Hepatic arterial therapy with oxaliplatin and systemic capecitabine for patients with liver metastases from breast cancer.

OBJECTIVES: Hepatic arterial treatment (HAT) for liver metastases in patients with metastatic breast cancer (MBC) has only been investigated in few studies. MATERIALS AND METHODS: Two phase II trials were initiated simultaneously to evaluate capecitabine in combination with oxaliplatin in patients with MBC and liver metastases. These two trials are reported together. Continuous capecitabine (1300 mg/m2) was combined with oxaliplatin (85 mg/m2) alternating between systemic treatment and HAT followed by degradable starch microspheres with EmboCept® S every second week. Four patients participated in a pharmacokinetic analysis of oxaliplatin. Each patient had samples taken when receiving oxaliplatin systemically and as HAT with and without EmboCept® S. RESULTS: Totally, 52 patients received HAT: 14 with liver metastases only and 38 patients with additional limited metastatic disease. The patients had previously received a median of 2 (range 0-6) chemotherapeutic regimens for MBC. The response rate was 42.3% (95% confidence interval (CI) 28.7-56.8%) with 7.7% complete and 34.6% partial responses. Median progression free survival was 10.8 months (95% CI 6.9-14.7 months) and median overall survival 27.6 months (95% CI 20.4-34.8 months). The toxicity was moderate with hand-foot syndrome (15.4%), neuropathy (9.6%), fatigue (9.6%), and abdominal pain (9.6%) being the most common grade 3 adverse events. There was no clear difference between systemic blood concentrations of oxaliplatin when given systemic or as HAT. CONCLUSION: HAT oxaliplatin in combination with capecitabine is safe and efficient in patients with MBC. The results are promising with high response rates and a long median progression free and overall survival.

Physical growth in phenylketonuria: I. A retrospective study.

A retrospective cross-sectional survey of phenylketonuria (PKU) was conducted in 1967. Questionnaires on 693 patients, clinically thought to have PKU, were reanalyzed to obtain information on growth in height and head circumference in patients with untreated and previously treated PKU. To provide a comparison to the growth findings of the Collaborative PKU Study, a definition of PKU was adopted to correspond to the one used in that study. Stature in 232 outpatients with untreated PKU was normal but, in 31 institutionalized individuals, the mean height was -1.4 standard deviations below the mean of a normal population. Head circumference in patients with untreated PKU was normal at birth, but showed an increasingly negative deviance with age and was -1.4 SD in untreated adults. Height measurements of 135 children with PKU in whom treatment was started before 121 days of age (age chosen to coincide with criteria for the Collaborative Study) had a significant reduction in height growth, -.8 SD. Head circumference measurements of 115 children treated for PKU were -.7 SD of normal. The depression in head circumference was less in treated subjects with PKU than in untreated ones of the same age. These findings are corroborated by a review of the literature, which contains no convincing report of normal growth during treatment of PKU.

Preventing mental retardation associated with gross obesity in the Prader-Willi syndrome.

Twenty-seven patients with Prader-Willi syndrome have been described, ten of whom did not receive comprehensive management, nine who were diagnosed and treated after becoming obese, and eight who were diagnosed in infancy and responded to early preventative treatment. Intelligence scores declined in the first two groups, but the group receiving early treatment maintained a mean IQ score 20 points higher than the other two. Even though the underlying mechanism of this disorder remains undefined, a comprehensive early intervention program appears to improve prognosis.

Physical growth in phenylketonuria: II. Growth of treated children in the PKU collaborative study from birth to 4 years of age.

Height, weight, and head circumference data up to age 4 years are reported for 124 children with phenylketonuria (PKU) who had been started on diet management before 4 months (121 days) of age and who were participating in the Collaborative Study of Children Treated for Phenylketonuria. Growth measurements of both the children and their parents corresponded with national and international standards. The growth of children with PKU was compared also with that of a group of normal children in the United States in whom corresponding longitudinal growth data had been obtained at the Fels Research Institute (FRI). Statistically significant differences betweeen the groups were not noted at any age. However, when these groups were compared on coefficients using curve fitting, a trend toward a greater increase in weight as they became older, noted in both sexes in the PKU study group, was significantly higher (P less than .005) in the PKU study girls compared with the FRI sample. Height growth was identical in both groups, and comparison with family data showed that the children with PKU grew as expected for their genetic endowment.

Prader-Willi syndrome: consensus diagnostic criteria.

The diagnosis of Prader-Willi syndrome (PWS) is based on clinical findings that change with age. Hypotonia is prominent in infancy. Obesity, mild mental retardation or learning disability, and behavior problems, especially in association with food and eating, result in a debilitating physical and developmental disability in adolescence and adulthood. No consistent biological marker is yet available for PWS in spite of recent research activity in cytogenetics and molecular genetics. Diagnostic criteria for PWS were developed by consensus of seven clinicians experienced with the syndrome in consultation with national and international experts. Two scoring systems are provided: one for children aged 0 to 36 months and another one for children aged 3 years to adults. These criteria will aid in recognition of the syndrome in hypotonic infants and in obese, mildly retarded, behaviorally disturbed adolescents and adults. They will also ensure uniform diagnosis for future clinical and laboratory research in PWS.

Deletion of chromosome 15 (q11-13) in a Prader-Labhart-Willi syndrome clinic population.

Deletion of the long arm of chromosome 15 has recently been reported in a number of patients with the Prader-Labhart-Willi syndrome who were studied with prometaphase banding. We performed cytogenetic analysis on 12 patients with this disorder in whom the clinical diagnosis was certain. A specific cytogenetic anomaly, del(15q11-13) was found in all of the 12 patients. In nine of the 12, the deletion was noted in all cells examined; in two, there was mosaicism, some cells having the deletion and others being normal; one patient had a 7;15 translocation. No clinical differences were evident between individuals with mosaicism for the translocation and those with the typical deletion in all cells examined. The finding that all of our patients with Prader-Labhart-Willi syndrome have a cytogenetic anomaly, with some patients having mosaicism, distinguishes the results of this study from those of previous reports. Prometaphase chromosome analysis is recommended in all individuals clinically suspected of having Prader-Labhart-Willi syndrome and should be considered in hypotonic infants without a specific diagnosis.

A two-year follow-up of autistic children treated with fenfluramine.

Six children with autism, who were treated with fenfluramine as part of a multi-center double-blind placebo-controlled crossover design study, were continued on an open trial of this medication. Follow-up evaluation of these children after 27 months indicated that numerous problems arose in the management of these children, most often resulting in discontinuation of the medication. Particularly noted were development of tolerance, appetite and weight problems, and requirements for other kinds of interventions including introduction of other psychotropic medications and change in custodial circumstances.

Feeding children with Down's syndrome.

A retrospective chart review of forty-nine children with Down's syndrome between the ages of six months and six and a half years seen before 1970 showed that 80 per cent had problems related to food or feeding. An interdisciplinary intervention program utilizing group sessions introduced in 1970 is described. In twenty-one children, most of the nutritional, behavioral, and environmental problems surrounding food previously encountered in children with Down's syndrome were successfully prevented or remedied. The incidence of obesity in Down's syndrome was reduced but not eliminated. Except for parental susceptibility to food faddism, most professional concerns regarding food and eating were non-existent in sixteen of the children reevaluated in a follow-up six years after the intervention program.

Rett syndrome: a case report from an audiovisual program.

A case report of a 13-yr-6-mo-old girl with the Rett syndrome is provided from an audiovisual program featuring home movies taken from 2 mos of age and onward. The patient shows the following symptoms not previously emphasized in the Rett syndrome: deceleration of head growth (rather than acquired microcephaly), fall-off in linear growth in infancy, early hypotonia, precocious puberty and respiratory alkalosis. Except for the precocious puberty, a second, 35-mo-old, patient has followed the same clinical course with similar laboratory findings.

Scoliosis in the Rett syndrome.

Of 32 patients with classical Rett syndrome, radiographs of the spine could be obtained in 30; two had moved. Five (17%), ranging in age from 3.2-11.5 years, had a curve of 10 degrees or less. Twenty-five (83%) had scoliosis. The age at first diagnosis of scoliosis ranged from 4.3 to 18 years of age. The curves ranged from 10 degrees to 86 degrees at a mean age of 14.9 years. Eight of the 21 curves, 38 percent, showed progression, which was first noticed from just before 5 to after 18 years of age. Bracing was done in five of the younger girls with progressive curves at ages 8.3-10.4 years. Three required surgery, performed at ages 10.9, 16.2 and 17.3 years respectively. Physicians following these patients need to refer them for orthopedic care at the first suspicious sign of scoliosis. Orthopedic surgeons taking care of children with the Rett syndrome (RS) should be aware of the clinical unpredictability of the scoliosis in this condition.

Rett's syndrome: a progressive developmental disability in girls.

Two girls are described who had normal physical and mental development during the first few months of life, documented on home movies in one. Gross motor development slowed during the second half of the first year followed by loss of acquired vocabulary and deterioration of fine motor skills. Linear growth and head growth decelerated. Stereotyped hand movements appeared around 2 to 3 years of age. Early appropriate social responses faded into a vacant stare. Neurological development was characterized by early hypotonia followed by ataxia and finally spasticity. One girl has been followed through adolescence. Additional symptoms in later childhood and adolescence included scoliosis, episodes of hyperpnea, vasomotor disturbances of the legs, and precocious puberty. The patients fit the criteria for a progressive neurological disorder called Rett's syndrome, which results in profound developmental disability and occurs only in girls. Etiology remains unknown.

Cognitive and psychiatric variability in three brothers with fragile X syndrome.

Three brothers were determined to have the fragile X syndrome. While sharing physical characteristics, their developmental and behavioral characteristics were diverse, as was the severity of the disorder. Each brother had evidence of developmental problems but demonstrated heterogeneity of presentation in the same sibship.

[Isovaleric acidemia]. / Isovalerianacidaemi.

The three first cases of isovaleric acidemia diagnosed in Scandinavia are described. The disorder is characterized by periodic vomiting, lethargy and coma accompanied by ketoacidosis and a "sweaty feet" odour. These attacks are often triggered of by upper respiratory tract infections or by ingestion of large amounts of protein. Often there are feeding difficulties because these children have aversion to protein-containing foods. Isovaleric acidemia can be subdivided into two types: an acute neonatal form and a chronic intermittent form. The basic defect is deficient activity of isovaleryl-CoA dehydrogenase, resulting in increased urinary excretion of mainly isovaleryl-glycine and 3-hydroxy-isovaleric acid. The defective gene is assigned to the long arm of chromosome 15, and at least five different mutations among 15 patients have been demonstrated. Therapy is symptomatic with correction of the metabolic acidosis and protein restriction and long term treatment with oral glycine and possibly carnitine.

[Surfactant treatment of newborn infants with respiratory distress syndrome primarily treated with nasal continuous positive air pressure. A pilot study]. / Surfaktantbehandling af nyfødte med respiratorisk distress-syndrom primaert behandlet med nasalt kontinuerligt positivt luftvejstryk. En pilotundersøgelse.

In this pilot study, Curosurf (200 mg/kg) was administrated to 34 patients with the respiratory distress syndrome in nasal-CPAP therapy with FiO2 requirements greater than 0.60 and/or TcPCO2 greater than 8 kPa. The surfactant was instilled during a short period of intubation or in a few cases via an intratracheal catheter (Ch. 6). The age of the patients on surfactant treatment ranged from two to 72 hours. Eighteen patients could be maintained on nasal-CPAP after treatment with Curosurf and only a few complications were seen in these infants. The other 16 patients subsequently required artificial ventilation and had a higher incidence of pulmonary and extrapulmonary complications. On the basis of these observations, we plan a randomized trial to investigate whether, administration of surfactant reduces the need for ventilator treatment and improves the odds for uneventful recovery in this category of patients.