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Biomedical subjects

L Baumbach

Publications and source records attributed to L Baumbach.

At least 19 recordsLinked to original sources
PubMed2005

Practice parameter: corticosteroid treatment of Duchenne dystrophy [RETIRED]: report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society.

BACKGROUND: The Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society develop practice parameters as strategies for patient management based on analysis of evidence. OBJECTIVE: To review available evidence on corticosteroid treatment of boys with Duchenne dystrophy. METHODS: Relevant literature was reviewed, abstracted, and classified. Recommendations were based on a four-tiered scheme of evidence classification, and areas for future research are defined. RESULTS: Seven class I studies and numerous less rigorous trials all demonstrated that corticosteroid treatment for 6 months with prednisone (0.75 or 1.5 mg/kg/day) increased muscle strength, performance, and pulmonary function and significantly slowed the progression of weakness. Two class I trials examined the effect of lower dosage of prednisone (0.30 and 0.35 mg/kg/day), demonstrated lesser but similar benefits, and showed a lower frequency of side effects (e.g., weight gain). The only significant side effects in all class I trials were weight gain and development of a cushingoid facial appearance. One longer-term trial of daily prednisone (0.3 to 0.7 mg/kg/day), a class III study, showed prolongation of functional ability and slower progression of weakness in patients during 3 years of treatment. One class IV, open trial of alternate-day prednisone (2 mg/kg for 2 months, then two-thirds dose every other day) extended ambulation by approximately 2 years in treated compared with untreated patients. Deflazacort, a corticosteroid similar in structure to prednisone, produced similar improvement in muscle strength and function with a similar side effect profile. CONCLUSIONS: Prednisone has been demonstrated to have a beneficial effect on muscle strength and function in boys with Duchenne dystrophy and should be offered (at a dose of 0.75 mg/kg/day) as treatment. If side effects require a decrease in prednisone, tapering to dosages as low as 0.3 mg/kg/day gives less robust but significant improvement. Deflazacort (0.9 mg/kg/day) can also be used for the treatment of Duchenne dystrophy in countries in which it is available. Benefits and side effects of corticosteroid therapy need to be monitored. The offer of treatment with corticosteroids should include a balanced discussion of potential risks.

Adolescent↗
PubMed2001

US-guided fine needle aspiration versus coarse needle biopsy of thyroid nodules.

OBJECTIVE: The aim of this study was retrospectively to evaluate ultrasound (US) guided fine-needle aspiration (FNA), in combination with US-guided coarse-needle biopsies, (CNB) from solitary or dominant thyroid nodules routinely performed during a 2 year period. METHODS: Seventy seven patients were biopsied using US-guided FNA and CNB. FNA was performed using a 21-Gauge needle and CNB using a 18-Gauge single action spring-activated needle biopsy system. The biopsies were performed with local anaesthesia. The Department of Pathology routinely examined the biopsy specimens. The retrieval rate in obtaining material for diagnostic evaluation was FNA (97%), CNB (88%), FNA and CNB (100%). RESULTS: In all, 41 of the 77 patients underwent neck-surgery. The surgical specimens were used to determine the results of diagnosing neoplasia. The accuracy, sensitivity and specificity for FNA were 80, 83, and 77%. For CNB 86, 78, and 94%. For both FNA and CNB 80, 89 and 73%. The diagnostic value of the two methods showed no significant difference (P < 0.05). CNB revealed contrary to FNA, however, one additional cancer. Also a higher number of false positive findings was noticed using FNA. No serious complications were registered. Adequate biopsies were obtained in all the patients using the combination of US-guided FNA and CNB. No patient underwent rebiopsy. CONCLUSIONS: The study demonstrated that neither US-guided CNB nor the combination of US-guided FNA and CNB were superior to US-guided FNA. US-guided CNB is only recommended in few selected patients.

Adult↗
PubMed2001

The UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase gene is mutated in recessive hereditary inclusion body myopathy.

Hereditary inclusion body myopathy (HIBM; OMIM 600737) is a unique group of neuromuscular disorders characterized by adult onset, slowly progressive distal and proximal weakness and a typical muscle pathology including rimmed vacuoles and filamentous inclusions. The autosomal recessive form described in Jews of Persian descent is the HIBM prototype. This myopathy affects mainly leg muscles, but with an unusual distribution that spares the quadriceps. This particular pattern of weakness distribution, termed quadriceps-sparing myopathy (QSM), was later found in Jews originating from other Middle Eastern countries as well as in non-Jews. We previously localized the gene causing HIBM in Middle Eastern Jews on chromosome 9p12-13 (ref. 5) within a genomic interval of about 700 kb (ref. 6). Haplotype analysis around the HIBM gene region of 104 affected people from 47 Middle Eastern families indicates one unique ancestral founder chromosome in this community. By contrast, single non-Jewish families from India, Georgia (USA) and the Bahamas, with QSM and linkage to the same 9p12-13 region, show three distinct haplotypes. After excluding other potential candidate genes, we eventually identified mutations in the UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase (GNE) gene in the HIBM families: all patients from Middle Eastern descent shared a single homozygous missense mutation, whereas distinct compound heterozygotes were identified in affected individuals of families of other ethnic origins. Our findings indicate that GNE is the gene responsible for recessive HIBM.

Amino Acid Sequence↗
PubMed2000

Changes in cardiac muscle mass and function in hemodialysis patients during growth hormone treatment.

BACKGROUND: Adult patients with chronic renal failure (CRF) often show symptoms as fatigue, wasting, and reduced working capacity with concomitant findings of reduced cardiac performance and muscle mass. This state may in part be caused by an imbalance in the somatostatin/somatomedine axis resulting in increased catabolism. During an attempt to correct this catabolic state by administration of exogenous growth hormone, cardiac muscle mass and performance were studied. METHODS: In a double-blind, placebo-controlled 6-month study comprising 20 adult enfeebled hemodialysis patients, 9 patients were treated with a single daily subcutaneous injection of recombinant human growth hormone (rhGH) 4 IU/m2 and 11 with placebo injections. Left ventricular muscle mass (LVM) and ejection fraction (EF) were evaluated by echocardiography and the maximal working capacity (MWC) was measured by a bicycle exercise test performed before and after the treatment period. Supplementary electrocardiography (ECG) was performed before and after 6-month treatment. RESULTS: Median LVM increased significantly from 172 to 220 g (p = 0.03) in the rhGH-treated group, while an insignificant decrease was observed in the placebo group from 281 to 200 g (p = 0.3). The EF showed no significant changes in the two groups. MWC showed a slight, insignificant decrease in both groups. From ECG no significant ST deviations were found and no significant changes regarding B-Hb, blood pressure or pulse were observed in the two groups. Irregular heart rhythm aggravated in one patient during the first month of treatment with rhGH, but was overcome by a -blocking agent. CONCLUSION: The treatment with rhGH of adult chronic hemodialysis patients for 6 months increased the left ventricular mass significantly, but without any effect on ejection fraction or maximal working capacity. No electrocardiographic signs of ischemia were associated with the increasing muscle mass and only one patient developed symptoms that might relate to ischemia. No changes in B-Hb, blood pressure or pulse were observed during the treatment period.

Adult↗
PubMed1999

Clinical and biochemical phenotype of familial anterior hypopituitarism from mutation of the PROP1 gene.

We have investigated the largest family with PROP1 deficiency reported to date. Eight patients, aged 17-40 yr, in two sibships with possibly related mothers but no parental consanguinity were 109-137 cm in height (-8.8 to [minus]5.9 SD score) and sexually immature. None had received hormonal therapy. Affected individuals had similarities to and significant differences from patients with insulin-like growth factor I (IGF-I) deficiency due to GH receptor deficiency (GHRD) and normal thyroid function and sexual maturation. The differences from patients with GHRD include normal hand and foot length in seven of eight, normal arm span with relatively long legs, and persistence of extremely low levels of IGF-I into adulthood; similarities include the degree of growth failure, frequent but not uniform increased body weight for height or body mass index, and the presence of limited elbow extensibility and blue scleras in six of eight. Three patients had markedly increased sella turcica area for height age and bone age, determined from lateral skull films. The degree of sellar enlargement is variable in these two sibships. Serum GH concentrations were 0.1 ng/mL or less after clonidine ingestion. Other results were: IGF-I, 3-11 ng/mL (normal, 114-492); IGF-II, 185-299 ng/mL (normal, 358-854); IGF-binding protein-1 (IGFBP-1), 12-200 ng/mL (normal, 13-73); IGFBP-2, 60-384 ng/mL (normal, 55-480); and IGFBP-3, 400-600 ng/mL (normal, 2000-4000). The very low IGF-I and normal IGFBP-1 and -2 levels differ from findings in adults with GHRD. The GH-binding protein concentration was 58-799 pmol/L, with two patients above the normal range of 66-306. LH and FSH levels were very low, with no sex differences between serum levels of estradiol (3-6 pg/mL) and testosterone (3-10 ng/dL). PRL levels all were below normal. Serum concentrations of cortisol were normal. Serum T4 levels were uniformly low (<0.2-0.5; normal, 0.8-2.7 ng/dL), free T3 values were less than normal in seven of eight subjects, and total T3 concentrations were below normal in five of eight, but TSH levels were normal (0.58-2.18; normal, 0.4-4.2 mU/L). DNA specimens from affected individuals in each sibship were homozygous for a 2-bp deletion in exon 2 of the PROPI (Prophet of Pit-I) gene, which causes a shift of reading frames and results in a translational stop signal at codon 109. The mutant protein, when expressed in vivo lacks DNA-binding and transcriptional activation functions. The consequences of the PROPI abnormality in this and other kindreds include gonadotropin deficiency as well as the expected deficiencies in products of Pit-I-dependent somatotrophs, lactotrophs, and thyrotrophs. The severity of the hormone deficiency phenotype is compatible with the complete loss of PROP1 activity.

Adolescent↗
PubMed1999

Homozygosity mapping to the USH2A locus in two isolated populations.

Usher syndrome is a group of autosomal recessive disorders characterised by progressive visual loss from retinitis pigmentosa and moderate to severe sensorineural hearing loss. Usher syndrome is estimated to account for 6-10% of all congenital sensorineural hearing loss. A gene locus in Usher type II (USH2) families has been assigned to a small region on chromosome 1q41 called the UHS2A locus. We have investigated two families with Usher syndrome from different isolated populations. One family is a Norwegian Saami family and the second family is from the Cayman Islands. They both come from relatively isolated populations and are inbred families suitable for linkage analysis. A lod score of 3.09 and 7.65 at zero recombination was reached respectively in the two families with two point linkage analysis to the USH2A locus on 1q41. Additional homozygosity mapping of the affected subjects concluded with a candidate region of 6.1 Mb. This region spans the previously published candidate region in USH2A. Our study emphasises that the mapped gene for USH2 is also involved in patients from other populations and will have implications for future mutation analysis once the USH2A gene is cloned.

Chromosomes, Human, Pair 1↗
PubMed1998

A novel mutation (V191G) in a German-British type 1 Gaucher disease patient. Mutations in brief no. 131. Online.

Gaucher disease results from mutations in the glucocerebrosidase gene located on human chromosome 1q21. Three clinical forms of Gaucher disease have been described: type 1, nonneuropathic; type 2, acute neuropathic; and type 3, subacute neuropathic. We have identified a novel mutation in a German-British patient with type 1 Gaucher disease which results in V191G of the glucocerebrosidase polypeptide. Because the mutation abolishes a HphI cleavage site, its presence was confirmed by HphI RFLP analysis of PCR-amplified genomic DNA. In the second allele of the patient, the mutation identified was g.5841A G(N370S). Sequence analysis of the remainder of the coding region of the gene as well as the exon-intron boundaries showed identity to normal controls. Because mutation N370S has so far been found only in type 1 Gaucher disease and postulated to result in mild clinical presentation, and since the clinical course of this patient has been relatively mild with minimal skeletal involvement, we speculate that the V191G/N370S genotype may also result in good prognosis.

Chromosomes, Human, Pair 1↗
PubMed1998

Growth hormone receptor mutations in children with idiopathic short stature.

Homozygous or compound heterozygous mutations in the GH receptor (GHR) gene result in GH insensitivity syndrome. Previous reports have shown that some heterozygous mutations may induce a partial insensitivity to GH, but others appear to have limited effect on growth. To investigate further these observations, we analyzed the GHR gene in 17 subjects with idiopathic short stature (ISS). All subjects had a height 2 SD or more below the mean and/or abnormal growth velocity. In addition, serum GH levels were 10 ng/mL or more and insulin-like growth factor I levels were normal or low. A novel heterozygous mutation resulting in a valine to isoleucine change (V144I) in exon 6 in the extracellular domain was found in one subject. His mother and one brother had significant short stature and also had the identical mutation. Affected family members also had a polymorphism in exon 6 of the GHR gene, which has been present in other subjects who had short stature and heterozygous mutations of the GHR gene. The other subjects with ISS had normal GHR genes. However, eight subjects had neutral polymorphisms distributed throughout the GHR locus. Accumulating evidence suggests that GHR gene mutations account for up to 5% of all ISS patients. These mutations should be considered when other causes of short stature have been eliminated.

Adolescent↗
PubMed1997

Clinical, biochemical, and molecular investigations of a genetic isolate of growth hormone insensitivity (Laron's syndrome).

We have characterized the GH receptor mutation that is responsible for extreme short stature and GH insensitivity in a Bahamian genetic isolate. Heights of affected individuals ranged from -4.0 to -6.3 SD. Like others with Laron's syndrome, they had normal to high serum GH concentrations and low serum insulin-like growth factor I concentrations. Circulating levels of GH-binding protein activity were below limits of detection. Amplification of exons 2-7 and screening with single strand conformational polymorphism analysis located an abnormality in exon 7. Sequencing identified homozygosity for a C to T transition in the third position of codon 236. Reverse transcription and PCR amplification of complementary DNA from lymphocytes showed that this same sense mutation generated a new splice donor site 63 bp 5' to the normal exon 7 splice site. This novel site was used to the exclusion of the normal site in homozygotes. Both normal and variant messenger ribonucleic acid species were detected in heterozygotes. The predicted protein lacks 21 amino acids, including those defining the WS-like motif of the GH receptor extracellular domain. The high frequency of Laron's syndrome in this isolated island population probably reflects the introduction of the G236 splice mutation by a settler early in the 300-yr history of English settlement.

Adolescent↗
PubMed1995

A gene for a severe lethal form of X-linked arthrogryposis (X-linked infantile spinal muscular atrophy) maps to human chromosome Xp11.3-q11.2.

X-linked arthrogryposis Type I (X-linked infantile spinal muscular atrophy) is a rare disorder showing hypotonia, areflexia, and multiple congenital contractures (arthrogryposis) associated with loss of anterior horn cells and death in infancy. We have studied an X-linked arthrogryposis family using highly polymorphic microsatellite markers throughout the X chromosome. Meiotic breakpoint analysis (concordance analysis) based on shared regions of the founder X chromosome was successful in localizing the X-linked arthrogryposis gene to Xp11.3-q11.2. In this region, the highest two-point lod score was found with DXS991 (Zmax = 2.63, theta = 0.00). In multipoint linkage analysis covering the entire X chromosome, only the region defined by MAOB and DXS991 showed positive lod scores and all other regions showed negative lod scores. These data establish the first gene mapping assignment of an X-linked lethal form of human lower motor neuron disease.

Adolescent↗
PubMed1991

242 breakpoints in the 200-kb deletion-prone P20 region of the DMD gene are widely spread.

Using whole cosmids as probes, we have mapped 242 DMD/BMD deletion breakpoints located in the major deletion hot spot of the DMD gene. Of these, 113 breakpoints were mapped more precisely to individual restriction enzyme fragments in the distal 80 kb of the 170-kb intron 44. An additional 12 breakpoints are distributed over the entire region, with no significant local variation in frequency. Furthermore, deletion sizes vary and are not influenced by the positions of the breakpoints. This argues against a predominant role of one or a few specific sequences in causing frequent rearrangements. It suggests that structural characteristics or a more widespread recombinogenic sequence makes this region so susceptible to deletion. Our study revealed several RFLPs, one of which is a 300-bp insertion/deletion polymorphism. Abnormally migrating junction fragments are found in 81% of the precisely mapped deletions and are highly valuable in the diagnosis of carrier females.

Chromosome Deletion↗
PubMed1989

Complementary DNA probes for the Duchenne muscular dystrophy locus demonstrate a previously undetectable deletion in a patient with dystrophic myopathy, glycerol kinase deficiency, and congenital adrenal hypoplasia.

Genomic DNA from a patient with dystrophic myopathy, glycerol kinase deficiency, and congenital adrenal hypoplasia was investigated using cDNA probes for the Duchenne muscular dystrophy (DMD) locus. Genomic probes had not detected a deletion in this patient. Southern analysis of Hind III-digested genomic DNA from this patient identified a deletion when the three distal Hinc II DMD cDNA fragments were used as probes. The deletion began in the genomic region corresponding to the 1.05-kb Hinc II cDNA fragment and extended through the 3' end of the DMD gene. This represents a centromeric breakpoint that corresponds to a position approximately 10.2-10.6 kb from the 5' end of the 14-kb DMD cDNA. These investigations demonstrate the value of the DMD cDNA probes for improved diagnoses in patients with molecular lesions involving the DMD locus. Furthermore, this novel deletion involving the coding portion of the 3' end of the DMD gene assists in the ordering of exons in this region and will provide insight into the functional role of the carboxy terminus of the DMD gene product, dystrophin.

Adrenal Insufficiency↗
PubMed1989

[Effect of tumor-promoting phorbol esters on retrovirus-infected human cells: scanning electron microscopy studies].

The effects of 12-O-tetradecanoylphorbol-13-acetate (TPA) on cultivated human cells infected with a human cell line derived retrovirus were examined by using scanning electron microscopy. The most prominent immediate morphological changes were the rounding up of cell surfaces, an enhanced formation of blebs and an increasing tendency to cell detachment. The production of virus particles under TPA treatment was markedly augmented, reaching 300 to 500 particles in individual cells. The production of particles appeared nearly random over the cell surface.

Cell Line↗
PubMed1987

Tachyphylaxis of juxtaglomerular epithelioid cells to angiotensin II. Differences between the electrical membrane response and renin secretion.

A study has been made of desensitization of the depolarizing response to angiotensin II of juxtaglomerular epithelioid and vascular smooth muscle cells in the mouse kidney afferent arteriole, of media cells from the mesenteric artery as well as of cultured smooth muscle and mesangial cells. In all cell types, desensitization to this effect of angiotensin II was observed. There was no cross-desensitization between angiotensin II and other depolarizing agonists. Hence, it is concluded that this desensitization is specific, i.e. of the tachyphylaxis type. Substances interfering with receptor recycling, such as chloroquine and monensin, did not block the recovery of the cells from desensitization after removal of the octapeptide. Desensitization to the action of angiotensin II was also observed with respect to its vasoconstrictor effect in the isolated perfused rat kidney. In contrast there was no desensitization of renin secretion in the isolated perfused rat kidney, nor in isolated hydronephrotic mouse tissue, nor in microdissected rat glomeruli.

Angiotensin II↗
PubMed1986

Renin release from different parts of rat afferent arterioles in vitro.

A technique was designed to study renin release from superfused rat glomeruli with short attached arterioles (SAG), from single glomeruli with long attached arterioles (LAG), and from single afferent arterioles (AA). The preparations obtained by magnetic isolation and microdissection were superfused individually, and the renin release was measured by an ultramicroradioimmunoassay with a detection limit of 3 X 10(-9) Goldblatt units. The renin content of one SAG was about one-fifth of that contained in one AA. Isoprenaline (10(-5) M) did not change renin release from SAG, whereas renin release from AA and LAG increased threefold (P less than 0.01). A 30-mosmol/kg reduction in medium sodium chloride concentration increased renin release from SAG 50% (P less than 0.01). This challenge caused no change in renin release from AA. It is concluded that the isoprenaline-sensitive juxtaglomerular (JG) cells are located in the afferent arteriole only at some distance from the glomerulus, whereas those cells sensitive to sodium chloride are located within and/or close to the glomerulus.

Animals↗
PubMed1986

[The biological effects of coordination compounds of transitional metals. 6. Effect of 4-methyl-2-aminopyridine-palladium chloride and cis-dichlorodiammine-platinum(II) on retroviruses and the virus-associated RNA polymerase of the influenza virus].

The effect on retroviruses of two transition metal complexes of known antiviral activity, 4-methyl-2-amino-pyridine-palladium-chloride (MAP) and cis-dichloro-diammine-platinum(II) (cis-DDP) has been investigated. The experiments included the evaluation of the action of compounds on virus particle-associated reverse transcriptase in exogenous assays, on virus propagation in persistently infected cell cultures and on virus infectivity in mice. In disrupted viruses and in the absence of excess protein, the reverse transcriptase was inhibited by MAP but not by cis-DDP. The same results were obtained when examining the activity of the virus-associated RNA polymerase of influenza virus A/WSN. Both compounds did not inhibit the replication of retroviruses in cell cultures, except at high dose levels which exerted toxic action on both cells and virus formation. The leukemogenicity of Rauscher murine leukemia virus was strongly inhibited when the virus had been incubated with MAP before inoculation. A similar treatment with cis-DDP did not influence viral leukemogenicity. Despite somewhat different results with both compounds tested, we conclude from the present results that the above mentioned compounds cannot be considered as antiretroviral drugs.

Animals↗