Treatment for hereditary angioedema with normal C1-INH and specific mutations in the F12 gene (HAE-FXII).

Hereditary angioedema with normal C1 esterase inhibitor and mutations in the F12 gene (HAE-FXII) is associated with skin swellings, abdominal pain attacks, and the risk of asphyxiation due to upper airway obstruction. It occurs nearly exclusively in women. We report our experience treating HAE-FXII with discontinuation of potential trigger factors and drug therapies. The study included 72 patients with HAE-FXII. Potential triggers included estrogen-containing oral contraceptives (eOC), hormonal replacement therapy, or angiotensin-converting enzyme inhibitors. Drug treatment comprised plasma-derived C1 inhibitor (pdC1-INH) for acute swelling attacks and progestins, tranexamic acid, and danazol for the prevention of attacks. Discontinuation of eOC was effective in 25 (89.3%) of 28 women and led to a reduction in the number of attacks (about 90%). After ending hormonal replacement therapy, three of eight women became symptom-free. Three women with exacerbation of HAE-FXII during intake of quinapril or enalapril had no further HAE-FXII attacks after discontinuation of those drugs. Eleven women were treated with pdC1-INH for 143 facial attacks. The duration of the treated facial attacks (mean: 26.6 h; SD: 10.1 h) was significantly shorter than that of the previous 88 untreated facial attacks in the same women (mean: 64.1 h; SD: 28.0 h; P < 0.01). The mean reduction in attack frequency was 99.8% under progestins after discontinuing eOC (16 women), 93.8% under tranexamic acid (four women), and 100% under danazol (three women). For patients with HAE-FXII, various treatment options are available which completely or at least partially reduce the number or duration of attacks.

Sleep disturbance in patients taking opioid medication for chronic back pain.

Poor sleep is an increasingly recognised problem with chronic pain and further increases the effect on daily function. To identify the relationship between chronic pain, opioid analgesia and sleep quality, this study investigated activity and sleep patterns in patients taking opioid and non-opioid analgesia for chronic back pain. Thirty-one participants (10 healthy controls, 21 patients with chronic pain: 6 on non-opioid medication; 15 on opioid medication) were assessed using actigraphy, polysomnography and questionnaires. Patients with chronic pain subjectively reported significant sleep and wake disturbances as shown by decreased overall sleep quality (Pittsburgh Sleep Quality Index, p < 0.001), increased symptoms of insomnia (Insomnia Severity Index, p < 0.001) and increased fatigue (Fatigue Severity Scale, p = 0.002). They also spent increased time in bed (p = 0.016), took longer to get to sleep (p = 0.005) and had high interindividual variability in other measures of activity but no overall irregular rest-activity pattern. Patients on high doses of opioids (> 100 mg morphine-equivalent/day) demonstrated distinctly abnormal brain activity during sleep suggesting that polysomnography is necessary to detect sleep disturbance in this population in the absence of irregular rest-activity behaviour. Night-time sleep disturbance is common in individuals suffering from chronic pain and may be further exacerbated by opioid treatment. Considerations must be made regarding the appropriate use of combined actigraphy and miniaturised polysomnography for future population-based studies.

Long-term FVII substitution in a preterm infant with severe gastrointestinal bleeding and FVII deficiency due to a homozygous donor splice mutation IVS4+1G-->A.

Congenital FVII deficiency is a rare bleeding disorder. Clinical complications are similar to those seen in hemophilia A, and an increased incidence of intracerebral hemorrhage related to birth trauma has been reported. The authors report on an infant who presented at the second day of life with melaena and hematemesis caused by congenital FVII deficiency with minimal activity of 4%. A homozygous mutation IVS4+G-->A, formerly described in 2 siblings, who died of brain hemorrhage within the first month of life, was identified. Severe bleeding events were prevented with prophylactic treatment. Early identification of the underlying mutation helps to assess the risk of hemorrhage and prevent severe bleeding by prophylactic FVII therapy.

Thrombosis in inherited factor VII deficiency.

Thrombosis in congenital factor (F) VII deficiency was investigated through extensive phenotypic and molecular-genetic studies. Patients with a history of thrombosis among 514 entries in the FVII Deficiency Study Group database were evaluated. Thrombotic events were arterial in one case, disseminated intravascular coagulation in another and venous in seven. Gene mutations were characterized in eight patients: three were homozygous, three compound heterozygous and two heterozygous. FXa and IIa generation assays were consistent with the genetic lesions. One patient was heterozygous for the FV Leiden and one for the FIIG20210A mutation. In seven patients, surgical interventions and/or replacement therapies had a close temporal relationship with thrombosis, while in the remaining, events were apparently spontaneous. Thromboses were not associated with any specific age, phenotype, mutation zygosity or thrombophilic abnormalities. In particular, severe FVII deficiency did not seem to offer protection from strong thrombosis risk factors such as surgery and replacement therapy.

Expression of N-acetyltransferases in periodontal granulation tissue.

Smoking is a major risk of periodontal diseases. At the site of first contact, the gingiva is exposed to aromatic amines and polycyclic hydrocarbons. These are metabolized by the N-acetyltransferases (NAT), leading to local detoxification and/or activation reactions contributing to the risk of periodontal destruction in smokers. The purpose of this study was to detect the expression of N-acetyltransferase isoenzymes NAT1 and NAT2 in periodontal granulation tissue. In 24 specimens obtained from periodontitis patients or control subjects, mRNA encoding for NAT1 and NAT2 was detected by RT-PCR, and proteins were identified by immunohistochemistry. In periodontal granulation tissues, immunoreactivity for NAT1 and NAT2 was detected in infiltrating leukocytes and fibroblasts. In normal gingiva, both enzymes were found in epithelial cells, whereas NAT1 was also detected in endothelial cells. The results suggest that these enzymes may play a role in the defense against xenobiotics and the accelerated progression of periodontal disease in smokers.

Occupational exposure and voluntary human immunodeficiency virus testing: a survey of Maryland hospitals.

A survey was conducted to estimate how often healthcare providers were exposed to patients' blood and the percentage of incidents in which patients agreed to human immunodeficiency virus (HIV) testing. Data from 38 hospitals with 53,508 employees revealed 2,244 exposures. Of 1,732 requests for information regarding the HIV status of the source patient, only 77 (6%) resulted in the patient's refusal to consent to an HIV test.

Worst-Fechner biconcave minus power phakic iris-claw lens.

OBJECTIVE: Evaluation of long-term results of correction of high myopia by implantation of a biconcave Worst-Fechner minus power iris-claw lens into phakic eyes. METHODS: One hundred and twenty-seven eyes of 70 patients were implanted with the phakic IOL between November 1986 and November 1991. The mean preoperative spherical equivalent refraction was -14.29 +/- 5.77 D (range -5.00 to -31.75 D). The total population decreased from 127 to 68 eyes (53.5%) at the 8-year examination. By this time, 26 of the 70 patients (37%) had been lost to follow-up for unknown reasons. Corneal endothelial density was estimated by comparing the image gained by non-contact specular microscopy with a graduated reticule (Karickhoff method). RESULTS: At the 6-month examination, mean deviation of achieved from calculated refractive correction was +0.52 +/- 1.46 D (range -2.25 to +6.50 D). Seventy-seven eyes (62.1%) deviated 1.00 D or less, and 15 eyes (12.1%) deviated by more than 2.00 D from the calculated correction. A refractive outcome of +/- 1.00 D was attempted in 68 eyes (54% of the 124 eyes) and was achieved in 51 eyes (75%). Mean spectacle-corrected visual acuity preoperatively was 0.54 +/- 0.27 (range 1.20 to 0.05). At the 6-month examination it was 0.73 +/- 0.3, and by the 8-year examination had decreased to 0.65 +/- 0.26. Statistical analysis of corneal endothelial cell density revealed a significant correlation of endothelial cell loss with age (> or = 45 years), anterior chamber depth (< or = 3.4 mm), and IOL power (> or = -11.00 D). Seventeen eyes (13.4%) had a decrease in endothelial cell density and projection to 8-year follow-up resulted in a decrease in 27% of eyes. Four eyes needed a penetrating keratoplasty. CONCLUSION: Implantation of a biconcave Worst-Fechner lens into a phakic eye effectively corrected high myopia with a stable refractive outcome, but 13.4% of implanted eyes suffered significant progressive reduction of endothelial cell density. This style lens is no longer in clinical use.

Iris-claw lens in phakic eyes to correct hyperopia: preliminary study.

PURPOSE: To evaluate the results of implanting convex, iris-fixated, anterior chamber intraocular lenses (IOLs) in phakic eyes to correct high hyperopia. SETTING: Robert Koch Hospital, Hannover-Gehrden, Germany (Center A), and Dr. Daljit Singh Eye Hospital, Amritsar, India (Center B). METHOD: Two eyes at Center A and 67 at Center B had implantation of an anterior chamber, convex, iris-fixated IOL. Follow-up of the 2 eyes at Center A was 91 months. Mean follow-up at Center B was 78 months +/- 24 (SD) (range 12 to 120 months). RESULTS: At Center B, all eyes except two in one patient had clear corneas and no iritis or glaucoma at the last follow-up. The patient with complications (glaucoma and corneal degeneration in both eyes) did not return for follow-up until more than 4 years postoperatively and thus did not have adequate postoperative care. CONCLUSION: Implantation of a convex iris-claw lens into the anterior chamber of phakic eyes to correct high hyperopia was successful from a refractive aspect. The clinical risks appear tolerable. However, life-long observation by endothelial microscopy is mandatory.

Relationship between human genotype and phenotype of N-acetyltransferase (NAT2) as estimated by discriminant analysis and multiple linear regression: 1. Genotype and N-acetylation in vivo.

Twenty-six healthy Caucasian subjects were evaluated for polymorphic N-acetyltransferase (NAT2) metabolic activity in vivo by sulfamethazine phenotyping and for their respective NAT2 genotype. Application of discriminant analysis allowed the separation of the rapid and slow acetylators solely on the base of their respective mutation pattern with identical results as achieved by the classical method of discrimination according to the phenotyping results. Multiple linear regression analysis was used to obtain a quantitative relationship between allelic pattern and the phenotypic outcome. It is shown that the computation methods produce relationships enabling the influence of particular mutations and/or allelic configurations on the metabolic activity in vivo to be estimated. This may be important in cases of discordant or overlapping phenotype and genotype results as well as in investigating the NAT2 polymorphism as a risk factor for cancer and other disease in epidemiological studies.

[Gastroesophageal reflux and "near miss" sudden infant death syndrome]. / Gastroøsofageal refluks og "near miss" pludselig uventet spaedbørnsdød-syndrom.

A case of an infant with gastro-oesophageal reflux is presented. Her symptoms, which were very similar to those of "near miss" sudden infant death syndrome (SIDS), were resolved by antireflux surgery. Two of her brothers died with the diagnosis SIDS.

Haemophilia B in female twins caused by a point mutation in one factor IX gene and nonrandom inactivation patterns of the X-chromosomes.

Haemophilia B is a X-linked recessive bleeding disorder with an incidence of 1:25,000-30,000 male birth. Usually female carriers are clinically normal. Phenotypic expression of the disease in female carriers is extremely rare. We describe cytogenetically inconspicuous female identical twins both with factor IX levels below 2%, prolonged bleeding after venipuncture as well as haematomas after intramuscular injections. The father, suffering from a severe haemophilia B, is deceased. By sequencing one point mutation was characterized in heterozygote condition in the factor IX gene of the probands at nt 17678. This mutation leads to the substitution cystein 88 to tyrosine in the growth factor domain of the factor IX. Investigation of the X-chromosomal inactivation by comparison of methylation patterns of genomic DNA at locus DXS255 after digestion with Pst I and Pst I +Hha I and hybridisation with the probe M27beta indicated a nonrandom pattern of X-chromosomal inactivation in the twins. In both girls, only the paternal X-chromosome was the active one leading to the phenotypic expression of haemophilia in the female carriers.

[Ataxia telangiectasia]. / Ataxia telangiectasia.

Ataxia telangiectasia is a genetically determined multi-system disorder in which senile skin changes are at an early stage. The patients have progressive neurological disability, cellular and humoral immunodeficiencies and increased cancer incidence. Heterozygous carriers of the gene, estimated to comprise about 1% of the general population, have an increased risk of cancer. We have initiated an identification of a cohort of patients and their relatives in order to evaluate their cancer risk.

[Early treatment with nasal continuous positive airway pressure and "minimal handling". Early and late prognosis in children with birth weight under 1,501 g]. / Tidlig behandling med nasalt kontinuerligt overtryk i luftvejene og "minimal handling". Tidlig- og senprognose hos børn med fødselsvoegt < 1.501 g.

During 1988 and 1989 a regional cohort of 81 infants with birth weights of less than 1501 g were treated with oxygen (n = 11), early continuous positive airway pressure (CPAP) (n = 68) or mechanical ventilation from birth (n = 2). We used an easily applicable lightweight CPAP system with nasal prongs and a gas jet supplemented with ventilator treatment if necessary, but with conservative criteria for ventilator treatment with tolerance of high PCO2. A total of 65 infants (80%) survived to discharge, 61 of whom were supported solely with CPAP or oxygen. Nineteen infants (26%) developed periventricular-intraventricular haemorrhage, but only four survivors (6%) developed prognostically significant bleedings of grade 2-4. No survivors had bronchopulmonary dysplasia. Follow-up at 1.5-5 years of age revealed definite disabilities in seven (11%). The results suggest that treatment by early CPAP with nasal prongs with tolerance of high PCO2 may be effective and lenient in most infants of more than 25 weeks' gestation.

[Trichothiodystrophy. Hair examination as a diagnostic tool]. / Trikotiodystrofi. Hårundersøgelse som nøgle til diagnoser.

Trichothiodystrophy is a neuroectodermal syndrome with features of a specific hair dysplasia associated with disorders in organs derived from ectoderm and neuroectoderm. The key finding is brittle hair with low sulfur content. Polarizing microscopy shows alternating dark and light bands with trichoscisis and absent or defective cuticle. Patients with trichothiodystrophy have short, sparse, dry and easily broken hair. Growth retardation and mental retardation are almost obligatory findings. The skin and the nails are very often affected; other neuroectodermal disorders are associated, but none is a constant feature. The disease is transmitted as an autosomal recessive trait.

Early treatment with nasal continuous positive airway pressure in very low-birth-weight infants.

During 1988 and 1989, a regional cohort of 81 infants with birth weights less than 1501 g were treated with oxygen only (n = 11), early continuous positive airway pressure (CPAP) (n = 68) or mechanical ventilation from birth (n = 2). We used an easily applicable lightweight CPAP system with nasal prongs and a gas jet supplemented with ventilator treatment if necessary, but with conservative criteria for ventilator treatment with tolerance of high PCO2. A total of 65 infants (80%) survived to discharge, 61 of whom were supported solely with CPAP or oxygen. Nineteen infants (26%) developed periventricular-intraventricular haemorrhage, but only 4 survivors (6%) developed prognostically significant bleedings grade 2-4. No survivors had bronchopulmonary dysplasia. Follow-up at 12-39 months of age revealed definite disabilities in 6 (10%) and suspected disabilities in 2 of 62 long-term survivors. The results suggest that treatment by early CPAP with nasal prongs with tolerance of high PCO2 may be effective and lenient in most infants more than 25 weeks' gestation.

[The properties and potential uses of the trimesic acid dosimeter]. / Eigenschaften und Anwendungsmöglichkeiten des Trimesinsäuredosimeters.

The trimesic acid dosimeter developed by Matthews is extremely sensitive to ionizing radiation. Tests on the characteristics of this detector show two serious differences to the Fricke dosimeter. With trimesic acid (1, 3, 5-benzentricarboacid) absorbed doses can be detected which are 1000 times smaller than with the Fricke solution. The radiochemical turnover here, as opposed to the Fricke dosimeter, is dependent on the dose rate up to 2.2 Gy/min. With high dose rates the trimesic acid dosimeter is well suitable for thin-layer dosimetry. For example in front of metallic scattering bodies (Al, Ti, Cu, Mo, Ag, W, Pb) exposed to cobalt-60-gamma, 9- and 15-MV bremsstrahlung and electron radiation with initial energies of 6.0, 8.0, 10.0 and 19.45 MeV the back scatter radiation can be measured easily.

RFLP analysis for diagnosis of haemophilia A in the German Democratic Republic.

The frequencies of Bcl I, Hind III and Xba I intragenic polymorphic sites in the population of the GDR were found to be 0.68, 0.38 and 0.48, respectively. No differences in composition and frequencies were detectable at DXS 52 locus in comparison with other Caucasian populations. A strong linkage disequilibrium between the intragenic Bcl I and Hind III sites could be confirmed. The observed heterozygosity for the flanking marker DXS 52 in combination with intragenic Bcl I and Xba I polymorphisms was 0.97. Using these three RFLPs, 122 females at risk in 41 independent haemophilia A families were investigated; 86 of them could be identified and 27 excluded as carriers; 9 females could not be classified. So far, four prenatal diagnoses in the first trimester of gestation have been performed by RFLP analysis.

Deletion screening in patients with Duchenne muscular dystrophy.

DNA of 35 patients with Duchenne muscular dystrophy (DMD) from 27 unrelated families from the northern part of GDR, Czechoslovakia and Hungary were analysed by means of 9 genomic probes and cDNA probes Cf 23a and Cf 56a, which detect exons of the central part of the DMD gene. Of the unrelated DMD patients, 63% have deletions for one or more intragenic and/or cDNA probes and 33% have deletions for genomic probes, mostly for pERT 87 (15%) and P 20 (15%). 48% of the DMD patients have deletions for one or more exon regions detected by Cf 56a and Cf 23a. The deletions were mapped. The genomic probe P 20 and the distal part of the cDNA probe Cf 23a detected the same part in the centre of the DMD gene. The deletions are heterogeneous in size and extent. In patients of the same family, identical deletions were detected in the DMD gene. The detection of deletions is useful for prenatal diagnosis and carrier detection.