A rare missense mutation in CHRNA4 associates with smoking behavior and its consequences.

Using Icelandic whole-genome sequence data and an imputation approach we searched for rare sequence variants in CHRNA4 and tested them for association with nicotine dependence. We show that carriers of a rare missense variant (allele frequency=0.24%) within CHRNA4, encoding an R336C substitution, have greater risk of nicotine addiction than non-carriers as assessed by the Fagerstrom Test for Nicotine Dependence (P=1.2 × 10(-4)). The variant also confers risk of several serious smoking-related diseases previously shown to be associated with the D398N substitution in CHRNA5. We observed odds ratios (ORs) of 1.7-2.3 for lung cancer (LC; P=4.0 × 10(-4)), chronic obstructive pulmonary disease (COPD; P=9.3 × 10(-4)), peripheral artery disease (PAD; P=0.090) and abdominal aortic aneurysms (AAAs; P=0.12), and the variant associates strongly with the early-onset forms of LC (OR=4.49, P=2.2 × 10(-4)), COPD (OR=3.22, P=2.9 × 10(-4)), PAD (OR=3.47, P=9.2 × 10(-3)) and AAA (OR=6.44, P=6.3 × 10(-3)). Joint analysis of the four smoking-related diseases reveals significant association (P=6.8 × 10(-5)), particularly for early-onset cases (P=2.1 × 10(-7)). Our results are in agreement with functional studies showing that the human α4ß2 isoform of the channel containing R336C has less sensitivity for its agonists than the wild-type form following nicotine incubation.

Clinical features in secondary and cryptogenic organising pneumonia.

SETTING: The clinical differences between cryptogenic organising pneumonia (COP) and secondary organising pneumonia (OP) have not been studied well. OBJECTIVE: To compare clinical features in COP and secondary OP. DESIGN: Causes, clinical features, treatment, radiographic studies and pathology were studied. RESULTS: After re-evaluation, 104 patients fulfilled the diagnostic criteria, 58 for COP and 46 for secondary OP. The mean age was 68 years. Most of the patients were smokers (79/104). Infections were the most common causes of secondary OP (21/46). Cough was the most common symptom and crackles the most common sign. Crackles were more common in patients with secondary OP (P = 0.02). Transbronchial biopsy was the diagnostic test in 81/104 cases. Most patients had lowered partial oxygen pressure (PO(2)) and mildly restrictive spirometry, with no differences between the two groups. Radiographic features were similar. Corticosteroids were the treatment in 70% of the patients, but 27% received no pharmacological treatment. The average initial dose of steroids was 42 mg prednisolone, and was similar for both groups. Relapses were seen in 20% of cases, with no difference between the two groups. CONCLUSION: There were no major differences in clinical features of COP and secondary OP, except that crackles were more common in secondary OP.

Acute Q fever: a cause of fatal hepatitis in an Icelandic traveller.

Domestic Q fever is rare in the Nordic countries; the infection is acquired abroad in the majority of cases. This is the first Nordic report of a fatal case of Q fever, which occurred in an Icelandic cancer patient who had travelled to the Canary Islands.

[Bronchoscopic diagnosis of lung malignancies.].

OBJECTIVE: To assess the diagnostic yield of fiberoptic bronchoscopy in patients with a variety of radiographic findings suspected of malignancy. MATERIAL AND METHODS: The study group was composed of all patients who underwent bronchoscopy in our hospital over a seven year period (1986-1993) where cytologic samples were obtained. Schematic drawings of endobronchial and radiographic findings done at the time of bronchoscopy were reviewed and the results of cytologic and histologic samples were compared for sensitivity and diagnostic accuracy. RESULTS: Bronchoscopy and cytologic sampling was performed on 189 patients. Tissue samples were obtained in 109 patients from visible endobronchial abnormalities or peripheral lesions using the transbronchial approach with fluoroscopic guidance. A total of 64 malignancies were diagnosed, 43 by bronchoscopy (67%). Among 58 patients who had primary malignancy of the lung, adenocarcinoma was the most frequent histologic type (50%) followed by squamous cell carcinoma (22%) and small cell carcinoma (17%). The diagnostic sensitivity of cytology was 30% whereas that of tissue biopsy was 70% among those patients where both tests were obtained. The two methods complemented each other to give a joint sensitivity of 76%. Among 13 patients with malignancy and normal endobronchial appearance, transbronchial biopsy was performed in 10 of which seven were diagnostic. Patients with primary malignancy who underwent surgery had a five year survival of 37% while the overall five year survival was 15.5%. CONCLUSIONS: In this study histology was much more sensitive than cytology as a sampling technique during bronchoscopy (p< 0.01). Adenocarcinoma has become the most frequent histologic type of primary lung malignancy in Iceland and overall survival among patients with primary tumors compares with recent international trends.

[Parathyroid surgery in Landakotsspítali 1973-1994.].

The results of 44 operations on 42 patients (nine men and 33 women) for primary hyperparathyroidism in Landakotsspitali, Reykjavik during the period 1973-1994 were studied. Only one patient needed reoperation because of persistent hypercalcemia. The operative success rate is 97.7%. One patient had two recurrent single adenomas with an interval of three years during which the patient was normocalcemic. Two patients were diagnosed having multiple endocrine neoplasia type I (MEN) before the operation. One of those had a brother with parathyroid carcinoma. Hyperparathyroidism was histologically verified in all 42 patients. Thirtyseven (88%) had adenoma, and four (9.5%) had chief cell hyperplasia. Double adenomas were diagnosed in four patients (9.5%). In two patients functioning oxyphil cell adenomas were encountered. One case (2.4%) could not be histologically sub typed. This patient had a brother who died of parathyroid carcinoma. One patient with type I MEN syndrome had adenoma, the other had chief cell hyperplasia. No parathyroid carcinoma was diagnosed. Thirtyone patients needed medical treatment for transient postoperative hypocalcemia. Permanent hypocalcemia was found in three patients. Vocal cord paralysis was recorded in one case. No other complication was found. Two patients had elevated parathyroid hormone (PTH), both nine years after the operation. One of those is normocalcemic and without symptoms, the other hypocalcemic for unexplainable reasons.

[Ganglioneuroma of the appendix. A case report.].

Ganglioneuroma of the appendix are among the most uncommon benign appendiceal tumours. They sometimes obstruct the lumen of the appendix and cause abdominal pain or appendicitis but some are diagnosed incidentally at autopsy or abdominal operations. The first known case in Iceland is represented and the literature reviewed.

Hypothalamic hamartoma causing precocious puberty treated by surgery: case report.

A 6-year-old girl was treated for precocious puberty secondary to a hypothalamic hamartoma by resection of the tumor. When she was six months old, her parents noticed incipient pubic hair and menses accompanied by breast development. Computed tomography was judged as normal. The girl was treated with monthly gonadotropin-releasing hormone analogue injections until 6 years of age, when magnetic resonance imaging (MRI) demonstrated a pedunculated isodense mass below the tuber cinereum. The hamartoma was totally removed using microsurgery. The symptoms and signs of precocious puberty disappeared after surgery. Follow-up MRI 1 year later showed no remaining tumor.

Flow cytometric DNA analysis of adenocarcinomas of the vermiform appendix. Brief report.

The DNA ploidy status and S-phase fraction of eight adenocarcinomas of the vermiform appendix diagnosed in Iceland during 1974-1990 were analyzed by flow cytometry. Four cases were classified as Dukes' stage B2 and four cases as Dukes' stage D. Seven tumors were diploid and one was aneuploid. The DNA aneuploid tumor was the only one which metastasized outside the abdominal cavity. The S-phase fraction in general was low. The results of this study do not indicate any significant correlation between ploidy status and clinical behavior.

Cancer of the pancreas in Iceland. An epidemiologic and clinical study, 1974-85.

A retrospective study was performed of all patients diagnosed as having pancreatic cancer in Iceland during the period 1974-85 (12 years). The incidence of the disease during the period according to this study was 10.7 per 100,000 males and 9.8 per 100,000 females, with age-adjusted world standard incidences of 9.0 per 100,000 males and 6.7 per 100,000 females. A total of 301 patients were identified; adequate information could be obtained for 281 patients, and 225 (74.8%) had the diagnosis histologically confirmed. Two hundred and five patients with adenocarcinoma were accepted for detailed analysis. Of the patients with adenocarcinoma 139 (67.8%) were diagnosed at laparotomy, and 33 of them had the tumour resected, with an operative mortality of 12.1%. The cancer was located in the head of the pancreas in 102 patients (49.8%), and in 159 (77.6%) metastases were found at the time of diagnosis. The median survival time for the patients with adenocarcinoma was 95.4 days (SD +/- 11.1 days), although there were two patients in this group who were alive 5 years after diagnosis. The median survival for the total group of 281 patients was 98.3 days (SD +/- 11.0 days), although 6 of these patients lived for more than 5 years. The percentage of histologically confirmed tumours in Iceland is high compared with many previously reported studies.

Adenocarcinoma of the vermiform appendix. A population study.

We report seven cases of adenocarcinoma of the vermiform appendix occurring in Iceland during 1974-1989. The patients ranged in age from 25-83 years, mean age 55.1 years. There were five males and two females. Five had mucinous adenocarcinoma, two had adenocarcinoma. Four patients presented with symptoms and signs of acute appendicitis and all had surgically resectable disease. Three of these patients were alive with no evidence of disease four months, two years and 15 years after presentation; one death of disease occurred seven years after ileocecal resection. In three cases, the clinical presentation was that of metastatic adenocarcinoma of unknown origin. Of these patients two were diagnosed at autopsy and one after appendectomy for perforated appendicitis. Survival in this group was six weeks, three months and twelve months, respectively. In none of our patients was the diagnosis made preoperatively and no tumors were found in appendices removed incidental to other intra-abdominal operations. The incidence of adenocarcinoma of the vermiform appendix in Iceland during 1974-1989 was approximately 0.2 cases/100.000/year.