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Down-regulation of p53 by double-stranded RNA modulates the antiviral response.

p53 has been well characterized as a tumor suppressor gene, but its role in antiviral defense remains unclear. A recent report has demonstrated that p53 can be induced by interferons and is activated after vesicular stomatitis virus (VSV) infection. We observed that different nononcogenic viruses, including encephalomyocarditis virus (EMCV) and human parainfluenza virus type 3 (HPIV3), induced down-regulation of p53 in infected cells. Double-stranded RNA (dsRNA) and a mutant vaccinia virus lacking the dsRNA binding protein E3L can also induce this effect, indicating that dsRNA formed during viral infection is likely the trigger for down-regulation of p53. The mechanism of down-regulation of p53 by dsRNA relies on translation inhibition mediated by the PKR and RNase L pathways. In the absence of p53, the replication of both EMCV and HPIV3 was retarded, whereas, conversely, VSV replication was enhanced. Cell cycle analysis indicated that wild-type (WT) but not p53 knockout (KO) fibroblasts undergo an early-G(1) arrest following dsRNA treatment. Moreover, in WT cells the onset of dsRNA-induced apoptosis begins after p53 levels are down-regulated, whereas p53 KO cells, which lack the early-G(1) arrest, rapidly undergo apoptosis. Hence, our data suggest that the down-regulation of p53 facilitates apoptosis, thereby limiting viral replication.

Animals↗

Assessment of scales of disability and handicap for stroke patients.

BACKGROUND AND PURPOSE: The purpose of the study is to compare the reliability of the Barthel activities of daily living score, which assesses disability, with the Rankin scale, which assesses handicap, and to determine their mutual agreement. METHODS: Fifty patients with stroke of varying severity were identified by a community-based stroke register and interviewed by two of three research nurses on two occasions that were 2-3 weeks apart. RESULTS: There was no evidence of a systematic difference between the first and second measurements. Repeatability was assessed using a kappa statistic with quadratic disagreement weights (kappa w) to take account of extreme differences. This measure was very good for both Barthel (kappa w = 0.98) and Rankin (kappa w = 0.95) scales. There was also excellent agreement between raters for the Barthel scale (kappa w greater than or equal to 0.88), but some indication of disagreement (kappa w = 0.75) between raters for the Rankin scale. Analysis of variance confirmed these findings. A conversion from the Barthel to the Rankin scale can be derived by assigning the most common Rankin score for the subjects with a given Barthel score, producing a kappa w of 0.91 for agreement. CONCLUSIONS: The Barthel scale is a more reliable and less subjective scale for assessing disability, from which a Rankin handicap score can then be derived to enable those managing stroke patients to assess aspects of handicap as well as disability.

Activities of Daily Living↗

5alpha-reductase activity in women with polycystic ovary syndrome.

The recent demonstration of high concentrations of 5alpha-androstane-3,17-dione in the follicular fluid of polycystic ovaries suggests a potential role for 5alpha-reduced androgens in the etiology of polycystic ovary syndrome (PCOS). The purpose of the present study was to determine whether there is increased 5alpha-reductase activity or messenger ribonucleic acid (mRNA) expression in polycystic ovaries. 5alpha-Reductase 1 and 5alpha-reductase 2 mRNAs were measured in thecal (TC) and granulosa (GC) cells from individual follicles of 18 women with PCOS and 26 regularly cycling control women. Both 5alpha-reductase 1 and 2 mRNA expression was higher in GC than in TC, and 5alpha-reductase 2 mRNA levels were approximately 3-fold higher than 5alpha-reductase 1 mRNA. 5alpha-Reductase 1 and 2 mRNA expression were similar in GC from PCOS and control women, but 5alpha-reductase mRNA was decreased in TC from PCOS follicles. In control women, 5alpha-reductase 2 mRNA was highest in GC from 3- to 5-mm follicles and decreased to undetectable levels in GC from 7-mm follicles. A similar pattern of expression was present in GC from PCOS follicles, but detectable levels of 5alpha-reductase 2 mRNA were present in GC from 7-mm follicles. 5alpha-Reductase activity was measured in whole follicles by measuring the conversion of radiolabeled testosterone to dihydrotestosterone. Kinetic analysis of total 5alpha-reductase activity at physiological pH revealed a Km of 1.46 micromol/L and a maximal velocity of 0.31 nmol/min x mg protein, indicating predominantly type 1 activity. The total 5alpha-reductase activity was approximately 4-fold higher in PCOS follicles than in control follicles. These data demonstrate elevated 5alpha-reductase activity in polycystic ovaries and support the hypothesis that 5alpha-reduced androgens may play a role in the pathogenesis of PCOS.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

In vivo metabolism of radiolabeled putrescine in gliomas: implications for positron emission tomography of brain tumors.

The in vivo uptake and metabolism of radiolabeled putrescine was examined in two glioma models: (a) the T9 gliosarcoma in the CD Fischer rat and (b) the U-87 MG human glioblastoma in the athymic (nude) mouse. Autoradiography after parenteral administration of [14C]putrescine revealed rapid and selective uptake by both tumors compared with normal brain. Polyamine analysis of the rat gliosarcoma demonstrated minimal conversion of labeled putrescine to its metabolites, spermidine and spermine, at 5 and 30 minutes after intravenous injection. The human glioblastoma also exhibited minimal polyamine conversion at 5 minutes, although there was a trend toward significant metabolism at longer time periods (30 and 45 minutes). In addition, the human glioblastoma produced nonpolyamine metabolites that suggest an alternative pathway of putrescine metabolism via gamma-aminobutyric acid. These in vivo findings are discussed in relation to the usefulness of putrescine as a marker for positron emission tomography of human gliomas.

Animals↗

Circulatory variables and the flight performance of birds.

When considering the 'burst' flight performance of birds, such as during take-off, one of the most important structural variables is the ratio of the mass of the flight muscle myofibrils with respect to body mass. However, when considering 'prolonged' flight performance the variable of interest should be the body mass ratio of the mass of the flight muscle myofibrils that can be perfused sustainably with metabolites via the blood supply. The latter variable should be related to blood flow (ml min(-1)), which in turn has been shown to be a function of heart muscle mass, the value of which is more easily obtainable for different species than that for the mass of perfused muscle. The limited empirical evidence available suggests that for birds and mammals the rate of maximum oxygen consumption scales with heart mass (Mh) as Mh 0.88 and that for birds Mh scales with body mass (Mb) as Mb 0.92, leading to the conclusion that the rate of maximum oxygen consumption in birds scales with an exponent of around Mb 0.82. A similar exponent would be expected for the rate of maximum oxygen consumption with respect to the flight muscle mass of birds. This suggests that the sustainable power output from the flight muscles may ultimately be limiting the flight performance of very large flying animals, but as a result of circulatory constraints rather than biomechanical considerations of the flight muscles per se. Under the particular circumstances of sustainable flight performance, calculations of rates of metabolic energy consumed by the flight muscles can be compared directly with the estimates of biomechanical power output required, as calculated using various aerodynamic models. The difference between these calculated values for rates of energy input and output from the muscles is equivalent to the 'apparent' mechanochemical conversion efficiency. The results of one such analysis, of the maximum sustainable flight performance of migratory birds, leads to the conclusion that the efficiency of the flight muscles appears to scale as Mb 0.14. However, much of this apparent scaling may be an artefact of the application and assumptions of the models. The resolution of this issue is only likely to come from studying bird species at either extreme of the size range.

Animals↗

HLA haplotypes and hormonal studies in 25 Italian families of patients with classical and non-classical 21-OH deficiency.

To investigate the genetic polymorphisms of the HLA region and the molecular defect of the P450c21B gene in congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency, we studied 89 individuals from 25 families of CAH patients (14 classical forms, 11 non-classical forms). The following immunogenetic and hormonal investigations were performed: HLA-A and B typing, restriction fragment length polymorphism (RFLP) analysis of 21-hydroxylase A and B genes, and serum 17-OH-progesterone values determined basally and 60 min after ACTH stimulation. In the patients affected by the classical form, RFLP analysis revealed 5 deletions and 1 gene conversion in 6 haplotypes and no molecular defect in the others, who probably carry point mutations. In the patients with non-classical form we found P450c21A duplication in 11/18 haplotypes; 9 of the 11 patients shared the HLA-B14 allele. Utilizing both hormonal and genetic data we identified two cryptic forms; hormonal data alone failed to differentiate heterozygous from normal individuals.

17-alpha-Hydroxyprogesterone↗

[In contact with genetic diseases: norm and reason as cultural traditions in medical staff discourse at the Fernandes Figueira Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil].

This study aims to detect the influence of deeply rooted traditions on physicians' discursive constructions concerning children with genetic diseases involving malformations and mental retardation. It also aims to capture the reflections resulting from the professional care for (and contact with) these children. All the physicians work at the Fernandes Figueira Institute, Oswaldo Cruz Foundation, in Rio de Janeiro, Brazil. Data were collected using oral interviews (in the form of conversational narratives) and were submitted to semiotic analysis. Four traditions were found in the medical discourse: norm, reason, family, and religion. This article focuses exclusively on norm and reason, highlighting how dismorphism, congenital malformations, and mental retardation associated with genetic diseases defy the established norms of perfection, beauty, and productivity. Therefore, feelings of uneasiness, powerlessness, and frustration are increased. The article also discusses how reason, one of the most important cultural traditions organizing modern thought, shapes medical discourse on genetic syndromes associated with mental retardation.

Brazil↗

Cost advantage of voriconazole over amphotericin B deoxycholate for primary treatment of invasive aspergillosis.

STUDY OBJECTIVES: Using data from a published clinical trial, our objectives were to compare the cost advantage of voriconazole over amphotericin B deoxycholate (AmBd) for primary treatment of invasive aspergillosis and to determine the financial impact the findings would have in a real-world clinical setting. DESIGN: Pharmacoeconomic analysis. SETTING: University hospital. PATIENTS: Two hundred seventy-seven patients in the modified intent-to-treat population. MEASUREMENTS AND MAIN RESULTS: An analysis was performed of drug acquisition costs for all patients in the modified intent-to-treat population, which consisted of 144 patients in the voriconazole group and 133 in the AmBd group. The analysis included costs of initial drug therapy; conversion from intravenous to oral treatment for patients receiving voriconazole; and the types, dosages, and duration of other licensed [Food and Drug Administration-approved] antifungal therapy (OLAT) for up to three OLAT regimens/patient. Current drug costs for our university hospital were used for all calculations. Total voriconazole costs were $784,405 ($581,008 for initial therapy with voriconazole, $203,397 for OLAT) compared with $852,238 for AmBd ($31,677 for initial AmBd therapy, $820,561 for OLAT). Over the 12-week study period, the cost/patient was $961 less for patients whose initial treatment was voriconazole than for those whose initial treatment was AmBd. Other licensed antifungal therapy accounted for 26% and 96% of total drug costs for voriconazole and AmBd, respectively. Other licensed antifungal therapy was given to 36% of voriconazole-treated patients and 80% of AmBd-treated patients. CONCLUSION: These data demonstrate the importance of evaluating total drug costs when comparing treatment regimens and not just initial therapy. Initial therapy with voriconazole had a cost advantage over AmBd in total antifungal drug cost/patient.

Administration, Oral↗

Effects of N1, N13-diethylnorspermine (DENSPM) and X-radiation treatment on human colorectal tumor clones with varying X-radiation and drug responses.

This study was designed to examine the effects of treatment with N1, N13-diethylnorspermine (DENSPM), a spermine analog, and X radiation on survival and on the polyamine and spermidine/spermine N1-acetyltransferase (SSAT) levels in closely related human colorectal tumor (HCT116) clones exhibiting a wide range of X-radiation and drug responses. After treatment with DENSPM and X radiation, clonogenic cell survival was measured. SSAT protein levels were measured by Western blot analysis and SSAT enzymatic activities by the conversion of [1-14C]acetyl-CoA into [1-14C]acetylspermidine. Polyamine [i.e. putrescine (PUT), spermine (SPM) and spermidine (SPD)] levels were measured with high-performance liquid chromatography. DENSPM enhanced the efficacy of radiation treatment in HCT116, HCT116-Clone2 (a radiation-resistant clone) and HCT116-Clone10 (a clone with similar X-radiation response as the parental HCT116 cells) but not in HCT116-CloneK (an X-radiation-sensitive but relatively drug-resistant clone). Treatment with DENSPM without X radiation caused the most significant increase in SSAT activity (approximately 22-fold) and an almost complete depletion of SPD levels in HCT116-CloneK. Our results suggest that (a) the lack of sensitization of X-radiation treatment by DENSPM in HCT116-CloneK was likely due to the prior depletion of SPD levels by DENSPM alone, (b) natural polyamine contents and/or inducibility of SSAT may be important factors influencing cellular response to combined X-radiation and DENSPM treatments, and (c) more importantly, there may be a potentially novel role for combining polyamine analogs such as DENSPM with X rays.

Antineoplastic Agents↗

Clinical outcome of dogs with grade-II mast cell tumors treated with surgery alone: 55 cases (1996-1999).

OBJECTIVE: To determine outcome for dogs with grade-II mast cell tumors treated with surgery alone. DESIGN: Retrospective study. ANIMALS: 55 dogs. PROCEDURES: Medical records were examined, and signalment; location and size of tumor; staging status; dates of local recurrence, metastasis, death, or last follow-up examination; status of surgical margins; previous surgery; postoperative complications; and cause of death were recorded. Follow-up information was obtained via reexamination or telephone conversations with owners or referring veterinarians. Univariate analysis was performed to identify prognostic factors. RESULTS: 60 tumors in 55 dogs were included. Median follow-up time was 540 days. Three (5%) mast cell tumors recurred locally; median time to local recurrence was 62 days. Six (11%) dogs developed another mast cell tumor at a different cutaneous location; median time to a different location was 240 days. Three (5%) dogs developed metastases; median time to metastasis was 158 days. Fourteen dogs died; 3 deaths were related to mast cell tumor, and 7 were unrelated. The relationship with mast cell tumor was not known for 4. Median survival times were 151, 841, and 827 days, respectively, for these 3 groups. Forty-six (84%) dogs were free of mast cell tumors during the study period. A reliable prognostic factor could not be identified. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that additional local treatment may not be required after complete excision of grade-II mast cell tumors and that most dogs do not require systemic treatment.

Animals↗

Tuberculosis control in the Caucasus: successes and constraints in DOTS implementation.

SETTING: The pilot projects for tuberculosis (TB) control, supported by the World Health Organization (WHO) and based on the WHO recommended control strategy, directly-observed treatment, short-course (DOTS) in the Caucasian countries (Armenia, Azerbaijan, Georgia). OBJECTIVE: To evaluate the results 2 years after the implementation of the pilot projects. METHODS: Analysis of data on case detection, sputum conversion and treatment outcome reported quarterly to the WHO from the Ministries of Health in each country. RESULTS: Since the establishment of the project, 1330, 764 and 4866 new cases and relapses, respectively, of TB have been detected in the pilot areas of Armenia, Azerbaijan and Georgia. In Armenia and Azerbaijan, respectively 46% and 57% of all cases were smear positive, whilst in Georgia, the corresponding figure was only 12%. After 3 months' treatment, 93% of new smear-positive patients had become smear-negative. The sputum conversion rate for relapses and other retreatment cases (failure, treatment interrupted) was 85%. In Armenia, 78.1% of new smear-positive patients were treated successfully (cured or completed treatment). The corresponding percentages for Azerbaijan and Georgia were 87.9% and 59.6%. Treatment success rates among retreatment cases was generally low, at respectively 46%, 64%, and 35%, in Armenia, Azerbaijan, and Georgia. CONCLUSION: The results of the implementation of the WHO TB control pilot projects in Armenia, Azerbaijan and Georgia suggest that the DOTS strategy is feasible in emergency situations in general, and in the Caucasus in particular.

Disease Notification↗

Information needs at the end of life: a content analysis of one person's story.

During the last phase of life, a person may need a variety of information to help her or him cope with dying and death. This article describes the nature of information needed during this stage. A content analysis was done of a book of conversations between a husband who was dying and his wife who is a grief counselor to determine his information needs. Four categories of needs were proposed, including physical, emotional, spiritual, and financial. Information needs germane to each category were identified. More research needs to be done by library and information science professionals to determine the information needs of people who are dying, as well as those of their families and the health professionals who care for them.

Aged↗

The morphogenesis of bone in replicas of porous hydroxyapatite obtained from conversion of calcium carbonate exoskeletons of coral.

The morphogenesis of bone in a porous hydroxyapatite substratum was studied after intramuscular implantation in adult primates. Replicas of porous hydroxyapatite that had been obtained after hydrothermal conversion of the calcium carbonate exoskeleton of coral (genus Goniopora) were implanted intramuscularly in twenty-four adult male baboons (Papio ursinus). Serial sections from specimens that had been harvested at three, six, and nine months showed that initially the formation of fibrous connective tissue was characterized by a prominent vascular component and by condensations of collagen fibers assembled at the interface of the hydroxyapatite. The morphogenesis of bone was intimately associated with the differentiation of the connective-tissue condensations. Bone formed without an intervening endochondral phase. Although the amount of bone varied considerably, in several specimens extensive bone developed, filling large portions of the porous spaces and culminating in total penetration by bone within the implants. The mean volume fraction composition of the specimens was 20.8 +/- 1.0 per cent (mean and standard error) for bone, 17.3 +/- 1.7 per cent for connective-tissue condensation, 31.9 +/- 1.0 per cent for fibrovascular tissue, 6.4 +/- 0.6 per cent for bone marrow, and 34.6 +/- 0.5 per cent for the hydroxyapatite framework. The amount of bone and marrow increased at each time-period, and the hydroxyapatite framework was significantly reduced between six and nine months. This indicated a moderate biodegradation over time, which was possibly a result of incomplete conversion of carbonate to hydroxyapatite. Linear regression analysis showed a negative correlation between the hydroxyapatite framework and the magnitude of bone formation within the porosities of the hydroxyapatite (p = 0.0001). Biochemical coating of the hydroxyapatite substratum with an allogeneic fibrin-fibronectin protein concentrate prepared from baboon plasma did not significantly increase the amount of bone formation within the porous spaces. The hydroxyapatite substratum may have functioned as a solid-phase domain for anchorage of bone morphogenetic proteins.

Animals↗

Reference range of total serum homocysteine level and dietary indexes in healthy Greek schoolchildren aged 6-15 years.

Elevated total serum homocysteine (tHcy) may be a possible risk factor for CVD. A 5 micromol/l increase in tHcy is associated with an approximately 70 % increase in relative risk of CVD in adults. Data for children and adolescents are, however, limited. The purpose of the present study was to provide a reference range for tHcy and investigate any relationship between tHcy and nutritional indexes in a Greek paediatric population. tHcy, folate, vitamin B12 levels and dietary indexes were measured in 520 healthy schoolchildren (274 boys, 246 girls) aged 6-15 years. As in adults, the tHcy distribution skewed to the right, with a geometric mean for both genders of 7.4 (range 3.4-29 micromol/l). Concentrations were lower in young children and increased with age. No statistically significant difference in tHcy level was observed between gender. The 95th percentiles for the three age groups were as follows: 6-9 years, 9.98 micromol/l; 10-12 years, 10.62 micromol/l; 13-15 years, 14.4 micromol/l. Using Pearson's coefficient analysis, tHcy level was correlated with age, serum folate, BMI and systolic blood pressure. Dietary analysis showed that folate, vitamin B12 and fibre intake were inversely related with tHcy; conversely, sugar and fat were positively associated with tHcy. However, in multiple linear regression analysis, only age (odds ratio 0.246, P < 0.05) and folate (odds ratio -0.346, P < 0.05) were significantly and independently associated with tHcy. This study provides age-specific reference data regarding tHcy concentration in a Greek paediatric population. tHcy levels increased as a function of age. Serum folate levels were significantly and independently associated with tHcy levels.

Adolescent↗

Analyses of promoter hypermethylation for RUNX3 and other tumor suppressor genes in nasopharyngeal carcinoma.

BACKGROUND: Aberrant methylation of cytosine in promoter CpG islands is a recognized contributory process to carcinogenesis. This study explores the methylation profile of RUNX3 in combination with p16, RASSF1A, CDH1 and hMLH1 in nasopharyngeal carcinoma (NPC) patients. MATERIALS AND METHODS: Genomic DNA was extracted from 19 fresh frozen NPC biopsies, which were then subjected to bisulfite conversion and methylation-specific PCR for analysis of promoter hypermethylation for the five respective genes. Three cell lines, SNU1, RKO and LS174T, were used as controls. RESULTS: The incidences of promoter methylation were as follows: RUNX3 0/19 (0%), p16 6/19 (32%), RASSF1A 13/19 (68%), CDH1 9/19 (47%) and hMLH1 4/19 (21%). Ninety-five percent of the tumor specimens displayed aberrant methylation in at least one of these genes. No significant correlation between methylation status of these genes and clinical parameters was found. CONCLUSION: Methylation of multiple genes is involved in critical pathways for cancer development in NPC. Promoter hypermethylation for RUNX3 was, however, not present.

Base Sequence↗

Characterization of the morphologic conversion of Helicobacter pylori from bacillary to coccoid forms.

Growth studies of Helicobacter pylori were performed involving analysis of the bacterium and its microenvironment, to lend insight into the factors responsible for the morphologic conversion phenomenon. H. pylori converted from bacillary to coccoid forms in broth culture after incubation for 5 days under microaerobic conditions with agitation. This morphologic conversion was paralleled by a dramatic decrease in colony-forming units per milliliter (CFU/ml) and a significant endogenous increase in the pH of the broth culture. In addition, removal of broth cultures from microaerobic conditions after 3 days of incubation resulted in a rapid increase in culture pH, a morphologic conversion, and a concomitant decrease of CFU/ml. These observations suggest an inhibitory effect of basic pH, endogenously produced, on the growth of H. pylori in vitro. Experiments designed to identify the reason for the endogenous increase in culture pH demonstrated that the urease enzyme of H. pylori is not primarily responsible for this phenomenon. Rather, H. pylori appears to produce a deaminase enzyme that is likely responsible for the generation of ammonia, which results in the increase in culture pH, the morphologic conversion, and the loss of culturability observed in vitro. Also indicated is the need for a buffering component (for example, bicarbonate) to maintain pH conditions favorable to the growth of H. pylori.

Atypical Bacterial Forms↗

Collagen turnover and the growth state in 3T6 fibroblast cultures.

The metabolic turnover of collagen in 3T6 fibroblast cultures was studied at various stages of growth by compartmental analysis of hydroxyproline content and of the conversion of radioactive proline to hydroxyproline. Quantitative and radioactive hydroxyproline measurements were directly parallel, although the latter method was more sensitive in demonstrating collagen synthesis in all phases of growth. Hydroxyproline formation as an index of collagen synthesis was abruptly accelerated at the time of confluence, and was well maintained at the new rate despite a gradual decline in the rate of general protein synthesis. Ethanol fractionation of growth medium proved superior to perchloric acid extraction in providing a pool of soluble hydroxyproline clearly derived from collagen degradation. Breakdown products were released at a constant rate per cell in all growth phases and accumulated to high levels in continuous culture. The fractional rate of collagen breakdown (percentage of hydroxyproline radioactivity) was highest in early logarithmic growth. Its gradual decline as cultures aged reflected the increased hydroxyproline content and improved stability of collagen under these conditions.

Cell Division↗

[Enzymatic colorimetric determination of phosphatidylglycerol in amniotic fluid].

Although the concentration of phosphatidylglycerol (PG) in amniotic fluid is generally considered indicative of fetal lung maturity, the thin layer chromatographic techniques currently used to measure this concentration have been criticized. We have investigated a highly sensitive method for determining amniotic fluid phosphatidylglycerol by using L-glycerol-3-phosphate (G-3-P).dihydroxyacetone phosphate enzymatic cycling reaction and relate this finding to the assessment of fetal lung maturity. Under the assay conditions described above, glycerol oxidase eliminates endogenous glycerol in the amniotic fluid prior to analysis. The subsequent enzymatic reaction sequence involves conversion of phosphatidylglycerol to G-3-P by phospholipase D and glycerol kinase in the presence of ATP. G-3-P is subsequently determined with amplification by enzymatic cycling reaction of G-3-P oxidase and G-3-P dehydrogenase in the presence of oxygen and NADH2. The absorbance is measured at 542 nm. The quantitation of phosphatidylglycerol is linear over the concentration range of 0-20 microM and the detection limit is 0.4 mumol/l. Within run CV's were found to be 1.25% at 13.8 mumol/l (n = 7) and 3.0% at 4.2 mumol/l (n = 7). The results obtained from 48 samples using this procedure, revealed that a level less than 1.0 mumol/l of PG persisted until the 29th week of gestation. A gradual increase in PG (more than 1.0 mumol/1) beginning in the 30th week of gestation was observed. A sharp increase in PG was also found in the 37th week of gestation.

Amniotic Fluid↗