Changes over time in the course of advanced pancreatic cancer treatment with systemic chemotherapy: a pooled analysis of five clinical trials from two decades of the German AIO study group.

BACKGROUND: Over the past two decades, our group has conducted five multicenter trials focusing on first-line systemic therapy for patients with advanced pancreatic cancer. The current pooled analysis was designed to evaluate prognosis over time and the impact of clinical characteristics on survival. PATIENTS AND METHODS: Individual patient data were derived from five prospective, controlled, multicenter trials conducted by the 'Arbeitsgemeinschaft Internistische Onkologie' (AIO): 'Gem/Cis', 'Ro96', 'RC57', 'ACCEPT' and 'RASH', which recruited patients between December 1997 and January 2017. RESULTS: Overall, 912 patients were included. The median overall survival (OS) for all assessable patients was 7.1 months. OS significantly improved over time, with a median OS of 8.6 months for patients treated from 2012 to 2017 compared with 7.0 months from 1997 to 2006 [hazard ratio (HR) 1.06; P < 0.004]. Eastern Cooperative Oncology Group performance status (HR 1.48; P < 0.001), use of second-line treatment (HR 1.51; P < 0.001), and Union for International Cancer Control (UICC) stage (III versus IV) (HR 1.34, P = 0.002) had a significant impact on OS. By contrast, no influence of age and gender on OS was detectable. Comparing combination therapy with single-agent chemotherapy did not demonstrate a survival benefit, nor did regimens containing epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) such as afatinib or erlotinib, compared with chemotherapy-only arms. Patients with early-onset pancreatic cancer (age at study entry of ≤50 years, n = 102) had a similar OS compared with those >50 years (7.1 versus 7.0 months; HR 1.13; P = 0.273). The use of a platinum-containing regimen was not associated with better outcomes in patients with early-onset pancreatic cancer. CONCLUSIONS: Within this selected group of patients treated within prospective clinical trials, survival has shown improvement over two decades. This effect is likely attributable to the availability of more effective combination therapies and treatment lines, rather than to any specific regimen, such as those containing EGFR-TKIs. In addition, concerning age and sex subgroups, the dataset did not provide evidence for distinct clinical behavior.

Early clinical trial unit tumor board: a real-world experience in a national cancer network.

PURPOSE: Early clinical trials are the first step into clinical therapies for new drugs. Within the six Bavarian university-based hospitals (Augsburg, Erlangen, Regensburg, Munich (LMU and TU), Würzburg) we have enrolled a virtual network platform for patient discussion. METHODS: The virtual Early Clinical Trial Unit Tumor Board (ECTU Tumor Board) is a secured web-based meeting to evaluate early clinical trial options for patients, where representatives from local ECTUs participate. We retrospectively analyzed patient cases discussed between November 2021 and November 2022. RESULTS: From November 2021 to November 2022, a total of 43 patients were discussed in the ECTU Tumor Board. Median age at diagnosis was 44.6 years (range 10-76 years). The median number of previous lines of therapies was 3.7 (range 1-9 therapies) including systemic treatment, surgery, and radiation therapy. A total of 27 different tumor entities were presented and 83.7% (36/43) patients received at least one trial recommendation. In total, 21 different active or shortly recruiting clinical trials were recommended: ten antibody trials, four BiTE (bispecific T cell engager) trials, six CAR (chimeric antigen receptor) T-cell trials, and one chemotherapy trial. Only six trials (28.6%) were recommended on the basis of the previously performed comprehensive genetic profiling (CGP). CONCLUSION: The ECTU Tumor Board is a feasible and successful network, highlighting the force of virtual patient discussions for improving patient care as well as trial recruitment in advanced diseases. It can provide further treatment options after local MTB presentation, aiming to close the gap to access clinical trials.

Cancer of unknown primary (CUP) through the lens of precision oncology: a single institution perspective.

PURPOSE: For patients with cancer of unknown primary (CUP), treatment options are limited. Precision oncology, the interplay of comprehensive genomic profiling (CGP) and targeted therapies, aims to offer additional treatment options to patients with advanced and hard-to-treat cancers. We aimed to highlight the use of a molecular tumor board (MTB) in the therapeutic management of CUP patients. METHODS: In this single-center observational study, CUP patients, presented to the MTB of the Comprehensive Cancer Center Munich LMU, a tertiary care center, were analyzed retrospectively. Descriptive statistics were applied to describe relevant findings. RESULTS: Between June 2016 and February 2022, 61 patients with unfavorable CUP were presented to the MTB, detected clinically relevant variants in 74% (45/61) of patients, of which 64% (29/45) led to therapeutic recommendation. In four out of 29 patients (14%), the treatment recommendations were implemented, unfortunately without resulting in clinical benefit. Reasons for not following the therapeutic recommendation were mainly caused by the physicians' choice of another therapy (9/25, 36%), especially in the context of worsening of general condition, lost to follow-up (7/25, 28%) and death (6/25, 24%). CONCLUSION: CGP and subsequent presentation to a molecular tumor board led to a high rate of therapeutic recommendations in patients with CUP. Recommendations were only implemented at a low rate; however, late GCP diagnostic and, respectively, MTB referral were found more frequent for the patients with implemented treatment. This contrast underscores the need for early implementation of CGP into the management of CUP patients.

Lost in translation? English- and Spanish-speaking women's perceptions of gestational weight gain safety, health risks and counseling.

OBJECTIVE: To determine English- and Spanish-speaking women's perceptions on gestational weight gain (GWG) counseling. STUDY DESIGN: We administered a written survey to 279 pregnant women regarding GWG counseling and knowledge. We compared English- and Spanish-speaking women's responses using X(2)-tests and logistic regression analyses. RESULT: Seventy-four (27%) women completed the survey in Spanish and 205 (73%) in English. More Spanish compared with English speakers did not know if their provider recommended weight gain goals (26% vs 10%, odds ratio (OR) 3.2, confidence interval (CI) 1.5 to 6.5); if there are risks to excessive GWG for mother (27% vs 11%, OR 3.1, CI 1.5 to 6.4) or infant (38% vs 16%, OR 3.3, CI 1.7 to 6.3); or if exercise (15% vs 1%, OR 12.1, CI 3.0 to 69.1) or weight loss (35% v 12%, OR 4.0, CI 2.0 to 8.0) were safe during pregnancy. CONCLUSION: Significant differences exist between Spanish- and English-speaking women's perception of GWG counseling, which may be due to language or cultural barriers.

Molecular cloning and sequencing of MHC class II beta 1 domain of turkey reveals high sequence identity with chicken.

We report the nucleotide sequences of turkey (Meleagris gallopavo) major histocompatibility complex (MHC) class II loci (beta 1 domain or exon 2 encoding the peptide-binding region). In the present investigation, three distinct sequences from the beta 1 domain of turkey MHC class II were isolated. A BLAST search and phylogenetic analysis revealed that turkey MHC sequences are most similar to chicken and peacock MHC. There was no strong evidence of recombination among the turkey MHC sequences or with other avian MHC, but diversity was high. The diversity in this peptide-binding region may be the result of point mutation and balancing selection or frequent gene conversion within turkey. However, more work and data are needed to understand the evolution of turkey and other avian MHC. Moreover, polymerase chain reaction-restriction fragment-length polymorphism analysis of exon 2 using the Hinf I restriction enzyme demonstrated three restriction patterns and a preliminary evidence of multiple beta loci in turkey. PCR-RFLP analysis of turkey MHC class II loci could be a promising method of MHC genotyping, when more sequences are available. Turkey MHC haplotypes identified earlier by RFLP analysis should be sequenced to standardize turkey MHC nomenclature and to develop DNA based method of haplotyping.

Plasma choline in normal newborns, infants, toddlers, and in very-low-birth-weight neonates requiring total parenteral nutrition.

Choline deficiency is associated with hepatic abnormalities in adult volunteers and patients administered total parenteral nutrition (TPN). Preliminary investigation has suggested that plasma-free choline concentration (PFCh) is greater in neonatal animals, including humans, than in adults. The aims of this study were to determine the normal PFCh and phospholipid-bound choline concentration (PPLBCh) for newborns, infants, and toddlers and to determine the change during TPN. We also sought to determine the degree of fetal choline extraction, the relation between maternal and newborn plasma choline concentrations, and the relation between plasma choline status and normal newborn length, weight, and gestational age. Blood samples were obtained from 104 full-term newborns in two centers (Ben Taub and Maimonides), 25 mothers, 21 normal infants aged 20.3 +/- 11.8 wk, 12 normal infants aged 62.4 +/- 3.9 wk, and 14 preterm infants (gestational age = 28.9 +/- 2.2 wk) who required TPN. The vein PFChs were 28.1 +/- 13.0 nmol/mL (Ben Taub) and 68.1 +/- 16.9 nmol/mL (Maimonides). The artery PFChs were 27.1 +/- 13.0 nmol/mL (Ben Taub) and 57.9 +/- 11.6 nmol/mL (Maimonides). The vein PPLChs were 1004.7 +/- 246.6 nmol/mL (Ben Taub) and 1121.2 +/- 289.6 nmol/mL (Maimonides). The artery PPLChs were 1065.7 +/- 469.3 nmol/mL (Ben Taub) and 1106.9 +/- 285.8 nmol/mL (Maimonides). The vein-minus-artery differences for PFCh were 1.0 +/- 9.7 nmol/mL (Ben Taub) and 10.2 +/- 10.9 nmol/mL (Maimonides). The vein-minus-artery differences for PPLCh were -51.9 +/- 398.2 nmol/mL (Ben Taub General Hospital, Houston, Texas) and 14.4 +/- 254.3 nmol/mL (Maimonides, New York, New York). Maternal venous PFCh was 8.4 +/- 3.1 nmol/mL. Maternal venous PPLCh was 2592.1 +/- 584.0 nmol/mL (range = 1227.8-3729.0). Maternal venous PFCh correlated with newborn arterial PFCh (r = 0.53, P < 0.05) but not with newborn venous PFCh. No correlation was seen between maternal venous and newborn PPLCh. No significant differences were seen in PPLCh or choline extraction in Ben Taub versus Maimonides patients, although PFCh was significantly greater in the newborns from Maimonides (P < 0.05). The mean venous PFCh and PPLCh in the preterm infants before beginning TPN was 21.2 +/- 6.3 and 1366.8 +/- 339.1 nmol/mL, respectively. Just before initiation of tube feeding (4.0 +/- 2.7 d after TPN had been started), mean venous PFCh and PPLCh was 18.4 +/- 5.3 and 2251.8 +/- 686.9 nmol/mL, respectively. When TPN was discontinued and tube feeding increased to goal, after 10.8 +/- 10.4 d, venous PFCh and PPLCh was 22.6 +/- 8.7 and 2072.5 +/- 540.6 nmol/mL, respectively. Venous PFCh and PPLCh was 13.4 +/- 2.5 and 1827.5 +/- 327.0 nmol/mL, respectively in the older infant group. In conclusion, newborn PFCh is significantly greater than PFCh in adults but falls to adult levels within the first year of life. Low maternal PFCh may be associated with low newborn PFCh. Normal newborn plasma choline status has no bearing on intrauterine growth, although the role of maternal choline deficiency in underweight newborns is unknown. Newborn PPLCh is substantially below that of adults, which suggests its use in membrane synthesis during growth.

Primate DAX1, SRY, and SOX9: evolutionary stratification of sex-determination pathway.

The molecular evolution of DAX1, SRY, and SOX9, genes involved in mammalian sex determination, was examined in six primate species. DAX1 and SRY have been added to the X and Y chromosomes, respectively, during mammalian evolution, whereas SOX9 remains autosomal. We determined the genomic sequences of DAX1, SRY, and SOX9 in all six species, and calculated K(a), the number of nonsynonymous substitutions per nonsynonymous site, and compared this with the K(s), the number of synonymous substitutions per synonymous site. Phylogenetic trees were constructed by means of the DAX1, SRY, and SOX9 coding sequences, and phylogenetic analysis was performed using maximum likelihood. Overall measures of gene and protein similarity were closer for DAX1 and SOX9, but DAX1 exhibited nonsynonymous amino acid substitutions at an accelerated frequency relative to synonymous changes, similar to SRY and significantly higher than SOX9. We conclude that, at the protein level, DAX1 and SRY are under less selective pressure to remain conserved than SOX9, and, therefore, diverge more across species than does SOX9. These results are consistent with evolutionary stratification of the mammalian sex determination pathway, analogous to that for sex chromosomes.

An endothelial nitric oxide synthase gene polymorphism is associated with preeclampsia.

OBJECTIVE: We sought to test the hypothesis that a polymorphism of the endothelial nitric oxide synthase gene (NOS3) is associated with preeclampsia. METHODS: We collected and performed polymerase chain reaction (PCR) on genomic DNA from pregnant patients with and without preeclampsia. Patient history and clinical course were evaluated. MAIN OUTCOME MEASURE(S): Frequency of the intron 4 polymorphism of NOS3 (designated allele A) among patients with preeclampsia compared with controls. Clinical features of patients with preeclampsia and the A allele compared with those patients with preeclampsia who did not have the A allele. RESULTS: The frequency of the A allele was 0.10 among controls versus 0.39 among patients with preeclampsia (p < 0.01). The odds ratio of developing preeclampsia when at least one A allele was present was 6.5 [95% confidence interval (CI): 2.1-19.7]. After adjusting for ethnic variation, the odds ratio increased to 7.2 (95% CI: 2.0-25.5). Among patients with preeclampsia, systolic blood pressure at the time of admission was higher for patients with at least one A allele compared with patients homozygous for the B allele (168 versus 156 mm Hg; p = 0.03), independent of gestational age (p = 0.01). CONCLUSION: These data provide evidence for an association between NOS3 and preeclampsia. In defined ethnic groups, this NOS3 may offer predictive information regarding the subsequent development of preeclampsia and its clinical course.

Use of the World Wide Web in research: randomization in a multicenter clinical trial of treatment for twin-twin transfusion syndrome.

OBJECTIVE: To describe the process involved in using the World Wide Web to coordinate a randomized, multicenter international trial of treatment for twin-twin transfusion syndrome. METHOD: A Web site was designed by members of the research team, a Web consultant, and a senior computer programmer. The original intent was to provide patient randomization only, but the Web site later was designed so that centers could download a data collection form. Data could be entered directly into the Web site and subsequently imported into a database at the coordinating center. EXPERIENCE: The Web site has been active for 3 years, with 13 participating centers and 31 patients enrolled. COMMENT: Use of the World Wide Web to coordinate an international, multicenter trial is an efficient method. Although there are many benefits, the most obvious is the capability to initiate and conduct a large international trial at minimal cost.

Noninvasive diagnosis by Doppler ultrasonography of fetal anemia due to maternal red-cell alloimmunization. Collaborative Group for Doppler Assessment of the Blood Velocity in Anemic Fetuses.

BACKGROUND: Invasive techniques such as amniocentesis and cordocentesis are used for diagnosis and treatment in fetuses at risk for anemia due to maternal red-cell alloimmunization. The purpose of our study was to determine the value of noninvasive measurements of the velocity of blood flow in the fetal middle cerebral artery for the diagnosis of fetal anemia. METHODS: We measured the hemoglobin concentration in blood obtained by cordocentesis and also the peak velocity of systolic blood flow in the middle cerebral artery in 111 fetuses at risk for anemia due to maternal red-cell alloimmunization. Peak systolic velocity was measured by Doppler velocimetry. To identify the fetuses with anemia, the hemoglobin values of those at risk were compared with the values in 265 normal fetuses. RESULTS: Fetal hemoglobin concentrations increased with increasing gestational age in the 265 normal fetuses. Among the 111 fetuses at risk for anemia, 41 fetuses did not have anemia; 35 had mild anemia; 4 had moderate anemia; and 31, including 12 with hydrops, had severe anemia. The sensitivity of an increased peak velocity of systolic blood flow in the middle cerebral artery for the prediction of moderate or severe anemia was 100 percent either in the presence or in the absence of hydrops (95 percent confidence interval, 86 to 100 percent for the 23 fetuses without hydrops), with a false positive rate of 12 percent. CONCLUSIONS: In fetuses without hydrops that are at risk because of maternal red-cell alloimmunization, moderate and severe anemia can be detected noninvasively by Doppler ultrasonography on the basis of an increase in the peak velocity of systolic blood flow in the middle cerebral artery.

Mutation takes no vacation: can structured treatment interruptions increase the risk of drug-resistant HIV-1?

We use a mathematical model to study the dynamics of HIV-1 replication during structured treatment interruptions (STIs) in infected patients. The model predicts rapid viral rebound, restoration of a latently infected cell pool, and critically, partially resistant mutant rebound that may be missed because of high levels of wild type virus. Because partially resistant viruses are capable of mutating to full resistance, a substantial increase in their numbers represents a threat to therapeutic response durability. Compared with continued treatment, STIs may increase the chance of mutation to full resistance by several thousandfold.

Discordance between fetal RhD typing using molecular methods and neonatal typing with serology.

Polymerase chain reaction (PCR)-based genotyping on amniotic fluid in an RhD-negative alloimmunized woman predicted an RhD-negative fetal blood type. The neonate was RhD-positive and developed hemolytic disease. Discrepant results were also observed on paternal testing. PCR analysis with a different set of primers correctly predicted the RhD-positive fetal and paternal blood type. Use of more than one set of primers and parental testing can avoid some of the problems associated with use of PCR genotyping.

Just a beta....

Traditional implementation of clinical information systems follows a predictable project management process. The selection, development, implementation, and evaluation of the system and the project management aspects of those phases require considerable time and effort. The purpose of this paper is to describe the beta site implementation of a knowledge-based clinical information system in a specialty area of a southeastern hospital that followed a less than traditional approach to implementation. Highlighted are brief descriptions of the hospital's traditional process, the nontraditional process, and key findings from the experience. Preliminary analysis suggests that selection of an implementation process is contextual. Selection of elements from each of these methods may provide a more useful process. The non-traditional process approached the elements of communication, areas of responsibility, training, follow-up and leadership differently. These elements are common to both processes and provide a focal point for future research.

A randomized double-blind study comparing the fetal effects of sulindac to terbutaline during the management of preterm labor.

OBJECTIVE: The object of this study was to compare the fetal effects of sulindac and terbutaline used in the management of preterm labor on the ductus arteriosus, middle cerebral artery, renal artery, umbilical artery, fetal urine production, and amniotic fluid index. STUDY DESIGN: In a randomized, double-blind study 20 patients with preterm labor and no evidence of fetal structural anomalies or intra-amniotic infection received either sulindac (200 mg orally every 12 hours for 6 doses) or terbutaline (5 mg orally every 4 hours) for 72 hours of therapy. All medications were administered from identical blister packs. Opaque glucose base tablets were given at 4-hour intervals in the sulindac treatment arm to mimic the dosing interval in the terbutaline arm of the study. The Doppler pulsatility indices for the ductus arteriosus, middle cerebral artery, renal artery and umbilical artery and also the fetal urinary output were obtained at baseline and 5, 12, 24, 48, and 72 hours after the medication was started. Doppler data were analyzed within each group with raw data and between groups with the change in pulsatility indices from baseline. Statistical analysis was performed with the Kolmogorov-Smirnov test for normality, repeated measures analysis of variance, Mann-Whitney rank sum test, and Student t test as appropriate. P <.05 (2-tailed) was used to denote statistical significance. RESULTS: There were 10 patients in each group, with no difference in gestational age between the 2 groups (32.3 vs 31.7 weeks). Sulindac was stopped in 2 patients after severe ductal constriction was noted, in 1 at 12 hours and in the other at 24 hours. One patient at 33 weeks' gestation was delivered because of fetal distress after 46 hours of sulindac therapy. When analyzed across time within groups, the pulsatility index in the ductus arteriosus decreased significantly at 12 and 24 hours in the sulindac group but not the terbutaline group. No significant differences were noted in the middle cerebral artery, umbilical artery, renal artery, or fetal urinary output within either group over time. Significant differences in the change from baseline in pulsatility index of the ductus arteriosus between the sulindac and terbutaline groups were noted at 5, 12, 24, and 48 hours. A similar effect was noted in the change from baseline in pulsatility index of the middle cerebral artery at 48 and 72 hours. There was a significant decrease in the amniotic fluid index in both groups at 24, 48, and 72 hours. The amniotic fluid index in the sulindac group was significantly lower than that in the terbutaline group at 48 and 72 hours of therapy. CONCLUSIONS: Sulindac constricted the fetal ductus arteriosus, with an effect noted within 5 hours of starting therapy. The constriction, which resolved in all cases within 48 hours of discontinuing therapy, had minimal effects on the pulsatility index of the middle cerebral artery, renal artery, and umbilical artery. Sulindac and terbutaline both resulted in a significant reduction in the amniotic fluid index, with sulindac having a greater effect.

[Molecular epidemiology of the human immunodeficiency virus type 1 in Santiago, Chile]. / Epidemiología molecular del virus de inmunodeficiencia humana tipo 1 en Santiago, Chile.

BACKGROUND: Most of the studies of HIV-1 infection in South America have been limited to Brazil and little is known about the viral variants that are causing disease elsewhere in the continent. AIM: To determine the characteristics of the viral variants present in Chile as well as patterns of viral transmission. MATERIAL AND METHODS: Viral sequences were obtained from 21 HIV-1 infected people from Santiago, Chile who were infected either via sexual contact or intravenous drug use. Cloned sequences obtained from both the third variable and conserved regions of the envelope as well as the viral protease were evaluated. RESULTS: We found only clade B subtype viruses in Santiago. An evaluation of the envelope gene revealed no evidence that the sequences were monophyletic by risk group. A number of the protease sequences were predicted to encode amino acid substitutions commonly found during selection for protease inhibitor resistance. CONCLUSIONS: The HIV-1 strains studied in Chile, belong to the subtype B. There is no molecular evidence of separate introductions of the virus into the different risk groups. A number of substitutions in the protease gene that may confer resistance to protease inhibitors were found in patients with no previous exposure to this class of drugs.

An animal model for hemolytic disease of the fetus or newborn in New Zealand white and New Zealand red rabbits: newborn effects.

OBJECTIVE: Our purpose was to study the neonatal effects of red blood cell alloimmunization in a rabbit model. STUDY DESIGN: Eighteen does were alloimmunized to incompatible red blood cells. Does were bred twice, once with a homozygous buck of incompatible blood type and once with a homozygous buck of compatible blood type. Fetal blood sampling was undertaken on day 27 of gestation (term 28 to 31 days). Does were delivered on day 30 and the neonatal pups were anesthetized. Direct cardiac samplings were performed for hemoglobin, reticulocyte count, and direct Coombs' test. Hepatic, splenic, and renal wet weights were measured. RESULTS: Twenty-two pregnancies (12 compatible and 10 incompatible) were studied. Neonatal hemoglobin was higher in the compatible litters (11.1 gm/dL [7.7 to 12.6 gm/dL] vs 4.9 gm/dL [2.1 to 9.1 gm/dL], P <.001), whereas no difference could be detected between the respective reticulocyte counts (34.0/100 red blood cells [27.3 to 36.1/100 red blood cells] vs 32.6/100 red blood cells [26.8 to 43.5/100 red blood cells], P =.55). The direct Coombs' assay was negative in 23 pups from 8 compatible litters and false positive (weakly positive result) in 2 pups of a ninth compatible litter. The Coombs' assay was positive in all 22 incompatible pups tested. Hepatosplenomegaly was noted in affected pups but not in controls. CONCLUSIONS: A disease analogous to human hemolytic disease of the newborn can be induced in the rabbit neonate.

A simple method to estimate volume for fetal intravascular transfusions.

We derived a constant termed the transfusion coefficient to simplify the estimation of the fetal intravascular transfusion volume. The product of the estimated fetal weight (g) and 0.02 (transfusion coefficient), estimates the transfusion volume (ml) required to increase the fetal hematocrit by approximately 10 percentage points. Our estimation was comparable to Mandelbrot's technique and better than Plecas' method for estimating fetal transfusion volumes. Utilizing the transfusion coefficient to estimate the intravascular transfusion volume for an anemic fetus is simple, rapid and accurate.

Comparison of intraocular pressure between normotensive and preeclamptic women in the peripartum period.

OBJECTIVE: Our purpose was to determine whether intraocular pressure differs between preeclamptic and normotensive women in the peripartum period. STUDY DESIGN: Eighteen preeclamptic (defined as blood pressure > 140/90 mm Hg and > or = 1+ proteinuria) and 18 normotensive women were studied. Intraocular pressure was determined with a handheld tonometer. Each intraocular pressure determination was obtained by repeatedly touching the cornea until signal averaging produced a single measurement with a variance < 5%. Right and left intraocular pressure, heart rate, and blood pressure were obtained intrapartum and 24 hours post partum with the patient in the seated, supine, and left lateral positions. Data are reported as mean +/- SD or median (range) as appropriate. Significance was set at p < 0.05. RESULTS: No differences existed in race, age, weight, gravidity, parity, cervical dilatation, and heart rate between the preeclamptic and normotensive groups. Gestational age was lower (39 [34 to 42] vs 41 [34 to 42] weeks, p = 0.003), and intrapartum mean arterial pressure (100.2 +/- 9.8 vs 81.0 +/- 8.3 mm Hg, p < 0.001) and degree of proteinuria (3 [1 to 4] vs 0, p < 0.001) were higher in the preeclamptic group. There was no effect of position or delivery on intraocular pressure in either group. Intraocular pressure was higher in the preeclamptic group in the intrapartum (18.8 +/- 3.0 vs 15.3 +/- 2.7 mm Hg, p < 0.001) and postpartum periods (20.2 +/- 4.5 vs 15.7 +/- 3.6 mm Hg, p = 0.002). CONCLUSION: Compared with normotensive women, preeclamptic women have increased intraocular pressure in the peripartum period.

Characterization of V3 loop of HIV type 1 spreading rapidly among injection drug users of Manipur, India: a molecular epidemiological perspective.

PIP: Blood samples were obtained from six HIV-infected IV drug users attending the Indian Council for Medical Research Clinic at Imphal, the capital of Manipur state, as part of a study to analyze the sequences of the third variable region (V3) of the HIV envelope in that population. 18 sequences were obtained from the study participants, men aged 24-29 years. A fragment of the envelope gene encompassing the entire V3 loop and partial sequences from the third conserved region was sequenced, while amplifications were performed on DNA extracted directly from patient peripheral blood mononuclear cells to avoid the introduction of artifacts during cell culture. One set of viruses seems to be most closely related to a prototypical virus recovered from IV drug users in Thailand (Thai B), while the other sequences clustered more closely with a North American clade B virus (HXB). Sequences recovered from one person are rather diverse.^ieng

In vivo sequence diversity of the protease of human immunodeficiency virus type 1: presence of protease inhibitor-resistant variants in untreated subjects.

We have evaluated the sequence diversity of the protease human immunodeficiency virus type 1 in vivo. Our analysis of 246 protease coding domain sequences obtained from 12 subjects indicates that amino acid substitutions predicted to give rise to protease inhibitor resistance may be present in patients who have not received protease inhibitors. In addition, we demonstrated that amino acid residues directly involved in enzyme-substrate interactions may be varied in infected individuals. Several of these substitutions occurred in combination either more or less frequently than would be expected if their appearance was independent, suggesting that one substitution may compensate for the effects of another. Taken together, our analysis indicates that the human immunodeficiency virus type 1 protease has flexibility sufficient to vary critical subsites in vivo, thereby retaining enzyme function and viral pathogenicity.