An untapped potential for imaging of peripheral osteomyelitis in paediatrics using [18F]FDG PET/CT -the inference from a juvenile porcine model.

PURPOSE: To examine parameters affecting the detection of osteomyelitis (OM) by [18F]FDG PET/CT and to reduce tracer activity in a pig model. BACKGROUND: [18F]FDG PET/CT is recommended for the diagnosis of OM in the axial skeleton of adults. In children, OM has a tendency to become chronic or recurrent, especially in low-income countries. Early diagnosis and initiation of therapy are therefore essential. We have previously demonstrated that [18F]FDG PET/CT is promising in juvenile Staphylococcus aureus (S. aureus) OM of peripheral bones in a pig model, not failing even small lesions. When using imaging in children, radiation exposure should be balanced against fast diagnostics in the individual case. METHODS: Twenty juvenile pigs were inoculated with S. aureus. One week after inoculation, the pigs were [18F]FDG PET/CT scanned. PET list-mode acquired data of a subgroup were retrospectively processed in order to simulate and examine the image quality obtainable with an injected activity of 132 MBq, 44 MBq, 13.2 MBq, and 4.4 MBq, respectively. RESULTS: All lesions were detected by [18F]FDG PET and CT. Some lesions were very small (0.01 cm3), and others were larger (4.18 cm3). SUVmax was higher when sequesters (p = 0.023) and fistulas were formed (p < 0.0001). The simulated data demonstrated that it was possible to reduce the activity to 4.4 MBq without compromising image quality in pigs. CONCLUSIONS: [18F]FDG PET/CT localized even small OM lesions in peripheral bones. It was possible to reduce the injected activity considerably without compromising image quality, impacting the applicability of PET/CT in peripheral OM in children.

Abolished ventilation and perfusion of lung caused by blood clot in the left main bronchus: auto-downregulation of pulmonary arterial blood supply.

It is generally assumed that the lungs possess arterial autoregulation associated with bronchial obstruction. A patient with pneumonia and congestive heart failure unexpectedly developed frequent haemoptysis. High-resolution CT and diagnostic CT were performed as well as ventilation/perfusion (V/Q) scintigraphy with single-photon emission CT (SPECT)/CT. V/Q SPECT/CT demonstrated abolished ventilation due to obstruction of the left main bronchus and markedly reduced perfusion of the entire left lung, a condition that was completely reversed after removal of a blood clot. We present the first pictorially documented case of hypoxia-induced pulmonary vasoconstriction and flow shift in a main pulmonary artery due to a complete intrinsic obstruction of the ipsilateral main bronchus. The condition is reversible, contingent on being relieved within a few days.

Sumatriptan increases the proliferation of peripheral blood mononuclear cells from HIV-infected individuals and healthy blood donors in vitro.

HIV infection is characterized by the loss of CD4+ T cells as well as the loss of T-cell function, leading to severe immunodeficiency. The proliferative capacity of T cells measured in vitro as responses to antigens and mitogens is severely reduced during HIV infection. An increased level of the intracellular second messenger adenosine 3',5'-cyclic monophosphate (cAMP) has been shown to cause impaired proliferative capacity of peripheral blood mononuclear cells (PBMC) from HIV-infected individuals in vitro. Sumatriptan, a 5HT1d receptor agonist, inhibits the activity of adenylyl cyclases, the enzymes responsible for regulation of the intracellular levels of cAMP. In a preliminary study sumatriptan increased the proliferative responses of PBMC to a polyclonal activator in vitro in 9 of 10 HIV-seropositive individuals (p=0.007), and in 7 of 9 healthy blood donors (p=0.05). This was probably due to a decrease in the intracellular level of cyclic AMP.

Serotonin modulates immune function in T cells from HIV-seropositive subjects.

We have shown earlier increased intracellular levels of cAMP in peripheral lymphocytes from HIV-seropositive subjects and that a chemically induced decrease in this level increases cell proliferation and cytotoxicity. Others have shown that serotonin indirectly decreases intracellular cAMP levels in normal peripheral lymphocytes. In this study, we show that addition of serotonin decreases intracellular levels of cAMP in lymphocytes from HIV-seropositive subjects and significantly increases the proliferative capacity in vitro. However, the effect of serotonin varies with the initial proliferative response; e.g., these with the highest initial responses have the highest increases. An increase in IL-2 production may be a part of this mechanism since addition of serotonin to in vitro cultures of PHA-stimulated cells increases the expression of mRNA for IL-2 and IFN-gamma. The effect on lymphocyte proliferation was most likely mediated through the serotonin 5HT1a receptor because similar results could be obtained by using DPAT, a specific activator of this receptor. Changes in the expression of 5HT1a receptors as judged by the expression of mRNA could not explain why serotonin in vitro had a stronger enhancing effect on cell proliferation in some HIV-seropositive individuals than in others.

Various functions of PBMC from colon cancer patients are not decreased compared to healthy blood donors.

The immune surveillance hypothesis suggests impaired immune responses to participate in development of cancer. This may partly be due to increased amounts of PGE2 and histamine, which inhibit cellular immunity. These effects are mediated by cAMP, which is increased and thereby may down-regulate IL-2 and its receptor proteins in T helper cells. The proliferative responses and IL-2 synthesis of PBMC have earlier been shown to be reduced in patients with colon cancer. Recently immune modulating agents have been demonstrated to increase the proliferative response of PBMC in vitro, probably by inhibition of adenylate cyclase activity and induction of IL-2 mRNA expression. We have therefore studied the proliferative responses of PBMC from colon cancer patients to PWM and tested the effect of immune modulating agents, such as Serotonin, Sumatriptan, and Buspirone on these PBMC. We found no difference in levels of intracellular cAMP, IL-2 mRNA expression, IL-2R mRNA expression, or proliferative responses of PBMC from colon cancer patients compared to healthy blood donors. There was no effect of the immune modulating agents on PBMC from colon cancer patients.

The serotonin analogue buspirone increases the function of PBMC from HIV-infected individuals in vitro.

HIV infection is characterized by the loss of CD4+ T cell numbers as well as loss of T cell function leading to severe immunodeficiency. The proliferative capacity of T cells, measured in vitro as response to antigens and mitogens, is severely reduced during HIV infection. An increased level of the intracellular second messenger cAMP has been demonstrated to cause impaired proliferative capacity of PBMC from HIV-infected individuals in vitro. We have identified a serotonin analogue, buspirone, that inhibits the activity of adenylyl cyclase, the enzyme responsible for regulation of intracellular levels of cAMP. Using this inhibitor the proliferative responses of PBMC to a polyclone activator in vitro were increased in 28/30 HIV-seropositive individuals (p < 0.00001). Further, we demonstrated that this was due to proliferation of CD4+ T cells and that buspirone induced expression of IL-2 mRNA.

[Menstrual cycle and surgery of breast cancer. Point of time for the surgery of primary breast cancer in connection with menstrual cycle is without prognostic significance]. / Menstruationscyklus og operation for mammacancer. Tidspunktet for operation for primoer mammacancer i forhold til menstruationscyklus er uden prognostisk betydning.

From 1977 to 1989 6488 patients under fifty years with primary breast cancer were registered in the nationwide Danish Breast Cancer Cooperative Group (DBCG). Among these information on last menstrual period prior to surgery was available in 1635 cases which constitute the study group of the present analysis. The group was representative of the total group with regard to prognostic factors and survival. In the study group time of surgery in relation to last menstrual period was found to have no influence on five- and ten year survival.

[Significance for prognosis of delayed diagnosis and treatment of breast cancer]. / Prognostisk betydning af forsinket diagnostik og behandling af brystkraeft.

In a study of 7608 patients with primary breast cancer the effect of patient's and doctor's delay on survival was examined. The delay was arbitrarily divided into the following intervals: Short (0-14 days), intermediate (15-60 days) and long (> 60 days). The delay had significant influence on survival. A long patient's delay was associated with an unfavourable outcome, as compared with a short delay. On the contrary, the prognosis was better for patients with a long doctor's delay compared to that of a short doctor's delay. Overall, when corrected for age, the prognostic value of delay in terms of mortality increased by 24% for a long patient's delay compared to a short one, and by 13% for a short doctor's delay compared to a long one. This suggests that all causes of delay should be kept at a minimum.

Timing of surgery in relation to menstrual cycle does not predict the prognosis in primary breast cancer. Danish Breast Cancer Cooperative Group.

From 1977 to 1989 6488 patients under 50 years with primary breast cancer were registered in the nationwide Danish Breast Cancer Cooperative Group (DBCG). Among these, information on last menstrual period prior to surgery was available in 1635 cases which constitute the study group of the present analysis. The group was representative of all women operated upon during the period with regard to prognostic factors and survival. In the study group time of surgery in relation to last menstrual period was found to have no influence on 5 and 10 years survival.

Patient's and doctor's delay in primary breast cancer. Prognostic implications.

In a study of 7,608 patients with primary breast cancer patient's and doctor's delay were examined in relation to age, tumour size, grade of anaplasia, and number of positive lymph nodes. The delays were arbitrarily divided into the following intervals: Short (0-14 days), intermediate (15-60 days) and long (> 60 days). The well-established patient and tumour characteristics were shown to have prognostic significance. Similarly the delays showed significant influence on survival. A long patient's delay was associated with an unfavourable outcome, as compared with a short delay. On the contrary, the prognosis was superior for patients with a long doctor's delay compared to those with a short doctor's delay. Overall, when corrected for age, the prognostic value of delay in terms of mortality increased by 24% for a long patient's delay compared to a shorter and by 13% for a short doctor's delay compared to a longer. This indicates that doctors are capable of distinguishing between more and less aggressive malignancies. The study also suggests that all sources of delays should be kept at a minimum.

Covalent modification of serum transferrin with phospholipid and incorporation into liposomal membranes.

A method is described for incorporation of water-soluble proteins into liposomal membranes using covalent protein-phospholipid conjugates in detergent solution. A disulfide derivative of phosphatidylethanolamine containing a reactive N-hydroxysuccinimide ester group is synthesized, and the derivative is reacted with serum transferrin in deoxycholate-containing buffer. Disulfide-linked transferrin-phosphatidylethanolamine conjugates containing up to 6 mol phospholipid/mol protein are prepared. The amphiphilic conjugates have solubility properties very similar to integral membrane proteins. The conjugates self-associate to form protein micelles of narrow size distribution (Stokes radii 6-7 nm), and in the presence of excess phospholipid (egg phosphatidylcholine), they readily incorporate into liposomal membranes upon removal of detergent. Stable incorporation into liposomes requires the introduction of two molecules of phosphatidylethanolamine into the transferrin. Using the disulfide linker to release transferrin from the liposomes, evidence is presented for a function of the phosphatidylethanolamine as an anchor-molecule into the liposomal lipid. Optimal conditions for preparation of homogeneous liposomes with diameters in the range 30-125 nm and with a varying content of transferrin are defined. The liposomes appear well suited for studies on liposome-cell membrane interactions.