[Guidelines for Non-Invasive and Invasive Home Mechanical Ventilation for Treatment of Chronic Respiratory Failure - Update 2017]. / S2k-Leitlinie: Nichtinvasive und invasive Beatmung als Therapie der chronischen respiratorischen Insuffizienz ­ Revision 2017.

Today, invasive and non-invasive home mechanical ventilation have become a well-established treatment option. Consequently, in 2010 the German Society of Pneumology and Mechanical Ventilation (DGP) has leadingly published the guidelines on "Non-Invasive and Invasive Mechanical Ventilation for Treatment of Chronic Respiratory Failure". However, continuing technical evolutions, new scientific insights, and health care developments require an extensive revision of the guidelines.For this reason, the updated guidelines are now published. Thereby, the existing chapters, namely technical issues, organizational structures in Germany, qualification criteria, disease specific recommendations including special features in pediatrics as well as ethical aspects and palliative care, have been updated according to the current literature and the health care developments in Germany. New chapters added to the guidelines include the topics of home mechanical ventilation in paraplegic patients and in those with failure of prolonged weaning.In the current guidelines different societies as well as professional and expert associations have been involved when compared to the 2010 guidelines. Importantly, disease-specific aspects are now covered by the German Interdisciplinary Society of Home Mechanical Ventilation (DIGAB). In addition, societies and associations directly involved in the care of patients receiving home mechanical ventilation have been included in the current process. Importantly, associations responsible for decisions on costs in the health care system and patient organizations have now been involved.The currently updated guidelines are valid for the next three years, following their first online publication on the home page of the Association of the Scientific Medical Societies in German (AWMF) in the beginning of July 2017. A subsequent revision of the guidelines remains the aim for the future.

Morbidity of urinary tract infection after urodynamic examination of hospitalized SCI patients: the impact of bladder management.

STUDY DESIGN: Non-interventional, descriptive-observational cohorts study. OBJECTIVES: To assess the incidence of urinary tract infection (UTI) after urodynamic examination in patients with spinal cord injury (SCI) according to bladder management. SETTING: Level 1 trauma center. METHODS: Between January and December 2010 a total of 133 consecutive, hospitalized SCI patients were included and classified according to their bladder management. Urine specimen was obtained at the beginning of the urodynamic studies (UDS) and 3-5 days thereafter. 'Significant bacteriuria' (SBU) is defined by a CBU per ml level ≥10(5) in a urine culture. UTI thus is defined as a combination of a SBU and ≥100 leukocytes per µl in urine analysis. RESULTS: The overall incidence of UTI post UDS was 15.79%. In patients with sterile urine prior to urodynamics UTI was ascertained in 8.6% (de-novo-UTI). In contrast, 32.5% of the patients with SBU prior to UDS showed UTI 3 days later. There were only minor differences in the incidence of de-novo-UTIs in SCI patients who emptied their bladder by intermittent self catheterization or intermittent catheterization by attendant (8.82% and 6.67%, respectively). In SCI patients with reflex voiding however, the frequency of de-novo-UTIs was twice as high (14.28%). CONCLUSION: The recommendation of antibiotic prophylaxis for all SCI patients undergoing urodynamic examination is not commonly accepted and according to our data not justified. However, the analysis of subgroups revealed that SCI patients with unsuspected SBU prior to UDS and patients with reflex voiding are possibly at higher risk to acquire post-UDS infection.

Quality of life and urological morbidity in tetraplegics with artificial ventilation managed with suprapubic or intermittent catheterisation.

STUDY DESIGN: Mono-centric, retrospective study. OBJECTIVE: Analysis of correlation between bladder management and age in respirator-dependant high-tetraplegic patients. Additionally suprapubic catheter (SPC) and intermittent catheterisation (IC) were reviewed concerning urological complications and quality of life (QoL). SETTING: Level 1 trauma centre. METHODS: A QoL questionnaire 'International Consultation on Incontinence' (ICIQ-SF) was sent to 56 tetraplegic respirator device-dependant (RDD)-spinal cord injury (SCI) patients. Their scores concerning urological morbidity were reviewed. For analysis reasons they were divided in three groups: SPC, IC and others. RESULTS: SPC 38, IC 12 and others 6 patients. Significant difference in age (SPC vs IC=49.9 vs 31.8 years) was observed but no disparity in gender. Within a follow-up period 2-26 years (median 8 years) significant urological complications in patients with IC (P<0.05) were ascertained. These were in general minor complications. Especially renal deterioration or bladder cancer was not diagnosed in any of the group. The questionnaire return rate was high (83.9%) with complete answers (SPC=32, IC=11). Self assessment of QoL with ICIQ-SF revealed no significant difference for both groups on low level, but SPC patients tend to score better. CONCLUSION: In our study, tetraplegic RDD-SCI patients with SPC suffered less urological complications and tend to score a better QoL. Therefore we recommend SPC as a serious alternative for these selected patients and concurrently underline the necessity of close urological surveillance at least annually.

How does knowledge about spinal cord injury-related complications develop in subjects with spinal cord injury? A descriptive analysis in 214 patients.

STUDY DESIGN: Monocentric cohort study. OBJECTIVE: To investigate the acquisition of knowledge about spinal cord injury (SCI)-related complications in SCI patients. SETTING: Level 1 trauma center. METHODS: All patients with a traumatic or non-traumatic SCI were included in the study. Data were collected at admission, post-admission at 1 and 3 months and post-discharge at 6, 18 and 30 months. The discharge of all patients was between 3 and 6 months post-admission. Knowledge about pressure ulcers and bladder management was tested using the 'Knowledge' score. This score has a minimum and maximum of 0 and 20 points. To detect differences across the multiple time intervals, the Friedman test was used. Differences in the number of patients with poor (0-8), average (9-12) and good knowledge (13-20) between the different age classifications (age at injury) were calculated using a χ (2)-test. RESULTS: A total of 214 patients were included. At discharge subjects had increased their knowledge score to 11.2 compared with 5.4 on admission (P < 0.001). After 30 months, however, the mean score decreased to 10.8 points. At the time of discharge, the number of patients who achieved poor, average or good knowledge were 48 (22.4%), 65 (30.4%) and 101 (47.2%), respectively. Subjects of ∼50 years old and tetraplegics had better (P < 0.001) knowledge compared with subjects of ∼50 years old and paraplegics, respectively. CONCLUSION: In this study, less than 50% of SCI patients had good knowledge about bladder management and pressure ulcers after being discharged.

Is the outcome in acute spinal cord ischaemia different from that in traumatic spinal cord injury? A cross-sectional analysis of the neurological and functional outcome in a cohort of 93 paraplegics.

STUDY DESIGN: Retrospective cohort study. OBJECTIVES: To compare the neurological outcome between paraplegic patients with acute spinal cord ischaemia syndrome (ASCIS) or traumatic spinal cord injury (tSCI) and to investigate the influence of SCI aetiology on the total Spinal Cord Independence Measure (SCIM)-II score. SETTING: Level 1 trauma centre. METHODS: Initial (0-40 days) and chronic-phase (6-12 months) American Spinal Injury Association (ASIA) sensory scores, lower extremity motor score (LEMS) and chronic-phase total SCIM-II scores were analysed. Differences between ASCIS and tSCI patients were calculated using Student's t-tests and Wilcoxon signed-rank tests. To assess which variables give rise to the prediction of total SCIM-II score, a multiple linear regression analysis was used. These predictor variables included complete (ASIA impairment scale A) or incomplete SCI (AIS B, C, and D), aetiology, age and gender. RESULTS: Out of 93 included patients, 20 ASCIS and 73 tSCI patients were identified. In the complete SCI group, the initial pinprick scores were higher (P<0.05) in ASCIS patients compared with tSCI patients, 37.9 (95% Confidence Interval (CI), 23.3-52.5) and 27.3 (95% CI, 24.1-30.4), respectively. No other relevant differences in neurological outcome were identified between ASCIS and tSCI patients; however, the total SCIM-II scores were higher (P<0.05) in tSCI patients after 12 months. Using the linear regression analysis, we were able to predict 31.4% of the variability. The aetiology was not significant in this model. CONCLUSION: The neurological outcome was independent of the diagnosis ASCIS or tSCI. Furthermore, the diagnosis ASCIS or tSCI was not a significant predictor for total SCIM II scores after 12 months. SPONSORSHIP: This study was granted by the 'Internationale Stiftung für Forschung in Paraplegie' (IFP), Zürich, Switzerland.

[What are the causes of death in patients with spinal cord injury today?--a descriptive analysis of 102 cases]. / Woran sterben Querschnittgelähmte heute?--Eine Nachuntersuchung von 102 Fällen.

As there are only few reliable data concerning mortality of SCI patients, this retrospective monocentric cohort study was carried out. Despite essential improvements in intensive medical care from the accident scene to clinic life, comprehensive rehabilitation, and implementation of a lifelong aftercare system, the life expectancy of SCI patients is still reduced. Especially patients with high tetraplegia die significantly earlier from pulmonary complications. The longer the onset of SCI is survived, the more patients die from age-related diseases. In old paraplegic patients, pressure sores are the only major SCI-related complication. Successful social reintegration and professional care are the most important factors for an expanded lifespan after occurrence of a SCI. Hence, the special impact of lifelong treatment of SCI patients ("comprehensive care") is confirmed.

Developmental and tissue-specific expression of nuclear proteins that bind the regulatory element of the major histocompatibility complex class I gene.

Expression of MHC class I genes varies according to developmental stage and type of tissues. To study the basis of class I gene regulation in tissues in vivo, we examined binding of nuclear proteins to the conserved cis sequence of the murine H-2 gene, class I regulatory element (CRE), which contains two independent factor-binding sites, region I and region II. In gel mobility shift analyses we found that extracts from adult tissues that express class I genes, such as spleen and liver, had binding activity to region I. In contrast, extracts from brain, which does not express class I genes, did not show region I binding activity. In addition, fetal tissues that express class I gene at very low levels, also did not reveal region I binding activity. Binding activity to region I became detectable during the neonatal period when class I gene expression sharply increases. Most of these tissues showed binding activity to region II, irrespective of class I gene expression. Although region II contained a sequence similar to the AP-1 recognition site, AP-1 was not responsible for the region II binding activity detected in this work. These results illustrate a correlation between region I binding activity and developmental and tissue-specific expression of MHC class I genes. The CRE exerts an enhancer-like activity in cultured fibroblasts. We evaluated the significance of each factor binding to CRE. Single 2-bp mutations were introduced into the CRE by site-directed mutagenesis and the ability of each mutant to elicit the enhancer activity was tested in transient CAT assays. A mutation that eliminated region I protein binding greatly impaired enhancer activity. A mutation that eliminated region II binding also caused a lesser but measurable effect. We conclude that region I and region II are both capable of enhancing transcription of the class I gene. These results indicate that in vivo regulation of MHC class I gene expression is mediated by binding of trans-acting factors to the CRE.

Influence of physical exercise on quality of life in individuals with spinal cord injury.

STUDY DESIGN: Retrospective cross-sectional study with anonymous postal data collection. OBJECTIVE: Regaining the best possible mobility and independence is not only the focus of the rehabilitation process for individuals with spinal cord injury (SCI), but also represents an important criterion for the individual's quality of life (QoL). Therefore, if and to what extent physical exercise (PE) influences the QoL of individuals with SCI was investigated. SETTING: The period of investigation extended from September 2007 to January 2008. Data were acquired from the BG Trauma Hospital Hamburg database and the German Wheelchair Sport Federation databases. METHODS: Analysis of 277 questionnaires of individuals with acquired SCI between the age of 16 and 65 years with complete wheelchair dependency in everyday life and lesion level lower C5. RESULTS: In all, 51.5% of all individuals were reported being actively involved in sports as opposed to 48.5% individuals not participating in sports. Individuals actively involved in sports have higher employment rate than physically inactive individuals with SCI. PE was identified as the main influencing determinant of QoL. This was particularly within the physical and psychological dimensions. CONCLUSION: In discovering the potential of individuals with SCI for getting involved in PE, the improvement of physical and coordinative skills with interaction between individuals with SCI and external sport groups should be an inherent part of the rehabilitation process. Individuals not having access to PE should be given the opportunity to participate in wheelchair mobility courses. This may improve the adherence to PE of individuals with SCI in post-clinical settings.

Diagnostic criteria of traumatic central cord syndrome. Part 1: a systematic review of clinical descriptors and scores.

STUDY DESIGN: Systematic review. BACKGROUND: The applied definition of traumatic central cord syndrome (TCCS) lacks specific quantified diagnostic criteria. OBJECTIVE: To review currently applied TCCS diagnostic criteria and quantitative data regarding the 'disproportionate weakness' between the upper and lower extremities described in original studies reporting on TCCS subjects. METHODS: A MEDLINE (1966 to 2008) literature search was conducted. The descriptors applied to define TCCS were extracted from all included articles. We included original studies that reported on the differences in motor score (based on the Medical Research Council scale) between the total upper extremity motor score (UEMS) and the total lower extremity motor score (LEMS), in a minimum of five TCCS patients at the time of hospital admission. The mean difference between the total UEMS and the total LEMS of the patients included in each study was calculated. Case reports were excluded. RESULTS: None of the identified studies on TCCS patients reported inclusion and/or exclusion criteria using a quantified difference between the UEMS and LEMS. Out of 30 retrieved studies, we identified seven different clinical descriptors that have been applied as TCCS diagnostic criteria. Nine studies reporting on a total of 312 TCCS patients were eligible for analysis. The mean total UEMS was 10.5 motor points lower than the mean total LEMS. CONCLUSIONS: There is no consensus on the diagnostic criteria for TCCS. Nevertheless, this review revealed an average of 10 motor points between the UEMS and LEMS as a possible TCCS diagnostic criterion. However, further discussion by an expert panel will be required to establish definitive diagnostic criteria.

Relevance of the diagnosis traumatic cervical Brown-Séquard-plus syndrome: an analysis based on the neurological and functional recovery in a prospective cohort of 148 patients.

STUDY DESIGN: Prospective multi-center cohort study. OBJECTIVES: To compare the neurological and functional recovery between tetraplegic Brown-Séquard-plus syndrome (BSPS) and incomplete tetraplegia (non-BSPS). SETTING: European Multicenter Study of Human Spinal Cord Injury (EM-SCI). METHODS: BSPS was defined as a traumatic incomplete spinal cord injury (SCI) with ipsilateral weakness and contralateral loss of pinprick sensation at neurologic levels C2-T1. Acute (0-15 days) and chronic phase (6 or 12 months) were assessed for the American Spinal Injury Association (ASIA) sensory scores, upper extremity motor scores and lower extremity motor scores. Furthermore, chronic phase scores of all Spinal Cord Independence Measure (SCIM) II items were analyzed. Differences in neurological and functional outcome between BSPS patients and non-BSPS patients were calculated using Student's t-tests and Wilcoxon signed rank tests. RESULTS: Out of 148 tetraplegic patients, 30 were diagnosed with BSPS. Patients with an ASIA impairment scale (AIS) B were significantly (P<0.001) more identified in non-BSPS patients (25%) compared with BSPS patients (3%), respectively. After 12 months, the median scores for sphincter management of the bladder for both BSPS and non-BSPS patients were 15. Both 25 and 75% quartile median scores were 15 for BSPS patients and 12 and 15 for non-BSPS patients (P<0.02). Except for the difference in bladder function, no significant differences were identified in other SCIM II subitems and ASIA motor or sensory scores between BSPS and non-BSPS patients when stratified for injury severity by excluding AIS B patients. CONCLUSION: Compared with incomplete tetraplegic patients, patients with cervical BSPS have a similar neurological and functional recovery when matched for the AIS.

[Urinary bladder cancer as a late sequela of spinal cord injury : Decision-making aids for assessment of this causal association]. / Harnblasenkarzinom als Spätfolge einer Querschnittlähmung : Entscheidungshilfe für eine Zusammenhangsbegutachtung.

BACKGROUND: There is to date no convincing literature that has assessed the association between traumatic spinal cord injury (SCI) and the later development of urinary bladder cancer. The aim of this work is to present medical experts as well as the national accident insurance and the social courts decision-making aids based on the latest medical scientific knowledge, for assessment of this causal association. MATERIALS AND METHODS: A study conducted between April 1998 and March 2017 in the BG Trauma Hospital Hamburg forms the basis for the decision-making aids. Urinary bladder cancer was diagnosed in 32 out of 6432 treated outpatient and inpatient SCI patients. Furthermore, relevant published literature was taken into consideration for the decision-making aids. RESULTS: It was found that urinary bladder cancer in SCI patients occurs at a considerably younger age as compared to the general population, more frequently shows muscle invasive carcinoma with a higher grade at first diagnosis and a higher proportion of the more aggressive squamous cell carcinoma than that of the general population. Correspondingly, the survival time is extremely unfavorable. For medical experts a matrix was compiled where the various influencing factors, either for or against the recognition of an association between SCI and urinary bladder cancer, were weighted according to their relevance. CONCLUSION: The results showed that urinary bladder cancer in SCI patients differs considerably from that of able-bodied patients. These differences drastically shorten the survival time. A study on patients with spina bifida, i.e., a congenital spinal cord disorder, corroborates these observations. They indicate histopathological differences that have so far been intangible.

Investigational new drugs submitted to the Food and Drug Administration that are placed on clinical hold: the experience of the Office of Cellular, Tissue and Gene Therapy.

BACKGROUND: Cell and gene therapies are medical products regulated by the U.S. Food and Drug Administration (FDA) within its Center of Biologics Evaluation and Research (CBER) in the Office of Cellular, Tissue, and Gene Therapy (OCTGT). Clinical research using cell and gene therapies in the United States must be conducted under an Investigational New Drug (IND) application. After an initial, 30-day review FDA either places an IND on clinical hold or allows the IND to proceed. METHODS: We reviewed letters sent by OCTGT to IND sponsors that were placed on clinical hold. We categorized each deficiency and determined its frequency. RESULTS: We found that similar deficiencies existed across IND applications and we tabulated the most common deficiencies. DISCUSSION: We discussed the deficiencies and the resources that can help individuals avoid those deficiencies. We believe that awareness of the common deficiencies along with the applicable resources can reduce the frequency of clinical holds and allow clinical studies to proceed without delay. We also believe that this information will guide the FDA as to how to facilitate development of safe and effective cell and gene therapies.

A constitutive damage-specific DNA-binding protein is synthesized at higher levels in UV-irradiated primate cells.

Using a DNA band shift assay, we have identified a DNA-binding protein complex in primate cells which is present constitutively and has a high affinity for UV-irradiated, double-stranded DNA. Cells pretreated with UV light, mitomycin C, or aphidicolin have higher levels of this damage-specific DNA-binding protein complex, suggesting that the signal for induction can either be damage to the DNA or interference with cellular DNA replication. Physiochemical modifications of the DNA and competition analysis with defined substrates suggest that the most probable target site for the damage-specific DNA-binding protein complex is a 6-4'-(pyrimidine-2'-one)-pyrimidine dimer: specific binding could not be detected with probes which contain -TT- cyclobutane dimers, and damage-specific DNA binding did not decrease after photoreactivation of UV-irradiated DNA. This damage-specific DNA-binding protein complex is the first such inducible protein complex identified in primate cells. Cells from patients with the sun-sensitive cancer-prone disease, xeroderma pigmentosum (group E), are lacking both the constitutive and the induced damage-specific DNA-binding activities. These findings suggest a possible role for this DNA-binding protein complex in lesion recognition and DNA repair of UV-light-induced photoproducts.

Inhibition of estrogen-responsive gene activation by the retinoid X receptor beta: evidence for multiple inhibitory pathways.

The retinoid X receptor beta (RXR beta; H-2RIIBP) forms heterodimers with various nuclear hormone receptors and binds multiple hormone response elements, including the estrogen response element (ERE). In this report, we show that endogenous RXR beta contributes to ERE binding activity in nuclear extracts of the human breast cancer cell line MCF-7. To define a possible regulatory role of RXR beta regarding estrogen-responsive transcription in breast cancer cells, RXR beta and a reporter gene driven by the vitellogenin A2 ERE were transfected into estrogen-treated MCF-7 cells. RXR beta inhibited ERE-driven reporter activity in a dose-dependent and element-specific fashion. This inhibition occurred in the absence of the RXR ligand 9-cis retinoic acid. The RXR beta-induced inhibition was specific for estrogen receptor (ER)-mediated ERE activation because inhibition was observed in ER-negative MDA-MB-231 cells only following transfection of the estrogen-activated ER. No inhibition of the basal reporter activity was observed. The inhibition was not caused by simple competition of RXR beta with the ER for ERE binding, since deletion mutants retaining DNA binding activity but lacking the N-terminal or C-terminal domain failed to inhibit reporter activity. In addition, cross-linking studies indicated the presence of an auxiliary nuclear factor present in MCF-7 cells that contributed to RXR beta binding of the ERE. Studies using known heterodimerization partners of RXR beta confirmed that RXR beta/triiodothyronine receptor alpha heterodimers avidly bind the ERE but revealed the existence of another triiodothyronine-independent pathway of ERE inhibition. These results indicate that estrogen-responsive genes may be negatively regulated by RXR beta through two distinct pathways.

Human osteosarcoma cell lines are dependent on insulin-like growth factor I for in vitro growth.

Osteogenic sarcoma is the most common bone tumor of childhood and typically occurs during the adolescent growth spurt when growth hormone and insulin-like growth factor I (IGF-I) may be at their lifetime highest levels. Since IGF-I is involved in normal bone growth and differentiation, we have evaluated the possible role of IGF-I signaling in the growth of human osteogenic sarcoma cell lines. In this study, we demonstrate that in vitro survival of cells is dependent on exogenously supplied IGF-I. Furthermore, we show that these cells display functional IGF-I receptors on their surface and that in vitro growth is inhibited by blocking these receptors either by monoclonal antibodies or by antisense oligonucleotides. These data demonstrate that human osteogenic sarcoma cell lines are dependent on signaling through the IGF-I receptor for in vitro survival and proliferation. Furthermore, they suggest that modulation of the growth hormone/IGF-I axis may affect the growth of these tumors in vivo.

H-2RIIBP expressed from a baculovirus vector binds to multiple hormone response elements.

H-2RIIBP is a member of the nuclear hormone receptor superfamily that binds to the region II enhancer of major histocompatibility complex class I genes. Based on its homology with Drosophila XR2C/CF1, H-2RIIBP may play a role in development. By using a baculovirus expression system, a large amount of recombinant H-2RIIBP was produced. The recombinant protein accumulated in the nucleus of insect cells. A series of monoclonal antibodies reacting with the recombinant H-2RIIBP was then generated. A DNA-protein immunoprecipitation assay was developed with these antibodies, enabling the DNA-binding specificity of H-2RIIBP to be distinguished from that of an endogenous region II binding factor expressed in uninfected insect cells. We show that H-2RIIBP binds to estrogen response elements with an affinity comparable to that for the region II enhancer. H-2RIIBP also bound to some, but not all, thyroid hormone response elements and retinoic acid response elements, albeit at a lower affinity. Binding to these elements was demonstrated without exogenous addition of a ligand. The H-2RIIBP binding specificity determined by this assay was in agreement with the specificity assessed by Southwestern and gel mobility shift assays. Furthermore, methylation interference assays indicated that H-2RIIBP recognizes the conserved hormone response motif GG(T/A)CA. Taken together, these data demonstrate that H-2RIIBP is capable of binding to hormone response elements of a variety of genes. They suggest that H-2RIIBP may exert a pleiotropic function.

Expression of major histocompatibility complex (MHC) class I genes in astrocytes correlates with the presence of nuclear factors that bind to constitutive and inducible enhancers.

The molecular basis of constitutive and inducible major histocompatibility complex (MHC) class I gene expression was studied in murine astrocytes in primary culture. Astrocytes constitutively expressed MHC class I molecules and treatment of these cells with interferon-gamma (IFN-gamma) further induced expression. The conserved region containing the upstream MHC class I regulatory element (MHC-CRE) and juxtaposed interferon consensus sequence (ICS) enhanced constitutive MHC class I promoter activity. As seen with cell surface expression of MHC molecules, treatment of astrocytes with IFN-gamma increased MHC class I promoter activity. Inducible expression required the presence of the MHC-CRE/ICS enhancer region. Nuclear factors that bind to the MHC-CRE and ICS were constitutively expressed in cultured astrocytes and IFN-gamma treatment further induced binding activity both to the MHC-CRE and ICS and correlated with induction of MHC class I gene expression. This study identifies the MHC-CRE and ICS as the major cis elements in controlling MHC class I promoter activity and suggests that the expression of nuclear factor binding activities to these enhancer elements is a basic transactivating mechanism for the expression of MHC class I genes in astrocytes.

Pain in pediatric human immunodeficiency virus infection: incidence and characteristics in a single-institution pilot study.

OBJECTIVE: Children with human immunodeficiency virus (HIV) infection have multiple complications associated with the disease process. Many of these complications are potentially painful and could affect the patient's quality of life. We examined the incidence and characteristics of the perception of pain in a cohort of families with children with HIV infection. METHODOLOGY: A questionnaire was developed and validated with a cohort of families with children with cancer. In a survey of families at the Pediatric Branch of the National Cancer Institute, 61 children with HIV infection and their care givers, along with 19 children with cancer and their care givers, were interviewed to determine the incidence and impact of pain. RESULTS: Fifty-nine percent of the HIV-infected children and 55% of their care givers described pain as a component of their illness that impacted on their lives. Younger children and girls tended to report more pain. There was also a tendency for biological parents to expect and to treat more pain than foster parents, although there was no difference in the incidence of pain that biological and foster parents reported for their children. No differences were found between parents who were HIV positive and those who were not. In addition, no correlations were noted in incidence, expectation, or impact of pain with disease progression or surrogate markers such as CD4 counts. Pain in HIV-infected patients tended to be either in the gastrointestinal tract or limbs and usually responded to nonsteroidal anti-inflammatory therapy. The patients with cancer reported an incidence (47%) and impact of pain similar to those of previously reported studies on pediatric patients with cancer. CONCLUSION: Pain is common among children infected with HIV and can adversely impact on their lives, and its management should be a component of the general care of these patients.

Neonatal circulatory changes: an echocardiographic study.

Serial echocardiograms were performed in the first three days of life on 38 normal full-term infants. Right ventricular systolic time intervals were measured from the pulmonic valve echogram and left ventricular systolic time intervals were determined from the aortic valve echogram. The heart rate, left ventricular pre-ejection period (LPEP), left ventricular ejection time (LVET), and LPEP/LVET ratio showed insignificant variation with increasing postnatal age. The right ventricular pre-ejection period (RPEP) shortened, the right ventricular ejection time (RVET) lengthened, and the RPEP/RVET ratio decreased with increasing age. The findings suggested that alterations in the RPEP/RVET ratio reflected the decreasing pulmonary artery diastolic pressure and pulmonary vascular resistance of the early neonatal period and may be valuable in the noninvasive evaluation of the newborn's pulmonary vascular bed.