Biomedical subjects

N Aslam

Publications and source records attributed to N Aslam.

32 records · Page 2Linked to original sources

PubMed1999

The expectant management of women with early pregnancy of unknown location.

OBJECTIVE: To assess the results of expectant management in women with pregnancy of unknown location and to identify diagnostic parameters that are predictive of spontaneous pregnancy resolution. DESIGN: Prospective, observational study. SUBJECTS: Women with a positive pregnancy test and suspected early pregnancy complications who were referred for ultrasound assessment. METHODS: Women were first examined by transvaginal ultrasound to establish the location and viability of pregnancy. All women with pregnancies that could not be located on the scan had a blood sample taken to quantify the serum human chorionic gonadotropin (hCG) and progesterone levels. Management was expectant until the pregnancy was identified, the condition resolved spontaneously or an intervention was required because clinical symptoms deteriorated or hCG levels did not decline. For each woman, age, clinical symptoms (pain and bleeding), menstrual dates, past gynecological history, endometrial thickness and levels of serum hCG and progesterone were recorded. All parameters were tested by univariate analysis and then analyzed in a stepwise procedure to form a logistic regression model for predicting spontaneous resolution of pregnancy. RESULTS: A total of 1625 women were included in the study. In 135 cases (8%) the location of pregnancy was unknown. Complete data sets were obtained in 127 cases. These included 34 (27%) normal intrauterine pregnancies, 11 (9%) miscarriages and 18 (14%) ectopic pregnancies. A total of 64 (50%) pregnancies resolved spontaneously. Stepwise analysis showed that four diagnostic parameters--vaginal bleeding, endometrial thickness, serum hCG level and progesterone level--contributed significantly to the predictive power of the logistic model. With the use of this model, spontaneous pregnancy resolution could be predicted at the initial visit with a sensitivity and specificity of 92%. CONCLUSIONS: The majority of pregnancies of unknown location are abnormal: many resolve spontaneously when managed expectantly. A logistic model may be used at the initial visit to identify those cases in which the pregnancy is likely to resolve without the need for intervention.

Adult↗

PubMed1999

Diurnal variation in uterine artery blood flow in post-menopausal women on oestrogen hormone replacement therapy.

Doppler ultrasound was used to investigate circadian variations in uterine artery blood flow in 20 post-menopausal women in the oestrogen-only phase of combined oestrogen hormone replacement therapy with cyclical oral norethisterone or dydrogesterone. All women were examined between 0800 and 0830 h and then again between 1800 and 1830 h on the same day. Mean arterial blood pressure, heart rate and a blood sample for measurement of serum oestradiol were taken at each visit. Indices of uterine artery blood flow included the pulsatility index, resistance index, peak systolic velocity and time-averaged maximum velocity. No significant differences in the mean arterial blood pressure, pulse rate and oestradiol concentrations were detected between morning and evening visits. Significant fluctuation was observed in the pulsatility index (P < 0. 001), resistance index (P < 0.001) and time-averaged maximum velocity (P < 0.01). The assessment of uterine artery blood flow in post-menopausal women should take into account the presence of circadian variations to ensure accuracy and reproducibility of Doppler investigations.

Arteries↗

PubMed1998

Directing differentiation in Theileria annulata: old methods and new possibilities for control of apicomplexan parasites.

Apicomplexan parasites are major pathogens of humans and domesticated animals. The ability of these organisms to evade the host immune response and the emergence of drug-resistant parasites indicates a need for the identification of novel control strategies. Ideally, selected targets should be shared by a range of apicomplexans and fundamental to parasite biology. One process of apicomplexan biology which may provide this type of target is the molecular regulation of stage differentiation. This paper has reviewed studies carried out on differentiation of Theileria annulata and has highlighted general similarities with other apicomplexan differentiation steps. Similarities include asynchrony of differentiation, the loss (attenuation) of differentiation potential and an association between reduced proliferation and differentiation. In addition, novel data are presented assessing a possible role for a signal transduction mechanism or a direct involvement of classical heat-shock polypeptides in regulating differentiation of T. annulata in vitro. These studies, and previously published data, have led to the postulation that progression to the next stage of the life-cycle can be predetermined and involves the attainment of a quantitative threshold by regulators of gene expression. A modification of this model takes into account that for certain in-vitro systems, or differentiation steps in vivo, the process has to be initiated by alteration of the extracellular environment. Work which has shown that the time taken to achieve differentiation can be increased or decreased is also outlined. The ability to change the timing of differentiation suggests that the associated regulatory mechanism could be manipulated directly to significantly influence the outcome of an apicomplexan infection. The observation that a number of existing drugs and control strategies may exert their protective effect by altering differentiation potential supports this possibility.

Animals↗

PubMed1997

Modulation of protein synthesis relative to DNA synthesis alters the timing of differentiation in the protozoan parasite Theileria annulata.

The control of differentiation through time is critical for the correct ordering of sequential developmental events. A timing mechanism based on the number of mitotic divisions has been proposed for both higher eukaryote and protozoan parasite cellular differentiation. However, the mitotic clock model has not been validated by experiments which altered the proliferation rate of cells in vitro. This study has used the drugs aphidicolin and oxytetracycline to investigate the modulation of differentiation in the protozoan parasite Theileria annulata. The results showed that the timing of macroschizont to merozoite differentiation correlated with expression levels of a merozoite surface antigen during the reversible phase of the differentiation process. In addition, analysis of the effect of the drugs and elevation of culture temperature indicated that altered timing of differentiation was associated with changes to the rate of protein synthesis relative to DNA synthesis. From these results we postulate that the differentiation clock runs on the basis of a progressive elevation of a regulator(s) of merozoite gene expression to a quantitative commitment threshold. We also propose that this mechanism of timing can be corrupted by modulation of the proliferation potential (DNA synthesis) and/or growth potential (factor production) of the cell. The relevance of this model to differentiation in vivo and to other eukaryotic systems is discussed.

Animals↗

PubMed1996

Inhibition of growth of Trypanosoma brucei parasites in chronic infections.

The growth of Trypanosoma brucei parasites in chronic infections was investigated by superimposing upon chronic infections, secondary infections in which all parasites expressed the same variable antigen type (VAT). The fate of trypanosomes in secondary infections could then be monitored using the VAT as a marker to discriminate cells in primary and secondary infections and thus enable growth to be observed separately from its interactions with antigenic variation on the part of the parasite and specific immune responses of the host. Our results show that as an infection proceeds, the growth rate is progressively inhibited in mice and sheep, suggesting that inhibition is a general feature of chronic infections. Inhibition was not specific to either the stock or the VAT of the trypanosome, but the degree of inhibition did vary between stocks. Inhibition appeared to be mediated by a lowering of the rate of replication of 'slender'-form parasites rather than by an increase in either the rate of differentiation from dividing slender to non-dividing 'stumpy' forms or the mortality caused by non-specific immune mechanisms. Evidence indicated that the development of specific immune responses to non-variant parasite antigens was also unlikely. These data constitute, we believe, the first evidence for negative regulation of growth in vivo, which may be an important determinant of the virulence of trypanosome infections.

Animals↗

PubMed1995

Replication, differentiation, growth and the virulence of Trypanosoma brucei infections.

This study had 2 objectives: first, to investigate how the processes of slender form replication, of differentiation from dividing slender to non-dividing stumpy forms, and of stumpy mortality, combine to determine the initial (acute-phase) growth rate of Trypanosoma brucei populations; second, to determine how acute-phase growth rates influence parasite densities during the subsequent, chronic phase of infection. During the acute phase, slender and stumpy populations both grew approximately exponentially, the latter more slowly than the former. Mathematical models showed how this difference in slender and stumpy growth rates can be explained in terms of heterogeneous replication and differentiation rates. Stumpy life-expectancy was determined for one stock and found to be age-dependent with a half-life of 48-72 h, much larger than observed population doubling times of 5-10 h. A comparison of cloned stocks showed that the highest parasite densities during the chronic phase were associated with the highest acute-phase growth rates of both the whole parasite population and of the subpopulation of slender forms. By contrast, high chronic-phase parasitaemias artificially produced following rapid syringe passage were associated with low acute-phase growth rates of slender forms. Syringe-passaging is a laboratory procedure which selects for virulent parasites, but these parasites behave differently from naturally virulent stocks.

Animals↗

PubMed1992

Mechanism of zinc uptake by microvilli isolated from human term placenta.

The mechanism of zinc (Zn) uptake by microvillous membrane vesicles prepared from human term placenta has been studied. The uptake was complex, with two processes being identified. In the first process, uptake was rapid, reaching equilibrium within 2 min, and was temperature dependent, with a Q10 of 1.5. Equilibrium Zn levels were sensitive to osmotic pressure, with Zn binding at infinite osmolarity being 69% iso-osmotic value. The uptake was saturable, with a Vmax of 58 +/- 2 nmol/mg protein/min and an apparent Kt of 128 +/- 13 microM. Uptake was inhibited by increasing extravesicular K+ concentration, dropping from 0.91 +/- 0.03 nmol/mg/min at 0 extravesicular K+ to 0.47 +/- 0.03 at an extravesicular K+ concentration of 150 mM ([Zn] = 1.0 microM). In the presence of both valinomycin, an electrogenic ionophore, and nigericin, an electroneutral exchanger, an outwardly directed K+ gradient stimulated Zn uptake. Similarly, preloading vesicles with Zn and imposing an inward gradient resulted in a temperature dependent efflux of Zn. The data suggest that there is a K+ dependent Zn transporter in vesicle membranes, and we suggest that the evidence is biased in favour of a Zn/K+ exchanger rather than Zn being dependent on the membrane potential.

Biological Transport↗

PubMed1992

The relationship of variable antigen expression and population growth rates in Trypanosoma brucei.

The relationship between variable antigen type (VAT) expression and trypanosome growth rates was investigated. Growth rates in mice were compared between pairs of cloned trypanosome populations, each of which homogeneously expressed a different VAT. All three pairwise combinations of GUTats (Glasgow University Trypanozoon antigen types) 7.3, 7.4 and 7.5 were analysed twice and all three combinations of GUTats 8.2, 8.3 and 8.4 were compared once. The lines expressing different VATs were of the same passage history within each group. In a sensitive assay of relative growth, no significant differences were found in four of six experiments using GUTats 7.3, 7.4 and 7.5 or in one of three experiments using GUTats 8.2, 8.3 and 8.4. In the experiments in which differences were observed, the data were analysed further to compare the population doubling times of lines. These times differed by less than 10% in all cases. We conclude that variable antigen expression exerts a small (possibly negligible) effect on rates of trypanosome population growth.

Animals↗

PubMed1992

Increased neuropeptide Y content in individual hypothalamic nuclei, but not neuropeptide Y mRNA, in diet-induced obesity in rats.

Neuropeptide Y (NPY) is the most powerful appetite stimulant known, and chronic administration leads to obesity. The hypothalamic content of NPY varies with nutritional status, suggesting that it is of physiological importance. We measured NPY in specific hypothalamic nuclei and NPY mRNA in the hypothalamus by Northern blotting in rats made obese by feeding a highly palatable diet compared with controls fed standard chow. In animals fed the palatable diet, NPY concentrations were increased in the paraventricular nucleus (mean +/- S.E.M.; 19.5 +/- 2.3 vs 11.1 +/- 1.1 fmol/micrograms protein, P less than 0.02), the arcuate nucleus (20.4 +/- 3.3 vs 9.3 +/- 0.6 fmol/micrograms protein, P less than 0.01), the medial preoptic area (9.1 +/- 0.9 vs 5.9 +/- 0.7 fmol/micrograms protein, P less than 0.02) and the anterior hypothalamus (2.7 +/- 0.2 vs 2.0 +/- 0.1 fmol/micrograms, P less than 0.02). Hypothalamic NPY mRNA measured by Northern blot analysis was, however, unchanged. These results suggest that the increase in NPY was due to decreased release rather than increased NPYergic activity. The findings are in accord with the neuroendocrine disturbance and increased thermogenesis observed in this model of obesity.

Animals↗

PubMed1991

The effects of genetic exchange on variable antigen expression in Trypanosoma brucei.

The inheritance of variant surface antigens in Trypanosoma brucei has been determined by identifying variable antigen types (VATs) in each of two cloned parental stocks and then examining the presence and abundance of these VATs in hybrid progeny produced when these stocks undergo genetic exchange during co-transmission through tsetse flies. Nine VATs have been identified from the repertoire of the parental stock STIB 247L and 5 VATs have been identified from the parental stock STIB 386AA; the identified VATs were exclusive to each stock. Their inheritance was elucidated using two assays. In the first, repertoire antisera (RAS) containing antibody specificities to many different VATs were raised in rabbits to the 2 parental stocks and 6 progeny clones. The presence of VAT-specific antibodies in these RAS was then determined by antibody-dependent complement-mediated lysis. In the second assay, the 2 parental stocks and 4 hybrid progeny clones were each independently transmitted through tsetse flies and VATs observed using VAT-specific antisera in indirect immunofluorescence of metacyclic trypanosomes and in bloodstream forms of fly-bitten mice. The results from both assays showed that (1) both metacyclic- and bloodstream-VATs were inherited into the progeny, (2) each hybrid progeny clone contained some VATs from both parents, (3) hybrids did not express all the VATs from either parent, (4) there was little apparent pattern as to which VATs had been inherited and which had not and (5) the VAT repertoires of the hybrid progeny appeared to be larger than those of the parents. In addition, two results indicated that control of VAT expression remains unaltered after genetic exchange.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMedDate not supplied

Malignant ascites: new concepts in pathophysiology, diagnosis, and management.

Malignant ascites is a manifestation of advanced malignant disease that is associated with significant morbidity. Mainstays of treatment include diuretics and recurrent large volume paracentesis. Although lymphatic obstruction has been considered the major pathophysiologic mechanism behind its formation, recent evidence suggests that immune modulators, vascular permeability factors, and metalloproteinases are contributing significantly to the process. These new observations offer the opportunity for development of new, more targeted therapies for the treatment of malignant ascites. This article uses a clinical case to highlight the problem, then reviews these new concepts in the pathophysiology of malignant ascites formation. The diagnosis and management of this challenging medical problem are subsequently discussed, with emphasis on how these new pathophysiologic insights are being applied to the development of novel therapies that may soon change how we manage this troubling clinical condition.

Ascites↗

PubMedDate not supplied

Peritoneal dialysis clearance can replace residual renal function.

OBJECTIVE: There is controversy whether increasing peritoneal clearance effectively substitutes for declining residual renal function. We studied the impact of renal and peritoneal clearances on outcome, controlling for comorbidity. DESIGN: Registry database. SETTINGS: Four dialysis centers. PATIENTS: Incident peritoneal dialysis patients. METHODS: Data were collected prospectively on 90 incident patients between 1991 and 1999. At the end of their first year on peritoneal dialysis, patients were divided into groups based on the first year's clearance results: group 1 (n = 62) had weekly Kt/W greater than or equal to 2.0 and creatinine clearance (CCr/1.73 m2) greater than or equal to 60 L throughout the first year; group 2 (n = 28) fell below these targets due to loss of residual renal function and then reached targets due to prescription change. MAIN OUTCOME MEASURES: Patient and technique survival. RESULTS: Both groups were similar in baseline characteristics except age (57 years vs 49 years, p = 0.02) and initial albumin (34.4 g/L vs 37.5 g/L, p = 0.001). One-year patient survival after grouping was similar in both groups (86.3% vs 80.9%, p = 0.72). Cox proportional hazard model, controlling for comorbidity, did not show "group" to be a significant predictor of outcome (p = 0.96). One-year technique survival after grouping was similar in both groups (77.3% vs 83.2%, log rank p = 0.89). For technique failure, Cox proportional hazard model showed peritonitis (p = 0.004) to be the only significant predictor of worse outcome. CONCLUSIONS: Peritoneal dialysis patients with improved clearances due to prescription changes had survival comparable to patients who never fell below target. This suggests that loss of residual renal function may be replaced by increasing peritoneal dialysis clearance. A large multicenter trial to study this important question further is needed.

Female↗

PubMedDate not supplied

The influence of demographic factors and modality on loss of residual renal function in incident peritoneal dialysis patients.

OBJECTIVE: To determine whether gender, race, diabetes, peritoneal dialysis (PD) modality, and comorbid conditions influence loss of residual renal function (RRF). DESIGN: Retrospective study of incident PD patients, using database of prospectively collected demographic, laboratory, and clearance data. SETTING: Peritoneal Dialysis Registry of the University of Pittsburgh Medical Center. PATIENTS: The study included 184 continuous ambulatory PD and automated PD patients who had at least two 24-hour urine collections for glomerular filtration rate (GRF) between April 1991 and March 2000. 836 urine collections were analyzed. OUTCOME MEASURES: Loss of RRF was defined as the slope of the decline in GFR as measured by the average of creatinine and urea clearances in 24-hour urine collections. Stepwise forward regression was used to identify demographic and laboratory factors associated with loss of GFR. Spearman correlations were used to assess the significance of associations. RESULTS: The median rate of decline of renal function was -0.17 mL/minute/month. Gender, race, diabetes, automated PD, peritoneal equilibration test, protein equivalent of nonprotein nitrogen appearance normalized to body surface area, and serum albumin did not predict loss of RRF. Cardiac disease was the only variable affecting decline of RRF (p = 0.045). CONCLUSION: Modality of PD and patient demographic factors do not contribute to the rate at which RRF is lost in incident PD patients. Additional study of the factors contributing to the decline and maintenance of RRF is needed.

Adult↗

PubMedDate not supplied

Should beta-blockers be withdrawn in post-myocardial infarction patients before treadmill test?

In most patients of myocardial infarction, beta-blockers are used for secondary prophylaxis and a treadmill test is required for risk stratification. To study the effect of oral beta-blockers on interpretation of treadmill test, 54 consecutive patients were subjected to treadmill test four to six weeks after myocardial infarction. Fourteen patients with strongly positive treadmill test were referred for coronary angiography. Treadmill test was repeated in 37 patients 72 hours after withdrawal of beta-blockers. The peak exercise heart rate was significantly different while off and on beta-blockers (148 +/- 13 bpm vs 124 +/- 14 bpm, respectively; p < 0.01). The test was negative on both the occasions in 17 patients. On stopping beta-blockers, the negative test became mildly positive in five and strongly positive in six patients. The mildly positive test became strongly positive in four patients and remained almost unchanged in five. In 10 patients there was conversion of negative or mildly positive treadmill test into strongly positive result after withdrawal of beta-blockers. Thus the risk stratification changed significantly in 27 percent patients. It is suggested that beta-blockers can and should be withdrawn in post-MI patients before doing treadmill test.

Administration, Oral↗