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Biomedical subjects

A S Patel

Publications and source records attributed to A S Patel.

At least 19 recordsLinked to original sources

Lipid adsorption onto hydrogel contact lens materials. Advantages of Nile red over oil red O in visualization of lipids.

An artificial tear solution containing the major types of proteins, glycoproteins, and lipids represented in human tears has been developed. The adsorption of lipids onto various hydrogel lens materials (polymacon, lidofilcon A, phemfilcon A, etafilcon A) was examined by exposing the lenses to our artificial tear solution for 18 h. The adsorbed lipids were detected using Nile red stain. The patterns of deposits obtained in vitro were similar to those obtained with human worn lenses. The Nile red stain appeared far more sensitive in detecting lipids adsorbed to hydrogel lenses than the oil red O stain. It was found that lipids adsorb to hydrogel materials quite readily either in a pure state or combined with mucin or other proteins. In view of this work more attention should be given to the role of lipids in the etiology of various contact lens wear complications.

Adsorption

Effect of proteins on water and transport properties of various hydrogel contact lens materials.

The effect of adsorbed substances on the properties of the water in various hydrogel contact lens materials was examined by exposing contact lenses (Hydron Zero 4, B&L 70, DuraSoft 3, Vistamarc, and Acuvue) to an artificial tear solution for various periods up to 14 days. The only materials affected were the high-water/ionic lenses which adsorbed a large amount of protein, predominantly lysozyme. In the DuraSoft 3 lenses the equilibrium water content (EWC) dropped from 49% to 46% and the freezing water from 28% to 21%. Similar changes were seen with the Vistamarc lenses. After a 10-day exposure of the Acuvue lens to artificial tears, the EWC decreased from 53% to 47% and the amount of freezing water from 33% to 23%. The decrease in the permeability of water seen with these materials was consistent with the decrease of the freezing water, i.e., the water able to participate in diffusion. Since the content of freezing water determines the transport through hydrogels it can be expected that any lens characteristics that depend upon the amount of this portion of water would be affected by the presence of proteins inside the polymer matrix. We extrapolated that an absolute change of 10% in the amount of freezing water could lead to a decrease in oxygen permeability of as much as 7 Dk units. In view of this work more attention should be given to changes in the properties of lenses during wear, in particular, in the high-water/ionic lenses.

Adsorption

Acute type A hepatitis presenting with hypotension, bradycardia, and sinus arrest.

The cardiovascular complications of viral hepatitis are not widely recognized. Profound hypotension and a variety of dysrhythmias, including sinus arrest, have been reported in association with viral hepatitis, but most of these cases were described before the advent of specific viral serologic markers. Furthermore, previous instances of cardiovascular complications occurred during the course of an established viral syndrome. We report the cases of two previously healthy women who presented with unexplained hypotension and bradycardia as the initial manifestations of acute icteric hepatitis A. This phenomenon appears to represent a variant clinical presentation of a common viral entity.

Acute Disease

At least two mutant alleles of ornithine delta-aminotransferase cause gyrate atrophy of the choroid and retina in Finns.

Gyrate atrophy of the choroid and retina (GA) is an inherited chorioretinal degeneration caused by deficiency of ornithine delta-aminotransferase (OAT; L-ornithine: 2-oxo-acid aminotransferase; EC 2.6.1.13). GA is one of the "Finnish genetic diseases," a group of several rare monogenic disorders that occur with increased frequency in the Finnish population. Using a combination of RNase A protection, genomic cloning, and polymerase chain reaction amplification of genomic DNA, we found one of two missense mutant OAT alleles to be present in each of 16 Finnish GA pedigrees. The first mutation R180T, in which arginine-180 is replaced by threonine, was present in homozygous form in patients from two pedigrees. The second mutation L402P, in which leucine-402 is replaced by proline, was present in homozygous form in patients from 14 pedigrees. Neither mutation was present in 19 Finnish controls. L402P was not present in 18 non-Finnish GA patients but R180T was found in an American GA patient. We constructed full-length mutant cDNAs by amplifying patient cDNA with the polymerase chain reaction and cloning a restriction fragment containing the mutation into an otherwise normal human OAT cDNA. These mutant cDNAs were then expressed in CHO-K1 cells, which lack endogenous OAT. Both R180T and L402P inactivate OAT. These results show molecular heterogeneity in GA alleles even in the Finnish population.

Alleles

Amebic colitis masquerading as acute inflammatory bowel disease: the role of serology in its diagnosis.

Amebic colitis needs to be considered in the differential diagnosis of infectious colitis or inflammatory bowel disease (IBD). Misdiagnosing amebic colitis as idiopathic inflammatory disease may be fatal. Although stool studies remain the initial approach to diagnosis, the incidence of false-negatives associated with this method is high. We report two cases of amebic colitis presenting as inflammatory bowel disease in which the diagnosis of amebic colitis was made by serology. Neither patient had any risk factors for acquiring amebiasis. Paired serology for amebic infections (2-4 weeks apart) should be performed in patients being evaluated for infectious colitis and inflammatory bowel disease.

Animals

Optimum anesthesia with intrapleural lidocaine during chemical pleurodesis with tetracycline.

Chemical pleurodesis with tetracycline is frequently complicated by pleuritic chest pain. The most promising approach to control pain is to optimize the use of intrapleural lidocaine. While administering amounts of intrapleural lidocaine larger than commonly reported, we attempted to determine a safe and more effective dose, by using a subjective and objective assessment of pain, by measuring serum concentrations of lidocaine, and by observing patients for possible toxic effects of lidocaine. Chemical pleurodesis with tetracycline was performed on ten patients receiving an intrapleural dose of 200 mg of lidocaine (group 1) and on ten patients receiving a 250-mg dose (group 2). A significantly greater number of patients in group 2 were free of pain following pleurodesis (7/10 vs 1/10; p = 0.006). Of the 80 serum lidocaine levels obtained, only one value (6.1 micrograms/ml), in an asymptomatic patient in group 1, exceeded the therapeutic range (1.5 micrograms/ml to 5.5 micrograms/ml). One patient in group 2 experienced transient numbness of the right hand, a possible side effect of lidocaine. We conclude that to achieve optimum anesthesia during chemical pleurodesis with tetracycline, it is necessary to use doses of intrapleural lidocaine large than previously reported. Until the feasibility of a further escalation is demonstrated, 250 mg should be considered the standard dose.

Anesthesia, Local

Synthetic keratophakia for the correction of aphakia.

Although the majority of aphakic patients will have intraocular lens implants (IOLs), there are several groups of patients for whom IOLs are not indicated. Synthetic keratophakia for the correction of aphakia has several inherent advantages over alternative forms of refractive surgery which use lathed corneal tissue. For example, the ability to produce a synthetic lens to precise specifications before surgery is a dramatic advantage over the use of lathed tissue lenses whose refractive properties cannot be determined until weeks or months after the lens is in place on the recipient cornea. Synthetic materials appear to behave in a predictable manner and are biocompatible. Both polysulfones and hydrogel materials can be used to correct aphakia in clinical situations where other modalities are less appropriate.

Animals

Keratoconus in a rhesus monkey.

A 15-year-old female rhesus monkey was observed to have bilaterally thinned and prominently curved corneas. Slit lamp observations, pachymetry, keratometry, and corneoscopy were consistent with a diagnosis of keratoconus, a relatively common corneal dystrophy in humans heretofore not described in a subhuman primate.

Animals

Myopic hydrogel keratophakia. Improvements in lens design.

In order for a refractive surgical procedure to be generally accepted, it must give a predictable result as well as generate a suitable optical surface. Previously, in a non-human primate model, we showed that hydrogel intracorneal lenses could flatten the cornea and thereby be used as a potential treatment for myopia. Over 20 D of central corneal flattening was observed in some cases. It was evident that the major corneal flattening occurred only in a very small area covered by the first corneascopic ring and that this area was irregular in that an elliptical reflection was generally obtained. We herein present the results of myopic hydrogel lens design modification. By enlarging the size of the lens and optical zone, the central corneal flattening became more regular as judged by corneascopic analysis. With the most recent lens designs, animals with high-minus implants showed circular corneascopic images with an average of 10.0 D of central flattening. This observation of corneal flattening was confirmed with autorefractor readings (average, -8.5 D) and keratometric readings (average, -9.0 D). These results are compared with earlier lens implants 5.5 mm in diameter where flattening was documented by reading the central corneascopic ring and could not be confirmed with either keratometric or autorefractor data. We feel these preliminary attempts at lens design modification have significantly enhanced the potential for future clinical application of this technique.

Animals

Hemophilia A. Detection of molecular defects and of carriers by DNA analysis.

To understand the molecular basis of hemophilia A and to provide heterozygote detection and prenatal diagnosis by DNA analysis, we used cloned factor VIII:C DNA fragments to study 10 affected families. In four of these families, inhibitors of factor VIII:C had developed in affected persons. In one such family a deletion of approximately 80 kb within the factor VIII:C gene was identified. Carriers of the deletion were identified through detection of an abnormal DNA fragment located at the deletion end points. In another family a single nucleotide change in the coding region of the factor VIII:C gene produced a nonsense codon leading to premature termination of factor VIII:C synthesis. Carrier detection was performed in eight female members of this four-generation family. In a third family a small change in the size of a restriction-endonuclease fragment correlated with the presence of the mutant gene, and in the other seven families the molecular defect has not yet been identified. In addition, we used two common polymorphic sites in the factor VIII:C gene to differentiate the normal from the defective gene in four of six obligate female carriers from families with patients in whom inhibitors did not develop. Carrier detection was possible in other members of these families. These data suggest that DNA analysis of the factor VIII:C gene provides an accurate method of carrier detection and, potentially, of prenatal diagnosis in at least 50 per cent of the pedigrees affected by hemophilia A.

Chromosome Deletion

Assessment of cervical carotid artery disease. A comparison between the Doppler "Echoflow" and conventional angiography.

Carotid artery disease is an important factor in the aetiology of stroke and cerebrovascular insufficiency. Angiography remains the definitive technique for the investigation of the carotid arteries, but the risk and expense involved has stimulated research into suitable non-invasive techniques. A comparison between a velocity-sensitive, colour-coded Doppler principle ultrasound flowmeter (Echoflow) and conventional angiography was conducted on 52 patients (101 arteries) investigated at Royal Perth Hospital over a 16-month period. An acceptable correlation was found in 78% of cases. Echoflow scanning proved to be particularly accurate in assessing normal arteries. Our results support the use of Echoflow as a first line of investigation, and in aiding the selection of cases requiring further study, although we caution against routine angiography in all patients with positive Echoflow scan results.

Adult

Analysis of DNA haplotypes suggests a genetic predisposition to trisomy 21 associated with DNA sequences on chromosome 21.

To test the hypothesis that there is a genetic predisposition to nondisjunction and trisomy 21 associated with DNA sequences on chromosome 21, we used DNA polymorphism haplotypes for chromosomes 21 to examine the distribution of different chromosomes 21 in Down syndrome and control families from the same ethnic group. The chromosomes 21 from 20 Greek families with a Down syndrome child and 27 control Greek families have been examined for DNA polymorphism haplotypes by using four common polymorphic sites adjacent to two closely linked single-copy DNA sequences (namely pW228C and pW236B), which map somewhere near the proximal long arm of chromosome 21. Three haplotypes, +, +---, and - with respective frequencies of 43/108, 24/108, and 23/108, account for the majority of chromosomes 21 in the control families. However, haplotype - was found to be much more commonly associated with chromosomes 21 that underwent nondisjunction in the Down syndrome families (frequency of 21/50; X2 for the two distributions is 9.550; P = 0.023; degrees of freedom, 3). The two populations (control and trisomic families) did not differ in the distribution of haplotypes for two DNA polymorphisms on chromosome 17. The data from this initial study suggest that the chromosome 21, which is marked in Greeks with haplotype - for the four above described polymorphic sites, is found more commonly in chromosomes that participate in nondisjunction than in controls. We propose an increased tendency for nondisjunction due to DNA sequences associated with a subset of chromosomes 21 bearing this haplotype.

Base Sequence