Biomedical subjects
Publications and source records attributed to S Bower.
Congenital nephrotic syndrome of the Finnish type (CNF) and diffuse mesangial sclerosis (DMS) are rare causes of renal failure in infants. We report two cases, one of each condition, presenting with increased nuchal translucency at the 11-14-week scan, and review the literature.
Blackfan-Diamond anemia is a congenital hypoplastic anemia with a birth prevalence of about 1 in 200,000, usually presenting in the first few months of life and commonly associated with cardiac, urogenital and digital anomalies. Congenital dyserythropoietic anemias are a group of rare congenital anemias characterized by ineffective erythropoiesis. We report on two cases of congenital fetal anemia, one with Blackfan-Diamond anemia and one with dyserythropoietic anemia, presenting with increased nuchal translucency at 12 weeks of gestation.
OBJECTIVE: Doppler ultrasound provides a non-invasive method for the study of the uteroplacental circulation. In normal pregnancy, impedance to flow in the uterine arteries decreases with gestation, which may be the consequence of trophoblastic invasion of the spiral arteries and their conversion into low-resistance vessels. Pre-eclampsia and fetal growth restriction are associated with failure of trophoblastic invasion of spiral arteries, and Doppler studies, in these conditions, have shown that impedance to flow in the uterine arteries is increased. A series of screening studies involving assessment of impedance to flow in the uterine arteries have examined the potential value of Doppler in identifying pregnancies at risk of the complications of impaired placentation. This review examines the findings of Doppler studies in unselected populations. METHODS: Searches of a computerized medical database were performed to identify relevant studies. Only those studies that provided sufficient data to allow calculation of the performance of the test were included in the analysis. Likelihood ratios were calculated for each study and are reported for pre-eclampsia, fetal growth restriction and perinatal death as well as for more severe forms of pre-eclampsia and fetal growth restriction. RESULTS: The literature search identified 19 relevant studies, four of which were excluded from the further analysis. The main characteristics and results of the 15 remaining studies provided discrepant results, which may be the consequence of differences in Doppler technique for sampling, the definition of abnormal flow velocity waveform, differences in the populations examined, the gestational age at which women were studied and different criteria for the diagnosis of pre-eclampsia and fetal growth restriction. Nevertheless, the studies provided evidence that increased impedance to flow in the uterine arteries is associated with increased risk for subsequent development of pre-eclampsia, fetal growth restriction and perinatal death. In addition, women with normal impedance to flow in the uterine arteries constituted a group that have a low risk of developing obstetric complications related to uteroplacental insufficiency. CONCLUSIONS: The review suggests that increased impedance to flow in the uterine arteries in pregnancies attending for routine antenatal care identifies about 40% of those who subsequently develop pre-eclampsia and about 20% of those who develop fetal growth restriction. Following a positive test, the likelihood of these complications is increased by about 6 and 3.5 times, respectively.
We report here the transplantation of extensively purified "mobilized" peripheral blood CD34Thy-1 hematopoietic stem cells from 22 patients with recurrent or metastatic breast cancer. Patients were mobilized with either high-dose granulocyte colony-stimulating factor (G-CSF) alone or cyclophosphamide plus G-CSE Median purity of the stem cell product at cryopreservation was 95.3% (range, 91.1%-98.3%), and viability was 98.6% (range, 96.5%-100%). After high-dose chemotherapy with carmustine, cisplatin, and cyclophosphamide, CD34+Thy-1 cells at a median dose of 11.3 x 10(5) per kilogram (range, 4.7-163 x 10(5) per kilogram) were infused. No infusion-related toxicity was observed. Neutrophil recovery was prompt, with median absolute neutrophil count >500/microL by day 10 (range, 8-15 days) and >1000/microL by day 11 (range, 8-17 days). Median platelet recovery (>20,000/microL) was observed by day 14 (range, 9-42 days) and >50,000/microL by day 17 (range, 11-49 days). Tumor cell depletion below the limits of detection of a sensitive immunofluorescence-based assay was accomplished in all patients who had detectable tumor cells in apheresis products before processing. Although CD4+ T-cell reconstitution was slow, no unusual infections were observed. Neither early nor late graft failure was observed, and no patient required infusion of unmanipulated backup cells. At a median follow-up of approximately 1.4 years and a maximum follow-up of 2.5 years, 16 of the 22 patients remain alive, with 9 free of disease progression, and have stable blood counts. In summary, highly purified CD34+Thy-1+ cells used as the sole source of the hematopoietic graft result in rapid and sustained hematopoietic engraftment.
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A new family of PDE4 inhibitors based on a benzimidazole framework is described. Several of these compounds are orally bioavailable and show efficacy in in vivo models of inflammatory disease.
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OBJECTIVE: Abnormal uterine artery Doppler waveforms in the second trimester of pregnancy can predict adverse outcome. The presence of a diastolic notch is a better predictor than measurement of impedance indices. A notch has generally been assessed subjectively, which has raised questions as to the reproducibility of the method. The aim of this study was to compare subjective and objective assessments of 50 abnormal waveforms. DESIGN: This was a retrospective study of 50 abnormal uterine artery waveforms collected during a previous screening study. Subjective and objective assessments were compared and related to adverse outcomes. Five impedance indices incorporating a measurement of the diastolic notch were compared. Three indices predictive of adverse outcome were compared to subjective assessment. RESULTS: There was good agreement between experienced operators in their subjective assessment of uterine artery waveforms. Adverse outcome was predicted by only moderately or severely abnormal waveforms. Three impedance indices predictive of adverse outcome were the pulsatility index (PI), A/C and (D - C)/B (where A is the peak systolic, D is the maximum diastolic and B is the end-diastolic frequency, and C is the nadir of the notch). The cut-off values combining the highest sensitivity for the lowest false-positive rate were 1.5 for PI, 3.0 for A/C and 0.15 for (D - C)/B. A PI of 1.5 had the highest sensitivity (100%) and positive predictive value (55%) for adverse outcome in this preselected group. These three indices were compared to subjective assessment using the kappa index and the (D - C)/B ratio had the closest agreement, although all three indices showed at least moderate agreement. The cut-off values of 1.5, 3.0 and 0.15 for PI, A/C and (D - C)/B, respectively appear to differentiate between mildly abnormal waveforms and moderately/severely abnormal waveforms. CONCLUSION: Objective assessment of uterine artery waveforms using cut-off values of PI, A/C and (D - C)/B provides an estimation similar to that provided by subjective assessment by an experienced operator. These ratios will now need to be used prospectively in an unselected population to compare their screening properties.
The perioperative pharmacokinetics of transdermally-delivered fentanyl were compared in 10 young adult (mean [range] age 32.7, [25-38] yr) and eight elderly (mean [range] age 73.7 [64-82] yr) patients following abdominal surgery. Transdermal fentanyl patches designed to release 50 micrograms h-1 were applied 2 h preoperatively and left in place for 72 h. Plasma fentanyl concentrations were measured by radioimmunoassay during patch application and for 30 h after patch removal. The mean half-time (time for plasma concentrations to double after patch application) was 4.2 h in the younger group and 11.1 h in the elderly group (P < 0.005). Mean maximum plasma concentrations were 1.9 ng ml-1 and 1.5 ng ml-1 in the younger and elderly groups respectively (ns). There were no differences in the time at which maximum plasma concentrations occurred (tmax), elimination half-life after patch removal, or AUC(0-infinity).
OBJECTIVE: To document perinatal changes in cerebral and renal artery haemodynamics in premature growth-retarded and normal term infants. DESIGN: Longitudinal study of individual infants. Doppler ultrasound measurements of blood flow velocity (BFV) in the middle cerebral and renal arteries were obtained before delivery, soon after delivery and during the first week of postnatal life. SETTING: Teaching hospital obstetric and neonatal units. SUBJECTS: 13 severely growth retarded infants born at 28-36 weeks gestation, and eight normally grown infants born at term. RESULTS: In both groups, BFV in the cerebral artery was significantly lower in the first few hours after birth than in fetal life, but subsequently increased to reach pre-delivery values by the end of the first week. In contrast, BFV in the renal artery during the first postnatal day was not significantly different from fetal values, but it also increased during the subsequent week. In six of the preterm growth-retarded infants, fetal blood gases were measured in samples obtained by cordocentesis, and in these cases an increase in blood oxygen content at birth was documented. CONCLUSIONS: Cerebral artery BFV falls at birth and is relatively low during the time that premature infants are at the greatest risk of developing periventricular haemorrhage.
OBJECTIVE: In spite of recent advances in the assessment and treatment of fetofetal transfusion syndrome, its underlying mechanism remains controversial. We aimed to determine whether the clinical features of fetofetal transfusion syndrome could be explained by unidirectional or bidirectional intertwin transfusion along placental vascular anastomoses. STUDY DESIGN: We constructed a dynamic computerized model of monochorial twin fetoplacental units on the basis of numerous interrelated hemodynamic, osmotic, and metabolic physiologic variables. The circulations were then linked by various combinations of direction and number of arteriovenous anastomoses. RESULTS: With unidirectional anastomoses disease severity, characterized by disparity in blood solids, depended on donor arterial pressure but not on the number of anastomoses. In the chronic state water movement resulting from raised osmotic pressure in the recipient and reduction in the donor produced hydroosmotic pressure equilibrium, reducing anastomotic flow to near zero. Atrial natriuretic peptide-driven urine production was markedly increased in the recipient because of the raised vascular hydrostatic pressure component. With bidirectional anastomoses recirculation between twins reduced discordancy in colloids and hematocrit, and the clinical picture was determined by the degree of asymmetry in the number of connections. CONCLUSIONS: Severe manifestations of fetofetal transfusion syndrome can be explained by unidirectional intertwin transfusion and lesser degrees by asymmetric bidirectional transfusion.
Peripheral administration of opioids has been suggested as a means of improving regional block. We studied 60 patients receiving axillary brachial plexus anaesthesia, allocated randomly to receive either normal saline 10 ml or normal saline 10 ml with alfentanil 10 micrograms/kg body weight through an axillary cannula. All patients received 1.5% lignocaine at a dose of 7 mg/kg body weight with adrenaline 1 in 200,000. The incidence of satisfactory block was similar in both groups. Although the percentage of patients with complete anaesthesia in the median nerve distribution was greater in the alfentanil group, there was no significant difference in any other distribution. The time to return of sensation and motor function was prolonged significantly in the alfentanil group (P < 0.05). After return of normal sensation, there was no significant difference between groups in postoperative analgesia. In a second part of the study, there was no significant increase in plasma concentrations of alfentanil in 10 patients given lignocaine and alfentanil, as outlined above. These observations suggest that alfentanil may have a peripheral local anaesthetic action.
DESIGN: Prospective audit of first six months. SETTING: Referral from a district general hospital on the Isle of Wight to a comprehensive tertiary referral service, the Centre for Fetal Care at Queen Charlotte's Hospital 120 km away in London. PARTICIPANTS: Women whose pregnancy was suspected, or at risk, of fetal abnormality. INTERVENTIONS: Remote consultation by transmitting ultrasound and video in real-time over ISDN 30 telephone lines. Contemporaneous questionnaire to referring practitioner and patient. MAIN OUTCOME MEASURES: Frequency, indication, technical success and duration of consultation. Qualitative and semi-quantitative image quality. Effect of teleconsultation on need for physical referral. RESULTS: Twenty-nine women underwent 39 teleconsultations, and image quality was sufficient for diagnosis in all but one. Fetal abnormalities were present in 76%. Referral in person was required for only four women, significantly fewer than the 13 the referring hospital indicated would have been physically referred in the absence of this service (P < 0.001). Most mothers were counselled by the specialist "face-to-face' over the link, and 80% felt teleconsultation reduced their anxiety. CONCLUSIONS: A fetal telemedicine service is technically and clinically feasible. This demonstration suggests that such a service reduces the need for physical referral while increasing the rate of consultation, allowing better selection of patients who might benefit from referral. Further evaluation in a variety of clinical settings is now indicated, along with cost-benefit analysis.
OBJECTIVES: In fetuses with a single umbilical artery the entire blood flow to the placenta is transported through the common and internal iliac arteries from the side of the single artery, whereas the pelvic vessels from the side of the missing artery do not participate in the fetoplacental circulation. The aim of this study was to investigate the effect of gestational age on pelvic arterial blood flow in fetuses with single umbilical artery. DESIGN: In 15 fetuses with a single umbilical artery (SUA), common iliac artery flow velocity waveforms were studied longitudinally using high resolution colour Doppler ultrasonography at three gestational ages: 18 to 20 weeks, 28 to 30 weeks, and 35 to 37 weeks. The pulsatility index was measured in each common iliac artery and mixed model analysis of variance was used to examine the effect of gestational age and side. RESULTS: There was a highly significant difference in pulsatility index between common iliac arteries at all gestational ages, the values always being higher on the side that did not participate in the fetoplacental circulation (P < 0.001). For increasing gestation, the pulsatility index fell significantly in the SUA side but remained high in the non-SUA side (P < 0.001). CONCLUSIONS: This study shows that the asymmetry in the pelvic arterial blood flow in fetuses with SUA increases as pregnancy progresses, consistent with decreasing vascular resistance in the placenta and increasing resistance in the lower extremities.
A 10-kb region of the Bacillus subtilis genome that contains genes involved in biotin-biosynthesis was cloned and sequenced. DNA sequence analysis indicated that B. subtilis contains homologs of the Escherichia coli and Bacillus sphaericus bioA, bioB, bioD, and bioF genes. These four genes and a homolog of the B. sphaericus bioW gene are arranged in a single operon in the order bioWAFDR and are followed by two additional genes, bioI and orf2. bioI and orf2 show no similarity to any other known biotin biosynthetic genes. The bioI gene encodes a protein with similarity to cytochrome P-450s and was able to complement mutations in either bioC or bioH of E. coli. Mutations in bioI caused B. subtilis to grow poorly in the absence of biotin. The bradytroph phenotype of bioI mutants was overcome by pimelic acid, suggesting that the product of bioI functions at a step prior to pimelic acid synthesis. The B. subtilis bio operon is preceded by a putative vegetative promoter sequence and contains just downstream a region of dyad symmetry with homology to the bio regulatory region of B. sphaericus. Analysis of a bioW-lacZ translational fusion indicated that expression of the biotin operon is regulated by biotin and the B. subtilis birA gene.
Northern (RNA) blot analysis of the Bacillus subtilis biotin operon, bioWAFDBIorf2, detected at least two steady-state polycistronic transcripts initiated from a putative vegetative (Pbio) promoter that precedes the operon, i.e., a full-length 7.2-kb transcript covering the entire operon and a more abundant 5.1-kb transcript covering just the first five genes of the operon. Biotin and the B. subtilis birA gene product regulated synthesis of the transcripts. Moreover, replacing the putative Pbio promoter and regulatory sequence with a constitutive SP01 phage promoter resulted in higher-level constitutive synthesis. Removal of a rho-independent terminator-like sequence located between the fifth (bioB) and sixth (bioI) genes prevented accumulation of the 5.1-kb transcript, suggesting that the putative terminator functions to limit expression of bioI, which is thought to be involved in an early step in biotin synthesis.
Severe chronic pain after groin hernia repair is uncommon but potentially debilitating. Fifteen patients with this condition were retrospectively reviewed. All patients had severe pain, which prevented their working or normal activity and was refractory to nonoperative treatment. Essentials of therapy included 1) a preoperative attempt to identify the involved nerve and 2) high ligation and division of the involved nerve identified at exploration. Twelve patients obtained excellent results and were able to return to normal activity with no requirement for analgesia. Understanding of the typical nerve anatomy, as well as the individual variation in nerve anatomy, can help prevent this complication and is essential for correction if the complication does develop.
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