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Biomedical subjects

C K Patel

Publications and source records attributed to C K Patel.

At least 19 recordsLinked to original sources

Hydrophobicity, a physicochemical factor in the inhibition of the enzyme estrone sulfatase (ES).

We report the initial structure-activity relationship study (SAR) (in particular logP) of a series of compounds based upon 4-sulfamated phenyl ketones as potent inhibitors of the enzyme estrone sulfatase (ES). The results of the study show that these compounds are irreversible inhibitors of ES and that they are more potent than COUMATE, but weaker than EMATE. Analysis of the SAR data shows a strong correlation between IC(50) and logP but also supports our previous study, which suggests a very strong relationship between pK(a) and IC(50).

Chemistry, Physical↗

The use of traction methods to correct severe cervical deformity in rheumatoid arthritis patients: a report of five cases.

STUDY DESIGN: A case series is presented. OBJECTIVES: To describe the methods of correction used in this study for flexible severe cervical deformity, and to report the results in patients with rheumatoid arthritis. SUMMARY OF BACKGROUND DATA: Long-standing rheumatoid arthritis can lead to severe cervical deformity, causing significant functional deficits and poor cosmesis. Information on the use of traction combined with surgical stabilization to achieve correction of flexible deformity in rheumatoid patients is sparse in the English literature. METHODS: A review of five cases, including pertinent history, physical examination, radiographic evaluation, traction techniques, surgical stabilization, and outcomes, was conducted. RESULTS: Excellent correction of deformity and radiographic union were achieved in all the patients. One patient had minimal loss of correction after surgery and thereafter remained stable. Pin tract infections were the only significant complication. CONCLUSIONS: Severe cervical flexible deformity in rheumatoid patients can cause significant disability and can be treated successfully with a combination of traction techniques and surgical stabilization.

Adult↗

Correlation of breath ammonia with blood urea nitrogen and creatinine during hemodialysis.

We have spectroscopically determined breath ammonia levels in seven patients with end-stage renal disease while they were undergoing hemodialysis at the University of California, Los Angeles, dialysis center. We correlated these measurements against simultaneously taken blood samples that were analyzed for blood urea nitrogen (BUN) and creatinine, which are the accepted standards indicating the level of nitrogenous waste loading in a patient's bloodstream. Initial levels of breath ammonia, i.e., at the beginning of dialysis, are between 1,500 ppb and 2,000 ppb (parts per billion). These levels drop very sharply in the first 15-30 min as the dialysis proceeds. We found the reduction in breath ammonia concentration to be relatively slow from this point on to the end of dialysis treatment, at which point the levels tapered off at 150 to 200 ppb. For each breath ammonia measurement, taken at 15-30 min intervals during the dialysis, we also sampled the patient's blood for BUN and creatinine. The breath ammonia data were available in real time, whereas the BUN and creatinine data were available generally 24 h later from the laboratory. We found a good correlation between breath ammonia concentration and BUN and creatinine. For one of the patients, the correlation gave an R(2) of 0.95 for breath ammonia and BUN correlation and an R(2) of 0.83 for breath ammonia and creatinine correlation. These preliminary data indicate the possibility of using the real-time breath ammonia measurements for determining efficacy and endpoint of hemodialysis.

Ammonia↗

Acid dissociation constant, a potential physicochemical factor in the inhibition of the enzyme estrone sulfatase (ES).

We report the initial results of the synthesis and biochemical evaluation of a series of aminosulfonate based compounds of phenol and the determination of the pKa of the parent phenol in an attempt to investigate the role of this physicochemical factor in the irreversible inhibition of the enzyme estrone sulfatase (ES). The results of the study show that there is a strong correlation between the observed pKa and inhibitory activity. We postulate that the stability of the phenoxide ion, as indicated by the acid dissociation constant, is an important factor in the irreversible inhibition of this enzyme.

Estrogens↗

Novel inhibitors of the enzyme estrone sulfatase (ES).

We report the initial results of our study into a series of simple 4-sulfamated phenyl alkyl ketones as potential inhibitors of the enzyme estrone sulfatase. The results of the study show that these compounds are potent inhibitors, possessing greater inhibitory activity than COUMATE, but weaker activity than EMATE. Furthermore, the compounds are observed to be irreversible inhibitors.

Alkanes↗

Posterior subcapsular and nuclear cataract after vitrectomy.

PURPOSE: To examine the morphological changes in the postvitrectomy lens and to monitor the development of these changes over time. SETTING: Oxford Eye Hospital, Oxford, United Kingdom. METHODS: In this prospective study, 33 consecutive phakic patients having pars plana vitrectomy were recruited. Cataract development was quantified by clinical grading and digital Scheimpflug image analysis. Slitlamp biomicroscopy and photography were used to document the morphological appearance. The main outcome measures were the incidence, morphology, and development of posterior subcapsular and nuclear cataract. RESULTS: A characteristic, transient posterior subcapsular cataract (PSC) was present in 89% (17 of 19) of tamponade patients within 24 hours of surgery. Of the patients who had vitrectomy without tamponade, 9% (1 of 11) developed similar changes. Nuclear opacity developed in 61% (11 of 18) of tamponade patients and in 50% (3 of 6) of nontamponade patients. A longer term retrospective review of the same patients' case notes revealed nuclear cataract in 67% (12 of 18) of tamponade cases and 30% (3 of 10) of nontamponade cases. Eighteen percent (2 of 11) of nontamponade cases and 67% (14 of 21) of tamponade cases had cataract surgery after a 10.7 month and a 12.4 month follow-up, respectively. CONCLUSIONS: Vitrectomy and tamponade produced a characteristic transient PSC in the immediate postoperative period. Disruption of fluid balance in the region of the posterior lens was suggested by the morphological appearance. The acute changes resolved but were followed by accelerated nuclear opacification.

Aged↗

First report of the investigation into the importance of pK(a) in the inhibition of estrone sulfatase by sulfamate containing compounds.

In an effort to rationalise the inhibitory activity of a range of aminosulfamate compounds and to further investigate the recently reported definitive pharmacophore estrone sulfatase (ES), we undertook extensive synthesis, biochemical evaluation and physicochemical property determination of a range of similar compounds. Here, we report the initial results of our study into a series of simple (aminosulfonate based) substituted phenol derivatives. Using these compounds, we investigated the role of pK(a) in the inhibition of ES. The results of the study suggest that there is a strong correlation between the inhibitory activity and the stability of the resulting O(-) anion (i.e., the pK(a) of the starting phenol).

Anions↗

Post-operative changes in the capsulorhexis aperture: a prospective, randomised comparison between loop and plate haptic silicone intraocular lenses.

PURPOSE: There is disagreement regarding whether the capsulorhexis aperture always decreases or may increase post-operatively. The aim of this study was to settle the controversy concerning loop haptic silicone lenses and to learn more of the dynamics of the capsulorhexis relating to plate haptic lenses. METHODS: We performed a prospective randomised study comparing the post-operative changes in capsulorhexis aperture in two groups of eyes implanted with either plate or loop haptic silicone intraocular lenses. All the surgery was performed, at a teaching hospital in the United Kingdom, by a single surgeon, using a standard technique of phacoemulsification. Patients were reviewed at 2 weeks and 6 months post-operatively. Digital retroillumination images of the anterior segment were captured. The area of the capsulorhexis aperture was determined by manually detecting its edge on a computer monitor. RESULTS: Forty-eight cases were randomised. The groups were comparable for demographic variables and mean initial aperture size (p > 0.05). There was an 8.4% mean decrease in aperture size for the loop haptics, contrasting with 4.5% expansion for the plate haptics (p < 0.05). Sixty-five per cent of patients with the plate haptic underwent enlargement of the aperture, contrasting with 25% for the loop haptic lens (p < 0.05). CONCLUSIONS: Silicone lenses with plate haptics undergo expansion of the capsulorhexis aperture more frequently than those with Prolene loop haptics.

Aged↗

Postoperative intraocular lens rotation: a randomized comparison of plate and loop haptic implants.

OBJECTIVE: To compare the postoperative rotation of plate and loop haptic implants of spherical power to ascertain the optimal design appropriate for toric intraocular lenses (IOLs). DESIGN: Randomized, controlled trial. PARTICIPANTS: Forty-eight patients attending for routine cataract surgery by phacoemulsification. METHOD: Patients with cataract as the only ocular disease were randomly implanted with plate or loop haptic implants after uncomplicated phacoemulsification. The baseline position of the IOL was determined from a video frame acquired at the conclusion of surgery. Postoperative IOL position was documented using digital retroillumination images at 2 weeks and 6 months after surgery. Capsular fusion patterns were recorded using slit-lamp biomicroscopy. Correlation of IOL rotation with axial length, capsular contraction, and fusion was attempted. MAIN OUTCOME MEASURES: Early IOL rotation, occurring between surgery and 2 weeks after surgery, was graded as mild (<10 degrees), moderate (10 degrees < to <30 degrees), or severe (>30 degrees) by a semiobjective online comparison of the images. Late IOL rotation, occurring between 2 weeks and 6 months, was measured more precisely using software developed specifically for the study. RESULTS: Twenty-three patients were allocated the loop haptic and 25 the plate haptic IOL. The groups were comparable for demographic variables and numbers of patients excluded from analysis (P > 0.05). Five (24%) of 21 of plate haptic IOLs underwent severe early rotation compared to 2 (9%) of 22 loop haptics (P = 0.36). The median late rotation was 6.8 degrees for loop haptics compared to 0.6 degrees for plate haptics (P = 0.0073). Between 2 weeks and 6 months, anticlockwise rotation had occurred in 16 (89%) of 18 loop haptic IOLs compared to 11 (52%) of 21 plate haptic IOLs (P = 0.0081). CONCLUSIONS: Plate haptic IOLs show greater rotational stability than do loop haptics made from polypropylene once capsular fusion has taken place. Loop haptics invariably rotate anticlockwise after 2 weeks.

Capsulorhexis↗

Fourier transform infrared spectroscopy reveals a rigid alpha-helical assembly for the tetrameric Streptomyces lividans K+ channel.

The structure of the tetrameric K+ channel from Streptomyces lividans in a lipid bilayer environment was studied by polarized attenuated total reflection Fourier transform infrared spectroscopy. The channel displays approximately 43% alpha-helical and 25% beta-sheet content. In addition, H/D exchange experiments show that only 43% of the backbone amide protons are exchangeable with solvent. On average, the alpha-helices are tilted 33 degrees normal to the membrane surface. The results are discussed in relationship to the lactose permease of Escherichia coli, a membrane transport protein.

Lipid Bilayers↗

Optimisation of outpatient resource utilisation in cataract management.

PURPOSE: We assessed whether patients referred with a diagnosis of cataract require outpatient assessment before listing for surgery or whether the general practitioner could have direct access to the waiting list. We also studied whether pre-assessment clinics made a significant difference to management even when waiting times were long. METHODS: Data about patients referred with a diagnosis of cataract to the Oxford Eye Hospital and associated hospitals were collected. Seventy-five patients were prospectively studied and 100 patient records were retrospectively analysed. RESULTS: Twenty-six per cent of patients had a misdiagnosis or additional problems affecting management. Optometrists provided more information than general practitioners, but their diagnostic accuracy was equal (73% optometrists, 75% general practitioners). At the pre-assessment clinic pupil dilatation changed management in only 4% of patients. CONCLUSION: Listing patients on the basis of referral letters would be inappropriate in 1 in 4 patients. Pre-assessment clinics rarely picked up a clinically relevant change. Thus if outpatient consultation included a decision on the exact surgical plan including implant power, then pre-assessment clinics may not be necessary.

Cataract↗

The lipid bilayer determines helical tilt angle and function in lactose permease of Escherichia coli.

The structure of lactose permease from Escherichia coli in its lipid environment was studied by attenuated total reflection Fourier transform infrared spectroscopy. The protein exhibits an alpha-helical content of about 65% and about 25% beta-sheet. Unusually fast hydrogen/deuterium (H/D) exchange to 90-95% completion suggests a structure that is highly accessible to the aqueous phase. An average tilt angle of 33 degrees for the helices was found with respect to the bilayer normal at a lipid-to-protein ratio of approximately 800:1 (mol/mol), and the permease exhibits optimal activity under these conditions. However, upon decreasing the lipid-to-protein ratio, activity decreases continuously in a manner that correlates with the decrease in the lipid order parameter and the increase in the average helical tilt angle. Taken together, the data indicate that the structure and function of the permease are strongly dependent on the order and integrity of the lipid bilayer.

Deuterium Oxide↗

Decentration of 5.1 mm intraocular lenses after continuous curvilinear capsulorhexis and in-the-bag fixation.

PURPOSE: To determine the incidence of decentration in eyes with 5.1 mm optic intraocular lenses (IOLs) and to assess the effect on vision. SETTING: Clinical Cataract Research Unit, Oxford Eye Hospital, Oxford, England. METHODS: Patients having phacoemulsification and small IOL implantation over 12 months were identified and invited for assessment. Intraocular lens decentration was measured geometrically using a modified, digital, retroillumination camera. The expected incidence of symptoms caused by decentration was estimated by determining the presence of an IOL edge within an artificial pupil overlaid on the digital image. RESULTS: In 13 eyes (20%), IOL decentration was more than 0.5 mm. Symptoms were expected in 38 patients (59%) but occurred in only 14 (22%). CONCLUSION: Decentration of the 5.1 mm optic IOL caused fewer clinical problems than anticipated, although the results raise concerns that such IOLs may be inappropriate in patients who need excellent vision in scotopic illumination.

Aged↗

The effect of age on residual strain in the rat aorta.

Residual stress is observed in many parts of the cardiovascular system and is thought to reduce transmural stress gradients due to intravascular pressure. Its development is closely associated with normal growth and pathological remodeling, although there appear to be few previous reports of the relationship between aging and residual stress. We have estimated residual strain (an indicator of the magnitude of residual stress) at ten sites along the aorta of rats aged 2.5 to 56 weeks by measuring the degree to which rings of vessel spring open when cut (opening angle). At all ages the opening angle decreased along the aorta, reaching a minimum near the renal arteries and increasing toward the aorto-iliac bifurcation, a result that confirms previous studies. During growth, although the unloaded circumference of the aorta increased steadily, the wall thickness and medial surface area fell to a minimum at the age of 6 weeks before continuing a steady increase. Similarly, the opening angle decreased between the ages of 2.5 and 6 weeks, thereafter increasing with age. In the abdominal aorta, a strong correlation between opening angle and wall thickness relative to midwall radius (h/R) was seen; whereas in the thoracic segment, in which no increase in h/R with age occurred, no such relationship was found. These observations are in keeping with a recently proposed hypothesis that residual stress will change in response to growth-related changes in vessel geometry driven by a tendency to minimize the nonuniform stress distribution inevitably found in pressurized thick-walled cylinders.

Aging↗

A pre-operative mydriatic regime using a single application of tropicamide Novel Ophthalmic Delivery System and guttae phenylephrine 10%.

Tropicamide Novel Ophthalmic Delivery System (NODS) and guttae (g.) phenylephrine 10% was applied once, 2 hours before cataract surgery, as an alternative to our standard pre-operative regime of g. cyclopentolate 1% and g. phenylephrine 10% used four times before surgery. The two treatment groups were compared using a randomised, prospective, observer-masked study design. The horizontal pupil diameter was significantly smaller using the new regime but the per-operative decrease in diameter was not significantly different, suggesting that surgical miosis was not influenced by reducing the number of mydriatic applications. There was no difference in the subjective grading of the pupil, suggesting that adequate mydriasis suitable for cataract surgery was obtained using the alternative regime. No major complications were documented in relation to the use of NODS. We discuss why less intensive mydriasis is likely to be as efficacious and describe its potential advantages.

Aged↗