-nitrosoimidazoles. The ability of INO to react rapidly with glutathione in Chinese hamster ovary cells treated with a sub-toxic and toxic level of the drug has been measured. The kinetics of GSH loss as well as oxidized GSH (GSSG) formation and loss were assessed at short times (0-15 min) after INO exposure using a high pressure liquid chromatography (HPLC) assay for GSH and GSSG. The results obtained were consistent with a model, based on previous chemical studies of the reaction of INO with GSH, whereby GSH reduces INO forming GSSG and as well reacts with a reduced form of INO to form an adduct (I-SG). These results suggest possible strategies for modifying the toxicity of reduction products of one-substituted-2-nitroimidazoles.
Although development of resistance in Candida albicans to amphotericin B is considered rare, C. albicans was persistently recovered from a 28-year-old man after a prolonged course of broad-spectrum antimicrobial therapy for a pancreatic abscess. Determination of the MICs of drugs for C. albicans in Sabouraud broth revealed MICs of 2.5 mg/l amphotericin B, greater than 40 mg/l ketoconazole, 2.5 mg/l miconazole, and greater than 40 mg/l 5-fluorocytosine. Synergy testing revealed a MIC of 0.3 mg/l amphotericin B in the presence of 2.5 mg/l 5-fluorocytosine. When intravenous 5-fluorocytosine was added to the patient's antifungal regimen, achieving levels of 125 mg/l, negative blood cultures resulted for the first time. This suggests there may be a clinical use for in vitro synergy testing as an adjunct to guide antifungal therapy for fungemia due to amphotericin B-resistant C. albicans.
We have described two patients who had coma without focal findings and who were found to have an ischemic stroke involving the midbrain and the thalamus. In both cases metabolic encephalopathy or drug overdose was initially suspected, but recognition of abnormal vertical eye movements led to the proper diagnosis. Examination of vertical eye movements in drowsy or comatose patients may be helpful in arriving at the correct diagnosis early and may prevent unnecessary investigations.
The 50-kDa component (gp50) present in Schistosoma mansoni eggs and secretions of the various life stages of the parasite was recognized by experimentally infected mice and by humans with S. mansoni, Schistosoma haematobium, and Schistosoma japonicum infection. All sera reacting with crude S. mansoni-soluble egg antigens (SEA) also reacted strongly with gp50 in enzyme-linked immunosorbent assay. No reactivity against gp50 was seen with sera from individuals without schistosomiasis, with the exception of sera from patients with Trichinella spiralis infection. All of 10 sera from patients with trichinellosis also reacted with schistosomes by immunofluorescence essentially recognizing testes, ovaries, ootype epithelium and ducts of the reproductive system. Cross-reacting antigens were seen in T. spiralis hypodermis, stichocytes and possibly germinal primordia using anti-gp50 monoclonal antibodies and anti-gp50-positive schistosomiasis patient sera. The results suggest that the anti-gp50 antibody response constitutes a significant part of the anti-SEA antibody response in infected individuals and is a major reason for the previously recognized serological cross-reactivity between T. spiralis and schistosome species.
The cellular reduction of 2-nitroimidazoles under hypoxic conditions can lead to cell killing. One of the postulated toxic intermediates is the two-electron reduction product, the nitrosoimidazole. 1-Methyl-2-nitrosoimidazole (INO) was used as a model to study the reactivity of 2-nitrosoimidazoles with sulfhydryls. INO reacted within minutes with bovine serum albumin (BSA) in a stoichiometric fashion as measured by the loss of its characteristic absorption at 360 nm. It appeared to react specifically with the SH group of BSA as demonstrated by the loss of 5,5'-dithiobis-2- nitrobenzoic acid (DTNB) reactive groups and by the loss of INO reactivity if BSA was previously reacted with DTNB. INO also depleted glutathione (GSH) and protein sulfhydryls (Pr-SH) in Chinese hamster ovary (CHO) cells in a concentration-dependent fashion. INO at 25 microM, a non-toxic concentration in terms of cell colony-forming ability, depleted GSH to 10-20% of control levels within 5 min after treatment. Pr-SH were depleted more slowly to 60% of control levels. GSH recovered to near control levels over 3-4 hr but Pr-SH remained depressed. The recovery of GSH was blocked by buthionine sulfoximine (BSO), suggesting that the recovery was due to de novo synthesis of GSH. At a toxic concentration of INO (45 microM), GSH was again depleted to 10-20% and Pr-SH to 50% of control levels. No recovery of either was observed up to 4 hr. The effect of this extensive oxidative stress on intracellular calcium (Ca2+i) levels was monitored using 1-[2-amino-5-(6-carboxyindole-2-yl)-phenoxyl]-2- (2'-amino-5'-methylphenoxy)-ethane-N,N,N',N'-tetraacetic acid pentaacetoxy methylester (INDO-1 AM). At toxic concentrations of INO, Ca2+i increased in a sustained, non-physiological manner starting at approximately 60 min after the addition of INO. No increase in Ca2+i was observed when cells were treated with nontoxic concentrations of INO. INO toxicity may be modulated by an uncontrolled influx of Ca2+ which can trigger the activation of cellular enzymes and lead to cell death.
Macrocytosis, without anaemia, was common in 82 de novo multiple sclerosis patients compared with a similar number of age and sex matched controls. This was an early phenomenon in the course of the disease and was not influenced by the age of the patients nor the duration of the disease. None of the patients proved to have pernicious anaemia, yet the similarity in the geographical and sex distribution as well as the similarity in HLA associations of multiple sclerosis and pernicious anaemia may indicate that both diseases are under similar genetic influence.
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A most unusual case of Munchausen's syndrome in an 18-year-old Yemeni female is described. The patient presented with bleeding from various sites; repeated subcutaneous emphysema of the face, orbit and upper chest; ulcers on the tongue, and dermatitis autogenica. The illness was confirmed to be factitious and self-induced when she was caught red-handed trying to inject air. We believe this to be the first report of a case where all these features occurred concurrently and only the second report where a patient developed self-induced orbital emphysema.
A patient with severe chronic asthma, who had become refractory to conventional antiasthma drugs, is described. As a last resort, therapeutic bronchoalveolar lavage was performed using beta-stimulant, steroid, and mucolytic solutions. The patient, who had had asthmatic attacks almost every day prior to lavage, showed a dramatic and sustained improvement in his condition. It is suggested that therapeutic bronchoalveolar lavage may be useful in chronic asthmatics who have become refractory to conventional treatment because of mucus plugging of their bronchi.
Pf155 (RESA), a malaria antigen in the membrane of infected red cells, was recently identified as a possible future malaria vaccine candidate. In this study the seroreactivities against this antigen were compared with those against crude parasitic antigens in 195 subjects from a Somali village with mesoendemic malaria. The seroreactivities were determined with immunofluorescence. With age, there was an increased seroreactivity to both Pf155 and the crude parasitic antigens. However, the acquisition of seroreactivity was much slower against Pf155. Hence in the age group 15-24 years, only half of the subjects had detectable antibodies against Pf155.
In a 12-month prospective study incorporating four neighbouring district general hospitals, 228 patients required a total of 236 admissions with intestinal obstruction. The aetiological factors included adhesions 75 (32 per cent), malignant disease 61 (26 per cent), strangulated hernias 59 (25 per cent), volvulus 10 (4 per cent), acquired megacolon 6 (3 per cent), pseudo-obstruction 4 (2 per cent), faecal impaction 6 (3 per cent) and miscellaneous 15 (6 per cent). The peak incidence for obstruction due to adhesions, malignant disease and strangulated hernias each occurred in the eighth decade. Surgery was performed within 48 h of admission in 29 per cent adhesive obstructions (22), 30 per cent obstructions due to malignant disease (18) and 68 per cent strangulated hernias (40)--bowel resection rates in these three groups were 13.5, 50 and 29 per cent, respectively. The overall mortality was 11.4 per cent (26 deaths) and postoperative mortality was 12.3 per cent (19 deaths). During the 12-month study period, 228 patients required a total of 2993 inpatient hospital days as a result of intestinal obstruction. Postoperative adhesions have become the commonest cause of intestinal obstruction but strangulated hernias and intra-abdominal malignant disease still account for 50 per cent of all cases and mortalities. Obstruction due to strangulated hernias and intra-abdominal malignant disease typically occurs in the elderly age group where a more aggressive policy of elective surgical intervention is likely to be associated with increased postoperative morbidity and mortality.
The senior author's experience has been reviewed in 353 operated meningiomas; so called "malignant meningiomas" have been discarded. The whole series has been split into two groups: the first (A) includes 273 cases operated before the CT era, the second (B) consists of 80 cases the operability of which was based mainly on the CT. In addition, during the time elapsed to constitute the second series surgery has been refused to 15 patients which were considered for CT and clinical reasons as surgically incurable when one wants to reduce the risk of mortality and morbidity. Therefore, we have reviewed in series B indisputable, questionable and incurable cases with respect to operability in the present condition of our technical possibilities including arterial hypotension, the operative microscope and the CUSA. Considering localization, we have made technical observations with respect to the principles on which operations have been based since 1958 when general anaesthesia became available in La Pitié. Among the patients of the whole series, 14 were admitted for a recurrence. The time interval between surgery and readmission has been given as well as the primary location of the meningiomas. The mortality rate has been 26 out of 353 (7%), and the main causes have been reviewed especially in series B. With regard to series B, we have been able to get in touch with 53 patients out of 80; 90% of them returned to work or family without sequelae. Intracranial meningiomas remain the most curable tumours, nevertheless some of them must be considered incurable like in meningiomatosis or when the dural attachment is extensive. For those cases surgery is not the final answer and we must accept the fact that in the future other kinds of treatment will develop.
To evaluate the role of ischaemia in the genesis of new septal wall motion abnormalities after coronary artery bypass surgery 45 patients were studied by cross sectional echocardiography before and 8-10 days after operation. Regional left ventricular wall motion was classified as normal, hypokinetic, akinetic, or dyskinetic. Septal wall motion abnormalities were correlated with electrocardiographic Q wave changes and serial serum MB creatine kinase measured before and 4, 7, 21, 48, and 72 hours after operation. Of the 14 patients who developed new septal wall motion abnormalities after operation two developed septal akinesis (both had perioperative infarction) and one new dyskinesis in the previously akinetic septal segment. Of the 11 patients with new septal hypokinesis, eight had normal serial creatine kinase MB values, two had raised values peaking four and seven hours after operation, with a return to normal values at 21 hours indicating transient ischaemia, and one had enzymatic criteria for perioperative infarction. Most new echocardiographic septal wall motion abnormalities after coronary artery bypass grafting are not caused by transient ischaemia, perioperative infarction, or generalised cell necrosis.
We ascertained the incidence of hypercalcemia in 79 consecutive patients with active pulmonary tuberculosis and a control group of 79 patients with chronic obstructive pulmonary disease. Twenty-two patients developed hypercalcemia (serum calcium greater than 10.5 mg/dl) within 4 to 16 weeks after initiation of chemotherapy for tuberculosis. The duration of hypercalcemia ranged from 1 to 7 months, and remission occurred spontaneously in all patients. The mean daily vitamin D supplement was greater in hypercalcemic patients than in the normocalcemic group. There was a positive correlation between daily vitamin D supplement and degree and duration of hypercalcemia. Mean serum calcium in patients with tuberculosis was higher than in patients with chronic obstructive pulmonary disease supplemented with the same dose of vitamin D. Hypercalcemia appears to be related to the activity of pulmonary tuberculosis and the intake of vitamin D; the exact mechanism, however, remains unknown.
The cases of ten patients with Budd-Chiari syndrome who were admitted to our medical centre between 1974 and 1986 were reviewed. There were three survivors; the remaining seven died after their disease had taken a rapid downhill course. The clinical course of Budd-Chiari syndrome and the various modalities of medical and surgical treatment are outlined.
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