Delivering cytokines at tumor site: The immunocytokine-conjugated anti-EDB-fibronectin antibody case

Although considerable efforts have been made in the discovery of new agents for cancer treatment, several promising therapeutics cannot be applied systemically because of their severe side effects. This is the case for various recombinant pro-inflammatory cytokines that, despite their potent anti-cancer activity, can not find their way to clinical exploitation due to their devastating toxicity shown during dose escalation to therapeutically active concentrations. To circumvent these problems, an elegant and efficient way to accumulate therapeutic agents at the tumor site, thus reducing systemic side effects, is their conjugation to tumor-specific antibodies. Here, we review preclinical data about immunocytokines conjugated to a promising single-chain human antibody that selectively targets tumor-associated stroma and blood vessels by binding with high affinity and specificity to the extra domain-B (EDB) of fibronectin.     

Feasibility of using interpolated contours of targets and organs at risk in intensity‐modulated radiation therapy treatment planning for advanced‐stage nasopharyngeal carcinoma

To assess the dosimetric effect of using interpolated contours in planning intensity‐modulated radiation therapy (IMRT) for advanced T‐stage nasopharyngeal carcinoma. The present study focused on T3–T4 tumours where the proximity of targets to neurological organs poses a stringent test on the feasibility of such an approach. Contours of targets and organs were delineated on CT images of 2.5‐mm interval and a reference IMRT plan was generated. An investigative (INV) IMRT plan was then generated with the same planning protocol, but based on interpolated contours that replaced deleted contours on alternate slices. The reference and INV plans were compared. Regarding target coverage, all targets in the INV plans met the acceptance criteria except for the PTV in one case. Regarding organs, the mean dose to 1% volume of the brainstem and spinal cord in the INV plans were kept below their dose limits. No significant differences in the mean doses to others organs were found. Satisfactory target coverage and protection of critical organs to a degree similar to full‐scale contouring could be achieved with use of interpolated contours. The saving in manpower time for contouring is expected to significantly improve the throughput of the IMRT planning process.     

Methotrexate-induced erythema multiforme

The folic acid antagonist, methotrexate, has many applications in the treatment of neoplastic disease. While methotrexate produces several well-recognized toxic effects, cutaneous reactions are rare. A patient who developed classical erythema multiforme while receiving low-dose methotrexate as treatment of nonmetastatic gestational trophoblastic neoplasia is presented. Erythema multiforme has been associated with a variety of pharmacologic agents. It typically presents as a pruritic papular dermatitis of the extensor surfaces of the extremities and may require multiple skin biopsies to establish the diagnosis. Spontaneous reversal usually occurs with discontinuation of therapy. Patients developing erythema multiforme related to antineoplastic agents should be switched to an alternate regimen.     

Autopsies of sudden infant death syndrome—classification and epidemiology

An enquiry into sudden infant death syndrome (SIDS) in 1987 furnished us with detailed epidemiological data for 281 cases that underwent a thorough post-mortem examination. This analysis uses these data to evaluate the role the autopsy plays in explaining sudden death. The cases were classified into three diagnostic groups: explained causes of death (group 1), unexplained deaths with anomalies (group 2), and no anomaly (group 3). These 281 cases show the three essential features that characterize SIDS: over-representation of males, increased deaths during the second and third months of life, and increased deaths during winter. The autopsy examination revealed that many of these deaths had a medical explanation. Almost half were assigned to group 1. At the time of autopsy, no precise pathology could be diagnosed for 147 deaths; of these, 140 showed histological anomalies. There were only seven sudden deaths for which no abnormal sign was evident at the autopsy. These results are compared with those of similar studies and discussed in connection with three factors: the initial selection of cases, the nature and degree of the investigations, and the possible interpretations of the symptoms uncovered.     

DNA testing for fragile X syndrome in schools for learning difficulties

Fragile X syndrome is the most common inherited cause of mental retardation. Early diagnosis is important not only for appropriate management of individuals but also to identify carriers who are unaware of their high risk of having an affected child. The disorder is associated with a cytogenetically visible fragile site (FRAXA) at Xq27.3, caused by amplification of a (CGG)n repeat sequence within the gene at this locus designated FMR1. Clinical and molecular studies have been undertaken to screen for fragile X syndrome in 154 children with moderate and severe learning difficulties of previously unknown origin. Southern blot analysis of peripheral blood showed the characteristic abnormally large (CGG)n repeat sequence associated with fragile X syndrome in four of the 154 children. The findings were confirmed by cytogenetic observation of the fragile site and by further molecular studies. The families of the affected children were offered genetic counselling and DNA tests to determine their carrier status. These findings show that there are still unrecognised cases of fragile X syndrome. Given the difficulty of making a clinical diagnosis and the implications for families when the diagnosis is missed, screening in high risk populations may be justified. The issues involved in screening all children in special schools for fragile X syndrome are discussed.     

Does age at the start of breast feeding influence infantile diarrhoea morbidity? A case–control study in periurban Guinea–Bissau

Colostrum protects the newborn from intestinal infection by its content of secretory immunoglobulin A and other immediately acting factors. It may also induce maturation of the child's gastrointestinal immune defences, thus contributing to the protection against diarrhoeal disease later in infancy. To test this hypothesis, a case–control study on breast feeding and diarrhoea was carried out in a periurban community in Guinea–Bissau. The child's age at the start of breast feeding was ascertained soon after birth ( n = 279). Subsequent cases of acute diarrhoea ( n = 66) were identified at 3–monthly examinations, and four concurrent controls were randomly selected among attendants. Three separate estimates of association showed that the cases tended to have started breast feeding later after birth than the diarrhoea–free controls, but no single test was statistically significant. Early breast feeding might have consequences for diarrhoeal morbidity after the neonatal period.     

Incidence and costs of acute medical conditions in long-stay incontinent nursing home residents

OBJECTIVES: To determine the incidence of acute medical conditions in incontinent nursing home residents, and associated costs of diagnostic testing and treatment DESIGN: Prospective, cohort study. SETTING: Three community nursing homes. PARTICIPANTS: 161 long-stay residents with urinary incontinence in (mean age 86 years, 77% female, 92% white). MEASUREMENTS: Acute medical conditions were identified prospectively through medical record review based on standardized criteria. All diagnostic testing and treatment provided for these conditions were recorded, and related costs in the nursing home were assigned based on 1997-1998 Medicare and Medicaid reimbursement. RESULTS: The highest incidences of illness were for dermatological conditions (107 episodes per 1000 patient-weeks, involving 70% of subjects), respiratory illnesses (29 per 1000 patient-weeks, 47% of subjects) and gastrointestinal illnesses (24 per 1000 patient-weeks, 36% of subjects). Among episodes with an incidence of at least 5 per 1000 patient-weeks, the illness events with the highest median diagnostic testing and treatment costs per episode were pneumonia, acute bronchitis, and depression. Only 42 out of the total 1071 episodes identified resulted in a hospitalization. Significant predictors of higher illness incidence included greater baseline comorbidity and higher number of routine medications (model adjusted R-square = 0.319, P = 0.021). CONCLUSION: Acute illness is very common among incontinent nursing home residents, and is generally diagnosed and treated at the nursing home site, with variation among conditions in associated costs. Important policy implications include resource allocation (including appropriate staffing patterns), educational and quality improvement activities, and future research and guideline development for the optimal management of medical conditions in the nursing home setting.     

Widespread livedoid vasculopathy

A 37-year-old woman with a 13-year history of widespread livedo reticularis and recurrent, painful ulcerative skin lesions was referred to our department because of a relapse of cutaneous manifestations of the skin lesions involving almost the whole body surface; malar erythema and oedema, non-scarring alopecia and fever were also associated. Routine laboratory data, immunological investigations and coagulation parameters were normal or negative. Histology was consistent with livedoid vasculopathy. A good clinical response was obtained using intravenous methylprednisolone combined with pentoxifylline. Livedoid vasculopathy is a rare, distinctive dermatosis that can be associated with systemic autoimmune disorders or present in an "idiopathic" form. The latter is at present regarded as a non-inflammatory thrombotic disease that may occur in patients with coagulation abnormalities. It is noteworthy that, in the present case, despite long-standing and dramatic cutaneous features, serious systemic complications have not developed and the patient's seroimmunologic and coagulative profile has remained normal.     

Sleep tendency as a measure of recovery after drugs used for ambulatory surgery

BACKGROUND: Although tests of psychomotor function indicate that drug effects after ambulatory anesthesia are short-lived, patients often feel washed out for long periods of time. Among the psychomotor tests that measure different motor and cognitive functions, none directly measures sleepiness or alertness. The authors hypothesized that sleepiness, measured by a sleep latency test, would be a more sensitive indicator of drug effect after an anesthetic than psychomotor tests. The second objective was to determine a sedation regimen that produced the least residual effect. METHODS: On four separate occasions, volunteers (N = 12) received an injection of propofol 2.5 mg/kg; propofol 2.0 mg/kg and fentanyl 2 microg/kg; propofol 2.0 mg/kg and midazolam 2 mg/70 kg; or midazolam 0.07 mg/kg and fentanyl 2 microg/kg. Dependent measures included the multiple sleep latency test (MSLT), Maddox Wing and digit symbol substitution tests, auditory and visual reaction times, and a divided attention task. RESULTS: The multiple sleep latency test demonstrated sleepiness up to 4 h after injection, and in some patients, sleepiness continued up to 8 h afterward. Psychomotor function was impaired only at 2 h after injection of the drug combination. CONCLUSION: The multiple sleep latency test may be a more sensitive measure of a drug's effect than other tests of psychomotor function. For up to 8 h after an injection of midazolam and fentanyl, patients must consider driving or operating heavy machinery unsafe activities.