Glycated haemoglobin A1c measurement in stored whole blood sample is reliable for clinical use.

Glycated haemoglobin A1c (HbA1c) gives an integrated plasma glycaemia for the previous 2-3 months and its measurement is central in the management of diabetic patients. However in many developing countries because kits/regents or expertise for HbA1c measurement are not always available and the test must be conducted on fresh whole blood samples, HbA1c tests are not routinely performed Thus, this study aimed to determine if the degradation products from whole blood sample storage are significant enough to compromise the diagnostic value of HbA1c measurements. Two hundred and thirty-one fresh whole blood samples with pre-determined HbA1c values were stored at between 2-8 degrees C and using boronate affinity immunoassay technique, HbA1c values were then measured in the same whole blood samples after 20 days of storage. The results showed that there were no significant differences in the mean values of the initial HbA1c measurement and the values obtained after storage (7.5 +/- 2.0 vs. 7.5 +/- 2.1, p > 0.05) and this was irrespective of gender. Furthermore, irrespective of gender there were significant correlations between the HbA1c values measured in fresh whole blood samples and values obtained after storage (r = 0.83, p < 0.01). Therefore, based on these findings and other previous reports, the effect of storage degradation product was not significant enough to compromise the clinical or research use of HbA1c test results from stored whole blood samples. However, we recommend that diagnostic laboratories should evaluate their HbA1c measurement techniques for HbA1c determination in stored whole blood samples. Any persistent upward or downward bias in stored whole blood samples should be reported to guide the physician in interpreting HbA1c results from stored whole blood samples from that laboratory and/or technique.

Insulin resistance, leptin and monocyte chemotactic protein-1 levels in diabetic and non-diabetic Afro-Caribbean subjects.

AIM: To determine how the levels of leptin and monocyte chemotactic protein-1 (MCP-1) are associated with insulin resistance (IR) in obese, non-obese, diabetic and non-diabetic subjects. METHODS: 112 type 2 diabetics and 43 non-diabetics were studied fasting. Anthropometric indices were measured and glucose, insulin, leptin and MCP-1 were measured in blood. IR was calculated. RESULTS: MCP-1 level was significantly higher in diabetics than non-diabetics irrespective of gender (p < 0.05). Irrespective of diabetes status, the serum leptin concentration was significantly higher (p < 0.05) in obese and females subjects than in non-obese and male subjects respectively. There were no significant correlations between IR and MCP-1 or leptin in all subgroups of subjects studied. General linear modelling analysis showed that only diabetes state significantly predicted MCP-1 levels (p < 0.05) whereas non of the factors predicted leptin levels (p > 0.05). CONCLUSION: Routine measurement of leptin and MCP-1 would be potentially useful in assessment of patients for the metabolic syndrome or coronary heart disease especially in black population.

Prediction of 10-year coronary heart disease risk in Caribbean type 2 diabetic patients using the UKPDS risk engine

OBJECTIVE: Primary prevention of Coronary Heart Disease (CHD) in diabetic patients should be based on absolute CHD risk calculation. This study was aimed to determine the levels of 10-year CHD risk in Caribbean type 2 diabetic patients using the diabetes specific United Kingdom Prospective Diabetes Study (UKPDS) risk engine calculator. SUBJECTS AND METHODS: Three hundred and twenty-five (106 males, 219 females) type 2 diabetic patients resident in two Caribbean Islands of Tobago and Trinidad met the UKPDS risk engine inclusion criteria. Records of their sex, age, ethnicity, smoking habit, diabetes duration, systolic blood pressure, total cholesterol, HDL-cholesterol and glycated haemoglobin were entered into the UKPDS risk engine calculator programme and the absolute 10-year CHD and stroke risk levels were computed. The 10-year CHD and stroke risks were statistically stratified into <15%, 15-30% and >30% CHD risk levels and differences between patients of African and Asian-Indian origin were compared. RESULTS: In comparison with patients in Tobago, type 2 diabetic patients in Trinidad, irrespective of gender, had higher proportion of 10-year CHD risk (10.4 vs. 23.6%, P<0.001) whereas the overall 10-year stroke risk prediction was higher in patients resident in Tobago (16.9 vs. 11.4%, P<0.001). Ethnicity-based analysis revealed that irrespective of gender, higher proportion of patients of Indian origin scored >30% of absolute 10-year CHD risk compared with patients of African descent (3.2 vs. 28.2%, P<0.001). CONCLUSIONS: The results of the study identified diabetic patients resident in Trinidad and patients of Indian origin as the most vulnerable groups for CHD. These groups of diabetic patients should have priority in primary or secondary prevention of coronary heart disease.

Insulin resistance, leptin and monocyte chemotactic protein-1 levels in diabetic and non-diabetic Afro-Caribbean subjects

AIM: To determine how the levels of leptin and monocyte chemotactic protein-1 (MCP-1) are associated with insulin resistance (IR) in obese, non-obese, diabetic and non-diabetic subjects. METHODS: 112 type 2 diabetics and 43 non-diabetics were studied fasting. Anthropometric indices were measured and glucose, insulin, leptin and MCP-1 were measured in blood. IR was calculated. RESULTS: MCP-1 level was significantly higher in diabetics than non-diabetics irrespective of gender (p < 0.05). Irrespective of diabetes status, the serum leptin concentration was significantly higher (p < 0.05) in obese and females subjects than in non-obese and male subjects respectively. There were no significant correlations between IR and MCP-1 or leptin in all subgroups of subjects studied. General linear modelling analysis showed that only diabetes state significantly predicted MCP-1 levels (p < 0.05) whereas non of the factors predicted leptin levels (p > 0.05). CONCLUSION: Routine measurement of leptin and MCP-1 would be potentially useful in assessment of patients for the metabolic syndrome or coronary heart disease especially in black population.

Glycated haemoglobin A1c measurement in stored whole blood sample is reliable for clinical use / La medición de la hemoglobina glicada en muestras de sangre entera almacenadas es confiable para el uso clínico

Glycated haemoglobin A1c (HbA1c) gives an integrated plasma glycaemia for the previous 2-3 months and its measurement is central in the management of diabetic patients. However, in many developing countries because kits/regents or expertise for HbA1c measurement are not always available and the test must be conducted on fresh whole blood samples, HbA1c tests are not routinely performed. Thus, this study aimed to determine if the degradation products from whole blood sample storage are significant enough to compromise the diagnostic value of HbA1c measurements. Two hundred and thirty-one fresh whole blood samples with pre-determined HbA1c values were stored at between 2-8°C and using boronate affinity immunoassay technique, HbA1c values were then measured in the same whole blood samples after 20 days of storage. The results showed that there were no significant differences in the mean values of the initial HbA1c measurement and the values obtained after storage (7.5 ± 2.0 vs. 7.5 ± 2.1, p > 0.05) and this was irrespective of gender. Furthermore, irrespective of gender, there were significant correlations between the HbA1c values measured in fresh whole blood samples and values obtained after storage (r = 0.83, p < 0.01). Therefore, based on these findings and other previous reports, the effect of storage degradation product was not significant enough to compromise the clinical or research use of HbA1c test results from stored whole blood samples. However, we recommend that diagnostic laboratories should evaluate their HbA1c measurement techniques for HbA1c determination in stored whole blood samples. Any persistent upward or downward bias in stored whole blood samples should be reported to guide the physician in interpreting HbA1c results from stored whole blood samples from that laboratory and/or technique.

La hemoglobina glicada o glicosilada A1c (HbA1c) produce una glicemia plasmática integrada en los últimos 2-3 meses y su medición es fundamental para el tratamiento de pacientes diabéticos. Sin embargo, en muchos países en vías de desarrollo - debido a que no siempre hay kits/reactivos o conocimiento experto para la medición de HbA1c, y la prueba tiene que realizarse con muestras de sangre entera fresca - no se realizan tests de HbA1c de forma rutinaria. Así, este estudio apuntó a determinar si los productos de degradación del almacenamiento de la muestra de sangre entera son suficientemente significativos como para comprometer el valor del diagnóstico de las mediciones de las dimensiones de HbA1c. Doscientos treinta y una muestras de sangre entera fresca con valores HbA1c pre-determinados, fueron almacenadas entre 2-8°C y usando la técnica de inmunoensayo de afinidad al boronato, los valores de HbA1c fueron entonces medidos en las mismas muestras de sangre entera después de 20 días de almacenamiento. Los resultados mostraron que no había ninguna diferencia significativa en los valores promedios de la medición inicial de HbA1c y los valores obtenidos después del almacenamiento (7.5 ± 2.0 vs. 7.5 ± 2.1, p > 0.05), independientemente del género. Además, con independencia del género, hubo correlaciones significativas entre los valores de HbA1c medidos en las muestras de sangre entera fresca y los valores obtenidos después del almacenamiento (r = 0.83, p < 0.01). Por lo tanto, basado en estos hallazgos y otros informes anteriores, el efecto del producto de la degradación por almacenamiento no fue suficientemente significativo como para comprometer el empleo clínico o investigativo de los resultados de la prueba de HbA1c a partir de muestras de sangre entera almacenada. Sin embargo, recomendamos que los laboratorios de diagnóstico evalúen sus técnicas de medición para la determinación de HbA1c en las muestras de sangre entera almacenada. Cualquier tendencia persistente ascendente o descendente en las muestras de sangre entera almacenada debe ser reportada a fin de orientar al médico en la interpretación de los resultados de HbA1c de las muestras de sangre entera almacenadas por el laboratorio y/o para la técnica.

Prediction of 10-year coronary heart disease risk in Caribbean type 2 diabetic patients using the UKPDS risk engine.

OBJECTIVE: Primary prevention of Coronary Heart Disease (CHD) in diabetic patients should be based on absolute CHD risk calculation. This study was aimed to determine the levels of 10-year CHD risk in Caribbean type 2 diabetic patients using the diabetes specific United Kingdom Prospective Diabetes Study (UKPDS) risk engine calculator. SUBJECTS AND METHODS: Three hundred and twenty-five (106 males, 219 females) type 2 diabetic patients resident in two Caribbean Islands of Tobago and Trinidad met the UKPDS risk engine inclusion criteria. Records of their sex, age, ethnicity, smoking habit, diabetes duration, systolic blood pressure, total cholesterol, HDL-cholesterol and glycated haemoglobin were entered into the UKPDS risk engine calculator programme and the absolute 10-year CHD and stroke risk levels were computed. The 10-year CHD and stroke risks were statistically stratified into <15%, 15-30% and >30% CHD risk levels and differences between patients of African and Asian-Indian origin were compared. RESULTS: In comparison with patients in Tobago, type 2 diabetic patients in Trinidad, irrespective of gender, had higher proportion of 10-year CHD risk (10.4 vs. 23.6%, P<0.001) whereas the overall 10-year stroke risk prediction was higher in patients resident in Tobago (16.9 vs. 11.4%, P<0.001). Ethnicity-based analysis revealed that irrespective of gender, higher proportion of patients of Indian origin scored >30% of absolute 10-year CHD risk compared with patients of African descent (3.2 vs. 28.2%, P<0.001). CONCLUSIONS: The results of the study identified diabetic patients resident in Trinidad and patients of Indian origin as the most vulnerable groups for CHD. These groups of diabetic patients should have priority in primary or secondary prevention of coronary heart disease.

A comparative study of the prevalence of the metabolic syndrome and its components in type 2 diabetic patients in two Caribbean islands using the new International Diabetes Federation definition.

BACKGROUND AND AIM: Tobago and Trinidad are two Caribbean islands with distinct genetic background and lifestyles; while Tobago is serene and a tourist centre, Trinidad is characterized by a hustling and bustling lifestyle. The study was aimed at determining and comparing the prevalence of the metabolic syndrome (MetS) and its critical components in type 2 diabetic patients using the new International Diabetes Federation (IDF) definition. METHODS: Four hundred and thirteen (166 Tobago, 247 Trinidad) type 2 diabetic patients visiting 10 lifestyle disease clinics were studied. Blood pressure, anthropometric parameters (height, weight, body mass index and waist circumference) and overnight fasting blood samples were taken. Plasma glucose and serum triglycerides, total cholesterol, LDL- and HDL-cholesterol, insulin, and adiponectin were determined. Insulin resistance (IR) was determined using the HOMA method. RESULTS: The patients in Tobago were significantly older than patients in Trinidad (p < 0.001) but the duration of diabetes (9.4 +/- 0.5 vs. 11.1 +/- 0.7 yr), medications, generalized (31.7 vs. 38.8%) and central (78.5 vs. 83.7%) obesity were similar (p > 0.05). In comparison with patients in Tobago, diabetic patients in Trinidad, irrespective of gender, had significantly higher prevalence of IDF critical components such as raised BP, raised triglycerides and reduced HDL-cholesterol (all, p < 0.001). Thus, while more patients in Trinidad were diagnosed with MetS based on three or four components, more patients in Tobago were diagnosed based on two components (p < 0.001). CONCLUSIONS: There were high prevalence rates of the components of the MetS in both the islands of Tobago and Trinidad. Quantitatively, the aggregation of the components is higher in patients in Trinidad, which constitute greater risk for adverse cardiovascular outcome. Controlling central obesity should be the target in preventing MetS in the two islands.

Acute hemorrhagic leukoencephalitis. A successful recovery.

A 50-year-old woman developed acute hemorrhagic leukoencephalitis approximately 7 days after the onset of a benign respiratory infection. Mycoplasmal pneumonia was suspected because of Coomb's positive hemolysis, cold agglutinins, and sensitivity to erythromycin base but was not proved. Acute hemorrhagic leukoencephalitis was demonstrated by brain biopsy 24 hours after admission. The patient recovered without lasting sequelae following reduction of increased intracranial pressure by mannitol, hyperventilation, and phenobarbital and prolonged immunosuppression by plasmapheresis, steroids, and cyclophosphamide.

Short latency somatosensory evoked potentials in infants.

Short latency somatosensory evoked potentials (SEPs) to unilateral median nerve electrical stimulation were recorded from normal infants at birth and at 2, 4, 6, 8, 10 and 12 months of age. Three channels were recorded: Erb's point-Fz; C II (over 2nd cervical vertebra)-Fz; contralateral C' (2 cm posterior to C3 or C4)-Fz. Sweep time = 50 msec. At birth, the C II potential was seen in all infants; the Erb's point and C' potentials were seen in two-thirds. All older infants had well developed potentials at all sites. The mean latency of the Erb's point potential was stable over time. The latency of the C II potential decreased with maturation. At C', 4 components were seen, the latencies of which decreased with maturation: N1, P1, N2 and P2. The duration of N1 and P1 decreased with maturation. Standard deviations were relatively small for latencies and large for amplitudes. SEPs were adversely affected by using the 60 c/sec filter. Increasing the low frequency filter from 1 to 30 c/sec changed SEP, particularly in younger infants. Abnormal SEPs were seen in prematures surviving periventricular hemorrhage.

Abnormal brainstem auditory evoked potentials and neuropathology in "locked-in" syndrome.

Brainstem auditory evoked potentials (BAEPs) were studied in a "locked-in" syndrome resulting from multiple occlusions of paramedian pontine arteries. Abnormality of BAEPs (first recorded 10 days after infarction) indicated that brainstem damage extended beyond the basis pontis, where, typically, interruption of corticospinal pathways results in the "locked-in" syndrome. Later, partial BAEP recovery suggested that the technique can be used to distinguish between permanent and transient brainstem involvement. Autopsy examination revealed close correspondence between permanent brainstem damage and persistent BAEP abnormalities. Persistent abnormal prolongation of III-V conduction time and aberration of wave IV were associated with damage near the lateral lemniscus contralateral to the stimulated ear.

The effects of flurazepam hydrochloride on brain electrical activity during sleep.

To further evaluate the effects of flurazepam on EEG during sleep, following 7 nights of placebo baseline, flurazepam (30 mg) was administered to 6 young adult poor sleepers for 10 additional nights while 6 other young adult poor sleepers continued to receive placebo capsules in a double-blind paradigm. Three placebo follow-up nights were recorded 2--3 weeks post-treatment. Twelve good sleepers received only placebo capsules for the first 7 nights. Delta waves, 0.5--2 c/sec, and sleep spindles were counted on-line by a phasic detector. Delta activity was also analyzed off-line by PDP-12 computer for only the first 4 h of sleep and involved a comparison over stages of sleep. Click-evoked K-complexes during NREM sleep were analyzed for 6 good sleepers and 11 poor sleepers. Repeated use of flurazepam caused a gradual decrease in delta amplitude and count, and a gradual increase in sleep spindle rate. The decrease in delta amplitude was seen in all sleep stages, but the decrease was significant only during SWS and stage 2. The decrease in delta amplitude was significant by the 3rd drug night, but the rate of amplitude decrease tended to slow with continued treatment. The decrease in delta count was less pronounced and more gradual over drug nights than the rate of decrease in amplitude. Flurazepam also significantly reduced evoked K-complex amplitude but did not affect latency. Sleep spindle rate was significantly increased by drug night 5. Results of this study indicate that the reduction of SWS with flurazepam during the initial drug nights is due primarily to the decrease in delta amplitude, but, with continued use, the decrease in delta count also contributes to the decrease in stage 4 sleep.

Brainstem auditory evoked responses in patients comatose as a result of blunt head trauma.

The brainstem auditory evoked response (BAER) was evaluated as an aid in the early diagnosis and prognosis of 17 comatose blunt head-injury patients. Click stimuli (60 dBSL, 10/sec) were presented monaurally through headphones. BAER's were recorded between Cz and ipsilateral mastoid; contralateral mastoid ground. No BAER waves occurred in three "brain-dead" patients. Two patients with initially abnormal BAER's did not show improvement in followup recordings, and died of their brain injuries. Recovery occurred in 12 patients with normal followup BAER's, regardless of whether initial BAER's had been abnormal (three patients) or normal (nine patients). Apparently, initial BAER's (mean, 31 hours postinjury) can be abnormal as the result of reversible damage. Followup BAER's (3 to 6 days postinjury) did correspond with patient outcome at a time when clinical prognoses were often uncertain. BAER's aided diagnostically in determining the extent of brainstem damage and the effectiveness of treatment.

Auditory arousal thresholds of good sleepers and poor sleepers with and without flurazepam.

Auditory arousal thresholds of good (N = 12) and poor (N = 12) sleepers (sleep onset insomniacs) were obtained during stage 2, stage 4, and REM sleep at various times of the night. Despite claims of being "light" sleepers who are easily awakened by noise, poor sleeper auditory arousal thresholds were the same as those of good sleepers. Flurazepam (30 mg) increased the auditory arousal thresholds of poor sleepers (N = 6), but the increase was statistically significant only during the period of peak effect which occurred 1--2 hr after ingestion. Consistent with poor sleeper complaints of trouble falling asleep, the return to sleep (i.e., sleep latency) was significantly longer for poor than for good sleepers following stimulus arousals during the first stage 2 and first stage 4 periods of the night. Sleep latencies for good and poor sleepers did not differ significantly following subsequent arousals. The sleep latency following the first stage 2 stimulus arousal was significantly reduced in poor sleepers during flurazepam-induced sleep.

Evoked K-complexes and cardiovascular responses to spindle-synchronous and spindle-asynchronous stimulus clicks during NREM sleep.

The hypothesis that the functional role of the sleep spindle is to preserve sleep by inhibiting sensory input (Yamadori 1971) was examined. Series of 44 dB, 10 msec, 1000 c/sec 'clicks' were presented to 12 subjects at a 30-sec ISI during stage 2 sleep either during spindle bursts (i.e. spindle-synchronous clicks) or during interburst periods (i.e. spindle-asynchronous clicks). Contrary to the spindle inhibitory hypothesis, cortical EEG and cardiovascular responses showed no evidence of spindle 'suppression'. Evoked K-complexes were potentiated by the spindle-synchronous stimulation. A second study with 7 subjects replicated this result and extended the finding to include stage 3--4 sleep. It was suggested that the potentiation of evoked K-complexes was due to phasic reductions in inhibitory action during sleep spindles resulting in increased transmission of sensory events or, perhaps, an increase in the lability of certain EEG response systems.

EEG event-related potentials and signal detection.

The purpose of this study was to determine whether certain previously reported relationships between event-related potentials and measures of signal detection performance occur in vigilance as well as psychophysical settings. In the course of the study, evidence was found which challenges previously proposed psychological correlates of "P300". EEG was recorded while 15 subjects carried out a 40-min signal detection test. CNV was measured between a warning click and the brief offset of a dim light denoting the possible (p = 0.5) occurrence of the signal, a faint tone in the constant background noise. P300 was measured at a point 300 msec following offset of the dim light. As reported previously in psychophysical settings, P300 amplitude was positively related to signal intensity and response confidence, and was larger for correct detections (Hits) than for correct rejections, misses or false alarms. From first to second half of the test both Hits and false alarms fell, response criterion beta rose, and the amplitude of both CNV and P300 fell. The latter negative relationship between beta and P300 contrasted with a positive one when subjects rated their signal reports at three levels of confidence; here the most confident ratings (high beta) were associated with the highest amplitude of P300. CNV reflected individual ability to sustain performance. Results are explained in terms of a two-factor version (Wilkinson, 1976) of the prior state/reactive change hypothesis (Karlin, 1970). It is suggested that time on task constitutes a prior state influence on P300, whereas other variables influence P300 by means of either reactive change or 'real' change in an endogenous P300 component.