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Biomedical subjects

S R Khan

Publications and source records attributed to S R Khan.

At least 73 records · Page 4Linked to original sources
PubMed1995

Deposition of calcium phosphate and calcium oxalate crystals in the kidneys.

Calcium phosphate (CaP) and calcium oxalate (CaOx) are the two most common crystalline constituents of human urinary stones. Calcium phosphate is often recognized as the nucleator of CaOx crystals, but the relationship between the two is not yet clearly understood. Using rat models of nephrolithiasis, we studied the role of CaP in renal deposition of CaOx. Calcium oxalate nephrolithiasis was brought about by inducing hyperoxaluria, while CaP CaOx nephrolithiasis was produced by dietary manipulation. Under similar urinary CaOx or CaP supersaturations, male rats were prone to form CaOx deposits while female rats were susceptible to produce CaP deposits in their kidneys. Crystal deposition in females was generally localized to the corticomedullary junction and in males to the renal papillae. The results indicate that gender plays an important role in the type and location of crystal deposition in the kidneys. In addition, deposition of CaP does not appear to influence the deposition of CaOx.

Animals↗
PubMed1995

Experimental calcium oxalate nephrolithiasis and the formation of human urinary stones.

Calcium oxalate nephrolithiasis in rats requires induction of hyperoxaluria which results in increased urinary calcium oxalate supersaturation. As a result of low to mild chronic hyperoxaluria, calcium oxalate crystals deposit first in the papillary collecting ducts. Crystal deposition in the kidneys is preceded by calcium oxalate crystalluria and starts with the retention of aggregated calcium oxalate crystals in the renal tubules. Retained crystals move from the tubules to the interstitium, and in the process, become anchored to the tubular basement membrane. Crystal aggregates present in the superficial peripheral collecting ducts of the renal papillae ulcerate through to the papillary surface and grow into the stones.

Animals↗
PubMed1995

Alterations in MDCK and LLC-PK1 cells exposed to oxalate and calcium oxalate monohydrate crystals.

Structural analysis of human kidney stones reveals the presence of cellular membranes and other cell fragments. Experimentally, calcium oxalate crystallization is facilitated when an exogenous nephrotoxin is given with ethylene glycol, thus providing cellular degradation products to act as heterogeneous nuclei. In this report, we tested whether oxalate alone could act as a cell toxin capable of producing damaged cells without the presence of an exogenous agent. Cultured LLC-PK1 and MDCK cells, when exposed to 1.0 mmol KOx, a concentration at the limit of metastability for calcium oxalate nucleation, were severely damaged as measured by specific lactate dehydrogenase (LDH) release in the spent media and by trypan blue exclusion. This effect was magnified by the addition of pre-formed calcium oxalate monohydrate crystals; the injury was significantly amplified when compared to exposure to oxalate alone. Scanning electron microscopy studies illustrated attachment of crystals to cells with loss of cell-to-cell and cell-to-substrate contact, as cells were released from the monolayer. In both oxalate and combined crystal-oxalate studies, more cells were released from the monolayer and exhibited considerably more damage when compared to controls. Oxalate, at the limit of metastability for calcium oxalate, is a cell toxin and can produce cellular degradation products. This effect is increased significantly by the addition of calcium oxalate monohydrate crystals.

Animals↗
PubMed1995

Heterogeneous nucleation of calcium oxalate crystals in mammalian urine.

It is generally recognized that calcium oxalate crystal formation in urine is induced by heterogeneous nucleation. However, there is no consensus as to the nature of the nucleation substrate. Evidence is provided in this paper that membranous cellular degradation products are the most likely candidates because they: (1) are ubiquitous in urine and urinary stones; (2) are found in close association with crystal deposits in the kidneys; and (3) can induce nucleation of crystals from a metastable solution of calcium oxalate in vitro and metastable urine in vivo.

Animals↗
PubMed1994

Madin-Darby canine kidney cells are injured by exposure to oxalate and to calcium oxalate crystals.

The reaction of Madin-Darby canine kidney cells (MDCK) to potassium oxalate (KOx), calcium oxalate monohydrate (COM) crystals, or a combination of the two was studied. The most noticeable effect of exposure of the cells to either KOx or COM crystals was loss of cells from the monolayer ranging from 20% to 30%, depending upon the particular treatment. Cellular enzyme values in the media were elevated significantly by 12 h of exposure, although in specific instances, elevated levels occurred at earlier time periods. As regards the monolayer, trypan blue exclusion was decreased significantly, although amounting to only a 4-5% reduction. Specific tritiated release occurred at 4 and 12 h after exposure to KOx and at 12 h after exposure to crystals. Structurally, COM-cell interactions were complex and extensive endocytosis was noted. Cells were released from culture either as cell-crystal complexes or from the intercellular spaces after exocytosis. When treatments were combined the effects were only slightly additive, but the two treatments potentiated each other: all media enzyme levels (with one exception) were elevated at 2 h, tritiated adenine release was present at 4 h, and there was more extensive cell loss from the culture monolayer. These data suggest that both KOx and COM crystals damage MDCK cells when applied alone, and in concert they act synergistically.

Adenine↗
PubMed1994

Calcium oxalate nephrolithiasis, a free or fixed particle disease.

The chances of stone formation occurring through a free particle mechanism were calculated using the approach of Finlayson and Reid [1]. For these calculations we used new data on nephron dimensions, supersaturation and crystal growth rates in urine, and also incorporated the size increasing effect of crystal agglomeration. The calculations were performed assuming different levels of oxalate excretion, simulating the diurnal variation and acute hyperoxaluria following a dietary load. In addition urinary flow conditions were varied according to changes in daily urinary volume. It is shown that during the normal transit time of urine through the nephron, particles can obtain a size big enough to be retained in the nephron. This is mainly due to the size-increasing effect of the agglomeration process. The precipitable amount of oxalate present is not limiting for the maximum attainable particle size. However, acute increases in oxalate excretion do pose a risk because supersaturation is reached earlier in the nephron and consequently the crystal particles are allowed more time to increase in size. In conclusion, the present calculations demonstrate that during the normal transit time through the kidney, crystalline particles can be formed which are large enough to be retained because of their size and thus form the nidus of a stone. The highest risk is encountered at the end of those collecting ducts where crystals formed in nephrons with a long loop of Henle meet and agglomerate.

Animals↗
PubMed1993

Role of organic matrix in urinary stone formation: an ultrastructural study of crystal matrix interface of calcium oxalate monohydrate stones.

Human calcium oxalate monohydrate (COM) urinary stones were decalcified by treatment with a mixture of ethylenediaminetetraacetic acid (EDTA) solution and Karnovsky's fixative after embedding in bactoagar. Decalcified stones were examined by light microscopy, and also by scanning and transmission electron microscopy. Stones had distinct nuclei that were occupied by amorphous or apatitic calcium phosphate or aggregates of spherulitic COM crystals. EDTA insoluble matrix was ubiquitous in stones and consisted largely of finely matted fibrous material. It was organized in concentric laminations in the peripheral area of the stone but appeared highly disorganized in the stone center. Crystals were replaced by crystal ghosts. Organic matrix was present both inside the crystals and in the intercrystalline spaces. The study indicates a very close association between crystals and organic matrix. The relationship appears to begin early in crystal formation and persists throughout the formative and growth phases of the urinary stones.

Calcium Oxalate↗
PubMed1993

Magnesium oxide administration and prevention of calcium oxalate nephrolithiasis.

We studied the effect of oral administration of magnesium oxide (MgO) on calcium oxalate (CaOx) nephrolithiasis in rats. Nephrolithiasis was induced by administration of 1.0% ethylene glycol (EG) in drinking water. Magnesium oxide was given mixed with food at 500 mg./100 g. rat chow. Dispensation of MgO resulted in a significant increase of urinary pH and a modest increase in urinary excretion of citrate. Urinary excretion of oxalate started to decline by day 14 and was significantly reduced on days 21 and 28. All rats receiving EG displayed crystalluria. From the group receiving EG only, 3 of 4 rats sacrificed on day 15 and 2 of 4 rats sacrificed on day 29 had CaOx crystal deposits in their kidneys. None of the 8 rats who received both EG and MgO had CaOx nephrolithiasis. Thus our findings indicate that dispensation of magnesium as MgO can be beneficial against calcium oxalate nephrolithiasis.

Animals↗
PubMed1993

Early child health in Lahore, Pakistan: I. Study design.

In this paper, details are given of a community based follow up study of four areas: a village, a periurban slum, an urban slum and an upper middle class control group living in and around Lahore, Pakistan. The aim was to characterize the determinants of child health in a rapidly urbanizing community. The study was undertaken in two steps. An initial cross-sectional survey collecting socio-economic and demographic background information was carried out between March to August 1984. This was followed by a longitudinal study of 1476 infants representing the outcome of the pregnancies registered continuously between September 1984 to March 1987 among the 3242 families in the study. These infants were followed monthly from birth to 3 years of age and thereafter less frequently. In this communication we describe the study design, the study population, the organization and the research methodology used, including the reasons for drop outs from birth to 24 months of age. The internal consistency of the data is also presented. After the initial examination of the newborns within between 0-7 days of birth, the infants were visited monthly for 24 months making a total of 20911 examinations. At 24 months of age 70% of the infants were still in the study, 11% had died before reaching this age, 13% had moved from the area and 6% had refused to participate in the study. The economic, conditions, social structure, and the quality of life were found, not surprisingly, to vary significantly among the four areas. This community-based project provides new, critical and reliable information for local health planners. The study highlights the importance of the development of a useful model for research collaboration between institutions in developed and developing countries.

Child Welfare↗
PubMed1993

Early child health in Lahore, Pakistan: V. Feeding patterns.

The feeding practices of children (n = 1476) from birth to 24 months, as determined in a longitudinal study, in Lahore, Pakistan, are presented. Four socioeconomic groups at various levels of urbanization were included; a village, periurban slum, urban slum and an upper middle class. Initiation of breastfeeding was delayed in all the neonates. Sixty-five percent of the periurban slum mothers and 45% of the village mothers had not started breastfeeding at 48 hours after the birth of the infant. Prelacteal feedings, especially of herb water and honey, were the norm. Breastfeeding was highly prevalent. Eighty-seven to 98% of the infants in all the areas were breastfed at one month of age. Exclusive breastfeeding was rare, with 9% at one month, declining rapidly with age and being highly influenced by season. Partial breastfeeding was the most common mode of feeding. Water in addition to human milk was given by 45-73% of the mothers living in the urban slum, village and periurban slum at one month of age. Fresh animal milk and/or commercial formula was already being given at 1 month by 22-64% of the mothers in all areas. Commercial formula was the preferred food in the upper middle class, while in the other three areas it was rare and fresh animal milk was mainly used. More than 50% of the mothers in the village and in the periurban slum gave diluted animal milk even beyond the age of 10-15 months. In the upper middle class 50% of the infants were fed semisolids at the age of four months, while in the village, the periurban and the urban slum at 6 months of age only 10%, 12% and 47% of the infants received semisolids. The results of this study indicate that breastfeeding was highly prevalent in the three poorest areas. However, in all the areas initiation of breastfeeding was delayed and prelacteal feeding was the norm. Exclusive breastfeeding was rare, feeding bottles were used by 82-100% of the mothers to feed supplements and human milk substitutes, in the four areas.

Breast Feeding↗
PubMed1993

Early child health in Lahore, Pakistan: VIII. Microbiology.

The causative agents of acute diarrhoea were investigated in children under the age of five years from 1985-1991 in three socio-economically different areas in Lahore, Pakistan. The aim was to determine the frequencies of the most common enteropathogens in faeces. The total isolation rate was 73.4%; two thirds (53.5%) were of bacterial and one third (19.9%) of viral origin. ETEC-LT (23.4%), Rota virus (19.9%), EPEC (15%) and Campylobacter (12%) were the single most frequent pathogens in all age groups and areas of living. The positivity of Campylobacter increased from 1.6% to 12% after the change of isolation technique. Shigella was isolated significantly (p > 0.001) more in children over than under one year of age. The incidence of bacterial infections was high during all seasons, while in certain years Rota virus was relatively low in the summer compared to the cooler months. The prevalence of ETEC-LT diarrhoea was higher in the periurban slum as compared to the village and the urban slum. The study is the first of its kind in Pakistan, and the results are similar to other comparable studies. It is thus possible to establish a well functioning and reliable microbiological laboratory in developing countries in a setting with restricted trained personnel and material resources.

Age Factors↗
PubMed1993

Early child health in Lahore, Pakistan: IX. Perinatal events.

In Pakistan there are a number of acute problems related to maternal and infant health in the perinatal period. There is also lack of reliable data needed for the formulation of action strategies. To provide a database 1490 women have been followed from the 5th month of pregnancy in four different areas at various levels of urbanization and socio-economic development. After adjusting for gestational age, the proportion of newborns with weight for length < -2SDS in relation to the Swedish National Standard was 12-31% for boys and 12-25% for girls, the figure being highest in the most deprived area. Preterm birth was infrequent compared with IUGR. The overall prevalence rate of birth defects was 21% out of which 8% were severe defects. The overall perinatal mortality rate was 56/1000 births, with rates of 60, 75, 36 and 33/1000 births for the village, periurban slum, urban slum and the upper middle class. Two thirds of the deaths were related to either a continuation of intrauterine disturbances or severe congenital defects incompatible with life. One third of the deaths were due to infection; mostly diarrhoea, clinical sepsis and ARI. Neonatal mortality was significantly related to birth length (< -2SDS, odds ratio 5.5) and length of gestation (< 37 weeks, odds ratio 5.6) and was to a lesser extent related to weight (< -2SDS, odds ratio 2.0) and weight for length (< -2SDS, odds ratio 1.3). Forty percent of the mothers had weight for height below -2SDS, 23-35% had height < -2SDS. Forty percent of mothers from a subset within the cohort had a hemoglobin < 10 gm/dl and 20% showed signs of pre-eclampsia. This presentation raises the issue of expanding the current Child Survival Programs into the perinatal period as well.

Adolescent↗
PubMed1993

Early child health in Lahore, Pakistan: X. Mortality.

Mortality during the first two years of life among 1476 Pakistani infants born between September 1984 and March 1987 is described according to age, causes of death, area of living, season of the year and sex. The mortality rate (deaths under two years/1000 live births) projected over the whole population of Pakistan was 127 and under one year 114. During the first two years of life, the mortality rate was 133/1000 in the village, 159 in the periurban slum, 107 in the urban slum and 17 in the upper middle class group. In the latter group all deaths had occurred within 72 hours after birth. The overall major causes of death were acute and prolonged diarrhoea (36%), asphyxia neonatorum (13%), respiratory infections (13%), septicaemia (11%) and tetanus (9%). A clear age dependency was noted with 14% of deaths occurring during the first 24 hours of life (asphyxia neonatorum in 86%), and 57% dying within the first 28 days of life. In the later age groups, infections were mainly responsible for 82% of total deaths. Early mortality was therefore extremely high in the poorer areas studied and the cause of death was highly age dependent. Any interventions for reducing mortality must therefore be directed towards better antenatal care and safe delivery and postnatally, towards preventing infections, especially during the first six months of life.

Age Factors↗
PubMed1992

Acute hyperoxaluria, renal injury and calcium oxalate urolithiasis.

Single intraperitoneal injections of three, seven, or 10 mg. of sodium oxalate per 100 gm. of rat body weight were administered to male Sprague-Dawley rats. At various times after the injection, urine samples were analyzed for oxalate, and urinary enzymes, alkaline phosphatase, leucine aminopeptidase, gamma-glutamyl transpeptidase, and N-acetyl-beta-glucosaminidase. The kidneys were processed for light microscopy and renal calcium and oxalate determination. Oxalate administration resulted in an increase in urinary oxalate and formation of calcium oxalate crystals in the kidneys. The amount and duration of urinary excretion of excess oxalate and retention of crystals in the kidneys correlated with the dose of sodium oxalate administered. At a low oxalate dose of three mg./100 gm., crystals moved rapidly down the nephron and cleared the kidneys. At higher doses crystals were retained in kidneys and at a dose of 10 mg./100 gm. were still there seven days post-injection. Crystal retention was associated with enhanced excretion of urinary enzymes indicating renal tubular epithelial injury.

Acute Disease↗
PubMed1992

Structure of rat kidneys following microwave accelerated fixation.

In contrast to fixation of tissue in externally heated fixative, microwave-irradiation can generate uniform internal heat, which is of utmost importance for successful fixation of biological tissue. To evaluate the effectiveness of microwave-accelerated chemical fixation, we compared the structure of rat kidney fixed by a conventional method and a microwave-accelerated method, by scanning and transmission electron microscopy. Following perfusion, rat kidney pieces 1-2 mm in size were irradiated in Karnovsky's fixative in a domestic Amana microwave oven, till the temperature of the fixative reached 45-50 degrees C. For conventional fixation, tissue pieces were fixed overnight at room temperature in the same fixative. Both types of samples were processed further for electron microscopy using identical protocols. The microwave fixed samples showed excellent preservation of structure comparable to the samples fixed by the conventional method. Glomeruli and the renal tubules showed normal morphology with no cellular swelling. The cytoplasm and nuclear matrix of the epithelial cells was uniformly dense. Other fixation sensitive organelles like mitochondria and Golgi apparatus showed superior preservation with continuous membranes. These results demonstrate that microwave accelerated chemical fixation results in excellent preservation of tissue structure, reduces processing time significantly and is therefore a practical alternative to conventional protocols.

Animals↗
PubMed1991

Effect of magnesium on calcium oxalate urolithiasis.

Previous studies have shown that hypomagnesuria induced by magnesium deficient diet causes calcium oxalate crystal deposition in renal tubules of hyperoxaluric rats and administration of magnesium to these rats results in prevention of calcium oxalate crystallization in their kidneys. Based on these studies magnesium was claimed to be beneficial for calcium oxalate stone patients. However, hypomagnesuria is not a common phenomenon. To better understand the role of magnesium as an inhibitor of calcium oxalate crystallization in urine, we studied the effect of magnesium on calcium oxalate urolithiasis in rats on a regular diet and a hyperoxaluric protocol. Excess magnesium was administered to male rats on regular diet and a lithogenic protocol. Magnesium administration to hyperoxaluric rats did not result in significant changes in urinary excretion of calcium or oxalate or in calcium oxalate relative supersaturation. Urinary excretion of citrate was also not significantly altered. Some animals from both groups, those on magnesium therapy and those not on magnesium therapy had crystals deposited in their renal tubules. We conclude that excess magnesium has no significant effect on calcium oxalate urolithiasis in normomagnesuric conditions.

Animals↗