Longitudinal Doppler Assessments in Late Preterm Fetal Growth Restriction.

PURPOSE: To assess the longitudinal variation of the ratio of umbilical and cerebral artery pulsatility index (UCR) in late preterm fetal growth restriction (FGR). MATERIALS AND METHODS: A prospective European multicenter observational study included women with a singleton pregnancy, 32+ 0-36+ 6, at risk of FGR (estimated fetal weight [EFW] or abdominal circumference [AC] < 10th percentile, abnormal arterial Doppler or fall in AC from 20-week scan of > 40 percentile points). The primary outcome was a composite of abnormal condition at birth or major neonatal morbidity. UCR was categorized as normal (< 0.9) or abnormal (≥ 0.9). UCR was assessed by gestational age at measurement interval to delivery, and by individual linear regression coefficient in women with two or more measurements. RESULTS: 856 women had 2770 measurements; 696 (81 %) had more than one measurement (median 3 (IQR 2-4). At inclusion, 63 (7 %) a UCR ≥ 0.9. These delivered earlier and had a lower birth weight and higher incidence of adverse outcome (30 % vs. 9 %, relative risk 3.2; 95 %CI 2.1-5.0) than women with a normal UCR at inclusion. Repeated measurements after an abnormal UCR at inclusion were abnormal again in 67 % (95 %CI 55-80), but after a normal UCR the chance of finding an abnormal UCR was 6 % (95 %CI 5-7 %). The risk of composite adverse outcome was similar using the first or subsequent UCR values. CONCLUSION: An abnormal UCR is likely to be abnormal again at a later measurement, while after a normal UCR the chance of an abnormal UCR is 5-7 % when repeated weekly. Repeated measurements do not predict outcome better than the first measurement, most likely due to the most compromised fetuses being delivered after an abnormal UCR.

Fetal cerebral Doppler changes and outcome in late preterm fetal growth restriction: prospective cohort study.

OBJECTIVES: To explore the association between fetal umbilical and middle cerebral artery (MCA) Doppler abnormalities and outcome in late preterm pregnancies at risk of fetal growth restriction. METHODS: This was a prospective cohort study of singleton pregnancies at risk of fetal growth restriction at 32 + 0 to 36 + 6 weeks of gestation, enrolled in 33 European centers between 2017 and 2018, in which umbilical and fetal MCA Doppler velocimetry was performed. Pregnancies were considered at risk of fetal growth restriction if they had estimated fetal weight and/or abdominal circumference (AC) < 10th percentile, abnormal arterial Doppler and/or a fall in AC growth velocity of more than 40 percentile points from the 20-week scan. Composite adverse outcome comprised both immediate adverse birth outcome and major neonatal morbidity. Using a range of cut-off values, the association of MCA pulsatility index and umbilicocerebral ratio (UCR) with composite adverse outcome was explored. RESULTS: The study population comprised 856 women. There were two (0.2%) intrauterine deaths. Median gestational age at delivery was 38 (interquartile range (IQR), 37-39) weeks and birth weight was 2478 (IQR, 2140-2790) g. Compared with infants with normal outcome, those with composite adverse outcome (n = 93; 11%) were delivered at an earlier gestational age (36 vs 38 weeks) and had a lower birth weight (1900 vs 2540 g). The first Doppler observation of MCA pulsatility index < 5th percentile and UCR Z-score above gestational-age-specific thresholds (1.5 at 32-33 weeks and 1.0 at 34-36 weeks) had the highest relative risks (RR) for composite adverse outcome (RR 2.2 (95% CI, 1.5-3.2) and RR 2.0 (95% CI, 1.4-3.0), respectively). After adjustment for confounders, the association between UCR Z-score and composite adverse outcome remained significant, although gestational age at delivery and birth-weight Z-score had a stronger association. CONCLUSION: In this prospective multicenter study, signs of cerebral blood flow redistribution were found to be associated with adverse outcome in late preterm singleton pregnancies at risk of fetal growth restriction. Whether cerebral redistribution is a marker describing the severity of fetal growth restriction or an independent risk factor for adverse outcome remains unclear, and whether it is useful for clinical management can be answered only in a randomized trial. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

Minimally-invasive fetal autopsy using magnetic resonance imaging and percutaneous organ biopsies: clinical value and comparison to conventional autopsy.

OBJECTIVES: Autopsy is an important investigation following fetal death or termination for fetal abnormality. Postmortem magnetic resonance imaging (MRI) can provide macroscopic information of comparable quality to that of conventional autopsy in the event of perinatal death. It does not provide tissue for histological examination, which may limit the quality of counseling for recurrence risks and elucidation of the cause of death. We sought to examine the comparability and clinical value of a combination of postmortem MRI and percutaneous fetal organ biopsies (minimally invasive autopsy (MIA)) with conventional fetal autopsy. METHODS: Forty-four fetuses underwent postmortem MRI and attempted percutaneous biopsy (using surface landmarks) of major fetal organs (liver, lung, heart, spleen, kidney, adrenal and thymus) following fetal death or termination for abnormality, prior to conventional autopsy, which was considered the 'gold standard'. We compared significant findings of the two examinations for both diagnostic information and clinical significance. Ancillary investigations (such as radiographs and placental histology) were regarded as common to the two forms of autopsy. RESULTS: In 21 cases conventional autopsy provided superior diagnostic information to that of MIA. In two cases the MIA provided superior diagnostic information to that of conventional autopsy, when autolysis prevented detailed examination of the fetal brain. In the remaining 21 cases, conventional autopsy and MIA provided equivalent diagnostic information. With regard to clinical significance, however, in 32 (72.7%) cases, the MIA provided information of at least equivalent clinical significance to that of conventional autopsy. In no case did the addition of percutaneous biopsies reveal information of additional clinical significance. CONCLUSIONS: Although in some cases MRI may provide additional information, conventional perinatal autopsy remains the gold standard for the investigation of fetal death. The utility of adding percutaneous organ biopsies, without imaging guidance, to an MRI-based fetal autopsy remains unproven. Postmortem MRI, combined with ancillary investigations such as placental histology, external examination by a pathologist, cytogenetics and plain radiography provided information of equivalent clinical significance in the majority of cases.

Feasibility of percutaneous organ biopsy as part of a minimally invasive perinatal autopsy.

To determine the feasibility of percutaneous fetal organ biopsies in the context of a 'minimally invasive' perinatal autopsy after stillbirth and termination for abnormality is the aim of this study. We assessed successful biopsy rate and the proportion adequate for histological examination in 30 fetuses undergoing organ sampling before autopsy. The relationship between gestational age, body weight, death-biopsy interval, operator experience and successful biopsy rate was investigated. Significant findings from conventional block histology were compared with corresponding percutaneous biopsies. Of 210 organ biopsies attempted from seven target organs, 107 were obtained, of which 94 were adequate for pathological comment. The median delivery-autopsy interval was 4 (range 2-11) days. Adequate samples were obtained from the lung in 86% cases (95% CI 68, 96%), liver 76% (95% CI 56, 90%) and less frequently for the myocardium, kidney, adrenal, thymus and spleen. There was no relationship between biopsy success and time to biopsy, gestational age, body weight and user experience. No histological abnormalities found at autopsy were diagnosed from needle biopsies. Although targeted percutaneous biopsies appear feasible for some organs, fewer than 50% of all biopsies are adequate for histological examination. This technique cannot be considered to provide useful clinical information as part of a 'minimally invasive' perinatal autopsy.

Palliative care for prenatally diagnosed lethal fetal abnormality.

Diagnosis of lethal fetal abnormality raises challenging decisions for parents and clinicians. Most parents opt for termination, which may include feticide. Advances in imaging seem unlikely to lead to earlier diagnoses. Perinatal palliative care offers an alternative. Parental decision making and the clinical aspects of perinatal palliative care were studied after a prenatal diagnosis of lethal fetal abnormality in 20 pregnancies. 40% of parents chose to continue the pregnancy and pursue perinatal palliative care. Six of these eight babies were liveborn and lived for between 1(1/2) h and 3 weeks.

Identification by cross-linking of a neuronal acceptor protein for dendrotoxin, a convulsant polypeptide.

Dendrotoxin, a lijow molecular weight protein from the venom of Dendroaspis angusticeps, is known to be a potent convulsant that attenuates one type of voltage-sensitive K+ channel in guinea-pig hippocampus. A biologically active preparation of 125I-labelled dendrotoxin has been cross-linked to its high-affinity protein acceptor in synaptic plasma membranes from rat cerebral cortex. On SDS gel electrophoresis, a complex with a Mr of 72,000 was observed which, assuming one toxin molecule is attached, yields an apparent size of 65,000 for this subunit of the acceptor. Unlike dendrotoxin, low concentrations of beta-bungarotoxin, another pre-synaptically active toxin, do not inhibit its labelling.

Treatment of cancer patients with a low-density-lipoprotein delivery vehicle containing a cytotoxic drug.

A cytotoxic drug (vincristine, VC) was incorporated into low-density lipoprotein (LDL) and given to cancer patients for the first time by repeated intravenous injection. Individuals presenting with ovarian or endometrial cancer received four or five weekly doses of 1.4 mg/m2 LDL/VC. The uptake of LDL/VC by the adrenal cortex and the liver was minimised by concurrent administration of prednisolone and chenodeoxycholic acid. No febrile, allergic or other reaction attributable to the LDL occurred, and no side effect on haemopoietic, adrenal or liver functions was observed. The neurotoxic side effects commonly seen during VC therapy appeared to be reduced. These results suggest that directed cytotoxic therapy might be achieved in humans through the use of LDL as a carrier. Thus, dose-range and comparative studies using LDL/VC vs VCSO4 are warranted in malignancies in which treatment with the latter drug has been established.

Gonadotrophin-releasing hormone analogues for endometriosis: bone mineral density.

BACKGROUND: Gonadotrophin-releasing hormone analogues (GnRHas) are generally well tolerated, and are effective in relieving the symptoms of endometriosis (Prentice 2003). Unfortunately the low oestrogen state that they induce is associated with adverse effects including an acceleration in bone mineral density (BMD) loss. OBJECTIVES: To determine the effect of treatment with gonadotrophin-releasing hormone analogues (GnRHas) on the bone mineral density of women with endometriosis, compared to placebo, no treatment, or other treatments for endometriosis, including GnRHas with add-back therapy. SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility Group's specialised register of controlled trials (23rd October 2002) and the Cochrane Central Register of Controlled Trials (Cochrane Library, issue 4, 2002). We also carried out electronic searches of MEDLINE (1966 - March Week 2 2003) and EMBASE (1980 - March Week 2 2003). We also searched the reference lists of articles and contacted researchers in the field. SELECTION CRITERIA: Prospective, randomised controlled studies of the use of GnRHas for the treatment of women with endometriosis were considered, where bone density measurements were an end point. The control arm of the studies was either placebo, no treatment, another medical therapy for endometriosis, or GnRHas with add-back therapy. DATA COLLECTION AND ANALYSIS: Two reviewers (JF and MS) independently assessed trial quality and extracted data. Study authors were contacted for additional information. MAIN RESULTS: Thirty studies involving 2,391 women were included, however only 15, involving 910 women, could be included in the meta-analysis. The meta-analysis showed that danazol and progesterone + oestrogen add-back are protective of BMD at the lumbar spine both during treatment and for up to six and twelve months after treatment, respectively. Between the groups receiving GnRHa and the groups receiving danazol/gestrinone, there was a significant difference in percentage change of BMD after six months of treatment, the GnRH analogue producing a reduction in BMD from baseline and danazol producing an increase in BMD (SMD -3.43, 95 % CI -3.91 to -2.95). Progesterone only add-back is not protective; after six months of treatment absolute value BMD measurements of the lumbar spine did not differ significantly from the group receiving GnRH analogues (SMD 0.15, 95 % CI -0.21 to 0.52). In the comparison of GnRHa versus GnRHa + HRT add-back, that is oestrogen + progesterone or oestrogen only, there was a significantly bigger BMD loss in the GnRHa only group (SMD -0.49, 95 % CI -0.77 to -0.21). These numbers reflect the absolute value measurements at the lumbar spine after six months of treatment. Due to the small number of studies in the comparison we are unable to conclude whether calcium-regulating agents are protective. No difference was found between low and high dose add-back regimes but again only one study was identified for this comparison. Only one study comparing GnRH analogues with placebo was identified, but the study gave no data. No studies comparing GnRH with the oral contraceptive pill (OCP) or progestagens were identified. REVIEWER'S CONCLUSIONS: Both danazol and progesterone + oestrogen add-back have been shown to be protective of BMD, while on treatment and up to six and 12 months later, respectively. However, by 24 months of follow-up there was no difference in BMD in those women who had HRT add-back. Studies of danazol versus GnRHa did not report long-term follow-up. The significant side effects associated with danazol limit its use.

Postmortem fetal organ volumetry using magnetic resonance imaging and comparison to organ weights at conventional autopsy.

OBJECTIVES: Following perinatal death, organ weights at autopsy may provide evidence of growth restriction and pulmonary hypoplasia. Whilst postmortem magnetic resonance imaging (MRI) may provide comparable information to autopsy about structural abnormalities, its ability to provide reproducible data about organ size has yet to be determined. We examined the feasibility of using postmortem MRI to provide estimates of organ size and weight. METHODS: Twenty-five fetuses of gestational age from 16 to 40 weeks underwent postmortem MRI prior to autopsy. Fetal lung, brain and liver volume estimations were performed by two observers using the stereology technique on postmortem MRI slices. Fetal lung, brain and liver weights were recorded at autopsy. Organ volume estimates and autopsy organ weights were compared using regression analysis, and estimates of fetal organ densities made. Interobserver variability was assessed using a Bland-Altman plot. Receiver-operating characteristics curve (ROC) analysis compared MRI brain : liver volume ratios to autopsy brain : liver weight ratios. RESULTS: A linear relationship between organ volume estimates and organ weight was observed. Estimated densities for the fetal brain, liver and lung were 1.08 g/cm(3), 1.15 g/cm(3) and 1.15 g/cm(3), respectively. Interobserver 5th and 95th percentile limits of agreement for fetal brain, liver and lung were - 5.4% to + 7.9%, - 11.8% to + 8.3% and - 14.3% to + 8.7%, respectively. For MRI organ volumes to detect a brain weight : liver weight ratio > or = 4, ROC analysis demonstrated an area under the curve of 0.61, with an optimal cut-off of 4.1. CONCLUSION: Postmortem MRI organ volumetry can be used to estimate weights of major fetal organs. This may increase the information obtained from a minimally-invasive perinatal autopsy, particularly in the context of pulmonary hypoplasia and intrauterine growth restriction, where differential organ growth plays a major part in assessment of the underlying pathology.

Use of a confidence scale in reporting postmortem fetal magnetic resonance imaging.

OBJECTIVES: Postmortem magnetic resonance imaging (MRI) may be an alternative to conventional autopsy. However, it is unclear how confident radiologists are in reporting such studies. We sought to determine the confidence with which radiologists report on various fetal organs by developing a scale to express their confidence of normality and abnormality, and to place this in the context of a pathological diagnosis of whether the organ was in fact normal or abnormal. METHODS: Thirty fetuses, aged 16-39 gestational weeks and weighing 61-3270 g, underwent postmortem MRI prior to conventional autopsy. MRI studies were reported by two radiologists with access to the clinical and sonographic history: a neuroradiologist, reporting head and neck, and a pediatric radiologist, reporting thorax, abdomen and pelvis. Radiologists used a scale (0 = definitely abnormal, 100 = definitely normal, 50 = unable to comment) to indicate their confidence of anatomical structures being normal or abnormal, using a checklist. Conventional autopsies were performed by pediatric pathologists blinded to the MRI findings, and these were considered the reference standard. RESULTS: Most normal fetal organs had high scores on postmortem MRI, with median confidence scores above 80. However, the atrioventricular valves, duodenum, bowel rotation and pancreas proved more difficult to assess, with median scores of 50, 60, 60 and 62.5, respectively. Abnormal cardiac atria and ventricles, kidneys, cerebral hemispheres and corpus callosum were always detected with high or moderate degrees of confidence (median scores of 2.5, 5, 0, 0 and 30 respectively). However, in two cases with abnormal cardiac outflow tracts, both cases scored 50. Kappa values, assessing agreement between MRI diagnoses of abnormality and autopsy, were high for the brain (0.83), moderate for the lungs (0.56) and fair for the heart (0.33). CONCLUSIONS: This scoring system represents an attempt to define the confidence of radiologists to report varying degrees of normality and abnormality following z ex-utero fetal MRI. While most fetal anatomy is clearly visualized on postmortem MRI, radiologists may lack confidence reporting such studies and there are particular problems with assessment of some cardiac and gastrointestinal structures, both normal and abnormal.

Interactions between discrete neuronal membrane binding sites for the putative K+-channel ligands beta-bungarotoxin, dendrotoxin and mast-cell-degranulating peptide.

1. beta-Bungarotoxin, a presynaptically active neurotoxin from the venom of Bungarus multicinctus, was radiolabelled with 125I and its binding to synaptic membranes from rat brain was analyzed. The interaction of these binding sites with those for dendrotoxin (a convulsant polypeptide from mamba venom) and mast-cell-degranulating peptide (from bee venom) was examined in the light of the known effects of all three toxins on voltage-dependent K+ currents. 2. When measured in Krebs/phosphate buffer, the binding appeared monotonic at low concentrations of radioiodinated beta-bungarotoxin (Kd 0.4 nM; Bmax 0.42 pmol/mg protein); higher concentrations of labelled toxin revealed an additional binding component of lower affinity, but computer analysis of the data failed to provide well-defined estimates of its Kd and Bmax values. 3. Equilibrium binding experiments conducted in imidazole-based buffers yielded distinctly biphasic Scatchard plots; computer analysis of the data revealed two populations of sites [Kd 0.26 (+/- 0.30) nM and 6.14 (+/- 5.68) nM; Bmax 0.16 (+/- 0.20) and 2.65 (+/- 1.21) pmol/mg protein]. 4. In Krebs medium, beta-bungarotoxin was a very weak antagonist of the binding of 125I-labelled dendrotoxin. In imidazole medium, however, the efficacy of the inhibition was markedly increased; analysis of this inhibition showed it to be non-competitive. 5. Dendrotoxin inhibited the binding of radioiodinated beta-bungarotoxin in Krebs medium with high potency, although the interaction was by a complex, non-competitive mechanism. 6. Mast-cell-degranulating peptide inhibited non-competitively the binding of both radiolabelled dendrotoxin and beta-bungarotoxin but with relatively low potency. 7. A speculative schematic model of the dendrotoxin/beta-bungarotoxin/mast-cell-degranulating peptide binding component(s) is proposed. Findings are discussed in terms of the likely involvement of these sites with voltage-dependent K+-channel proteins.

Mutations to nitrofurantoin and nitrofurazone resistance in Escherichia coli K12.

The isolation and properties of nitrofurantoin- and nitrofurazone-resistant mutants have been compared. Nitrofurantoin-resistant mutants were easier to obtain and showed a higher resistance level. There was some cross-resistance at lower drug concentrations but not at higher levels. There was no difference in the UV resistance of most of the mutants obtained although a recB strain, AB2470, did yield nitrofurantoin-resistant mutants with increased UV resistance. This was however the only repair-defective strain which could be mutated to nitrofurantoin resistance. It is suggested that there is a mechanism for nitrofurantoin resistance in Escherichia coli K12 which does not confer resistance to nitrofurazone and which may be associated with the repair of damaged DNA. This mechanism is in addition to that which also confers resistance to nitrofurazone.

Transferable nitrofuran resistance conferred by R-plasmids in clinical isolates of Escherichia coli.

A high proportion of nitrofuran-resistant strains has been found in a collection of antibiotic-resistant Gram-negative bacteria isolated from patients with urinary tract infections. Some of the Escherichia coli carried R-plasmids that conferred resistance to nitrofurantoin and nitrofurazone. The mechanism of resistance is not clear; only in lactose non-fermenting recipients was there a decrease in the nitrofuran-reducing ability of whole-cell suspensions. One of the plasmids conferred enhanced resistance to UV light on DNA repair defective mutants but not on repair efficient strains. In some resistant strains, the total resistance was apparently the result of a combination of chromosomal and plasmid-borne genes. The presence of the plasmid may allow the development of higher resistance levels by mutation of chromosomal genes.

Nitrofuran reductase activity in nitrofurantoin-resistant strains of Escherichia coli K12: some with chromosomally determined resistance and others carrying R-plasmids.

The nitrofuran reductase activity of Escherichia coli K12 strains was separated into two components by passage through Sepharose 4B-200. The components differed in their sensitivity to 2 M urea and their reactivity with NADH and NADPH. Some nitrofurantoin-resistant mutants had lost one component (alpha) while retaining the other (beta). Other mutants, resistant to higher levels of nitrofurantoin, had lost most of the beta component as well. Transconjugants which had received plasmids conferring nitrofurantoin resistance were found to have only the alpha component and it was markedly less active when NADH rather than NADPH was supplied as co-enzyme.

The effects of chlorate- and streptomycin-resistance mutations on nitrofurantoin resistance in Escherichia coli K-12.

Chlorate-resistant mutants with none of the usual pleiotropic effects such as defective nitrate reductase activity were isolated from Escherichia coli K-12. These chlorate-resistant mutants (designated chlHW) did not yield strains with a high level of nitrofurantoin resistance following selection with nitrofurantoin. The chlorate-resistance mutation reduced the nitrofurantoin resistance of high-level mutants to an intermediate level. Further mutation to resistance to streptomycin and other aminoglycoside antibiotics suppressed the effect of chlHW on the level of nitrofurantoin resistance. Other chlorate-resistance genes examined did not have the same effect on nitrofurantoin resistance as chlHW. The gene was cotransducible (Pl) with intermediate-level nitrofurantoin resistance and proC. It is suggested that the chlHW mutation may enhance the accumulation of nitrofurantoin inside the cell since it is known that a multiple aminoglycoside-resistance mutation with pleiotropic effects on the cell membrane can also confer high-level resistance to nitrofurantoin.

The enhancement of R-plasmid-mediated resistance to aminoglycoside antibiotics by mutations to nitrofurantoin resistance in Escherichia coli.

Mutation to high level resistance to nitrofurantoin of a strain of Escherichia coli carrying an R-plasmid conferring resistance to gentamicin, kanamycin and other antibiotics resulted in greatly increased resistance to the two aminoglycosides but not the other antibiotics. A similar result was observed when the R-plasmid was transferred to high level nitrofurantoin-resistant mutants. The enhanced resistance was accompanied by a 30% increase in 3-N-acetyltransferase activity. Resistance to chloramphenicol in a strain carrying an R-plasmid coding for chloramphenicol acetyltransferase was not increased although the same strain showed increased resistance to kanamycin. These observations may have considerable significance in the development of resistance to gentamicin and other aminoglycoside antibiotics.

Gentamicin- and neomycin-resistant mutants of Escherichia coli K-12 cross-resistant to nitrofurans.

Gentamicin and neomycin-resistant mutants of Escherichia coli K-12 were isolated some of which were resistant to nitrofurans, chlorate, P1 and lambda bacteriophages as well as to all aminoglycoside antibiotics tested. Previously isolated nitrofuran-resistant mutants were not cross-resistant to the tested aminoglycosides, chlorate and bacteriophages. The aminoglycoside-resistant mutants exhibiting cross-resistance had enhanced membrane Mg2+-ATPase and decreased periplasmic alkaline phosphatase activity compared to their parent sensitive strains. The mutants were also defective in the fermentation of sugars, reduction of nitrate and nitrite, and in formate dehydrogenase activity. Preliminary genetic studies indicated that the pleiotropic mutation might be located in the upper left quadrant of the E. coli K-12 chromosome linkage map. It is postulated that such mutants with gross membrane alterations have impaired accumulation of aminoglycoside and nitrofuran antibiotics.

Solution structure of human calcitonin gene-related peptide by 1H NMR and distance geometry with restrained molecular dynamics.

The structure of human calcitonin gene-related peptide 1 (hCGRP-1) has been determined by 1H NMR in a mixed-solvent system of 50% trifluoroethanol/50% H2O at pH 3.7 and 27 degrees C. Complete resonance assignment was achieved by using two-dimensional methods. Distance restraints for structure calculations were obtained by semiquantitative analysis of intra- and interresidue nuclear Overhauser effects; in addition, stereospecific or X1 rotamer assignments were obtained for certain side chains. Structures were generated from the distance restraints by distance geometry, followed by refinement using molecular dynamics, and were compared with experimental NH-C alpha H coupling constants and amide hydrogen exchange data. The structure of hCGRP-1 in this solvent comprises an amino-terminal disulfide-bonded loop (residues 2-7) leading into a well-defined alpha-helix between residues 8 and 18; thereafter, the structure is predominantly disordered, although there are indications of a preference for a turn-type conformation between residues 19 and 21. Comparison of spectra for the homologous hCGRP-2 with those of hCGRP-1 indicates that the conformations of these two forms are essentially identical.