Search PubMed⌕ Search

Biomedical subjects

C Lauritzen

Publications and source records attributed to C Lauritzen.

At least 37 records · Page 2Linked to original sources

The long-term tolerability and efficacy of OESCLIM: results of a 1-year study.

OBJECTIVES: A 1-year, open-label, non-comparative study evaluated the long-term tolerability and acceptability of a new generation matrix patch in post menopausal women with estrogen deficiency. METHODS: Menopausal women (224) from 37 centres in five European countries received OESCLIM 50 microg/d (17-beta estradiol) for 3 months, titrated if necessary to either 25 or 100 microg/d for a further 9 months. Patients received either a continuous or discontinuous estradiol regimen with concomitant sequential progestogen (except hysterectomised patients). Skin tolerability was assessed by patient diaries and questionnaires. Global tolerability, efficacy, laboratory parameters and global acceptability were also monitored. RESULTS: Almost two-thirds of women did not experience any kind of skin reaction and only 4.3% of all applications (752/17,702) caused site reactions. Of these, the majority caused only slight or no discomfort (63.2%). Only 0.37% of total applications required patch removal; none required therapy. A low percentage of patients withdrew due to tolerability issues: 2.7% due to skin reactions; 7.5% due to hyperestrogenism. The mean number of hot flushes experienced by symptomatic women reduced by 91% from 4.0 at baseline to 0.4 after 2 months. Total cholesterol reduced by 3.9% and LDL cholesterol by 5.1%, with no increase in triglyceride levels. Investigators assessed treatment as effective in 96.8% of cases; well tolerated locally in 93.1% and well tolerated generally in 89.5%. At the end of this 1 year study, 79% of patients wished to continue therapy. CONCLUSION: OESCLIM is well tolerated locally and systemically in long-term therapy with a high proportion of patients wishing to continue therapy after 1 year.

Administration, Cutaneous↗

Treatment of sleep apnoea with continuous positive airway pressure in children with craniofacial malformations.

We conducted sleep studies in a consecutive series of 21 children with craniofacial malformations and suspected obstructive sleep apnoea. Thirteen had sleep apnoea, and one patient with a tracheostomy could not be tested. Twelve children were admitted for initiation of treatment with nasal continuous positive airway pressure (nCPAP). Ten patients accepted nCPAP, two did not. Seven children use home treatment successfully. Obstructive sleep apnoea in most children is completely eliminated with nCPAP. The treatment is safe, effective, and leads to a reduction in the number of operations done for children with craniofacial malformations. Aesthetic operations can be delayed until facial growth is complete.

Child↗

Reconstruction of eyelid defects: a prefabricated multilayer sandwich graft.

We have developed a new technique for reconstruction of full thickness eyelid defects. A composite three-layer skin-cartilage-mucosal unit is manufactured and tailored three-dimensionally. Use of this sandwich graft in our patients proved to be simple and safe for eyelid reconstruction and has given good results without complications in four patients.

Adult↗

13C NMR, X-ray, and differential scanning calorimetry investigations of truncated BPTI (aprotinin) analogues.

Truncated BPTI missing residues 1 and 2 is investigated together with variants thereof (Lys-15, Arg-17, and Arg-42 are replaced by other residues in various combinations). A comparison of the X-ray structure of BPTI with that of 3-58BPTI(K15R,R17A,R42S) shows only minor variations for the backbone, but the lack of salt bridge between the terminals and the lack of two N-terminal residues provide a structure open at one end. Comparisons of amide exchange rates show a dramatic increase for the most slowly exchanging NH protons of 3-58BPTI and the analogues thereof, as compared to those of the wild-type despite only small differences in the structures. The amide exchange rates for truncated analogues increase with decreasing TTEP (temperature top endothermic peak) values. On the basis of the known structural changes comparisons to 13C chemical shifts are made. 13C chemical shifts are assigned using the D-isotope and HMBC techniques. Excellent resolution is obtained in these 1D natural abundance spectra. 13C NMR chemical shifts are shown to be able to gauge structural changes. A comparison of 13C chemical shifts of WT BPTI (aprotinin) and 3-58BPTI reveals effects caused by (i) the removal of the salt bridge of the terminii, (ii) the charge of the N-terminus, and (iii) the increased mobility of the side chain of Tyr-23. Small effects are also seen due to a conformational change of the aromatic ring of Phe-4. Ring current shifts at 13C chemical shifts are calculated. The difference in the calculated ring current effects are small comparing the wild-type with 3-58BPTI(K15R,R17A,R42S) provided the structures are relaxed. Protein unfolding as a function of pH and temperature is studied by DSC. Unfolding occurs at lower temperature with N-terminally truncated analogues, and the maximum is shifted toward higher pH.

Amino Acid Substitution↗

Active recombinant rat dipeptidyl aminopeptidase I (cathepsin C) produced using the baculovirus expression system.

An active form of rat dipeptidyl aminopeptidase I (DPPI, cathepsin C) was obtained by heterologous expression in insect cells. Baculoviruses carrying a cDNA sequence encoding the entire rat DPPI precursor was used to infect High Five cells in a serum-free medium. Recombinant DPPI (rDPPI) was secreted into the medium from which it was purified by a combination of ammonium sulfate fractionation, hydrophobic interaction chromatography (HIC), and ion-exchange chromatography. A polyhistidine-tagged form of the enzyme (HT-rDPPI) was purified from the medium by immobilized metal affinity chromatography (IMAC). In vivo activation of native rat DPPI involves at least three chain cleavages per subunit and the ability of the expression system to imitate this processing was investigated. Both rDPPI and HT-rDPPI were secreted into the medium as unprocessed and inactive proenzymes and gradually converted into their active forms in the medium. This process was not completed at the time of harvest but mature enzyme processed similarly to native rat and human DPPI could be obtained by incubating the eluates from the HIC and IMAC columns at pH 4.5 and 5 degrees C for 18-40 h. The yield of purified and matured enzyme was approximately 50 mg/liter, and it was shown that rDPPI and HT-rDPPI were active against both a dipeptide-p-nitroanilide substrate and human growth hormone N-terminally extended with an Ala-Glu dipeptide.

Animals↗

Spring mediated dynamic craniofacial reshaping. Case report.

A new technique of using implantable springs as an adjunct after corrective surgery for craniofacial malformations is presented. A 6-month-old boy with multiple premature craniosynostoses and extreme turricephaly underwent surgery of limited extensiveness but supplemented with a set of indwelling springs for gradual postoperative skull reshaping. At spring removal three months later the skull was normalised both clinically and on cephalogram. A 5-year-old boy with Apert syndrome, severe midface retrusion, exorbitism, and sleep apnoea underwent a monobloc full face disjunction without repositioning, but was fitted with two springs for postoperative facial advancement. Three months postoperatively cephalometric analysis revealed 14 mm advancement at incisor level and at least 16 mm in the frontal region. There was no more exorbitism or clinically noticeable midface retrusion. Sleep studies revealed that the sleep apnoea was significantly improved, meaning complete cure except when sleeping flat on the back. It was concluded from these first clinical applications of spring assisted craniofacial distraction that springs hold significant promise for the future in many respects.

Acrocephalosyndactylia↗

Reuse of tumorous calvarial bone after gamma irradiation.

Reconstruction of calvarium after tumor resection may present several technical difficulties. The authors reused the resected calvarial bone in four patients after submitting the bone to a lethal dose of gamma radiation. The authors conclude that resected, irradiated, tumorous bone can be reused for the reconstruction of its own defect. This provides a simple method of reconstruction. Partial bone resorption should be anticipated but further reconstruction, if needed, will be facilitated.

Adult↗

[Estrogen-gestagen substitution in geriatric gynecology. Long-term prevention for the third segment of life after menopause].

On average, post-menopausal women still have one-third of their lives ahead of them. It must be considered a task for the physician through the prophylactic and therapeutic application of estrogen (gestagen) replacement to secure for these women as high a quality of life as possible. The positive effects of replacement treatment affect, for example, the cardiovascular system, the urogenital system, osteoporosis and cognitive and mental functions. An absolute indication for estrogen replacement is very pronounced climacteric symptomatology that negatively influences the patient's quality of life, further marked complaints resulting from atrophic changes to the urogenital system, and manifest osteoporosis at the time of the menopause. Over and beyond this, numerous additional indications for such treatment can be listed, with only few contraindications.

Aged↗

Roentgencephalometric follow-up after early osteotomies in patients with scaphocephaly.

The main objective of surgical treatment of scaphocephaly is to improve the shape of the patient's skull. Since 1989 we have used a modified pi-plasty method, and the aim of this report was to study how effective surgery had been. A sample of 25 patients was investigated. All patients were operated on during their first year of life (mean: 6 months). They had roentgencephalometric records preoperatively as well as at a follow-up at age 3 years. Certain measurements were taken from the cephalograms and compared with normative data. It was found that the average skull length had decreased from a preoperative 114% of normal to 107% at follow-up. The skull width had improved from 92% to 98% of normal. The cephalic index had improved as well but was still not within the normal range. The cephalograms were also classified according to the occurrence of digital markings. Before surgery at 6 months none had these signs, but at follow-up every second patient displayed evolution of digital markings. It was concluded that the modified pi-plasty method improves skull morphology considerably but does not completely normalize the shape of the average patient's skull. The cranial length, in particular, needs further improvement.

Cephalometry↗

Dynamic cranioplasty for brachycephaly.

In craniofacial surgery, the most common techniques for treatment of brachycephaly have been either to let the forehead float on the brain or to fix it in an advanced position. Since neither of these techniques renders acceptable results with enough consistency, we have developed a different way of addressing the problem. In principle, the design of the operation is to restrict upward and transverse growth of the cranium but to allow anterior and posterior expansion. This is accomplished by producing transverse tension across the skull and letting it expand anteriorly by means of a superiorly hinged fronto-orbital flap and posteriorly by an inferiorly based occipital flap. To prevent upward expansion at the squamosal sutures when still open, these junctions are bridged with miniplates. This surgical technique has brought definite improvement to the results even in some Apert syndrome children. During a 2-year period, we have treated 14 infants with this technique and followed 10 of them with roentgencephalometry, 3 for more than 1 year, and 4 for more than 6 months. The diagnoses were the following: nonsyndromal bicoronal synostosis (4), Apert (7), bicoronal synostosis with midline cleft, Saethre-Chotzen, and Antley-Bixler (1 each). The mean age of surgery was 6.6 months (range 3 to 16 months). There were no major complications.

Acrocephalosyndactylia↗

Craniofacial dysostosis: airway obstruction and craniofacial surgery.

Craniofacial surgery in craniofacial dysostosis on airway obstruction was studied retrospectively in a consecutive series of patients. The records of 76 patients were reviewed, 27 with Apert syndrome, 47 with Crouzon's syndrome, and two with Pfieffer's syndrome. Of 172 operations, 148 were done for cosmetic reasons, hydrocephalus, or papillary oedema, and 24 were done for airway distress. Forty patients (23%) were children less than 13 years of age, and 22 underwent midface advancement procedures. Only 13 of these operations had been done for airway distress. Two were cured by operation and seven improved. After operation had failed to relieve the airway obstruction, a nasal continuous positive airway pressure device (nCPAP) was fitted to seven patients. The nCPAP relieved or improved airway obstruction recorded by a sleep study. As midface advancement in childhood rarely results in lasting improvement in breathing or aesthetics, it may well be advisable to postpone operation until the early teens. We conclude that with nCPAP operation can in most cases be deferred until a time when a permanent result can be achieved.

Airway Obstruction↗

HRT prescribing guidelines: dream or reality?

An international round-table meeting was held in the UK in June 1995, with the aim of developing simple, practical guidelines for hormone replacement therapy (HRT). Great emphasis was placed on initial and on-going counselling as a means of promoting compliance. The choice of preparation will depend on whether the patient has an intact uterus, and, if so, whether she is willing to accept regular bleeding. Hysterectomized women should receive continuous estrogen alone, while, for non-hysterectomized women, the first choice of treatment is continuous estrogen with sequential progesterone for at least 10 days in each month. Continuous combined treatment may be given as an alternative. Symptomatic side effects are most likely to occur at the beginning of treatment and can usually be easily managed by a change in the preparations. Despite misleading information in package inserts, there are few absolute contra-indications to HRT.

Contraindications↗

Osteopenia in primary and secondary amenorrhea.

This study aimed at investigating the prevalence of osteopenia among a hypoestrogenic group of patients with primary or secondary amenorrhea. Twenty-seven patients with amenorrhea were examined. Sixteen of them presented with secondary amenorrhea (mean age 27.8 +/- 1.9 yrs), and 11 with primary amenorrhea (mean age 21.3 +/- 1.6 yrs). Ten regularly menstruating women (mean age 28.9 +/- 1.4 yrs) served as controls. Estradiol serum levels as well as lumbar spine bone mineral density were measured. All 11 patients with primary amenorrhea showed osteopenia with a mean bone mineral density Z-score of 71 +/- 2% and mean estradiol levels of 30.6 +/- 5.9 pg/ml. The secondary amenorrheic patients were significantly demineralized with a mean Z-score of 82 +/- 3%; 10 of them had osteopenia. Their mean estradiol levels were 34.3 +/- 2.9 pg/ml. The bone density in the primary amenorrheic patients was significantly lower as compared with the secondary amenorrheic women. In comparison, lumbar spine bone density in all control women was normal with a mean Z-score of 104 +/- 3%. In summary, 21 of the 27 patients had osteopenia, higher than that reported in post-menopausal women. Since it is not proven whether the bone mineral deficit of amenorrheic patients can ever be compensated, early diagnostic steps and estrogen-progestogen replacement for the prevention of further bone loss and subsequent fractures are recommended.

Adolescent↗

[Splenopeptides for climacteric complaints. Comparison of ovarian stimulation with transdermal estradiol substitution].

256 women aged 45 to 60 years with climacteric complaints participated in an open randomized clinical study comparing spleno-peptides (SPS 1187, Solcosplen) with transdermal estrogen (CAS 50-28-2, E2) substitution (4 mg) in respect of efficacy and tolerability. The primary criterion, defined as the Kupperman Index, and the safety parameter of the drugs were estimated prior to and after 1, 4 and 8 weeks of therapy. In the pre-, peri- and early postmenopause the results of treatment with the spleno-peptides were comparable to those with transdermal E2 substitution (4 mg). Pretreatment with estrogens impaired the results of treatment significantly. Although the menopausal status (in most cases < 3 years) did not influence the results essentially, the efficacy of SPS 1187 is expected to decrease 2 to 3 years postmenopause. Therefore SPS 1187 should be used in pre-, peri- and early postmenopause only. The tolerance of SPS 1187 was found to be significantly better than that of the E2 patch. With respect to the claimed indication, i.e. climacteric complaints in the pre-, peri- and early postmenopause, SPS 1187 having an equivalent efficacy compared to that of the E2 patch shows a better tolerability (total collectives) and better benefit/risk ratio.

Administration, Cutaneous↗