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M David

Publications and source records attributed to M David.

At least 19 recordsLinked to original sources
PubMed2006

Quantification of atelectatic lung volumes in two different porcine models of ARDS.

BACKGROUND: Cyclic recruitment during mechanical ventilation contributes to ventilator associated lung injury. Two different pathomechanisms in acute respiratory distress syndrome (ARDS) are currently discussed: alveolar collapse vs persistent flooding of small airways and alveoli. We compare two different ARDS animal models by computed tomography (CT) to describe different recruitment and derecruitment mechanisms at different airway pressures: (i) lavage-ARDS, favouring alveolar collapse by surfactant depletion; and (ii) oleic acid ARDS, favouring alveolar flooding by capillary leakage. METHODS: In 12 pigs [25 (1) kg], ARDS was randomly induced, either by saline lung lavage or oleic acid (OA) injection, and 3 animals served as controls. A respiratory breathhold manoeuvre without spontaneous breathing at different continuous positive airway pressure (CPAP) was applied in random order (CPAP levels of 5, 10, 15, 30, 35 and 50 cm H(2)O) and spiral-CT scans of the total lung were acquired at each CPAP level (slice thickness=1 mm). In each spiral-CT the volume of total lung parenchyma, tissue, gas, non-aerated, well-aerated, poorly aerated, and over-aerated lung was calculated. RESULTS: In both ARDS models non-aerated lung volume decreased significantly from CPAP 5 to CPAP 50 [oleic acid lung injury (OAI): 346.9 (80.1) to 96.4 (48.8) ml, P<0.001; lavage-ARDS: 245 17.6) to 42.7 (4.8) ml, P<0.001]. In lavage-ARDS poorly aerated lung volume decreased at higher CPAP levels [232 (45.2) at CPAP 10 to 84 (19.4) ml at CPAP 50, P<0.001] whereas in OAI poorly aerated lung volume did not vary at different airway pressures. CONCLUSIONS: In both ARDS models well-aerated and non-aerated lung volume respond to different CPAP levels in a comparable fashion: Thus, a cyclical alveolar collapse seems to be part of the derecruitment process also in the OA-ARDS. In OA-ARDS, the increase in poorly aerated lung volume reflects the specific initial lesion, that is capillary leakage with interstitial and alveolar oedema.

Animals↗
PubMed2006

Initiation of high-frequency oscillatory ventilation and its effects upon cerebral circulation in pigs: an experimental study.

BACKGROUND: Current practice at high-frequency oscillatory ventilation (HFOV) initiation is a stepwise increase of the constant applied airway pressure to achieve lung recruitment. We hypothesized that HFOV would lead to more adverse cerebral haemodynamics than does pressure controlled ventilation (PCV) in the presence of experimental intracranial hypertension (IH) and acute lung injury (ALI) in pigs with similar mean airway pressure settings. METHODS: In 12 anesthetized pigs (24-27 kg) with IH and ALI, mean airway pressure (P(mean)) was increased (to 20, 25, 30 cm H(2)O every 30 min), either with HFOV or with PCV. The order of the two ventilatory modes (cross-over) was randomized. Mean arterial pressure (MAP), intracranial pressure (ICP), cerebral perfusion pressure (CPP), cerebral blood flow (CBF) (fluorescent microspheres), cerebral metabolism, transpulmonary pressures (P(T)), and blood gases were determined at each P(mean) setting. Our end-points of interest related to the cerebral circulation were ICP, CPP and CBF. RESULTS: CBF and cerebral metabolism were unaffected but there were no differences between the values for HFOV and PCV. ICP increased slightly (HFOV median +1 mm Hg, P<0.05; PCV median +2 mm Hg, P<0.05). At P(mean) setting of 30 cm H(2)O, CPP decreased during HFOV (median -13 mm Hg, P<0.05) and PCV (median -17 mm Hg, P<0.05) paralleled by a decrease of MAP (HFOV median -11 mm Hg, P<0.05; PCV median -13 mm Hg, P<0.05). P(T) increased (HFOV median +8 cm H(2)O, P<0.05; PCV median +8 cm H(2)O, P<0.05). Oxygenation improved and normocapnia maintained by HFOV and PCV. There were no differences between both ventilatory modes. CONCLUSIONS: In animals with elevated ICP and ALI, both ventilatory modes had effects upon cerebral haemodynamics. The effects upon cerebral haemodynamics were dependent of the P(T) level without differences between both ventilatory modes at similar P(mean) settings. HFOV seems to be a possible alternative ventilatory strategy when MAP deterioration can be avoided.

Air Pressure↗
PubMed2006

[Structural damage of epidural catheters during combined spinal epidural anaesthesia: a lightmicroscopical study].

BACKGROUND: The purpose of this study was to investigate whether there is a risk of epidural catheter damage during the advancement of the spinal needle through an epidural needle in clinical use. METHODS: A total of 100 catheters (50 from CSE kits with a pencil-point type spinal needle and 50 from CSE kits with a Quincke type spinal needle) which had been used for routine CSE blocks were microscopically examined for any defects within the first 150 mm of the catheter. Additionally 10 unused new catheters were investigated. RESULTS: Among 10 unused catheters 5 slight scratches were found, 92 out of 100 used catheters did not show any signs of use or scratches, 7 showed some signs of use and longitudinal scratches whereas another 1 showed a moderate scratch of less than 25% of the wall thickness. There was no difference in the prevalence of scratches between the CSE kits with pencil-point type spinal needles compared to those with Quincke-type spinal needles. CONCLUSION: The CSE technique with either pencil-point type or Quincke-type spinal needles for subarachnoidal punctures was safe and showed no relevant epidural catheter damage.

Adult↗
PubMed2006

[Albert and Gustav Döderlein -- a critical view to the biographies of two German professors].

Albert Döderlein and his son Gustav had as professors in Munich and Jena a formative influence on the German gynecology in the first half of the 20(th) century. Albert Döderlein discovered the lactobacillus named after him and its function, he was one of the first who employed radiotherapeutics in cancer therapy and introduced the rubber glove in obstetrics and gynecology. But he also wrote the gynecologic text to the "Bill for prevention of progeny suffering from an inherited disease dated 14(th) June 1933". After his time at the university hospital Charité, between 1936 and 1945 he was medical superintendent of the department of gynecology and obstetrics at the Police Hospital in Berlin. He can be regarded as the founder of antenatal care in Germany. Both scientific and historic aspects of the biographies of these two professors are critically looked right past.

Eugenics↗
PubMed2006

[Out-of-hospital births in Germany--a comparison of "large", "medium", and "small" free-standing birth centres].

BACKGROUND: How do maternal and foetal outcomes in out-of-hospital births vary in relation to birth centre size? PATIENTS AND METHODS: Routine perinatal data from out-of-hospital births in 80 birth centres in Germany between 1999 and 2002 were analysed. Birth centres were grouped according to their annual mean birth rate into small (< or = 70 births per year), medium (71 - 155 births per year), and large (> 155 births per year) units. Breech births (n = 43) and twins (n = 14) were excluded from the analysis (level of significance p < 0.01). RESULTS: Pregnancy and perinatal risks, foetal and maternal morbidity and mortality, perineal lacerations and transfer of newborns to NICU did not differ between the three groups which comprised a total of 14,629 births. Less episotomies were performed in large birth centres compared to small or medium-sized birth centres. Significantly less women were transferred from medium-sized birth centres to hospital following delivery. Five minute Apgar scores < or = 7 were significantly more frequent in birth centres with the highest birth rates. During labour significantly less women were transferred to hospital from medium-sized birth centres than from small or large centres. The transfer rate difference between nulliparae and multiparae was 4 : 1. CONCLUSION: Perinatal parameters appear to differ in some aspects according to how the birth centres were labelled. Nevertheless, these differences have only little clinical significance and may be explained by the demographic characteristics of the population. These results do not allow the general conclusion that the quality of out-of-hospital care in Germany differs in relation to the annual birth rates of the birth centres.

Birthing Centers↗
PubMed2006

Intrapartum transfer from a birth centre to a hospital - reasons, procedures, and consequences.

BACKGROUND: Investigation of the reasons for the transfer of women from a birth centre to a hospital in the course of childbirth as well as modalities and effects. PATIENTS AND METHOD: In the prospective investigation from September 1, 1999 to August 31, 2001, information was collected for all women in Berlin and Bavaria transferred intrapartum from a birth centre to a hospital concerning the reason for the transfer, stage of delivery at the start of transfer, details of the transport, accompaniment, state of mother and medical diagnosis on arrival at the hospital, further progress of delivery, and the condition of the baby postnatum. Comparison groups were formed by all birth centre deliveries in Berlin and Bavaria 1999/2000 (n = 3060) and hospital deliveries in Berlin and Bavaria 1998/1999 (selected data, n = 89 696 births). RESULTS: Three hundred and sixty transfer cases could be evaluated, and a majority of these were nulliparous. The most frequent reasons for transfer were prior premature rupture of membranes and failure to progress in labor. Fifty-seven percentages of the women who were transferred subsequently delivered spontaneously, with an episiotomy rate of approximately 30%. 1-min Apgar value < or = 7 were frequently in nulliparous and multiparous patients in the transfer group than in the comparison groups, as were 5-min Apgar values < or = 7 and pH < 7.10 in arterial cord blood in particular for nulliparous in the transfer group. Hospitalisation of neonates born to the transfer group and in particular the nulliparous was significantly more common. CONCLUSIONS: Women delivering in a birth centre represent in general a low-risk group as a result of careful preselection by the centres. However, some neonatal data and the high rate of operative deliveries (cesarean section, forceps, and vaginal extraction) indicate that the intrapartum-transferred women, in particular when nulliparous, represent than a special high-risk group.

Adult↗
PubMed2006

Human T-cell lymphotropic virus type 1 provirus and phylogenetic analysis in patients with mycosis fungoides and their family relatives.

BACKGROUND: Mycosis fungoides (MF) is a cutaneous T-cell lymphoma of unknown aetiology. A pathogenic role of human T-cell lymphotropic virus type 1 (HTLV-1) has been suggested but remains controversial. To determine whether MF is linked to HTLV-1. METHODS: Blood samples were collected from 60 patients, 15 family relatives of patients with MF (MFRs), 20 healthy controls and 10 patients with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The presence of HTLV-1 antibodies in serum was tested by the Western blot rp21e-enhanced test. DNA was extracted from the blood with the Qiagen blood kit. We used 500 ng of DNA either in conventional HTLV-1-specific polymerase chain reaction (PCR) or in real-time PCR using primers sk43 and sk44 together with a tax-specific fluorescent probe. RESULTS: In Western blot, antibodies against three to four HTLV-1 antigens were detected in 52% of patients with MF. All of the patients with HAM/TSP were positive, while only 7% of the MFRs and none of the 20 healthy controls reacted with HTLV-1 antigens in Western blot. One of 60 patients with MF and one of 15 MFRs were positive in HTLV-1 PCR. These two PCR-positive samples which were quantified in real-time PCR showed that fewer than five in 10(6) cells were HTLV-1 infected. We succeeded in amplifying and sequencing the 5' end of the provirus from the blood of the PCR-positive MFR by seminested PCR. A positive result was also obtained in this test. Phylogenetic tree analyses revealed a high homology of this sequence with other HTLV-1 sequences from the Middle East. The above PCR-positive MFR was the brother of a PCR-negative patient with MF. CONCLUSIONS: These findings demonstrate that HTLV-1 is probably not the aetiological agent of MF. However, it may play a role in immunosuppression and in the spreading of the disease.

Adult↗
PubMed2006

Insect-bite-like Wells' syndrome in association with mantle-zone lymphoma.

Wells' syndrome is a multifaceted dermatosis with a wide morphological spectrum, ranging from characteristic cellulitis-like erythema and wheals to an unusual presentation of vesicles and bullae. We describe a patient in whom Wells' syndrome presented as an insect-bite-like eruption and was associated with underlying mantle-cell lymphoma. We recommend meticulous investigation of patients diagnosed with Wells' syndrome manifesting as an insect-bite-like eruption.

Diagnosis, Differential↗
PubMed2006

Mycosis fungoides associated with B-cell malignancies.

BACKGROUND: The coexistence of mycosis fungoides, a peripheral T-cell lymphoma, and B-cell malignancies or Hodgkin's lymphoma in the same patient is unusual. Most descriptions are isolated case reports and case series are strikingly sparse. OBJECTIVES: To detect cases of mycosis fungoides associated with B-cell malignancies or Hodgkin's lymphoma and to analyse the characteristics of and the interplay between the lymphoproliferative neoplasms. METHODS: Patients with mycosis fungoides who had B-cell malignancies or Hodgkin's lymphoma were selected from among 398 patients either treated or followed up in two tertiary medical centres during a 7-year period. RESULTS: Eleven patients with mycosis fungoides and B-cell malignancy were detected (seven of non-Hodgkin's lymphoma, three of chronic lymphocytic leukaemia, one of multiple myeloma). No case of Hodgkin's lymphoma was found. In seven patients the mycosis fungoides preceded the B-cell malignancy whereas in four it was the B-cell malignancy which occurred first. The time elapsed between onset of the two malignancies ranged from 4 to 22 years (average: 12 years). Patients who had mycosis fungoides as the first neoplasm presented with earlier stages of mycosis fungoides (four of seven: IA, three of seven: IB) than those who had mycosis fungoides as their second neoplasm (of four, one: IB, one: folliculotropic, two: IIB). Among the four patients in whom the appearance of mycosis fungoides followed the B-cell malignancy, three had been treated with multiagent chemotherapy. Two patients who presented with early-stage mycosis fungoides (IA) as the first lymphoma developed mycosis fungoides tumours after becoming immunosuppressed. In two patients infiltrates composed of both malignant T- and B-cell populations were found in a single biopsy. One showed two distinct populations of the malignant cells in the skin tumour, thus constituting a classical composite lymphoma of mycosis fungoides and chronic lymphocytic leukaemia, while in the other patient the two malignant populations of marginal B-cell lymphoma and mycosis fungoides (as evidenced by both phenotypic and genotypic findings) were intermingled. CONCLUSIONS: This case series indicates that while the coexistence of Hodgkin's lymphoma and mycosis fungoides is extremely rare, the association of mycosis fungoides and B-cell malignancies is not as rare as reflected in the literature, with non-Hodgkin's lymphoma constituting the most common associated B-cell malignancy. In this series as well as in the cases reported in the literature mycosis fungoides usually preceded the development of B-cell malignancies, which may be in accordance with previous reports of an increased risk of developing a second haematological neoplasm. The importance of a competent immune system for patients with mycosis fungoides is well demonstrated in these cases. It is suggested that for greater precision the criteria for diagnosis of composite lymphoma of the skin should include both phenotypic and genotypic features.

Adult↗
PubMed2006

Basal cell carcinoma arising over facial port wine stain: a single-centre experience.

BACKGROUND: A growing number of reports point to a possible connection between basal cell carcinoma (BCC) and port wine stain (PWS). Researchers suggest that either the elevated temperature induced by the increased dermal vasculature or an oncogenic factor produced by the ectatic vessels makes the overlying epidermis more susceptible to ultraviolet or ionizing radiation. OBJECTIVE: To check the prevalence of BCC in patients with PWS at a large national vascular amomalies centre. METHODS: The study group included 68 patients, 44 women and 24 men, with facial PWSs. Detailed data were collected on background features, past treatments and past exposure to radiation, and a comprehensive physical examination was performed. Biopsy samples were taken from suspect lesions for histological study. RESULTS: Four patients (5.9%) were found to have histologically proven BCC, 3 nodular and one multifocal. All had been exposed to radiation during childhood. Treatment consisted of excision; there was one recurrence. CONCLUSION: Although the co-occurrence of BCC and PWS is probably related to radiation treatment in childhood, these findings should alert physicians to regularly examine PWSs for cancerous changes, especially in patients at risk.

Adult↗
PubMed2006

Are desmoglein autoantibodies essential for the immunopathogenesis of pemphigus vulgaris, or just "witnesses of disease"?

Pemphigus vulgaris (PV) is fascinating to dermatologists, epithelial biologists and immunologists alike, as its pathogenesis has been clarified to a much greater extent than that of most other organ-specific autoimmune diseases, and as it has provided abundant novel insights into desmoglein biology and pathology along the way. Historically, the most influential PV pathogenesis concept is that of Stanley and Amagai. This concept holds that autoantibodies against desmogleins are both essential and sufficient for epidermal blister formation (acantholysis) by impeding the normal functioning of these major adhesion proteins. However, as with most good theories, this landmark concept has left a number of intriguing and important questions open (or at least has not managed to answer these to everyone's satisfaction). Moreover, selected dissenting voices in the literature have increasingly called attention to what may or may not be construed as inconsistencies in this dominant PV pathogenesis paradigm of the recent past. The present debate feature therefore bravely rises to the challenge of re-examining the entire currently available evidence, as rationally and as undogmatically as possible, by provocatively asking a carefully selected congregation of experts (who have never before jointly published on this controversial topic!) to discuss how essential anti-desmoglein autoantibodies really are in the immunopathogenesis of PV. Not surprisingly, some of our expert "witnesses" in this animated debate propose diametrically opposed answers to this question. While doing so, incisive additional questions are raised that relate to the central one posed, and our attention is called to facts that may deserve more careful consideration than they have received so far. Together with the intriguing (often still very speculative) complementary or alternative pathogenesis scenarios proposed in the following pages, this offers welcome "food for thought" as well as very specific suggestions for important future research directions--within and beyond the camp of PV aficionados. The editors trust that this attempt at a rational public debate of the full evidence that is currently at hand will constructively contribute to further dissecting the exciting--and clinically very relevant!--immunopathogenesis of PV in all its complexity.

Animals↗
PubMed2006

Changes in nitrogen metabolism of the freshwater fish Cirrhinus mrigala following exposure to cypermethrin.

We studied the effect of a synthetic pyrethroid insecticide, cypermethrin, on some aspects of nitrogen metabolism in the gills, liver, and muscle tissue of the Indian major carp, Cirrhinus mrigala. Free amino acid levels and protease activity showed an elevation in all tissues following exposure to lethal (5.13 microg/L) and sublethal (1.026 microg/L) doses of cypermethrin, with significant changes noticed on day 4. The normal condition was restored only at a sublethal concentration.

Amino Acids↗
PubMed2006

Roflumilast, a once-daily oral phosphodiesterase 4 inhibitor, lacks relevant pharmacokinetic interactions with inhaled salbutamol when co-administered in healthy subjects.

OBJECTIVE: Roflumilast is an oral, once-daily phosphodiesterase 4 inhibitor under investigation for the treatment of chronic obstructive pulmonary disease and asthma. In clinical practice, the drug is likely to be co-administered with inhaled bronchodilating beta2-adrenoceptor agonists. Therefore, this study investigated the pharmacokinetic characteristics of roflumilast and its pharmacodynamically active metabolite roflumilast N-oxide when co-administered with orally inhaled salbutamol in healthy subjects. METHODS: In this open, randomized clinical study, 12 healthy male subjects received repeated doses of oral roflumilast 500 microg once daily, orally inhaled salbutamol 200 microg 3 times daily, and a combination of both drugs over 7 days according to a 3-period, changeover design with 14 days washout between treatments. RESULTS: Co-administration of roflumilast and salbutamol did not markedly change roflumilast or roflumilast N-oxide disposition. Point estimates (90% confidence intervals) of area under the curve from 0-24 h (AUC 0-24) and maximum plasma concentration in steady state (Cmax,ss) for roflumilast with salbutamol versus roflumilast alone were 1.05 (0.94, 1.17) and 0.97 (0.84, 1.10); the respective point estimates (90% confidence intervals) for AUC 0-24 and Cmax,ss of roflumilast N-oxide were 0.98 (0.91, 1.06) and 0.98 (0.92, 1.03). Roflumilast co-administration did not alter the pharmacokinetics of steady state salbutamol. The respective point estimates (90% confidence intervals) for AUC 0-6 and Cmax,ss of salbutamol with roflumilast versus salbutamol alone were 1.10 (0.99, 1.21), 1.08 (0.91, 1.28). The combination of both drugs was well tolerated. CONCLUSION: There were no relevant pharmacokinetic interactions between roflumilast and salbutamol at therapeutically effective doses.

Adrenergic beta-Agonists↗
PubMed2005

Treatment of uterine fibroids by embolization--advantages, disadvantages, and pitfalls.

Uterine fibroids are the most common benign tumors of the female genital tract. Apart from vaginal or abdominal hysterectomy, which has been in use for more than 100 years, the more recently established techniques of laparoscopy and hysteroscopy provide two additional treatment approaches. In cases of symptomatic uterine fibroids, the most widely accepted alternative to surgery is the catheter-supported embolization of uterine arteries (uterine artery embolization, UAE). All patients who wish to be treated by UAE because of symptomatic fibroids should be presented to both gynecologists and radiologists. To the best of our knowledge, there are no interdisciplinary guidelines for UAE. Therefore, it would be very helpful if gynecologists and radiologists could reach an agreement for both indications and treatment strategies. However, there is no defined "gold standard" for fibroid therapy at all. In this respect, the therapeutic approach should be influenced less by the preference of the (potential) surgeon, and more by factors like size, localization, and number of fibroids. In addition, symptoms, ethnicity, and the wish to have children should be considered. Cooperation between radiologists and gynecologists is absolutely necessary, not only for the choice of the optimal treatment and care of patients, but also for the development of useful guidelines and future studies. UAE may be a therapeutic approach for selected patients. In these special cases, embolization is a safe and practical alternative to the established treatment options.

Adolescent↗
PubMed2005

Hypoxaemia associated with an enlarged aortic root: a new syndrome?

OBJECTIVE: To assess the mechanisms through which an enlarged aortic root may facilitate right to left shunting through a patent foramen ovale. PATIENTS: 19 patients with the platypnoea-orthodeoxia syndrome (POS) were compared with 30 control patients without platypnoea. INTERVENTIONS: Multiplane transoesophageal echocardiography. MAIN OUTCOME MEASURES: The aortic root diameter, atrial septal dimension behind the aortic root, and amplitude of the phasic oscillation of the septum were measured. Four groups of patients were compared: 12 platypnoeic patients with a dilated aortic root (POS-D), 7 platypnoeic patients with a normal aortic root (POS-N), 15 control patients with a dilated aortic root (CONT-D), and 15 control patients with a normal aortic root (CONT-N). RESULTS: In POS-D and CONT-D patients, the apparent atrial septal dimension was 16.3 (2.7) mm and 17.4 (5.9) mm respectively, compared with 24.4 (5.2) mm in POS-N patients and 25 (4) mm in CONT-N (p < 0.005). Furthermore, the amplitude of septal oscillation was 14.7 (2.5) mm in the POS-D group versus 5.8 (2.4) mm in CONT-N (p < 0.001) compared with 23.3 (3) mm in seven patients with an atrial septal aneurysm (p < 0.001). CONCLUSION: Patients with an enlarged aorta have an apparently smaller dimension and increased mobility of the atrial septum. These findings appear to result from compression by the aortic root and decreased septal tautness. Consequently, a "spinnaker effect" with the inferior vena caval flow may take place, opening the foramen ovale and leading to sustained right to left shunting.

Adult↗
PubMed2005

[Adrenal hypoplasia congenita: four new cases in children].

Adrenal hypoplasia congenita (AHC) is an extremely uncommon disease of early onset. This condition can be lethal in the absence of adapted treatment. Some of these diseases are related to changes in the gene DAX1 that encodes a member of the superfamily of hormone nuclear receptors. It is a transcriptional repressor that is central in the morphogenesis of the adrenals and the gonadic differentiation. Here we report on four cases of X- linked AHC. In the first two familial cases, mutations were identified and mothers were heterozygotes. Abnormally low levels of estriol were evidenced during the pregnancy leading to an early diagnosis and adapted care of the affected male neonates. These children are doing well with a 21-and 20 months follow-up with hormone replacement at the present time. The two last cases corresponded to a contiguous gene syndrome associating AHC to glycerol-kinase deficiency that was revealed respectively at six days and seven years of age by acute adrenal insufficiency.

Adolescent↗
PubMed2005

21-Hydroxylase deficiency: an exemplary model of the contribution of molecular biology in the understanding and management of the disease.

Congenital adrenal hyperplasia (CAH) is a family of autosomal recessive disorders caused by mutations in genes encoding the enzymes involved in one of the various steps of adrenal steroid synthesis. Steroid 21-hydroxylase deficiency (21-OHD) is responsible for over 95% of the 5 forms of CAH, and results due to enzymatic defect owing to mutation in the CYP21 gene. The disease has two major clinical presentations. The "classical" form is severe, and divided into a salt wasting (SW) and simple virilizing (SV) subgroups. In both, affected female fetuses undergo virilization of the external genitalia prenatally and present at birth with sexual ambiguity. In addition, in both sexes infants with SW CAH are at risk of life-threatening adrenal crisis without treatment. This is why it is so important to make a diagnosis and to counsel the families. The diagnosis is easy by measuring the plasma levels of 17-hydroxyprogesterone (17-OHP) in antenatal (amniotic fluid), or perinatal samples (peripheral blood). Confirmation by molecular genetic analysis is advised. The second form of 21-OHD is called "non classical" because the presentation is much less severe and the onset of clinical expression occurs long after birth, often in the peripubertal period, as non-specific symptoms of hyperandrogeny. The unambiguous diagnosis of the latter requires a simple short ACTH test, with the measurement of 17-OHP at 60 min. In both forms, the mutations on the gene CYP21 responsible for the disease are now well known and can be identified by molecular biology techniques. There is a good correlation between phenotypes and genotypes, due to variable amount of the 21-hydroxylase-enzyme activity left (null to 50-60%). SW, SV and NC forms are associated with distinct mutations or combination of mutations. Nowadays, by combining hormonal and molecular tests, it is possible to predict the clinical form of the disease in a given family in the context of a prenatal diagnosis, which can lead to a prenatal treatment. Therefore, 21-OHD genotyping also appears essential for a new approach of genetic counseling, prediction of clinical form after postnatal screening and to define the post-ACTH 17-OHP values indicating the cut-off lines between NC, heterozygote and normal subjects.

Chromosome Deletion↗