Biomedical subjects

A Rahim

Publications and source records attributed to A Rahim.

At least 19 recordsLinked to original sources

PubMed2005

Placebo controlled trial of methotrexate in systemic sclerosis.

Eighteen adult patients of systemic sclerosis were included in this prospective study from Rheumatology Clinic of Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka during the period of July 1997 to December 1999 to observe the effectiveness of treatment with methotrexate (MTX) versus placebo. Among the eighteen patients 9 patients were randomly assigned to MTX and 9 to placebo therapy. Nine patients were dropped out (6 in placebo and 3 in the MTX group), because of toxicity and non-compliance. Clinical improvement following treatment was observed in 33.33% of the patient in MTX group but none in placebo group, but this difference was not statistically significant. Anorexia, nausea and occasional vomiting were common side effects in MTX group and subsided in most cases with the passage of time despite the continuation of therapy.

Adolescent↗

PubMed2004

Reduced toxicity of F-deficient Sendai virus vector in the mouse fetus.

Current concerns over insertional mutagenesis by retroviral vectors mitigate investigations into alternative, potentially persistent gene therapy vector systems not dependent on genomic integration, such as Sendai virus vectors (SeVV). Prenatal gene therapy requires efficient gene delivery to several tissues, which may not be achievable by somatic gene transfer to the adult. Initially, to test the potential and tropism of the SeVV for gene delivery to fetal tissues, first-generation (replication- and propagation-competent) recombinant SeVV, expressing beta-galactosidase was introduced into late gestation immunocompetent mice via the amniotic and peritoneal cavities and the yolk sac vessels. At 2 days, this resulted in very high levels of expression particularly in the airway epithelium, mesothelium and vascular endothelium, respectively. However, as expected, substantial vector toxicity was observed. The efficiency of gene transfer and the level of gene expression were then examined using a second-generation SeVV. The second generation was developed to be still capable of cytoplasmic RNA replication and therefore high-level gene expression, but incapable of vector spread due to lack of the gene for viral F-protein. Vector was introduced into the fetal amniotic and peritoneal cavities, intravascularly, intramuscularly and intraspinally; at 2 days, expression was observed in the airway epithelia, peritoneal mesothelia, unidentified cells in the gut wall, locally at the site of muscle injection and in the dorsal root ganglia, respectively. Mortality was dramatically diminished compared with the first-generation vector.

Adenoviridae↗

PubMed2004

Vitamin A deficiency in Afghanistan.

PURPOSE: To evaluate children 6 years old and younger, lactating mothers, and women of childbearing age for vitamin A deficiency in the districts of Kabul City, Afghanistan. METHODS: A set number of patients selected randomly in all 13 districts of the city limits were examined between August and September 2000 for ocular signs of vitamin A deficiency. RESULTS: Night blindness, Bitot's spot, corneal ulceration, and corneal scars were seen in increased amounts as defined by the World Health Organization among the sampled population. CONCLUSIONS: Vitamin A deficiency is a moderate to severe public health problem in children and lactating mothers in Kabul City, Afghanistan.

Adult↗

PubMed2001

The diagnosis of growth hormone deficiency (GHD) in successfully treated acromegalic patients.

Due to persistent qualitative abnormalities in GH secretion following treatment, and lack of a sensitive marker of GHD in mid-adult life it is extremely difficult to diagnose GHD in treated acromegalic patients. The diagnosis of GHD in patients with pituitary disease relies on provocative tests of GH reserve. Arginine releases GH by reducing somatostatin inhibition of GH release, whereas GH secretagogues (GHS) affect GH release by direct stimulation of the GHS receptor, though an intact GH releasing hormone (GHRH) axis is a prerequisite. The peak GH response to insulin-induced hypoglycaemia and arginine in acromegalic patients, in whom basal serum GH levels of less than 5 mU/l have been achieved, is greatly diminished in those treated by hypothalamo-pituitary irradiation. We aimed to study the response of successfully treated acromegalic patients to the growth hormone secretagogue hexarelin in view of its different putative mechanism of action, and in addition, to determine whether it has any value in the diagnosis of GH deficiency in this subset of patients. Nineteen acromegalic patients, in whom mean serum GH levels below 5 mU/l have been achieved through treatment, were recruited. Eight of the patients had been treated by surgery alone (Group A) and 11 had received primary or postoperative irradiation (Group B). All patients underwent 20 min blood sampling to provide a 24-h GH profile. Serum IGF-I was measured from a sample drawn between 0900 h and 1000 h. On a second visit arginine 20 g/m2 was infused over 30 min, blood samples were taken before commencing the infusion and at 30-min intervals thereafter for 180 min. At the final visit hexarelin 1.5 mcg/kg was administered as an intravenous bolus at t = 0. Blood was drawn at 15-min intervals from - 30 to 180 min. All patients in group A showed an increment in serum GH following hexarelin (DeltaGHHEX) > 20 mU/l, a normal response to arginine, and a mean 24-h GH > 0.5 mU/l. In group B only 4/11 achieved a DeltaGHHEX > 20 mU/l, 5/11 producing a response of < 2 mU/l. Four of the five patients with a DeltaGHHEX < 2 mU/l were also demonstrated to have a mean 24-h GH of < 0.5 mU/l and serum IGF-I SDS < + 0.5. All four patients in Group B who achieved a DeltaGHHEX > 20 mU/l, were observed to show an absent or minimal GH response to arginine. Despite loss of the GH response to arginine, the DeltaGHHEX is retained in a proportion of those patients in whom "safe" GH levels were achieved following irradiation. From the putative mechanisms of action of these provocative agents a plausible explanation would be that the GHRH axis is more resilient than endogenous somatostatin-secreting neurones to radiation-induced damage. Furthermore, GH secretagogues may have a role, in combination with serum IGF-I levels, in the diagnosis of GH deficiency in treated acromegaly.

Acromegaly↗

PubMed2001

The impact of irradiation on growth hormone responsiveness to provocative agents is stimulus dependent: results in 161 individuals with radiation damage to the somatotropic axis.

GH provocative tests remain the mainstay for the diagnosis of GH deficiency and at present the insulin tolerance test (ITT) is the gold standard. There are, however, a variety of other stimulation tests used in clinical practice. Each necessitates the use of a specific cut-off derived from normative data, but there remains a widely held view that the implications from a "failed" test are independent of the nature of the stimulus. We sought to examine whether this is the case in individuals with evidence of radiation damage to the somatotropic axis. One hundred and sixty-one nonacromegalic patients were identified who had undergone an arginine stimulation test (AST) and an ITT within a 3-month period as part of routine testing between 1975 and 1999. They were divided into those tested before (n = 81; 48 males) and those tested after (n = 80; 36 males) completion of growth and puberty. Patients were considered for inclusion in the study if they had a history of cranial irradiation and a GH response to one provocative test of less than 8 microg/L, taken as indicating that some damage to the GH axis may have occurred. The patients were compared with 2 control groups. The first comprised 35 adults (18 males) and the second consisted of 16 prepubertal children (10 males). The median peak (range) GH response to the ITT was significantly greater (P < 0.0001) than that to the AST in the adult controls: 24.9 (4.1--76.9) vs. 12.2 (0.88--35.0) microg/L, respectively. However, in the patients the GH responses were similar (P = 0.28): 2.2 (0.2--25.7) vs. 1.4 (0.2--12.8) microg/L to the ITT and AST, respectively. In contrast to the pattern seen in the adult controls, the response to an ITT in childhood controls was of similar magnitude (P = 0.5) to that to the AST: 17.5 (8.1--40.0) vs. 19.4 (7.3--53.8) microg/L, respectively. However in the patients, the GH response to the AST was greater than that to the ITT (P < 0.0001): 4.3 (0.7--17.2) vs. 3.0 (0.4--18.1) microg/L, respectively. In summary, we have shown that the impact of irradiation on GH responsiveness to provocative agents is stimulus dependent. The GH response to an AST appears to be more resistant to the effects of irradiation than that to the ITT. When investigating the impact of irradiation on GH secretory status, the GH response to an AST may be a less sensitive guide to the functional ability of the GH axis.

Adult↗

PubMed2000

Cancer incidence in Karachi, Pakistan: first results from Karachi Cancer Registry.

No cancer incidence data from Pakistan have been published in the 5 decades since independence. Incidence data for the period 1995-1997 from the population of the Karachi South district (1.7 million) are presented here. A total of 4,268 new cancer cases were registered during this period: 2,160 cases in males and 2,108 cases in females. Overall, 95.3% of the incident cases were microscopically verified. The incidence rates for all cancers combined were 80.5 per 100,000 (crude) and 136.7 per 100,000 (age- standardised rates [ASR]) for males and 91.8 (crude) and 163.2 per 100,000 (ASR) for females. In males, lung cancer (ASR 20.3) was the most frequently recorded malignancy followed by oral cavity (ASR 13.8) and larynx cancer (ASR 8.6). In females, breast was the most common site of cancer, accounting for one third of female cancers (ASR 51.7), followed by oral cavity (ASR 14.1) and ovarian cancer (ASR 10.2). Karachi reports the highest incidence of breast cancer for any Asian population, except Jews in Israel. Tobacco smoking is estimated to be responsible for 40% of cancers in males and tobacco chewing for a further substantial proportion of head and neck cancers.

Adolescent↗

PubMed1999

Reduced bone mineral density in young adults following cure of acute lymphoblastic leukaemia in childhood.

Bone mineral density (BMD), serum osteocalcin and type I collagen C-telopeptide (ICTP) were assessed in a cohort of 31 (16 males) adults who had received cranial irradiation in childhood as part of their treatment for acute lymphoblastic leukaemia (ALL). Markers of bone turnover were compared with those of 35 age and body mass index (BMI) matched young adults (18 male). Growth hormone status had previously been determined using an insulin tolerance test and arginine stimulation test. Eight patients were classified as severe growth hormone deficiency (group 1), 12 patients as growth hormone insufficient (group 2) and 11 patients as normal (group 3). Vertebral trabecular BMD, lumbar spine and femoral neck integral BMD and forearm cortical bone mineral content (BMC) was measured 17.8 (6.8-28.6) years after cranial irradiation and was expressed as Z (standard deviation) scores. There was a significant reduction in vertebral trabecular BMD (median Z score -1.25, P < 0.001), in lumbar spine integral BMD (median Z score -0.74, P = 0.001), in forearm cortical BMC (median Z score -1.35, P < 0.001), and less so in femoral neck integral BMD (median Z score -0.43, P = 0.03). There was no difference among the growth hormone status groups for the following BMD measurements: vertebral trabecular BMD, lumbar spine integral BMD or femoral neck integral BMD (P = 0.8, P = 0.96 and P = 0.4 respectively). There was only a marginal significant difference for BMD at the wrist between growth hormone status groups (P = 0.04). There was no correlation between the BMD measurements with time since or age at diagnosis and no difference in markers of bone turnover between patients and controls; median serum osteocalcin 13.3 and 12.0 ng ml (P = 0.7), respectively, and for ICTP 5.0 and 4.9 microg L (P = 0.67) respectively. In conclusion, there is a highly significant reduction in BMD in young adults following treatment for ALL in childhood. The reduction in BMD affects both trabecular and cortical bone but did not seem to be related to time since diagnosis, age at diagnosis, or current growth hormone status. Possible explanations include a direct effect of chemotherapy, steroids or both on bone during childhood and hence an effect on the accretion of bone mass. In view of the risk of fractures in patients with osteopenia, adults treated for ALL in childhood may be at an increased risk of bone fractures later in life irrespective of the underlying cause of the osteopenia and thus intervention should be considered.

Adolescent↗

PubMed1999

The effect of chronic hexarelin administration on the pituitary-adrenal axis and prolactin.

OBJECTIVE: With the development of growth hormone (GH) releasing agents and their use in human subjects, it is clear that these agents are not specific for GH release. More recent studies in humans have demonstrated acute increases in adrenocorticotrophic hormone (ACTH), cortisol and prolactin (PRL) after boluses of intravenous or subcutaneous GHRPs. The potential adverse effects of repeated episodes of transient hyperprolactinaemia and hypercortisolaemia during long-term therapy with growth hormone releasing peptides (GHRPs) and similar agents have raised concern. We have therefore assessed the impact of chronic hexarelin administration on the pituitary-adrenal axis and serum prolactin levels. DESIGN: Each subject received twice-daily subcutaneous hexarelin therapy (1.5 micrograms/kg body weight) for 16 weeks. The ACTH, cortisol and PRL responses to the morning subcutaneous injection of hexarelin were assessed. Hexarelin was administered at time 0 and blood samples were taken at -10, 0, 10, 20, 30, 40, 50, 60, 90, 120, 170 and 180 min. The ACTH and PRL responses were assessed at baseline and after 16 weeks of therapy. The cortisol response was assessed at baseline, 16 weeks and also 4 weeks after completion of hexarelin therapy. Basal levels of cortisol binding globulin (CBG), 24-h urinary free cortisol (UFC) estimations, thyroid stimulating hormone (TSH) and total thyroxine (TT4) were performed at baseline, weeks 16 and 20. RESULTS: The mean (+/- SEM) area under the cortisol curve (AUCCORT) at baseline, week 16 and week 20 were 1506 (+/- 77) nmol/l/h, 1222 (+/- 92) nmol/l/h and 1586 (+/- 58) nmol/l/h, respectively. There was a significant change in AUCCORT over the study period (P = 0.008). Compared with baseline, AUCCOPRT had decreased significantly (P < 0.05) after 16 weeks of hexarelin therapy. Four weeks after completion of hexarelin therapy, the AUCCORT increased significantly compared with AUCCORT at week 16 (P < 0.01) and was no longer significantly different from baseline values. There were no significant changes in UFC (P = 0.3), basal cortisol measurements (P = 0.19), area under the ACTH curve (AUCACTH) (P = 0.24) or CBG (P = 0.6) over the study period. The mean (+/- SEM) area under the PRL curve (AUCPRL) at the baseline and week 16 were 624 (+/- 82) mU/l/h and 641 (+/- 83) mU/l/h, respectively. There was no significant change in AUCPRL over the study period (P = 0.35). CONCLUSION: The present study demonstrates clearly that in this hexarelin dosage regimen, over-stimulation of the pituitary adrenal axis and prolactin secretion do not occur. In fact the impact of chronic hexarelin therapy on the pituitary-adrenal axis, i.e. decreased AUCCORT, contradict the findings reported after acute hexarelin administration and cannot be explained by changes in CBG. The lack of change in UFC, however, suggests that these changes are unlikely to be of clinical significance although the underlying mechanism requires further study.

Administration, Cutaneous↗

PubMed1999

Hyperleptinaemia in young adults following cranial irradiation in childhood: growth hormone deficiency or leptin insensitivity?

OBJECTIVE: In order to explore the mechanism of obesity in long-term survivors of childhood leukaemia, fat mass, lean body mass and serum leptin were assessed in a cohort of 32 (17 males) adults who had received cranial irradiation (XRT) in childhood as part of their treatment for acute lymphobiastic leukaemia (ALL), and compared with 35 age and body mass index (BMI) matched young adults (18 male). DESIGN: Thirty-one patients and 18 controls had fat mass and lean body mass assessed by dual x-ray absorptiometry (DEXA), using a lunar DPX-L scanner. Serum leptin concentrations were also measured in 27 patients and all controls. Growth hormone status had previously been determined using an insulin tolerance test and arginine stimulation test. Nine patients were classified as severe growth hormone (GH) deficient (group 1), 12 patients as GH insufficient (group 2) and 11 patients as normal (group 3). RESULTS: BMI and absolute fat mass were not significantly different between the patients and controls regardless of their gender (P = 0.1 and P = 0.14 respectively). In contrast, absolute lean mass was significantly reduced (P < 0.01) and leptin concentrations were significantly increased (P < 0.001) in patients compared with controls. BMI, fat mass and leptin concentrations but not lean mass were significantly different between the three GH status groups (P < 0.01, P < 0.01, P = 0.004, and P = 0.67 respectively). When leptin concentrations were expressed per unit of fat mass, they were increased in the patients compared with the controls (P = 0.03) with significant differences between the GH status groups (P = 0.004), being significantly higher in the severe GH deficient group. CONCLUSIONS: Young adults who receive cranial irradiation in childhood are prone to GH deficiency and hyperleptinaemia. The pathophysiological significance of the hyperleptinaemia remains to be established but it has occurred either as a consequence of radiation induced hypothalamic damage or GH deficiency.

Adolescent↗

PubMed1999

Dose titration and patient selection increases the efficacy of GH replacement in severely GH deficient adults.

OBJECTIVE: Previous studies of GH replacement in adults have used unselected cohorts of GH deficient (GHD) adults and weight-based dosing regimens resulting in supraphysiological serum IGF-I levels and a high frequency of side-effects and withdrawal from these studies. By choosing patients with a high level of morbidity at baseline and using a low dose GH titration regimen we aimed to avoid over-replacement and increase the efficacy of treatment. DESIGN: An open study of GH replacement, initiating treatment with a dose of 0. 8 U/day and titrating the dose by 0.4 U increments to normalize the IGF-I SDS between - 2.0 and + 2.0 SD of the age-related normal range. PATIENTS: 65 severely GHD patients (peak GH < 9 mU/l to provocative testing), 25 males, of mixed adult and childhood-onset and mean age 38.7 (range 17-72) years. Inclusion criterion was that of subjectively poor quality of life on clinical interview. MEASUREMENTS: Height, weight, waist and hip circumference were measured to allow calculation of body mass index (BMI) and waist-hip ratio (WHR). Bone mineral density (BMD) was measured by dual X-ray absorptiometry (DEXA). Serum haemoglobin A1C (HbA1C), lipid profile and insulin like growth factor 1 (IGF-I) were measured. The Psychological General Well-Being Schedule (PGWB) and Adult Growth Hormone Deficiency Assessment (AGHDA) self-rating questionnaires (SRQ) were used to assess quality of life. RESULTS: Baseline characteristics were consistent with those previously described in severely GHD adults; mean IGF-I SDS - 2.4 (+/- 2.7), BMI 28.8 (+/- 5. 4) kg/m2, total cholesterol 6.17 (+/- 1.2) mmol/l, reduced BMD z-scores at the lumbar spine (- 0.8 +/- 1.2) and femoral neck (- 0. 44 +/- 1.4), and SRQ scores considerably lower than reported in previous studies of GH deficient adults and normal controls. Following initiation of GH serum IGF-I SDS was increased significantly from baseline to a mean level of 0.15 +/- 2.7 (P < 0. 001) and 0.31 +/- 2.0 (P < 0.001) at three and eight months, respectively. The mean PGWB score increased from 59.7 +/- 19.9 to 75. 8 +/- 15.0 (P < 0.001) and 73.7 +/- 19.5 (P = 0.001) at three and eight months, respectively. An increase of 14 points represents the largest improvement in quality of life, using this index, that has been reported in GHD adults. The mean AGHDA score also demonstrated considerable improvement, falling from 15.3 +/- 6.0 to 10.4 +/- 6.2 (P < 0.001) and 9.8 +/- 6.5 (P < 0.001) at three and eight months, respectively. The changes observed in both the PGWB and AGHDA scores between baseline and at both three and eight months were shown to correlate significantly with the respective baseline score. A significantly greater improvement was observed in the PGWB following GH replacement in those with a baseline PGWB score of < 60 than in those with a score > 60. This observation was significant at both three (27.1 vs 6.7, P = 0.0001) and eight (25.6 vs 3.3, P = 0.0003) months. All PGWB subscales showed significant improvement though that of vitality was of greatest magnitude. A strong correlation was observed between the generic and disease-specific SRQ (r = - 0.73, P < 0.001). CONCLUSIONS: The observed improvement in quality of life in GH deficient adults is proportional to the degree of impairment before commencing therapy. The use of low-dose titration and selection of a population with greater morbidity reduces the occurrence of over-replacement and increases the efficacy of treatment. This allows direction of resources to those in greatest need.

Adolescent↗

PubMed1999

How many tests are required to diagnose growth hormone (GH) deficiency in adults?

OBJECTIVE: The diagnosis of GH deficiency in adults relies on the results of GH provocative testing. Whilst in some patients the testing strategy is clear, this is not the case in all patients. The objective of this study was to further examine the concordance between the GH responses to two different provocative stimuli, to correlate this with the number of additional pituitary hormone deficits, and to produce guidelines as to which patients require two GH provocative tests and which require only one. STUDY DESIGN AND PATIENTS: The results of GH provocative tests were reviewed in 103 patients (mean age 28 years, 48 male), with documented or potential hypothalamic-pituitary disease and 35 normal volunteers (mean age 21 years, 18 male). All patients and normal volunteers underwent an insulin tolerance test (ITT) and an arginine stimulation test (AST). Severe GH deficiency was defined as a GH response to an ITT of < 5 mU/l and a GH response to an AST of < 2 mU/l, utilizing data from previous studies in this unit. Patients were divided into four groups according to the number of anterior pituitary hormone deficits present other than possible GH deficiency: no other pituitary hormone deficits (GHD0) or one, two or three other hormone deficits (GHD1, GHD2 or GHD3). RESULTS: The 103 patients were divided between the four groups as follows: 69 (67%) in GHD0, 15 (14. 6%) in GHD1, six (5.8%) in GHD2, and 13 (12.6%) in GHD3. There was a significant decline in the median GH peak to both the ITT and the AST with increasing numbers of other pituitary hormone deficits (P < 0.0001). If the magnitude of the difference between each individual's GH response to the ITT and AST is plotted against the mean GH value a clear trend is seen (Spearmans rank correlation = 0. 88, P < 0.0001) indicating that the magnitude of the difference between the GH responses to an ITT and AST increases with the underlying mean GH value. These data allow the estimation of the median ITT/AST ratio as 1.17 (CI 0.98, 1.39). None of the control subjects and 14.1% (10), 26.7% (four), 83% (five) and 92.3% (12) of groups GHD0, 1, 2 and 3, respectively, had severe GHD. The concordance between the AST and ITT (percent of patients in whom both tests confirmed or refuted the biochemical diagnosis of severe GHD) was 100%, 76.8%, 66.6%, 83.3%, and 92.3% in the controls, GHD0, 1, 2, and 3, respectively. Thus, 16/69 GHD0, 5/15 GHD1, 1/6 GHD2 and 1/13 GHD3 patients were misclassified by one or other test. CONCLUSION: We have demonstrated that a constant ratio links the GH response to an ITT and AST in an individual, rather than a constant difference, and that the difference between the GH responses to two provocative stimuli is greater in those patients with milder degrees of GH deficiency or insufficiency. These patients tend to have one or no additional pituitary hormone deficits and may be misclassified if a single GH provocative test is performed. We suggest that whilst a single GH provocative test can be used with confidence in patients with two or three additional pituitary hormone deficits, in patients with suspected isolated GH deficiency or with only one additional pituitary hormone deficit, two GH provocative tests should be performed.

Adult↗

PubMed1999

Influences on quality of life in GH deficient adults and their effect on response to treatment.

OBJECTIVE: Studies of the effect of GH on quality of life (QOL) in growth hormone deficient (GHD) adults have reported conflicting results. Recently, however, we have demonstrated that by selecting only those patients with impaired QOL the efficacy of GH replacement on QOL can be greatly improved. The improvement in QOL was observed to correlate significantly with that recorded before commencing GH therapy. This study aims to assess if demographic variables affect QOL in untreated GHD adults or the improvement in QOL following GH therapy. DESIGN: An open study of GH replacement, initiating treatment with a dose of 0.8 IU/day and titrating the dose by 0.4 IU increments to normalize the IGF-I SDS between - 2.0 and + 2.0 SD of the age related normal range. PATIENTS: 65 severely GHD patients (peak GH < 9 mU/l to provocative testing), mean age 38.7 (range 17-72) years. Inclusion criterion was that of subjectively poor quality of life on clinical interview. MEASUREMENTS: Blood was taken for insulin-like growth factor 1 (IGF-I). The Psychological General Well-Being Schedule (PGWB) and Adult Growth Hormone Deficiency Assessment (AGHDA) self-rating questionnaires were used to assess quality of life at baseline, three and eight months after commencing GH. RESULTS: The patients were subgrouped on the basis of gender, age of onset of GHD, pathology and presence of additional pituitary hormone deficits. The cohort consisted of 40 females and 25 males, 45 of adult-onset (AO) and 20 of childhood-onset (CO). GH deficiency resulted from a hypothalamo-pituitary pathology, or treatment thereof, in 36 patients and as a result of cranial irradiation for a primary brain tumour or prophylaxis in acute lymphoblastic leukaemia in 29 patients. Isolated GH deficiency (IGHD) was present in 25 patients, and 32 patients were demonstrated to have at least two additional pituitary hormone deficits (MPHD). No significant difference was detected between baseline PGWB scores of the subgroups. Multiple linear regression analysis revealed the age of onset of GHD to be a significant determinant of both the baseline PGWB (P = 0.05) and AGHDA (P = 0.025) scores, AO patients perceiving the greater distress. A significant improvement, from baseline, in both QOL scores was observed in all subgroups at three months, and in all subgroups at eight months except IGHD, where a trend towards improvement in the AGHDA score was observed but failed to reach significance. The mean improvement in the PGWB following GH therapy was not significantly different between subgroups. Multiple linear regression analysis confirmed baseline PGWB and AGHDA scores to be the most important variable in prediction of the level of improvement in respective scores following GH therapy. Age of onset was also observed to be a significant determinant of the PGWB scores following GH therapy (P = 0.02), the CO cohort experiencing the greater improvement. A similar relationship between age of onset and AGHDA scores was not observed (P = 0.22). CONCLUSIONS: Baseline QOL as assessed by self-rating questionnaires is influenced by the age of onset of the GH deficiency, adult onset patients expressing the greater distress. Improvements in QOL scores are influenced by both baseline score and to a lesser extent the age of onset of GHD, the greater improvement being observed in childhood onset patients. The degree of improvement was observed to be independent of gender, pathology and number of pituitary hormone deficits. In a cohort selected by subjectively impaired QOL, we have demonstrated childhood onset GHD patients perceive themselves to have less impairment of QOL pretreatment. In contrast to previous data in unselected cohorts, however, we have shown that those childhood onset GHD patients in whom QOL is significantly reduced, show a capacity for improvement that is equal to, if not greater, than that seen in adult onset-GHD patients.

Adolescent↗

PubMed1999

Survivors of childhood cancer: long-term endocrine and metabolic problems dwarf the growth disturbance.

The long-term effects of radiotherapy and chemotherapy are becoming increasingly recognized as the cure rates of certain childhood malignancies improve. The endocrine system is particularly sensitive to cancer therapies. Long-term survivors of childhood cancer who received cranial irradiation have been shown to have lower than predicted height, an increased prevalence of obesity and reductions in strength, exercise tolerance, bone mineral density, quality of life and academic achievement. Growth hormone deficiency (GHD) is the most frequent endocrine deficiency observed following cranial irradiation. Adults with GHD resulting from primary hypothalamic-pituitary disease during childhood have been shown to exhibit a clinical picture similar to that described in long-term survivors of childhood cancer: increased fat mass and reduced lean mass, strength, exercise tolerance, bone mineral density and quality of life. This review considers the possible contribution of GHD to the adverse sequelae observed in long-term survivors of childhood malignancy and includes our preliminary experience in treating 14 adults with GHD resulting from the treatment of childhood malignancies.

Adult↗

PubMed1999

Selective lack of growth hormone (GH) response to the GH-releasing peptide hexarelin in patients with GH-releasing hormone receptor deficiency.

The mechanism of the synergistic relationship between GH-releasing peptide (GHRP) and GHRH with respect to GH secretion is poorly understood. We report the response to hexarelin, a potent GHRP, in patients affected with a homozygous mutation in the GHRH receptor gene, with consequent GHRH resistance and GH-deficient dwarfism. This newly described syndrome is the human homolog of the little (lit/lit) mouse. Intravenous administration of hexarelin (2 microg/kg) to four male adult patients (dwarfs of Sindh) resulted in a complete lack of elevation in plasma GH levels (< 1 ng/mL), an at least 50- to 100-fold deviation from the normal response. In contrast, plasma PRL, ACTH, and cortisol levels rose in a normal manner in response to hexarelin. We conclude that an intact GHRH signaling system is critical for GHRPs to exert their effect on GH release, but that the GHRH system is not necessary for the effect of GHRP on PRL and ACTH secretion. Hexarelin (and probably other GHRPs) are not effective agents for the treatment of patients with GHRH resistance due to GHRH receptor deficiency.

Adrenocorticotropic Hormone↗

PubMed1999

The pattern of malignancies in Karachi (1995 to 1996).

OBJECTIVE: To determine the cancer pattern of the city of Karachi for the years 1995-1996. METHODS: The Karachi Cancer Registry, established in 1995 by the Government of Sindh, in collaboration with the IARC is an active registry. The staff collect the data pertaining to cancer patients and record it on the registry forms. Hospitals in Karachi, district south as well as some of the hospitals in other districts of the city, where patients are likely to go for treatment or diagnosis are visited. People residing in the district for more than six months prior to the onset of the malignancy were considered "residents". All the cases diagnosed on or after 1st January 1995 till 31st December 1996 were considered for analysis. RESULTS: In the years 1995-96, the most common cancer sites among males were cancers of the lung, oral cavity and lymph nodes. For females, breast cancer ranked first, followed by cancer of the oral cavity and ovary. The age standardized rate for all cancers was 96.3 per 100,000 in males and 96.9 per 100,000 in females. At this early stage of registration we assume that the registry has a missing rate of approximately 20-25%. CONCLUSION: The pattern of malignancies in Karachi is similar to the western countries, with lung and breast being the commonest tumors amongst the males and females respectively. The Asian countries have stomach/lung/oral cavity/liver as the commonest tumors amongst the males and cervix/breast amongst the females. Pakistan being a Muslim country, the incidence of cervical cancer showed an expected low figure.

Adolescent↗

PubMed1998

Does desensitization to hexarelin occur?

Hexarelin, a potent growth hormone (GH)-releasing peptide, is capable of causing profound GH release in normal individuals. If the GH response to hexarelin in humans becomes appreciably attenuated following long-term administration, this would seriously limit the potential therapeutic use of hexarelin and similar agents. The effect of twice-daily subcutaneous injections of hexarelin on GH release was therefore investigated over a period of 16 weeks in 12 healthy elderly individuals. The mean (+/- SEM) areas under the GH curve (AUCGH) at weeks 0, 1, 4 and 16 were 19.1 +/- 2.4, 13.1 +/- 2.3, 12.3 +/- 2.4 and 10.5 +/- 1.8 microg/l/hour, respectively. There was a significant change in AUCGH over the study period (P = 0.0003). Further analysis showed that the decreases in AUCGH at weeks 4 and 16 were significant (P < 0.05 and P < 0.01, respectively) compared with baseline values. Four weeks after completion of the 16-week study period, hexarelin was again administered. On this occasion, AUCGH increased significantly compared with that at week 16 (from 10.5 +/- 1.8 to 19.4 +/- 3.7 microg/l/hour; P < 0.05) and was not significantly different compared with that at week 0. These results show that attenuation of the GH response after long-term hexarelin therapy is partial and reversible.

Aged↗

PubMed1998

Growth hormone status in adults treated for acute lymphoblastic leukaemia in childhood.

OBJECTIVE: Growth hormone status was assessed in a cohort of 32 (16 male) adults who had received cranial irradiation (XRT) in childhood as part of their treatment for acute lymphoblastic leukaemia (ALL) and compared with 35 age matched young adults (18 male). DESIGN: Height and weight were measured in all subjects and the heights of the patients at XRT were obtained from their case notes. Each patient and control underwent two provocative tests of growth hormone (GH) secretion using insulin (0.2 IU/kg body weight) and arginine (20 g/m2). Basal serum insulin like growth factor-1 (IGF-1) and IGFBP-3 (binding protein-3) concentrations were also measured. RESULTS: The patient group had a significantly lower peak GH response to both provocative tests (P < 0.01), and lower IGF-1 and IGFBP-3 levels compared with the normal controls (P < 0.01). Nine of the patient group were severely GH deficient (peak GH response < 9 mU/l to both provocative agents) and a further 12 patients were GH insufficient (peak GH response < 20 mU/l to both tests with at least one peak GH response > 9 mU/l). Overall a significant median change in height from XRT to final height of -0.5 SDS was found which was even greater in the severely GH deficient group (median change in height of -2.1 SDS). CONCLUSION: These data suggest that a significant proportion of adults treated with cranial XRT in childhood with irradiation doses between 18-25 Gy, as part of their treatment for ALL, are severely GH deficient now and should be considered for GH replacement. Changes in GH secretion evolve with time following irradiation-induced damage to the hypothalamic-pituitary axis; therefore long-term surveillance will be required in those remaining patients, in whom GH status is considered currently to be insufficient or even normal.

Adolescent↗

PubMed1998

Long-term change in the bone mineral density of adults with adult onset growth hormone (GH) deficiency in response to short or long-term GH replacement therapy.

OBJECTIVE: Only two previous studies have assessed the effects of long-term GH replacement therapy on bone mineral density (BMD) in patients with adult onset GH deficiency. To date no study has looked at the long-term impact on BMD after a short course (6-12 months) of GH replacement. In two groups of patients with adult onset GH deficiency we have studied BMD either (a) after 3 years of continuous GH replacement or (b) 2 years after completion of a short course of GH. DESIGN: An open GH therapeutic study in which patients were recruited from a previous double-blind placebo-controlled study. The BMD status of all patients was unknown to the physician and patient at the time of recruitment. PATIENTS: Group A (n = 7, three females) all received GH replacement continuously for 3 years. Group B (n = 8, five females) included six patients who received GH replacement for 6 months and two who received GH replacement for 12 months with BMD being measured at 6-monthly intervals. METHODS: Single photon absorptiometry (SPA) and later single X-ray absorptiometry (SXA) were used to measure forearm cortical BMD. Dual-energy X-ray absorptiometry (DXA) was used to measure lumbar spine, trochanteric, femoral neck and Ward's area BMD. RESULTS: In group A lumbar spine and trochanter BMD had increased significantly from baseline by 3.7% (DXA: median change = 0.045 g/cm2; P = 0.028) and 4.0% (DXA: median change = 0.031 g/cm2; P = 0.046), respectively. There were non-significant decreases in femoral neck (1.9%) (DXA: median change = -0.02 g/cm2; P = 0.39), Ward's area (6.5%) (DXA: median change = -0.06 g/cm2; P = 0.09) and forearm (2.6%) (SPA/SXA: median change = -0.013 g/cm2; P = 0.18). In group B, compared with baseline, only trochanter BMD changed significantly, increasing by 5.9% (DXA: median change = 0.0485 g/cm2; P = 0.049). Lumbar spine (DXA: median change = -0.001 g/cm2) Ward's area (DXA: median change = 0.0135 g/cm2), femoral neck (DXA: median change = -0.005 g/cm2) and forearm cortical (SPA/SXA; median change = -0.01 g/cm2) BMD did not change significantly (P = 0.67, P = 0.57, P = 0.86 and P = 0.31, respectively). Median percentage changes compared with baseline were -0.1%, 1.8%, -0.5% and -2.1%, respectively. From the time of completion of GH therapy however, BMD increased significantly at lumbar spine, (median change = 0.023 g/cm2), Ward's area (median change = 0.03 g/cm2) and trochanter (median change = 0.056 g/cm2) (P = 0.036, P = 0.049 and P = 0.012, respectively) but not at the femoral neck (median change = 0.017 g/cm2; P = 0.31) or forearm (median change = 0 g/cm2; P = 0.75). CONCLUSION: Long-term GH replacement therapy for three years appears to have beneficial effects on bone in patients with adult onset GH deficiency particularly at the lumbar spine and trochanter; the effects on femoral neck and forearm cortical BMD, however, are less impressive. A short course (6-12 months) of GH replacement therapy results in an increase in trochanter BMD several years later, and after an initial decline in BMD whilst on GH replacement, lumbar spine and Ward's area BMD return towards their baseline values. These results emphasize that not all types of bone and skeletal sites respond to GH therapy identically. Furthermore a short course of GH replacement over 6-12 months may result in significant changes in BMD several years later.

Absorptiometry, Photon↗