Evaluation of point-of-care maternal glucose measurements for the diagnosis of gestational diabetes mellitus.

OBJECTIVE: Using updated laboratory standards as the reference, we aimed to compare point-of-care (POC) maternal capillary glucose testing with the diagnostic accuracy of reference and customary venous samples. DESIGN, SETTING, POPULATION: Women screened selectively with a one-step 75-g oral glucose tolerance test (OGTT) at 24-28 weeks' gestation were conveniently recruited to this prospective observational study. METHODS: Two venous samples and one capillary sample were taken at each OGTT time point. Venous sample one was a fluoride-EDTA (FE) tube placed on an ice-slurry until cell separation and analysis within 30 minutes (reference standard). Venous sample two was transported in a tube containing FE (without ice) (customary practice). A capillary sample was used for POC testing. Various cut-off points for the POC sample were examined to evaluate diagnostic accuracy. MAIN OUTCOME MEASURES: The sensitivity, specificity, positive and negative predictive values and accuracy of POC capillary glucose for the diagnosis of GDM. RESULTS: Of 108 women, GDM was detected in 47.2% (n = 51), 17.6% (n = 19) and 24.1% (n = 26) using the reference standard, customary practices and POC, respectively (P < 0.001). However, based on adjustment of the POC fasting diagnostic threshold from ≥5.1 to ≥4.8 mol/l (aPOC), sensitivity, specificity, PPV, NPV and accuracy improved to 92.5, 76.5, 69.8, 94.5 and 94.5%, respectively. CONCLUSIONS: POC capillary maternal glucose tests were superior to customary laboratory practices for diagnosing GDM. This has considerable potential, particularly in healthcare settings where facilities for phlebotomy are distant from the laboratory or pre-analytical sample handling is substandard. TWEETABLE ABSTRACT: Adjusted point-of-care glucose measurements have potential in the diagnosis of gestational diabetes mellitus.

In vivo efficacy of anuran trypsin inhibitory peptides against staphylococcal skin infection and the impact of peptide cyclization.

Staphylococcus aureus is a virulent pathogen that is responsible for a wide range of superficial and invasive infections. Its resistance to existing antimicrobial drugs is a global problem, and the development of novel antimicrobial agents is crucial. Antimicrobial peptides from natural resources offer potential as new treatments against staphylococcal infections. In the current study, we have examined the antimicrobial properties of peptides isolated from anuran skin secretions and cyclized synthetic analogues of these peptides. The structures of the peptides were elucidated by nuclear magnetic resonance (NMR) spectroscopy, revealing high structural and sequence similarity with each other and with sunflower trypsin inhibitor 1 (SFTI-1). SFTI-1 is an ultrastable cyclic peptide isolated from sunflower seeds that has subnanomolar trypsin inhibitory activity, and this scaffold offers pharmaceutically relevant characteristics. The five anuran peptides were nonhemolytic and noncytotoxic and had trypsin inhibitory activities similar to that of SFTI-1. They demonstrated weak in vitro inhibitory activities against S. aureus, but several had strong antibacterial activities against S. aureus in an in vivo murine wound infection model. pYR, an immunomodulatory peptide from Rana sevosa, was the most potent, with complete bacterial clearance at 3 mg · kg(-1). Cyclization of the peptides improved their stability but was associated with a concomitant decrease in antimicrobial activity. In summary, these anuran peptides are promising as novel therapeutic agents for treating infections from a clinically resistant pathogen.

Identifying the immunomodulatory components of helminths.

Immunomodulatory components of helminths offer great promise as an entirely new class of biologics for the treatment of inflammatory diseases. Here, we discuss the emerging themes in helminth-driven immunomodulation in the context of therapeutic drug discovery. We broadly define the approaches that are currently applied by researchers to identify these helminth molecules, highlighting key areas of potential exploitation that have been mostly neglected thus far, notably small molecules. Finally, we propose that the investigation of immunomodulatory compounds will enable the translation of current and future research efforts into potential treatments for autoimmune and allergic diseases, while at the same time yielding new insights into the molecular interface of host-parasite biology.

Maternal Obesity and Neck Circumference.

Obese women are more likely to require general anaesthesia for an obstetric intervention than non-obese. Difficult tracheal intubation and oxygen desaturation is more common in pregnancy. Failed tracheal intubation has been associated with an increase in neck circumference (NC). We studied the relationship between maternal obesity and NC as pregnancy advanced in women attending a standard antenatal clinic. Of the 96 women recruited, 13.5% were obese. The mean NC was 36.8cm (SD 1.9) in the obese women compared with 31.5cm (SD 1.6) in women with a normal BMI (p < 0.001) at 18-22 weeks gestation. In the obese women it increased on average by 1.5cm by 36-40 weeks compared with an increase of 1.6 cm in women with a normal BMI. The antenatal measurement of NC is a simple, inexpensive tool that is potentially useful for screening obese women who may benefit from an antenatal anaesthetic assessment.

Improved quality of life in adults undergoing tonsillectomy for recurrent tonsillitis. Is adult tonsillectomy really a low priority treatment?

There is a paucity of studies on patient-reported outcome measures in adult tonsillectomy. Our aim was to add to the body of health-related quality of life (HRQOL) evidence on adult tonsillectomy at a time when this intervention is being branded a low priority treatment in the United Kingdom (UK). We designed a prospective questionnaire study that was carried out in two UK district general hospitals. 41 patients were recruited into the study and completed a pre-operative short form 36 questionnaire. All 41 were contacted at least 1 year after tonsillectomy and were asked to complete the same SF-36 questionnaire and three additional HRQOL questions. There was a significant improvement in quality of life shown by both the mean SF-36 scores and the HRQOL questions. The SF-36 summary measures and the total SF-36 scores improved significantly (p < 0.01). The study emphasises the importance of tonsillectomy being available on the National Health Service to adults with recurrent tonsillitis. This proven quality of life improvement is also highly likely to confer a secondary health economic benefit from less GP attendances and fewer missed work days.

Heavy methanes as atmospheric tracers.

Methane-21 ((13)CD(4)) is potentially a useful nonradioactive tracer for testing atmospheric transport and diffusion models on a continental scale. In an experiment to demonstrate this long-range utility, the release of 84 grams of methane-21 was detected at distances of 1500 to about 2500 kilometers at concentrations of about 1 part in 2 x 10(16) parts (by volume) in the air by a technique in which methane was separated and the methane-21 content was measured with a mass spectrometer.

[CT evaluation of locoregional spread of carcinoma of the gallbladder]. / Evaluation de l'extension locorégionale des tumeurs de la vésicule biliaire par la tomodensitométrie.

OBJECTIVE: This study aims to assess the diagnostic capability of CT to preoperatively detect evidence of locoregional spread of gallbladder cancer. PATIENTS AND METHODS: Two radiologists independently performed retrospective review of CT scans on 20 patients who had undergone surgical resection for carcinoma of the gallbladder. Local spread was categorized by the TNM system and the results were correlated with surgical and pathologic findings. RESULTS: All cases of hepatic spread (14 cases), common bile duct extension (four cases), pancreatic spread (three cases) and duodenal spread (three cases) were correctly diagnosed by helical CT. One of three cases of peritoneal spread and two of three cases of gastric spread were misdiagnosed. CT evaluation of T stage (T1: one case [5%]; T2: four cases [20%]; T3: four cases [20%], and T4: 11 cases [55%]) was accurate in 85%. The sensitivity and positive predictive value (PPV) of T1-T2 lesions were 80%. The specificity and negative predictive value (NPV) were 93%. For T4 lesions sensitivity, specificity, PPV and NPV were 100%. CONCLUSION: Helical CT provided 85% accuracy in the diagnosis of the locoregional extent of gallbladder cancer. It allows an acceptable classification according to the TNM staging system and predicts prognosis.

Five year trends in maternal smoking behaviour reported at the first prenatal appointment.

BACKGROUND: Maternal smoking is a key modifiable risk factor in preventing adverse pregnancy outcomes such as intrauterine growth restriction, preterm birth and stillbirth. AIM: This observational study examined annual trends of maternal smoking reported at the first prenatal visit in women who delivered in a large university maternity hospital for the 5 years 2011-2015. METHODS: We examined clinical and sociodemographic data computerised routinely for women who presented for prenatal care at the hospital between 2011 and 2015. Multinomial logistic regression was used to determine the maternal characteristics, health behaviours and psychiatric history associated with smoking behaviours. RESULTS: Of the 42,509 women the mean age was 31.4 ± 5.5 years, mean Body Mass Index (BMI) was 25.6 ± 5.1 kg/m2, and 39.5% were nulliparas. Overall, 52.6% reported they had never smoked, 34.9% were ex-smokers, 10.5% smoked ≤10 cigarettes per day, 1.9% smoked ≥11 cigarettes per day and 0.1% smoked e-cigarettes. Between 2011 and 2015 the prevalence of maternal cigarette smoking decreased from 14.3 to 10.9% (P < 0.001). Smoking during pregnancy was most strongly associated with younger age, multiparity, unemployment, unplanned pregnancy, a history of psychiatric problems, alcohol intake and illicit drug usage. CONCLUSIONS: The number of women who reported smoking at the first prenatal visit decreased annually. Amongst women who continue to smoke during pregnancy, there is a clustering of adverse lifestyle behaviour and psychological problems that may need to be addressed if smoking cessation interventions are going to succeed in improving fetal programming.

Maternal obesity and physical activity and exercise levels as pregnancy advances: an observational study.

BACKGROUND: Increases in clinical complications associated with maternal obesity have generated interest in increasing physical activity (PA) and exercise levels as an intervention to improve pregnancy outcomes. AIMS: The objective of this study was to examine the relationship between BMI categorisation and PA and exercise levels as pregnancy advances. METHODS: This was an observational study in a large university maternity hospital. Women were recruited at their convenience before they left hospital after delivering a baby weighing 500 g or more. They completed a detailed customised physical activity and exercise questionnaire. BMI categorisation was based on the measurement of weight and height in early pregnancy. RESULTS: Of the 155 women recruited, 42.5 % (n = 66) were primigravidas and 10.3 % (n = 16) were smokers. Mean Body Mass Index (BMI) was 24.6 kg/m(2) and 14.2 % (n = 22) were obese, based on a BMI >29.9 kg/m(2). Overall, women decreased their exercise from an average 194 min (range 0-650 min) per week pre-pregnancy to 98 min antenatally (range 0-420 min) (p < 0.0001). Obese women exercised least pre-pregnancy and antenatally at 187.5 and 75 min per week, respectively, compared with 193.2 and 95.5 min per week in the normal BMI group and 239.3 and 106.7 min per week in the overweight group. The mean gestation at which all women reduced their activity levels was 29 weeks. CONCLUSIONS: We found that women decreased their PA  and exercise levels significantly in the third trimester and, thus, in the absence of a medical contra-indication there is considerable scope for an exercise intervention to improve activity  and exercise levels as pregnancy advances. However, an increase in PA levels in obese women needs further studies to determine whether it will improve the clinical outcomes for the woman and her offspring.

Plant cyclotides: A unique family of cyclic and knotted proteins that defines the cyclic cystine knot structural motif.

Several macrocyclic peptides ( approximately 30 amino acids), with diverse biological activities, have been isolated from the Rubiaceae and Violaceae plant families over recent years. We have significantly expanded the range of known macrocyclic peptides with the discovery of 16 novel peptides from extracts of Viola hederaceae, Viola odorata and Oldenlandia affinis. The Viola plants had not previously been examined for these peptides and thus represent novel species in which these unusual macrocyclic peptides are produced. Further, we have determined the three-dimensional structure of one of these novel peptides, cycloviolacin O1, using (1)H NMR spectroscopy. The structure consists of a distorted triple-stranded beta-sheet and a cystine-knot arrangement of the disulfide bonds. This structure is similar to kalata B1 and circulin A, the only two macrocyclic peptides for which a structure was available, suggesting that despite the sequence variation throughout the peptides they form a family in which the overall fold is conserved. We refer to these peptides as the cyclotide family and their embedded topology as the cyclic cystine knot (CCK) motif. The unique cyclic and knotted nature of these molecules makes them a fascinating example of topologically complex proteins. Examination of the sequences reveals they can be separated into two subfamilies, one of which tends to contain a larger number of positively charged residues and has a bracelet-like circularization of the backbone. The second subfamily contains a backbone twist due to a cis-Pro peptide bond and may conceptually be regarded as a molecular Moebius strip. Here we define the structural features of the two apparent subfamilies of the CCK peptides which may be significant for the likely defense related role of these peptides within plants.

Solution structure by NMR of circulin A: a macrocyclic knotted peptide having anti-HIV activity.

The three-dimensional solution structure of circulin A, a 30 residue polypeptide from the African plant Chassalia parvifolia, has been determined using two-dimensional 1H-NMR spectroscopy. Circulin A was originally identified based upon its inhibition of the cytopathic effects and replication of the human immunodeficiency virus. Structural restraints consisting of 369 interproton distances inferred from nuclear Overhauser effects, and 21 backbone dihedral and nine chi1 angle restraints from spin-spin coupling constants were used as input for simulated annealing calculations and energy minimisation in the program X-PLOR. The final set of 12 structures had mean pairwise rms differences over the whole molecule of 0.91 A for the backbone atom, and 1.68 A for all heavy atoms. For the well-defined region encompassing residues 2-12 and 18-27, the corresponding values were 0.71 and 1.66 A, respectively. Circulin A adopts a compact structure consisting of beta-turns and a distorted segment of triple-stranded beta-sheet. Fluorescence spectroscopy provided additional evidence for a solvent-exposed Trp residue. The molecule is stabilised by three disulfide bonds, two of which form an embedded loop completed by the backbone fragments connecting the cysteine residues. A third disulfide bond threads through the centre of this loop to form a "cystine-knot" motif. This motif is present in a range of other biologically active proteins, including omega-contoxin GVIA and Cucurbita maxima trypsin inhibitor. Circulin A belongs to a novel class of macrocyclic peptides which have been isolated from plants in the Rubiaceae family. The global fold of circulin A is similar to kalata B1, the only member of this class for which a structure has previously been determined.

Enhancement by misonidazole of metastatic tumor nodule formation in the lungs of mice.

Investigations were performed to determine whether misonidazole, a hypoxic cell radiosensitizer, influences formation of tumor nodules in the lung of C3Hf/Kam mice and whether it affects the enhancement of tumor nodule formation caused by local thoracic irradiation (LTI). Cells from a chemically-induced fibrosarcoma (FSa) and a spontaneously-developed fibrosarcoma (NFSa) formed twice as many tumor colonies in the lungs of mice that received misonidazole as in untreated mice. The effect was observed only with doses of misonidazole of 1 mg/g or higher given within 2 days prior to i.v. injection of tumor cells. A similar twofold amplification of the effect of LTI occurred when 1 mg/g misonidazole was given 30 min before or 0.5 to 2 hours after irradiation. This increase was independent of the dose of LTI and the absolute number of tumor nodules in the lung. The mechanistic possibilities and clinical relevance of the misonidazole effect are discussed.

Carcinoma of the cervical stump: a review of 213 cases.

From 1970 to 1987, 213 cases of carcinoma of the cervical stump were accrued in a multi-institutional prospective cooperative study. This group accounted for 5.5% of cervical carcinoma diagnosed during the same period. 13 had in situ carcinoma and 200 had invasive carcinoma (96% squamous cell carcinoma, 4% adenocarcinoma). Radiotherapy alone (external and brachytherapy) was given to 77%, brachytherapy and surgery to 15% and surgery alone to 8%). FIGO stage distribution was: I (31%), IIa (15%), IIb (27%), IIIa (5%), IIIb (17%) and IV (5%). Five-year locoregional control per stage was 100% in Ia, 85% in Ib, 82% in IIa, 71% in IIb, 45% in IIIa, 54% in IIIb and 30% in IV. Corrected 5-year survival per stage was 82% in Ib, 78% in IIa, 73% in IIb, 69% in IIIa, 38% in IIIb and 0% in IV. The diameter of disease in stage II strongly influenced the 5-year locoregional control (81% for tumours of less than 3 cm vs. 68% for tumours more than 3 cm). Lymphangiogram was associated with a 44.5% 5-year locoregional control when positive vs. 74% when non-positive. Brachytherapy was advantageous in obtaining locoregional control in patients receiving external irradiation and brachytherapy: 81.5% vs. 38.5% in patients treated with external radiotherapy alone. Surgery was performed only for in situ carcinoma and for part of stages Ia, Ib and IIa. There is no significant difference in locoregional control at equal stage between radiotherapy alone and treatment schemes including surgery. However, lethal complications were observed in 6% of the patients of the surgical group as compared to 0.6% of the patients treated with radiotherapy alone. Radical radiotherapy seems to provide similar results of locoregional control and survival at equal stages in carcinoma of the cervical stump compared to carcinoma developed on an intact uterus. The rate of severe complications reported with the French-Italian glossary is 13% for G3 and 3% for G4, which is close to the observed rate during the same period in our series of radical radiotherapy to the intact uterus.

Treatment of carcinoma of the penis by iridium 192 wire implant.

Since 1971, a group of 22 adult patients with squamous cell carcinoma of the penis have been treated by iridium 192 wires implant. There were 6 T1 tumors, 14 T2 tumors and 2 T3; only one patient (T3) presented with local failure after implant. Local necrosis occurred in 2 patients without local tumoral recurrence, but was sufficient enough to warrant amputation. Thus 19/22 (86%) patients were locally cured with penile conservation. In these patients the most frequent post-therapeutic complication is chronic urethral stenosis (9/19 patients, 47%) requiring repeated instrumental dilations. Four patients presented with initial inguinal metastatic nodes; only one was cured by radiosurgical treatment. Among patients without metastatic nodes at the time of diagnosis, none had delayed metastatic nodes. Three patients died of nodal evolution, 5 patients died of intercurrent disease without evidence of disease and 14 are now alive and NED. It appears that iridium 192 wires implant is the most effective conservative treatment of invasive squamous cell carcinoma of the penis; however, these results confirm that no particular treatment is required for inguinal nodal areas for patients who initially present with no disease.

Combined postoperative radiotherapy and weekly cisplatin infusion for locally advanced squamous cell carcinoma of the head and neck: preliminary report of a randomized trial.

A prospective clinical trial was designed to evaluate efficacy, toxicity, and patient compliance of concomitant postoperative radiotherapy and Cisplatin infusion in patients with Stage III or IV S.C.C. of the head and neck and histological evidence of extra-capsular spread of tumor in lymph node metastase(s). Cisplatin 50 mg IV with forced hydration was given or not every week (i.e., 7 to 9 cycles) concurrently with radiotherapy. Between 1984 and 1988, 83 patients were randomized: 44 were treated by irradiation without chemotherapy (RT group) and 39 by the combined modality (CM group). There was no significant difference between the two groups in terms of patient characteristics, primary sites, tumor differentiation, T.N. stages, or postoperative prognostic factors. All patients completed the planned radiotherapy. There were seven severe toxicities (greater than grade 3) in the RT group. In the CM group, 30 severe toxicities occurred in 16/39 (41%) patients but none was life-threatening. Seven of 39 (18%) patients received less than two-thirds of the scheduled Cisplatin courses because of intolerance, mainly nausea and vomiting. Preliminary results show a better disease-free survival for the CM group (65% at 24 months) than for the RT group (41% at 24 months). This significant difference is largely due to increased loco-regional control in the CM group (79% vs 59%), the actuarial distant metastasis rates in patients controlled above the clavicles not being statistically different in the two groups.

Radiosensitivity of jejunal mucosa after whole abdomen irradiation and CDDP pretreatment.

Pretreatment of mice with a single radiation dose of 11.5 Gy or with fractionated irradiation (2 x 6.5 or 7.5 Gy, with an interval time of 12 hr) led to a relative decrease in the radiosensitivity of jejunal crypt cells when a second single dose of radiation was delivered 2 months later. When the same irradiation pretreatment was combined with CDDP (6 mg/kg, i.p.) injected 12 hr after single radiation or between two equal doses of radiation, similar crypt cells resistance was obtained. The combination of CDDP with irradiation did not modify the radiosensitivity of jejunal crypts in comparison with irradiation alone, even when the total radiation dose was delivered in 2 split doses. This induced radioresistance was demonstrated to be a reflection of late injury on intestinal tissue, presumably due to hypoxia resulting from vascular damage. It seems that the administration of CDDP did not change the possible hypoxia suspected in crypt cells of mice pretreated with single radiation dose. However, mouse lethality increased significantly when CDDP was combined with irradiation.

Fractionated radiotherapy of small inoperable lesions of the brain using a non-invasive stereotactic frame.

Arteriovenous malformations (AVMs) and benign or low grade, small malignant tumors can be treated by stereotactic radiotherapy in a single fraction. This report describes a technique for stereotactic treatment of small lesions using conventional, fractionated, photon beam irradiation. The Laitinen's stereoadapter, non-invasive head frame was used. This device was tested for accuracy by serial mountings and found to be accurate within 1 mm. The accuracy of the dose delivered was within 2%. Adaptation of this device to the linear accelerator required the design of secondary circular collimators which decreased the penumbra from 3-4 mm to 2-3 mm. The dose fall off outside the target volume is steep enough when using two non-coplanar arcs (90 to 10% within 1 cm). Thermoluminescent dosimetry (TLD) in a humanoid phantom showed good correlation with the calculated dose. This system permits delivery of fractionated radiation therapy to small volumes, easily and accurately, under stereotactic conditions.

Iridium-192 interstitial therapy for squamous cell carcinoma of the penis.

From February 1971 through February 1989, 51 patients with biopsy proven epidermoid carcinoma of the penis were treated with interstitial therapy (Iridium 192). The breakdown according to the stage was T1s = 3, T1 = 14, T2 = 28, T3 = 6, N0 = 43, N1 = 7, N2 = 1. The dose ranged from 50 to 65 Gy (mean: 60 Gy). Patients without clinical nodal involvement received no treatment to the nodes. Stage N1 and N2 patients had surgery and external irradiation to the inguinal and iliac nodes. Six of fifty-one (12%) patients developed nodal and/or metastatic disease following therapy. Five of six presented initially with clinical nodal involvement. Seven of fifty-one (14%) developed local recurrence only, requiring surgery (four partial penectomies, three total penectomies). Six of these seven patients are alive and free of disease with a mean follow-up of 5.5 years. Nine of thirty eight (23%) patients with local control developed local necrosis. The treatment consisted of local excision (one patient), partial amputation (six patients) or total amputation (two patients). Partial urethral stenosis was noted in 17/38 (45%) of the patients. Foreskin sclerosis occurred in 3/38 (8%) uncircumcised patients. Interstitial irradiation for penile carcinoma provided effective local control rates, especially for T1-T2 patients (91%). Local failures could be treated successfully with surgery. Complications could be treated conservatively in most patients. Local control with penile conservation was achieved in 67% of all patients and 75% of patients with T1-T2 disease.