Next generation sequencing to determine the cystic fibrosis mutation spectrum in Palestinian population.

An extensive molecular analysis of the CF transmembrane regulator (CFTR) gene was performed to establish the CFTR mutation spectrum and frequencies in the Palestinian population, which can be considered as an understudied population. We used a targeted Next Generation Sequencing approach to sequence the entire coding region and the adjacent sequences of the CFTR gene combined with MLPA analysis of 60 unrelated CF patients. Eighteen different CF-causing mutations, including one previously undescribed mutation p.(Gly1265Arg), were identified. The overall detection rate is up to 67%, and when we consider only CF patients with sweat chloride concentrations >70 mEq/L, we even have a pickup rate of 92%. Whereas p.(Phe508del) is the most frequent allele (35% of the positive cases), 3 other mutations c.2988+1Kbdel8.6Kb, c.1393-1G>A, and p.(Gly85Glu) showed frequencies higher than 5% and a total of 9 mutations account for 84% of the mutations. This limited spectrum of CF mutations is in agreement with the homozygous ethnic origin of the Palestinian population. The relative large portion of patients without a mutation is most likely due to clinical misdiagnosis. Our results will be important in the development of an adequate molecular diagnostic test for CF in Palestine.

Studies of preventive nephrology: self-urinalysis as a feasible method for early detection of renal damage.

The ever expanding pool of ESRF patients is exerting considerable strain on the health care resources of all nations of the world. Rationing, in one form or the other has therefore become the norm for most countries. Because dialysis prolongs life and is more readily available, and because ethically acceptable donor kidneys remain in short supply, thus limiting the potential of renal transplantation, this rather exasperating situation is bound to continue unless the entry point into the pool can be actively tacked. As part of our initial effort in this direction, we have examined the feasibility of self urinalysis by the general population as an epidemiological tool for detecting evidence of early renal damage by a total population cross-sectional survey of Faizia East Primary Health District (FEPHD) of Buraidah, capital city of the Gassim region of Saudi Arabia. Out of a de facto population of 7,695, 75.37% (5,800) cooperated fully. Majority of those who could not cooperate (881 [11.44%]) were infants and children. A total of 969 subjects (12.59%), mostly males at work, were not available. Only 45 (0.58%) subjects refused to participate. Housewives were significantly more amenable to the organisation of family self-urinalysis than head of the family (92.2% vs 61.4%; chi square = 321.78; df: 3; P < 0.0001). The mean family size was 7.82 (+/- SD: 3.82). Above the age of 4 years, 66.5% of males (2108/3170) as against 81.7% of females (2,641/3232) were able to carry our self-urinalysis. 11.76% of boys and 8.5% of girls below the age of 5 years were able to carry out self-urinalysis. Only 0.05% of male subjects and 0.03% of females failed to interpret colour change for proteinuria correctly. Similar remarkable competence was demonstrated for glycosuria by the population. We conclude that self-urinalysis is quite feasible in the general population, even if illiterates, if young. It can form a sound foundation, if properly harnessed, for a renal registry.

Some aspects of the pattern of systemic hypertension in the adult population of Gassim, Saudi Arabia: age distribution of the subsets of hypertensives.

As part of our studies in prevent nephrology, we have recorded causal blood pressure during a total population cross-sectional survey of the Faizia East Primary Health District of Buraidah (FEPHD), capital of Gassim region of Saudi Arabia. Out of 5671 subjects whose blood pressure could be recorded, 2222 were above 19 years of age and constituted our adult population. For this report, hypertension have been defined as equal to and greater than 140/90 mm Hg. Total hypertensive population had been divided into three subsets, based on this basic definition, namely combined systolic and diastlic hypertension (S/DHPN), isolated systolic hypertension (ISHPN) and isolated diastolic hypertension (IDHPN), a format which is not generally clear in previous studies on the subject. The overall prevalence of systemic hypertension was found to be 23.58%, which is lower than the figure of 36% for USA (pre-primary prevention intensive campaign). It is assumed that all the three subsets mentioned above have been used in calculating the latter. Although males tended to be more hypertensive than females (OR = 1.22; Chi Square = 3.89; P = 0.05; C.I.: 1.00 < OR < 1.49), the marginal difference (25.7% vs 22.10%) was largely due to the IDHPN subset (OR = 1.73; Chi Square = 4.48; P = 0.034; C.I.: 1.01 < OR < 2.96). In both the S/DHPN and ISHPN: statistical significance was not achieved. Significantly, ISHPN subset constituted the bulk--56.68%--of the hypertensive population while IDHPN constituted the least--11.64%. When analysed into 10-year-age cohorts, ISHPN showed the steepest rise in prevalence with age. Rather suprisingly, the IDHPN did not rise with advancing age while the S/DHPN slope was in between the two. We are unable to identify this pattern in our literature search on the subject. We cannot assess its significance by this study, but we wonder whether or not it carries any prognostic significance in terms of target organ damage. It is possible that this pattern may be peculiar to the sub-region but it certainly is not spurious and in our view deserves further scrutiny. We wish to suggest that clear definition of the three subsets of hypertensive population should be mandatory when defining prevalence. This may provide some further clues in the prognosis and pathogenesis of target organ damage.

Blood pressure pattern in Saudi population of Gassim.

Blood pressure pattern for the Kingdom of Saudi Arabia has not been defined. In a total cross-sectional population survey of the Faizia East Primary Health District of Buraidah, capital of Gassim region, Saudi Arabia, 5671 subjects out of a de facto population of 7695 got their blood pressure recorded. The study district consisted of an urban section and a rural sector. Mean systolic and diastolic blood pressure were computed for the total population in conventional 5-year age cohorts as well as in an arbitrary functional age groups. The curve pattern and trends of the percentiles, were defined. Mean blood pressure (systolic and diastolic) was found to rise with age in both genders (male SBP: r = 0.66, P < 0.000001: female SBP: r = 0.58, P < 0.00001; male DBP: r = 0.53, P < 0.00001; female DBP: r = 0.45, P < 0.00001) and to correlate significantly with BMI. Both systolic and diastolic values were consistently higher in females than males. Overall means (+/- SD) were: for SBP, male 109.9 (+/- 21.57) vs female 114.33 (+/- 21.22) mm Hg; df: 5669: P < 0.00000; CI: -5.5, -2.0; for DBP, male 62.85 (+/- 16.89) vs female 64.67 (+/- 14.99) mm Hg; df: 5669; P < 0.0000; CI: -2.65, -0.989. Proteinuria (macroalbuminuria) was found to correlate positively and very significantly with both systolic and diastolic blood pressure: for SBP: r = 0.074, P < 0.0001; DBP: r = 0.055, P < 0.0001. Perhaps more significantly, in the context of preventive nephrology, is the observation that the intercept of the regression line with blood pressure was below the level conventionally regarded as hypertensive, suggesting that nephron damage may have occurred at this lower level. Overall mean diastolic blood pressure but not systolic was found to be significantly higher in the rural environment than the urban setting: mean rural DBP: 66.43 (+/- 15.699) vs urban: 62.78 (+/- 78); P < 0.00001; rural SBP: 113.71 (+/- 23.95) vs urban: 112.69 (+/- 19.87), P = NS. No discernible effect of consanguinity in marriage on blood pressure could be detected in this study but we believe that further details are required before a definite statement can be made on this important subject. The percentiles presented can only be regarded as foundation figures requiring further validation before they can be useful in determining cut-off levels for hypertension for the Saudi population.

Body mass index (BMI) in the Saudi population of Gassim.

In a total cross-sectional population survey of the Faizia East Primary Health District of Buraidah, Gassim region of Saudi Arabia, 6,044 (2727 male and 3317 females) subjects out of a de facto population of 7695 got their BMI computed because infants and restless or bedridden subjects could not be examined. Mean (+/- SD) and percentiles (25th & 75th) were calculated in the conventional 5-year age cohorts as well as in functional age groups, namely, 0-5, 6-12, 13-49, 50-69 and 70+ years. 5th, 10th, 25th, 50th, 75th, 90th and 95th percentiles were computed only for the functional age groups. In general, the trend was for BMI to increase with age in both genders but the curve pattern showed some plateauing from about the age of 50 with slight decline in later life. Females had significantly higher indices than males, this becoming quite prominent from the 10-14 year age cohort. This difference persisted irrespective of the types of age grouping or residential location. Overall means (+/- SD) were 20.14 +/- 5.98 vs 22.22 +/- 7.21 for males and females respectively; df: 5771; p = 0.0000; 95% CI: -2.43, -1.735. Subjects in the urban living environment had significant higher indices than their rural counterpart: (21.666.92 vs 20.446.33: df: 5771; P = 0.0000; 95% CI: 1.595, -0.840). From the age of 15 about one quarter of females are overweight (BMI at the 75th percentile > 25) and from 30 years the same proportion are frankly obese (BMI > 30). Both systolic and diastolic blood pressure were significantly positively correlated with BMI in both genders: male SBP: r = 0.22, P < 0.0001; male DBP: r = 0.21, P < 0.00001; female DBP: r = 0.18, P < 0.00001.

Studies on preventive nephrology: Systemic hypertension in the pediatric and adolescent population of Gassim, Saudi Arabia.

Casual blood pressure was recorded for subjects of Faizia East Primary Health District during a cross-sectional population survey. Valid information was obtained from 5671 subjects, out of which 3299 (1561 males and 1738 females) were between the ages of three and 18, constituting therefore the pediatric/adolescent (P/A) sector of our study population. The prevalence of hypertension (HPN), defined as A(3) 95th percentile for total HPN population (mild and severe) and A(3) 99th percentile for severe, was calculated for the three-year age cohorts suggested by the Task Force on Blood Pressure Control in Children (1987). The three subsets of HPN were derived from the suggested cut-off levels without any modifications. Overall prevalence of HPN was, for the P/A, found to be 10.65% (351/3299). Females in all the age cohorts were significantly more hypertensive than males, overall gender prevalence being 7.94% (124/1561) for males against 13.06% (227/1738) for females: P=0.0000019; CI: 0.45

Studies on preventive nephrology: pattern of the subsets of hypertension in the paediatric, adolescent and adult population of Gassim, Saudi Arabia.

As part of our studies in preventive nephrology, we have recorded the casual blood pressure during a total population cross-sectional survey of the Faizia East Primary Health District (FEPHD). A total of 5671 subjects had adequate records. Of these 2222 were adults (> 19 years). The prevalence of systemic hypertension (HPN) was calculated, using as cut-off levels, > or = 140/90 for the adult population and > or = 95th percentile as recommended by the Task Force for Blood Pressure Control in Children (1987) for the paediatric and adolescents (3-18 years). Using these definitions without modification, the three subsets of HPN viz. combined systolic/diastolic (S/DHPN), isolated systolic (ISHPN) and isolated diastolic (IDHPN) were derived for each of the age cohorts studied-10-year age cohorts for the adults and the Task Force 3-year age cohorts for the paediatric/adolescent (P/A) population. In both adult and P/A population ISHPN constituted the bulk of the hypertensive population (56.68% for the adults and 51.57% for P/A). the IDHPN subset was the least for adults making up 11.64% while the S/DHPN was in between constituting 31.68%: For the P/A population S/DHPN was the least, 15.95% and IDHPN (32.48%) was in between. When distributed into 10-year age cohorts for the adults, ISHPN showed the steepest gradient depicting increasing prevalence with advancing age. On the other hand, IDHPN did not rise with age; if at all, it tended to fall. The slope for S/DHPN was sandwiched in between. For the P/A population, for all the 3-year age cohorts, and for all the three subsets, there was an initial peak in childhood followed by a decline in adolescence. However, some variations were discernible in each subset. ISHPN in girls peaked at 10-12 before declining but in boys it virtually followed an even keel. IDHPN, in both boys and girls peaked sharply at 6-9 before a rapid decline in prevalence into adolescence. S/DHPN also peaked at 6-9 but both the upward slope and the subsequent decline were more gentle than the other subsets. When viewed together for our study population, assuming equivalence in cut-off levels for HPN, both ISHPN and S/DHPN seem to exhibit a bimodal curve, with one peak in childhood and a second rise in adulthood continuing into old age. IDHPN showed a unimodal curve, with the one peak in childhood followed by a continuing decline through adolescence into adulthood to virtual disappearance in old age. We believe these slopes may have prognostic significance which are not entirely clear at the moment but our findings reinforce the importance of the systolic blood pressure and that diastolic blood pressure alone should no longer be used as the index treatment or complication of high blood pressure.