Biomedical subjects
Publications and source records attributed to F Mohamed.
On-the-fly dynamics is used to analyze the remarkably anharmonic infrared spectroscopy of crystalline HCl monohydrate, an ionic solid composed of H3O+ and Cl-. The dominant intense infrared feature is shown to originate from specific sections of the hydronium trajectory, in which one of the H-atoms interacts strongly with a neighboring Cl-.
BACKGROUND: Acute organophosphorus (OP) pesticide poisoning is a major clinical problem in the developing world. Textbooks ascribe most deaths to respiratory failure occurring in one of two distinct clinical syndromes: acute cholinergic respiratory failure or the intermediate syndrome. Delayed failure appears to be due to respiratory muscle weakness, but its pathophysiology is unclear. AIM: To describe the clinical patterns of OP-induced respiratory failure, and to determine whether the two syndromes are clinically distinct. DESIGN: Prospective study of 376 patients with confirmed OP poisoning. METHODS: Patients were observed throughout their admission to three Sri Lankan hospitals. Exposure was confirmed by butyrylcholinesterase and blood OP assays. RESULTS: Ninety of 376 patients (24%) required intubation: 52 (58%) within 2 h of admission while unconscious with cholinergic features. Twenty-nine (32%) were well on admission but then required intubation after 24 h while conscious and without cholinergic features. These two syndromes were not clinically distinct and had much overlap. In particular, some patients who required intubation on arrival subsequently recovered consciousness but could not be extubated, requiring ventilation for up to 6 days. DISCUSSION: Respiratory failure did not occur as two discrete clinical syndromes within distinct time frames. Instead, the pattern of failure was variable and overlapped in some patients. There seemed to be two underlying mechanisms (an early acute mixed central and peripheral respiratory failure, and a late peripheral respiratory failure) rather than two distinct clinical syndromes.
BACKGROUND: Peritoneal mesothelioma is a rare disease with few therapeutic options. Recently, the combination of cytoreductive surgery with intraperitoneal hyperthermic chemotherapy (HIPEC) has shown promising results. METHODS: Fifteen patients with peritoneal mesothelioma who were treated by cytoreductive surgery and HIPEC between 1989 and 2004 were identified from a prospective database. HIPEC was performed with cisplatin and mitomycin C for 90 minutes by using the closed-abdomen technique. RESULTS: All patients but one (multicystic) had malignant disease of the following pathologic types: 12 epithelial and 2 biphasic. After surgical resection, 11 patients were considered to have a CC-0 or CC-1 resection (macroscopic complete resection or diameter of residual nodules <2.5 mm). No postoperative death occurred, and six postoperative complications were recorded. All but one patient had resolution of ascites. The overall median survival for the 14 patients with malignant mesothelioma was 35.6 months. The median survival was 37.8 months for patients treated with a CC-0 or CC-1 resection, whereas it was 6.5 months for those treated with a CC-2 or CC-3 resection (diameter of residual nodules >2.5 mm; P < .001). In a univariate analysis, the only other significant prognostic factor was the carcinomatosis extent (P = .02). CONCLUSIONS: A therapeutic strategy combining cytoreductive surgery with HIPEC seems to provide an adequate and efficient locoregional treatment for peritoneal mesothelioma. It is associated with acceptable morbidity when performed by an experienced surgical team. The completeness of cytoreduction is the major determinant of survival.
Acid solvation states are investigated in the recently discovered mixed ether:acid crystalline solids. The solids are simulated using on-the-fly molecular dynamics as implemented in the density functional code QUICKSTEP employing Gaussian basis sets. The solids are shown to display a remarkably broad range of acid solvation states, depending on the ether:acid ratio, including proton sharing in the 1:1 case, proton transfer to the ether in 1:2, and perturbed molecular acid in 1:6. The observed variation of the infrared spectra with the composition is accounted for qualitatively with the help of the calculations.
BACKGROUND AND OBJECTIVES: Peritoneal surface malignancy is a common manifestation of failure of treatment for abdominal cancers. Best results of treatment have been achieved with complete cytoreduction followed by heated intraoperative chemotherapy. Melphalan is a chemotherapeutic agent that shows increased pharmacological activity with heat. But the combination of intraperitoneal administration and heat have never been tested for this drug. The purpose of this study was to evaluate the effect of hyperthermia on the pharmacokinetics and tissue distribution of intraperitoneal melphalan in a rodent model. METHODS: Melphalan was given by the intraperitoneal route to 20 Sprague-Dawley rats at a dose of 12 mg/kg over 90 min. Rats were randomized into two groups according to the temperature of the peritoneal perfusate: group NT received normothermic (33.5 degrees C) melphalan; group HT received hyperthermic (42 degrees C) melphalan. During the course of intraperitoneal chemotherapy, peritoneal fluid and blood were sampled at 5, 15, 30, 60 and 90 min. At the end of procedure, the rats were killed and tissues samples (heart, liver, ileum, jejunum, colon, omentum, and abdominal wall) were collected. Concentrations of melphalan were determined in peritoneal fluid, plasma, and tissues by high-performance liquid chromatography. RESULTS: The area under the curve (AUC) of peritoneal fluid melphalan was significantly lower in the HT group than in the NT group ( P=0.001), whereas no significant difference in plasma AUC was found. AUC ratios (AUC peritoneal fluid/AUC plasma) were 12.1 for the NT group and 12.3 for the HT group. The mean time to reach the plasma peak was shorter in the HT group than in the NT group ( P=0.004). The HT group exhibited increased melphalan concentrations in all intraabdominal tissues. These differences were significant for the ileum ( P=0.03) and jejunum ( P=0.04). CONCLUSION: Hyperthermia affected the pharmacokinetics of intraperitoneal melphalan by decreasing the AUC of peritoneal fluid melphalan without increasing the plasma AUC. It increased intraabdominal tissue concentrations.
BACKGROUND: Use of unlicensed and off-label medications is common in hospital based paediatric practice. Whilst inpatient prescription can be closely monitored within the hospital setting, it is subspecialties like paediatric gastroenterology, caring for chronically ill children on an outpatient basis that require administration of regular medications in the community. Local practitioners rely on available paediatric formularies or information provided by the tertiary unit for monitoring and dispensing further prescriptions. AIM: To assess the proportion of unlicensed and off-label medications prescribed in a paediatric gastroenterology unit to children discharged to the community and assess adequacy of information about these medications in commonly used British formularies. METHODS: All prescriptions prescribed over a six-month period (Jan-Jul 2002) either in the paediatric gastroenterology outpatient department or for children discharged home after an inpatient stay, were retrieved from the pharmacy database. The main outcome measures were to assess the proportion of medications prescribed for unlicensed or off-label use. RESULTS: 308 patients received 777 prescriptions of which 384 (49%) were for unlicensed or off-label use. Of these 291 (76%) were off-label; 208 in relation to indication and 83 to child's age. 93 of the prescribed medications were unlicensed; 37 were due to manipulation of formulation. Of the commonly used formularies in the UK, only 'Medication for Children(R)' contained dosage information on more than half (9/13) of the most often prescribed off-label/unlicensed medications in paediatric gastroenterology. CONCLUSIONS: Use of unlicensed and off-label medications remains a problem in paediatric practice. Until licensing laws change and more drugs are licensed in children, paediatric gastroenterologists remain responsible for provision of information to families, local practitioners, nurses and pharmacists. Of the commonly used formularies, 'Medicines for Children' is the most detailed and comprehensive, and should be available to all general practitioners and pharmacists in the UK. Clear communication between specialist units and local practitioners is imperative to ensure safe and effective prescribing to children.
Subsystems of category learning have been identified on the basis of general domains of content (e.g., tools, faces). The present study examined categories from the standpoint of internal structure and determined brain topography associated with expressing two fundamentally different category rule structures (criterion attribute, CA, and family resemblance, FR). CA category learning involves processing stimuli by isolated features and classifying by properties held by all members. FR learning involves processing stimuli by integral wholes and classifying on overall similarity among members without sharing identical features. fMRI BOLD response to CA and FR categorization was measured with pseudowords as stimuli. Category knowledge for both tasks was mastered prior to brain imaging. Areas of activation emerged unique to the structure of each category and followed from the nature of the rule abstraction procedure. CA categorization was implemented by strong target monitoring and expectation (medial parietal), rule maintenance in working memory, feature selection processes (inferior frontal), and a sensitivity to high frequency components of the stimulus such as isolated features (anterior temporal). FR categorization, consistent with its multi-featural nature, involved word-level processing (left extrastriate) that evoked articulatory rehearsal (medial cerebellar). The data suggest category structure is an important determinant of brain response during categorization. For instance, anterior temporal structures may help attune visual processing systems to high frequency components to support the learning of criterial, highly predictive rules.
AIM: Intraperitoneal chemotherapy administration results in high drug concentration locally with low systemic toxicity. We compared the pharmacokinetics of paclitaxel infused intraperitoneally in two isotonic carrier solutions, 1.5% dextrose peritoneal dialysis solution (peritoneal dialysis solution) and hetastarch (6% hydroxyethyl starch), a high molecular weight solution. METHODS: Twenty patients with peritoneal carcinomatosis were randomized into one of two groups to receive early postoperative intraperitoneal chemotherapy with paclitaxel for 5 consecutive days following cytoreductive surgery. One group (8 patients) received paclitaxel in one litre of peritoneal dialysis solution; the other group (12 patients) received paclitaxel in one litre of hetastarch. Samples of peritoneal fluid and venous blood were taken during the 23 h dwell time. Volumes of chemotherapy solution were recorded and concentrations of paclitaxel determined by high performance liquid chromatography. RESULTS: Hetastarch clearance from the peritoneal cavity was reduced when compared to peritoneal dialysis solution. The mean volume of fluid remaining in the peritoneal cavity at 23 h was 900 ml +/-373.7 (SD) with hetastarch, and 285 ml (+/-157.5) with peritoneal dialysis solution (P=0.0022). The mean total amount of paclitaxel in the peritoneal cavity at 23 h was 2.597 mg (+/-1.57) with hetastarch and 0.772 mg (+/-0.667) with peritoneal dialysis solution (P=0.0152). CONCLUSION: These data show that hetastarch increased the exposure of peritoneal surfaces to paclitaxel by increasing the volume of solution with no decrease in drug concentration. Residual tumour cells within the peritoneal cavity may show an increased response to paclitaxel with hetastarch as a carrier solution.
Magnetic resonance (MR) imaging with multi-planar, gated Half-Fourier Acquisition Single-Shot Turbo Spin-Echo (HASTE) imaging was performed to evaluate a woman with dysrhythmia. MR examination for right ventricular dysplasia revealed a Morgagni hernia. The HASTE images depicted well the diaphragmatic defect and the organs involved, yielding valuable diagnostic and pre-operative information. HASTE imaging may be beneficial in the evaluation of Morgagni hernia.
Administration of exogenous endothelin-1 (ET-1) has been shown to stimulate neointimal hyperplasia following arterial balloon angioplasty (BA). However, the specific effects of ET-1 on the cellular and extracellular matrix response of the vessel wall after balloon injury and the persistence of these ET-1 effects have not been studied. The objectives of this study were to determine the acute (1 week) and long term (10 weeks) effects of administering exogenous ET-1 after arterial BA on neointimal hyperplasia, collagen synthesis and content, cellular proliferation, and ET(A) and ET(B) receptor expression. Thirty-one rabbits were randomized to receive subcutaneous ET-1 (500 pmol/kg/day for 1 week) or placebo time-release pellets and sacrificed at either 1 or 10 weeks after BA. At 1 week, there was a significant two-fold increase in intimal cross-sectional area (CSA) in ET-1 treated animals compared with placebo. ET-1 treated animals showed significant increases in collagen synthesis (ten-fold) and collagen content (three-fold) compared to placebo treated animals. ET-1 treated animals also had a significant increase (two-fold) in proliferation rates. In addition, ET(A) and ET(B) receptor expression were significantly upregulated in ET-1 treated animals. By 10 weeks these stimulatory effects on intimal CSA and collagen content were no longer evident with a 'catch up' phenomenon observed in the placebo treated animals. Similarly, ET(A) and ET(B) mRNA levels had declined significantly in both groups. Therefore, exogenous ET-1 acutely stimulates extracellular and cellular processes including increased expression of ET(A) and ET(B) receptors contributing to intimal hyperplasia. However, these effects are transient and not maintained long term after withdrawal of exogenous ET-1 stimulation.
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BACKGROUND AND PURPOSE: Endothelin 1 (ET-1) is a potent vasoconstrictor that may play a role in cerebral vasospasm following subarachnoid hemorrhage (SAH). However, data regarding its pathogenic role in the development of vasospasm are controversial. We planned a prospective, observational clinical study to investigate the temporal relationship between increased ET-1 production and cerebral vasospasm or other neurological sequelae after SAH. METHODS: ET-1 levels in cerebrospinal fluid (CSF) were measured in 20 SAH patients from admission (within 24 hours from the bleeding) until day 7. Patients received a daily transcranial Doppler study and a neurological evaluation. On day 7, angiography was performed to verify the degree and extent of vasospasm. Patients were then classified as having (1) clinical vasospasm, (2) angiographic vasospasm, (3) no vasospasm, or (4) poor neurological condition without significant vasospasm (low Glasgow Coma Scale score [GCS]). RESULTS: On admission, ET-1 levels were increased in the low-GCS group compared with the other groups (P=0.04). On day 4 ET-1 levels were not significantly different among groups, whereas on day 7 ET-1 levels were significantly increased in both the clinical vasospasm and low-GCS groups compared with the angiographic vasospasm and no vasospasm groups (P<0.005). Moreover, when the low-GCS group was excluded, there was a significant relationship between vasospasm grade and CSF ET-1 levels (R(2)=0.73). CONCLUSIONS: CSF ET-1 levels were markedly elevated in patients with clinical manifestations of vasospasm (day 7) and with a poor neurological condition not related to vasospasm. However, ET-1 levels were low in clinical vasospasm patients before clinical symptoms were evident (day 4) and remained low in angiographic vasospasm patients throughout the study period. Thus, our data suggest that CSF ET-1 levels are increased in conditions of severe neuronal damage regardless whether this was due to vasospasm or to the primary hemorrhagic event. In addition, CSF ET-1 levels paralleled the neurological deterioration but were not predictive of vasospasm.
The effects of in vitro treatment of cercariae, schistosomula, and adult worms of Schistosoma mansoni with 4 hypothalamic-pituitary-adrenal (HPA) axis hormones are described. Dehydroepiandrosterone (DHEA) had the strongest effect on viability. Cercariae were more susceptible to this hormone than schistosomula and adults. Mechanically transformed schistosomula showed 100% mortality (determined microscopically by progressive internal disorganization, development of lucent areas in the cytoplasm, and progressive loss of motility) after 48 hr, whereas physiologically induced schistosomula were more resistant, maintaining viability for up to 5 days of exposure. Males were considerably less sensitive than females to the lethal action of DHEA. When adult worms were paired, DHEA lethality was markedly reduced, with viability beginning to decrease only after 4 days in culture. Cortisol reduced the viability of each of the stages tested about equally. Corticotropin-releasing hormone (CRH) and adrenocorticotropin (ACTH) did not affect the viability of any stage. DHEA and cortisol significantly inhibited in vitro oviposition, whereas CRH and ACTH did not. DHEA and cortisol exerted their effects on schistosome viability and oviposition in a concentration-dependent manner. These results suggest possible new avenues for the control of schistosomiasis.
This study investigates the effect of arousal on visual selection processes. Arousal is predicted to narrow the window of attention surrounding a point of focus. BOLD response to a letter discrimination task was measured under aroused (aversive noise) and non-aroused conditions (n = 8). Results revealed spatially distinct responses for trials invoking a narrow versus wide attentional focus. Under arousal a wide focus showed posterior thalamic activation similar to that associated with the narrowed attentional focus. This reflects altered stimulus filtering and supported the hypothesis. Relevant neuroanatomy involving the locus coeruleus and a triangular circuit of selective attention is discussed. The data demonstrates the intersection of arousal and visual stimulus selection systems, identifies a cognitive consequence of arousal, and provides the first fMRI evidence for brain stem autonomic arousal.
Baboons with primary or secondary exposure to Schistosoma mansoni were compared with each other over a 12-week infection period and with baseline values obtained from uninfected baboons with respect to serum levels of the hypothalamic-pituitary-adrenal (HPA) axis hormones-corticotropin-releasing hormone, adrenocorticotropic hormone, dehydroepiandrosterone sulfate (DHEA-S), and cortisol. Baboons with primary infections, when worm recovery and oviposition rates were high and hepatic schistosome egg granulomas were large, had decreasing levels of these hormones as infection progressed, compared with both uninfected and reexposed baboons. The most reduced hormone level was that of DHEA-S. Reduction of DHEA-S and cortisol levels also occurred in primary murine infections. Reexposed baboons with low worm recovery and oviposition rates and small (modulated) hepatic granulomas showed the opposite pattern: HPA axis hormone levels were maintained at, or exceeded, the baseline values of uninfected baboons. These results suggest that HPA axis hormones may play a role in regulating the establishment, maturation, and oviposition of schistosomes and the progression of schistosomiasis.
Randomly distributed extracellular colloidal accumulations were observed in the pars distalis of viscacha (Lagostomus maximus maximus). They were preferentially located in the peripheral zone of the gland and showed variability in shape and size. Two different types of colloidal accumulations were found by electron microscopy: 1) those surrounded by nongranulated follicular cells that correspond to characteristic follicles, and 2) those surrounded by granulated cells. In the follicles lined by nongranulated follicular cells, long, prominent microvilli and cytoplasmic processes protruded into the lumen. The frequency of these accumulations varies during the year in adult male animals, showing an increase in number during summer and a decrease during winter. The lowest value was registered in August (winter). The mean follicular diameter did not vary seasonally. The number of colloidal accumulations did not vary seasonally in adult female viscachas, but a significant difference in the mean follicular diameter between pregnant and non-pregnant females was observed. Pituitaries of immature animals contain fewer colloidal accumulations than those of adults. In fetuses, these accumulations were absent. The administration of melatonin provoked a decrease in the number of these structures. The numeric changes of the colloidal accumulations observed in this study are associated with: 1) the seasonal reproductive activity in adult males, and 2) the reproductive condition, body weight and sexual maturity in males and females. The fact that melatonin administration decreases the population of colloidal accumulations in males suggests participation of the pineal gland in these changes.
We investigated the effect of lithium chloride administration (Sigma): 1 mmol/kg b.w. i.p./day for 35 days on the testes and sperm of viscacha (Lagostomus maximus maximus), a nocturnal rodent found only in the pampas of Argentina. The histological study showed that hypospermatogenesis and the sperm number per mL decreased markedly in comparison with the controls (treatment group: 315 x 10(6) +/- 77 x 10(6); control group: 693 x 10(6) +/- 39 x 10(6), Means +/- SEM, Student's t-test: p < 0.05). The sperm motility and viability were also affected. Under the same treatment, the testicular tissue and the sperm of rats were not damaged. Moreover, lithium induced these changes when the plasm levels were within the therapeutic range in humans. Our results provide evidence for the claim that viscacha testes and sperm react very sensitively to low doses of lithium, whereas these concentrations do not produce damage in rats.
OBJECTIVE: The purpose of this study was to determine the frequency of apparent stenosis of normal aortic branches in patients on first-pass gadolinium-enhanced three-dimensional (3D) MR angiography and to reproduce the same phenomenon in a pulsatile flow phantom model. CONCLUSION: Apparent stenosis of normal vessels on gadolinium-enhanced 3D MR angiography seen on the first-pass acquisition was observed in only a small proportion (approximately 2%) of our patients. The pseudostenosis was reproducible in the phantom model using rapid injection. A stenosis on first-pass images should be interpreted with caution. Confirmation of the findings on other sequences, such as the second-pass gadolinium-enhanced 3D MR angiography or 3D phase-contrast MR angiography, prevented overdiagnosis of significant stenoses.