Documentation of ethical conduct of human subject research published in Saudi medical journals.

We evaluated the documentation of ethical conduct (obtaining institutional review board approval and consent and following ethical guidelines) of human subject research studies published in Saudi Arabian medical journals between 1979 and 2007. Studies were classified as retrospective, prospective noninterventional, interventional or survey/interview. Of 1838 studies published in 286 journal issues of 11 Saudi Arabian medical journals, only 0.9% documented the ethical guidelines followed, with a significantly higher rate for studies published after year 2000 (1.7%). Of 821 studies requiring institutional review board approval, 8.6% documented obtaining the approval and informed consent, with a significantly higher rate for interventional studies (19.4%), post-year 2000 studies (19.7%) and studies performed outside Saudi Arabia (15.9%). The low documentation rate suggests editor's lack of rigor and/or investigators' ignorance of guidelines. The higher documentation rate after year 2000 suggests an ongoing improvement.

Documentation of ethical conduct of human subject research published in Saudi medical journals

We evaluated the documentation of ethical conduct [obtaining institutional review board approval and consent and following ethical guidelines] of human subject research studies published in Saudi Arabian medical journals between 1979 and 2007. Studies were classified as retrospective, prospective noninterventional, interventional or survey/interview. Of 1838 studies published in 286 journal issues of 11 Saudi Arabian medical journals, only 0.9% documented the ethical guidelines followed, with a significantly higher rate for studies published after year 2000 [1.7%]. Of 821 studies requiring institutional review board approval, 8.6% documented obtaining the approval and informed consent, with a significantly higher rate for interventional studies [19.4%], post-year 2000 studies [19.7%] and studies performed outside Saudi Arabia [15.9%]. The low documentation rate suggests editor's lack of rigor and/or investigators' ignorance of guidelines. The higher documentation rate after year 2000 suggests an ongoing improvement

Medical chaperoning at a tertiary care hospital in Saudi Arabia: survey of physicians.

BACKGROUND: Medical chaperones (MC) are underutilised. The influence of Islamic culture on the use of MC is not known. AIM: To examine physicians' use and perception of MC in Islamic culture. SETTING: A major tertiary care hospital in Saudi Arabia. METHODS: 315 self-administered questionnaires were distributed to attendees of grand rounds of 13 departments. RESULTS: 186 (59%) questionnaires were completed. 64.5% of the respondents were 30-49 years old, 75.8% were men and 31.2% were in training; 79% had a clinic load of under 50 patients per week and 47.8% had postgraduate training (PGT) in an Islamic country. MC were reported to be infrequently (< or =25% of the time) used by 44.1% (69.2% female vs 39% male physicians, p = 0.001; 58.6% in training vs 36.8% attending, p = 0.007; 52.1% PGT in Islamic vs 35.6% in western countries, p = 0.027), offered by 52.7% (78.9% female vs 46.8% male physicians, p<0.001) and requested by 79% of patients. MC were reported to be commonly (>75% of the time) used, offered by physicians and requested by patients by 38.2%, 29% and 7.5% of respondents, respectively. The most frequently cited reasons for not using MC were privacy/confidentiality (36.6%) and understaffing (30.5%). Equal numbers of respondents perceived MC use as a protection for physicians or patients (67.7% and 65.6%, respectively). CONCLUSIONS: MC are underutilised even in Islamic culture, especially among female physicians. Training in western countries is favourably associated with MC use. Underutilisation appears to be related to privacy/confidentiality, understaffing and failure of patients to request a MC.

Differential effects of in vitro and in vivo hyperthermia on the production of interleukin-10.

OBJECTIVE: To determine whether hyperthermia activates an anti-inflammatory response. DESIGN: A prospective study. SETTING: Heatstroke Center, Makkah, and King Faisal Specialist Hospital, Riyadh, Saudi Arabia. PATIENTS: Twenty-five heatstroke patients pre-cooling (rectal temperature 42.4 +/- 0.8 degrees C) (group 1) and 13 normothermic heat-stressed subjects were studied (group 2). Twelve of the 25 heatstroke patients were also studied post-cooling (group 3). Mononuclear cells from six healthy blood donors resting at 24 degrees C were used for in vitro study. INTERVENTIONS: Mononuclear cells were cultured at a concentration of 1 x 10(6)/ml without and with lipopolysaccharide (LPS) added at concentration of 10, 100, and 1000 ng/ml. The cells were incubated for 24 h at 37, 39, 41, and 43 degrees C. ELISA was used to measure IL-10 in the supernatant and plasma from heatstroke and heat-stressed subjects. RESULTS: All patients in group 1, 40% of group 2, and 37% of group 3, showed elevation of IL-10 (1289 +/- 2519, 248 +/- 393, and 172 +/- 226 pg/ml, respectively) compared with normal control levels, (< 100 pg/ml) P < 0.05. IL-10 level on admission did not correlate with degree of hyperthermia. During 24 h incubation at 37 degrees C without LPS, no IL-10 was detected, whereas with 10 ng/ml LPS, monocytes released 658 +/- 291 pg IL-10/10(6) cells. At 39 degrees C and 41 degrees C IL-10 release was decreased to 225 +/- 114, and 245 +/- 90 pg/10(6) cells, respectively; and was completely inhibited at 43 degrees C (67 +/- 10 pg/10(6) cells), P < 0.0001. CONCLUSION: Heat-stress with and without hyperthermia is associated with anti-inflammatory response in vivo. However, it does not seem to be the direct effect of heat on monocytes, suggesting that other environmental or genetic factors may be involved.

Radioiodine uptake in the head and neck.

OBJECTIVE: To report two cases of sinusitis-associated radioiodine uptake in patients with thyroid cancer and to review the reported causes of false-positive radioiodine uptake in the head and neck area. METHODS: We present the radiologic findings in two patients who had undergone treatment for papillary thyroid cancer and discuss other settings in which radioiodine uptake suggested the presence of metastatic disease. RESULTS: Radioiodine whole-body scans of two patients who had had thyroid cancer demonstrated uptake in the sphenoid and maxillary sinuses, respectively, mimicking bone or brain metastatic involvement. The thyroglobulin levels were low. Computed tomographic (CT) scanning disclosed mucosal swelling in the sinuses, consistent with sinusitis. The radioiodine uptake cleared on a follow-up scan in one case and was more localized than the CT findings in the other. Eighteen causes of false-positive radioiodine uptake in the head and neck area have been reported. On the basis of the mechanism of uptake, they can be classified into four categories: (1) physiologic uptake (ectopic thyroid tissue), (2) nonthyroidal pathologic conditions (dacryocystitis, sinusitis, sinus mucocele, sialadenitis, folliculitis, Warthin's tumor, parotid cyst, porencephaly, posttraumatic cerebromalacia, and inflammation due to dental disease or a nose ring), (3) internal retention (ectasia of the carotid artery and an artificial eye), and (4) external contamination by body secretions (sweat and nasal, tracheobronchial, lacrimal, and salivary secretions). The estimated prevalence of external contamination in the head and neck area on whole-body radioiodine scans is 0.3%. CONCLUSION: Physicians should rule out the presence of radioiodine uptake by inflamed mucosa of the paranasal sinuses, as well as various other causes of false-positive radioiodine uptake, before metastatic thyroid cancer in the head and neck area is diagnosed.

Primary hypothyroidism-associated TSH-secreting pituitary adenoma/hyperplasia presenting as a bleeding nasal mass and extremely elevated TSH level.

A 41-year-old male with primary hypothyroidism and a huge TSH-secreting pituitary tumor presented with a bleeding nasal mass that was initially misdiagnosed as a paraganglioma. Other unique features of the case include lack of complaints related to hypothyroidism, an extremely elevated TSH level of 3474 mU/l, and a low prolactin level. The presence of primary hypothyroidism made differentiating TSH-secreting pituitary adenoma from secondary thyrotroph hyperplasia difficult. A low molar ratio of alpha-subunit to TSH on presentation, together with normalization of TSH level and a 50% reduction in the size of the tumor after 6 weeks of thyroxine replacement therapy, suggested the presence of thyrotroph hyperplasia. However, the lack of further decrease in the size of the tumor that was associated with increased metabolic activity on 18-FDG PET scan, intense uptake on octreotide scan, and an elevated alpha-subunit to TSH molar ratio despite the normalization of free T4 and TSH levels for 16 months suggested the coexistence of thyrotroph adenoma. Together, the findings support the view that thyrotroph adenoma/irreversible hyperplasia can result from long standing primary hypothyroidism.

Radioiodine uptake in inactive pulmonary tuberculosis.

Radioiodine may accumulate at sites of inflammation or infection. We have seen such accumulation in six thyroid cancer patients with a history of previously treated pulmonary tuberculosis. We also review the causes of false-positive radioiodine uptake in lung infection/inflammation. Eight foci of radioiodine uptake were seen on six iodine-123 diagnostic scans. In three foci, the uptake was focal and indistinguishable from thyroid cancer pulmonary metastases from thyroid cancer. In the remaining foci, the uptake appeared nonsegmental, linear or lobar, suggesting a false-positive finding. The uptake was unchanged, variable in appearance or non-persistent on follow-up scans and less extensive than the fibrocystic changes seen on chest radiographs. In the two patients studied, thyroid hormone level did not affect the radioiodine lung uptake and there was congruent gallium-67 uptake. None of the patients had any evidence of thyroid cancer recurrence or of reactivation of tuberculosis and only two patients had chronic intermittent chest symptoms. Severe bronchiectasis, active tuberculosis, acute bronchitis, respiratory bronchiolitis, rheumatoid arthritis-associated lung disease and fungal infection such as Allescheria boydii and aspergillosis can lead to different patterns of radioiodine chest uptake mimicking pulmonary metastases. Pulmonary scarring secondary to tuberculosis may predispose to localized radioiodine accumulation even in the absence of clinically evident active infection. False-positive radioiodine uptake due to pulmonary infection/inflammation should be considered in thyroid cancer patients prior to the diagnosis of pulmonary metastases.

Bone mineral density of the spine and femur in healthy Saudi females: relation to vitamin D status, pregnancy, and lactation.

Bone mineral density (BMD) measurements of the anterio-posterior lumbar spine and the proximal femur using dual-energy x-ray absorptiometry, as well as relevant clinical and biochemical parameters, were determined in 321 healthy Saudi females in order to establish reference values and to study the effects of physical and lifestyle factors on BMD. Mean +/- SD of age, body mass index (BMI), number of pregnancies, and total duration of lactation were 35.4 +/- 11.3 years, 26.5 +/- 5.2 kg/m2, 3.1 +/- 3.1, and 23.7 +/- 42.4 months, respectively. Mean +/- SD of serum calcium, 25-hydroxyvitamin D (25OHD), and PTH levels were 2.37 +/- 0.09 mmol/liter, 24.5 +/- 17.2 nmol/liter, and 52.0 +/- 30.8 pg/ml, respectively. Peak BMD values were observed around age 35 years at the spine and earlier at the femur. Compared with USA females, Saudi females had lower weight-matched Z scores at the spine (-0.126 +/- 1. 078, P = 0.04), femoral neck (-0.234 +/- 0.846, P < 0.0001), and Ward's triangle (-0.269 +/- 1.015, P < 0.0001). Further, the prevalence of osteopenia and osteoporosis in subjects >/=31 years old were 18-41% and 0-7%, respectively, depending on the site examined. Severe hypovitaminosis D (25OHD level

PIP: This paper examines the relationship between bone mineral density (BMD) of the spine and femur and vitamin D status, pregnancy, and lactation among women in Saudi Arabia. The aims of the study are the following: 1) establish normative data for BMD at the anterio-posterior lumbar spine and femur using dual x-ray absorptiometry; 2) compare the BMD of Saudi females and their US counterparts; and 3) examine the relation of BMD to vitamin D status, pregnancy, and lactation. Samples included 321 healthy Saudi females recruited from the city of Riyadh, Saudi Arabia. Results suggest that the mean standard deviation (SD) of age, body mass index, number of pregnancies, and total duration of lactation were, respectively, 35.4 +or- 11.3 years, 26.5 +or- 5.2 kg/sq. m, 3.1 +or- 3.1, and 23.7 +or- 42.4 months. Mean +or- SD of serum calcium, 25-hydroxyvitamin D (25OHD), and PTH levels were 2.37 +or- 0.09 mmol/liter, 24.5 +or- 17.2 nmol/liter, and 52.0 +or- 30.8 pg/ml, respectively. Peak BMD values were observed around age 35 years at the spine and earlier at the femur. Compared with US females, Saudi females had lower weight-matched Z scores at the spine, femoral neck, and Ward's triangle. On the other hand, the number of pregnancies and total duration of lactation correlated with weight-matched BMD Z scores at the spine. This made the BMD in healthy Saudi females significantly lower than their US counterparts. This may due to the increase number of pregnancies and longer duration of lactation together with prevalent vitamin D deficiency.

Tissue inhibitor of metalloproteinases-1 (TIMP-1) mRNA is elevated in advanced stages of thyroid carcinoma.

Tumour cell invasion and metastasis is a multistep process that involves the degradation of extracellular matrix proteins by matrix metalloproteinases (MMPs). Tissue inhibitors of metalloproteinases (TIMPs) act as negative regulators of MMPs and thus prevent tumour cell invasion and metastasis by preserving extracellular matrix (ECM) integrity. In the present study we examined the expression of one member of TIMPs, TIMP-1, in 39 thyroid tumour specimens and two thyroid carcinoma cell lines (NPA and SW579). We also investigated the effect of high TIMP-1 expression on the invasive potential of NPA cells. Northern blot analysis showed that TIMP-1 mRNA levels correlated directly with tumour aggressiveness: the highest number of TIMP-1 transcripts was found in stages III and IV vs benign goitre (P < 0.0001). However, TIMP-1 expression was not increased in NPA and SW579 cells, both of which are derived from poorly differentiated thyroid tumours. Immunohistochemical study showed strong TIMP-1 staining in the stroma cells of advanced stages of carcinomas. Overexpression of TIMP-1 by gene transfer resulted in a significant suppression of the malignant phenotype of NPA cells as judged by an in vitro tumour invasion assay. These results suggest that high levels of TIMP-1 transcripts in advanced stages of thyroid carcinoma likely come from stroma rather than thyroid cancer cells, and TIMP-1 may function as a thyroid tumour invasion/metastasis suppressor.

Prevalence and severity of hyponatremia and hypercreatininemia in short-term uncomplicated hypothyroidism.

Hypothyroidism is widely accepted as a cause of hyponatremia and hypercreatininemia. However, the prevalence and severity of hyponatremia and hypercreatininemia in hypothyroid patients without comorbid conditions have not been well documented. We retrospectively studied serum sodium and creatinine levels in thyroid-ablated patients with differentiated thyroid cancer off (no.=128) and on (no.=60) thyroid hormone therapy. In the hypothyroid state, mean(+/-SD) TSH, sodium, and creatinine levels were 130.3+/-104.8 mU/l, 139.3+/-2.7 mEq/l, and 89.4+/-20 mmol/l respectively. Twenty-four patients (18.8%) had creatinine levels above the age- and sex-adjusted normal range, whereas only five patients (3.9%) had sodium levels below 135 mEq/l. No patient had a sodium level less than 130 mEq/l. Compared to their euthyroid values, mean sodium and creatinine levels of the hypothyroid patients changed by -1.18 mEq/l (p=0.003) and 17.2 mmol/l (p<0.0001), respectively. There was significant correlation of TSH levels in the hypothyroid state with the changes from the euthyroid state to the hypothyroid state in creatinine levels (r=0.29, p=0.02) but not with the corresponding changes in sodium levels (r=0.06, p=0.6). In thirty-seven patients studied in two hypothyroid episodes, there was a significant correlation between a) TSH levels in hypothyroid state 1 and hypothyroid state 2 (r=0.56, p=0.0003), and b) the change in creatinine levels from the euthyroid state to hypothyroid state 1 and the corresponding change from the euthyroid state to hypothyroid state 2 (r=0.48, p=0.003). There was no significant correlation between the change in sodium levels from the euthyroid state to hypothyroid state 1 and the corresponding change from the euthyroid state to hypothyroid state 2 (r=0.32, p=0.05). We conclude that hyponatremia is very uncommon, whereas mild to moderate elevation in serum creatinine level is not uncommon in patients with short-term uncomplicated hypothyroidism.

Radioiodine secretion in tears.

UNLABELLED: Lacrimal secretion of radioiodine has been suspected from previous scintigraphic observations. We semiquantitated radioiodine secretion in the tears of a thyroid-ablated patient with an artificial eye while the patient was on thyroxine treatment. METHODS: After an oral dose of 555 MBq (15 mCi) 123I, 12 tear samples were collected over 24 hr by using Schirmer papers. Radioactivity in each sample was determined in a well counter 27 hr after radioiodine ingestion and was corrected for decay and counting efficiency. RESULTS: Radioactivity was detectable at 15 min and at up to 24 hr after radioiodine ingestion and peaked at around 60 min (215 Bq/microl or 39 x 10(6)% of the administered dose/microl. Considering a tear-flow rate of 1 microl/min, the total radioactivity secreted in the first 4 hr was estimated to be 56 kBq, representing about 0.01% of the administered dose. CONCLUSION: An appreciable amount of ingested radioiodine could be secreted in tears. The potential damage of the lacrimal gland after high doses of 131I treatment deserves further study.

Lymphocyte subsets and adhesion molecules expression in heatstroke and heat stress.

We examined the specificity of the recently reported alterations in circulating lymphocytes in heatstroke by determining lymphocyte subsets in 14 consecutive heatstroke patients before and after cooling and in 7 heat-stressed controls using single- or two-color immunofluorescence flow cytometry. The relationship with catecholamine levels was also studied. In heatstroke, percentages of T (CD3(+)/CD19(-)), T-helper (CD4(+)/CD8(-)), T-inactive [CD3(+)/human leukocyte antigen-DR-], CD11a+, CD11c+, and CD44(+) lymphocytes were significantly decreased, whereas percentages of T-suppressor-cytotoxic (CD8(+)/CD4(-)), natural killer (NK; CD3(-)/CD16(+) or CD56(+)), CD3(+)/CD16(+) or CD56(+), and CD54(+) lymphocytes were significantly increased, compared with 11 normal controls. The changes in the absolute numbers of lymphocyte subsets were in the same direction and were significant for T-helper, T-suppressor-cytotoxic, NK, CD3(+)/CD16(+) or CD56(+), and CD11c+ lymphocytes. Milder but significant changes in percentages of T-helper, T-suppressor-cytotoxic, CD11c+, and CD44(+) lymphocytes were seen in heat stress. Cooling was associated with partial or complete normalization, further derangement (CD11a+, CD11c+), or overcorrection (NK, T-suppressor-cytotoxic, CD11b+) of abnormal percentages of lymphocyte subsets. Norepinephrine levels were significantly elevated in heatstroke (4.7-fold) and heat stress (3.2-fold), but did not significantly correlate with lymphocyte subsets. We conclude that heatstroke is associated with significant changes in percentages and in absolute numbers of a wide range of circulating lymphocyte subsets that are not related to elevated catecholamine levels or totally normalized by cooling. Similar, albeit milder, changes are seen in heat stress, suggesting that the two syndromes represent a continuum.

Primary hyperparathyroidism-associated polyostotic fibrous dysplasia: absence of McCune-Albright syndrome mutations.

Several cases of sporadic primary hyperparathyroidism in association with fibrous dysplasia of the bone have been reported in the English literature. Since fibrous dysplasia is a major feature and hyperparathyroidism is occasionally found in the McCune-Albright syndrome, we hypothesized that such cases may represent a variant of this syndrome. A 28-year-old male had primary hyperparathyroidism associated with polyostotic fibrous dysplasia but no other manifestations of the McCune-Albright syndrome. Genomic DNA samples from his parathyroid adenoma, dysplastic bone sample, and peripheral leukocytes were analyzed for the presence of activating mutations of the stimulating G protein alpha subunit gene (gsp). Allele-specific hybridization revealed the presence of normal sequences only, coding for arginine and glutamine at codons 201 (exon 8) and 227 (exon 9), respectively. Further, single strand conformational analysis of a 224 base pair fragment of exon 8 revealed no conformational aberrations. Furthermore, the sequences of a 164 base pair fragment of exon 8 and a 170 base pair fragment of exon 9 were normal. The results strongly suggest that gsp mutation is absent in affected and normal tissues in this patient and that the association of hyperparathyroidism and fibrous dysplasia may not represent a variant of the McCune-Albright syndrome.

Concentrations of soluble tumor necrosis factor and interleukin-6 receptors in heatstroke and heatstress.

OBJECTIVE: Increased proinflammatory cytokine concentrations have been implicated in the pathogenesis of heatstroke. Soluble cytokine receptors can modulate circulating cytokine activities. We examined the possible role of soluble tumor necrosis factor receptors (sTNFR 60, sTNFR 80) and interleukin-6 receptor (sIL-6R) in heatstroke by determining their concentrations before and after cooling, as well as in heatstressed controls. DESIGN: Prospective controlled study. SETTING: Heatstroke Center, Makkah, Saudi Arabia (1993 pilgrimage). PATIENTS: Twenty-five consecutive heatstroke patients before and after cooling, 14 heatstressed controls (HSC), and 13 normal controls (NC). MEASUREMENTS AND MAIN RESULTS: Concentrations of sTNFR 60, sTNFR 80, and sIL-6R, as well as their ligands, were measured using commercially available enzyme-linked immunosorbent assay kits. Mean sTNFR 60 concentration was increased in heatstroke (p <.0001, vs. NC; p < .0001, vs. HSC) and in HSC (p = .004, vs. NC). Mean sTNFR 80 concentration was increased in heatstroke and decreased in HSC (p = .01, heatstroke vs. HSC). Mean sIL-6R concentration was decreased in heatstroke and increased in HSC (p = .04, heatstroke vs. NC; p = .001, heatstroke vs. HSC). IL-6 was undetectable in NC and mean IL-6 concentration was more increased in heatstroke than in HSC (p = .001). Rectal temperature and creatinine concentrations correlated significantly with sTNFR 60, sTNFR 80, sIL-6R, and IL-6 concentrations. After cooling, mean concentrations of sIL-6R and sTNFR 80 increased significantly, whereas the mean sTNFR 60 concentration did not change. Residual neurologic deficits were associated with higher precooling IL-6 (p = .002) and postcooling sTNFRs (p < .0001) concentrations. CONCLUSIONS: Significant changes in cytokine receptor concentrations are associated with heatstress. In heatstroke, the changes are more pronounced, and for some cytokine receptors, the changes are in the opposite direction (compared with changes in heatstress). Concentrations of IL-6 and sTNFRs correlate with hyperthermia and outcome. Cooling did not normalize sTNFR concentrations, suggesting failure to control the inflammatory response.