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Two 12-year-old boys with severe sleep apnea syndrome but normal-sized tonsils were satisfactorily corrected by tonsillectomy and uvulopalatopharyngoplasty. One of the boys had muscular hypotony as contributing cause of the condition. The other had mandibular hypoplasia in combination with a long soft palate. Thorough preoperative anamnesis and examination in a sleep laboratory are necessary to determine which cases will benefit from surgery in spite of normal-sized tonsils and which surgical procedure will be most helpful. [ABSTRACT FROM AUTHOR]

Diabetic and nondiabetic control mice were given silver by ingestion. The glomerular basement membrane was labeled with silver granles and the labeling was marked in the diabetic animals. The retinal capillaries failed to incorporate silver both in normal and diabetic animals. [ABSTRACT FROM AUTHOR]

The prevalence of breathing obstruction was determined in a cohort of 4-year-old children. Craniofacial morphology was studied in obstructed children and compared with data from a control group of 4-year-old children with ideal occlusion. Dental arch morphology was compared in obstructed and non-obstructed children in the group. Parents of 95.5 per cent of the study base of 644 children answered a questionnaire concerning their child's nocturnal behaviour and related questions. The 48 children who, based on parental report, snored every night or stopped breathing when snoring (the 'snoring group'), showed a higher rate of disturbed sleep, mouth-breathing, and a history of throat infections as compared with the rest of the cohort. These children were examined by both an orthodontist and an otorhinolaryngologist and, when indicated, they were also monitored in a sleep laboratory. Twenty-eight of the children were diagnosed as having a breathing obstruction (4.3 per cent of the cohort) and six children (0.9 per cent) had sleep apnoea (mean apnoea-hypopnoea index of 17.3), using the same definition as that for adults. Cephalometric values among the obstructed children differed from those of a Swedish sample of the same age with ideal occlusion. They had a smaller cranial base angle and a lower ratio of posterior/anterior total fact height. Small, but not significant differences were seen for NSL-ML and NL-ML. Compared with 48 asymptomatic children from the same cohort, the obstructed children had a narrower maxilla, a deeper palatal height, and a shorter lower dental arch. In addition, the prevalence of lateral crossbite was significantly higher among the obstructed children. [ABSTRACT FROM AUTHOR]

In response to the 2009-2010 influenza A(H1N1)pdm09 pandemic, a mass vaccination programme with the AS03-adjuvanted influenza A(H1N1) vaccine Pandemrix was initiated in Sweden. Unexpectedly, there were a number of narcolepsy cases amongst vaccinated children and adolescents reported. In this review, we summarize the results of a joint cross-disciplinary national research effort to investigate the adverse reaction signal from the spontaneous reporting system and to better understand possible causative mechanisms. A three- to fourfold increased risk of narcolepsy in vaccinated children and adolescents was verified by epidemiological studies. Of importance, no risk increase was observed for the other neurological and autoimmune diseases studied. Genetic studies confirmed the association with the allele HLA- DQB1*06:02, which is known to be related to sporadic narcolepsy. Furthermore, a number of studies using cellular and molecular experimental models investigated possible links between influenza vaccination and narcolepsy. Serum analysis, using a peptide microarray platform, showed that individuals who received Pandemrix exhibited a different epitope reactivity pattern to neuraminidase and haemagglutinin, as compared to individuals who were infected with H1N1. Patients with narcolepsy were also found to have increased levels of interferon-gamma production in response to streptococcus-associated antigens. The chain of patient-related events and the study results emerging over time were subjected to intense nationwide media attention. The importance of transparent communication and collaboration with patient representatives to maintain public trust in vaccination programmes is also discussed in the review. Organizational challenges due to this unexpected event delayed the initiation of some of the research projects, still the main objectives of this joint, cross-disciplinary research effort were reached, and important insights were acquired for future, similar situations in which a fast and effective task force may be required to evaluate vaccination-related adverse events. [ABSTRACT FROM AUTHOR]

Objectives: The cell cycle regulator cyclin D1 plays an important role in parathyroid tumourigenesis. The NciI polymorphism in exon 4 has recently been associated with early onset of hereditary nonpolyposis colorectal cancer and is a prognostic indicator of nonsmall cell lung cancer and squamous cell carcinomas. Furthermore, a limited study of 28 primary hyperparathyroidism (pHPT) patients displayed a tendency of NciI influence on HPT development. We hypothesized that the NciI polymorphism may relate to a risk of developing pHPT.Design, Setting and Subjects: We genotyped 182 patients with sporadic pHPT and matched controls for the cyclin D1 polymorphism. A total of 88 pHPT patients and controls were recruited via a health-screening.Results: The frequency distribution of the NciI genotypes NN, Ni, and ii were in pHPT patients and controls 22, 44 and 34%, and 26, 49 and 25%, respectively. The calculated allele frequencies were A = 0.56; G = 0.44 in cases and A = 0.49; G = 0.51 in controls. The frequency distributions did not differ comparing cases and controls when subgrouped after age and menopausal status. The NciI genotypes were not significantly associated with age of the individuals, serum (s)-calcium, s-parathyroid hormone (PTH), bone mineral density (BMD) or parathyroid tumour weight in any of the groups of pHPT patients or controls.Conclusions: No significant differences in distribution of the genotypes could be detected between the groups, suggesting that the polymorphism has minor or no pathogenic importance in the development of pHPT. Our results suggest that determination of the NciI polymorphism in the cyclin D1 gene is not a clinically useful tool for prediction of pHPT. [ABSTRACT FROM AUTHOR]

Background: Laparoscopic splenectomy of normal-sized spleens is performed with increasing frequency. By using a handPort, which allows the intraperitoneal introduction of one surgeon's hand, massively enlarged spleens may also be extirpated via a laparoscopy-assisted technique.Methods: Seven patients (54-80 years) with massive splenomegaly (3.5-5.8 kg) underwent handPort-assisted laparoscopic splenectomy. All patients had spleens that extended beyond the umbilicus, hypersplenism, and discomfort in the upper left quadrant due to intractable hematological malignancy.Results: Both the operation and recovery were uneventful in five of the patients, but one patient had to be converted to an open procedure due to splenic damage and bleeding, and another was reoperated for hemorrhage from a trocar. The handPort allowed splenic protection while the trocars were introduced and instruments changed. It also enabled splenic mobilization, particularly prior to stapling of the hilar structures and dissection of the upper splenic pole.Conclusions: HandPort-assisted laparoscopic splenectomy seems to be a viable alternative for massive splenomegaly, but it requires further evaluation with respect to safety, efficacy, and indication. [ABSTRACT FROM AUTHOR]

Objectives. Patients with mild primary hyperparathyroidism (pHPT) often appear asymptomatic, and have previously been regarded as not requiring treatment. However, increased cardiovascular morbidity and dyslipidaemia have also been recognized in mild pHPT, which also seem to be normalized after parathyroidectomy. The present study explores whether postmenopausal women with mild pHPT have decreased bone mineral density (BMD) compared with age-matched healthy controls, and the effects on BMD of parathyroidectomy. Design, Subjects and Intervention. A population-based health screening of 5202 postmenopausal women identified 87 overtly asymptomatic patients with mild pHPT as well as age-matched healthy controls. A 5-year follow-up included 49 cases who had undergone parathyroidectomy. BMD was measured with DXA at the femoral neck, the lumbar spine and the total body. Results. At study entry, BMD was 5–6% lower in the lumbar spine (L2-L4) and femoral neck in cases compared with matched controls. After the 5-year follow-up, BMD increased in L2-L4 by 2.9% ( P = 0.002) in the parathyroidectomized cases and remained stable in the femoral neck. However, femoral neck BMD increased 4.1% ( P = 0.013) for cases <67 years old (50% of the cohort). Conclusion. In accordance with recent NIH guidelines for pHPT treatment, the level of BMD per se in the investigated group of patients justifies parathyroidectomy in almost half of the cases with mild pHPT. Surgery could be expected to increase BMD in L2-L4 to the level of the controls, to increase femoral neck BMD in patients <67 years of age and to preserve femoral neck BMD in the elderly population. [ABSTRACT FROM AUTHOR]

Background: The features of primary hyperparathyroidism (PHPT) in developing countries have rarely been examined. This study explored the clinical characteristics of PHPT in India with the hypothesis that this may improve understanding of the pathogenesis of the disease worldwide. Methods: Consecutive patients with PHPT (24 women, five men) were examined prospectively before and after parathyroidectomy. Results: All patients had osteitis fibrosa cystica with a median symptom duration of 2·5 (range 1–26) years. Single or multiple fragility fractures were present in 14 patients (eight were bedridden); 20 had brown tumours. Mean preoperative serum calcium was 3·1 mmol/l, while mean serum intact parathyroid hormone (iPTH) and total alkaline phosphatase (ALP) levels were 17-fold and 12-fold higher than normal respectively. Nine patients had overt renal damage, mainly nephrocalcinosis. Parathyroidectomy invariably resulted in severe hypocalcaemia, necessitating long-term vitamin D treatment. The mean parathyroid gland weight was 8·6 (range 2·0–36·6) g and features of carcinoma were found in four patients. Serum calcidiol level correlated inversely (P < 0·05) with serum iPTH and ALP, and parathyroid gland weight. Conclusion: PHPT in Indians is a severe, symptomatic disorder with skeletal, muscular and renal manifestations at a young age. The presence of this severe variant of PHPT in vitamin D-sufficient Indians, and the lack of skeletal disease in other vitamin D-deficient populations, raises the possibility of additional pathogenetic factors. [ABSTRACT FROM AUTHOR]

Objective:  Necrotizing enterocolitis (NEC) classically is diagnosed by radiographic demonstration of pneumatosis intestinalis/portal venous gas (PI/PVG). This study examines clinical characteristics of NEC confirmed by independent evaluation of abdominal radiographs, taken for clinical signs of NEC, or by pathologic findings at laparotomy or autopsy (confirmed NEC [cNEC])., Study Design:  The investigated cohort included 1,382 extremely low birth weight (BW) infants (BW range: 500-1,000 g) with median 27 weeks (range: 23-32) gestational age (GA) at birth. They were randomized into the placebo-controlled "Connection Trial" of the new biological drug candidate IBP-9414 with cNEC as one primary endpoint., Results:  Total 119 infants (8.6%) had cNEC diagnosed at median 14 days of age by confirming PI/PVG at X-ray adjudication ( n  = 111) and/or by surgery/autopsy ( n  = 21). Sixteen percent of cNEC cases died. Adverse events of NEC were reported in 8.5% of infants and 4.1% had NEC diagnosed by radiology and surgery/autopsy at the participating centers. Regression analyses showed that the risk of cNEC decreased by 11 to 30% for every 100-g increment in BW and single-week increment in GA and associated cNEC with odds ratios (ORs) > 2.0 for gastrointestinal (GI) perforation and obstruction, hypotension, hypokalemia, hypophosphatemia, and death. Comparing risks of cNEC in infants below and above 750-g BW showed higher ORs (2.7-4.3) for GI perforation, hypotension, hypokalemia, and renal complications in the smaller infants, whereas the bigger infants had higher ORs (1.9-3.2) for serious non-GI events, late-onset sepsis (LOS), and death. Predictors of cNEC (hazard ratio, HR > 1.5) included serious non-GI events (mainly infections), hyponatremia, and hyperglycemia, whereas the HR was 0.52 for intravenous antibiotics. After cNEC diagnosis, there were higher rates of GI perforation and obstruction, hypotension, hypokalemia, and LOS., Conclusion:  Independent adjudication of abdominal radiographs increased radiological recognition of NEC and proved to be feasible in a multicenter study setting as well as able to diagnose clinically relevant NEC., Key Points: · Independent adjudication of abdominal radiographs in ELBW infants increased NEC recognition.. · Risk of NEC decreased by 11 to 30% with every 100-g increment in BW and GA week.. · In infants with BW 750 to 1,000 g, the risk of death from NEC was almost twice that in infants with BW 500 to 749 g. · Infants with NEC received antibiotics during one-third and parenteral nutrition during half of the first 7 postnatal weeks.., Competing Interests: J.N. is the global coordinating investigator of the Connection Trial sponsored by Infant Bacterial Therapeutics. R.S., M.D., J.F.-T., M.H., and J.A.Z. are principal investigators of the Connection Trial sponsored by Infant Bacterial Therapeutics. A.K., J.R., and S.S. are employees of the sponsor Infant Bacterial Therapeutics. M.T. is a consultant statistician employed by the sponsor Infant Bacterial Therapeutics., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Objective: Investigate daily feeding volumes and their association with clinical variables in the early postnatal care of premature infants of the "Connection Trial.", Study Design: A total of 641 infants of 510 to 1,000-g birth weight (BW, mean: 847 g) and mean 27 weeks' gestational age at birth (GA) were analyzed for total daily enteral (TDE) feeding volumes of 10, 20, 40, 80, and 120 mL/kg/d and their association with 24 clinical variables. Uni- and multivariable Cox regression models were used to calculate hazard ratios (HR) with 95% confidence intervals as a measure of the chance of reaching each of the TDE volumes., Results: Daily feeding volumes were highly variable and the median advancement from 10 to 120 mL/kg/d was 11 mL/kg/d. Univariable analyses showed the lowest chance (HR, 0.22-0.81) of reaching the TDE volumes for gastrointestinal (GI) serious adverse events (SAEs), GI perforation, GI obstruction, and necrotizing enterocolitis, as well as respiratory SAEs, persistent ductus arteriosus, and hypotension. Each GA week, 100-g BW, and point in 5-minute Apgar score at birth associated with 8 to 20% increased chance of reaching the TDE volumes. Multivariable analyses showed independent effects for BW, GA, Apgar score, GI SAEs, abdominal symptoms/signs, respiratory SAEs, days on antibiotics, and hypotension., Conclusion: This observational analysis demonstrates the variable and cautious progression of enteral feedings in contemporary extremely low BW infants and the extent to which clinical variables associate with this progression., Key Points: · Total feedings of 10 and 120 mL/kg/d were reached at median 4 and 14 day of age, respectively, and at a daily increase of 11 mL/kg.. · Each incremental GA week, 100-g BW, and point in 5-minute Apgar score associated with 8 to 20% increased chance of reaching enteral feedings of 10 to 120 mL/kg/d.. · Progression of enteral feeding associated with several clinical events and was slower than advocated in common feeding protocols.., Competing Interests: J.N. is the global coordinating investigator of the Connection Trial sponsored by Infant Bacterial Therapeutics. P.A., V.C., A.L., P.P., R.R., B.S. are principal investigators of the Connection Trial sponsored by Infant Bacterial Therapeutics Inc. M.T. is a consultant statistician employed by Infant Bacterial Therapeutics Inc. A.K., S.S., and J.R. are all employees of Infant Bacterial Therapeutics Inc. sponsoring the Connection Trail., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Introduction: National competent authorities (NCAs) for medicines coordinate communication relating to the safety of medicines in Europe. The effectiveness of current communication practices has been questioned, particularly with regard to reaching general practitioners (GPs)., Objective: The aim of this study was to assess current European NCA safety communication practices and to investigate European GPs' awareness of and preferences for safety communications on medicines., Methods: Web-based surveys were distributed among European NCAs and healthcare professionals (HCPs). The survey among regulators was emailed to a representative of each of the 27 European countries participating in the Strengthening Collaboration for Operating Pharmacovigilance in Europe (SCOPE) Joint Action. HCPs from nine European countries (Denmark, Spain, Croatia, Ireland, Italy, The Netherlands, Norway, Sweden, and the UK) were asked about their preferences through a link to the survey on websites, in newsletters, and/or in a direct email. From this survey, data from GPs were used and descriptive analyses were conducted., Results: Current NCA practices were reported for 26 countries. In 23 countries (88%), NCAs published direct healthcare professional communications (DHPCs, i.e. urgent communication letters for serious safety issues) on their website in addition to distribution to individual HCPs. Educational materials were available on the NCA's website in 10 countries (40%), and 21 NCAs (81%) indicated they had their own bulletin/newsletter, which is often presented on the NCA's website (15 countries; 60%). More than 90% of the 1766 GPs who completed the survey were aware of DHPCs. The most preferred senders of safety information were NCAs and professional bodies, while the preferred channels for keeping up to date with safety information were medicines reference books and clinical guidelines. GPs found the repetition of safety issues useful (range of 80% in the UK to 97% in Italy). Preference for an electronic copy rather than a hardcopy varied per country (36% in Sweden to 72% in Spain)., Conclusions: NCAs use similar methods for safety communications on medicines. Most GPs were aware of urgent communications and preferred similar senders of safety communications; however, their preferences towards the format differed per country.

A man with chronic renal failure was referred to the hand clinic because of massive osteolytic tumours in his right arm. Secondary hyperparathyroidism and brown tumours were suggested, and he was treated by subtotal parathyroidectomy. Rapid reduction of the vast tumours was noted postoperatively.

Objective: Case reports have described associations between calcium metabolism disturbances and primary hyperparathyroidism with preeclampsia, suggesting parathyroid involvement in preeclampsia etiology. This study examines whether parathyroid adenoma, the main cause of hyperparathyroidism, diagnosed and treated before pregnancy is associated with preeclampsia., Design: We conducted a register-based study to assess the association between parathyroid adenoma and subsequent preeclampsia., Setting: Births among Sweden's general population were studied., Population: The study population included 52 women with a diagnosis of parathyroid adenoma and 519 without, all of whom had a subsequent singleton pregnancy between 1973 and 1997., Methods: We performed a conditional logistic regression investigating the association of parathyroid adenoma with subsequent preeclampsia in the first singleton pregnancy with adjustment for potential confounding factors., Main Outcome Measure: The main outcome was a diagnosis of preeclampsia that does not include women with prior chronic hypertension. To ensure that treatment of parathyroid adenoma was completed before pregnancy, those with a diagnosis of parathyroid adenoma made less than 2 yr before delivery (and the matched comparison women) were excluded., Results: Statistically, parathyroid adenoma prior to delivery is significantly (P < 0.001) associated with preeclampsia, producing an adjusted odds ratio of 6.89 (95% confidence interval, 2.30, 20.58)., Conclusion: A history of parathyroid adenoma should be viewed as a risk for preeclampsia.

Context: Primary hyperparathyroidism (PHPT) and associated morbidity are comprehensively assessed in elderly females; however, less is known of the disease in younger women., Objectives: Our objectives were to estimate the prevalence of mild disturbances in calcium homeostasis, which could be analogous with early PHPT, in a premenopausal population, and determine the potential presence of associated morbidity., Design: Initial results from this longitudinal study are from 2002-2004., Setting: We conducted a population-based screening of serum (s)-calcium in conjunction with routine mammography., Participants: Participants included premenopausal women, 40-50 yr of age (n = 1900). Cases fulfilling previously evaluated biochemical criteria for PHPT (n=214) were matched to controls (n = 214)., Main Outcome Measurements: All participants underwent investigation, including screening of parameters of calcium homeostasis, dual x-ray absorptiometry, and body mass index assessment, and filled out extensive health and quality of life (SF-36) questionnaires. Participants were divided into four groups depending on the relation between s-calcium/intact PTH. Statistical comparisons between cases and controls as well as among the four groups were performed to evaluate morbidity., Results: The prevalence of assumed mild PHPT, i.e. inappropriate intact PTH value in relation to total s-calcium, was estimated to be 5.1% (n = 96). Women with mild disturbances in calcium homeostasis had statistically significant lower bone mineral density in the proximal femur and femoral neck, higher body mass index, and lower scores for vitality and general health in the analysis of SF-36., Conclusions: Mild disturbances in calcium homeostasis in premenopausal women were more prevalent than previously thought and were associated with obesity, lower bone mineral density, and decreased quality of life.

Due to concerns related to treatment with erythropoietin (EPO) and possible negative effects on tumour control, a workshop was organised by the Medical Products Agency of Sweden with the aim to revise national treatment guidelines if needed. In patients with solid tumours, conflicting results have been reported with respect to tumour control and survival. Until further notice it is therefore recommended that EPO should be used restrictively in the treatment of patients with cancer and that the anticipated improvement in quality of life should be evaluated against potential risks.

Objective: Dyslipidemia, hypertension, diabetes mellitus and also primary hyperparathyroidism (pHPT) are associated with an increased risk of cardiovascular diseases. Metabolic abnormalities in mild pHPT have been reported, but never in cases with normal calcium and high parathyroid hormone (PTH) levels, i.e. suffering from 'normocalcemic pHPT'. Our aim was to explore the occurrence of these metabolic abnormalities in individuals with normocalcemic pHPT identified in a population-based screening, and the effects of parathyroidectomy vs conservative treatment on metabolic variables., Design and Methods: A population-based screening of 5202 post-menopausal women identified 30 patients with normal calcium, inappropriately high PTH and normal creatinine. A 5-year follow-up included 15 parathyroidectomized (PTx) and nine conservatively followed cases, in a non-randomized setting, together with age-matched controls. Biochemical variables and body mass index (BMI) were investigated., Results: At study entry, cases had higher calcium, PTH, glucose, low-density lipoprotein (LDL)/high-density lipoprotein (HDL)-cholesterol, very low-density lipoprotein (VLDL)-cholesterol, total triglycerides, and BMI compared to controls (P = < 0.0001-0.035). The cases had a lower HDL-cholesterol value (P = 0.013) and one third of the cases had hypertriglyceridemia. During follow-up, the PTx cases decreased in calcium, PTH, LDL/HDL-cholesterol, total and LDL-cholesterol (P = 0.0076-0.022). Investigated biochemical variables remained adverse in conservatively followed cases during follow-up except a decreased LDL-cholesterol value. All surgically treated patients had parathyroid adenoma., Conclusions: Cases with normocalcemic pHPT have increased proatherogenic lipoprotein levels, BMI and glucose levels compared to age-matched controls. Parathyroidectomy has positive effects on some of these variables and reverses them to the same level as the controls, while conservative treatment fails to normalize the investigated metabolic variables.

On 2 earlier occasions, in 2002 and 2003, the Swedish Medical Products Agency (MPA) and the Swedish Reference Group for Antiviral Therapy (RAV) have jointly publicized recommendations for the treatment of HIV infection. A working group from the same expert team that produced the 2002 report has now revised the text again. Since the publication of the last treatment recommendations, 4 new medicines have become available: emtricitabine, atazanavir, fosamprenavir, and enfuvirtid. The last-mentioned belongs to a new class of HIV medications called fusion inhibitors (Box 1). It is likely that tipranavir will also be on the market soon. Simultaneously, the drug zalcitabin has been deregistered. The following updated recommendations parallel the earlier ones, but increased knowledge allows us to be more specific in our recommendations. Thus, it is now suggested that the initial treatment for HIV infection consist of 2 nucleoside reverse transcriptase inhibitors (NRTIs) and 1 non-nucleoside reverse transcriptase inhibitor (NNRTI); or 2 NRTIs and 1 protease inhibitor (PI). In the group of the NRTIs, stavudine is no longer recommended for this purpose. In the NNRTI group, efavirenz should be preferred to nevirapine, except under special circumstances. Finally, PIs ought to be boosted with ritonavir (PI/r). Also new are recommendations regarding treatment choices for patients co-infected with hepatitis B virus (HBV) or tuberculosis (TB). As in the case of the previous publication, recommendations are evidence-graded in accordance with the Oxford Centre for Evidence Based Medicine, 2001 (see http://www.cebm.net/levels&#95;of&#95;evidence.asp#levels), and have been supplemented with references to newly-added sections and data not referred to in earlier background documentation.

Background: Primary hyperparathyroidism (pHPT) has been associated with premature death in cardiovascular diseases. Short-term prospects for normalization of cardiovascular derangements have been described after parathyroidectomy. This study explores long-term effects of parathyroidectomy on cardiovascular functions in pHPT., Methods: Thirty consecutive patients with pHPT were reexamined 1 and 5 years after parathyroidectomy, together with 30 matched controls, with echocardiography and a bicycle exercise test., Results: Serum calcium was normal in all patients and control subjects at follow-up. The maximal blood pressure during the exercise was higher before parathyroidectomy (median 223 [range, 200-268] mm Hg vs 202 [165-277] mm Hg, P < .05) but not 5 years after (230 [155-270] mm Hg vs 219 [165-252] mm Hg. The ST-segment depression diminished from -1.4 (-8.3-0) to -0.8 (-3.3-0) mm 1 year after parathyroidectomy and further to -0.1 (-3.3-0.0) mm after 5 years but was unchanged in the control group. The number of ventricular extrasystolic beats at exercise testing in the pHPT group before parathyroidectomy was higher than in the control group (1 [0-340] vs 0 [0-3]). The isovolemic relaxation time at rest was prolonged before parathyroidectomy (mean 100 +/- 17 ms [SD] vs 89 +/- 14 ms, P < .05)., Conclusion: Parathyroidectomy can induce long-lasting improvement in regulation of blood pressure, left ventricular diastolic function, cardiac irritability (ventricular extrasystolic beats), and other signs of myocardial ischemia, with potential implications for the postoperative life expectancy of patients with pHPT who have undergone parathyroidectomy.

Midgut carcinoid tumors are rare and have a markedly better prognosis than adenocarcinoma in the small intestine. New diagnostic methods and medical as well as surgical therapies have evolved during the last decades, leading to more active care of these patients. Patients with small intestinal carcinoids diagnosed from 1960 to 2000 in the duodenum (n = 89) and jejunum/ileum (n = 2437) were identified in the Swedish Cancer Registry. Cases without histologic verification and autopsy cases were excluded. Overall, cause-specific and relative survival were calculated. The overall 5-, 10-, and 15 year survivals were, respectively, 60%, 46%, and 28% for duodenal tumors and 56%, 36%, and 23% for jejunal/ileal tumors. Cause-specific 5-, 10-, and 15-year survival was 94% for all three follow-up periods for duodenal tumors and 87%, 80%, and 77% for those in the jejunum/ileum. The corresponding relative survivals were, respectively, 72%, 67%, and 51% for duodenal tumors and 67%, 54%, and 44% for those in the jejunum/ileum. Sex did not influence overall or cause-specific survival. The age at diagnosis correlated inversely with overall and cause-specific survival for tumors in the jejunum/ileum. For tumors in the jejunum/ileum, the overall and cause-specific survival correlated with the time period of diagnosis, with a more favorable prognosis for those diagnosed in recent years. A multivariate Cox proportional hazards model showed similar results. We concluded that young age and diagnosis in recent years are positive predictors of survival for patients with midgut carcinoids. The divergence between cause-specific and relative survival implies the need for a more detailed analysis of the causes of death of these patients.

Background: The risk of dying from primary hyperparathyroidism (pHPT) is controversial and has been explored mainly in single parathyroid gland disease. The present study investigates mortality in pHPT due to multiple parathyroid gland disease., Methods: We used the nationwide Swedish In-patient Register and Cause-of-Death Registry to compare the mortality in 3485 Swedish patients subjected to parathyroidectomy during 1964 to 1999 with that of the Swedish population (standardized for age, gender, and calendar year). The patient cohort includes 36,596 person years., Results: Increased risk of death beyond the first postoperative year (standardized mortality ratio, 1.4; 95% CI, 1.37-1.52) was found in both sexes and for all age intervals below 80 years. The increased risk persisted more than 15 years postoperatively and related to cardiovascular diseases, diabetes mellitus, urogenital diseases, and malignant disorders. The increased risk of dying in cardiovascular diseases normalized during 1990 to 1999., Conclusions: pHPT caused by multiple parathyroid gland enlargement is associated with an excessive mortality similar to pHPT of single parathyroid adenoma. The findings substantiate that modern modes of surgical treatment for pHPT normalize the risk of dying from cardiovascular complications and that the hyperpararthyroid state per se is the possible cause of the premature death.

In the absence of metastases or overgrowth to adjacent organs, the lack of reliable markers for malignancy is a well-recognized problem for clinicians managing patients with endocrine tumors. Apart from inactivation of the multiple endocrine neoplasia type 1 (MEN1) gene, the molecular mechanisms involved in tumorigenesis of the endocrine organs and MEN1-associated nonendocrine lesions are vastly unknown. To try to learn more about down-stream effects on MEN1 gene inactivation, we used the BON1 cells, showing low levels of endogenous menin, and transfected them with a MEN1 gene construct. On restoring the menin expression, we recorded inhibition of cell growth. We also performed macroarray and present data on differentially expressed genes in the transfected cells, after corroboration by Northern blots and quantitative PCR. JunD was up-regulated in menin-expressing clones, whereas delta-like protein 1/preadipocyte factor-1 (involved in differentiation and growth of the pancreatic endocrine cells), proliferating cell nuclear antigen, and QM/Jif-1 (a negative regulator of c-Jun) became down-regulated. These findings might contribute to the understanding of the tissue-specific features of MEN1. We also show that homozygous inactivation of the MEN1 gene statistically correlates to higher expression of delta-like protein 1/preadipocyte factor-1, proliferating cell nuclear antigen, and QM/Jif-1, as well as lower MEN1 expression, in a limited sample of malignant endocrine pancreatic tumors.

Background: Primary hyperparathyroidism has been associated with premature death in cardiovascular diseases, but reversibility and background mechanisms are uncertain. This study investigates autonomic nervous function in hyperparathyroidism because disturbances in this respect have been related to increased cardiovascular morbidity., Methods: Twenty-one consecutive patients with hyperparathyroidism and 23 matched control subjects without interfering medication underwent electrocardiographic recordings and ambulatory blood pressure (ABP) determination during a 24-hour period. Patients were re-examined at normocalcemia 1 year after parathyroidectomy. Heart rate variability was analyzed in subjects with sinus rhythm and normal atrioventricular conduction; time domain measures were calculated from the RR-intervals, and frequency domain variables were obtained with an autoregressive algorithm, which expressed power distribution (high, low, or very low frequency)., Results: Nocturnal increase in low frequency was blunted in cases versus control subjects (103+/-128 m(2) vs 430+/-171 m(2); P=.03). Very low frequency at nighttime correlated inversely with serum parathormone (r=-0.33; P<.05) and increased postoperatively (P=.03). ABP was higher both at daytime and nighttime (P<.05) in patients and remained unchanged after surgery. Systolic ABP correlated with the parathormone (r=0.47; P<.01)., Conclusion: Results suggest altered circadian autonomic function in hyperparathyroidism that can improve after parathyroidectomy. Despite elevated blood pressure, ABP shows retained diurnal rhythm, which indicates different pathophysiologic mechanisms behind the 2 predictors of cardiovascular death in hyperparathyroidism.

Primary hyperparathyroidism (HPT) is a common endocrine disease, in most cases without obvious symptoms of hypercalcemia and parathyroid hormone excess. The only curative treatment outside clinical trials is parathyroidectomy. Many patients are undiagnosed and left untreated, and the indications for curative treatment are still controversial. In 1990, NIH presented recommendations on the management of asymptomatic HPT, which was defined as HPT without symptoms and signs of renal or bone disease. Since then many studies have shed new light on mainly the cardiovascular complications and increased mortality of the disease, and the 1990 recommendations have been questioned. A workshop in 2002 revised the recommendations for handling of asymptomatic HPT in the United States. These recommendations are discussed from a Swedish perspective together with recent data on mortality in a large Swedish HPT cohort.

Background: Phospholipase C beta 3 (PLCB3) plays an important role in the signal transduction of the seven transmembrane receptors. The gene is located in the vicinity of the Multiple Endocrine Neoplasia type 1 (MEN1) gene on chromosome 11q13. Transfection of PLCB3 to neuroendocrine cell lines lacking expression suppresses the neoplastic phenotype and affects the gene expression of S100A3 and human mismatch repair protein, suggesting a role for PLCB3 in neuroendocrine tumorigenesis., Materials and Methods: We used RNA-RNA in situ hybridisation for PLCB3 on a total of 82 samples including 34 from MEN1 patients., Results: We show that the PLCB3 transcript is missing in 8 out of 14 MEN1-associated neoplasias as well as in 4 out of 10 bronchial carcinoids, 2 out of 10 exocrine pancreatic cancers and one sporadic adrenocortical carcinoma., Conclusion: Low or lack of PLCB3 expression in a subset of endocrine tumours, together with earlier published in vitro data on suppressor characteristics upon transfection, indicate that PLCB3 could be involved in the tumorigenesis in a subset of endocrine tumours.

The Swedish guidelines (SwG) for treatment of human immunodeficiency virus (HIV) infection have several important roles. A major task involves the promotion of a uniformly high standard of care in all HIV treatment clinics in Sweden and the identification of strengths, weaknesses and relevance of recent research findings. CD4+ T-cell counts < 200 cells/microl are clear indications for the initiation of treatment, whereas high viral loads serve as an indication for increased vigilance rather than a criterion for therapy. It is recommended that the first regimen consists of 2 nucleoside reverse transcriptase inhibitors in combination with 1 protease inhibitor or 1 non-nucleoside reverse transcriptase inhibitor. The definition of treatment failure is rigorous. Treatment change should be considered if the viral load has not fallen by at least 1.5 log in 4 weeks or is undetectable within 3-4 months. Resistance testing is endorsed at primary infection, in the event of treatment failure and in pregnant women. Interaction with experts in HIV resistance testing is emphasized. Therapeutic drug monitoring is advocated. Patients with treatment failure should be handled individually and the decision on therapeutic strategy should be based on treatment history, resistance testing and other clinical facts. The SwG do not give recommendations for some important issues such as prolonged drug holidays and preferences in initial treatment regimens. More scientific data are likely to be available soon and the SwG will be refined accordingly. The present guidelines are translated from Swedish; they are published on the Medical Products Agency (MPA) and Swedish Reference Group for Antiviral Therapy (RAV) websites (www.mpa.se and www.rav.nu.se), including 7 separate papers based on a thorough literature search. A complete reference list is available on request from the MPA.