The recent discovery of two genes, termed p63 and p73, encoding transcription factors highly homologous to p53 presents unexpected challenges and opportunities for the understanding and treatment of cancers. The questions raised are many but center on determining whether these new genes possess novel tumor suppressor functions, cooperate with p53, or impart oncogenic effects. At present there is considerable discord in the field concerning these concepts with some favoring a tumor suppressor role for the p53 family members and others an oncogenic influence. In support of a tumor suppressor role is the ability of p73 and p63 isoforms to transactivate p53 target genes and the large body of work linking p73, and to some extent p63, in apoptotic events in response to cellular stresses generally considered the purview of p53. More recently, p73 has been implicated in cell death following T cell activation, the response of cancers to chemotherapy, and finally, along with p63, to the function of p53 itself. Opposing this view is the fact that the p73 and p63 genes are rarely mutated in cancers and the stark absence of tumors in the p73 null mouse. Moreover, the high expression of dominant negative (dn) versions of the p73 and p63 proteins supports an anti-p53 function and therefore possibly an oncogenic effect. Indeed, the p63 gene is located in a region of chromosome three amplified in squamous cell carcinomas and the number of reports of dn-p63 overexpression in these diseases is increasing. This review will examine both sides of these arguments in an attempt to decipher common themes and to identify opportunities these genes represent for understanding tumorigenesis.
Animals ; Carcinogenesis ; Carcinoma, Squamous Cell ; Cell Death ; DNA Damage ; Drug Therapy ; Humans ; Mice ; Protein Isoforms ; Transcription Factors

In the Eastern Highlands Province (EHP) of Papua New Guinea (PNG) measles outbreaks have occurred regularly every 3 to 4 years since 1980. The latest was between September 1998 and March 2000. Between July 1999 and March 2000 314 children with measles were reviewed at Goroka Base Hospital. The majority of these children were very young: 55% were under 1 year and 27% under 6 months. The median age of the measles cases was 11 months (range 10 days to 13 years). 40% of the children had a verifiable history of having received at least one dose of measles vaccine. The majority were vaccinated during the epidemic and included many children who either were below 6 months of age or who developed measles within 2 weeks of vaccination. Measles complications occurred in 82% of the children, the most common being pneumonia. Serious complications, particularly severe pneumonia, were more common among the unvaccinated children than in those who had received at least a single dose of the measles vaccine. No deaths occurred among 82 children who had received measles vaccine more than 2 weeks before the onset of clinical measles, compared with 10 deaths in 206 children who had never been vaccinated against measles or were vaccinated in the 2 weeks before presentation (p=0.067). The overall case fatality was 4%: 14% among the hospital-acquired and 2.5% in community-acquired measles. Improvement in the measles vaccination coverage and supplementary vaccination campaigns are required to prevent measles outbreaks in PNG. Intensified measles vaccination campaigns, such as the one conducted in EHP in 1999, are recommended during epidemics to minimize deaths due to measles and to rapidly control outbreaks. The efficacy of measles vaccination can only be measured in total mortality, not in the prevention of clinical measles.
Adolescent ; Child, Preschool ; Disease Outbreaks ; Measles - epidemiology ; Measles - prevention & ; control

AIMTo improve workflow and usability by introduction of a new electronic patient record (EPR) and database.

METHODSEstablishment of an EPR based on open source technology (MySQL database and PHP scripting language) in a tertiary care andrology center at a university clinic. Workflow analysis, a benchmark comparing the two systems and a survey for usability and ergonomics were carried out.

RESULTSWorkflow optimizations (electronic ordering of laboratory analysis, elimination of transcription steps and automated referral letters) and the decrease in time required for data entry per patient to 71%+/-27%, P<0.05, lead to a workload reduction. The benchmark showed a significant performance increase (highest with starting the respective system: 1.3+/-0.2 s vs. 11.1+/-0.2 s, mean+/-SD). In the survey, users rated the new system at least two ranks higher over its predecessor (P<0.01) in all sub-areas.

CONCLUSIONWith further improvements, today's EPR can evolve to substitute paper records, saving time (and possibly costs), supporting user satisfaction and expanding the basis for scientific evaluation when more data is electronically available. Newly introduced systems should be versatile, adaptable for users, and workflow-oriented to yield the highest benefit. If ready-made software is purchased, customization should be implemented during rollout.

Andrology ; organization & administration ; Benchmarking ; Databases as Topic ; standards ; Ergonomics ; Germany ; Hospitals, University ; Humans ; Male ; Medical Records Systems, Computerized ; standards ; Outpatient Clinics, Hospital ; organization & administration ; Systems Analysis ; User-Computer Interface ; Work Simplification ; Workload ; statistics & numerical data

STUDY DESIGN: Retrospective comparative study and technical note. PURPOSE: To determine if there is a difference in clinical and radiographic parameters between unilateral and bilateral kyphoplasty in a uniform cancer population and to stress the importance of preoperative planning. OVERVIEW OF LITERATURE: While unipedicular kyphoplasty is gaining popularity, a few comparative studies have reported on superior kyphotic reduction with the bipedicular approach. METHODS: We reviewed 69 myeloma patients with 105 operated levels (51 levels were done bilaterally vs. 54 unilaterally). Pain reduction, height restoration, cement volume and complications were recorded up to three months postoperatively. A technical note to identify the skin entry point on the basis of the magnetic resonance imaging and fluoroscopy (lateral view) is being described. RESULTS: Both procedures resulted in significant pain reduction (5.4-5.6/10 points, p=0.8). There was significant height restoration after the operation (p<0.001), while there was no sustained difference between the procedures (p=0.5) up to three months postoperatively. More cement was injected in the bilateral group (4.1 mL vs. 4.9 mL, p=0.002); no difference in cement extravasation in the spinal canal was observed (p=0.5). CONCLUSIONS: There was no difference in the clinical or radiological outcomes between the unilateral and bilateral approaches. Therefore, unilateral kyphoplasty may be performed whenever it is technically feasible and this may be determined preoperatively.
Fluoroscopy ; Fractures, Compression ; Humans ; Kyphoplasty* ; Magnetic Resonance Imaging ; Multiple Myeloma* ; Retrospective Studies ; Skin ; Spinal Canal

The lateral lumbar interbody fusion (LLIF) is a relatively new technique that allows the surgeon to access the intervertebral space from a direct lateral approach either anterior to or through the psoas muscle. This approach provides an alternative to anterior lumbar interbody fusion with instrumentation, posterior lumbar interbody fusion, and transforaminal lumbar interbody fusion for anterior column support. LLIF is minimally invasive, safe, better structural support from the apophyseal ring, potential for coronal plane deformity correction, and indirect decompression, which have has made this technique popular. LLIF is currently being utilized for a variety of pathologies including but not limited to adult de novo lumbar scoliosis, central and foraminal stenosis, spondylolisthesis, and adjacent segment degeneration. Although early clinical outcomes have been good, the potential for significant neurological and vascular vertebral endplate complications exists. Nevertheless, LLIF is a promising technique with the potential to more effectively treat complex adult de novo scoliosis and achieve predictable fusion while avoiding the complications of traditional anterior surgery and posterior interbody techniques.
Adult ; Congenital Abnormalities ; Constriction, Pathologic ; Decompression ; Humans ; Pathology ; Psoas Muscles ; Scoliosis ; Spondylolisthesis

Nitric oxide (NO) is endogenously released in the airways, and the fractional concentration of NO in exhaled breath (FeNO) is now recognized as a surrogate marker of eosinophilic airway inflammation that can be measured using a noninvasive technique suitable for young children. Although FeNO levels are affected by several factors, the most important clinical determinants of increased FeNO levels are atopy, asthma, and allergic rhinitis. In addition, air pollution is an environmental determinant of FeNO that may contribute to the high prevalence of allergic disease. In this review, we discuss the mechanism for airway NO production, methods for measuring FeNO, and determinants of FeNO in children, including host and environmental factors such as air pollution. We also discuss the clinical utility of FeNO in children with asthma and allergic rhinitis and further useful directions using FeNO measurement.
Air Pollution ; Asthma ; Biomarkers ; Child* ; Eosinophils ; Humans ; Inflammation ; Nitric Oxide ; Prevalence ; Rhinitis

BACKGROUND: The indications for surgical airway management in patients with Robin sequence (RS) and severe airway obstruction have not been well defined. While certain patients with RS clearly require surgical airway intervention and other patients just as clearly can be managed with conservative measures alone, a significant proportion of patients with RS present with a more confusing and ambiguous clinical course. The purpose of this study was to describe the clinical features and objective findings of patients with RS whose airways were successfully managed without surgical intervention. METHODS: The authors retrospectively reviewed the medical charts of infants with RS evaluated for potential surgical airway management between 1994 and 2014. Patients who were successfully managed without surgical intervention were included. Patient demographics, nutritional and respiratory status, laboratory values, and polysomnography (PSG) findings were recorded. RESULTS: Thirty-two infants met the inclusion criteria. The average hospital stay was 16.8 days (range, 5–70 days). Oxygen desaturation (<70% by pulse oximetry) occurred in the majority of patients and was managed with temporary oxygen supplementation by nasal cannula (59%) or endotracheal intubation (31%). Seventy-five percent of patients required a temporary nasogastric tube for nutritional support, and a gastrostomy tube placed was placed in 9%. All patients continued to gain weight following the implementation of these conservative measures. PSG data (n=26) demonstrated mild to moderate obstruction, a mean apneahypopnea index (AHI) of 19.2±5.3 events/hour, and an oxygen saturation level <90% during only 4% of the total sleep time. CONCLUSIONS: Nonsurgical airway management was successful in patients who demonstrated consistent weight gain and mild to moderate obstruction on PSG, with a mean AHI of <20 events/hour.
Airway Management* ; Airway Obstruction ; Catheters ; Classification ; Demography ; Disease Management ; Gastrostomy ; Humans ; Infant ; Intubation, Intratracheal ; Length of Stay ; Nutritional Support ; Oxygen ; Pierre Robin Syndrome* ; Polysomnography ; Retrospective Studies ; Songbirds* ; Weight Gain

STUDY DESIGN: Level 4 retrospective review. PURPOSE: To compare the radiographic and clinical outcomes between posterior lumbar interbody fusion (PLIF) and lateral lumbar interbody fusion (LLIF) with posterior segmental spinal instrumentation (SSI) for degenerative lumbar spondylolisthesis. OVERVIEW OF LITERATURE: Both PLIF and LLIF have been performed for degenerative spondylolisthesis with good results, but no study has directly compared these two techniques so far. METHODS: The electronic medical and radiographic records of 78 matched patients were analyzed. In one group, 39 patients underwent PLIF with SSI at 41 levels (L3-4/L4-5), while in the other group, 39 patients underwent the LLIF procedure at 48 levels (L3-4/L4-5). Radiological outcomes such as restoration of disc height and neuroforaminal height, segmental lumbar lordosis, total lumbar lordosis, incidence of endplate fracture, and subsidence were measured. Perioperative parameters were also recorded in each group. Clinical outcome in both groups was assessed by the short form-12, Oswestry disability index and visual analogue scale scores. The average follow-up period was 16.1 months in the LLIF group and 21 months in the PLIF group. RESULTS: The restoration of disc height, foraminal height, and segmental lumbar lordosis was significantly better in the LLIF group (p<0.001). The duration of the operation was similar in both groups, but the average blood loss was significantly lower in the LLIF group (p<0.001). However, clinical outcome scores were similar in both groups. CONCLUSIONS: Safe, effective interbody fusion can be achieved at multiple levels with neuromonitoring by the lateral approach. LLIF is a viable treatment option in patients with new onset symptoms due to degenerative spondylolisthesis who have had previous lumbar spine surgery, and it results in improved sagittal alignment and indirect foraminal decompression.
Animals ; Decompression ; Follow-Up Studies ; Humans ; Incidence ; Lordosis ; Retrospective Studies ; Spine ; Spondylolisthesis*

AIMTo characterize the coexpression of survivin, an inhibitor of apoptosis (IAF), and human telomerase reverse transcriptase (hTERT) in human testes with varying spermatogenic function.

METHODSTranscript levels of survivin mRNA and hTERT mRNA were determined in normal testes (n=11) and testes with defective spermatogenesis (n=28) using real-time reverse-transcription polymerase chain reaction (RT-PCR). The histological work-up was performed according to a modified Johnsen score.

RESULTSExpressions of both survivin and hTERT were highest at median levels of 96.8 and 709 in normal spermatogenesis and dropped to 53.3 and 534 in testes with postmeiotic spermatogenic arrest (n=10). In severe spermatogenic failure (n=18), survivin expression was lacking in most specimens (n=16), whereas at least low levels of testicular hTERT expression were largely detectable with a normalized expression of 73 in premeiotic spermatogenic arrest (n=7) and 45 in patients with Sertoli cell-only syndrome (SCOS) (n=3). Both survivin and hTERT expressions increased with a progressing Johnsen score (P for trend=0.001).

CONCLUSIONAlthough both survivin and hTERT are correlated with spermatogenic function, they show different expression patterns in testes of infertile patients. These findings substantiate results from studies in the rodent testis suggesting a predominant expression of survivin in meiotically dividing germ cells.

Biopsy ; DNA-Binding Proteins ; biosynthesis ; Gene Expression ; physiology ; Humans ; Infertility, Male ; metabolism ; Inhibitor of Apoptosis Proteins ; Male ; Microtubule-Associated Proteins ; biosynthesis ; Neoplasm Proteins ; biosynthesis ; Spermatogenesis ; physiology ; Telomerase ; biosynthesis ; Testis ; metabolism

Adult ; Cervix Uteri ; pathology ; Female ; Humans ; Sarcoma, Alveolar Soft Part ; diagnosis ; Uterine Cervical Neoplasms ; diagnosis