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Biomedical subjects

M Falk

Publications and source records attributed to M Falk.

At least 37 records · Page 2Linked to original sources

Serial radiography in the infant shaken impact syndrome.

Certain CT and/or MRI abnormalities have been used medicolegally to time intracranial injuries from the infant shaken impact syndrome (ISIS). For example, parenchymal hypodensities on CT scans are said to arise only after 6-48 h have elapsed postinjury, and the presence of chronic or mixed subdural hematomas suggests injury that occured 1-4 weeks prior. However, these statements are based largely upon inference from data obtained in other conditions such as ischemic anoxic injury and chronic subdural hemorrhage in adults. Direct evidence about the evolution of intracranial injuries in infants with ISIS is sparse, and the radiographic changes following ISIS have never been systematically studied on serial imaging studies. One hundred-seventeen serial CT and MRI scans obtained from 33 infants with ISIS were reviewed retrospectively. The exact scan dates and times were obtained directly from the scans. Acute subdural hemorrhage was the most common intracranial abnormality and was present in 27 (81%) of the 33 infants. Other intracranial abnormalities included chronic subdural collections, subarachnoid hemorrhage, epidural hematomas, parenchymal hypodensities, edema and contusions, and atrophy and encephalomalacia. In 15 of the 33 infants, the injury could be timed with reasonable certainty, and the evolution of the radiographic changes followed over time. Six of the 15 infants had evidence of prior cranial trauma such as chronic subdural collections (5 infants) or mild atrophy (1 infant). Of the remaining 9 infants, parenchymal abnormalities such as hypodensities, edema and contusion appeared in virtually all of the initial scans performed approximately 3 h following the report of injury. One 'chronic' subdural collection was absent on the first scan performed 2.75 h postinjury, but appeared on a second scan performed 17 h later, suggesting that some 'chronic' subdural fluid collections may arise much sooner than previously thought. These findings challenge some of the current dogma about the timing of radiographic changes following abuse and are important in timing the alleged abuse for legal purposes.

Battered Child Syndrome↗

Conformation of kainic acid in solution from molecular modelling and NMR spectra.

Conformational behaviour of kainic acid in aqueous solution was elucidated by molecular mechanics and dynamics. The pucker of the five-membered ring in kainic acid was examined and compared with that of model compounds. In cyclopentane there is no barrier to pseudorotation, so that all puckered states coexist. In pyrrolidinium, the presence of a hetero-atom in the ring introduces a small barrier (about 0.6 kcal mol(-1)) to pseudorotation, separating two stable regions, A and B, which are equivalent by symmetry. In proline, the presence of the carboxylate group on C2 removes the symmetry but two stable conformational minima, A and B, remain. In kainic acid, the presence of side-chains on C3 and C4 introduces complications resulting in additional sub-minima in both regions, A and B. In solution, kainic acid is a complex mixture of conformers with comparable energies, because of the combination of several stable states of the pyrrolidinium ring with the torsional degrees of freedom arising from the two side-chains. The individual geometries, energies, and estimates of relative populations of these conformers were obtained from molecular dynamics simulations. The calculations were validated by a comparison of predicted inter-proton distances and vicinal proton coupling constants with the experimental quantities derived from NMR spectra.

Excitatory Amino Acid Agonists↗

Expansion of the nonadherent myeloid cell population by monoclonal antibodies against tenascin-C in murine long-term bone marrow cultures.

Tenascin-C, a predominantly mesenchymal extracellular matrix protein, has a restricted distribution in adult tissues. It has previously been shown that this protein is expressed in the bone marrow. In this paper we show that murine myeloid and lymphoid long-term bone marrow cultures differ in their expression of tenascin-C splice variants. In the adherent stromal layer of myeloid cultures, the 260-kDa polypeptide encoded by the 8-kb mRNA was the major splice variant, whereas in the stromal layer of lymphoid cultures both the shorter 210-kDa polypeptide encoded by the 6-kb mRNA and the 260-kDa polypeptide were abundantly expressed. However, in both culture systems the larger 260-kDa tenascin-C polypeptide was the major isoform secreted in the culture supernatant. This finding is in agreement with previous reports indicating that the smaller 210-kDa isoform is preferentially deposited in the stroma, whereas the alternatively spliced segment in the 260-kDa tenascin-C may contain anti-adhesive domains. Glucocorticoids in myeloid long-term bone marrow cultures and in the MC3T3-G2/PA6 cell line downregulated the expression of tenascin-C. In the present study we observed that this was due primarily to downregulation of the 8-kb major splice variant of the tenascin-C mRNA. We also studied the possible role of tenascin-C in the bone marrow by using antibodies against tenascin-C in long-term bone marrow cultures. We found that three monoclonal antibodies against the carboxyterminal type III fibronectin repeats of tenascin-C (TNCfn 7-8) increased the number of the non-adherent myeloid cells in myeloid long-term bone marrow cultures. It has recently been suggested that the TNCfn 6-8 domain of tenascin-C binds to the alpha8beta1 integrin. Using Northern blotting, we found that the integrin alpha8 subunit was expressed in adherent cells in bone marrow cultures, raising the possibility that tenascin-C acts in bone marrow cultures by binding to the alpha8beta1 integrin.

Animals↗

[Avalanche emergency. New aspects of the pathophysiology and therapy of buried avalanche victims].

A series of investigations on the pathophysiology and management of persons buried in an avalanche has been undertaken over the past few years in response to increased awareness of the importance of emergency medical treatment of avalanche victims and the fact that the high mortality rate has not decreased in spite of the improvement in rescue techniques. This paper is the very first review of the problems encountered in avalanche disasters. The developments over the past 20 years, in particular, are summarized and discussed. Furthermore, current opinions and recommendations on optimal rescue procedure, as well as the prevention of such emergencies are presented. Precise assessment of the survival probability after burial under an avalanche and recognition of the prognostic importance of an air pocket, but only limited role of hypothermia, provide the basis for new concepts governing therapy and triage by the emergency doctor. Resulting guidelines have been endorsed by the Emergency Medicine Subdivision of the International Commission of the Alpine Rescue Services (ICAR) and these recommendations are intended for implementation by organised rescue teams in order to reduce secondary deaths following successful extrication of victims from the avalanche masses. However, the chance of being rescued alive depends primarily on the rapidity of extrication, i.e. how quickly the rescue teams are alerted and transported to the disaster area in the first instance, then how quickly the victims are located and extricated. In order to reduce the mortality additional preventive measures must be introduced to avoid complete burial if possible, or appreciably hasten the rescue procedure. The very steep drop ("fatal kink") in survival probability as from 15 minutes after burial underlines the absolute necessity of the mastery of efficient rescue procedure by uninjured companions. Improvement of the technical developments for the avoidance of total burial (avalanche air bag) and optimization of the electronic location (transceiver) of buried skiers by uninjured companions are essential future requirements. Nonetheless, primary prevention remains of paramount importance in governing decision making by offpiste skiers. Correct assessment of the inherent risks according to the prevailing circumstances and strict adherence to safety rules take precedence over all other considerations.

Asphyxia↗

Improvement of prostate cancer screening by determination of the ratio free/total PSA in addition to PSA levels.

BACKGROUND: The measurement of prostate specific antigen (PSA) is widely used in screening programs for early detection of prostate cancer. However the specificity for cancer detection is limited because serum PSA is also elevated in patients with benign prostatic-hyperplasia (BPH) and/or prostatitis. It has been shown recently, that the ratio of free/total PSA in serum is lower in malignant prostatic disorders than in non-malignant ones and therefore might be a parameter to improve screening specificity. In a retrospective study, we tested whether free/total PSA helps to distinguish between BPH and prostatic carcinoma in men with elevated serum PSA. METHODS: A total of 266 men have been identified with age-specific elevated serum PSA levels using a conventional PSA determination kit. Subsequently their disease was proven by biopsies. Free and total PSA levels in these serum samples were measured using the DELFIA PSA dual label free/total PSA kit. RESULTS: The mean free/total PSA of 64 patients with prostate cancer was 0.10 and was significantly (P = 0.001) different from the mean free/total PSA of 202 men who were histologically free of cancer, which was 0.17. Receiver-operating-characteristic curve (ROC) analysis showed that using a free/total PSA ratio of 0.18 as a biopsy criterion in men with an elevated PSA serum level, 37% of the negative biopsies could be eliminated while still detecting 94% of all carcinomas. CONCLUSIONS: These results show that the ratio of free/total PSA is a useful determination and can improve specificity of prostate cancer screening.

Aged↗

Active compression-decompression cardiopulmonary resuscitation in standing position over the patient: pros and cons of a new method.

Active compression-decompression cardiopulmonary resuscitation (ACD-CPR) has been introduced to improve outcome of CPR after cardiac arrest. Usually, ACD-CPR is performed with the rescuer kneeling beside the patient (ACD-B), but ACD-CPR with the rescuer in standing position (ACD-S) has been taught and applied in some centres in addition to conventional ACD-CPR (ACD-B). The aim of this randomised and cross-over study was to evaluate the new technique of ACD-S and to compare it with conventional ACD-B. Twelve professional rescuers (aged 30.8 +/- 7.9 years) applied both methods of ACD-CPR on a manikin. We obtained the following results. (1) Duration of CPR performance was comparable for ACD-S (13.2 +/- 7.1 min) and ACD-B (15.5 +/- 10.2 min, P = 0.48). (2) Pain in the upper extremity and pain in the vertebral column were the main reasons for break-off by the rescuers. Exhaustion was judged to be similar during ACD-S (5.3 +/- 2.3) and ACD-B (6.2 +/- 2.1; on a rating scale with 1 = no and 9 = complete exhaustion). (3) Oxygen consumption was significantly higher during ACD-S (P < 0.005), whereas heart rate and lactate levels did not differ. (4) Decompression forces were lower than compression forces. The averaged decompression forces in both methods were similar during the first 2 min and the last min. Compression forces decreased in ACD-S from 55.1 to 48.9 kp (P = 0.002) and in ACD-B from 52.8 to 47.0 kp (P = 0.069). We conclude that ACD-CPR in standing position can be considered equal to ACD-B in view of maximal duration of CPR, exhaustion of the rescuers and decompression forces. The decrease of compression forces in ACD-S and ACD-B as well as the difference between compression forces in ACD-S and ACD-B seem to be of no clinical relevance, and exhaustion was judged to be similar despite oxygen consumption being higher in ACD-S than in ACD-B.

Adult↗

Physician and patient evaluation of hypertension-related risks and benefits from treatment.

Implementation of management programmes in hypertension in accordance with current guidelines needs the participation not only of physicians and other health professionals, but also of the patients themselves. Patients' knowledge of, and attitudes to, cardiovascular risk factors, as well as patients' perceptions of the benefits and potential risks of treatment, are factors likely to be of importance regarding their compliance, their opinions and their acceptance of treatment. The extent to which patients are able to assess the absolute and relative risks of having hypertension, as well as individual benefits from treatment, is yet largely unexplored. Compared with a number of common drug treatments, the general adult population perceives the risks from receiving antihypertensive drug therapy as intermediate to low. Improving patients' knowledge and acceptance of antihypertensive therapy by improving the physician-patient relationship will involve patients more in their own treatment decisions, thereby probably improving the management and treatment as a whole.

Adult↗

c-myc activation renders proliferation of Epstein-Barr virus (EBV)-transformed cells independent of EBV nuclear antigen 2 and latent membrane protein 1.

Two genetic events contribute to the development of endemic Burkitt lymphoma (BL) infection of B lymphocytes with Epstein-Barr virus (EBV) and the activation of the protooncogene c-myc through chromosomal translocation. The viral genes EBV nuclear antigen 2 (EBNA2) and latent membrane protein 1 (LMP1) are essential for transformation of primary human B cells by EBV in vitro; however, these genes are not expressed in BL cells in vivo. To address the question whether c-myc activation might abrogate the requirement of the EBNA2 and LMP1 function, we have introduced an activated c-myc gene into an EBV-transformed cell line in which EBNA2 was rendered estrogen-dependent through fusion with the hormone binding domain of the estrogen receptor. The c-myc gene was placed under the control of regulatory elements of the immunoglobulin kappa locus composed a matrix attachment region, the intron enhancer, and the 3' enhancer. We show here that transfection of a c-myc expression plasmid followed by selection for high MYC expression is capable of inducing continuous proliferation of these cells in the absence of functional EBNA2 and LMP1. c-myc-induced hormone-independent proliferation was associated with a dramatic change in the growth behavior as well as cell surface marker expression of these cells. The typical lymphoblastoid morphology and phenotype of EBV-transformed cells completely changed into that of BL cells in vivo. We conclude that the phenotype of BL cells reflects the expression pattern of viral and cellular genes rather than its germinal center origin.

Antigens, CD↗

Analysis of the initiation period of spontaneous autoimmune thyroiditis (SAT) in obese strain (OS) of chickens.

The early, predictable, onset of spontaneous autoimmune thyroiditis (SAT) in Obese strain (OS) chickens provides a unique opportunity to analyse the mechanisms initiating autoimmunity which is virtually impossible to obtain in humans. In this study we focused on the respective roles of viruses and macrophages in the initiation of SAT. To analyse viruses, leukosis virus-free OS chickens were bred over three generations and reared under gnotobiotic conditions. By 2 weeks of age there were no differences in the levels of thyroid mononuclear cell infiltration between these and control animals. The role of mononuclear phagocytes in SAT was determined by their depletion via injecting newborn OS chicks with silica or carrageenan and dichloro-methylene diphosphonate encapsulated into liposomes. Although this treatment did not substantially change the amount of macrophages in primary lymphoid organs or blood, there was destruction of splenic architecture and, most importantly, mononuclear cell infiltration of the thyroids was significantly lower compared to controls. The role of activated macrophages in SAT is discussed.

Animals↗

Incidence of urethral tumor involvement in 910 men with bladder cancer.

Urethral tumor involvement was examined in 910 patients treated for bladder cancer at a single institution over a period of 25 years. The overall incidence in 2,052 primary and recurrent bladder-tumor events was 6.1%. Risk factors for urethral tumor occurrence are tumors at the bladder neck and recurrent multifocal tumors. Carcinoma in situ (CIS) of the bladder not involving the bladder neck and muscle-invasive tumors with or without lymph-node involvement are not significantly correlated with urethral cancer. Patients at risk for urethral tumors as outlined should be worked up very carefully (multiple urethral biopsies and/or urethral brushings, frozen section of the membranous urethra) before they are considered for an orthotopic neobladder. Altogether, 17 of 89 patients had 1-6 urethral tumor recurrences. The majority of urethral tumors were treated with a single conservative treatment session and did not recur thereafter. A conservative approach toward superficial urethral tumor recurrences in patients with an orthotopic neobladder to the urethra may therefore be feasible.

Adult↗

Circulating interleukin-1 receptor antagonist levels in neonates.

UNLABELLED: Circulating interleukin-1 receptor antagonist (IL-1 Ra) levels have been shown to reflect disease activity in certain conditions in adults. We determined circulating IL-1Ra references values for healthy neonates (healthy preterms and term infants with mild disease only) on days 2 (n = 17) and 4 of life (n = 23). Mean gestational age was 35 +/- 2.6 weeks. On the 2nd day of life IL1-Ra levels were 0.78 ng/ml (0.49/2.65), on day 4 0.38 ng/ml (0.20/0.48) (median, 25th/75th percentile, P = 0.01). The values were not influenced by gender. In neonates with severe illness (septicaemia, asphyxia, neonatal respiratory distress syndrome), who received invasive intensive care, circulating IL-1Ra levels were significantly higher than in the reference group of healthy newborns. On the 2nd day of life (14.72 ng/ml (4.38/18.67) versus 0.78 ng/ml (0.49/2.65), P < 0.0001; on day 4 of life, 3.38 ng/ml (0.80/11.99) versus 0.38 ng/ml (0.20/0.48), P < 0.005 (values are median; 25th/75th percentile, Mann-Whitney U-Wilcoxon Rank Sum W Test, two-tailed P). CONCLUSION: Compared to healthy individuals beyond the neonatal period, Il-1Ra concentrations are physiologically elevated within the first days of life and decline to low levels within days. In contrast, IL-1Ra levels are strikingly elevated in sick neonates.

Biomarkers↗

Does eosinophilia predict clozapine induced neutropenia?

The atypical antipsychotic clozapine carries a high risk of inducing agranulocytosis. We attempted to investigate whether eosinophilia during clozapine treatment has predictive value for subsequent neutropenia/agranulocytosis. One hundred and seventy-seven patients were studied in a prospective naturalistic design using haloperidol as the reference compound. Clozapine was found to differ from haloperidol in respect to their influence on neutrophil granulocytes. In the clozapine group patients with eosinophilia showed a decrease in neutrophil count (less than 2000/mm3 neutrophil granulocytes) significantly more often than patients without eosinophilia.

Adolescent↗

Interferon alpha-2c therapy of patients with chronic myelogenous leukemia: long-term results of a multicenter phase-II study. Austrian Biological Response Modifier (BRM) Study Group.

In a prospective multicenter phase-II trial 80 patients with Philadelphia (Ph)-positive chronic myelogenous leukemia (CML) were treated with recombinant interferon (IFN) alpha-2c, administered subcutaneously at an absolute dose of 3.5 megaunits (MU)/day. Complete hematological remission was achieved in 29 (39%) and partial hematological remission in 26 (35%) of the 74 patients evaluable for response. Major cytogenetic responses were observed in ten (13%) and minor cytogenetic responses in 11 patients (15%). Median duration of cytogenetic response was 33 months (range, 2-90); relapses were seen in all of the 11 patients with minor and in three of the ten patients with major cytogenetic responses. Median survival estimates for pretreated (n = 19) and untreated (n = 58) patients were 51 months (95% confidence interval [CI], 30-72) and 77 months (95% CI, 43-111), and the survival probabilities at 5 years were 45% and 54% for the two groups, respectively. Hematological response after 3 months of treatment demonstrated a clear-cut discriminative capacity with 5-year survival probabilities of 100%, 67% and 24% for patients achieving CHR (n = 6), PHR (n = 34), and less than PHR (n = 35), respectively. Landmark analysis at 12, 18, and 24 months after start of IFN therapy and an analysis treating time to cytogenetic response as a time-dependent covariate showed that cytogenetic response was associated with longer survival. The impact of a low-dose IFN regimen on survival in CML patients is unclear and requires further clarification by randomized clinical trials. Early hematological and cytogenetic response to IFN-alpha treatment identifies patients with a favorable long-term prognosis.

Adolescent↗

Rescuer's work capacity and duration of cardiopulmonary resuscitation.

Specific training in the techniques of cardiopulmonary resuscitation (CPR) has been the major aim of CPR education for both health care professionals and lay people over the past few decades. We performed a randomized trial to evaluate individual physiological parameters of 12 professional rescuers influencing duration and quality of standard CPR and active compression-decompression CPR. CPR duration was assessed according to individual work capacity after grouping rescuers as untrained and trained individuals, according to their work capacity of up to and including 100% and over 100%. The average work capacity of all the rescuers was determined by incremental exercise testing, resulting in 110.0 +/- 26.5% compared with data for the normal population. With 29.3 +/- 12.8 min duration, standard CPR was significantly longer than active compression-decompression CPR with 15.5 +/- 10.2 min duration (P = 0.009). No changes in the forces of compression and decompression were measured during active compression-decompression CPR, thus demonstrating maintenance of constant CPR quality. Duration of resuscitation was influenced by the CPR method performed and by the individual work capacity (P = 0.004 and P = 0.027, respectively). We conclude that the duration of CPR depends both on the method applied and the rescuers' individual work capacity and recommend improvement of work capacity by aerobic training especially for professional rescuers.

Adult↗

Epstein-Barr virus nuclear antigen 2 (EBNA2)-oestrogen receptor fusion proteins complement the EBNA2-deficient Epstein-Barr virus strain P3HR1 in transformation of primary B cells but suppress growth of human B cell lymphoma lines.

To develop a transformation system with a conditional Epstein-Barr virus nuclear antigen 2 (EBNA2) gene, we fused the hormone binding domain of the oestrogen receptor to the N or C terminus of EBNA2. In promoter transactivation as well as primary B cell transformation assays these chimeric EBNA2 proteins are able to substitute for wild-type EBNA2 in the presence of oestrogen. Here we provide evidence that this transformation is the result of double infection of a cell with two virions, the P3HR1 virus genome and a mini-EBV plasmid carrying the chimeric EBNA2 gene. Unexpectedly, expression of the same EBNA2-oestrogen receptor fusion protein in established human B cell lymphoma lines resulted in growth retardation or growth arrest upon the addition of oestrogen. By titrating the oestrogen concentration in these stably transfected cells, the growth retarding and the transactivating function of the chimeric proteins could not be dissociated. We propose that growth inhibition of established B cell lymphoma lines is a novel function of EBNA2 which has not been detected in the absence of an inducible system. It remains open whether the growth retarding property of the EBNA2-oestrogen receptor fusion protein in B cell lymphoma lines is due to unphysiologically high expression of the chimeric protein or to interference with a cellular programme driving proliferation in these cell lines.

Antigens, Viral↗

Early sensitization to farming-related antigens among young farmers: analysis of risk factors.

It was the aim of this study to investigate the prevalence of and risk factors for IgE- and IgG-mediated allergy in young farmers. We investigated 147 young men attending a farming college in the Austrian Tyrol and 57 age-matched pupils at a grammar school. All individuals completed a questionnaire and had spirometry, skin prick tests, total and specific IgE analysis, and testing for precipitins against thermophilic actinomycetes and true fungi. In the farming group, a family history of atopy or asthma was reported less frequently than in the control group (p < 0.001) but there were no differences in the frequencies of actual respiratory symptoms. Forced expiratory volume in the first second (FEV1) was slightly lower in the farmers than in the pupils (p < 0.05). There was no difference in the prevalence of IgE-mediated allergy. Nine of the farmers but none of the pupils had precipitating antibodies against Faeni rectivirgula (p < 0.05). Overall reactivity (as defined by at least one positive finding with the skin prick test, specific IgE, or precipitins) was associated with larger farming estates, lack of a haydrying device, use of mouldy hay, and positive family history of asthma (p < 0.05). We conclude that in farmers, precipitin formation may occur at an early age and that even in younger age groups there is a clear relationship between allergic sensitization and occupational allergen exposure.

Adolescent↗

Cost-benefit analysis of diabetic eye disease.

Diabetic retinopathy is the main cause of blindness in adults 25-74 years of age in Western countries. At 100% diagnosability and 100% treatability, with laser photocoagulation vision can be retained in at least one eye in 73% of patients with proliferative retinopathy and in 67% of patients with diabetic maculopathy. The cost-benefit analysis draws a comparison of the costs incurred through benefits granted to a blind diabetic and those incurred through proper screening, examination and treatment to avoid blindness as much as possible. These calculations are valid for the State of Tyrol in Austria. The anticipated annual costs for blindness are thus ATS 19,000,000, of which ATS 14,600,000 could be avoided through an optimal screening, examination and therapy program. The maximum costs for examination and therapy amount to ATS 10,700,000, thus giving a minimum saving of ATS 3,900,000 in favor of preventive medicine.

Adult↗

CEOP-IMVP-Dexa in the treatment of aggressive lymphomas: an Austrian multicenter trial.

PURPOSE: This trial evaluated the efficacy, toxicity, and practicability of a new intensive chemotherapy regimen in a multicenter setting of university and community hospitals. PATIENTS AND METHODS: We tested a hybrid protocol of two non-cross-resistant regimens, cyclophosphamide, epirubicin, vincristine, and prednisolone (CEOP) and ifosfamide, etoposide (VP-16), methotrexate, and dexamethasone (IMVP-Dexa) given every fourth week, three to six times according to response, in patients with untreated intermediate- and high-grade non-Hodgkin's lymphoma. Ten Austrian centers entered 81 patients onto this multicenter trial. Eleven patients were excluded. The median age was 55 years. Twenty-six of 70 patients had stage III or IV disease. The distribution among international risk categories low, intermediate-low, intermediate-high, and high was 20%, 34%, 23%, and 23%, respectively. RESULTS: Of 70 eligible patients, 56 (80%) had a complete remission and seven (10%) a partial remission. After a median observation time of 36 months, the estimated time to relapse and overall survival rates are 67% and 72%, respectively. Age and Karnofsky index were the only independent risk factors for survival. Toxicity was primarily hematologic, with a median granulocyte nadir of 0.56 x 10(9)/L. Sixty-seven percent of patients had infections; 25.7% were severe World Health Organization (WHO) grade III or IV. There were three treatment-related deaths. CONCLUSION: CEOP-IMVP-Dexa chemotherapy is safe and feasible on a groupwide basis even when used in community hospitals. Neutropenic infections are the major complications. A 72% 3-year survival rate in patients with intermediate- and high-grade non-Hodgkin's lymphoma warrants further studies. These data are the basis for a randomized trial to compare cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) with CEOP/IMVP-Dexa.

Adolescent↗