18F FDG-PET/CT has poor diagnostic accuracy in diagnosing shoulder PJI.

PURPOSE: Chronic low-grade periprosthetic joint infection (PJI) of a shoulder replacement can be challenging to diagnose. 18F-FDG PET/CT is suggested as a modality to diagnose lower-limb PJI, but no studies on shoulder replacements exist. The aim of this study was therefore to determine the diagnostic accuracy of 18F-FDG PET/CT in diagnosing chronic PJI of the shoulder. METHODS: Patients evaluated for a failed shoulder replacement during a 3-year period were prospectively included in the study. All patients underwent pre-operative 18F-FDG PET/CT, and were evaluated for signs of infection by three independent reviewers using shoulder-specific criteria. Interrater-agreement was calculated between the reviewers. If the patient had revision surgery, biopsy specimens were obtained and cultured with bacterial growth in the cultures serving as gold standard of infection. RESULTS: A total of 86 patients were included in the study. Nine patients were 18F-FDG PET/CT positive for infection, with only three true positive. Using the gold standard, infection was diagnosed after revision surgery in 22 cases. All infections were chronic and caused by low-virulent microbes. The sensitivity of 18F-FDG PET/CT was 0.14 95% CI (0.03-0.36), specificity 0.91 95% CI (0.81-0.97), positive predictive value was 0.40 95% CI (0.15-0.71) and negative predictive value 0.71 95% CI (0.67-0.75). The inter-observer agreement was 0.56 (Fleiss' kappa), indicating moderate agreement of the visual FDG-PET evaluation using the shoulder-specific criteria. CONCLUSION: 18F-FDG PET/CT has poor diagnostic accuracy in diagnosing low-grade PJI of the shoulder. 18F-FDG PET/CT cannot be recommended as a part of the routine preoperative workup to diagnose low-grade infection of a shoulder replacement.

Influence of calcium on the metabolism of intact parathyroid hormone by isolated perfused rat kidney and liver.

The metabolism of synthetic human PTH [PTH-(1-84)] 10(-9) M was studied in isolated rat kidneys and livers, perfused at a calcium concentration of 1 mM or 4 mM. Clearances were measured by an assay specific for intact PTH, and by assays specific for NH2-terminal, mid-molecule, and COOH-terminal immunoreactive PTH (iPTH). Production of PTH fragments was analyzed by HPLC. The kidneys cleared PTH mainly by filtration. The glomerular filtration rate was not lower at 4 mM calcium than at 1 mM calcium, and no significant differences were found between the clearance of PTH at 4 mM and at 1 mM calcium. At 1 mM calcium the kidneys cleared intact PTH without release of detectable fragments. At 4 mM calcium there was significant (P less than 0.05) accumulation of mid-molecule and COOH-terminal iPTH in the perfusate. Both at low and at high calcium the livers cleared NH2-terminal iPTH at the same rate as intact PTH, whereas mid-molecule and COOH-terminal iPTH was cleared significantly (P less than 0.005) slower. In the livers, metabolic clearance of PTH was 60% faster at 4 mM calcium than at 1 mM calcium (P less than 0.001). Assuming that the hepatic metabolism of PTH represents degradation of the biologically active hormone and hormone fragments, rather than activation of the hormone, the present results suggest a homeostatic control of PTH degradation in the liver to enhance inactivation of the hormone at high serum levels of calcium.

Metabolism of N-terminal and C-terminal parathyroid hormone fragments by isolated perfused rat kidney and liver.

The metabolism of added N-terminal and C-terminal synthetic human PTH (synhPTH) fragments was studied in isolated perfused rat livers and in filtering and nonfiltering kidneys. Initial concentrations: synhPTH-(1-34), 14 pmol/liter, synhPTH-(39-84) 85 pmol/liter, synhPTH-(1-84) 3 pmol/liter, or 1000 pmol/liter of each fragment and intact PTH. Clearances were measured by assays specific for intact PTH, N-terminal, midmolecule, and C-terminal immunoreactive PTH. Metabolism of the added PTH into smaller circulating fragments was analyzed by HPLC. The clearance of synhPTH-(1-34) in the filtering kidneys was not significantly different from the clearance of synhPTH-(39-84) and inulin, and HPLC demonstrated no metabolism of synhPTH-(1-34) or synhPTH-(39-84) in the kidneys. The livers did not clear synhPTH-(39-84), while the clearance of synhPTH-(1-34) was significant (P < 0.005). HPLC demonstrated no metabolism of synhPTH-(39-84) by the livers, but extensive metabolism of synhPTH-(1-34). The livers cleared synhPTH-(1-34) significantly (P < 0.05) faster than synhPTH-(1-84). In conclusion, the kidneys cleared N-terminal PTH fragments at the same rate as C-terminal fragments mainly by filtration. The livers cleared N-terminal fragments faster than intact PTH, but did not clear C-terminal fragments. This differential hepatic clearance may play a major role in maintaining the differences between the circulating levels of N-terminal and C-terminal immunoreactive PTH.

Effect of uremia on aldosterone metabolism in the isolated perfused rat liver.

The effect of uremia on hepatic metabolism of aldosterone was studied in the isolated perfused liver of female Wistar rats. Uremia was induced by five-sixths partial nephrectomy 4 weeks before experiments. Isolated livers of normal and uremic rats were perfused at a constant flow rate with a hemoglobin-free medium, to which 4-14C-D-aldosterone was added at 3 nmol/L. Aldosterone was analyzed by radioimmunoassay (RIA) and 4-14C-D-aldosterone radiometabolites in perfusate and bile were assayed by high-performance liquid chromatography (HPLC). Uremic rats had a 10% lower body weight (P < .01) and increased plasma urea, creatinine, and parathyroid hormone (PTH) levels (258%, 200%, and 208%, respectively; P < .01-.001). Blood pressure and plasma K+, Na+, and aldosterone levels were similar. Plasma renin activity was suppressed by 68% in uremic rats (P < .001). Liver wet weight and hepatic function were similar in livers of both groups of rats. Hepatic elimination of aldosterone was compatible with a first-order kinetics. Hepatic clearance of aldosterone per liver and per gram liver was similar; however, when expressed per 100 g rat body weight, a 21% higher value was observed in uremic rats (11.6 +/- 1.8 mL/min) compared with normal rats (9.6 +/- 1.5 mL/min, P < .01). Polar aldosterone radiometabolites accumulated in the perfusate to approximately 40% of the initial 14C added at 15 minutes, and were eliminated in bile at a similar rate in both groups. No qualitative difference was found in the pattern of radiometabolites of aldosterone in perfusate and bile.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of incisional plastic drapes and redisinfection of operation site on wound infection following caesarean section.

In a randomized prospective multicentre study of post-caesarean wound infection among 1,340 women in eight hospitals, the effect of redisinfection of the skin around the incision before skin closure and the effect of adhesive skin drapes were investigated. The overall rate of wound infection with pus was 5.0% (range 3.5-8.9%). The study showed a reduction in postoperative wound infection associated with redisinfection (P = 5.5%), while no benefit from adhesive plastic drapes could be demonstrated.

Determination of bone Gla protein (osteocalcin) by enzyme-linked immunosorbent assay.

Bone Gla protein (BGP, osteocalcin) is a marker of bone formation. We present a novel enzyme-linked immunosorbent assay for measuring BGP in plasma and serum. The antibody used was raised in rabbits following immunisation with highly purified bovine BGP conjugated with keyhole limpet hemocyanin. The binding of the antibody to BGP was calcium-dependent. The sensitivity, inaccuracy, and imprecision of the assay equal or exceed existing radioimmunoassays, and the present assay is less tedious. Plasma BGP in 249 healthy adults, aged from 20 to 93 yr, was 8.3 +/- 6.6 micrograms/l (mean +/- 2 SD). A significant decrease was seen in both sexes from the third to the forth decade of life. A subsequent significant increase was seen with age in women. but not in men. Plasma BGP was significantly higher in young men than in young women, and significantly higher in elderly women than in elderly men. Values were in the same range as those found with existing radioimmunoassays.

Influence of glucocorticoid on the metabolism of aldosterone in the isolated perfused rat liver and kidney.

The effect of glucocorticoid deficiency and excess on the extraadrenal metabolism of D-[4-14C]aldosterone (at 4 nM) was studied by radioimmunoassay and by high-performance liquid chromatography in the isolated perfused liver and kidney of adult Wistar rats. Bilateral adrenalectomy was performed 3 weeks before experiments. In nonadrenalectomized rats, 0.3 mg/kg/day dexamethasone was continuously infused subcutaneously for 1 week before experiments. Adrenalectomy did not affect hepatic or renal metabolism of aldosterone. Dexamethasone treatment did not change the renal handling of aldosterone. However, the hepatic clearance of aldosterone was 19% lower (P less than 0.05) in livers of dexamethasone treated rats than in livers of normal rats. After 5 minutes, perfusate [4-14C]aldosterone metabolites were lower in livers of dexamethasone-treated than in livers of normal rats (P less than 0.05). Similar perfusate levels were then obtained. Radiometabolite peaks with similar relative retention times were found in the hepatic perfusate of all groups. However, the ratio between circulating polar metabolites of aldosterone and the metabolites less polar than tetrahydroaldosterone, after 5 and 15 minutes, was highest in livers of dexamethasone-treated rats. Biliary elimination of 14C was similar in all groups. Significant amounts of conjugated tetrahydroaldosterone were only excreted in the bile of dexamethasone-treated rats. In conclusion, glucocorticoid excess reduced the hepatic clearance of aldosterone and changed the pattern of the hepatic metabolites of aldosterone both in circulation and in bile.

Calcium concentration in the CAPD dialysate: what is optimal and is there a need to individualize?

OBJECTIVE: To evaluate risk/benefit of various continuous ambulatory peritoneal dialysis (CAPD) dialysate calcium concentrations. DATA SOURCES: A review of the literature on the effects of various CAPD dialysate Ca concentrations on plasma Ca, plasma phosphate, plasma parathyroid hormone (PTH), doses of calcium carbonate, doses of vitamin D analogs, and requirements of aluminum-containing phosphate binders. STUDY SELECTION: Eleven studies of nonselected CAPD patients, and 13 studies of CAPD patients with hypercalcemia were reviewed. RESULTS: In nonselected CAPD patients, treatment with a reduced dialysate Ca concentration (1.00, 1.25, or 1.35 mmol/L) improved the tolerance to calcium carbonate and/or vitamin D metabolites and reduced the need for Al-containing phosphate binders. When using dialysate Ca 1.25 or 1.35 mmol/L, the initial decrease of plasma Ca and increase of PTH could easily be reversed with an immediate adjustment of the treatment. After 3 months, stable plasma Ca and PTH levels could be maintained using only monthly investigations. In patients with hypercalcemia and elevated PTH levels, treatment with dialysate Ca concentrations below 1.25 mmol/L implied a considerable risk for the progression of secondary hyperparathyroidism. When hypercalcemia was present in combination with suppressed PTH levels, a controlled increase of PTH could be obtained with a temporary discontinuation of vitamin D and/or a reduction of calcium carbonate treatment in combination with a dialysate Ca concentration of 1.25 or 1.35 mmol/L. CONCLUSION: Most CAPD patients can be treated effectively and safely with a reduced dialysate Ca concentration of 1.35 or 1.25 mmol/L. Treatment with dialysate Ca concentrations below 1.25 mmol/L should not be used. A small fraction of patients with persistent hypocalcemia need treatment with high dialysate Ca, such as 1.75 mmol/L.

[Evaluation and treatment of patients with kidney calculi]. / Vurdering og behandling af patienter med nyresten.

Renal stone disease is a common disorder causing much discomfort and high rates of sick-leave. Surgical treatment has improved dramatically with extracorporeal shock wave lithotripsy, but the recurrence rate is high, and it would be desirable to be able to offer the patients effective steps in prevention of further stone formation. The biochemical abnormalities associated with stone formation are complex and not fully elucidated. It should, however, be possible to reduce the recurrence rate with a relatively simple programme for investigation of the patients. The pathogenesis of renal stones is, therefore, reviewed with reference to a plan for the practical approach to the prevention and management of nephrolithiasis, that has recently been recommended by The National Kidney Foundation, USA.

[Total parathyroidectomy and autotransplantation of parathyroid tissue. Functional assessment of the autograft 5-10 years after surgery with the help of local ischemic blockade]. / Total paratyreoidektomi og autotransplantation af parathyreoideavaev. Vurdering af autotransplantatets funktion 5-10 år efter operationen ved hjoelp af lokal iskoemisk blokade.

The aim of the present study was to assess the long-term function of autotransplanted parathyroid tissue. From the medical records of a consecutive series of 21 patients we found that during the time of follow-up (79 months) one patient developed parathyroid graft dependent recurrent hyperparathyroidism (HPT) and one patient suffered from hypoparathyroidism. Nine of the patients were available for measurements of the plasma concentrations of intact parathyroid hormone (iPTH) at rest and during a shortlasting ischaemic blockade of the autotransplant. In eight patients, the ischaemic blockade reduced the concentration of iPTH with on average 62% as compared to baseline values. In one patient, the autotransplant had been resected and as expected, iPTH did not change during ischaemic blockade. Our results indicate that total parathyroidectomy with autotransplantation provides a rational alternative to the surgical treatment of secondary HPT and that the ischaemic blockade manoeuvre seems suitable for assessment of the function of parathyroid autotransplants.

[Primary hyperparathyroidism. An underdiagnosed disease in Denmark?]. / Primaer hyperparatyreoidisme. En underdiagnosticeret sygdom i Danmark?

Population-based investigations measuring serum calcium levels seem to indicate a prevalence of primary hyperparathyroidism (pHPT) of 0.4-1% in adults with a figure of about 3% in women over 60 years of age. Annual incidence rate varies and is found to be about 25-30 new cases per 100,000 adults with routine use of serum calcium measurements in diagnostic work-up. In women over 60 years of age the incidence approaches 200 instances per 100,000 individuals. Autopsy studies have demonstrated parathyroid disease in about 10%, one third as solitary adenomas and two thirds as hyperplasia. Annual incidence of surgical interventions, however, is currently found to be low with a frequency of about 2 instances per 100,000 inhabitants in Denmark, but with somewhat higher figures in Sweden and Finland. Recently, the preoperative diagnosis of pHPT has been considerably simplified and requires in most cases solely the demonstration of sustained raised serum calcium levels associated with elevated serum concentration of intact PTH. Investigations indicate that pHPT is underdiagnosed in Denmark, and indications for surgical treatment appear to be restrictive. Compared with Swedish operation series the weight of parathyroid adenomas in Danish series is found to be 3 times higher and the mass of hyperplasia 9 times higher consistent with significantly more elevated serum calcium concentrations. Arguments are presented in favour of an increased interest in diagnosing pHPT and a more liberal approach in the selection of patients for surgical treatment of mild or even asymptomatic disease. Routine measurement of serum calcium concentration in blood samples from patients might be considered in order to increase the incidence rate.(ABSTRACT TRUNCATED AT 250 WORDS)

The combined effect of parathyroid hormone and bone graft on implant fixation.

Impaction allograft is an established method of securing initial stability of an implant in arthroplasty. Subsequent bone integration can be prolonged, and the volume of allograft may not be maintained. Intermittent administration of parathyroid hormone has an anabolic effect on bone and may therefore improve integration of an implant. Using a canine implant model we tested the hypothesis that administration of parathyroid hormone may improve osseointegration of implants surrounded by bone graft. In 20 dogs a cylindrical porous-coated titanium alloy implant was inserted into normal cancellous bone in the proximal humerus and surrounded by a circumferential gap of 2.5 mm. Morsellised allograft was impacted around the implant. Half of the animals were given daily injections of human parathyroid hormone (1-34) 5 µg/kg for four weeks and half received control injections. The two groups were compared by mechanical testing and histomorphometry. We observed a significant increase in new bone formation within the bone graft in the parathyroid hormone group. There were no significant differences in the volume of allograft, bone-implant contact or in the mechanical parameters. These findings suggest that parathyroid hormone improves new bone formation in impacted morsellised allograft around an implant and retains the graft volume without significant resorption. Fixation of the implant was neither improved nor compromised at the final follow-up of four weeks.

[Premature rupture of fetal membranes and chorioamnionitis]. / For tidlig fostervannsavgang og korioamnionitt.

The article presents a survey of preterm rupture of the amniotic membranes at term (more than 1 hour prior to uterine contractions) and preterm (< 37 weeks). The diagnosis of rupture can be suspected from the history alone in 90% of the cases, and confirmed by inspection. In doubtful cases the pH in fluid from the posterior fornix of the vagina is determined and microscopy is performed. Amniotic fluid is alkaline. Microscopy of a dried specimen shows "ferning" when amniotic fluid is present (crystallization test). Staining with Nil blue will reveal orange foetal cells in fresh specimens, usually only late in pregnancy (after the 38 week). The crystallization test is useful, however, in all three trimesters. The cause of membrane rupture and of chorioamnionitis may be infection. Chorioamnionitis is a serious clinical condition, but can be subclinical and may occur with intact membranes. It can lead to preterm delivery. It is important that chorioamnionitis be diagnosed (maternal fever, tachycardia, uterine contractions, abdominal pain, foul smelling vaginal discharge and elevated C-reactive protein). The condition is treated with antibiotics and labour must be induced.

Aldosterone metabolism in combined isolated perfused rat liver and kidney.

The metabolism of aldosterone (Aldo) at 4 nM was studied by radioimmunoassay and by high-performance liquid chromatography in isolated perfused liver (IPL), isolated perfused kidney (IPK), and combined isolated perfused liver and kidney (CIPLK) of male Wistar rats. Effect of D[4-(14)C]aldosterone (D [4-(14)C]Aldo) on the function of IPK of intact and adrenalectomized (ADX) rats was also studied. Aldo clearance in the liver was most important, 16.3 +/- 1.7 ml/min. In IPK, the total clearance of Aldo was 0.27 +/- 0.36 ml/min (39% of the glomerular filtration rate) (GFR). Fractional excretion (FE) of Aldo was 16 +/- 8%. Metabolic clearance of Aldo was (0.21 +/- 0.23 ml/min), 78% of total renal clearance. In CIPLK, the kidney inhibited hepatic clearance of Aldo by 23% when compared with IPL (P less than 0.05). Hepatic Aldo metabolites were predominantly eliminated by biliary excretion of polar metabolites. Several hepatic polar metabolites and tetrahydroaldosterone (THA) accumulated in perfusate and were excreted in the urine in a similar pattern. After hydrolysis of the polar metabolites, some coeluated with THA and dihydroaldosterone (DHA), whereas other metabolites remained more polar than Aldo. Without addition of Aldo, in IPK of ADX rats FENa was higher (P less than 0.01), and FEK was lower (P less than 0.01), resulting in three- to fourfold higher urinary Na-K ratio (P less than 0.01) when compared with IPK and CIPLK of intact rats. In IPK of ADX rats with Aldo in perfusate, only FEK was restored. Addition of Aldo to IPK of intact rats had no effect. However, only in CIPLK, addition of Aldo resulted in an increasing kaliuresis in three subsequent periods of 30 min (0.56-0.95, P less than 0.01). Thus the hepatic metabolites of Aldo could in part mediate the kaliuretic effect of Aldo.

Isolated perfused rat kidney and liver combined. A new experimental model.

Interaction between hepatic and renal metabolism is found in many endocrine systems. We therefore developed a new experimental model, combining the isolated perfused rat kidney and rat liver. Krebs-Henseleit buffer with bovine serum albumin 67 g X l-1 and amino acids was recirculated to both organs through two rolling pumps, four 8 microns Millipore filters and two specially designed membrane lungs. The kidney was cannulated by a modification of the technique described by Nishiitsutsuji-Uwo 1967 and the liver was cannulated by a modification of the technique described by Hems 1966. Kidney function: Perfusion pressure 12.4 +/- 1.1 kPa (93 +/- 8 mmHg), flow 28 +/- 6 ml X min-1 X g-1, FRNa 94.0 +/- 2.9%, GFR 491 +/- 191 microliters X min-1 X g-1, urine production 48 +/- 34 microliters X min-1 X g-1, FEK 60 +/- 36%. Liver function: Flow 25 ml X min-1 (fixed), portal vein pressure 12 +/- 3 cm H2O, bile flow 0.18 +/- 0.13 ml X h-1, oxygen consumption 2.0 +/- 0.2 mumol X min-1 X g-1. Only minor differences were found between single perfusions (N = 25) and combined perfusions (N = 6). We conclude that it is possible to combine the isolated perfused rat kidney and rat liver without impairment of the function of either.

Metabolism of intact parathyroid hormone in isolated perfused rat liver and kidney.

Metabolism of synthetic human parathyroid hormone (PTH) 2 X 10(-10) to 5 X 10(-9) M was studied in 16 isolated perfused rat kidneys and 12 isolated perfused rat livers. Organ clearances were measured by assays specific for intact PTH. Production of fragments was analyzed by high-performance liquid chromatography (HPLC) and radioimmunoassays specific for NH2-terminal, midmolecule, and COOH-terminal PTH. The livers cleared intact PTH and NH2-terminal immunoreactive PTH (iPTH) at the same rate. Midmolecule iPTH was cleared significantly (P less than 0.001) slower, as was COOH-terminal iPTH (P less than 0.005), and HPLC studies demonstrated production of midmolecule/COOH-terminal PTH fragments, while no NH2-terminal fragments were found. Clearance in the kidneys of intact PTH and of NH2-terminal, midmolecule, and COOH-terminal iPTH was not significantly different from clearance of inulin. No clearance of intact PTH was found in nonfiltering kidneys. HPLC studies did not demonstrate release of any PTH fragments from the kidneys. In conclusion, the liver was not selective for intact PTH, and differential hepatic clearance, possibly together with direct glandular secretion, may contribute to the predominance of COOH-terminal PTH fragments in plasma.

Metabolism of parathyroid hormone in isolated perfused rat kidney and liver combined.

Metabolism of synthetic, intact, human parathyroid hormone (PTH) 10(-9) M was studied in a new experimental model using the isolated perfused rat kidney and liver combined. The combined organs cleared intact PTH significantly faster than the single kidneys (P less than 0.02) or livers (P less than 0.02), but not faster than the sum of the clearances in the single organs. The kidneys cleared intact PTH without accumulation of NH2-terminal, mid-molecule or COOH-terminal iPTH, and high-performance liquid chromatography (HPLC) studies did not reveal any PTH fragments. The livers cleared mid-molecule and COOH-terminal iPTH significantly slower (P less than 0.002) than intact PTH, and HPLC demonstrated generation of mid-molecule and COOH-terminal PTH fragments. The combined organs accumulated significantly less mid-molecule (P less than 0.001) and COOH-terminal (P less than 0.03) iPTH than the single livers, and HPLC demonstrated mid-molecule peaks that were smaller but not qualitatively different. In conclusion, the predominance of COOH-terminal PTH fragments in plasma may be maintained by differential clearance mainly in the liver, excessive accumulation being prevented by filtration in the kidneys.