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Biomedical subjects

G Wolff

Publications and source records attributed to G Wolff.

At least 55 records · Page 3Linked to original sources
PubMed1996

"Sero-switch" adenovirus-mediated in vivo gene transfer: circumvention of anti-adenovirus humoral immune defenses against repeat adenovirus vector administration by changing the adenovirus serotype.

Recombinant, replication-deficient adenovirus (Ad) vectors have been successfully used to transfer and express the normal human cystic fibrosis transmembrane conductance regulator (CFTR) cDNA in vivo in the respiratory epithelium of experimental animals and humans with cystic fibrosis (CF). Since Ad-directed gene expression wanes over time, repeat administration is necessary to achieve an effective treatment for CF. A major hurdle to such a strategy is the possibility that anti-Ad humoral immunity may prevent gene expression in individuals with pre-existing anti-Ad immunity or following repeat administration. One strategy to circumvent such a problem would be alternating the use of Ad vectors belonging to different subgroups. Neutralizing antibodies developed with the administration of one Ad serotype do not cross-react with an Ad belonging to a second serotype in a manner that blocks infection and gene expression. To test this hypothesis, an immunizing dose of wild-type Ad5 (subgroup C), Ad4 (subgroup E), or Ad30 (subgroup D) was administered intratracheally to experimental animals, followed by an intratracheal administration of a replication-deficient subgroup C-derived vector coding for marker genes (chloramphenicol acetyl transferase or beta-galactosidase) or for the normal human CFTR cDNA. As expected, studies with vectors coding for marker genes or for CFTR cDNA demonstrated that airway administration of a vector does not yield efficient gene transfer, if there has been prior recent airway administration of the same Ad subgroup. In contrast, effective expression from the second administration can be achieved with an adenovirus vector belonging to a subgroup different from the first adenovirus administered. These data support the paradigm of alternating Ad vectors derived from different subgroups as strategy to circumvent anti-Ad humoral immunity, thus permitting the use of Ad vectors as a means to treat the respiratory manifestations of CF.

Adenoviruses, Human↗
PubMed1996

Community attitudes to mental illness.

BACKGROUND: The baseline findings from a controlled study of the effect of a public education campaign on community attitudes to mental illness are presented. METHOD: A census of attitudes to mental illness was conducted in two areas, prior to the opening of supported houses for the mentally ill. Factor analysis of the Community Attitudes toward the Mentally Ill (CAMI) inventory revealed three components: Fear and Exclusion, Social Control and Goodwill. RESULTS: The only determinant of Fear and Exclusion was having children. The main determinants of Social Control were social class, ethnic origin, age, having suffered mental illness and having children. The main determinant of Goodwill was educational level. The attitude factors were predictive of respondents' behavioural intentions toward the mentally ill. Respondents with children and non-Caucasians were more likely to object to the mentally ill living in their neighbourhood. CONCLUSIONS: Any intervention aimed at changing attitudes to mentally ill people in the community should be targeted at people with children and non-Caucasians, as these groups are more likely to object.

Adolescent↗
PubMed1996

Community knowledge of mental illness and reaction to mentally ill people.

BACKGROUND: We test the hypothesis that negative attitudes to mentally ill people may be fuelled by a lack of knowledge. METHOD: A census of knowledge of mental illness was conducted in two areas prior to the opening of long-stay supported houses for the mentally ill in each area. Three attitudinal factors (Fear and Exclusion, Social Control and Goodwill) which had been extracted by factor analysis of the Community Attitudes toward the Mentally Ill (CAMI) inventory (see previous paper) were analysed in respect of their associations with knowledge of mental illness. RESULTS: Most respondents (80%) knew of somebody who had a mental illness but a substantial proportion of respondents had little knowledge about mental illness. Social Control showed an association with knowledge of mental illness. Groups who showed more socially controlling attitudes (especially those over 50 years old, those of lower social class, and those of non-Caucasian ethnic origin) had less knowledge about mental illness. Regression analysis revealed that when knowledge was taken into account, age had no effect on Social Control, and the effect of social class and ethnic origin was diminished. Respondents with children, who showed more Fear and Exclusion, were not less knowledgeable about mental illness. CONCLUSIONS: The results support the hypothesis that negative attitudes, especially in older people, are fuelled by a lack of knowledge. Negative attitudes among people with children are not related to a lack of knowledge.

Adolescent↗
PubMed1996

Public education for community care. A new approach.

BACKGROUND: The findings from a controlled study of the effect of a public education campaign on community attitudes to mentally ill people are presented. METHOD: A census of neighbours' attitudes toward mental illness was conducted in two areas before the opening of supported houses for the mentally ill. In one area an educational campaign was conducted. The attitude survey was then repeated in both areas and patients' social contact with neighbours was recorded. RESULTS: Respondents exposed to the didactic component of the campaign showed only a small increase in knowledge about mental illness but there was a lessening of fearful and rejecting attitudes in the experimental area and not in the control area. Neighbours in the experimental area were more likely to make social contact with both staff and patients. It was social contact which was directly associated with improved attitudes rather than education per se. Patients in the experimental area made contact and even friendships with neighbours whereas those in the control area did not. CONCLUSIONS: The public education campaign did not lead to significant change in neighbours' knowledge of mental illness. However, their attitudes improved and patients' social integration was enhanced.

Activities of Daily Living↗
PubMed1996

Clinical course of hypophosphatemic rickets in 23 adults.

Twenty-three adult patients (19 females, 4 males) with x-linked hypophosphatemic rickets (HPR) underwent a retrospective evaluation of the clinical course and a clinical examination by a nephrologist, orthopedic surgeon and dentist. Blood and urine analysis, bone density measurements with QCT and DEXA, ultrasonic examination of the kidneys were performed and the patients were asked to fill in a standardized questionnaire on pain and psychosocial rehabilitation. Mean final height was 152.4 cm +/- 8.5 SD in females and 157.3 cm +/- 8.9 SD in males. Decreased joint mobility was seen in all patients, deviations of the normal leg axis in 18/23 patients in spite of 69 correcting osteotomies in the past. Dental (n = 14) and psychosocial problems were associated with inability to work (n = 8). There was a trend that patients with a very low Tp/GFR had a more severe course of the disease. Early therapy with vitamin D metabolites and phosphate had a beneficial effect on growth, bone density and deformations. Eight patients had nephrocalcinosis due to vitamin D and phosphate therapy and had normal kidney function. Four patients had urinary tract abnormalities. We conclude that patients with HPR should receive continuous interdisciplinary care given by nephrologists, orthopedic surgeons, physiotherapists and dentists not only during childhood but also as adults.

Adult↗
PubMed1995

Mutations in FGFR1 and FGFR2 cause familial and sporadic Pfeiffer syndrome.

Pfeiffer syndrome (PS) is an autosomal dominant skeletal disorder which affects the bones of the skull, hands and feet. Previously, we have mapped PS in a subset of families to chromosome 8cen by linkage analysis and demonstrated a common mutation in the fibroblast growth factor receptor-1 (FGFR1) gene in the linked families. Here we report a second locus for PS on chromosome 10q25, and present evidence that mutations in the fibroblast growth factor receptor-2 (FGFR2) gene on 10q25 cause PS in an additional subset of familial and sporadic cases. Three different point mutations in FGFR2, which alter the same acceptor splice site of exon B, were observed in both sporadic and familial PS. In addition, a T to C transition in exon B predicting a cysteine to arginine substitution was identified in three sporadic PS individuals. Interestingly, this T to C change is identical to a mutation in FGFR2 previously reported in Crouzon syndrome, a phenotypically similar disorder but one lacking the hand and foot anomalies seen in PS. Our results highlight the genetic heterogeneity in PS and suggest that the molecular data will be an important complement to the clinical phenotype in defining craniosynostosis syndromes.

Abnormalities, Multiple↗
PubMed1995

Time constant/volume relationship of passive expiration in mechanically ventilated ARDS patients.

Since the adult respiratory distress syndrome (ARDS) lung is known to be inhomogeneous, one could expect an uneven distribution of expiratory time constant during uninterrupted mechanical ventilation. We investigated the time constant/volume relationship of passive expiration, and their modification by external resistive elements. In 12 paralysed intubated ARDS patients, we determined the expiratory time constant (tau E) as a function of the expired volume (VE) during uninterrupted mechanical ventilation. Mean expiratory time was 2.9 +/- 0.3 s (+/- SD). VE was divided into five equal volume slices (portions) and a mean tau E calculated from the expiratory tidal volume/flow curve for each slice. The mean values of tau E for each volume slice did not differ significantly throughout expiration, averaging 690 +/- 218 ms (mean +/- SD of five slices and 12 patients). We show that the flow-dependent resistance of the endotracheal tube (RETT) is mainly responsible for the observed time constant homogeneity. We conclude that in ARDS patients during uninterrupted mechanical ventilation the time constants of passive expiration are markedly modified by the flow-dependent resistance of the endotracheal tube (RETT), and also by the external resistance of tubing and ventilator (REX). RETT and REX render tau E about three times larger than the time constant of the patient's respiratory system alone.

Adult↗
PubMed1995

An analysis of desynchronization between the spontaneously breathing patient and ventilator during inspiratory pressure support.

It is common practice to convert patients with acute respiratory insufficiency (ARI) from controlled mechanical ventilation to some form of assisted spontaneous breathing as early as possible. A widely used mode of assisted spontaneous breathing is patient-triggered inspiratory pressure support (IPS). We investigated 11 patients with ARI during weaning from mechanical ventilation using IPS and found that in 9 of these patients, desynchronization between patient and ventilator occurred, ie, that the ventilator did not detect and support all the patients' breathing efforts. Five of these 9 patients displayed severe desynchronization lasting at least 5 min and with less than half of all breathing efforts being supported by the ventilator. We present the analysis of gas flow, volume, esophageal pressure, airway pressure, and tracheal pressure of 1 patient with ARI displaying desynchronization under IPS. Our results imply that desynchronization can occur due to the following: (1) inspiratory response delays caused by the inspiratory triggering mechanisms and the demand flow characteristics of the ventilator; (2) a mismatch between the patient's completion of the inspiration effort and the ventilator's criterion for terminating pressure support; and (3) restriction of expiration due to resistance from patient's airways, endotracheal tube, and expiratory valve. From our analysis, we have made proposals for reducing desynchronization in clinical practice.

Aged↗
PubMed1995

Two unrelated children with developmental delay, short stature and anterior chamber cleavage disorder, cerebellar hypoplasia, endocrine disturbances and tracheostenosis: a new entity?

Two unrelated children with developmental delay, anterior chamber-cleavage disorder, proportionate short stature and striking similarity in facial appearance appear to have an identical syndrome. Peters' plus syndrome has to be considered but additional abnormalities not described in this syndrome and their apparently different facies may be evidence for a hitherto undescribed condition. The further malformations both children have in common are cerebellar hypoplasia, hypothyroidism, tracheostenosis and dislocated hips.

Abnormalities, Multiple↗
PubMed1994

Complete sequence of the mitochondrial DNA of the chlorophyte alga Prototheca wickerhamii. Gene content and genome organization.

The complete nucleotide sequence of the circular mitochondrial (mt) DNA of the chlorophyte alga Prototheca wickerhamii has been determined (55,328 base-pairs, A+T content 74.2%). The genes identified encode three subunits of the cytochome oxidase, apocytochrome b, nine subunits of the NADH dehydrogenase complex (nad1 to 7, nad4L and nad9), three ATPase subunits (atp6, atp9, atp1 (also referred to as atpA)), three ribosomal RNAs (5 S (rrn5), small subunit (srn) and large subunit (lrn) RNA), 26 tRNAs, and 13 ribosomal proteins. A total of five group I introns reside in lrn and cox1, two of which include intronic open reading frames (ORFs). Five free-standing ORFs longer than 60 codons are present. Three of these ORFs are counterparts to genes encoding proteins of unknown function in plant mitochondria (orf25 and orfB of angiosperms and orf244 of liverwort), whereas two of them are unique. Mitochondrial genes are encoded on both DNA strands in a way that suggests the existence of two transcription units, each including approximately one half of the mitochondrial genome. The two intergenic regions in which transcription is believed to initiate and terminate are about ten times longer than the other intergenic regions (1118 and 1993 nt versus 100 to 150 nt). A total of 29 recurring sequence motifs (30 to 200 nt long) have been found in intergenic regions. Nine different types of motifs are present, most of them arranged as tandem repeats. These motifs may be implicated in transcription, e.g. as signals for initiation, termination and/or processing. Phylogenetic analysis on the basis of the cox1 gene strongly suggested that P. wickerhamii and plant mitochondrial genomes are monophyletic. The finding of plant-specific mitochondrial genes such as orf25, orf244, orfB and rrn5 in P. wickerhamii mitochondria corroborates this idea.

Amino Acid Sequence↗
PubMed1994

Changes in the retinal pigment epithelium close to retinal vessels in familial adenomatous polyposis.

Congenital hypertrophy of the retinal pigment epithelium (CHRPE) is known to occur in patients with familial adenomatous polyposis. Its relation to the course of the retinal blood vessels is emphasized in this publication. A 15-year-old girl with familial polyposis coli showed a longitudinal strip of whitish change following the course of a superior nasal artery of the left eye, falsely appearing to enclose the blood vessel like a sheath. A 34-year-old woman from another family with polyposis coli also showed a longitudinally orientated area of hypo- and hyperpigmentation close to temporal retinal veins. Two further patients revealed hyperpigmentation of the RPE under retinal vessels. It is hypothesized that these changes indicate an effect of the hypo- and hyperpigmentations of the RPE on the development of retinal vessels. In four patients, multiple dotlike hyperpigmentations were found in the extreme periphery of the retina; however, the bigger patchy hyperpigmentations were predominantly located in the midperiphery of the retina.

Adenomatous Polyposis Coli↗
PubMed1994

Two brothers with characteristic facial appearance, severe psychomotor retardation, hypospadias, contractures, and other symptoms: a new recessive syndrome?

We report on two severely mentally retarded male children of consanguineous parents who seem to be affected by an identical syndrome. The main physical anomalies are typical facial stigmata with a broad nasal bridge, a bulbous nose, upward slanting palpebral fissures, microretrognathia, low hair line, and large ears with an incompletely developed upper helix. In addition, both brothers had hypospadias type II, limb contractures, and delayed bone age. One child had a bilateral cleft lip with cleft palate and cryptorchidism, and developed scoliosis during adolescence. The other had bilateral inguinal hernias and strabismus. Chromosome analysis showed a normal karyotype in both. The striking similarity between the brothers, the dissimilarity to other known syndromes, and the parental consanguinity argue in favour of a new, hitherto undescribed, possibly autosomal recessive syndrome.

Abnormalities, Multiple↗
PubMed1994

Presymptomatic diagnosis in families with adenomatous polyposis using highly polymorphic dinucleotide CA repeat markers flanking the APC gene.

A panel of five multiallelic and highly informative dinucleotide CA repeat markers flanking the APC gene was used for presymptomatic diagnosis of familial adenomatous polyposis coli (FAP). Marker regions were amplified by PCR. DNA fragments were separated by electrophoresis in denaturing polyacrylamide gels and visualised by ethidium bromide staining. Two or more markers were found to be informative in all nine families tested, and all 23 persons at risk could be diagnosed as affected or unaffected by the disease gene, the probability being > 99.9% in 14 cases from six families in which flanking markers were informative. We found no indication for locus heterogeneity of the disease in our sample. The polyposis phenotype and its extracolonic manifestations co-segregated with a distinct haplotype determined by the markers flanking the APC gene. In one family with no remaining living affected members, we could infer the high risk haplotype from genotyping of first degree relatives. The segregation of this haplotype is consistent with the occurrence of CHRPEs in the progeny. In a sporadic case we made use of the typical early extracolonic manifestations of the disease (osteomas, desmoids) to identify the high risk haplotype. We conclude from our experience that indirect genotyping of FAP with this particular panel of closely linked and highly polymorphic microsatellite markers is a rapid, efficient, and highly reliable method for presymptomatic diagnosis of FAP.

Adenomatous Polyposis Coli↗