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Biomedical subjects

M Patel

Publications and source records attributed to M Patel.

At least 163 records · Page 9Linked to original sources
PubMed1999

Hippocampal/amygdala volumes in geriatric depression.

BACKGROUND: The hippocampus, amygdala and related functional circuits have been implicated in the regulation of emotional expression and memory processes, which are affected in major depression. Several recent investigations have reported abnormalities in these structures in adult and elderly depressives. METHODS: Elderly DSM-III-R unipolar depressives (N = 40) and normal controls (N = 46) participated in a magnetic resonance imaging study (1.0T). Brain images were obtained in the coronal plane. Using established anatomical guidelines for structure delineation, volumetric measurements of left and right hippocampus and anterior hippocampus/amygdala complex were completed under blinded conditions using a semi-automated computer mensuration system, with patients and controls in random order. RESULTS: Medial temporal volumes did not significantly distinguish either elderly depressed and age-similar normal control subjects, or late onset and early onset depressed patients (ANCOVA). Major overlap of measured volumes existed between patient and control groups. In depressives, hippocampal volumes significantly correlated with age, and cognitive and depression ratings, but not with number of prior depressive episodes or age-at-onset of first depression. CONCLUSIONS: Hippocampal volumes do not discriminate a typical clinical population of elderly depressed patients from age-similar normal control subjects. If hippocampal dysfunction contributes to a diagnosis of syndromal depression in the elderly, such dysfunction does not appear to be regularly reflected in structural abnormalities captured by volumetric measurement as conducted. On the other hand, relationships between hippocampal volumes and clinical phenomena in depressives, but not controls, suggest potentially meaningful interactions between hippocampal structure and the expression of major depression in the elderly.

Aged↗
PubMed1999

A novel formulation of VIP in sterically stabilized micelles amplifies vasodilation in vivo.

PURPOSE: To determine whether human vasoactive intestinal peptide (VIP)-poly(ethylene glycol) (PEG)-grafted distearoyl-phosphatidylethanolamine (DSPE) micelles elicit potent and stable vasodilation in vivo. METHODS: PEG-DSPE micelles were prepared by co-precipitation. VIP was loaded into micelles by incubation at room temperature. Vasoactivity of VIP in SSM was determined by monitoring changes in diameter of resistance arterioles in the in situ hamster cheek pouch using intravital microscopy. RESULTS: VIP easily undergoes self-assembly into small PEG-DSPE micelles (mean [+/-SEM] size, 18+/-1 nm) in a time-dependent fashion. This generates a potent vasoactive matrix at nanomole concentrations of VIP as manifested by approximately 3-fold potentiation and prolongation of vasodilation relative to that evoked by aqueous VIP alone (p < 0.05). This response is specific and mediated by the L-arginine/nitric oxide (NO) biosynthetic pathway. Micellar VIP dispersion remains vasoactive for at least 14 days after preparation and storage at 4 degrees C. CONCLUSIONS: A novel, self-associated, small and stable PEG-DSPE micellar formulation of VIP amplifies vasodilation in the in situ peripheral microcirculation in a specific fashion by elaborating NO. An optimized formulation could be considered for certain cardiovascular disorders associated with L-arginine/NO biosynthetic pathway dysfunction.

Animals↗
PubMed1999

Eating in labour.

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Analgesia, Obstetrical↗
PubMed1999

Need for intensive care after operations for head and neck cancer surgery.

We compared the postoperative morbidity of 44 patients who had had major head and neck oncological resections and who were nursed postoperatively on a general ward with that of 33 who were nursed on an intensive care unit at North Manchester General Hospital and Withington Hospital, South Manchester, respectively. There was no difference in the general morbidity (9/44, 20% compared with 9/33, 27%, 95%, CI of difference -0.26 to 0.13). We conclude that it is safe to nurse the patients on a general ward provided that certain conditions are fulfilled.

Adult↗
PubMed1999

Clinical and pathologic predictors of survival in patients with thymoma.

OBJECTIVE: To evaluate the Johns Hopkins Hospital experience with 136 thymomas over the past 40 years. This number of patients allowed quantitative estimation of the independent influence of common clinicopathologic risk factors using multivariate analysis. SUMMARY BACKGROUND DATA: Thymomas vary widely in terms of recurrence and influence on overall survival. Several series have indicated the importance of initial tumor invasion, as well as the extent of surgical resection, as predictors of recurrence and survival after thymoma resection. However, findings have been equivocal when other predictors of prognosis were examined. METHODS: The authors evaluated 136 patients seen at the Johns Hopkins Hospital between 1957 and 1997 with a pathologic diagnosis of thymoma. Demographic information, clinical staging data, surgical and adjuvant treatment details, and patient follow-up data were obtained from the patient record and from detailed patient or family interviews. Microscopic sections of all 136 patients were reviewed by two pathologists blinded to the clinical data. All data were analyzed by multivariate Cox regression analysis, which allowed the quantification of the independent predictive value of 12 putative clinicopathologic prognostic indicators. RESULTS: Completeness of follow-up was 99%, 99%, and 98% of eligible patients at 5, 10, and 15 years, respectively. Forty percent of the patients had associated myasthenia gravis and 27% had a secondary primary malignancy. Overall patient survival rates were 71%, 56%, 44%, 38%, and 33% at 5, 10, 15, 20, and 25 years, respectively. Overall, the thymoma-related mortality rate was 14%; the nonthymoma-related mortality rate was 26%. Incomplete resection, preoperative absence of myasthenia gravis, and advanced Lattes/Bernatz pathologic class were found to be independent predictors of poorer overall survival. CONCLUSIONS: These findings support a policy of aggressive, complete surgical resection of all thymomas when feasible. Thymoma behaves as a rather indolent tumor, with most deaths from causes unrelated to thymoma or its direct treatment. Clinicians should have an increased awareness of the possibility of second primary malignancies in patients with thymoma.

Adolescent↗
PubMed1999

Leaky gut in alcoholic cirrhosis: a possible mechanism for alcohol-induced liver damage.

OBJECTIVE: Only 30% of alcoholics develop cirrhosis, suggesting that the development of alcohol-induced liver injury requires one or more additional factors. Animal studies have shown that gut-derived endotoxin is one such factor. Because increased intestinal permeability has been shown to cause endotoxemia, we hypothesized that increased gastrointestinal permeability contributes to the pathogenesis of alcoholic liver disease. This study aimed to measure gastroduodenal and intestinal permeability in alcoholics with and without chronic liver disease and in nonalcoholic subjects with chronic liver disease. METHODS: Gastroduodenal permeability was assessed by measurement of urinary excretion of sucrose after oral administration. Intestinal permeability was assessed by measurement of urinary lactulose and mannitol after oral administration of these sugars. RESULTS: Alcoholics with no liver disease showed a small but significant increase in sucrose excretion. Alcoholics with chronic liver disease demonstrated a marked and highly significant increase in urinary sucrose excretion relative to the controls, to the alcoholics with no liver disease, and to the nonalcoholics with liver disease. Alcoholics with chronic liver disease demonstrated a marked and highly significant increase in both lactulose absorption and in the urinary lactulose/mannitol ratio (alcoholics 0.703 vs controls 0.019, p = 0.01). In contrast, alcoholics with no liver disease and nonalcoholics with liver disease showed normal lactulose absorption and normal lactulose/mannitol ratio. CONCLUSION: Because only the alcoholics with chronic liver disease had increased intestinal permeability, we conclude that a "leaky" gut may be a necessary cofactor for the development of chronic liver injury in heavy drinkers.

Aged↗
PubMed1999

Thymidylate synthase protein and p53 mRNA form an in vivo ribonucleoprotein complex.

A thymidylate synthase (TS)-ribonucleoprotein (RNP) complex composed of TS protein and the mRNA of the tumor suppressor gene p53 was isolated from cultured human colon cancer cells. RNA gel shift assays confirmed a specific interaction between TS protein and the protein-coding region of p53 mRNA, and in vitro translation studies demonstrated that this interaction resulted in the specific repression of p53 mRNA translation. To demonstrate the potential biological role of the TS protein-p53 mRNA interaction, Western immunoblot analysis revealed nearly undetectable levels of p53 protein in TS-overexpressing human colon cancer H630-R10 and rat hepatoma H35(F/F) cell lines compared to the levels in their respective parent H630 and H35 cell lines. Polysome analysis revealed that the p53 mRNA was associated with higher-molecular-weight polysomes in H35 cells compared to H35(F/F) cells. While the level of p53 mRNA expression was identical in parent and TS-overexpressing cell lines, the level of p53 RNA bound to TS in the form of RNP complexes was significantly higher in TS-overexpressing cells. The effect of TS on p53 expression was also investigated with human colon cancer RKO cells by use of a tetracycline-inducible system. Treatment of RKO cells with a tetracycline derivative, doxycycline, resulted in 15-fold-induced expression of TS protein and nearly complete suppression of p53 protein expression. However, p53 mRNA levels were identical in transfected RKO cells in the absence and presence of doxycycline. Taken together, these findings suggest that TS regulates the expression of p53 at the translational level. This study identifies a novel pathway for regulating p53 gene expression and expands current understanding of the potential role of TS as a regulator of cellular gene expression.

Animals↗
PubMed1999

Exogenous calmodulin potentiates vasodilation elicited by phospholipid-associated VIP in vivo.

The purpose of this study was to determine whether exogenous calmodulin potentiates vasoactive intestinal peptide (VIP)-induced vasodilation in vivo and, if so, whether this response is amplified by association of VIP with sterically stabilized liposomes. Using intravital microscopy, we found that calmodulin suffused together with aqueous and liposomal VIP did not potentiate vasodilation elicited by VIP in the in situ hamster cheek pouch. However, preincubation of calmodulin with liposomal, but not aqueous, VIP for 1 and 2 h and overnight at 4 degrees C before suffusion significantly potentiated vasodilation (P < 0.05). Calmodulin-induced responses were significantly attenuated by calmidazolium, trifluoperazine, and NG-nitro-L-arginine methyl ester (L-NAME) but not D-NAME. The effects of L-NAME were reversed by L- but not D-arginine. Indomethacin had no significant effects on calmodulin-induced responses. Calmodulin had no significant effects on adenosine-, isoproterenol-, acetylcholine-, and calcium ionophore A-23187-induced vasodilation. Collectively, these data indicate that exogenous calmodulin amplifies vasodilation elicited by phospholipid-associated, but not aqueous, VIP in the in situ peripheral microcirculation in a specific, calmodulin active sites-, and nitric oxide-dependent fashion. We suggest that extracellular calmodulin, phospholipids, and VIP form a novel functionally coordinated class of endogenous vasodilators.

Acetylcholine↗
PubMed1999

Effects of cyclosporin A and dinactin on T-cell proliferation, interleukin-5 production, and murine pulmonary inflammation.

We compared the effects of cyclosporin A (CSA) and a macrotetrolide antibiotic, dinactin, on human T-cell proliferation and cytokine production induced by stimulation of the T-cell receptor alone (monoclonal antibody [mAb] directed against CD3) or in combination with costimulatory signals (mAbs directed against CD3 and CD28). These agents were also examined in a murine model of interleukin (IL)-5-mediated pulmonary inflammation. Dinactin inhibited T-cell proliferation induced by IL-2, by mAb to CD3, and by mAbs to CD3 plus alpha-CD28 with identical dose-response curves (IC50 = 10-20 ng/ml). Dinactin inhibited cytokine production with IC50 values of 10 ng/ml for IL-4 and IL-5 and 30 or 60 ng/ml for interferon-gamma or IL-2, respectively. Unlike CSA, exogenous IL-2 did not alter the dinactin-mediated effects on T cells, and nuclear run-on and steady-state messenger RNA (mRNA) analysis showed that dinactin inhibited cytokine production through a post-transcriptional mechanism. CSA selectively blocked T-cell receptor-induced T-cell proliferation and cytokine production (IC50 = 10 ng/ml). Under costimulatory conditions, IL-5 synthesis was only minimally inhibited by high concentrations of CSA, and at CSA concentrations of less than 125 ng/ml, IL-5 was significantly increased above control values. Dinactin and CSA reduced pulmonary eosinophilia when administered within 1 d of airway antigen challenge. Of the cytokine mRNAs examined in the lungs of CSA-pretreated, antigen-challenged mice, IL-5 mRNA levels were the least reduced, paralleling the resistance of IL-5 to CSA observed in vitro and suggesting a role for CD28 in the in vivo induction of IL-5.

Animals↗
PubMed1999

Neuropsychological functioning and MRI signal hyperintensities in geriatric depression.

OBJECTIVE: The purpose of this study was to examine the relationship between signal hyperintensities--a probable marker of underlying pathology--on T2-weighted magnetic resonance brain scans and neuropsychological test findings in elderly depressed and normal subjects. METHOD: Elderly subjects with a DSM-III-R diagnosis of major depression (N=41) and normal elderly comparison subjects (N=38) participated in a magnetic resonance imaging study (1.0-T) of signal hyperintensities in periventricular, deep white matter, and subcortical gray matter. Hard copies of scans were rated in random order by research psychiatrists blind to diagnosis; the modified Fazekas hyperintensity rating scale was used. Cognitive performance was independently assessed with a comprehensive neuropsychological battery. Clinical and demographic differences between groups were assessed by t tests and chi-square analysis. Relationships between neuropsychological performance and diagnosis and hyperintensities and their interaction were analyzed by using analysis of covariance, with adjustment for age and education. RESULTS: Elderly depressed subjects manifested poorer cognitive performance on several tests than normal comparison subjects. A significant interaction between hyperintensity location/severity and presence/absence of depression on cognitive performance was found: depressed patients with moderate-to-severe deep white matter hyperintensities demonstrated worse performance on general and delayed recall memory indices, executive functioning and language testing than depressed patients without such lesions and normal elderly subjects with or without deep white matter changes. CONCLUSIONS: Findings validate cognitive performance decrements in geriatric depression and suggest possible neuroanatomic vulnerabilities to developing particular neuropsychological dysfunction in depressed subjects.

Aged↗
PubMed1999

Developing algorithms to enhance the sensitivity of cancellation tests of visuospatial neglect.

We describe a set of algorithms that enhance the sensitivity of cancellation tests used in assessing visuospatial neglect. The algorithms can be readily implemented on a computer and can provide temporal and nontemporal data on strategies used during cancellation. We also present preliminary results from a group of 68 right-hemisphere brain-damaged patients and 12 age-matched control participants, which demonstrate the clinical significance of the measures we have defined.

Adult↗
PubMed1999

Increased acetylation of histones induced by diallyl disulfide and structurally related molecules.

In previous studies, diallyl disulfide induced differentiation in DS19 mouse erythroleukemic cells. A mechanism mediated by increased histone acetylation was investigated. Diallyl disulfide caused increased acetylation of H4 and H3 histones in DS19 cells and K562 human leukemic cells. Diallyl disulfide was more effective than diallyl monosulfide and diallyl sulfone. Acetylation was also induced in rat hepatoma and human breast cancer cells by diallyl disulfide or its metabolite, allyl mercaptan. Allyl mercaptan was a more potent inhibitor of histone deacetylase than diallyl disulfide. Differentiation in erythroleukemic cells by diallyl disulfide and allyl mercaptan may be mediated through induction of histone acetylation.

Acetylation↗
PubMed1999

The effect of iron on the toxigenicity of Vibrio cholerae.

In vitro and in vivo studies were conducted to assess the response of cholera toxin (CT) production to increasing iron concentrations in an aquatic environment. Production of CT by seven of eight Vibrio cholerae strains tested, including the Bengal strain (O139), was significantly enhanced in the presence of iron concentrations of 1.0 and 10 g/L. The exception (El Tor Ogawa) had a significant CT response only in the presence of 10 g of iron/L. Enhancement of CT production also occurred at iron concentrations less than 1.0 g/L, but not to a statistically significant degree. The high iron concentrations, which in this study were found to stimulate CT production, have been described by others in association with sediments, water plants, and chitinous fauna. Other investigators have shown a predilection by V. cholerae to attach to these sites in the aquatic environment. The importance of excess in vivo iron with respect to the pathogenicity of several gram-negative bacilli is well recognized. However, the possible impact of environmental iron on the in vitro toxigenicity of a microorganism, in this case V. cholerae in its aquatic environment, is to the best of our knowledge a new finding with important epidemiologic implications. These findings, coupled with the fact that iron concentration is considerably enhanced in industrially polluted waters and sediments, may reflect a causal link between the concurrent global upsurge of industrialization and pandemic occurrence of cholera during the latter half of the 20th century. Enhanced toxigenicity may also cause clinical disease following ingestion of lower than usual infective doses of cholera vibrios, thereby increasing the incidence of symptomatic cases and, possibly, of severe cases.

Animals↗
PubMed1999

Radiation dosimetry of a 99mTc-labeled IgM murine antibody to CD15 antigens on human granulocytes.

UNLABELLED: 99mTc-labeled anti-stage specific embryonic antigen-1 (anti-SSEA-1) is an injectable IgM antibody derived from mice. It binds to CD15 antigens on some granulocytic subpopulations of human white blood cells in vivo after systemic administration. The purpose of this study was to measure biodistribution of 99mTc-labeled anti-SSEA-1 and perform radiation dosimetry in 10 healthy human volunteers. METHODS: Transmission scans and whole-body images were acquired sequentially on a dual-head camera for 32 h after the intravenous administration of about 370 MBq (10.0 mCi) of the radiopharmaceutical. Renal excretion fractions were measured from 10 to 14 discrete urine specimens voided over 27.9 +/- 2.0 h. Multiexponential functions were fit iteratively to the time-activity curves for 17 regions of interest using a nonlinear least squares regression algorithm. The curves were integrated numerically to yield source organ residence times. Gender-specific radiation doses were then estimated individually for each subject, using the MIRD technique, before any results were averaged. RESULTS: Quantification showed that the kidneys excreted 39.5% +/- 6.5% of the administered dose during the first 24 h after administration. Image analysis showed that 10%-14% of the radioactivity went to the spleen, while more than 40% went to the liver. Residence times were longest in the liver (3.37 h), followed by the bone marrow (1.09 h), kidneys (0.84 h) and the spleen (0.65 h). The dose-limiting organ in both men and women was the spleen, which received an average of 0.062 mGy/MBq (0.23 rad/mCi, range 0.08-0.30 rad/mCi), followed by the kidneys (0.051 mGy/MBq), liver (0.048 mGy/MBq) and urinary bladder (0.032 mGy/MBq). The effective dose equivalent was 0.018 mSv/MBq (0.068 rem/mCi). CONCLUSION: The findings suggest that the radiation dosimetry profile for this new infection imaging agent is highly favorable.

Adult↗
PubMed1999

Semantic processing deficits in patients with Parkinson's disease: degraded representation or defective retrieval?

OBJECTIVE: To determine whether degraded representations (characterized by small differences between word sense frequencies), or defective competitive processes (high levels of word sense lateral inhibition), individually or jointly, can give rise to parkinsonian semantic deficits. DESIGN: Computer model of semantic processing. OUTCOME MEASURES: Correct sense selection, defined by the activation of the word sense unit that first reaches the 0.5 activation threshold. If Parkinson disease (PD)-like errors are observed only at high levels of lateral inhibition, independently of low or high sense frequency deltas (SFDs), this would indicate that a defective competitive process alone could account for the errors. Alternatively, if PD-like errors were observed at any level of lateral inhibition, exclusively with low SFD words, this would indicate that degraded representations alone could account for the errors. RESULTS: Neither degraded representations nor defective competitive processes alone can account for parkinsonian semantic errors. An interaction between the 2, however, correctly reproduces both increased errors and longer latency responses. CONCLUSIONS: Competing explanations for semantic deficits in patients with Parkinson's disease need to be integrated in order to develop effective interventions (e.g., estimating the amount of context required to improve semantic processing performance).

Humans↗
PubMed1999

Effects of a 99mTc-labeled murine immunoglobulin M antibody to CD15 antigens on human granulocyte membranes in healthy volunteers.

UNLABELLED: An injectible, 99mTc-labeled, murine immunoglobulin M antibody to stage-specific embryonic antigen-1 has been developed that can localize infections by binding to CD15 glycoproteins expressed on the cell membranes of human granulocytes in vivo after systemic administration. The purpose of this study was to measure its clinical effects on healthy people. METHODS: Multiple blood samples were aspirated before and after the intravenous administration of about 125 microg antibody labeled with approximately 370 MBq (10.0 mCi) 99mTc in 10 healthy human volunteers. Complete blood cell counts were performed at each time point. Whole-body scans were acquired contemporaneously with a dual-head gamma camera. The fraction of the administered dose at each time point was quantified in 18 regions of interest. Statistical analyses included paired t tests. RESULTS: Administration was associated with a transient decrease in the concentration of red and white blood cells in the whole blood. The effect always began within 3 min of administration. Its nadir was always reached 15-20 min after administration. There was full recovery with mild overcompensation in about an hour. The hematocrit dropped by a mean of 3.8% (P<0.002), whereas the total white blood cell count fell 44.0%+/-3.1% (P<0.001). The effect was most pronounced on the number of circulating granulocytes, which fell from 5.7+/-2.1 to 3.2+/-1.3x10(3)/microL blood. The drop paralleled a decrease in the percentage of whole blood radioactivity bound to the white blood cell membranes, which peaked at 50.4%+/-7.6% at 3 min after injection and then fell to 26.1%+/-9.3% over the next 30+/-13.4 min before recovering to 40.7%+/-8.2% at 2 h. Image analysis showed that the effect was temporally associated with an increase in the amount of radioactivity within the liver and the spleen. Recovery was associated with a decrease in hepatosplenic radioactivity. No evidence of cell destruction or agglutination could be detected. CONCLUSION: This study confirmed that administration of this radiolabeled antibody is associated with a transient decrease in the number of circulating granulocytes. However, there also seems to be a secondary hemodilutionlike effect on all blood components that has not been reported previously. The effect appears to be clinically silent and very short-lived.

Adult↗
PubMed1999

Pregnancy- and lactation-related folate deficiency in South Africa--a case for folate food fortification.

OBJECTIVE: Characterisation of patients presenting with megaloblastic anaemia according to clinical, sociological, haematological and aetiological aspects of their disease, and use of these findings to increase awareness among clinicians and to make recommendations regarding changes in national health policy. METHODS: This study included 104 patients presenting with megaloblastic anaemia to a large referral hospital over a 1-year period. Data were collected and analysed in terms of age, gender, parity, gravidity, duration of lactation, socio-economic status, geographical origins, diet, previous haematinic treatment, clinical presentation and haematological measurements. RESULTS: The most common cause of megaloblastic anaemia was pernicious anaemia or probable pernicious anaemia (50%), followed by pregnancy- and lactation-related folate deficiency (32%); of these patients, the majority (28) presented postpartum while lactating; 5 patients were in the immediate puerperal period of 6 weeks, and a further 16 were seen during the first year and 7 during the second year following delivery. Only 4 patients were pregnant, and it is noteworthy that 2 of these were still lactating at 34 weeks' gestation. CONCLUSION: Pregnancy- and lactation-related folate deficiency up to 2 years after delivery remains a common cause of megaloblastic anaemia in South Africa. Certain communities in rural South Africa have recently been shown to have high incidences of both neural tube defects and folate deficiency. The fortification of a staple food (e.g. maize or flour) with folic acid is feasible, inexpensive, safe and likely to be beneficial. This practice should reduce the prevalences of megaloblastic anaemia in fertile women, neural tube defects, other congenital abnormalities, intra-uterine growth retardation, prematurity and possibly cardiovascular disease. There is urgent need for a national policy in this regard.

Adolescent↗