Comparison between isoprenaline infusions and bolus injections to assess beta-adrenoceptor function in man, with special reference to cardiac contractility and the influence of autonomic reflexes.

The present study was performed to characterize cardiovascular responses to isoprenaline and the influence of autonomic reflexes on these responses. Nine healthy volunteers received infusions and bolus injections of isoprenaline before and after 'autonomic blockade' produced by intravenous atropine 0.04 mg kg-1 and clonidine 300 micrograms. Heart rate, blood pressures, systolic time intervals and various echocardiographic measures of cardiac contractility were registered. No significant differences in responsiveness to isoprenaline were seen when infusions were repeated on the same day without 'autonomic blockade'. After 'blockade', delta responses at 1 nmol l-1 isoprenaline (infusions) were increased for diastolic blood pressure and decreased for systolic blood pressure and stroke volume. Bolus injections of 2 micrograms isoprenaline caused enhanced delta responses after 'autonomic blockade' of diastolic blood pressure, left ventricular diameter in systole, ventricular circumferential fibre shortening, mean posterior wall velocity (Vmean PW), stroke volume, systemic vascular resistance, electromechanical systole (QS2) and pre-ejection period. Systolic blood pressure decreased, in contrast to a small increase without 'blockade'. These findings are explained by differences in haemodynamic effects of isoprenaline and by the dependence of responses on reflexes when isoprenaline is administered in different ways. When heart rate was increased by bolus doses of atropine, in the presence of beta-blockade (propranolol), pre-ejection period and left ventricular diameter in systole were unaffected, and Vmean PW and ventricular circumferential fibre shortening showed only small increases (compared with alterations induced by isoprenaline). However, left ventricular ejection time, QS2 and ejection time (by echocardiography), were markedly dependent on heart rate alterations. Thus, pre-ejection period, left ventricular diameter in systole Vmean PW and ventricular circumferential fibre shortening are parameters which can be useful in order to evaluate cardiac beta-adrenoceptor sensitivity in vivo in man.     

Lymphoma incidence in a Swedish county during 1969-1987.

The incidence of lymphoid malignancies (acute leukemias and myelomatosis excluded) during 1969-1987 in the County of Uppsala was calculated on the basis of the regional cancer register and local registers from the only oncological, hematological, dermatological and pathological departments in this well-defined geographical area. Of the 774 patients included, 639 had histopathological specimens available, all of which were re-examined. Seventy-nine patients were diagnosed on the basis of bone marrow investigations (greater than 70% re-examined, all had a low-grade non-Hodgkin's lymphoma = NHL) and 54 on fine-needle aspiration biopsies (not re-examined). Seventy-nine of the lymphoma diagnoses were based on autopsy specimens. The overall age standardized incidence was 16.2/100,000/year (NHL: 13.6, Hodgkin's disease = HD: 1.5) according to the Swedish 1970 census (according to world standard population: 10.2); male: 20.9 (12.9) and female: 12.4 (7.9). The annual change in trend was +3.0% +/- 2.6 (NHL: +3.6% +/- 2.4, HD: no change). The omission of the 54 'fine needle cases' led to an overall incidence of 15.0 (9.7) and an annual change in trend of +3.5% +/- 1.9. Among the histopathological specimens, an NHL was found in 524 patients and HD in 69. In 46 registered patients, the diagnosis malignant lymphoma was wrong. The diagnosis changed to NHL in 43 patients registered as HD.     

Hypocalcemic symptoms during plateletpheresis using the COBE Spectra: A comparison of oral combination of 600mg calcium+300mg magnesium+100IU vitamin D3 vs. a 1000mg calcium in symptomatic donors.

BACKGROUND: The aim of this study was to find an effective treatment for hypocalcemic symptoms during plateletpheresis and to evaluate if a combination of calcium, magnesium and vitamin D3 is more effective in comparison to routine calcium supplementation. MATERIAL AND METHODS: A study group consisting of 10 donors, having a history of previous hypocalcemic symptoms during plateletpheresis, donated platelets twice in a one-month period. During the first donation combination tablets (600mg Ca+300mg Mg+100IU vitamin D3) were used to treat hypocalcemic symptoms while routine treatment calcium carbonate tablets (1000mg Ca) were used during the second donation. If symptoms persisted after 10min the same dose was repeated. A control group, with no supplementation, consisting of five donors, with no history of hypocalcemic symptoms, were included. Donor subjective symptoms were graded and recorded on four occasions: at the start of plateletpheresis, when symptoms appeared, 10min after the first tablet and at the end of donation. Samples for analysis of ionized calcium (iCa), magnesium and potassium were also taken at the same occasions. RESULTS: All donors from the study group experienced minor or medium hypocalcemic symptoms and needed a second dose of supplementation. Calcium carbonate tablets completely relieved the hypocalcemic symptoms in six donors, it had no effect on three donors and one donor experienced aggravated symptoms. The combination tablets completely relieved the symptoms in three donors, one donor experienced a partial relief and six donors had no relief of symptoms. There were no significant differences in iCa, potassium and magnesium levels were noted in the study group irrespective of which tablets were used for treatment of hypocalcemic symptoms. After plateletpheresis the median iCa levels declined by 30% and potassium levels declined by 3-11% in all donors while the magnesium levels were not significantly affected. There was no correlation between the presence of symptoms and the changed levels of iCa or magnesium. CONCLUSION: Addition of magnesium and vitamin D3 to calcium seems to have no beneficial effect in the treatment of hypocalcemic symptoms in plateletpheresis donors.     

PMM2 mutation spectrum, including 10 novel mutations, in a large CDG type 1A family material with a focus on Scandinavian families

Carbohydrate-deficient glycoprotein syndrome type IA (CDG IA) is an autosomal recessive disease characterized clinically by severe involvement of the central and peripheral nervous system, and biochemically by complex defects in carbohydrate residues in a number of serum glycoproteins. CDG IA is caused by mutations in the PMM2 gene located in chromosome region 16p13. In this study, 61 CDG type IA patients (122 chromosomes) were screened for mutations in the PMM2 gene using a combination of SSCP and sequence analysis. More than 95% of the mutations could be detected. All of them were missense mutations. Mutations 422G>A and 357C>A were strikingly more common in the material and comprised 58% of mutations detected. Of the 20 mutations found, 10 were not reported previously. Seven mutations, e.g. 26G>A (five alleles) and 548T>C (seven alleles), were found only in Scandinavian families. The most common genotype was 357C>A/422G>A (36%). Three patients were homozygous, 357C>A/357C>A (two cases), and 548T>C/548T>C (one case). No patients homozygous for the most common mutation 422G>A were detected. The different mutations were clustered e.g., in that most were located in exon 5 (five) and exon 8 (six), while no mutation was detected in exon 2. When the frequencies of each mutation were included, exon 5 comprised 61% (65 chromosomes) of the mutations; in Scandinavian patients the frequency of these mutations was 72%. Thus, analysis of exon five in these patients enables both reliable and time-saving first screening in prenatal diagnostic cases. This could be followed by a second step of additional strategies for the detection of other mutations.     

Hereditary multiple and isolated sporadic exostoses in the same kindred: identification of the causative gene (EXT2) and detection of a new mutation, nt112delAT, that distinguishes the two phenotypes

Hereditary multiple exostoses (HME) is a well known autosomal dominant hereditary orthopedic disorder. Isolated exostoses, on the other hand, occur as sporadic events or as secondary post-traumatic sequel. The occurrence of solitary exostoses in individuals from pedigrees affected with HME may distort conclusions about carrier status and/or diagnosis. Both conditions are potentially malignant and both are associated with genetic alterations in either EXT1 or EXT2 genes. In this study, we present a seven-generation family from western Sweden consisting of 170 blood relatives, 38 of whom had multiple cartilaginous exostoses, while 8 had isolated exostoses. Linkage analysis aimed to discern one of the known EXT genes demonstrated linkage of the HME phenotype to the EXT2 gene. Subsequent mutation analysis revealed a novel mutation, nt112delAT, in this gene. All carriers of the detected mutation had multiple exostoses, indicating full penetrance. None of the pedigree members with isolated exostoses were carriers of the detected mutation. Two of the mutation carriers developed chondrosarcoma yielding a 5.2% risk of malignant development for this mutation. The detection of this mutation has enabled us to provide appropriate genetic counseling concerning this complex situation.     

Parent Support Programmes for Families Who are Immigrants: A Scoping Review

Journal of Immigrant and Minority Health - Parental support is of paramount importance in the promotion of positive parenting, strengthening parenthood and protecting children from disadvantages...     

Analysis of location and integrity of the human PITSLRE (p58(cdc2L1)) genes in neuroblastoma cell genomes

The family of PITSLRE kinase genes, located in chromosome 1p36, has recently been associated with neuroblastoma tumorigenesis. In order to evaluate the role of these genes as putative tumor suppressor genes, we have analyzed the integrity of the coding region in primary tumors and its location relative to a neuroblastoma consensus deletion. A subset of aggressive neuroblastoma tumors with allelic loss of different parts of chromosome 1p were investigated. Single-strand conformation polymorphism (SSCP), heteroduplex (HD) and sequencing analysis of tumor DNA did not reveal any significant changes in the coding region. In particular, a primary tumor with an interstitial allelic deletion in 1p36 did not reveal concomitant loss of heterozygosity of the PITSLRE gene region when analyzed with a C/T DNA sequence polymorphism in exon 5 of PITSLRE1. FISH analysis on neuroblastoma cell lines with small interstitial deletions and with a balanced translocation in 1p36 revealed that the PITSLRE gene cluster was localized distal to the neuroblastoma consensus deletion. against an involvement of the PITSLRE genes in neuroblastoma tumorigenesis.     

Loss of heterozygosity of 3p markers in neuroblastoma tumours implicate a tumour-suppressor locus distal to the FHIT gene.

Neuroblastoma is a heterogeneous childhood tumour of the sympathetic nervous system, in which deletions of chromosomal region 1p and amplification of the MYCN oncogene correlate with aggressive tumour behaviour. However, the majority of neuroblastoma tumours show neither of these aberrations, indicating that other chromosomal regions may be involved in tumorigenesis. Here, we report findings of loss of heterozygosity (LOH) on chromosome 3. In our neuroblastoma material, nine of 59 (15.3%) tested tumours showed allelic loss of chromosome 3p markers. We found significant clinical and biological differences between tumours with the loss of one entire chromosome 3 vs tumours with partial loss in chromosome region 3p. All children with tumours with whole chromosome 3 loss are long-term survivors, whereas all children with tumours showing partial 3p LOH have died from tumour progression. A consensus region found to be deleted in all the tumours with 3p deletions was defined by markers D3S1286 and D3S1295, i.e. 3p25.3-p14.3, distal to the FHIT gene.