The effect of vitamin D status on the severity of bone disease and on the other features of primary hyperparathyroidism (pHPT) in a vitamin D deficient region.

A clear relationship between vitamin D status and the clinical indices of primary hyperparathyroidism (pHPT) severity has not been convincingly established. We proposed that such a relationship might exist, in so far as vitamin D deficiency could contribute to the severity of metabolic bone disease and promote the growth of the parathyroid tumor. Accordingly, we undertook a retrospective study and analyzed the clinical, biochemical, radiological and histopathological findings in a group of 49 patients who underwent parathyroidectomy at our center. Patients who had skeletal X-rays were grouped, according to their X-ray findings, in group A (19 patients; 45%) if they had severe bone changes, or group B (23 patients; 55%) if they had mild or no bone changes. Patients were also stratified according to their 25-hydroxyvitamin D (25-OHD) levels in tertiles. The 2 groups were compared using Fisher's exact test or analysis of variance as appropriate. Group A patients were younger (p=0.001), had more musculoskeletal symptoms (p=0.0003), and complained more frequently of fatigue (p=0.02). They had higher alkaline phosphatase (AP; p=0.0002), PTH index (p=0.0007), and serum Ca level (p=0.006). There were more patients from the lower and middle vitamin D tertiles and fewer patients from the upper vitamin D tertile in group A (p=0.02). Post-operative severe hypo-calcemia was more prevalent in group A patients (p<0.0001). Resected parathyroid tumors were larger in size in group A patients (p=0.01), and weighed more (p=0.01). There was a positive correlation between the weight of the parathyroid tumor and the PTH index (p=0.002), and AP level (p=0.0007). We concluded that vitamin D deficiency is a contributing factor to both the severity of bone disease and the high activity of parathyroid tumors seen in many patients with pHPT in vitamin D deficient regions.

Impact of cervical lymph node dissection on serum TG and the course of disease in TG-positive, radioactive iodine whole body scan-negative recurrent/persistent papillary thyroid cancer.

In the management of papillary thyroid cancer (PTC), surgery is indicated for locoregional recurrent/persistent disease. In this study, we examined the effect of such surgery on serum TG and the course of the disease in 21 patients with PTC (mean age 38.5 yr), who after the initial surgery and radioactive iodine (RAI) ablation developed high TG (>10 ng/ml) and negative 123I whole body scan (DxWBS). All patients had neck persistent/recurrent PTC that was confirmed by ultrasound-guided fine needle aspiration. Prior to neck re-exploration, radiological studies (chest X-rays, CT scan of the chest, and fluoro-18-deoxyglucose positron emission tomography [FDG-PET]) showed no evidence of distant metastases. TG autoantibodies were negative in 19 patients. Second surgery consisted of unilateral (13 patients) or bilateral (8 patients) modified neck dissection. The mean+/-SE TG prior to neck re-exploration was 184.8+/-79.0 ng/ml and declined after surgery to 127.5+/-59.0 ng/ml (p=0.25). The corresponding TSH values were 150.6+/-23.0 and 143.4+/-20.0 mU/l, respectively (p=0.34). After a mean follow-up of 20.7+/-3 months, TG increased to 168+/-68.0 ng/ml. This increase, however, was NS (p=0.67). The corresponding TSH values were 143.4+/-20.0 and 132.0+/-22.0 mU/l (p=0.27). Following second surgery, only 4 patients achieved remission, the other 17 patients received one or more of the following therapies; RAI (10 patients), third surgery (5 patients), and/or external radiation (7 patients). Thirteen patients continued to have persistent disease and 4 patients showed progressive course of their disease (distant metastases or grossly palpable neck disease). In conclusion, second surgery for recurrent/persistent PTC leads to remission in only a minority of cases but the course of the disease tends to be stable in most cases.

Detection of metastatic parathyroid carcinoma with Tc-99m sestamibi imaging.

PURPOSE: To assess the use of Tc-99m sestamibi to localize recurrent and metastatic parathyroid carcinoma. METHODS: A patient with a history of parathyroid carcinoma that was resected 6 months before had high serum calcium and high serum parathyroid hormone levels. Tc-99m sestamibi imaging was performed to localize the recurrence. RESULTS: Tc-99 sestamibi imaging detected the recurrence and the metastatic lymph nodes. These findings were confirmed surgically and pathologically. CONCLUSION: Tc-99m sestamibi can be useful in diagnosing and localizing metastatic parathyroid carcinoma.

Insulin treatment of elderly type 2 diabetic patients: effects on retinopathy.

Insulin treatment is reportedly associated with the transient progression of retinopathy, possibly with the development of macular oedema in middle-aged Type 2 diabetic patients. The purpose of this study was to investigate the effect of insulin treatment on eye-grounds in elderly (> 65-year-old) Type 2 diabetic patients with secondary failure of oral antidiabetic-drug therapy. Eye examinations were performed in 37 patients randomized to insulin (n = 19) or sulphonylurea (n = 16) treatment and re-investigated after one year. Insulin treatment reduced HbA1c from 9.3% to 7.3% (p < 0.001) after one year. In the sulphonylurea-treated group, HbA1c did not change (9.1 vs. 9.3%). At the start, 65% of the patients had retinopathy, and after one year progression was noted in 7/35 patients (20%; 5 insulin- and 2 sulphonylurea-treated). In the insulin-treated group, the 5 patients with progression had higher initial fasting blood-glucose levels than other patients in the group (15.8 vs 13.1 mmol/L, p < 0.05). Initial HbA1c levels did not differ between the groups (9.8 vs. 9.1%, n.s.), nor the reduction of HbA1c levels during treatment (2.2 vs. 1.3% n.s.). Thus, diabetic retinopathy in this study was common among elderly Type 2 diabetic patients. The progression of retinopathy may in fact be associated with insulin treatment or improvement of metabolic control.

An overview of breast cancer.

Breast cancer is a major health problem in many parts of the world. Its impact in Saudi Arabia will be more obvious when the national data is released from the National Cancer Registry (NCR) in the near future. It is the most common cancer referred to the King Faisal Specialist Hospital and Research Centre (KFSH&RC). This is a retrospective review of all female breast cancer cases treated at KFSH&RC over a 15-year period. Patients were divided into two groups at the time of their referral to KFSH&RC: metastatic and nonmetastatic. We describe the demographic data, cancer-related information and the treatments offered to all patients. Comparisons were made between Saudi and non-Saudi, and the Saudis were examined in relation to their region of referral and observed to see if any changes occurred during the study period. As well, we tried to compare our results with experience elsewhere. A total of 1584 female breast cancer patients were treated at KFSH&RC between 1975 and 1991. Early breast cancer (Stages I, II) represented 36%, while 64% presented with advanced or metastatic disease (Stages III, IV). The majority of patients were premenopausal (64%). For patients with Stages I-III (1005), mastectomy was performed in 85% and lymph node dissection in 93%. Only 30% had no pathologic lymph node involvement and in 49% of the patients, lymph node dissection was adequate (>/= 10 nodes removed). Estrogen and progesterone receptors were known in 30% of the patients. Sixty-two percent and 72% of patients referred from the central region and the northern region had Stages II and III, respectively. For the non-Saudis, we observed more premenopausal patients (76%) and fewer Stage III. At 15 years, the relapse-free survival in Stages I, II and III was 33%, 36% and 18%, and the overall survival was 80%, 64% and 45%, respectively. Breast cancer in this population affects younger patients (premenopausal) and a higher proportion present with metastatic or locally advanced disease. Management strategies should incorporate conservative surgery when appropriate, and adequate lymph node dissection. This should be coupled with increasing public awareness and education and institution of screening programs. Overall survival is clearly linked to the stage of the disease.

A study of 875 cases of thyroid cancer observed over a fifteen-year period (1975-1989) at the King Faisal Specialist Hospital and Research Centre.

Thyroid cancer (TC) is a common malignancy encountered at King Faisal Specialist Hospital and Research Centre (KFSH&RC). Of 19,885 different malignant tumors seen during the period fro 1975 to 1989, there were 875 cases (4.4%) of TC. Of 1374 tumors of endocrine glands seen during the same period, 67% were thyroid neoplasms. TC represented 7.5% (618 cases) of all neoplasms in the females, second only to breast cancer. All types of TC were seen, with papillary thyroid carcinoma (PC) being the most common (79%). Anaplastic, medullary, follicular (FC), malignant lymphoma and Hürthle cell cancer accounted for 5.4%, 5.3%, 4.3%, 3.6% and 0.9% respectively. The frequency of PC was very similar (16%) in each of the third, fourth and fifth decades. The relative frequency (RF) of different types of TC was highest for PC with a ration of 18:1 between PC and FC, which could be the highest ever reported. There was a clearly progressive increase in the number of thyroid tumors referred between 1975 and 1989. Although this increase was evident for both sexes, it was more apparent for females. There was also a distinct increase (P<0.01) in the RF of PC from 76% (1975 to 1980) to 85% (1986 to 1989) with a decrease in FC from 9% to 2.5% over the same periods.

Pheochromocytoma and pregnancy: report of three cases.

Three cases of pheochromocytoma associated with pregnancy are reported. Two patients had adrenal pheochromocytoma coexistent with normal pregnancy and one patient had a bladder pheochromocytoma coexistent with molar pregnancy (gestational trophoblastic disease). The diagnosis was made antenatally in the two normal pregnancy patients, both underwent planned tumor resection, one at mid-trimester, complicated by postoperative miscarriage, while the other had tumor resection during cesarean section at term. Bladder pheochromocytoma, preoperatively mistaken for invasive trophoblastic tumor, was resected at the time of planned abdominal hysterectomy for molar pregnancy, pheochromocytoma was recognized only after microscopic study of the resected bladder tumor. The three patients survived with no evidence of disease.

Detection of the H-RAS oncogene in human thyroid anaplastic carcinomas.

We have transfected high-molecular-weight DNA from human thyroid carcinomas into murine 3T3 cells. As a result we identified several foci of morphologically distinct transformed cells in each of the tumour DNA transfected cultures. After a total of three rounds of transfection, the transformed cells were shown to form tumours in nude mice. Southern blot analysis of DNA prepared from third-round transfectants demonstrated the presence of human Alu repetitive sequences and, after hybridization with probes for known oncogenes, indicated the presence of the human H-RAS oncogene in 3T3 cells transfected with three out of four anaplastic carcinoma DNA samples. It appears therefore that activation of RAS genes may be an important event in the development of the anaplastic thyroid tumours.

Abnormal expression of the MOS proto-oncogene in human thyroid medullary carcinoma.

We have been studying the expression of a range of proto-oncogenes in human thyroid tumour tissue by using Northern blot analysis. We have demonstrated the expression of a MOS mRNA of 1 kb in all thyroid samples. Furthermore, in a medullary carcinoma sample we also observed additional mRNA species of 1.7 and 2.2 kb. Southern blot analysis of DNA prepared from the same tumour sample did not reveal a rearrangement of the gene. These findings are the first report of MOS expression in any human tissue, and indicate that MOS oncogene activation might be important in the development of some thyroid tumours.

Intraocular infestation by the reindeer warble fly larva: an unusual indication for acute vitrectomy.

A case of ophthalmomyiasis interna posterior (OIP) caused by the larva of the Reindeer warble fly is reported. The larva was initially found intraretinally in the inferior parts of the fundus. From this position it moved into the macula lutea within two days, causing decreased visual acuity. Acute vitrectomy was performed and the larva was removed through a retinotomy. About two months afterwards a small retinal detachment appeared near the ora serrata, where the larva had entered the eye. The retina was reattached with a scleral buckling procedure. The patient regained most of his vision postoperatively. Pars plana vitrectomy is a safe procedure and we consider that in any case of OIP, with a living larva in the eye, acute vitrectomy should be considered, since the larva may damage vital parts of the eye. Furthermore, the site of entrance should be treated with photocoagulation to prevent retinal detachment.

Dietary modulation of retina phospholipids and photoreceptor function with particular reference to phosphatidylinositol.

The effect of dietary partially hydrogenated herring oil (HHO) on the fatty acid composition of the phospholipids of rat retina and on the amplitude of the a-wave of the electroretinogram (ERG) was studied in rats raised for several generations on an essential fatty acid poor diet. The most significant effect of the dietary treatment was a decreased content of arachidonic acid (C20:4 omega 6) and an increased concentration of docosahexaenoic acid (C22:6 omega 2) and 18:1 isomers associated with the phosphatidylinositol (PI). The a-wave of the ERG showed a decreasing amplitude during the experiment and was reduced with about 30% (P less than 0.004) of the initial value in all rats at the end of the experiment. The pronounced change in the arachidonic content in PI and the decreased amplitude of the a-wave of the ERG suggest that arachidonic acid of the PI has an important function in the visual phototransduction process.

Studies on the effect of 4-methylpyrazole on methanol poisoning using the monkey as an animal model: with particular reference to the ocular toxicity.

Young cynomolgus monkeys (Macaca fascicularis) were chosen as a model to investigate the ocular toxicity in animals poisoned with methanol and treated with 4-methylpyrazole (4-MP). The metabolism of methanol in the monkey was investigated after administration of 4-MP. Plasma levels of methanol, formic acid, 4-MP and 4-hydroxy-MP (4-OH-MP) were determined. After intramuscular injection, 4-MP was rapidly absorbed and depressed the elimination rate of methanol as well as the accumulation of formate in the blood. The results show the same great individual variations in monkeys as in humans regarding the susceptibility to methanol poisoning. Administration of a single dose of 5 g/kg induces a serious intoxication in most monkeys, causing death to some of them. Two monkeys receiving a single dose of 6 g/kg of methanol developed a serious initial inebriation and were treated with 4-MP. These monkeys survived and showed no signs of toxicity on ocular examinations which included ophtalmoscopy and electroretinogram (ERG) recordings.

Pancreatic polypeptide-producing tumors. Report on two cases.

Histochemical, chemical and clinical features of two malignant endocrine pancreatic tumors were studied. Both tumors contained pancreatic polypeptide (PP)-immunoreactivity in the majority of tumor cells. In addition, one tumor contained a few scattered serotonin-fluorescent cells and the other scattered gastrin-immunoreactive cells. Pancreatic polypeptide hypersecretion was established from both tumors. Serotonin was produced by one tumor and gastrin was secreted by the other. No PP-associated endocrine symptoms were present, whereas the hypergastrinemia may have caused a bleeding duodenal ulcer in one patient. Although both tumors were highly malignant the clinical courses in the two patients were very different; one patient died within a few months whereas the other is alive 2 years after the diagnosis.