Utility of the Tono-Pen in Measuring Intraocular Pressure in Trinidad: A Cross-sectional Study.

AIM: To determine the sensitivity and specificity of the Reichert™ Tono-Pen AVIA® when used by novice medical students in an ethnically diverse population in Trinidad. SUBJECTS AND METHOD: Participants were residents of Trinidad between the ages of 20 and 90 years attending the Ophthalmology Clinic at the Eric Williams Medical Sciences Complex (EWMSC). Intraocular pressure (IOP) was measured using the Goldmann applanation tonometer (the gold standard) for ophthalmology clinic patients as part of their routine care. Intraocular pressure measurements were then taken using the Tono-Pen. RESULTS: One hundred persons participated, consisting of Indo-Trinidadians (55%), Afro-Trinidadians (36%), Mixed (8%) and 1% of Caucasian descent. Fourteen per cent reported a diagnosis of glaucoma, with 70.6% of these being of African descent. One hundred and ninety-eight readings of IOP were taken. At a cut-off point of 21 mmHg, there were nine true positives, four false positives, seven false negatives and 178 true negatives. The sensitivity and specificity were found to be 56.3% (95% CI 33.2, 76.9) and 97.8% (95% CI 94.5, 99.1), respectively. The positive predictive value was calculated as 69.2% (95% CI 42.4, 87.3) while the negative predictive value was 96.2% (95% CI 92.4, 98.2). The prevalence of elevated IOP in this population was 8.1% (95% CI 4.8, 13.0). The likelihood ratio of a positive result was calculated to be 25.6 (95% CI 8.6, 73.9). CONCLUSION: The high specificity and negative predictive value suggests that the Tono-Pen can be used with minimal training, and can prove beneficial at the primary care level in the exclusion of increased IOP in an ethnically diverse high-risk Caribbean population.

Ophthalmic manifestations of haematological disorders.

Five case histories are presented. Waldenstrom's macroglobulinaemia caused bilateral central retinal vein occlusion, proptosis was the presenting feature of retro-orbital plasmacytoma in relapsed multiple myeloma, a red painful eye was due to neovascular glaucoma in primary polycythaemia, bilateral VIth nerve palsy caused convergent squint and diplopia in meningeal relapse of acute lymphoblastic leukaemia and lymphoma of the eyelid caused complete ptosis. Interdisciplinary management is described. Ophthalmological lesions in haematological disease should be promptly recognized and managed. Collaboration between ophthalmology and haematology departments may be effective for palliative management.

A 100K well screen for a muscarinic receptor using the Epic label-free system--a reflection on the benefits of the label-free approach to screening seven-transmembrane receptors.

Seven-transmembrane receptors (7TMRs) are a family of proteins of great interest as therapeutic targets because of their abundance on the cell surface, diverse effects in modulating cell behavior and success as a key class of drugs. We have evaluated the Epic label-free system for the purpose of identifying antagonists of the muscarinic M3 receptor. We compared the data generated from the label-free technology with data for the same compounds in a calcium flux assay. We have shown that this technology can be used for high throughput screening (HTS) of 7TMRs and as an orthogonal approach to enable rapid evaluation of HTS outputs. A number of compounds have been identified which were not found in a functional HTS measuring the output from a single pathway, which may offer new approaches to inhibiting responses through this receptor.

Biometry of the silicone oil-filled eye: II.

PURPOSE: In phakic silicone oil-filled eyes, removal of the silicone oil can be combined with phacoemulsification and intraocular lens (IOL) implantation. True axial length (AL) of the silicone oil-filled (viscosity 1300 centistokes) eye can be estimated from the measured AL (MAL) obtained on A and/or B scan echography, by multiplying MAL by a conversion factor of 0.71. IOL power can then be calculated using current biometry formulae (SRK/T). This study aims to evaluate the conversion factor in clinical practice. METHODS: Eleven patients undergoing combined removal of silicone oil and phacoemulsification with IOL implant were studied. Patients were divided into two groups. In Group 1 (seven patients), the IOL was placed in the capsular bag and in Group 2 (four patients) the IOL was placed in the ciliary sulcus. Calculated AL (CAL) was obtained by multiplying the MAL of the silicone oil-filled eye (as measured on A or B scan ultrasonagraphy) by the conversion factor of 0.71. IOL power was then estimated using the CAL in the SRK/T formula. The spherical equivalent of the postoperative refractive error was compared to predicted refractive error. RESULTS: The mean difference in actual and predicted refractive error was 0.74 dioptres (D) (standard deviation 0.75 D) for Group 1 and 1.31 D (standard deviation 1.4 D) for Group 2. CONCLUSIONS: The conversion factor of 0.71 corrects for the apparent increase in AL induced by silicone oil of viscosity 1300 centistokes. This allows accurate prediction of the required IOL power in eyes undergoing combined cataract extraction, removal of silicone oil and lens implant. Sulcus placement of the IOL gives a less predictable result than placement in the capsular bag.

Biometry of the silicone oil-filled eye.

PURPOSE: The advent of silicone oil tamponade has resulted in improved success rates in complicated retinal detachment surgery. Its use, however, can induce cataract formation in phakic eyes. In selected patients, removal of silicone oil can be combined with phacoemulsification of the cataract and intraocular lens (IOL) implantation, thus avoiding a further operation. This, however, poses a problem when trying to decide the power of IOL to be used, since the echographically measured axial length (AL) of an eye is greater in the presence of silicone oil. We performed ultrasound examination in the presence of silicone oil of viscosity 1300 centistokes, in order to determine whether the measured AL varied from the true AL by a constant factor. METHODS: The ALs of 7 phakic eyes were measured by A-mode echography, with and without silicone oil of viscosity 1300 centistokes in the posterior segment. The retina was attached in all cases. The control group consisted of 6 phakic eyes with attached retinae undergoing vitrectomy without the use of silicone oil. The ALs in the control group were measured before and after vitrectomy. RESULTS: The mean ratio of true AL to measured AL in the presence of silicone oil was 0.71 (standard deviation 0.01; range 0.70-0.73; median 0.71) in the 7 eyes in this study. In the control group, vitrectomy appeared to have no significant effect on AL. CONCLUSIONS: We have established a constant which corrects for the apparent increase in AL induced by silicone oil of viscosity 1300 centistokes. This conversion factor, when used in existing biometry formulae (SRK/T), allows estimation of the power of IOL required in eyes undergoing combined cataract extraction, removal of silicone oil and lens implantation.

Long-term evolution of cardiomyopathy in dialysis patients.

BACKGROUND: Left ventricular enlargement is very common at the inception of dialysis therapy, and highly predictive of future cardiac morbidity and mortality. It is not known whether cardiac size increases further while on dialysis therapy and whether potentially reversible risk factors for later progression can be identified. METHODS; Baseline and yearly echocardiograms were performed in a prospective inception cohort of 433 dialysis patients. The mean patient follow-up was 41 months; 29 patients had four consecutive echocardiograms at yearly intervals. RESULTS: The patient subset with four echocardiograms was older (58 vs. 51 years, P = 0.02) and had a lower mass ventricular mass index (128 vs. 149 g/m2, P = 0.02) than the parent group. Using repeated measures analysis of variance, applied to those with four echocardiograms, there were progressive increases over time in posterior wall thickness (P = 0.015), left ventricular end-diastolic diameter, left ventricular mass index (P = 0.001), and cavity volume index (P = 0. 001). Mass-to-volume ratios did not change. The biggest changes in mass (18 g/m2 - 14%)and volume index (13 ml/m2 - 18%) occurred between baseline and year 1, although increases in both were seen after year 1. Hemodialysis versus peritoneal dialysis (41 g/m2, P = 0.008) and anemia (10 g/m2 per 1 g/dl drop in hemoglobin, P = 0.02) were associated with progressive left ventricular enlargement, but only within the first year of dialysis therapy. The left ventricular enlargement seen after year 1 was independent of anemia, blood pressure, serum albumin and mode of dialysis. CONCLUSIONS: Progressive cardiac enlargement, particularly left ventricular dilation with compensatory hypertrophy, continues after starting dialysis therapy. Most of the additional cardiac enlargement seems to occur in the first year of dialysis therapy, suggesting that intervention beyond one year may be relatively ineffective.

Mode of dialysis therapy and mortality in end-stage renal disease.

Despite considerable differences in technique and blood purification characteristics, hemodialysis and peritoneal dialysis have been thought to have similar patient outcomes. An inception cohort of 433 end-stage renal disease patients was followed prospectively for a mean of 41 mo. The outcomes of hemodialysis (HD) and peritoneal dialysis (PD) patients were compared using intention to treat analysis based on the mode of therapy at 3 mo. After adjustment for PD patients less likely to have chronic hypertension and more likely to have diabetes, ischemic heart disease, and cardiac failure at baseline (P < 0.05), a biphasic mortality pattern was observed. For the first 2 yr, there was no statistically significant difference in mortality. After 2 yr, mortality was greater among PD patients with an adjusted PD/HD hazard ratio of 1.57 (95% confidence interval [CI], 0.97 to 2.53). Both the occurrence (adjusted hazards ratio 6.87 [95% CI, 2.01 to 23.5]) and the direction (toward PD, adjusted hazards ratio 6.25 [95% CI, 1.54 to 25]) of a therapy switch were subsequently associated with mortality after 2 yr. Progressive clinical and echocardiographic cardiac disease were not responsible for this late mortality. Lower mean serum albumin levels in PD patients in the first 2 yr of therapy (3.5 +/- 0.5 versus 3.9 +/- 0.5 g/dl, P < 0.0001) accounted for a large proportion of the increase in subsequent mortality. Hemodialysis has a late survival advantage over peritoneal dialysis; antecedent hypoalbuminemia is a major marker of the increased late mortality in PD patients.

Cardiac disease in diabetic end-stage renal disease.

Little is known about the epidemiology of cardiac disease in diabetic end-stage renal disease. We therefore prospectively followed a cohort of 433 patients who survived 6 months after the inception of dialysis therapy for an average of 41 months. Clinical and echocardiographic data were collected yearly. At baseline, diabetic patients (n = 116) had more echocardiographic concentric left ventricular hypertrophy (50 vs 38%, p = 0.04), clinically diagnosed ischaemic heart disease (32 vs 18%, p = 0.003) and cardiac failure (48 vs 24%, p < 0.00001) than non-diabetic patients (n = 317). After adjusting for age and sex, diabetic patients had similar rates of progression of echocardiographic disorders, and de novo cardiac failure, but higher rates of de novo clinically diagnosed ischaemic heart disease (RR 3.2, p = 0.0002), overall mortality (RR 2.3, p < 0.0001) and cardiovascular mortality (RR 2.6, p < 0.0001) than non-diabetic patients. Mortality was higher in diabetic patients following admission for clinically diagnosed ischaemic heart disease (RR 1.7, p = 0.05) and cardiac failure (RR 2.2, p = 0.0003). Among diabetic patients older age, left ventricular hypertrophy, smoking, clinically diagnosed ischaemic heart disease, cardiac failure and hypoalbuminaemia were independently associated with mortality. The excessive cardiac morbidity and mortality of diabetic patients seem to be mediated via ischaemic disease, rather than progression of cardiomyopathy while on dialysis therapy. Potentially remediable risk factors include smoking, left ventricular hypertrophy, and hypoalbuminaemia.

Basal release of nitric oxide induces an oscillatory motor pattern in canine colon.

1. The consequences of intrinsic, basal nitric oxide release on electrical and contractile activity of canine proximal colon were examined. Membrane potential and contraction were simultaneously recorded from the circular muscle in the presence of drugs to block adrenergic and cholinergic responses. 2. Electrical slow waves were recorded from muscle cells near the submucosal surface of the circular layer. Spontaneous contractions were initiated by each slow wave. Contractile amplitude increased 1.9-fold when nerves were blocked with tetrodotoxin (TTX, 1 microM). 3. Muscle cells near the myenteric surface displayed myenteric potential oscillations (MPOs) averaging 16 cycles per minute (c.p.m.) in frequency and 10 mV in amplitude. Twenty-five per cent of muscles displayed an additional slow, neurogenic oscillation (mean frequency, 1 c.p.m.; amplitude, 14 mV) superimposed upon the MPO rhythm. 4. The nitric oxide (NO) synthase inhibitor N omega -nitro-L-arginine (L-NA, 100 microM; n = 16) abolished neurogenic oscillations, depolarized cells, and increased MPO upstroke velocity, amplitude and frequency. The actions of L-NA were mimicked by N omega-nitro-L-arginine methylester (L-NAME, 100 microM) and oxyhaemoglobin (3%). 5. Spontaneous contractions were increased 2.3-fold by L-NA, and TTX had no effect on contractions after addition of L-NA. 6. The NO-donor sodium nitroprusside (SNP, 1 microM) reversed the electrical and mechanical effects of L-NA and initiated slow oscillations similar to the neurogenic oscillations. Slow oscillations were also evoked with S-nitroso-N-acetylpenicillamine (SNAP, 1 microM). The effects of NO donors were blocked by oxyhaemoglobin. 7. Slow electrical oscillations could not be elicited by SNP after removal of a thin strip of circular muscle along the myenteric edge. 8. These data suggest that the spontaneous electrical and contractile activity of the proximal colon is tonically suppressed by basal release of NO. Basal NO causes an oscillatory pattern of electrical and mechanical activity. This activity does not require patterned firing of nerves; rather a continuous, low level release of NO would be capable of producing the neurogenic oscillatory behaviour. The slow oscillatory activity depends upon the presence of the myenteric region of the circular muscle layer, which contains cell bodies of enteric neurons and interstitial cells of Cajal.

Electroretinographic findings in Fuchs' heterochromic cyclitis.

PURPOSE: Fuchs' heterochromic cyclitis (FHC) is an inflammatory disease of unknown aetiology. Although anterior segment signs and vitreous changes are well recognised, retinal features are unusual. To assess the extent of retinal involvement, we performed electrophysiological testing in a group of FHC patients. METHODS: Retinal function was assessed by means of flash electroretinogram (ERG) using a Ganzfeld stimulus, and pattern electroretinogram (PERG) using a checkerboard stimulus of spatial frequency 0.5 and 1.0 cycle per degree reversing at 6 Hz. A total of 21 patients with unilateral, normotensive FHC with visual acuities of 6/5 to 6/9 were studied. RESULTS: In the flash ERG, selective scotopic b-wave abnormalities occurred in 9 (43%) of 21 FHC eyes. Despite clear media and no history of ocular surgery, 7 patients showed abnormalities of the PERG. CONCLUSIONS: These electrophysiological findings suggest subclinical damage to the inner retinal layers, but not involving the photoreceptors, in eyes with FHC.

Rationale and perspectives on the development of fungicides.

Fungicides continue to be essential for the effective control of plant diseases. New classes of fungicides with novel modes of action are being developed in the 1990s. These include the strobilurins, phenylpyrroles, anilinopyrimidines, phenoxyquinolines, and compounds that trigger defense mechanisms in the plant. For the foreseeable future, new toxophores will be identified through a process of random screening, with natural products representing a rich source of fungicide leads. Progress is being made in the development of high-throughput screens comprised of target enzyme sites or cell-based assays; these techniques will improve the probability of discovery. Following the identification of suitable leads, biorational design is used to optimize specific properties. In vivo glasshouse screens and field trials are expected to remain the dominant methods for characterizing new compounds. Low toxicity to humans and wildlife, low environmental impact, low residues in food, and compatibility with integrated pest management (IPM) programs are increasingly important considerations in the selection of fungicides for development.

The impact of anemia on cardiomyopathy, morbidity, and and mortality in end-stage renal disease.

To determine the possible association between anemia and clinical and echocardiographic cardiac disease, a cohort of 432 end-stage renal disease patients (261 on hemodialysis and 171 on peritoneal dialysis) who started dialysis therapy between 1982 and 1991 were followed prospectively for an average of 41 months. Baseline demographic, clinical, and echocardiographic assessments were performed, as well as monthly serial clinical and laboratory tests while the patients were on dialysis therapy. The mean (+/-SD) hemoglobin level during dialysis therapy was 8.8 +/- 1.5 g/dL. After adjusting for age, diabetes, and ischemic heart disease, as well as for blood pressure and serum albumin levels measured serially, each 1 g/dL decrease in mean hemoglobin was independently associated with the presence of left ventricular dilatation on repeat echocardiogram (odds ratio, 1.46; P = 0.018) and the development of de novo (relative risk [RR] = 1.28; P = 0.018) and recurrent (RR = 1.20; P = 0.046) cardiac failure. In addition, each 1 g/dL decrease in the mean hemoglobin level was independently associated with mortality while the patients were on dialysis therapy (RR = 1.14; P = 0.024). Anemia had no independent association with the development of ischemic heart disease while the patients were on dialysis therapy. Anemia, an easily reversible feature of end-stage renal disease, is an independent risk factor for clinical and echocardiographic cardiac disease, as well as mortality in end-stage renal disease patients.

Outcome and risk factors for left ventricular disorders in chronic uraemia.

BACKGROUND: Left ventricular disease occurs frequently in dialysis patients. It may be manifest as concentric LV hypertrophy, LV dilatation with or without LV hypertrophy, or systolic dysfunction. Little is known concerning the clinical outcome and risk factors for these disorders. METHODS: A cohort of 432 end-stage renal disease patients who survived at least 6 months had an echocardiogram on initiation of dialysis therapy. Clinical, laboratory and echocardiographic data was obtained annually during follow-up. RESULTS: On initiation of ESRD therapy 16% of patients had systolic dysfunction, 41% concentric LV hypertrophy, 28% LV dilatation, and only 16% had normal echocardiograms. Median time to development of heart failure was 19 months in patients with systolic dysfunction, 38 months in concentric LV hypertrophy and 38 months in LV dilatation. The relative risks of heart failure in the three groups were significantly worse than in the normal group, after adjusting for age, diabetes and ischaemic heart disease. Median survival was 38 months in systolic dysfunction, 48 months in concentric hypertrophy, 56 months in LV dilatation, and >66 months in the normal group. Two hundred and seventy-five patients had a follow-up echocardiogram 17 months after starting dialysis therapy together with serial measurement of potential risk factors prior to the echocardiogram. On follow-up echocardiogram the degree of concentric LV hypertrophy was independently related to hypertension while on dialysis, older age, and anaemia while on dialysis; the degree of LV dilatation was related to ischaemic heart disease, anaemia, hypertension and hypoalbuminemia while on dialysis; the degree of systolic dysfunction was associated with ischaemic heart disease and anaemia during follow-up. CONCLUSIONS: Manifestations of left ventricular disease are frequent and persistent in chronic uraemia, and are associated with high risks of heart failure and death. Potentially reversible risk factors include anaemia, hypertension, hypoalbuminaemia and ischaemic heart disease.

Impact of hypertension on cardiomyopathy, morbidity and mortality in end-stage renal disease.

A cohort of 432 ESRD (261 hemodialysis and 171 peritoneal dialysis) patients was followed prospectively for an average of 41 months. Baseline and annual demographic, clinical and echocardiographic assessments were performed, as well as serial clinical and laboratory tests measured monthly while on dialysis therapy. The average mean arterial blood pressure level during dialysis therapy was 101 +/- 11 mm Hg. After adjusting for age, diabetes and ischemic heart disease, as well as hemoglobin and serum albumin levels measured serially, each 10 mm Hg rise in mean arterial blood pressure was independently associated with: the presence of concentric LV hypertrophy (OR 1.48, P = 0.02), the change in LV mass index (beta = 5.4 g/m2, P = 0.027) and cavity volume (beta = 4.3 ml/m2, P = 0.048) on follow-up echocardiography, the development of de novo cardiac failure (RR 1.44, P = 0.007), and the development of de novo ischemic heart disease (RR 1.39, P = 0.05). The association with LV dilation was of borderline statistical significance (OR 1.48, P = 0.06). Mean arterial blood pressures greater than 106 mm Hg were associated with both echocardiographic and clinical endpoints. Paradoxically, low mean arterial blood pressure (RR 1.36 per 10 mm Hg fall, P = 0.009) was independently associated with mortality. The association of low blood pressure with mortality was a marker for having had cardiac failure prior to death. We conclude that even moderate hypertension worsens the echocardiographic and clinical outcome in ESRD patients, especially in those without previous clinical cardiac disease.