[Comparison of extracorporeal shockwave therapy (ESWT) with roentgen irradiation in supraspinatus tendon syndrome--a prospective randomized single-blind parallel group comparison]. / Vergleich der extrakorporalen Stosswellentherapie (ESWT) mit der Röntgenreizbestrahlung beim Supraspinatussehnensyndrom--Ein prospektiver randomisierter einfachblinder Parallelgruppenvergleich.

AIM: Extracorporal shock wave therapy (FSWT) is applied in the case of supraspinatus tendinitis if conservative therapies have failed. So far there has been no controlled study comparing the effectiveness of ESWT with an established conservative method of therapy such as X-ray stimulation radiotherapy. METHOD: Thirty patients with chronic supraspinatus tendinitis were admitted into the prospective randomised study. After randomisation, the patients were treated either three times with 2000 pulses (energy flux density ED+ 0.33 mJ/mm2) with a Storz Minilith SL1 after one week, or with X-ray stimulation radiotherapy with 6 x 0.5 Gy on the ICRU reference point (1 neutral fraction/day) with cobalt 60 gamma rays. Primary endpoint was the age-corrected constant score. RESULTS: In the ESWT group the average age-corrected constant score rose from 50.1 points before ESWT to 91.5 points after 12 weeks and to 97.8 after 52 weeks. In the radiotherapy group it improved from 47.6 through 79.5 points to 87.4 points. CONCLUSION: No statistically significant differences were proven between ESWT and radiotherapy. ESWT appears to be at least equivalent to radiotherapy in treating chronic supraspinatus tendinitis syndrome and can avoid a dose of radiation for patients and staff. A comprehensive randomised study is, however necessary to ensure the equivalence of ESWT.

Inhibin and CD99 (MIC2) expression in uterine stromal neoplasms with sex-cord-like elements.

Uterine mesenchymal neoplasms with sex-cord-like elements are designated as endometrial stromal tumor with sex-cord-like elements (ESTSCLE) or uterine tumor resembling ovarian sex-cord tumor (UTROSCT), depending on the extent of sex-cord-like differentiation. Occasionally, sex-cord elements similar to those in ESTSCLE and UTROSCT occur in uterine adenosarcomas. To determine whether the sex-cord-like elements in these tumors show immunohistological evidence of sex-cord differentiation, we studied a series of uterine neoplasms for expression of inhibin, a peptide hormone expressed by normal ovarian granulosa cells and ovarian sex-cord neoplasms, and CD99, a protein also expressed by granulosa cells, Sertoli cells, and some ovarian sex-cord tumors. Thirty uterine mesenchymal neoplasms (five epithelioid or plexiform smooth muscle tumors, three endometrial stromal tumors, two mixed endometrial stromal and smooth muscle tumors, 10 ESTSCLE, five UTROSCT, and five miscellaneous stromal processes) and five epithelial neoplasms were evaluated for expression of CD99 (clone 12E7) and inhibin (clone R1) in formalin-fixed, paraffin-embedded tissue. Three of 10 (30%) ESTSCLE and five of five (100%) UTROSCT were inhibin and CD99 immunoreactive. Inhibin staining was confined to the areas with sex-cord-like differentiation, and staining was generally much stronger and more extensive in areas featuring prominent foam cells. There were no differences in the degree or intensity of staining for inhibin in premenopausal and postmenopausal women. CD99 expression tended to correlate with inhibin and was typically confined to similar cell types in the individual neoplasms. Weak CD99 immunoreactivity was seen in one additional epithelioid smooth muscle tumor, whereas all other mesenchymal and epithelial neoplasms studied for inhibin and CD99 were negative. These results provide further immunohistological support for true sex-cord differentiation within uterine mesenchymal proliferations and suggest that the degree of sex-cord differentiation may correlate with the expression of these markers.

Histochemical evaluation of placental dipeptidyl peptidase IV (CD26) in pre-eclampsia: enzyme activity in villous trophoblast indicates an enhanced likelihood of gestational hypertensive disorders.

PROBLEM: To determine whether differences in placental dipeptidyl peptidase IV (DPP IV, CD26) activities occurred in hypertensive complicated pregnancies as compared with uncomplicated pregnancies. METHOD: DPP IV activity was detected with H-Gly-Pro-4M2NA as the substrate in placental cryostat sections from 65 patients with gestational hypertension and 67 patients with uncomplicated pregnancies. The graduated intensities of the reaction product in the villous trophoblast were scored semiquantitatively by light microscopy and were related to the relative frequencies of hypertensive disorders (proportional odds model). After detection of enzyme activity, the same tissue samples were homogenized and used for kinetic fluorometric measurements. RESULTS: Enhanced villous trophoblastic DPP IV activity was significantly associated with an increased frequency of proteinuric hypertension in pregnant women (cumulative odds ratio theta1 = 1.6; P < 0.01). CONCLUSION: This study demonstrates for the first time that increased villous trophoblastic DPP IV activity indicates an increased likelihood of the presence and of the severity of hypertensive disorders in pregnancy.

Hypokalaemia in pregnant women treated with the beta 2-mimetic drug fenoterol--a concentration and time dependent effect.

The effect of tocolytic treatment with fenoterol on plasma potassium concentrations was studied in 83 pregnant women on intravenous tocolytic therapy. Plasma concentrations of fenoterol and potassium were measured simultaneously, the time interval between initiation of therapy and taking the blood sample varying from 2 hours to 100 days. In a subset of 13 patients this blood sample was taken after two hours of therapy and pretreatment potassium concentrations were measured also. Pretreatment potassium concentrations were normal in these 13 patients and declined to 2.88 mmol/L (median) fenoterol concentrations being 320 ng/L through 1164 ng/L. Potassium concentrations measured later than 24 hours after initiation of therapy were all in the normal range corresponding fenoterol concentrations varying from 200 ng/L to 2504 ng/L. The multivariate statistical model for the description of all data showed that the duration of treatment was the only variable which explained the data to a significant extent. This might indicate that tolerance to the potassium lowering effect of fenoterol had developed within 24 hours after initiation of therapy. In the subset of 13 patients pretreatment potassium concentrations were found to be more important in explaining potassium concentrations than fenoterol concentrations at two hours. As we did not observe any adverse events in patients with low potassium concentrations and potassium concentrations were normal within 24 hours, we conclude that hypokalaemia due to fenoterol in the treatment of premature labor is not of clinical concern.

Value of inhibin in the identification of granulosa cell tumors of the ovary.

Inhibins are peptide hormones that participate in the regulation of the pituitary-gonadal feedback system and are selectively expressed by cells of sex cord-stromal derivation. To determine the efficacy of this marker for distinguishing granulosa cell tumors, 134 primary and metastatic lesions of the ovary were evaluated for expression of the alpha-subunit of inhibin in routinely processed formalin-fixed, paraffin-embedded tissue. A variety of sex cord-stromal tumors (SCST), including 35 adult and juvenile granulosa cell tumors, 14 fibroma-thecomas, and 18 other sex cord-stromal proliferations, were studied. In addition, 33 surface epithelial neoplasms, 12 germ cell tumors, 11 metastases, and 11 miscellaneous ovarian neoplastic proliferations were evaluated. Among the non-granulosa cell neoplasms, special emphasis was placed on primary neoplasms and metastases that histologically simulated granulosa cell tumors. Thirty-three of 35 (94%) granulosa cell tumors were immunoreactive compared with 2 of 12 (17%) primary ovarian endometrioid tumors, one of nine (11%) primary ovarian transitional cell (Brenner) proliferations, and 3 of 17 (18%) other primary and metastatic poorly differentiated (undifferentiated) carcinomas. In 31 of the 35 granulosa cell tumors, inhibin staining was of moderate to strong intensity or was present in at least half of the constituent cells, whereas only 2 of 33 primary surface epithelial neoplasms fulfilled the same criteria, showing weak staining of 70% to 80% of the cells. In contrast, 10 of 14 (71%) ovarian fibroma-thecomas and 17 of 18 (94%) other sex cord-stromal proliferations were positive for inhibin. Nonneoplastic luteinized stromal cells stained for inhibin in 29 of 85 cases in which they could be evaluated. The results of this study show that although it is not completely specific and cannot reliably distinguish granulosa cell tumors from fibroma-thecomas or other ovarian sex cord-stromal proliferations, inhibin can be used to help distinguish sex cord-stromal neoplasms from most primary and metastatic non-SCST. Caution should be exercised in the interpretation of inhibin-positive cells, because a wide variety of primary and metastatic ovarian tumors may contain significant numbers of positively staining luteinized cells.

Histochemical evaluation of placental angiotensinase A in pre-eclampsia: enzyme activity in villous trophoblast indicates an enhanced likelihood of gestational proteinuric hypertension.

The aim of this study was to examine whether differences in placental angiotensinase A (glutamyl aminopeptidase, EC 3.4.11.7) activities occurred in hypertensive complications of pregnancy compared with uncomplicated pregnancies. Biochemical and semiquantitative histochemical methods were used and compared for their applicability. Angiotensinase A activity was detected using L-alpha glutamyl-4-methoxy-2-naphthylamide (alpha-Glu-MNA) as substrate and Fast Blue B salt for simultaneous azo-coupling in cryostat sections of placental tissue samples from 32 patients with pre-eclampsia, 11 patients with pregnancy-induced hypertension and 44 participants with uncomplicated pregnancies. The graduated intensity of reaction product in the villous trophoblast and in fetal blood vessels was evaluated semiquantitatively in a double-blind study by light microscopy (semiquantitative score method). Score levels were related to relative frequencies of hypertensive disorders (proportional odds model) and correlated to the severity of gestational hypertension (Spearman's rank correlation). After detection of enzyme activity, the same tissue samples were homogenized and used for kinetic fluorometric measurements under the same substrate and buffer conditions as in enzyme histochemistry. Enhanced villous trophoblastic angiotensinase A activity was significantly associated with an increased frequency of pre-eclampsia in pregnant women (cumulative odds ratio x 0(1) 6.37; P < 0.001) and showed significant correlations with the severity of gestational hypertensive disorders, represented by systolic (r = 0.31; P < 0.05) and diastolic (r = 0.34; P < 0.05 blood pressure and by concomitant proteinuria (r = 044; P < 0.01). Histochemical evaluation of fetal blood vessels and biochemical measurements revealed no statistically significant results. In conclusion this study demonstrates for the first time that increased villous trophoblastic angiotensinase A activity indicates an increased likelihood of the presence of pre-eclampsia and the severity of hypertensive disorders in pregnancy.

Expression of the estrogen receptor gene in developing and adult human breast.

Although studies of the estrogen receptor gene abound in rodent models and breast cancer cell lines, little is known about expression of this gene in normal human breast. Information regarding the physiology of this gene's expression is important if we are to elucidate abnormalities of the gene that may be involved in breast carcinogenesis. We evaluated levels of mRNA expression of the estrogen receptor (ER) gene and its protein product in a set of 89 breasts from clinically normal female infants, children, adolescents, and adult premenopausal and post-menopausal women. mRNA expression of the gene varied with the hormonal status. Relatively higher levels of gene transcripts were found in breasts of peri-menarchal girls, women in the luteal phase of the menstrual cycle, and in those with fibrocystic change. Higher levels were also occasionally found in breasts of infants and in most pre-adolescent children. Lower levels were seen in breasts of women in the follicular phase of the menstrual cycle, during pregnancy, and after menopause. Nuclear protein staining was common in breasts of normal children and peri-menarchal adolescents, and in post-menopausal atrophic breasts. Nuclear ER protein was infrequently detected in reproductive aged women's breasts, but was more often seen in follicular than in luteal menstrual phase or pregnant breast. ER protein was more frequently seen in post-menopausal than in pre-menopausal breasts with fibrocystic change. The results fit a model in which circulating levels of estrogen are inversely related to levels of mRNA transcribed from the estrogen receptor gene in normal physiologic states. Abnormally high levels of gene transcription may occur in some cases of fibrocystic change.

Concentration-effect relationship of the positive chronotropic and hypokalaemic effects of fenoterol in healthy women of childbearing age.

OBJECTIVE: To analyse fenoterol-induced tachycardia and hypokalaemia, the most important and most frequent adverse effects of tocolytic therapy with beta 2-adrenoceptor agonists in females of childbearing age. METHODS: The study was performed as a double blind, randomised, placebo controlled, cross over trial. Seven healthy women aged 22-38 y, received intravenous infusions of fenoterol at 3 different rates within the therapeutic range for tocolysis (0.5,1.0, and 2.0 micrograms.min-1) and placebo. The time courses of the plasma concentrations of fenoterol and potassium, and the heart rate were analysed with mixed effects pharmacokinetic-pharmacodynamic (PKPD) modeling using NONMEM. RESULTS: The plasma concentration-time course followed a linear two compartment model. Fenoterol-induced tachycardia was described by a linear concentration-effect model with baseline. The estimated baseline and slope parameters were 78 beats.min-1 and 0.032 beats.min-1.microgram-1.1, respectively. Fenoterol-induced hypokalaemia could be described by a physiological indirect response model including feedback; the Estimated basal plasma potassium concentration was 3.93 mmol.1-1 and the slope factor for the fenoterol-induced relative increase in the efflux of potassium from the extracellular space was 6.22*10(-4) ng.1(-1). CONCLUSION: The estimated population parameters permitted calculation of the expected time course of tachycardia and hypokalaemia in women after the initiation of tocolysis with fenoterol over the clinically relevant concentration range, and prediction of its variability. Based on simulation, our model predicted that a continuous infusion of 2.0 micrograms.min-1 (highest rate examined) would increase heart rate to 113 beats.min-1 at steady state and lower the plasma potassium concentration to 2.77 mmol.1(-1) 1.5 h after beginning the infusion. Thereafter, the plasma potassium concentration would slowly return to normal.

Antibodies to cytokeratins bind to epitopes in human uterine smooth muscle cells in normal and pathological pregnancies.

Cytokeratin antibodies have been widely used for the identification of trophoblast cells in the placental bed, following their invasion from the developing conceptus. Their identification centres upon the expression of cytokeratin in epithelial cells, from which trophoblast cells are derived. Our recent observations indicate that this strict relationship may be more complex than was thought. Cryostat and paraffin sections of human decidua and myometrium, taken from the placental bed and the uterotomy cut, were examined immunocytochemically for cytokeratins using ten antibody clones selected to identify different cytokeratin proteins and antigenic epitopes. Biopsy specimens were obtained from normal and pathological pregnancies (pre-eclampsia, fetal retardation, amnioninfection, hysterorrhexis, placenta praevia) at the time of caesarean section (26-41 weeks of pregnancy). Antibodies against nine clones, CAM 5.2, MNF 116, AE1/AE3, CK5, KS-B17.2, CY-90, M20, E3, and 34 beta E12 identified, as expected, syncytial giant cells and mononuclear trophoblasts within the placental bed and glandular epithelial cells throughout the uterus. In addition, they stained numerous fusiform cells that were classified by established criteria to represent smooth muscle cells, both within blood vessels and myometrium. No staining differences were observed between normal and pathological disorders. These results indicate that cytokeratin antibodies CAM 5.2, MNF 116 and AE1/AE3, and other antibodies targeting proteins 8 and 18, cross-react with epitopes expressed in cells other than giant trophoblastic cells and mononuclear trophoblasts in the uterus and, thus, caution has to be used when such antibodies are used for the diagnostic characterization of tissues related to the placental bed.

Biliary excretion of mezlocillin in patients with hepatic disease.

In three patients with liver disease (2 patients with alcoholic liver cirrhosis and 1 patient with chronic cholangitis) total, renal, biliary and metabolic clearance of the acylureidopenicillin mezlocillin was examined under steady state conditions. Mezlocillin was infused for 6 hours at a constant infusion rate of 10 mg/min. Renal clearance was calculated based on urinary excretion rates. Duodenal perfusion and marker dilution technique was applied to determine biliary excretion rates of the drug. Clearances were estimated by dividing the excretion rate by the respective plasma concentration. Total clearance was calculated by dividing the infusion rate by the plasma concentration. Biliary clearance was markedly reduced in the patients compared to the data of 8 healthy controls (0.65 +/- 0.33 ml/min vs 98.6 +/- 42.5 ml/min). Total and renal clearance were diminished (total clearance: 121.4 +/- 21.6 ml/min vs 286.5 +/- 54.6 ml/min, renal clearance, 65.4 +/- 1.0 ml/min vs 137.6 +/- 32.6 ml/min). In contrast, metabolic clearance was not changed (53.3 23.1 ml/min vs 50.3 +/ 24.2 ml/min). As mezlocillin is well tolerated and has a wide margin of safety we do not recommend reduced dosage. On the contrary, it might even be necessary to increase the dose when treating biliary tract infections in patients with cholestasis in order to assure effective drug concentrations in the bile.

Fenoterol metabolism in man: sulphation versus glucuronidation.

1. Plasma levels of fenoterol (F) and its conjugate metabolites were determined in healthy female subjects and in pregnant women treated for preterm labour. Sulphate (S) and glucuronide (G) conjugates could be quantified. 2. In the healthy volunteers, AUC of both the metabolites was half that of parent compound (AUC-S/AUC-F: 0.42; 0.14-1.16) (AUC-G/AUC-F: 0.49; 0.18-0.86) during i.v. administration of the drug and was several fold that of parent drug (AUC-S/AUC-F: 116.9; 36.4-353.3, AUC-G/AUC-F: 19.9; 5.1-57.5) after p.o. administration indicating extensive presystemic elimination. 3. In the healthy subjects, the AUC ratio of G:S was 1.1 (0.5-2.6) and 0.16 (0.10-0.27) after i.v. and p.o. administration, respectively, thus indicating that sulphation is the prevailing metabolic pathway in the presystemic elimination. 4. In patients, concentration ratios were used for the analysis. During continuous i.v. treatment, Css-S/Css-F was 3.8 (2.5-4.8) and Css-G/Css-F was 1.5 (0.7-2.1). During p.o. treatment Csstrough S/Csstrough-F was 69.4 (32.1-145.7) and Csstrough-G/Csstrough-F 9.4 (5.6-13.2).(ABSTRACT TRUNCATED AT 250 WORDS)

[Importance of measuring blood flow in monitoring pregnancy-induced hypertension and IUGR]. / Die Bedeutung der Blutflussmessung in der Uberwachung von Schwangerschaften mit SIH and IUGR.

Doppler flow velocimetry of uterine and fetal vessels is carried out in high risk pregnancies. However, there is controversy about the predictive value of elevated resistance indices (RI) with respect of adverse fetal outcome. Therefore we estimated the frequency of elevated RI in uterine and fetal vessels in pregnant women with documented pregnancy induced hypertension (SIH, n = 9), intrauterine growth retardation (IUGR, n = 16) and uncomplicated pregnancies (n = 8). The results of the doppler flow velocimetry were compared to the fetal outcome. Elevated RI were observed in all vessels in the two groups with SIH and IUGR. In contrast, all RI in the control group were found to be in the normal range. The frequency of elevated RI in the a. uterine was slightly but not significantly higher in the SIH group than in the IUGR group. Approximately 50% of the infants of the groups with SIH and IUGR were born prematurely. However, in all but 4 infants apgar score and pH of cord blood were in the normal range. Decision for premature delivery in the IUGR group were mostly based on elevated RI. It is concluded that this may have led to delivery before fetal decompensation occurred and thus may have had a positive effect on fetal outcome.

Fine needle aspiration of abdominal fat for the diagnosis of amyloidosis.

Amyloidosis is a dysproteinemia characterized by extracellular deposition of amyloid fibrils. Its diagnosis depends on the demonstration of the characteristic apple-green birefringence in tissue stained with Congo red. Aspiration of subcutaneous fat as a means of procuring tissue has received attention in the internal medicine literature. However, this application of fine needle aspiration biopsy has not been investigated extensively by cytopathologists. We therefore report our experience. Over the past two years we performed 18 aspirations of subcutaneous fat on 17 patients in whom amyloidosis was clinically suspected. Eight aspirates were positive for amyloid, and nine were negative. There were no known false-negative results. False positives were more problematic, occurred early in our experience and were due to overinterpretation of occasional long, slender, green strands representing collagen. The true positives were all characterized by large numbers of short, apple-green strands intimately associated with the fat, oriented in multiple directions and occurring in much, if not all, of the aspirated fat. Attention to details of the aspirated material other than the presence or absence of apple-green birefringence can lead to a correct distinction between amyloid and collagen. We conclude that abdominal fat pad aspiration is useful in the workup of suspected amyloidosis, especially since it is a safe, easily performed procedure.

Pharmacokinetics of fenoterol in pregnant and nonpregnant women.

The pharmacokinetics of the beta 2-adrenergic drug fenoterol, which is used as a tocolytic agent in pregnancy, has been investigated in pregnant (n = 9) and nonpregnant (n = 5) women during a constant rate intravenous infusion. Clearance and mean residence time were found to be 1990 (1879/2220; Median, Q25/Q75) ml/min and 9.2 (8.0/14.0) min in the pregnant and 2126 (1915/2130) ml/min and 16.6 (16.5/32.1) min in the nonpregnant women, respectively. In addition, fenoterol clearance was estimated in 88 women from a single blood sample collected at steady state during IV therapy and the effect of gestational age on clearance was studied. Clearance displayed large interindividual variation. There was no apparent correlation between clearance and gestational age. We conclude that there is no need to adjust the dose on pharmacokinetic grounds in the course of pregnancy.

Mechanical force, manually assisted short lever chiropractic adjustment.

OBJECTIVES: Chiropractic mechanical force, manually assisted short lever adjusting is a spinoff of the specific toggle recoil adjusting techniques, which were based on the original chiropractic subluxation theory propounded by Daniel David Palmer in 1895. This article reviews: a) the principles of the chiropractic subluxation complex from the standpoint of its historical origin and present-day scientific status; b) the purpose and objectives of specific spinal manipulative techniques; c) the use of mechanical adjusting instruments to effect a velocity/direction controlled adjustive thrust; and d) an assessment of scientific and clinical data relating to the biomechanical and neurological aspects of mechanical force, manually assisted short lever adjusting. DATA SOURCES: Prime sources were from the National Library of Medicine's on-line Index Medicus database, the Chirolars Research Resource Retrieval database, the Chiropractic Research Abstract Collection and the Chiropractic Library Consortium's reference works. Direct search of other nonindexed chiropractic sources was limited to those available in the collection of the National Institute of Chiropractic Research. Early information never documented by publication was obtained by written personal communication. STUDY SELECTION: The principal author selected articles reporting data (as opposed to anecdotal reports) from conference proceedings and peer-reviewed journals. DATA EXTRACTION: Data quality was assessed based on experimental conditions such as sample size, study design and statistical analysis. DATA SYNTHESIS: While mechanical force, manually assisted short lever adjusting seemingly is capable of beneficially altering the cause/effect relationship of spinal subluxations, more research in the nature of controlled clinical trials is needed to ascertain its benefits in the chiropractic treatment of specific conditions. CONCLUSIONS: Basic research is needed in order to establish the scientific basis for the chiropractic subluxation syndrome regardless of the technique employed.

The pharmacokinetics of the beta 2-adrenoceptor agonist fenoterol in healthy women.

We have studied the pharmacokinetics of fenoterol in healthy women during and after a 3 h intravenous infusion of different doses within the therapeutic range for tocolysis (0.5 microgram.min-1, 1.0 micrograms.min-1, and 2.0 micrograms.min-1). A specific and sensitive radioimmunoassay was used for the determination of fenoterol. For compartmental analysis the plasma concentration time data were fitted with the TOPFIT program, assuming two exponentials. The total clearance of fenoterol increased with dose (1299 ml.min-1 at 0.5 microgram.min-1, 1483 ml.min-1 at 1.0 micrograms.min-1, and 1924 ml.min-1 at 2.0 micrograms.min-1), as did the apparent volume of distribution (from 49 l at the lowest to 85 l at the highest dose). In contrast, the apparent half-lives were not dose-dependent, with t1/2.lambda 1 4.8 min and t1/2.lambda z 52 min.

Improvement of metabolic control and changes of fatty acid composition do not alter platelet aggregability and thromboxane production in type 2 diabetes mellitus.

To evaluate whether improvement of metabolic control or changes in fatty acid composition of serum lipids may alter thromboxane (TXB2) formation and platelet function we followed up 25 newly diagnosed type 2 diabetics without angiopathy for about 6 months. Improvement of metabolic control was associated with significant decrease in total cholesterol (C), HDL-C, LDL-C, triglycerides (TG) and ratios of total C/HDL-C and LDL-C/HDL-C, respectively. Palmitic acid of TG and phospholipids decreased significantly whereas linoleic acid increased in the two serum lipids. The ADP-induced platelet aggregability and sensitivity were not altered. There was even no effect on TXB2 synthesis capacity of clotting whole blood during 6 months of treatment. Platelet aggregability and TXB2 formation were not correlated to the degree of metabolic control, nor was there any correlation to serum lipids and their fatty acid composition.