Mortality in sporadic primary hyperparathyroidism: nationwide cohort study of multiple parathyroid gland disease

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.     

Variation in NCB5OR: studies of relationships to type 2 diabetes, maturity-onset diabetes of the young, and gestational diabetes mellitus

Recent data show that homozygous Ncb5or(-/-) knock-out mice present with an early-onset nonautoimmune diabetes phenotype. Furthermore, genome-wide scans have reported linkage to the chromosome 6q14.2 region close to the human NCB5OR. We therefore considered NCB5OR to be a biological and positional candidate gene and examined the coding region of NCB5OR in 120 type 2 diabetic patients and 63 patients with maturity-onset diabetes of the young using denaturing high-performance liquid chromatography. We identified a total of 22 novel nucleotide variants. Three variants [IVS5+7del(CT), Gln187Arg, and His223Arg] were genotyped in a case-control design comprising 1,246 subjects (717 type 2 diabetic patients and 529 subjects with normal glucose tolerance). In addition, four rare variants were investigated for cosegregation with diabetes in multiplex type 2 diabetic families. The IVS5+7del(CT) variant was associated with common late-onset type 2 diabetes; however, we failed to relate this variant to any diabetes-related quantitative traits among the 529 control subjects. Thus, variation in the coding region of NCB5OR is not a major contributor in the pathogenesis of nonautoimmune diabetes.     

Spontaneous resolution of high grade infantile vesicoureteral reflux

PURPOSE: We studied the spontaneous resolution rate in a group of infants with high grade vesicoureteral reflux (VUR). The influence of gender, prenatal or postnatal diagnosis, recurrent urinary tract infections (UTIs) and bladder dysfunction on the resolution rate was also evaluated. MATERIALS AND METHODS: This prospective study comprised 115 infants (80 boys and 35 girls) with high grade VUR (grades III to V). Bilateral reflux was seen in 70% of cases. The majority of patients (71%) were diagnosed after UTI during infancy and only 26% were prenatally diagnosed. Median age at diagnosis was 2.7 months. Patients were followed according to a program of repeat video cystometry and noninvasive 4-hour voiding observations. Median followup was 39 months. RESULTS: The overall spontaneous resolution rate to grade II or less for all grades was 39% with no difference between boys and girls. However, when comparing the more severe grades IV and V, we found a significantly higher resolution rate in boys during the infant year. No difference in VUR disappearance could be detected when comparing the groups according to presentation, prenatal ultrasound or pyelonephritis. Breakthrough UTIs were seen in 47% of cases despite antibacterial prophylaxis and they significantly correlated with VUR nonresolution. Bladder dysfunction was found in 37% of patients and it also significantly correlated with nonresolution. CONCLUSIONS: The spontaneous resolution rate for high grade (grades IV and V) congenital VUR was high in boys during the infant year (29%), whereas in girls and boys after the infant year the resolution rate was 9% yearly during followup. Negative prognostic factors for resolution were recurrent UTIs and bladder dysfunction.     

Indium-111-labelled donor-lymphocyte infusion by way of hepatic artery and radio-frequency ablation against liver metastases of renal and colon carcinoma after allogeneic hematopoietic stem-cell transplantation

BACKGROUND: In patients with metastatic solid cancer, antitumor effects occur after allogeneic stem-cell transplantation (SCT). However, this treatment is not as effective in the liver as against pulmonary and lymph-node metastases. To intensify the effect of donor-lymphocyte infusions (DLI) against liver metastases, intra-arterial (IA) cell injection by way of the hepatic artery (HA) can be used. METHODS: To trace infused cells, three patients with colorectal, three with renal, and one with breast carcinoma were treated with Indium-111 (111-In)-oxinate-labeled lymphocytes. Four patients received the DLI IA, all after radio-frequency ablation (RFA) of liver metastases. Three patients with other metastases received 111-In DLI intravenously (IV). One of them had RFA before SCT. RESULTS: Localization of the IA 111-In DLI activity on scintigrams homed to the liver. After IA injection, the liver to sternum ratio of radioactivity was higher compared with IV injection. Cells (CD3+, 19+, and 56+) of donor origin in biopsies of liver metastasis in two patients treated with IA injection increased to 80% to 100%. Two of four patients treated using the IA DLI showed stable size and number of liver metastases for 5 and 21 months, respectively. Both are alive 18 and 34 months after SCT. Two of three patients receiving DLI IV are doing well, with a stable metastatic disease or still without metastases 21 and 20 months after cell infusions (26 and 34 months after SCT), respectively. Three patients died because of progressive disease. CONCLUSION: When infused by way of the HA, 111-In-labeled lymphocytes home to the liver and its metastases. The liver metastasis infiltrating cells of donor origin increased. DLI by way of the HA combined with RFA may be used to treat liver metastases after SCT.     

Low Quality of Life Prior to Screening for Abdominal Aortic Aneurysm: A Possible Risk Factor for Negative Mental Effects

The objective of this study was to evaluate the effect on quality of life (QOL) of screening for abdominal aortic aneurysm (AAA) in a population-based AAA screening program. Twenty-four patients with screening-detected AAA and 45 controls with normal aortic diameter were studied in a prospective, controlled, population-based study. Prior to and 12 months after the ultrasonography examination, all participants completed Short-Form 36 and at 12 months, 10 AAA-specific questions were added. Comparisons were made between the two groups (AAA patients and controls), within each group, and between the groups and norms for the general Swedish population in the same age interval. Our results showed that screening for AAA results in impairment of QOL among those who have the disease and who suffered a low QOL prior to screening. Among those who had an age-adjusted normal QOL prior to screening and who were found to have the disease, and among those who were found to have normal aortas, no negative effect on QOL was observed. Thus, low QOL before screening is a possible risk factor for negative mental effects of diagnosing an AAA by screening.     

Oxygen free radical-dependent activation of extracellular signal-regulated kinase mediates apoptosis-like cell death after traumatic brain injury

Mitogen-activated protein kinase (MAPK) cascades are membrane-to-nucleus signaling modules that recently have been implicated as mediators of cellular injury. In this study, we investigated the involvement of the MAP kinase p44/p42 (extracellular signal-regulated kinase [ERK1/2]) in traumatic brain injury (TBI) in rats. There was a strong increase in activated, phosphorylated ERK 1/2 (p-ERK 1/2) protein at 10 min up to 24 h after the injury. Expression of p-ERK occurred in cells identified as neurons, astrocytes, and microglia. Most of the cells expressing p-ERK were TUNEL positive at later time points. Treatment with the MEK inhibitor U0126 or the free radical scavenger S-PBN, both with neuroprotective properties in TBI, attenuated the early activation of ERK and resulted in less activation of caspase-3 and subsequent DNA fragmentation. Post-treatment with U0126 resulted in a significant decrease (-60%) in cortical cavity size and cortical atrophy at 2 weeks after trauma. Overall, the results suggest that ERK activation is initiated by increased oxygen radical activity and that overactivation of ERK sets off secondary cell death mechanisms in TBI. Clinical studies are warranted to evaluate the concept of MEK inhibition in head-injured patients.     

Desflurane increases intracranial pressure more and sevoflurane less than isoflurane in pigs subjected to intracranial hypertension

Desflurane and sevoflurane may have advantages over isoflurane in neuroanesthesia, but this is still under debate. A porcine model with experimental intracranial hypertension was used for paired comparison of desflurane, sevoflurane, and isoflurane with respect to the effects on cerebral blood flow (CBF), cerebrovascular resistance (CVR), and intracranial pressure (ICP). The agents, given in sequence to each of six pigs, were compared at 0.5 and 1.0 minimal alveolar concentrations (MAC) and three mean arterial blood pressure (MAP) levels (50, 70, and 90 mm Hg) at normocapnia and one MAP level (70 mm Hg) at hypocapnia. MAC for each agent had been previously determined in a standardized manner for comparison reliability. CBF was measured with Xe. MAP was lowered by inflation of a balloon catheter in the inferior caval vein and raised by inflation of a balloon catheter in the descending aorta. ICP was measured intraparenchymally. Two Fogarty catheters positioned extradurally were inflated to a baseline ICP of 20 to 22 mm Hg at 0.2 MAC of each agent. CBF and ICP with the three agents at normocapnia and MAP 70 and 90 mm Hg at both 0.5 and 1.0 MAC were as follows (P < 0.05): desflurane > isoflurane > sevoflurane. None of the agents abolished CO2 reactivity. High-dose desflurane resulted in a higher CBF at hypocapnia than corresponding doses of sevoflurane or isoflurane, but there were no significant differences between the agents in ICP at hypocapnia. The present study showed that desflurane increased ICP more and sevoflurane less than isoflurane during normoventilation, but the differences disappeared with hyperventilation.     

Dose-dependent efficacy of diclofenac-cholestyramine on pain and periarticular ossifications after total hip arthroplasty: a double-blind,prospective, randomised trial

Introduction To investigate the efficacy of treatment with diclofenac-cholestyramine on postoperative pain and functional outcome after total hip arthroplasty, a randomised double-blind study was conducted.Materials and methods A total of 245 patients received postoperative treatment with 75 mg or 150 mg diclofenac p.o. daily for 14 days.Results Patients who received 75 mg diclofenac per day needed paracetamol as an additional analgesic significantly more often (p=0.0162) than patients who were treated with 150 mg diclofenac daily (75 mg twice a day). The incidence of adverse gastrointestinal events was significantly lower in the group receiving 75 mg diclofenac daily than in the group receiving the higher dose (23.1% vs 37.1%; p=0.025). Six months after the operation, no differences were observed between the two groups with regard to pain or functionality measured in terms of overall mobility of the hip. No patient of either group developed clinically relevant heterotopic ossifications.Conclusion Treatment with a dose of 75 mg diclofenac once daily—if necessary with the additional use of paracetamol—is a favourable option for the postoperative care of THA.     

Diagnosis of cystocele – the correlation between clinical and radiological evaluation

In patients with genital prolapse involving several compartments simultaneously, radiologic investigation can be used to complement the clinical assessment. Contrast medium in the urinary bladder enables visualization of the bladder base at cystodefecoperitoneography (CDP). The aim of the present study was to evaluate the correlation between clinical examination using the Pelvic Organ Prolapse Quantification system (POP-Q) and CDP. Thirty-three women underwent clinical assessment and CDP. Statistical analysis using Pearsons correlation coefficient (r) demonstrated a wide variability between the current definition of cystocele at CDP and POP-Q (r=0.67). An attempt to provide an alternative definition of cystocele at CDP had a similar outcome (r=0.63). The present study demonstrates a moderate correlation between clinical and radiologic findings in patients with anterior vaginal wall prolapse. It does not support the use of bladder contrast at radiologic investigation in the routine preoperative assessment of patients with genital prolapse.Abbreviations CDP Cystodefecoperitoneography Editorial Comment: The authors attempt to correlate the visceral position of the bladder on fluoroscopy to the anterior vaginal wall measurements on POP-Q examination. Consistent with other published reports, they show only moderate statistical correlations. Clinically, the correlations are probably not useful. Thirty-eight percent of women with radiographic cystoceles had no clinically significant prolapse (stage III or IV). Based on their findings the authors conclude that the routine use of radiologic investigation might not be warranted in the preoperative assessment of women with pelvic organ prolapse. This must be interpreted with caution when generalizing their data to all women with prolapse. Only 17% of the women in this study had had prior pelvic surgery. The authors also do not address how cystodefecoperitoneography results affected the diagnosis of enterocele or rectocele. Other authors have shown a significant increase in enterocele diagnosis using cystodefecoperitoneography.