Quality of care of patients with chronic lymphoedema in Germany.

BACKGROUND: The management of lymphoedema is complex and should be based on guidelines. To date, no data assessing quality of care in lymphoedema in Germany are available. OBJECTIVE: We aimed at evaluating the quality of care of lymphoedema in the metropolitan area of Hamburg using guideline-based indicators. METHODS: Cross-sectional, community-based study including patients with lymphoedema. Assessment included a structured interview, clinical examination and patient-reported outcomes. Quality indicators derived from guidelines by a Delphi consensus were applied. RESULTS: 348 patients (median age 60.5 years) with lymphoedema (66.4%), lipoedema (9.5%) or combined oedema (24.1%) were included. 86.4% performed compression therapy, 85.6% received lymphatic drainage. On average 55.0% of the quality of care criteria were met; 64.8% were satisfied with care. The distribution curve of the health care index was almost normal. Treatment by specialists led to a higher quality of care index. CONCLUSION: Although overall quality of care in lymphoedema is fair, many patients are not treated properly according to guidelines.

Chromosome breakage in the Prader-Willi and Angelman syndromes involves recombination between large, transcribed repeats at proximal and distal breakpoints.

Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are distinct neurobehavioral disorders that most often arise from a 4-Mb deletion of chromosome 15q11-q13 during paternal or maternal gametogenesis, respectively. At a de novo frequency of approximately.67-1/10,000 births, these deletions represent a common structural chromosome change in the human genome. To elucidate the mechanism underlying these events, we characterized the regions that contain two proximal breakpoint clusters and a distal cluster. Novel DNA sequences potentially associated with the breakpoints were positionally cloned from YACs within or near these regions. Analyses of rodent-human somatic-cell hybrids, YAC contigs, and FISH of normal or rearranged chromosomes 15 identified duplicated sequences (the END repeats) at or near the breakpoints. The END-repeat units are derived from large genomic duplications of a novel gene (HERC2), many copies of which are transcriptionally active in germline tissues. One of five PWS/AS patients analyzed to date has an identifiable, rearranged HERC2 transcript derived from the deletion event. We postulate that the END repeats flanking 15q11-q13 mediate homologous recombination resulting in deletion. Furthermore, we propose that active transcription of these repeats in male and female germ cells may facilitate the homologous recombination process.

Vertical mammaplasty: technique and complications.

Vertical mammaplasty is among a group of mammaplasty procedures designed to minimize the extent of skin excision, and thus the potential for aesthetically unpleasing scars. However, these less traditional techniques have not enjoyed the same usage as classic inverted-mammaplasties, and thus the accumulated experience in these techniques is less. Vertical mammaplasty can yield excellent results when applied appropriately, but the learning curve can be significant. Details of operative technique are presented along with potential compfications, with the objective of maximizing the safety and outcome of vertical mammaplasty.

Acute otitis media and facial paralysis in children.

We reviewed 10 children who presented with facial paralysis after the onset of acute otitis media. The objective of the study was to examine the outcome of facial paralysis in children with acute otitis media treated without facial nerve decompression. Two groups were identified: 8 patients with incomplete paralysis and 2 with complete paralysis. Seven of the 8 patients with incomplete paralysis had rapid return of function after myringotomy and intravenous antibiotics. The eighth patient had delayed recovery requiring 9 months before complete return of function. The 2 patients with complete paralysis required mastoidectomy to control otorrhea and fever after initial myringotomy and antibiotics. Both patients had a prolonged recovery requiring 3 and 7 months for complete recovery. Patients with incomplete paralysis generally show rapid improvement following wide myringotomy and antibiotic treatment. A more protracted recovery may be expected in patients with complete paralysis; excellent return of function is expected when mastoidectomy without facial nerve decompression is employed.

Cytogenetic and molecular analysis in Angelman syndrome.

We report on cytogenetic and molecular analyses of 29 Angelman syndrome (AS) individuals ascertained in 1990 through the first National Angelman Syndrome Conference. High resolution GTG- and GBG-banded chromosomes were studied. Standard molecular analysis with six 15q11q13 DNA sequences was used to analyze copy number and parental origin of 15q11q13. Concordance between molecular and cytogenetic data was excellent. The combined data showed that 23 of the 27 probands (85%) on whom we had definitive results have deletions of the chromosome 15q11q13 region. Two classes of deletion were detected molecularly: most patients were deleted for the 5 more proximal probes, but in 2 cases the deletion extended distally to include in sixth probe. In the 13 cases where the parental origin of the deleted chromosome 15 could be established, it was maternal. There were no cases of uniparental disomy. Cytological observations of the relative sizes of the heterochromatic regions of the short arm of chromosome 15 suggested that chromosomes with large heterochromatic blocks may be more prone to de novo deletion.

Evaluation of potential models for imprinted and nonimprinted components of human chromosome 15q11-q13 syndromes by fine-structure homology mapping in the mouse.

Prader-Willi and Angelman syndromes are complex neurobehavioral contiguous gene syndromes whose expression depends on the unmasking of genomic imprinting for different genetic loci in human chromosome 15q11-q13. The homologous chromosomal region in the mouse genome has been fine-mapped by using interspecific (Mus spretus) crosses and overlapping, radiation-induced deletions to evaluate potential animal models for both imprinted and nonimprinted components of these syndromes. Four evolutionarily conserved sequences from human 15q11-q13, including two cDNAs from fetal brain (DN10, D15S12h; DN34, D15S9h-1), a microdissected clone (MN7; D15F37S1h) expressed in mouse brain, and the gene for the beta 3 subunit of the gamma-aminobutyric acid type A receptor (Gabrb3), were mapped in mouse chromosome 7 by analysis of deletions at the pink-eyed dilution (p) locus. Three of these loci are deleted in pre- and postnatally lethal p-locus mutations, which extend up to 5.5 +/- 1.7 centimorgans (cM) proximal to p; D15S9h-1, which maps 1.1 +/- 0.8 cM distal to p and is the mouse homolog of the human gene D15S9 (which shows a DNA methylation imprint), is not deleted in any of the p-locus deletion series. A transcript from the Gabrb3 gene, but not the transcript detected by MN7 at the D15F37S1h locus, is expressed in mice homozygous for the p6H deletion, which have an abnormal neurological phenotype. Furthermore, the Gabrb3 transcript is expressed equally well from the maternal or paternal chromosome 7 and, therefore, its expression is not imprinted in mouse brain. Deletions at the mouse p locus should serve as intermediate genetic reagents and models with which to analyze the genetics and etiology of individual components of human 15q11-q13 disorders.

Paternal uniparental disomy of chromosome 15 in a child with Angelman syndrome.

Angelman and Prader-Willi syndromes are clinically distinct neurobehavioral disorders most commonly resulting from large deletions of chromosome 15q11-q13. The deletions arise differentially during maternal or paternal gametogenesis, respectively. A subgroup of patients with either syndrome have no apparent deletion, and because many such patients with Prader-Willi syndrome display inheritance of two copies of chromosome 15 from the mother only (uniparental disomy; UPD), we suggested that paternal UPD might be found in patients with Angelman syndrome. We report here clinical, cytogenetic, and molecular evidence on the 1 patient with paternal UPD for chromosome 15 who was found in our study population. This represents, to our knowledge, the first patient with paternal UPD to be studied with DNA probes from the chromosome 15q11-q13 critical region. In contrast to our findings for patients with Prader-Willi syndrome, in which maternal UPD was common, our data demonstrate that paternal UPD is infrequent in patients with Angelman syndrome.

The frequency of uniparental disomy in Prader-Willi syndrome. Implications for molecular diagnosis.

BACKGROUND: Prader-Willi syndrome is a genetic disorder characterized by infantile hypotonia, obesity, hypogonadism, and mental retardation, but it is difficult to diagnose clinically in infants and young children. In about two thirds of patients, a cytogenetically visible deletion can be detected in the paternally derived chromosome 15 (15q11q13). Recently, patients with Prader-Willi syndrome have been described who do not have the cytogenetic deletion but instead have two copies of the 15q11q13 region that are inherited from the mother (with none inherited from the father). This unusual form of inheritance is known as maternal uniparental disomy. Using molecular genetic techniques, we sought to determine the frequency of uniparental disomy in Prader-Willi syndrome. METHODS: We performed molecular analyses using DNA markers within 15q11q13 and elsewhere on chromosome 15 in 30 patients with Prader-Willi syndrome who had no cytogenetically visible deletion. We also studied their parents. Three patients with Prader-Willi syndrome who had a cytogenetic deletion served as controls. RESULTS: In 18 of the 30 patients without a cytogenetic deletion (60 percent), we demonstrated the presence of maternal uniparental disomy for chromosome 15 and its association with advanced maternal age. In another eight patients (27 percent), we identified large molecular deletions. The remaining four patients (13 percent) had evidence of normal biparental inheritance for chromosome 15; three of these patients were the only ones in the study who had some atypical clinical features. CONCLUSIONS: In about 20 percent of all cases, Prader-Willi syndrome results from the inheritance of both copies of chromosome 15 from the mother (maternal uniparental disomy). With the combined use of cytogenetic and molecular techniques, the genetic basis of Prader-Willi syndrome can be identified in up to 95 percent of patients.

The Mr 115 kd fiber cell-specific protein is a component of the lens cytoskeleton.

Electron microscope level immunocytochemistry was used to localize a lens fiber cell-specific protein with an Mr of 115 kd. Affinity-purified polyclonal antibodies were utilized on sections of detergent-extracted, acrylic-embedded lens cortical fiber cells. Monoclonal antibodies were utilized for pre-embeddment labelling of a subcellular fraction of lens fiber cells generated by homogenization, and high-speed centrifugation. The results indicate that the Mr 115 kd antigen is a component of the lens fiber cell cytoskeleton, specifically the beaded filament (BF), a cytoskeletal element thought to be unique to the differentiated lens fiber cell.

[Inhibition of 24-hour acidity by nizatidine]. / Hemmung der 24-Stunden-Azidität durch Nizatidin.

In a randomized, double-blind, placebo-controlled, comparative cross-over study, we studied the effect of four H2-receptor antagonists on intragastric 24-hour acidity, nocturnal volume and acid output. Ten healthy male volunteers were administered 300 mg or 150 mg nizatidine, 800 mg cimetidine, 300 mg ranitidine, 40 mg famotidine, or placebo on several days, in each case at 9:000 PM. Nocturnal intragastric H+ concentration (mmol/l) (11:00 PM to 7:00 AM) was significantly reduced by all H2 blockers compared with placebo. We obtained the following inhibition rates: Cimetidine 67%; ranitidine 95%; famotidine 89%; nizatidine 80% (300 mg) and 69% (150 mg). Nocturnal acid (mmol/l) and volume output (ml/h) were also significantly (compared with placebo) inhibited by all four H2-receptor antagonists. Inhibition of nocturnal acid secretion was almost identical on nizatidine 300 mg nocte, ranitidine 300 mg nocte, famotidine 40 mg nocte, and cimetidine 800 mg nocte. Nizatidine 300 mg nocte and 150 mg nocte exclusively reduced acid secretion at night, without an aftereffect into the following day (8:00 AM to 6:00 PM). These results suggest that the clinical efficacy of these H2-receptor antagonists is identical with respect to healing peptic ulcer disease and providing freedom from pain. It is generally accepted today that gastric acid inhibitors used in the treatment of peptic ulcer disease should interfere with daytime gastric acid secretion as little as possible, particularly since the acid protects the stomach from bacteria ingested with the food during the day.

Ultrastructural studies of the early events of the human sperm acrosome reaction as initiated by human follicular fluid.

It has been suggested that the morphology of the human sperm acrosome reaction (AR) is markedly different from that of other mammalian sperm. The present study examines the fine structural events of the early stages of the human sperm AR as initiated by preovulatory human follicular fluid. Human sperm, capacitated in vitro for 6 hr at 40 degrees C (90% motility) were diluted with equal volumes of follicular fluid before fixing in cacodylate-buffered glutaraldehyde at 5, 10, 15, 20, and 180 sec. Fixed sperm were treated with either tannic acid or thiocarbohydrazine and OsO4. Over 2,000 sperm were viewed. By 5 sec, 2% of the sperm had initiated the AR. By 15 sec, 8% of the sperm were in some stage of the reaction, and after 180 sec 40% of the sperm had completed the acrosome reaction. The initial stages of the human AR are characterized by a swelling or decondensation of the acrosomal matrix. The fusion between the plasma membrane and outer acrosomal membrane begins at the most anterior tip of the head and progresses toward the equatorial segment. Fusion and fenestration ended at the equatorial segment. With thiocarbohydrazine + OsO4 fixation the fused membranes are distinct hybrid vesicles with the outer acrosomal membrane being far more electron dense. The acrosomal matrix is retained by 20 sec, but by 180 sec the matrix is completely dispersed, even when viewed after tannic acid fixation. Also by 180 sec, vesicles were being progressively lost. It is therefore concluded that the morphology of the human sperm AR, as initiated by human follicular fluid, is not unique, but is similar to that described for other mammalian sperm.

Partial characterization of a fraction from human follicular fluid that initiates the human sperm acrosome reaction in vitro.

A human follicular fluid (HFF) fraction prepared by Sephadex G-75 column chromatography has been previously shown by this laboratory to initiate the human sperm acrosome reaction (AR) in vitro. In the present report, the apparent molecular weight (MW) of this AR activity determined by a longer G-75 column than was used in the previous work was 50,000 +/- 5,106. The G-75 Sephadex void volume fractions of some but not all HFF samples were also found to contain some AR-initiating activity. The occasional void volume activity was less potent than that of the 50,000 MW fraction and was not studied further. Further characterization of the 50,000 MW fraction was carried out. A time-course study demonstrated that maximum AR were obtained within 5 min following the addition of the 50,000 MW fraction. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) followed by silver staining revealed that the 50,000 MW fraction was still a relatively crude preparation. Treatment of the 50,000 MW fraction with chloroform:methanol did not extract the AR-initiating activity into the lipid phase. The AR-initiating activity of the untreated 50,000 MW fraction was precipitated when it was boiled, but the activity was partially resistant to boiling after overnight incubation. Treatment of the 50,000 MW fraction with pronase E or with several glycosaminoglycan hydrolases did not destroy the activity. Pronase treatment resulted in a higher amount of boiling-resistant AR-initiating activity. The AR-initiating activity of the untreated 50,000 MW fraction was partially dialyzable, but the activity of an undialyzed fraction did not pass through an ultrafiltration membrane with a 10,000 MW cut-off. However, treatment of the 50,000 MW fraction with protease, peptide:N-glycosidase F, and to a lesser extent chondroitinase ABC yielded an active lower MW activity which could pass through such an ultrafiltration membrane. The lower MW activity released by peptide:N-glycosidase F eluted in the included volume (5,000-1,000) of a Sephadex G-25 column. Neutral hexose but not protein or peptide was detected in the G-25 peak of AR-initiating activity. These results suggest that the AR-initiating activity present in the 50,000 MW fraction of HFF: 1) is present either as two different AR factors (a high-MW factor and a low-MW, noncovalently bound factor) or as a single factor responsible for both the nondialyzable and dialyzable AR-initiating activities (the latter being enzymatically released from the former), and 2) may be at least partially associated with N-linked oligosaccharides of a glycoprotein or proteoglycan.

Nocturnal doses of ranitidine and nizatidine do not affect the disposition of diazepam.

The disposition of diazepam (D) after a single oral dose of 10 mg was evaluated in nine healthy male volunteers under the following conditions (randomized, double-blind, crossover design): D + comedication of placebo and D + nocturnal dosing with 300 mg ranitidine or 300 mg nizatidine. Plasma concentrations of D and its major active metabolite, desmethyldiazepam (DD), were monitored by a gas-liquid chromatography-electron-capture detection assay for 84 hours. Neither ranitidine nor nizatidine had any significant effect on the hepatic elimination of D as characterized by its terminal half-life (mean +/- SD) of 35.3 +/- 24.2 hours (+ ranitidine: 30.1 +/- 9.9 hr; + nizatidine: 37.3 +/- 18.3 hr) or total plasma clearance of 28.2 +/- 12.0 mL/min (+ ranitidine: 26.5 +/- 7.9 mL/min; + nizatidine: 26.7 +/- 10.4 mL/min). Likewise, the formation of DD as measured by its AUC was not affected by ranitidine or nizatidine. Thus, it can be concluded that concomitant once-daily dosing (300 mg nocturnally) with ranitidine or nizatidine does not impair hepatic drug metabolism.

Biochemical studies of metalloendoprotease activity in the spermatozoa of three mammalian species.

Ejaculated porcine and human spermatozoa, hamster spermatozoa from the cauda epididymidis, isolated hamster sperm heads and hamster cytoplasmic droplets contained activity that hydrolyzed the metalloendoprotease substrate ABZ-Ala-Gly-Leu-Ala-NBA (AAGLAN). Hamster sperm heads were isolated by treating spermatozoa with proteinase K and removing sperm tails with Dowex-50W beads. Hamster sperm activity was characterized using spermatozoa from which cytoplasmic droplets were removed by sonication and centrifugation. Porcine sperm preparations were essentially free of cytoplasmic droplets, while human sperm preparations retained somewhat more droplet material. Activity from all of these sources was inhibited by the metalloendoprotease inhibitors phosphoramidon, 1,10-phenanthroline, CBZ-D-Phe and CBZ-L-Phe but was not competitively inhibited by the metalloendoprotease substrate CBZ-Ser-Leu-amide. The AAGLAN hydrolyzing activity found in intact spermatozoa of all three species had a pH optimum of 6.2, while the optimum of the hamster sperm cytoplasmic droplet activity was 7.0. In addition, hamster sperm preparations were inhibited by ZnCl2 and dithiothreitol, but were not affected by toluene, benzamidine or chymostatin. The AAGLAN hydrolyzing activity of hamster sperm preparations was reduced, but not eliminated, by dialysis. It is concluded that spermatozoa from all three species, hamster sperm heads and hamster cytoplasmic droplets contain metalloendoprotease activity. Furthermore, metalloendoprotease activity found in hamster cytoplasmic droplets is different from that found in spermatozoa.

The 24-hour acid suppression profile of nizatidine.

To determine the antisecretory potency of bedtime doses of the new thiazole H2-receptor antagonist nizatidine in the suppression of nocturnal acid secretion, this randomized, cross-over, single-blind study was performed in 10 healthy male subjects. The actions of a single bedtime (2100 h) dose of the H2-receptor antagonist nizatidine (150 mg and 300 mg), ranitidine (300 mg), cimetidine (800 mg), and famotidine (40 mg), as well as placebo on nocturnal gastric acid and volume secretion (2400 to 0600 h) and on overall 24 h H+-ion concentration were studied. Compared with placebo, night-time (2300 to 0700 h) H+ ion concentration was reduced by 70, 79, 95, 75, and 89% (p less than 0.05 to p less than 0.01). Nocturnal acid secretion, too, was significantly lower for the H2-blockers than for placebo (p less than 0.01). A significant reduction in total night-time gastric volume secretion was observed (p less than 0.01). Nizatidine 300 mg nocte, ranitidine, cimetidine and famotidine had no significant carry-over effects on daytime acidity (0800 to 1800 h). No significant pharmacodynamic differences between nizatidine 300 mg nocte, ranitidine 300 mg nocte, cimetidine 800 mg nocte and famotidine 40 mg nocte were observed. Thus, it may be concluded that these four H2-blockers will be equally effective in accelerating peptic ulcer healing and pain relief.

Nocturnal acid suppression with a new H2 receptor antagonist--nizatidine.

To determine the potential efficacy of bedtime doses of the new furan H2 receptor antagonist nizatidine in the suppression of nocturnal acid secretion, this randomized, crossover, single-blind study was performed in 10 healthy male subjects. The actions of a single bedtime (21:00 hour) dose of the H2 receptor antagonists nizatidine (150 mg and 300 mg), ranitidine (300 mg) and cimetidine (800 mg), as well as placebo on nocturnal gastric acid and volume secretion (01:00 to 07:00 hours, and on overall 24 hour H+ ion concentration were studied. Compared with placebo, night-time (23:00 to 07:00 hours) H+ ion concentration was reduced by 70, 79, 95, and 76% (p less than 0.05-p less than 0.01). Nocturnal acid secretion, too, was significantly lower for the H2 blockers than for placebo (p less than 0.05-p less than 0.01). A significant reduction in night-time gastric volume secretion was observed in the hourly intervals from 04:00 to 07:00 hours and in total volume in the whole 6 hours period (p less than 0.05-p less than 0.01). Nizatidine 300 mg nocte, ranitidine and cimetidine significantly decreased H+ concentration for only 1 hour (08:00 to 09:00 hours, p less than 0.05-p less than 0.01) during the subsequent daytime period (08:00 to 13:00 hours). Since no significant pharmacodynamic differences between nizatidine 300 mg nocte, cimetidine 800 mg nocte and ranitidine 300 mg nocte were observed, it may be concluded that at the doses employed, these three H2-blockers will all be similarly effective in the acute therapy of peptic ulcer disease.

Medical instrumentation and nosocomial infection.

A current major concern of the medical community is the incidence of nosocomial, or hospital-related infection. One of the chief ways a patient may get a nosocomial infection is through medical instrumentation which has been improperly sterilized or incorrectly utilized. The clinical engineer, because of his critical involvement with medical instrumentation, must, in addition to his conventional duties, instruct hospital personnel in the proper sterilization and use of medical instrumentation. In order to accomplish this, the clinical engineer must understand the relationship between nosocomial infection and medical instrumentation, and he must become familiar with basic sterilization procedures as they apply to each class of medical instrumentation.