Jak Jervell

Sandostatin® LAR®: A promising therapeutic tool in the management of acromegalic patients

A stable and sustained suppression of growth hormone (GH) secretion was noted in 101 patients treated long term with individual doses (20 and 30 mg in 89 patients, 40 mg in 12 patients) of Sandostatin LAR (Sandoz Pharma Ltd, Basel, Switzerland). Doses of 20 mg and 30 mg at 4-week intervals delivered average octreotide concentrations of 1,348 +/- 483 ng/L and 2,631 +/- 1,026 ng/L, respectively, in steady-state conditions and provided adequate control of patients who had been well controlled during treatment with 0.1 mg and 0.2 mg thrice-daily subcutaneous (SC) Sandostatin. Suppression of GH serum concentrations to less than 5 micrograms, 2 micrograms, and even 1 microgram/L was recorded in more patients and more consistently during long-term treatment with Sandostatin LAR than Sandostatin. A marked decrease or even a normalization of insulin-like growth factor-1 (IGF-1) serum concentrations was observed after the first double-blind 10-, 20-, or 30-mg dose of Sandostatin LAR. A progressive improvement was recorded during long-term treatment, with normalization of IGF-1 serum concentrations in 65.3% of patients. A marked clinical improvement was observed in parallel, with 36 of 101 patients (35.6%) becoming asymptomatic after the nineteenth injection of Sandostatin LAR. A greater than 20% shrinkage of the GH-secreting adenoma was also recorded in 12 of 14 patients treated with Sandostatin LAR after receiving only 2 to 4 weeks of treatment with SC Sandostatin and in 11 of 18 patients receiving Sandostatin LAR as adjuvant therapy after failure of surgery. The systemic tolerability of Sandostatin LAR was good, and most adverse events were mild and short term (1 to 2 days). No impairment of thyroid function was detected. Newly occurring gallstones were recorded in four of 101 patients and microlithiasis in four of 101 after up to 30 months of treatment with Sandostatin LAR. Due to its excellent efficacy, good tolerability, convenience of administration, and acceptability by patients, Sandostatin LAR is considered a promising therapeutic tool in the management of acromegalic patients.

Cardiovascular diseases, diabetes mellitus, and cancer in the occupied Palestinian territory

Heart disease, cerebrovascular disease, and cancer are the major causes of morbidity and mortality in the occupied Palestinian territory, resulting in a high direct cost of care, high indirect cost in loss of production, and much societal stress. The rates of the classic risk factors for atherosclerotic disease-namely, hypertension, diabetes mellitus, tobacco smoking, and dyslipidaemia-are high and similar to those in neighbouring countries. The urbanisation and continuing nutritional change from a healthy Mediterranean diet to an increasingly western-style diet is associated with reduced activity, obesity, and a loss of the protective effect of the traditional diet. Rates of cancer seem to be lower than those in neighbouring countries, with the leading causes of death being lung cancer in Palestinian men and breast cancer in women. The response of society and the health-care system to this epidemic is inadequate. A large proportion of health-care expenditure is on expensive curative care outside the area. Effective comprehensive prevention programmes should be implemented, and the health-care system should be redesigned to address these diseases.

Sandostatin LAR®: Pharmacokinetics, pharmacodynamics, efficacy, and tolerability in acromegalic patients

Abstract Sandostatin LAR® was developed by incorporating octreotide in microspheres of the biodegradable polymer poly( dl -lactide-coglycolide glucose). One hundred acromegalics, 85 of whom were known to be “responders” to octreotide (subcutaneous [SC] Sandostatin® 0.1 to 0.2 mg three times daily), as measured by mean 12-hour growth hormone (GH) serum concentrations below 5 μg/L, were switched after a washout period of at least 3 days to single doses of 3, 6, 9, 12, 10, 20, and 30 mg Sandostatin LAR®. Octreotide and GH serum concentrations were assessed hourly from 8 am to 8 pm , during screening, at baseline (after washout), and on days 1 (day of injection), 7, 14, 21, 28, 35, 42 (for doses of 3, 6, 9, and 12 mg), and 60 (for doses of 10, 20, and 30 mg). The pattern of octreotide release was similar for all doses tested. A rapid increase in octreotide serum concentrations was noted after the intramuscular (IM) injection of Sandostatin LAR®, with a peak occurring within 1 hour of injection and followed by a progressive decrease to low octreotide levels within 12 hours. On days 2 through 7, after single doses of Sandostatin LAR®, lower octreotide serum concentrations were recorded. Thereafter, an increase in the serum octreotide concentration occurred and dose-dependent plateau concentrations were observed between days 14 and 42, followed by a progressive decrease from day 42 onward. In the plateau phase (days 14 to 42), daily average octreotide plasma concentrations remained very stable over the 12-hour observation period, comparing well with those seen after continuous SC infusion. The peak level on day 1 (for the 10-, 20-, and 30-mg doses) was lower than plateau octreotide concentrations, and the area under the peak on the Sandostatin LAR® injection day was no greater than 0.5% of the total area under the curve ([AUC] 0 to 60 days). A dose-dependent increase in the octreotide maximum concentration and AUC occurred in the dose range of 10 to 30 mg. There is an almost linear relationship between plateau octreotide concentrations and the dose administered. Plateau octreotide concentrations were approximately 350 ng/L for the 10-mg dose, 750 for the 20-mg dose, and 1,300 for the 30-mg dose. No accumulation of octreotide was noted after repeated injections at 4-week intervals in 40 patients who received up to seven injections of Sandostatin LAR®. Steady-state octreotide serum concentrations were reached after multiple injections (three injections at 4-week intervals) and were higher by a factor of 1.6 in comparison to plateau octreotide levels noted after the first injection. Plateau octreotide concentrations lasting for a period of 20 to 30 days point to once-a-month dosing in long-term treatment. The pattern of GH secretion irrespective of dose showed an initial suppression for 8 to 12 hours, followed by a return to almost preinjection values on days 2, 3, and 7 after the first injection. From days 14 to 42, the maximum suppression of GH secretion was recorded for each dose tested. Reproducible and stable suppression of GH secretion was noted after single-dose administration of 10, 20, or 30 mg and repeated injections of 20, 30, or 40 mg Sandostatin LAR®, and this mirrored the consistent and stable octreotide concentration. A trend toward progressive suppression of GH secretion and insulin-like growth factor-I (IGF-I) serum concentrations was noted during long-term treatment (up to 35 weeks) with repeated (up to seven) IM injections of Sandostatin LAR®. Administered at 4-week intervals, the 20- and 30-mg doses provided a very good clinical control of acromegalic symptoms/signs in all patients, including the “partial responders” (with GH concentrations not suppressed to below 5 μg/L). The local tolerability was very good, with mild to moderate local pain on injection days. Systemic tolerability of Sandostatin LAR®, including gallstone formation, compared well with the SC treatment with Sandostatin®. As a result of the convenience of administration, very good acceptance, very stable and consistent octreotide serum concentrations in long-term treatment, and very good biological and clinical efficacy, it is expected that Sandostatin LAR® will become the medical treatment of choice in acromegalic patients.

Obesity in a rural and an urban Palestinian West Bank population

OBJECTIVE: To compare the prevalence of obesity, household food consumption patterns, physical activity patterns and smoking between a rural and an urban community in the Palestinian West Bank and to describe the associations of the latter factors with body mass index (BMI).DESIGN: A population-based cross-sectional survey in a rural and an urban Palestinian West Bank community.SUBJECTS: A total of 549 women and 387 men aged 30–65 y, excluding pregnant women.MEASUREMENTS: Obesity was defined as BMI ≥30 kg/m2.RESULTS: The prevalence of obesity was 36.8 and 18.1% in rural women and men, respectively, compared with 49.1 and 30.6% in urban women and men, respectively. The mean difference (s.e) in BMI levels was 1.6 (0.52) kg/m2 between urban and rural women and 0.9 (0.46) kg/m2 in men. At the household level, the mean energy consumption from 25 selected food items was 13.8 MJ (3310 kcal)/consumption unit/day in the rural community compared to 14.5 MJ (3474 kcal)/consumption unit/day in the urban community (P=0.021). BMI was positively associated with age in both men and women and with urban residence in women. BMI was negatively associated with smoking and physical activity in men and with educational level in women.CONCLUSION: BMI was associated with urban residence in women after adjusting for age, smoking, education, physical activity and nutrition-related variables, suggesting that the differences in the conventional determinants of obesity could not fully explain the difference in the prevalence of obesity between the two communities. Among men, the measured determinants explained the rural–urban differences in BMI.

Obesity and selected co-morbidities in an urban Palestinian population

OBJECTIVE: To assess the prevalence of obesity and central obesity in an urban Palestinian population and their associations with selected co-morbidities, including diabetes, hypertension and dyslipidaemia.DESIGN: A population-based cross-sectional survey in an urban Palestinian community.SUBJECTS: Men and women aged 30–65 y residing in the urban community, excluding pregnant women.MEASUREMENTS: According to WHO guidelines, obesity for men and women was defined as BMI≥30 kg m−2, while pre-obesity was defined as BMI 25–29.9 kg m−2. Central obesity was defined as a waist-to-hip ratio (WHR) of >0.90 in men and >0.85 in women.RESULTS: The prevalence of obesity in this population was high at 41% (49% and 30% in women and men, respectively). Central obesity was more prevalent among men (59% compared to 25% in women). After adjusting for the effects of age, sex, smoking and each other, obesity and central obesity were found to be significantly associated with diabetes, low HDL-cholesterol and elevated triglycerides in separate logistic regression analyses. Central obesity was also significantly associated with hypertension (OR 2.26, 95% CI 1.30–3.91).CONCLUSION: Obesity and central obesity are prevalent in the urban Palestinian population. Their associations with diabetes, hypertension, and dyslipidaemia point to a potential rise in cardiovascular disease (CVD). An understanding of the reasons behind the high prevalence of obesity is essential for its prevention as well as for the prevention of the morbidities to which it may lead.

Type 2 diabetes mellitus, impaired glucose tolerance and associated factors in a rural Palestinian village

SUMMARY

Severe or Life-Threatening Hypoglycemia in Insulin Pump Treatment

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Novopen--a useful aid also for blind diabetic patients.

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The utility of a single glucometer measurement of fasting capillary blood glucose in the prevalence determination of diabetes mellitus in an urban adult Palestinian population.

This paper aims to evaluate the utility of a single glucometer fasting capillary blood glucose (FCBG) measurement in determining the prevalence of diabetes mellitus in a homogeneous adult population. FCBG measurements were compared with results of the oral glucose tolerance test (OGTT) in 445 subjects aged 30-65 years in an urban cross-sectional study in Old Ramallah. Prevalence of diabetes, sensitivity, specificity and predictive values were calculated at different cut-off levels of FCBG, using OGTT as the reference. The prevalence of OGTT-diagnosed diabetes was 2.7%, while it varied considerably using different cut-off levels of FCBG. The sensitivity of a single glucometer (Exac Tech II) measurement of FCBG at the cut-off level of 6.7 mmol l-1 was 33.3%, with a specificity of 98.8%. Using the cut-off level of 6.1 mmol l-1 as suggested by the 1998 provisional report of a WHO consultation, the sensitivity increased to 41.7%. At a cut-off level of 5.6 mmol l-1, a sensitivity of 66.6% was reached, but the specificity decreased slightly. It can be concluded that a single glucometer measurement of FCBG in an adult population is not useful in determining the prevalence of diabetes mellitus.This paper aims to evaluate the utility of a single glucometer fasting capillary blood glucose (FCBG) measurement in determining the prevalence of diabetes mellitus in a homogeneous adult population. FCBG measurements were compared with results of the oral glucose tolerance test (OGTT) in 445 subjects aged 30-65 years in an urban cross-sectional study in Old Ramallah. Prevalence of diabetes, sensitivity, specificity and predictive values were calculated at different cut-off levels of FCBG, using OGTT as the reference. The prevalence of OGTT-diagnosed diabetes was 2.7%, while it varied considerably using different cut-off levels of FCBG. The sensitivity of a single glucometer (Exac Tech II) measurement of FCBG at the cut-off level of 6.7 mmol 1(-1) was 33.3%, with a specificity of 98.8%. Using the cut-off level of 6.1 mmol 1(-1) as suggested by the 1998 provisional report of a WHO consultation, the sensitivity increased to 41.7%. At a cut-off level of 5.6 mmol 1(-1), a sensitivity of 66.6% was reached, but the specificity decreased slightly. It can be concluded that a single glucometer measurement of FCBG in an adult population is not useful in determining the prevalence of diabetes mellitus.