Biomedical subjects

V Klingmüller

Publications and source records attributed to V Klingmüller.

At least 19 recordsLinked to original sources

PubMed2005

[Influence of continuous positive airway pressure (CPAP) on blood flow velocity in the venous vascular system of the liver -- duplex sonographic investigations].

OBJECTIVE: In the last years, noninvasive techniques of artificial ventilation like continuous positive airway pressure (CPAP) have become more and more important. However, the effects of such procedures on the circulation of the hepatosplanchnic area are, except for the indocyanine green plasma clearance, not yet representative by means of noninvasive investigation methods. METHODS: We studied maximum blood flow velocity in defined areas of hepatic and portal veins by duplex ultrasonography in 20 healthy volunteers (12 male, 8 female; age: 24,7 +/- 4,7 years [mean +/- SD]) before, during and after application of CPAP (10 cm H(2)O). As many measurements as possible were taken in both vascular systems. After division into five minute intervals arithmetical mean values were calculated for each interval. The experiment was divided into a control interval ("before CPAP"), three "CPAP" intervals and finally two "after CPAP" intervals. Heart rate and blood pressure were taken at the beginning of these intervals. RESULTS: Compared with the control interval, maximum blood flow velocity in the area of the hepatic vein decreased significantly by 13,2 %, 16,8 % and 15,7 % (p < or = 0,001 in each case) during each of the three "CPAP" periods. In the portal venous area blood flow velocity decreased by 4,3 %, 8,8 % and 7,0 %, respectively, with a significant decrease only in the second "CPAP" interval (p < or = 0,005). After CPAP, changes returned to baseline within a few minutes. Heart rate and blood pressure showed no significant differences during the whole experiment. CONCLUSION: Parameters taken in both venous vascular areas of the liver show clear correspondence with the results of former studies, which have been determined by means of more invasive investigation methods. Maximum blood flow velocity seems to be useful for monitoring liver blood flow and its individual time course during CPAP, noninvasively and semiquantitatively. Further trials under conditions of controlled mechanical ventilation should be performed to optimize ventilation strategies for the critically ill.

Adult↗

PubMed2004

[Cranial sonography for newborn screening: a 10-year retrospective study in 11,887 newborns].

We retrospectively analyzed the results of a sonographic cranial screening study, performed between 1985 and 1994 to determine the incidence of intracranial hemorrhage and cerebral anomalies based on obstetrical risk factors. In the Department of Obstetrics and Gynecology of the University Giessen, Giessen, Germany, 94.6 % (n = 11,887) of all children born during the study period were included and underwent sonographic cranial screening within the first 10 days after birth. Cerebral abnormalities were found in 653 (= 5.5 %) cases, and peri-/intraventricular hemorrhages (PIVH, grade I-IV) in 303 cases. Periventricular leucomalacia, porencephaly, subarachnoidal hemorrhage and hydrocephaly were rare (< or = 0.2 %). The Apgar index proved to be a good prognostic factor, particularly at 1 and 5 minutes after birth (p < 0.0001). In contrast, correlation between PIVH and cardiotocography, arterial cord blood gases, and pH was poor. We did not observe a higher incidence of PIVH in newborns with growth retardation, preeclampsia and premature ruptures of membranes or prolonged labor. With decreasing gestational age, the frequency of PIVH increased progressively from 0.4 % at 39 weeks to 53.2 % at 27 weeks (p < 0.001). We also found a higher risk of intracranial hemorrhage in preterm newborns with amniotic infections (38.1 %, p < 0.001). In mature babies, we did not find a difference between the incidence of PIVH and delivery-modes; however, we noted a higher risk of PIVH Grade IV in preterm newborns with breech presentation for vaginal delivery versus caesarean section (38.5 % versus 7.4 %, p = 0.005). The incidence of PIVH over this 10 year time period did not increase despite an increasing number of preterm newborns over time. In conclusion, this study, which represents one of the largest patient cohorts studied for PIVH, indicates that neonatal sonographic cranial screening is an important tool to define quality control in obstetrics.

Apgar Score↗

PubMed2004

[Increased signal intensity of velocity measurements in duplex sonography by using the contrast agent levovist: a prospective, randomized study in a fetal sheep model].

PURPOSE: To evaluate the potential diagnostic advantages of the contrast agent Levovist for signal enhancement of small adjoining fetal vessels and to study the effect of Levovist before and during acute fetal hypoxia on the fetal circulation and the fetal blood flow velocities. MATERIALS AND METHODS: A prospective, randomized study was performed in 12 fetal sheep before and during acute fetal hypoxia produced by complete occlusion of the maternal common iliac artery. Two groups of animals were studied, comprising animals with (study group, n = 6) and without (control group, n = 6) Levovist. In the study group, Levovist was administered intravenously by a pump (modified IVAC P 4000, Schering, Berlin). Duration and intensity of signal enhancement were measured in the fetal aorta, the common carotid artery and the ophthalmic artery of both groups before and during hypoxia. Concurrently, fetal heart rates as well as systolic and diastolic blood flow velocities in all three vessels were recorded in both groups. RESULTS: The increased signal intensity of up to 15 dB in the study group resulted in improved differentiation and imaging quality of adjoining small fetal vessels when compared with the control group. Neither before nor during acute hypoxia, significant differences of the fetal heart rate and the systolic and diastolic blood flow velocities were observed between the two groups (p > 0.05). In the study group, no emboli were caused by Levovist in any fetal tissue or in the placenta. CONCLUSION: The contrast agent Levovist improves the detection and accuracy of monitoring flow velocities in small fetal vessels by increasing the intensity of the Doppler signal without affecting fetal heart rate or fetal blood flow velocities.

Acute Disease↗

PubMed2002

[Sonography in callus distraction of the hypoplastic mandible].

OBJECTIVES: Since the early 1990's when callus distraction of hypoplastic mandibles was developed, surgeons have been looking for a reliable method to monitor distraction treatment. X-rays films resulted in insufficient quality of images of low calcified structures and are only of little support in follow-up. Therefore, a standardised protocol using ultrasound was introduced. METHODS: 24 patients were included (aged 4 - 29 years with hemifacial microsomy [19], mandibulary micrognathia [5]), 20 intraoral (Howmedica-Leibinger/Mühlheim) and 9 extraoral distractors (Normed/Tuttlingen). Standard procedures for intra- and extraoral distraction were carried out and all postsurgical treatment steps were monitored by ultrasound. RESULTS: The mineralisation of the neocallus shows the following sequence: echogenic dots, needles directed along the distraction direction, bands, plaques, and modulation of the neocompacta. Additional therapeutically relevant questions of distraction distance, inflammation or occurrence of pus, arising during treatment were answered by sonography. Distance measurements could be performed reliably. CAT scan and MRI cannot be carried out because of metal artefacts. X-ray pictures like orthopantomogram and Clementschisch projection cannot show the early mineralisation and do not allow an exact distance measurement. CONCLUSIONS: Sonography is a effective, method to investigate the callus field without using X-rays and supports monitoring and decision making in distraction treatment of hypoplastic mandibles.

Adolescent↗

PubMed2000

[3D-spectrogram of the doppler signal in real time].

AIM: Doppler signals are normally displayed as an x/y-graph. The frequency is plotted in the y-direction, and the intensity is represented by the brightness. This represents less information than is contained in the acoustic signal: often one can hear more one can see. We are investigating the question as to whether it is feasible to render the complete information visible without the use of expensive additional equipment. METHOD: The sound card (SB16 P&P value edition) in a Pentium-PC (200 MHz 32 MB RAM) was used as a 16 bit dual channel a/d converter and connected to the ultrasound system Sonoline Elegra (Siemens, Erlangen, Germany). We used a standard 32 bit dual channel real-time FFT-software (SpectraPro, Sound Technology, California) to display a 3D-spectrogram on the PC-screen in real-time mode. This system was first tested on a flow model both with laminar steady flow and with pulsatile flow. Following this, measurements were made of the arteries and veins in healthy volunteers. RESULTS: In the 3D-Spectrogram the character of the flow can easily be seen. The quantitative parameters of velocity (Doppler frequency), direction and intensity of flow can be readily determined. Additional information about quality of flow, erythrocyte clusters and changes occurring in areas of slight stenoses can be used for diagnostic evaluation. The orthograde and retrograde flow are displayed separately using the dual channel technique. The arterial and venous flow in small and closely neighbouring vessels, such as the central retinal artery and vein, can easily be differentiated. The venous flow in particular is more turbulent in the 3D-spectrogram than would be expected from the normal display mode. CONCLUSION: The 3D-spectrogram provides much additional information in comparison with the normal Doppler spectrogram of the ultrasound system. This 3D-spectrogram can be easily obtained using inexpensive standard hard- and software.

Arteries↗

PubMed2000

[Doppler sonography of the short posterior ciliary artery in patients with primary open angle glaucoma].

AIM: The area of primary damage in glaucomas is the optic nerve head. This region is directly supplied by the peripapillary choroid and the short posterior ciliary arteries (SPCA). This study was designed to evaluate the choroidal and SPCA haemodynamics in high tension (HTG) and normal tension (NTG) primary open angle glaucoma patients, as well as in healthy controls (CTL). METHODS: 20 HTG, 12 NTG, and 32 age matched volunteers (CTL) without clinically relevant extracranial stenosis of the carotid arteries were evaluated for ocular pulse amplitude (OPA; OBF-System OBF Labs, UK) and for temporal SPCA peak systolic flow (PSV), enddiastolic flow (EDV), pulsatility (PI) and resistance indices (RI) using a 9 MHz phased array (Elegra Advanced System; Siemens, Germany). RESULTS: (mean +/- SD): In the control group the PSV (cm/s) of the SPCA was 10.90 +/- 1.53; EDV (cm/s) was 3.24 +/- 0.24, PI was 1.30 +/- 0.39, RI was 0.69 +/- 0.11, OPA (mm Hg) was 2.2 +/- 0.25; IOP (mmHg) was 14.6 +/- 1.5. When compared to CTL matched for age, sex, and refraction, NTG-patients showed the following results: OPA was significantly (p < 0.05) reduced, dopplersonography showed a significant (p < 0.05) reduction in diastolic flow patterns and a significant (p < 0.05) increase in PI and RI. In HTG-patients the parameters investigated where not significantly (p > 0.05) altered. CONCLUSION: These data suggest reduced haemodynamics in the choroid and in the SPCA of NTG patients, which may contribute to progression of the optic neuropathy. In HTG the Doppler parameters and the OPA are not altered compared with the control group.

Ciliary Arteries↗

PubMed1998

[Standardized ultrasound follow-up of callus distraction of the mandible].

Up to now the clinical follow-up in mandibular callus distraction was supported by radiologic methods, although low-mineralized structures are only insufficiently described by X-rays. Mandibular callus distraction was performed on 14 patients suffering from uni- or bilateral mandibular hypoplasia, using either intra- or extraoral devices. The clinical follow-up was supplemented by standardized sonographic investigations. With the exception of postoperative pin placement control, which was done by using X-rays, all interesting items of treatment could be visualized by sonography. We found a reliable correlation between sonographically measured distances and distances measured on the device. Due to early detection of complications, a premature ossification was detected in one case and an infection was diagnosed in another, using ultrasound. Sonography proved to enhance the possibilities of monitoring in mandibular callus distraction treatment and can be recommended in clinical routine.

Adolescent↗

PubMed1998

[Ocular pulse amplitude during manipulation of systemic perfusion parameters].

BACKGROUND: The mechanism for the control of choroidal perfusion is unclear. The present study was designed to investigate for the effect of standardized alteration of systemic perfusion parameters on choroidal hemodynamics in healthy volunteers. METHODS: Intraocular pressure (IOP; German abbreviation: IOD), Ocular Pulse Amplitude (OPA), systemic blood pressure, and pulse rate were measured, and ocular perfusion pressure was calculated in 14 otherwise non-smoking, healthy volunteers prior to and following exercise and smoking. RESULTS: Exercise significantly (sig., p < 0.05) increased pulse rate, systolic blood pressure and ocular perfusion pressure, while it sig. (p < 0.05) reduced IOP and diastolic blood pressure. However OPA was not sig. (p > 0.1) affected by changes in these parameters. Smoking sig. (p < 0.05) increased systolic blood pressure, diastolic blood pressure, pulse rate, and ocular perfusion pressure but did not sig. (p > 0.09) alter OPA. CONCLUSION: Despite affecting ocular and systemic perfusion parameters, exercise and smoking did not alter OPA, suggesting functional isolation i.e. autoregulation of the choroidal and/or ophthalmic artery circulation.

Adult↗

PubMed1998

[Peak pulse blood volume in controlled modification of local perfusion parameters].

BACKGROUND: Choroidal autoregulation is discussed controversially. The present study was designed to investigate for the effect of standardized manipulation of local perfusion parameters on choroidal hemodynamics in cynomolgus monkey eyes with lasersurgically induced glaucoma (CMG; German abbreviation: RA-LHDG). METHODS: CMG unilaterally received 2-3 laser treatments so as to develop the lasered-eye glaucoma model. Intraocular pressure (IOP; German abbreviation: IOD) and Ocular Pulse Amplitude (OPA) were measured and Peak Pulse Blood Volume (PPBV; German abbreviation: PGBV) was determined. RESULTS: In CMG PPBV was not significantly (sig., p > 0.05) altered in laser-treated eyes--despite a sig. (p < 0.05) increase in IOP. Untreated contralateral control eyes of monkeys with an IOP-increase > 5 mm Hg in laser-treated eyes showed a sig. (p < 0.05) increase in PPBV. CONCLUSION: Unchanged PPBV in laser-treated eyes of CMG and an increase in PPBV in control eyes point at a bilateral autoregulatory compensatory mechanism, which is more manifest in eyes with IOPs in the normal range.

Animals↗

PubMed1998

[Preliminary examinations on the effects of the breed characteristic feature "feather crest" on skull and brain anatomy of domestic ducks (Anas platyrhynchos f. dom.)].

As mentioned in older sources, the crested breed of the domestic duck is described as variety with high pre- and postnatal mortalities, malformations in skull and brain anatomy, and several central nervous deficiencies in affected birds. Therefore this breed is to be called defective and abnormal in the sense of section 11b of the German protection of animals legislation. Poultry fanciers reject these findings as incorrect, but accurate scientific examinations that bear out this allegation are not available. Preliminary examinations have demonstrated that brain and skull anatomy of living animals can be described by using non-invasive diagnostic techniques (magnet-resonance-imaging, computerized tomography, radiography). The use of this progressive methods enables to expressive findings on present stocks of domestic ducks. Many of the test animals investigated in preliminary examinations by using magnet-resonance-imaging and radiography showed abnormal tissue deposits in the tentorium cerebelli, meningo-encephalocele, cranial malformations, and variable bone formations in the thickened hypodermis of the crest. If crested ducks are mated against each other, numerous offspring show malformations of upper beak and cranium, encephalocele, as well as craniopagal parasites in form of rudimentary legs.

Animals↗

PubMed1997

Peri/intraventricular haemorrhage: a cranial ultrasound study on 5286 neonates.

OBJECTIVE: We launched a prospective cranial ultrasound study at the Department of Obstetrics and Gynaecology of the University of Giessen. In this study we examined the incidence and severity of brain damage in neonates and related them to various obstetrical risk factors. STUDY DESIGN: More than 90% of all neonates born between 1984 and 1988 were included in the study (n = 5286) and were screened by ultrasound for cerebral abnormalities on 5-8 days post-partum. The relation between the incidence of peri/intraventricular haemorrhages (PIVH) and obstetrical risk factors were analyzed by contingency tables. RESULTS: The most frequent abnormality was PIVH (3.6%) of various degrees (grade I-III). Periventricular leucomalacia, porencephalia, subarachnoidal haemorrhages, and hydrocephali were rare (< or = 0.2%). The incidence of PIVH increased progressively with decreasing gestational age, e.g. from 1.6% at 38-43 weeks up to 50.0% at 24-30 weeks of gestation. A large percentage of babies with PIVH were clinically normal. In immature neonates there was a close inverse relationship between Apgar score at 1, 5 and 10 min and both incidence and severity of PIVH. This was in contrast to findings in mature neonates where a marked increase in the incidence of PIVH was found only with Apgar scores as low as 0-4 points. The relation between the incidence of PIVH and both cardiotocography and arterial cord blood pH was poor, independent of the gestational age. The incidence of PIVH was increased in growth retarded fetuses (pH < or = 7.29), premature rupture of membranes, fever sub partu and gestosis. It is interesting to note that in mature fetuses there was no difference in the incidence of PIVH between vaginally delivered (0.8%) and sectioned breech presentations (2.1%). In preterms at 35-37 weeks with prolonged labour and secondary cesarean section, the incidence of PIVH was very high (11.2%). CONCLUSION: From the present study we conclude that the incidence of PIVH especially in immature neonates is highly associated with low Apgar scores at birth. Since the Apgar score reflects the clinical condition and the degree of circulatory centralisation of neonates that is influenced by various ante- and intranatal risk factors, a protective obstetrical management is necessary to reduce the incidence of PIVH in neonates.

Acid-Base Equilibrium↗

PubMed1997

[Ultrasonic determination of the size of adrenal glands in newborn infants].

PURPOSE: To develop a model to evaluate the size and volume of neonatal adrenal glands. METHOD: In a prospective study the adrenal glands of 205 healthy newborn (113 male and 92 female, 1610 to 5210 g birth weight) were measured by ultrasound. Using a longitudinal and a transversal scan during inspiration for each side 6 parameters were taken and a formula developed to determine the volume of the gland. The model take in consideration both the "V" and the "Y" form. RESULTS: In the group with a birth weight of 2800-4000 g the total volume of both glands was 3.42 +/- 1.08 ml (minimum 1.27, maximum 8.02). The ratio of total volume and birth weight changes from 1.1795 ml/kg at the first day of life to 0.7935 at the eighth day; this means an involution of 67%. There was no significant sex difference; the right side contributed 56%; the left side, 44% to the total volume. The total volume was positively correlated to body weight and body surface. CONCLUSION: With this method the size and the volume of the neonatal adrenal gland can be easily be determined and followed.

Adrenal Glands↗

PubMed1997

Conventional and modified nasal potential-difference measurement in cystic fibrosis.

Cystic fibrosis (CF) is associated with impaired ion transport across epithelial membranes and an increased transepithelial potential difference (PD) that can be measured in airway epithelium. The aim of this study was to investigate the diagnostic value of nasal PD in CF, and to test a modified approach to the measurement of this PD. The reproducibility and diagnostic sensitivity and specificity of nasal PD measurements were tested with the perfusion technique and with a simplified modification of the technique done with a novel, solid-state exploring electrode. With the perfusion method, basal PD values were different in CF patients (mean +/- SEM: -51.6 +/- 0.9 mV, n = 104) than in normal (-15.5 +/- 0.9 mV, n = 58, p < 0.01) subjects. CF patients with acute rhinitis or other nasal pathology had mean PD values that were intermediate between those of the patients and normal and disease-control groups (-28.3 +/- 1.2 mV, n = 40, p < 0.01, different from normal). The diagnostic sensitivity of the perfusion method for CF was 91.3%, and the specificity was 96.4%. PD measurements with the modified technique correlated highly with the results achieved with the perfusion method (r = 0.94, n +/- 158). The measurement of nasal PD effectively distinguishes CF from control subjects. Care must be taken in the interpretation of measurements made on acutely inflamed epithelium. The modified method was simpler than the conventional perfusion technique, and equally effective.

Adolescent↗

PubMed1992

[Risk of cerebral hemorrhage in premature and mature newborn infants].

We launched a prospective cranial ultrasound screening study at the Maternity Hospital of the University of Giessen to examine the incidence and severity of brain damage in newborns. More than 90% of all neonates born during 1984-86 were included in the study (n = 2781) and were screened for cerebral abnormalities on 5.9 +/- 3.3 (SD) day post partum. There were in 7.8% sonographic abnormalities, the most frequent being peri/intraventricular haemorrhages (5.2% PIVH of various degrees (grade I-III). Periventricular leucomalacia, porencephalia, subarachnoidal haemorrhages, and hydrocephali were rare (less than or equal to 0.2%). The incidence of PIVH increased progressively with decreasing gestational age, e.g. from 1.5% at 41 weeks up to 61% at 24-30 weeks of gestation. A large percentage of babies with cerebral haemorrhages were clinically normal. There was a close inverse relationship between the Apgar score at 1,5 and 10 min and both incidence and severity of PIVH. However, the relation between PIVH and both cardiotocography (matched-pairs analysis) and arterial cord blood-pH was poor. The incidence of PIVH was increased in growth retarded newborns (pH less than or equal to 7.29), preterm multiples and amnionitis, but not after preeclampsia and premature rupture of membranes. It is interesting to note that, in mature newborns (greater than or equal to 38 weeks), there was no difference in the incidence of PIVH between spontaneous deliveries, vacuum extractions, and Caesarean sections, and that there was no difference between vaginally delivered (1.5%) and sectioned breech presentations (3.5%) in this group. In preterms at 35-37 weeks with protracted labour and secondary Caesarean section, the incidence of PIVH was high (19%). We conclude, that neonatal cranial ultrasound screening is an important tool for risk assessment and quality control in obstetrics. It clearly improves both the quality of the advice given to the patients and the clinical management of high-risk pregnancies.

Acid-Base Equilibrium↗

PubMed1992

[Characteristics of thyroid sonography in infants and children].

In a prospective study the thyroid glands of 598 healthy boys and girls (newborn to 17 years old) were examined by ultrasound. The volume of the normal gland was 1.1 cm3 in neonates, 2 cm3 in 4 year-old-children, and 8.7 cm3 in schoolchildren. The gland of a normal newborn, a girl with congenital hypothyroidism, a girl with inflammation of a median cervical cyst, a girl with insulin-dependent diabetes mellitus and autoimmune thyroiditis, and a girl with an adenoma all showed typical differences in ultrasonic structure from the normal adult gland. Sonography of the thyroid gland discloses valuable information, especially in childhood.

Adolescent↗

PubMed1991

[Ultrasonographically determined thyroid gland volume in children].

The size of the thyroid was evaluated by sonography in 199 boys and 237 girls age one month to 17 years. The volume is 1.2/1.06 ml in boys/girls during the first month, 1.2/1.6 ml at the end of the first year of life, 1.7/2.4 ml at age four, 3.2/3.4 ml with eight years and up to the age of 12 years 5.7/5.7 ml. In juveniles older than 12 years the average volume is 8 ml, sex independently. However, the range appears to be rather wide (1.5-14.5 ml). The right lobe is usually larger than the left one. The rates of the length of the right lobe and the body length, of the total volume and the body weight, and of the total volume and the body surface area are almost independent of age for schoolchildren. There is no significant difference of the thyroid volume between the sexes.

Adolescent↗

PubMed1990

[The vascularized pedicled flap of superior gluteal artery to hip bone chip--a new concept in the revascularization of hip necrosis in adults].

The development and introduction of microsurgical technique has made possible completely new concept of revascularisation surgery in femoral head necrosis. The bone graft described in this presentation is a pedicled one from the lateral ilium. In five femoral head necrosis a pedicled corticocancellous pelvic graft, supplied by the deep branch of the superior gluteal artery, was transplanted in the femoral head. In all cases it was possible to lift out the pelvic graft from the same side as the affected hip joint. Contrary to the medial iliac bone graft (deep circumflex iliac artery) the lateral iliac bone graft (deep branch of the superior gluteal artery) is inserted into the femoral head dorsally. Preoperatively and postoperatively performed selective angiographies are necessary and presented. In all cases an unimpeded perfusion could be shown three months postoperatively. Advantages and indications of the pedicled bone graft are discussed.

Adult↗

PubMed1990

[Efficacy and side effects of differential calcium and phosphate administration in prevention of osteopenia in premature infants].

The prevention of osteopenia and frequency of renal and intestinal side effects of mineral supplementation was studied in 24 preterm infants with birth weight under 1,500 g, prospectively (gestational age 26-34 weeks). Calcium intake varied from 2.5 vs. 3.75 vs. 5 mmol/kg/day, phosphate was offered in dose of 2.5 mmol/kg/day. At the expected birth date 40% of infants with low calcium dose showed an activity of serum alkaline phosphatase greater than five times the maximum adult normal value which is defined as a reliable marker; for osteopenia no infant with medium or high calcium intake reached this critical value (p = 0.03). Medium and high calcium doses resulted in an increased risk for hypercalcuria (25 vs. 50%) (p = 0.03). Half of these infants developed typical signs of nephrocalcinosis on ultrasound examination. No significant difference of fecal fat content was observed with increased calcium intake; but more episodes of abdominal distension occurred during the first days of high calcium supplementation (p = 0.03). We conclude, that a calcium intake of 3.75 mmol/kg/day in combination with phosphate 2.5 mmol/kg/day is sufficient for adequate bone mineralization on a low level of side effects. Calcium excretion in urine has to be observed for early diagnosis of nephrocalcinosis.

Alkaline Phosphatase↗