Search PubMed⌕ Search

Biomedical subjects

D Jung

Publications and source records attributed to D Jung.

At least 55 records · Page 3Linked to original sources
PubMed1998

Oral ganciclovir dosing in transplant recipients and dialysis patients based on renal function.

BACKGROUND: An oral formulation of ganciclovir (GCV) was recently approved for the prevention of cytomegalovirus disease in solid organ transplant recipients. This study was designed to determine the bioavailability of GCV and to test a dosing algorithm in transplant and dialysis patients with different levels of renal function. METHODS: Pharmacokinetic studies were carried out in 23 patients who were either a recipient of an organ transplant or on hemodialysis. Drug dosing was established by the following algorithm based on calculated creatinine clearance (CrCl): CrCl = [(140-age) x body weight]/(72 x Cr) x 0.85 for women that is, CrCl >50 ml/min, 1000 mg every 8 hr; CrCl of 25-50 ml/min, 1000 mg every 24 hr; CrCl of 10-24 ml/ min, 500 mg every day; CrCl < 10 ml/min (or on dialysis), 500 mg every other day after dialysis. GCV was taken within 30 min after a meal. The patients received oral GCV for between 12 days and 14 weeks. Serum specimens (or plasma from patients on hemodialysis) obtained at steady state were analyzed for GCV concentrations by high-performance liquid chromatography. In nine of the transplant recipients, absolute bioavailability was determined by comparing GCV levels after single oral and intravenous doses of GCV. RESULTS: The following GCV concentrations (mean +/-SD) were determined: with CrCl of > or =70 ml/min, the minimum steady-state concentration (Cmin) and maximum concentration (Cmax) were 0.78+/-0.46 microg/ml and 1.42+/-0.37 microg/ml, respectively, with a 24-hr area under the concentration time curve (AUC0-24) of 24.7+/-7.8 microg x hr/ml; with CrCl of 50-69 ml/min, the Cmin and Cmax were 1.93+/-0.48 and 2.57+/-0.39 microg/ml, respectively, with an AUC0-24 of 52.1+/-10.1 microg x hr/ml; with CrCl of 25-50 ml/min, the Cmin and Cmax were 0.41+/-0.27 and 1.17+/-0.32 microg/ml, respectively, with an AUC0-24 of 14.6+/-7.4 microg x hr/ml. For one patient with a CrCl of 23.8 ml/min, the Cmin and Cmax were 0.32 and 0.7 microg/ml, respectively, with an AUC0-24 of 10.7 microg x hr/ml. With CrCl of <10 ml/min, the mean Cmin and Cmax were 0.75+/-0.42 and 1.59+/-0.55 microg/ml, respectively, with a mean AUC0-24 of 64.6+/-18.8 microg x hr/ml. Absolute bioavailability, for the nine patients so analyzed, was 7.2+/-2.4%. For those patients with end-stage renal failure, GCV concentrations fell during dialysis from a mean of 1.47+/-0.48 microg/ml before dialysis to 0.69+/-0.38 microg/ml after dialysis. CONCLUSIONS: The bioavailability of oral GCV in transplant patients was similar to that observed in human immunodeficiency virus-infected patients. However, levels between 0.5 and 1 microg/ml (within the IC50 of most cytomegalovirus isolates) could be achieved with tolerable oral doses. The proposed dosing algorithm resulted in adequate levels for patients with CrCl greater than 50 ml/min and for patients on dialysis. For patients with CrCl between 10 and 50 ml/min, the levels achieved were low and these patients would likely benefit from increased doses.

Administration, Oral↗
PubMed1998

The MDM2 gene amplification database.

The p53 tumor suppressor gene is inactivated in human tumors by several distinct mechanisms. The best characterized inactivation mechanisms are: (i) gene mutation; (ii) p53 protein association with viral proteins; (iii) p53 protein association with the MDM2 cellular oncoprotein. The MDM2 gene has been shown to be abnormally up-regulated in human tumors and tumor cell lines by gene amplification, increased transcript levels and enhanced translation. This communication presents a brief review of the spectrum of MDM2 abnormalities in human tumors and compares the tissue distribution of MDM2 amplification and p53 mutation frequencies. In this study, 3889 samples from tumors or xenografts from 28 tumor types were examined for MDM2 amplification from previously published sources. The overall frequency of MDM2 amplification in these human tumors was 7%. Gene amplification was observed in 19 tumor types, with the highest frequency observed in soft tissue tumors (20%), osteosarcomas (16%) and esophageal carcinomas (13%). Tumors which showed a higher incidence of MDM2 amplification than p53 mutation were soft tissue tumors, testicular germ cell cancers and neuro-blastomas. Data from studies where both MDM2 amplification and p53 mutations were analyzed within the same samples showed that mutations in these two genes do not generally occur within the same tumor. In these studies, 29 out of a total of 33 MDM2 amplification-positive tumors had wild-type p53. We hypothesize that heretofore uncharacterized carcinogens favor MDM2 amplification over p53 mutations in certain tumor types. A database listing the MDM2 gene amplifications is available on the World Wide Web at http://www. infosci.coh.org/mdm2 . Charts of MDM2 amplification frequencies and comparisons with p53 genetic alterations are also available at this Web site.

Animals↗
PubMed1998

Transplacental uptake of glucose is decreased in embryonic lethal connexin26-deficient mice.

Mice that harbor a targeted homozygous defect in the gene coding for the gap junctional protein connexin26 died in utero during the transient phase from early to midgestation. From day 10 post coitum onwards, development of homozygous embryos was retarded, which led to death around day 11 post coitum. Except for growth retardation, no gross morphological alterations were detected between homozygous connexin26-defective embryos and wild-type littermates. At day 9 postcoitum, when chorioallantoic placenta started to function, connexin26 was weakly expressed in the yolk sac epithelium, between syncytiotrophoblasts I and II in the labyrinth region of the placenta, and in the skin of the embryo. At day 10 post coitum, expression of connexin26 in the placenta was much stronger than at the other locations. To analyze involvement of connexin26 in the placental transfer of nutrients, we have measured embryonic uptake of the nonmetabolizable glucose analogue 3-O-[14C]methylglucose, injected into the maternal tail vein. At day 10 post coitum, viable, homozygous connexin26-defective embryos accumulated only approximately 40% of the radioactivity measured in wild-type and heterozygous littermates of the same size. We conclude that the uptake of glucose, and presumably other nutrients as well, from maternal blood into connexin26-deficient mouse embryos was severely impaired and apparently not sufficient to support the rapid organogenesis during midgestation. Our results suggest that connexin26 gap junction channels likely fulfill an essential role in the transfer of maternal nutrients and embryonic waste products between syncytiotrophoblast I and II in the labyrinth layer of the mouse placenta.

3-O-Methylglucose↗
PubMed1998

Pharmacokinetics of oral ganciclovir alone and in combination with zidovudine, didanosine, and probenecid in HIV-infected subjects.

The aim of this study was to determine whether oral ganciclovir interacted pharmacokinetically with zidovudine (AZT), didanosine (ddI), or probenecid. A multicenter, open-label, randomized, crossover pharmacokinetic study with four phases was undertaken at an outpatient private research center and at university research clinics. Twenty-six HIV-infected adults (23 men, 3 women) with cytomegalovirus (CMV) seropositivity and CD4+ T-lymphocyte count > or =100 cells/microl were studied. Patients had to be stable on antiretroviral therapy for at least 4 weeks. Patients with a history of opportunistic infection or gastrointestinal symptoms were excluded. Measurements included serial blood and urine samples during the dosing intervals at steady state. The steady-state pharmacokinetics of ganciclovir were determined after the participants had stabilized and were tolerating AZT or ddI therapy. When a 1000-mg dose of oral ganciclovir was taken every 8 hours, there was a significant mean increase in Cmax and dosing interval area under the serum concentration time curve over a dosing interval (AUC) for the two antiretroviral drugs: for AZT, 61.6% and 19.5%, respectively; for ddI when administered sequentially (2 hours before ganciclovir), 116.0% and 114.6%; and for ddI administered simultaneously with ganciclovir, 107.9% and 107.1%, respectively. There was no significant change in renal clearance for either antiretroviral drug, suggesting that the interaction did not occur through a renal mechanism. There was no significant change in mean ganciclovir Cmax and AUC(0-8) when coadministered with AZT. Mean increases in Cmax and AUC(0-8) of oral ganciclovir averaged 40.1% and 52.5%, respectively, when coadministered with probenecid, but decreased by 22.1% and 22.7%, respectively, when oral ganciclovir was administered 2 hours after ddI. There was no change in the mean ganciclovir Cmax or AUC(0-8) when administered simultaneously with ddI. The mean renal clearance of oral ganciclovir was not affected by AZT or ddI coadministration intake, but there was a mean decrease of 19% when coadministered with probenecid. We conclude the increased serum concentration and reduced renal clearance of ganciclovir suggests competition with probenecid for secretion at the renal tubule. The mechanism of the interaction of oral ganciclovir with either AZT or ddI remains to be determined. The magnitude of the effect of oral ganciclovir on ddI pharmacokinetics may result in an increase in ddI concentration-related toxicities. Similarly, the small but significant decrease in ganciclovir concentration with sequential combination ddl therapy may impair the efficacy of oral ganciclovir. For HIV-infected patients receiving ganciclovir and ddI, clinicians should recommend administering the two drugs simultaneously, and patients should be monitored closely for ddI-associated toxicities.

Administration, Oral↗
PubMed1998

Strong immunogenic potential of a B7 retroviral expression vector: generation of HLA-B7-restricted CTL response against selectable marker genes.

The stimulation of a specific immune response is an attractive goal in cancer therapy. Gene transfer of co-stimulatory molecules and/or cytokine genes into tumor cells and the injection of these genetically modified cells leads to tumor rejection by syngeneic hosts and the induction of tumor immunity. However, the development of host immune response could be either due to the introduced immunomodulatory genes or due to vector components. In this study, human renal cell carcinoma cell lines were modified by a retrovirus to express the co-stimulatory molecule B7-1 together with the hygromycin/thymidine kinase fusion protein (HygTk) as positive and negative selection markers. These B7-1-transduced renal cell carcinoma cell lines were able significantly to activate allogeneic T cell proliferation. The cytolytic activity of these T cells was determined by employing several transduced and nontransduced renal cell carcinoma cell lines as targets. Evidence for a strong vector-specific T cell reactivity induced by the Hyg/Tk protein was obtained in autologous renal cell carcinoma systems. Antibody blocking experiments as well as peptide binding assays demonstrated an HLA-B7-restricted T cell response directed against both the Hyg and the Tk genes. Thus, the vector itself may mask the generation of immune reactivity against tumor antigens and may even detract from it. Vectors with immunogenic potential may be useful for tumor vaccination via cross priming in vivo, whereas antivector reactivities would be detrimental in situations where gene defects are being corrected and where long term expression of a therapeutic protein is required.

Antigens, Neoplasm↗
PubMed1998

[Treatment strategy in first traumatic anterior dislocation of the shoulder. Plea for a multi-stage concept of preventive initial management].

The purpose of this paper is to outline the treatment protocol for the first time traumatic anterior shoulder dislocator, with options including conservative, arthroscopic and open surgical treatment. Regarding the subclassification of the first time traumatic anterior dislocater, it is imparitive to differentiate between the unidirectional dislocator with and without hyperlaxity. This subclassification takes into account the structural quality of the stabilizing ligamentous structures of the glenohumeral capsule. The patient with hyperelastic ligaments exhibit elastic deformation of the glenohumeral ligaments at the time of dislocation and thus, sustain less interstitial structural damage to the ligament. Therefore, these patients benefit from non-operative treatment. There are extrinsic and intrinsic factors which determine the outcome of the primary traumatic anterior shoulder dislocation. Extrinsic factors are those that are not related to changes in the shoulder morphology. The most important extrinsic factor is the age of the patient at the time of injury. The younger the patient at the time of injury the greater the risk of recurrence. As a rule, those patients 25 years of age or less, at the time of initial injury are less likely to spontaneously stabilize without surgical intervention, than they are to develop recurrence. Secondly, the type and level of sport participation is related to recurrence. Although the severity of the trauma can not be quantified, it certainly has an influence on recurrence. Immobilization remains controversial. A rehabilitation program is more likely to be successful in atraumatic instability. Patient compliance is important regardless of the type of treatment selected. Intrinsic factors include injury to the various anatomic structures about the shoulder, occurring at the time of primary anterior shoulder dislocation. A deep Hill Sachs lesion is more likely to result in recurrence secondary to both the impaction of the bone, as well as, the reduction of the area of articular surface. A displaced bony Bankart is a highly unstable situation secondary to the loss of the butress to retain the humeral head. In contrast to a Hill Sachs lesion or a bony Bankart, a concomittent fracture of the greater tuberosity is unlikely to result in recurrent dislocation. Isolated laberal detachment is not related to recurrence, but a complete disruption of the laberal ligament complex is highly correlated with recurrence. A rare subluxation erecta, as a special form of traumatic inferior instability, has a high recurrence rate. With increasing age there is a higher risk of concomittent rotator cuff tear. In most situations surgical repair of the rotator cuff tear results in resolution of the instability. The essential issue in determining the treatment protocol is to define concomittent hyperlaxity in the injured shoulder. Concomittent hyperlaxity precludes initial surgical treatment. The orthopedic surgeon treating the patient at the time of injury needs to design a concise treatment protocol for the patient based on the assessment of the extrinsic and intrinsic factors. An unreducable shoulder dislocation or associated vascular injury requires emergent intervention. Absolute indications for surgical treatment include: persistent dislocation, bony Bankart, a grossly displaced greater tuberosity fracture, and rupture of the subscapularis tendon. Surgical stabilization of primary anterior traumatic dislocation is indicated if the following strict criteria are met: adequate trauma, no self reduction, unidirectional instability without hyperlaxity, Hill Sachs lesion, age below 26 years, high level of sport activity and the special situation of luxatio erecta. Post primary stabilization is indicated for persistent subluxation, subjective instability or demonstrated pathologic instability tests. Rotator cuff tears due to traumatic dislocation in the elderly population require surgical repair.

Arthroscopy↗
PubMed1998

A study of the pharmacokinetics, antiviral activity, and tolerability of oral ganciclovir for CMV prophylaxis in marrow transplantation.

Oral ganciclovir is effective in preventing cytomegalovirus (CMV) disease in HIV-infected patients despite a bioavailability of only 6-9%. To determine safety, pharmacokinetics, and the influence of acute gastrointestinal graft-vs.-host disease (GI-GVHD) on the bioavailability and antiviral effect of oral ganciclovir after marrow transplantation, CMV seropositive patients received oral ganciclovir (1000 mg 3 times per day) from day 35 (+/- 7 days) until day 100 after transplantation. Single-dose (intravenous and oral) and steady-state oral pharmacokinetic profiles and weekly trough levels were performed. Twenty-one patients received oral ganciclovir (seven with GI-GVHD, 14 without); 17 had steady-state pharmacokinetic profiles and seven had single-dose profiles. The absolute bioavailability was similar in patients with or without acute GI-GVHD (7.2 vs. 6.9%). At steady state, the extent and rate of absorption of oral ganciclovir were comparable in these same patient subgroups (area under the curve [AUC] = 13.5 and 10.2 mg x hours/L, respectively; time to peak serum ganciclovir concentrations = 5.5 and 3.8 hours, respectively). Breakthrough CMV antigenemia, viremia, or plasma polymerase chain reaction positivity occurred in eight of 21 (38%) patients (four of seven with GVHD and four of 14 without). Drug discontinuation because of GI adverse effects was required in six of 21 (29%) patients. Neutropenia occurred in two of 15 (13%) patients who had received oral ganciclovir for more than 10 days. In conclusion, the bioavailability of oral ganciclovir seems similar to that reported in other settings. The presence of acute GVHD of the GI tract did not appear to adversely affect absorption of oral ganciclovir. The use of oral ganciclovir was limited by the presence of GI intolerance in the early posttransplant period. The efficacy of oral ganciclovir in preventing CMV infection in marrow transplant recipients is being assessed in a separate randomized controlled trial.

Administration, Oral↗
PubMed1998

Steady-state relative bioavailability of three oral ganciclovir dosage regimens delivering 6,000 mg/day in patients with human immunodeficiency virus.

This study was designed to determine the steady-state relative bioavailability of ganciclovir after three dosage regimens designed to deliver 6,000 mg/day. The study design was an open-label, randomized, three-treatment crossover design in which 22 human immunodeficiency virus (HIV) and cytomegalovirus (CMV) seropositive patients received in random order multiple oral doses of ganciclovir 1,000 mg six times a day, 1,500 mg four times a day, and 2,000 mg three times a day. Blood samples were obtained on day 3 of each oral regimen over a 24-hour time interval. Mean steady-state average serum concentrations of ganciclovir were greater than 1.0 microgram/mL, which exceeds the median in vitro inhibitory concentration (IC50) of most CMV isolates (0.5-1.0 microgram/mL). All three regimens resulted in values for area under the concentration-time curve from 0 to 24 hours (AUC0-24) that were comparable to those seen after maintenance ganciclovir intravenous infusions of 5 mg/kg/day. The 1,000 mg six times daily regimen resulted in an AUC0-24 that was significantly higher than that of the 1,500 mg four times daily or the 2,000 mg three times daily regimens, although the differences were less than 12.5%.

Administration, Oral↗
PubMed1998

Effect of high-dose oral ganciclovir on didanosine disposition in human immunodeficiency virus (HIV)-positive patients.

This study was designed to investigate the interaction between high-dose oral ganciclovir (6,000 mg/day) and didanosine at steady state in patients who were seropositive for human immunodeficiency virus (HIV) and cytomegalovirus (CMV) infection. The study was conducted as an open-label, randomized, three-period crossover study. Patients received (in random order) multiple oral doses of didanosine 200 mg every 12 hours alone, ganciclovir 2,000 mg every 8 hours alone, and ganciclovir 2,000 mg every 8 hours in combination with didanosine 200 mg every 12 hours. Blood and urine samples for determinations of drug concentrations were obtained on day 3 of each dose regimen. When ganciclovir was administered either before or 2 hours after didanosine, the mean increases in maximum concentration (Cmax), area under the concentration-time curve (AUC0-12), and percent excreted in urine of didanosine were 58.6% and 87.3%, 87.3% and 124%, and 100% and 153%, respectively. There were no statistically significant effects of didanosine on the steady-state pharmacokinetics of ganciclovir in the presence of didanosine, irrespective of sequence of administration. There were no significant changes in renal clearance of didanosine, suggesting that the mechanism for the interaction does not involve competition for active renal tubular secretion. The mechanism responsible for increased didanosine concentrations and percent excreted in urine during concurrent ganciclovir therapy may be a result of increased bioavailability of didanosine. However, the mechanism appears to be saturated at oral ganciclovir doses of 3 g/day.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Immunologic findings in workers formerly exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin and its congeners.

One hundred ninety-two workers in a German pesticide factory who were exposed to polychlorinated dibenzodioxins and -furans (PCDD/PCDF) were investigated for former and present diseases and laboratory changes of the immune system. Moreover, in a subgroup of 29 highly exposed and 28 control persons, proliferation studies were performed. In addition to assays such as blood count, immunoglobulins, serum electrophoresis, monoclonal bands, surface markers, autoantibodies, and lymphocyte proliferation, two new methods, the rise of tetanus antibody concentration after vaccination and the in vitro resistance of lymphocytes to chromate, were used to diagnose the morphologic and functional state of the immune system. There was no stringent correlation of actual PCDD/PCDF concentrations with the occurrence of infections or with one of the immune parameters. In addition, outcomes of the tetanus vaccination and the chromate resistance test were not correlated with PCDD/PCDF. However, the chromate resistance of lymphocytes stimulated by phytohemagglutinin of highly exposed persons was significantly lower than that for the control group. These findings indicate that the function of lymphocytes can be stressed and possibly impaired by high exposure to PCDD/PCDF.

Adult↗
PubMed1998

Absolute bioavailability and dose proportionality of oral ganciclovir after ascending multiple doses in human immunodeficiency virus (HIV)-positive patients.

This study was designed to determine the bioavailability and dose linearity and proportionality of ganciclovir after multiple oral administrations of 3,000 mg to 6,000 mg per day. In an open-label, randomized, four-treatment crossover design, 24 patients seropositive for human immunodeficiency virus (HIV) and cytomegalovirus (CMV) received in random order multiple oral doses of ganciclovir 1,000 mg every 3 hours (six times a day), 1,000 mg four times a day, and 1,000 mg three times a day and a single 5-mg/kg intravenous infusion (over 1 hour) of ganciclovir. Blood samples for pharmacokinetic determinations were obtained on day 3 of each oral regimen and on the day of the intravenous infusion over a 24-hour time interval. Mean steady-state average serum concentrations of ganciclovir were 0.54, 0.79, and 0.99 microgram/mL, respectively, with the 3, 4, and 6 g/day oral regimens. The steady-state area under the concentration-time curve (AUC0-24) for the 6,000 mg/day oral regimen approached that of the single-dose intravenous regimen. There was a proportional increase in AUC0-24 between the 3 and 4 g/day dosage regimens, but not between the 4 and 6 g/day regimens. This suggests nonlinear absorption of ganciclovir at higher dosages, although the departure from proportionality was less than 11%.

Adult↗
PubMed1998

[Current status of shoulder arthroscopy].

Arthroscopic and open shoulder surgery have to be combined for a successful surgical therapy of the shoulder joint. A surgeon performing open surgery only or just treating by arthroscopic measurements can not cover the full spectrum of modern shoulder surgery. Isolated diagnostic arthroscopy is rarely indicated. Far more common, diagnostic arthroscopy is combined with an operative procedure both to confirm preoperative assessment of pathology and to uncover associated lesions. The results of arthroscopic stabilisation of chronic anterior posttraumatic dislocations fail to compare with high success rates of open procedures. Better patient selection will probably be the key to improving results. In case of acute traumatic first time dislocation in young highly sportive athletes the arthroscopic repair of the isolated Bankart-Perthes lesion offers the attractive advantage of anatomic reconstruction with minimal soft tissue dissection. Further indications for arthroscopic measurements of pathologies of the glenohumeral joint are synovectomy in rheumatoid arthritis, capsulotomy of shrunk capsule in frozen shoulder and tenodesis for lesions of the long head of the biceps. The arthroscopic subacromial decompression according to Ellman is the most often and successful performed procedure at the shoulder joint and has overcome the classic Neer open acromioplasty. For smaller tears of the supraspinatus tendon the arthroscopic acromioplasty can be combined with an all arthroscopic suture repair or with an mini-open repair. Larger tears of the rotator cuff are still the domain for open reconstructive procedures. In case of associated or isolated AC-joint arthritis an arthroscopic Mumford procedure can be performed. For chronic calcific tendinitis isolated arthroscopic excision of the calcium deposit is of great value. Additionally, acromioplasty is needed for true mechanical obstruction of the subacromial space.

Acromioclavicular Joint↗
PubMed1997

Transient expression of Dp140, a product of the Duchenne muscular dystrophy locus, during kidney tubulogenesis.

Dystroglycan is a cell surface complex which in muscle links the extracellular matrix protein laminin-2 to the membrane associated cytoskeletal protein dystrophin. Recently it was found that dystroglycan is also expressed in developing epithelial cells. Moreover, antibodies against dystroglycan can perturb epithelial cell development in kidney organ culture. Dystroglycan could provide a link between the basement membrane and the intracellular space also in epithelial cells. However, there is no dystrophin in epithelial cells. By in situ hybridization here we show prominent expression of a shorter isoform of dystrophin, Dp140, in embryonic kidney tubules. In addition, another isoform, Dp71, is expressed by all studied embryonic epithelial cells. Both isoforms share the dystroglycan-binding region of dystrophin but lack the region known to bind to actin. Here we also characterized monoclonal antibodies against different domains of dystrophin and used these to study the distribution of Dp140 protein. In embryonic kidney tubules the dystrophin antibody VIA4(2)A3 stained an intracellular antigen close to the basal cells. In contrast, no staining was observed in adult kidney. We suggest that Dp140 is a structural component during kidney tubulogenesis but it may also be involved in signal transduction.

Animals↗
PubMed1997

A biochemical, genetic, and clinical survey of autosomal recessive limb girdle muscular dystrophies in Turkey.

Autosomal recessive limb girdle muscular dystrophy (LGMD2) is a clinically and genetically heterogenous group of diseases involving at least six different loci. Five genes have already been identified: calpain-3 at LGMD2A (15q15), and four members of the sarcoglycan (SG) complex, alpha-SG at LGMD2D (17q21), beta-SG at LGMD2E (4q12), gamma-SG at LGMD2C (13q12), and delta-SG at LGMD2F (5q33-q34). The gene product at LGMD2B (2p13-p16) is still unknown and at least one other gene is still unmapped. We investigated 20 Turkish families (18 consanguineous) diagnosed as having LGMD2. Most of our patients had onset of symptoms before age 10. The phenotypes varied from severe to benign. We analyzed the SG complex by immunofluorescence and/or western blot. Genotyping was performed using markers defining the six known loci and the suspected genes were screened for mutations. Six of 17 index cases showed deficiency of the SG complex, by immunofluorescence and/or western blot. Seven cases involved one of the known genes of the SG complex (alpha, 2; beta, 1; and gamma, 4 cases), and five mutations were documented in the alpha- and gamma-SG genes. After linkage analysis, 10 families were characterized as having LGMD2A (calpain-3 deficiency), and all mutations were eventually identified. One family was classified as having LGMD2B and 1 family that has normal SGs was linked to the chromosome 5q33-q34 locus (LGMD2F). In 1 family there was no linkage to any of the known LGMD2 loci. It appears that in Turkey, there is a broad spectrum of genes and defects involved in LGMD2. It may be possible to correlate genotype to phenotype in LGMD2. All severe cases belonged to the gamma-SG-deficiency group. Nine calpain-3-deficient cases had intermediate and 1 had moderate clinical courses. The LGMD2B patient had a moderate clinical expression, whereas the LGMD2F case was truly benign.

Adolescent↗
PubMed1997

[Arthroscopic surgical measures in the shoulder joint].

Arthroscopic and open surgery have to be combined for successful surgical therapy of the shoulder joint. A surgeon performing open surgery alone or just using arthroscopic measures cannot cover the full spectrum of modern shoulder surgery. Isolated diagnostic arthroscopy is rarely indicated. Far more common, diagnostic arthroscopy is combined with an operative procedure both to confirm preoperative assessment of pathology and to uncover associated lesions. The results of arthroscopic stabilization of chronic anterior post-traumatic dislocations fail to compare with the high success rates of open procedures. Better patient selection will probably be the key to improving results. In cases of acute traumatic first-time dislocation in young, highly athletic people, arthroscopic repair of the isolated Bankart-Perthes lesion offers the attractive advantage of anatomic reconstruction with minimal soft-tissue dissection. Further indications for arthroscopic measurements of pathologies of the glenohumeral joint are synovectomy in rheumatoid arthritis, capsulotomy in frozen shoulder and tenodesis for lesions of the long head of the biceps. Arthroscopic subacromial decompression according to Ellman is the procedure performed most often and most successfully in the shoulder joint and has overcome the classic Neer open acromioplasty. For smaller tears of the supraspinatus tendon, arthroscopic acromioplasty can be combined with an all arthroscopic suture repair or with mini-open repair. Larger tears of the rotator cuff are still the domain for open reconstructive procedures. In associated or isolated AC joint arthritis, an arthroscopic Mumford procedure can be performed. For chronic calcific tendinitis, isolated arthroscopic excision of the calcium deposit is of great value. Additionally, acromioplasty is needed for true mechanical obstruction of the subacromial space.

Arthritis, Rheumatoid↗
PubMed1997

Blue-yellow deficiency in workers exposed to low concentrations of organic solvents.

OBJECTIVES: To evaluate the effects of low concentrations of organic solvents on color vision. METHODS: Color vision was examined in 24 workers exposed to mixtures of solvents and in 24 control subjects. Exposure to mixtures was below the threshold-limit values. Color vision ability was assessed using the Ishihara plates (to screen for congenital dyschromatopsia), the Farnsworth panel D-15 test, the Lanthony desaturated panel D-15 test, and the Standard Pseudoisochromatic Plates part 2 (SPP2 test). RESULTS: The comparatively less sensitive Farnsworth panel D-15 test failed to show any difference between the groups, but the Lanthony panel D-15 desaturated test as well as the SPP2 test showed a significant impairment in the exposed group. Errors were of the blue-yellow type. CONCLUSION: This study gives further evidence that even mixtures of organic solvents at concentrations below the threshold-limit values may impair color vision.

Adult↗
PubMed1997

Elimination of beta-hexachlorocyclohexane in occupationally exposed persons.

The elimination of beta-hexachlorocyclohexane (beta-HCH) in humans was investigated in a group of 40 former workers of a lindane-producing plant by analyzing at least 2 blood specimens (3 specimens in 3 workers) from different time points. Assuming a first-order kinetic model for excretion, the median half-life of beta-HCH is 7.2 yr calculated by concentrations in whole blood and 7.6 yr calculated by concentrations in extractable lipids. In univariate analyses an influence of age, percent body fat, and liver disease (additionally in whole blood an influence of contents of extractable lipids) on clearance was observed. All factors show a positive correlation with half-life. According to a multiple regression model, influence of percent body fat calculated according to Deurenberg et al. (1991) is an important covariate in the description of the variations of the clearance rate (calculated on the basis of extractable lipids) of beta-HCH. The data support the assumption of first-order kinetics.

Adipose Tissue↗