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Biomedical subjects

C Unger

Publications and source records attributed to C Unger.

At least 19 recordsLinked to original sources
PubMed1999

Synthesis and PLA2-inhibitory properties of 2(R)-acetamido-alkylphosphomethanols with a variable aggregate anchor.

Acylamino inhibitors of 14 kDa-PLA2 were synthesized which differ in the moiety that is not bound into the enzyme's active site but immersed in the lipid aggregate when a ternary inhibitory complex is formed. Our results indicate that this part of the inhibitors does not significantly influence inhibitory properties as long the amphiphilic character is retained. So, inhibitory and biophysical properties should be variable independently.

Acetamides↗
PubMed1999

Vascular endothelial growth factor in the sera and effusions of patients with malignant and nonmalignant disease.

BACKGROUND: Clinical data clearly indicate a correlation between tumor neovascularization, aggressiveness of tumor growth, and metastatic spread. One of the key factors capable of stimulating tumor angiogenesis is vascular endothelial growth factor (VEGF). Using an immunoassay for VEGF, we assessed the levels of soluble VEGF in the sera and effusions of patients with malignant and nonmalignant disease as well as in the sera of healthy controls. METHODS: Using a sandwich enzyme-linked immunoadsorbent assay, the concentration of VEGF was measured in serum specimens (n=445) and effusions (n=56) collected from a total of 212 patients with various types of cancer, 88 patients with nonmalignant disease, and 145 healthy individuals. RESULTS: Low and rather stable levels of VEGF were detected in the serum of healthy individuals (median, 294 pg/mL; range, 30-1752 pg/mL; 95th percentile, 883 pg/mL). Compared with healthy individuals, serum levels in patients with acute infections were elevated (P=0.03), whereas patients with chronic cirrhosis had lower serum VEGF levels. Among patients with various types of neoplasia, VEGF serum levels in patients with ovarian or gastrointestinal carcinoma were significantly higher than in healthy individuals. Moreover, VEGF concentrations in sera from patients with metastatic disease were higher than in sera from patients with localized tumors. Maximum serum concentrations of VEGF (median, 1022 pg/mL; range, 349-7821 pg/mL) were found in patients with metastatic ovarian carcinoma. Median VEGF levels (and ranges) in malignant effusions were up to 10-fold higher than in matched serum samples: 5528 pg/mL (468-49269 pg/mL) in ovarian carcinoma, 885 pg/mL (77-14,337 pg/mL) in breast carcinoma, and 813 pg/mL (372-18,331 pg/mL) in gastrointestinal carcinoma. In contrast, ascitic fluid from patients with cirrhosis contained only 303 pg/mL (median, range 116-676 pg/mL) of VEGF, corresponding to the low serum levels in this patient group. CONCLUSIONS: Depending on the tumor type, elevated levels of VEGF are detectable in the serum of only 0-20% of patients with localized cancer but in 11-65% of patients with metastatic cancer. Of cytology-proven malignant ascites or peritoneal exudates from various malignancies, 46-96% show VEGF levels above the upper limit (95th percentile, 676 pg/mL) of nonmalignant ascites. Maximum VEGF concentrations in malignant effusions indicate abundant local release of VEGF within the pleural or peritoneal cavity. These results suggest that VEGF might play an important role in tumor progression and the formation of malignant effusions. Further studies are warranted to determine the clinical value of soluble VEGF as a tumor marker, a prognostic factor, and a surrogate indicator of tumor angiogenesis.

Adult↗
PubMed1999

Clinical activity and benefit of irinotecan (CPT-11) in patients with colorectal cancer truly resistant to 5-fluorouracil (5-FU).

The aim of this prospective study was to assess the efficacy, clinical benefit and safety of CPT-11 (irinotecan) in patients with stringently-defined 5-fluorouracil-resistant metastatic colorectal cancer (CRC). 107 patients with documented progression of metastatic CRC during 5-FU were treated with CPT-11 350 mg/m2 once every 3 weeks in a multicentre phase II study. Tumour response and toxicity were assessed using WHO criteria. Changes in performance status (PS), weight and pain were also measured. The WHO response rate was 13/95 (13.7%, 95% CI 7.5% to 22.3%) eligible patients with a median duration of response of 8.5 months (37 weeks, range: 18-53+). There was also a high rate of disease stabilisation (44.2%) with a median duration of 4.8 months. The probability of being free of progression at 4 months was 50%. Median survival from first administration of CPT-11 was 10.4 months or 45 weeks (range: 3-66+ weeks). There was weight stabilisation or gain in 81% (73/90) of patients, a favourable outcome in PS in 91% (82/90) (improvement of WHO PS 2 or stabilisation of PS 0-1), and pain relief in 54% (26/48). There were no toxic deaths. Neutropenia was short-lasting and non-cumulative. Diarrhoea grade > or = 3 occurred in 7% of cycles and 28/107 (26%) of patients. CPT-11 350 mg/m2 once every 3 weeks has an encouraging degree of activity in progressive metastatic CRC truly resistant to 5-FU with a relatively high rate of tumour growth control translated into clinical benefit. The toxicity profile of CPT-11 is becoming better understood and has been considerably improved.

Adult↗
PubMed1999

Identification of a clinically relevant immunodominant region of collagen IV in Goodpasture disease.

BACKGROUND: The characteristic feature of Goodpasture disease is the occurrence of an autoantibody response to the noncollagenous domain of the alpha3 chain of type IV collagen [alpha3(IV)NC1] in the alveolar and glomerular basement membrane. These antibodies are associated with the development of a rapidly progressive glomerulonephritis, with or without lung hemorrhage, whereas autoantibodies specific for the other alpha chains of the heterotrimeric type IV collagen probably do not cause disease. In this study, we have investigated whether differences in fine specificity of autoimmune recognition of the alpha3(IV)NC1 correlate with clinical outcome. METHODS: For mapping of antibody binding to type IV collagen, chimeric collagen constructs were generated in which parts of the alpha3(IV)NC1 domain were replaced by the corresponding sequences of homologous nonreactive alpha1(IV). The different recombinant collagen chimeras allowed the analysis of antibody specificities in 77 sera from well-documented patients. RESULTS: One construct that harbors the aminoterminal third of the alpha3(IV)NC1 was recognized by all sera, indicating that it represents the dominant target of the B-cell response in Goodpasture disease. Seventy percent of the samples recognized other parts of the molecule as well. However, only reactivity to the N-terminus of the alpha3(IV)NC1 correlated with prognosis, that is, kidney survival after six months of follow-up. CONCLUSION: The results indicate the crucial importance of antibody recognition of this particular domain for the pathogenesis of Goodpasture disease, thereby opening new avenues for the development of better diagnostic and therapeutic procedures.

Anti-Glomerular Basement Membrane Disease↗
PubMed1998

Synthesis and in vitro efficacy of transferrin conjugates of the anticancer drug chlorambucil.

One strategy for improving the selectivity and toxicity profile of antitumor agents is to design drug carrier systems employing soluble macromolecules or carrier proteins. Thus, five maleimide derivatives of chlorambucil were bound to thiolated human serum transferrin which differ in the stability of the chemical link between drug and spacer. The maleimide ester derivatives 1 and 2 were prepared by reacting 2-hydroxyethylmaleimide or 3-maleimidophenol with the carboxyl group of chlorambucil, and the carboxylic hydrazone derivatives 5-7 were obtained through reaction of 2-maleimidoacetaldehyde, 3-maleimidoacetophenone, or 3-maleimidobenzaldehyde with the carboxylic acid hydrazide derivative of chlorambucil. The alkylating activity of transferrin-bound chlorambucil was determined with the aid of 4-(4-nitrobenzyl)pyridine (NBP) demonstrating that on average 3 equivalents were protein-bound. Evaluation of the cytotoxicity of free chlorambucil and the respective transferrin conjugates in the MCF7 mammary carcinoma and MOLT4 leukemia cell line employing a propidium iodide fluorescence assay demonstrated that the conjugates in which chlorambucil was bound to transferrin through non-acid-sensitive linkers, i.e., an ester or benzaldehyde carboxylic hydrazone bond, were not, on the whole, as active as chlorambucil. In contrast, the two conjugates in which chlorambucil was bound to transferrin through acid-sensitive carboxylic hydrazone bonds were as active as or more active than chlorambucil in both cell lines. Especially, the conjugate in which chlorambucil was bound to transferrin through an acetaldehyde carboxylic hydrazone bond exhibited IC50 values which were approximately 3-18-fold lower than those of chlorambucil. Preliminary toxicity studies in mice showed that this conjugate can be administered at higher doses in comparison to unbound chlorambucil. The structure-activity relationships of the transferrin conjugates are discussed with respect to their pH-dependent acid sensitivity, their serum stability, and their cytotoxicity.

Animals↗
PubMed1998

Inhibition of 14-kDa PLA2 by 2-acylamino-alkylphospholipids: the influence of amide acidity.

2-Acylamino-alkyl phospholipids are potent competitive inhibitors of 14-kDa phospholipases A2 (e.g., human nonpancreatic secretory PLA2). As concluded from X-ray studies the amide hydrogen of these inhibitors forms a hydrogen bond to His-48 in the active site of the enzyme. We investigated the quantitative contribution of this hydrogen bond to inhibition using especially designed inhibitors that bear different acyl chains with and without electron withdrawing or donating substituents, thus differing in amide acidity. Relative free enthalpies DeltaDeltaG of enzyme-inhibitor complex formations were calculated from Xi(50) values determined by pH-stat titration using a mixed micelles assay and PLA2 from Naja mocambique mocambique. A quantitative relationship between amide acidity and DeltaDeltaG values is presented. Comparison of isoacidic and isosteric inhibitors reveals that (i) the hydrogen bond of the amide proton to His-48 is crucial for strong PLA2 inhibition, (ii) regardless of the headgroup unsubstituted N-acyl groups result in optimal amide acidity for PLA2 inhibition and (iii) the exceptionally strong inhibition by acetamides and the isosteric fluoroacetamides is due to an additional steric effect.

Amides↗
PubMed1998

Arthritis-related B cell epitopes in collagen II are conformation-dependent and sterically privileged in accessible sites of cartilage collagen fibrils.

In collagen-induced arthritis, a murine autoimmune model for rheumatoid arthritis, immunization with native but not heat-denatured cartilage-specific collagen type II (CII) induces a B cell response that largely contributes to arthritogenicity. Previously, we have shown that monoclonal antibodies established from arthritis prone DBA/1 mice require the triple-helical conformation of their epitopes for antigen recognition. Here, we present a novel approach to characterize arthritis-related conformational epitopes by preparing a panel of 130 chimeric collagen X/CII molecules. The insertion of a series of CII cassettes into the triple-helical recombinant collagen X allowed for the first time the identification of five triple-helical immunodominant domains of 5-11 amino acid length, to which 75% of 36 monoclonal antibodies bound. A consensus motif, "R G hydrophobic," was found in all immunodominant epitopes. The antibodies were encoded by a certain combination of V-genes in germline configuration, indicating a role of the consensus motif in V-gene selection. The immunodominant domains are spread over the entire monomeric CII molecule with no apparent order; however, a highly organized arrangement became apparent when the CII molecules were displayed in the quarter-staggered assembly within a fibril. This discrete epitope organization most likely reflects structural constraints that restrict the exposure of CII epitopes on the surface of heterotypically assembled cartilage fibrils. Thus, our data suggest a preimmune B cell selection process that is biased by the accessibility of CII determinants in the intact cartilage tissue.

Animals↗
PubMed1998

Albumin conjugates of the anticancer drug chlorambucil: synthesis, characterization, and in vitro efficacy.

In our efforts to improve the selectivity and toxicity profile of antitumor agents, four maleimide derivatives of chlorambucil (1-4) were bound to thiolated human serum albumin which differ in the stability of the chemical link between drug and spacer. 1 is an aliphatic maleimide ester derivative of chlorambucil, whereas 2-4 are acetaldehyde, acetophenone, and benzaldehyde carboxylic hydrazone derivatives. HPLC stability studies at pH 5.0 with the related model compounds 5, 7, 8, and 9, in which chlorambucil was substituted by 4-phenylbutyric acid, demonstrated that the carboxylic hydrazone derivatives have acid-sensitive properties; the acid lability of 7 was particular prominent with a half-life of only a few hours. The alkylating activity of albumin-bound chlorambucil was determined with the aid of 4-(4-nitrobenzyl)-pyridine (NBP), demonstrating that on average three equivalents were protein-bound. Evaluation of the cytotoxicity of free chlorambucil and the respective albumin conjugates in the MCF7 mamma carcinoma and MOLT4 leukemia cell line employing a propidium iodide fluorescence assay demonstrated that the conjugate in which chlorambucil was bound to albumin through an ester bond was not as active as chlorambucil. In contrast, the conjugates in which chlorambucil was bound to albumin through carboxylic hydrazone bonds were as or more active than chlorambucil in both cell lines. In particular, the conjugate in which chlorambucil was bound to albumin through an acetaldehyde carboxylic hydrazone bond exhibited IC50 values which were approximately 4-fold (MCF7) to 13-fold (MOLT4) lower than those of chlorambucil. Preliminary toxicity studies in mice showed that this conjugate can be administered at higher doses in comparison to unbound chlorambucil.

Animals↗
PubMed1998

Transferrin conjugates of doxorubicin: synthesis, characterization, cellular uptake, and in vitro efficacy.

One strategy for improving the antitumor selectivity and toxicity profile of antitumor agents is to design drug carrier systems employing suitable carrier proteins. Thus, thiolated human serum transferrin was conjugated with four maleimide derivatives of doxorubicin that differed in the stability of the chemical link between drug and spacer. Of the maleimide derivatives, 3-maleimidobenzoic or 4-maleimidophenylacetic acid was bound to the 3'-amino position of doxorubicin through a benzoyl or phenylacetyl amide bond, and 3-maleimidobenzoic acid hydrazide or 4-maleimidophenylacetic acid hydrazide was bound to the 13-keto position through a benzoyl hydrazone or phenylacetyl hydrazone bond. The acid-sensitive transferrin conjugates prepared with the carboxylic hydrazone doxorubicin derivatives exhibited an inhibitory efficacy in the MDA-MB-468 breast cancer cell line and U937 leukemia cell line comparable to that of the free drug (employing the BrdU (5-bromo-2'-deoxyuridine) incorporation assay and tritiated thymidine incorporation assay, respectively, IC50 approximately 0.1-1 mM), whereas conjugates with the amide derivatives showed no activity. Furthermore, antiproliferative activity of the most active transferrin conjugate (i.e. the conjugate containing a benzoyl hydrazone link) was demonstrated in the LXFL 529 lung carcinoma cell line employing a sulforhodamine B assay. In contrast to in vitro studies in tumor cells, cell culture experiments performed with human endothelial cells (HUVEC) showed that the acid-sensitive transferrin conjugates of doxorubicin were significantly less active than free doxorubicin (IC50 values approximately 10-40 higher by the BrdU incorporation assay), indicating selectivity of the doxorubicin-transferrin conjugates for tumor cells. Fluorescence microscopy studies in the MDA-MB-468 breast cancer cell showed that free doxorubicin accumulates in the cell nucleus, whereas doxorubicin of the transferrin conjugates is found localized primarily in the cytoplasm. The differences in the intracellular distribution between transferrin-doxorubicin conjugates and doxorubicin were confirmed by laser scanning confocal microscopy in LXFL 529 cells after a 24 h incubation that revealed an uptake and mode of action other than intercalation with DNA. The relationship between stability, cellular uptake, and cytotoxicity of the conjugates is discussed.

Chromatography, High Pressure Liquid↗
PubMed1998

Clinical phase I study with one-hour paclitaxel infusion.

BACKGROUND: Paclitaxel (PAC) is one of the major anti-cancer drugs, effective in different tumors. Studies with 24-hour infusion with 135 mg/m2 and a three-hour infusion with 175 mg/m2 showed a significant schedule-dependent toxicity. We evaluated a one-hour infusion schedule within a phase I study to determine the dose limiting toxicity (DLT), the maximum tolerated dose (MTD), and the anti-cancer efficacy. PATIENTS AND METHODS: Patients with advanced malignant tumors were treated within cohorts by one-hour infusional paclitaxel starting with 150 mg/m2 and stepwise escalation with 25 mg/m2 increments. Therapy was repeated in three-week intervals. Cycles were repeated until progression. Toxicity was closely monitored, anti-cancer efficacy was only evaluated in those patients who received at minimum two treatment cycles. RESULTS: Thirty-four patients entered the study (11 NSCLC, five SCLC, seven ovarian cancer, one cervix cancer, nine MBC, one HN cancer). The MTD was PAC 250 mg/m2. The DLT was central and peripheral neuropathy (WHO grade 3). Other significant toxicities were fatigue, myalgia/arthralgia and paraesthesia. No significant myelotoxicity was observed. Totally twentyone patients were evaluable for response. A partial response was observed in five (24%) patients (two NSCLC, two ovarian cancer, one head and neck cancer). Three (14%) patients had stable disease and in 13 (62%) patients progressive disease was observed. CONCLUSIONS: Paclitaxel 225 mg/m2 on day 1 administered as one-hour infusion and repeated every three weeks can be given safely, featured no relevant myelotoxicity, and is the recommended dose for phase II studies.

Adult↗
PubMed1998

Clinical and pharmacologic phase I study of Cemadotin-HCl (LU103793), a novel antimitotic peptide, given as 24-hour infusion in patients with advanced cancer. A study of the Arbeitsgemeinschaft Internistische Onkologie (AIO) Phase I Group and Arbeitsgruppe Pharmakologie in der Onkologie und Haematologie (APOH) Group of the German Cancer Society.

PURPOSE: To determine the maximum tolerable dose (MTD), principal toxicity, and pharmacologic behaviour of Cemadotin-HCl, a novel antimitotic peptide. PATIENTS AND METHODS: Cemadotin-HCl (10.0 to 27.5 mg/m2/day every three weeks) was administered as a 24-hour intravenous (i.v.) continuous infusion to patients with advanced cancer. Pharmacokinetic analyses were performed during the first treatment cycle. Blood samples were taken over 48 hours and analyzed by radioimmunoassay. RESULTS: Hypertension was the dose-limiting toxicity (DLT). This type of toxicity was observed at all dose levels, but grade 3 (CTC) was observed only at dose levels 20.0, 25.0 and 27.5 mg/m2. This effect was reversible but in three patients associated with signs of cardiac ischemia. Other significant toxic effects were neutropenia, asthenia, tumor pain and transient liver enzyme elevation. A linear pharmacokinetics was observed. The best curve fit was obtained with a two-compartment model with a terminal half-life of approximately 10 hours at each dose level, a volume of distribution at steady state of approximately 9 l/m2 and a total clearance of approximately 0.6 l/hour/m2. Neither partial nor complete responses were observed although minor tumor regressions were seen in a patient with carcinoma of unknown primary (CUP) and in another patient with liver metastases from a colon cancer. CONCLUSIONS: Hypertension was the dose-limiting toxicity of Cemadotin-HCl administered as a continuous 24-hour infusion. The recommended dose for further evaluation of its anticancer efficacy in disease-oriented phase II studies with this schedule is 15.0 mg/m2. The nature of the principal cardiovascular toxicity remains unclear. The observed toxicities appeared to be significant but manageable.

Adult↗
PubMed1998

Wild-type function of the p53 tumor suppressor protein is not required for apoptosis of mouse hepatoma cells.

The role of the tumor suppressor protein p53 in apoptosis of mouse hepatoma cells was studied. Different lines were used which were either p53 wild-type or carried various types of heterozygous or homozygous p53 mutations. The presence of mutations was demonstrated to correlate with a lack in transactivating activity of p53. While UV-light effectively produced apoptosis in cells of all lines, irrespective of their p53 mutational status, gamma-irradiation induced the formation of micronuclei but failed to induce apoptosis. Both UV- and gamma-irradiation led to nuclear accumulation and increases in p53 protein in p53 wild-type cells. Similarly, no significant differences in apoptotic response between p53 wild-type and p53 mutated cells were seen with other apoptotic stimuli like CD95/APO-1/Fas or TNFalpha. These data suggest that wild-type p53 is not required for induction of apoptosis in mouse hepatoma cells which may explain the apparent lack of p53 mutations in mouse liver tumors.

Animals↗
PubMed1998

Preparation, characterization and in vitro efficacy of albumin conjugates of doxorubicin.

One strategy for improving the antitumor selectivity and toxicity profile of antitumor agents is to design drug carrier systems with suitable transport proteins. Thus, four maleimide derivatives of doxorubicin were bound to thiolated human serum albumin which differed in the stability of the chemical link between drug and spacer. In the maleimide derivatives, 3-maleimidobenzoic or 4-maleimidophenylacetic acid was bound to the 3'-amino position of doxorubicin through a benzoyl or phenylacetyl amide bond and 3-maleimidobenzoic acid hydrazide or 4-maleimidophenylacetic acid hydrazide was bound to the 13-keto position through a benzoyl hydrazone or phenylacetyl hydrazone bond. The acid-sensitive albumin conjugates prepared with the carboxylic hydrazone doxorubicin derivatives exhibited an inhibitory efficacy in the MDA-MB-468 breast cancer cell line and U937 leukemia cell line comparable with that of the free drug (using the BrdU-(5-bromo-2'-deoxyuridine)-incorporation assay and tritiated thymidine incorporation assay respectively, IC50 approximately 0.1-1 microM) whereas conjugates with the amide derivatives showed no or only marginal activity. These results demonstrate that antiproliferative activity depends on the nature of the chemical bond between doxorubicin and carrier protein. Acid-sensitive albumin conjugates are suitable candidates for further in vitro and in vivo assessment.

Antibiotics, Antineoplastic↗
PubMed1997

A microtiter-based fluorescence assay for (1,3)-beta-glucan synthases.

A high-throughput assay for UDP-Glc:(1,3)-beta-glucan synthase(EC 2.4.1.34, UDP-glucose:1,3-beta-D-glucan, 3-beta-glucosyltransferase) from fungi and higher plants is described. The assay is performed in microtiter plates and is extremely inexpensive compared to other standard assays for these enzymes. The reduction in price is achieved by replacing the conventional substrate UDP-[14C]Glc with its nonradioactive counterpart, and the nonradioactive glucan produced is quantified as a fluorescent complex following specific interaction with the fluorochrome present in commercial aniline blue. In addition to a > 100-fold reduction in cost, the assay is highly reproducible and nearly as sensitive as radioactive assays and has the additional advantages of increased safety and avoidance of the need for filtration and washing steps to collect the glucan product. As such, the assay is highly suitable for high-throughput screening for inhibitors of these enzymes.

Aniline Compounds↗
PubMed1997

Premenopausal node-negative breast cancer: may adjuvant chemotherapy be indicated by the analysis of nuclear DNA dynamics?

The management of premenopausal node-negative breast cancer patients is discussed controversially. Accurate cellular as well as biochemical markers are essential for this cancer group to identify high risk patients needing adjuvant chemotherapy. In the present study, flow cytometric DNA analysis (DNA-ploidy status, DNA-index, S-phase fraction, S+(G2+M)-phase fraction) and clinico-pathological variables (clinical stage, tumor size, receptor status, age, histological type and grade) as prognostic factors were determined on paraffin-embedded tumors to predict overall survival (OS) and disease-free survival (DFS). Median observation time was 6.1 years (n = 57). S+(G2+M)-phase fraction was the only flow cytometric DNA predictor of overall survival in the univariate analysis (log-rank test): As compared to the patients with lower S+(G2+M)-phase fraction (< or = 9.3%), patients with S+(G2+M)-phase fraction greater than 9.3% had shorter survival (P = 0.039). Of all the clinico-pathological parameters analyzed (univariate analysis), the survival time was found to be longer when estrogen- and/or progesterone-receptor status was positive (overall survival: P = 0.039; disease-free survival: P = 0.017) and the histological grade was low (overall survival: I + II vs III: P = 0.024; I vs II vs III: P = 0.046). In the multivariate analysis, receptor status was the strongest predictor for overall and disease-free survival. These results suggest that S+(G2+M)-phase fraction in premenopausal node-negative breast cancer could be an additional valuable prognostic factor to classify high risk breast cancer patients needing adjuvant chemotherapy.

Adult↗
PubMed1997

Premature contractions: possible influence of sonographic measurement of cervical length on clinical management.

In a retrospective case control study with historical controls, the influence of the introduction of vaginal sonographic cervical length measurement on the utilization of hospital services and pregnancy outcome of gravid women at risk of preterm delivery was examined. Prior to the introduction of vaginal ultrasonography to measure cervical length, we registered 76 hospitalizations totalling 1827 hospitalization days due to premature cervical ripening and/or premature labor in 1991 and 1992. In 1994 and 1995, after vaginal ultrasonography was introduced and intravenous tocolysis was limited to cases with cervical shortening to less than 3 cm, there were 64 admissions resulting in just 869 hospitalization days. Long-term hospitalizations (over 10 days) were reduced from 55 to 25 cases (p < 0.0001) and the median length of hospital stay decreased from 18 to 8 days (p < 0.0001). The number of preterm births (< or = 37 weeks) remained stable: 12 cases in 1991-1992 and 13 cases in 1994-1995. In conclusion, vaginal sonographic measurement of cervical length provides an objective criterion for cervical shortening with premature labor. The method could therefore be a suitable means of reducing unnecessary therapeutic interventions in gravid women with premature contractions and/or cervical dilatation. A prospective randomized trial to confirm these findings is suggested.

Case-Control Studies↗