Cause of intrauterine and neonatal death in twin pregnancies (CoDiT): development of a novel classification system.

OBJECTIVE: Twin pregnancies have a significantly higher perinatal mortality than singleton pregnancies. Current classification systems for perinatal death lack twin-specific categories, potentially leading to loss of important information regarding cause of death. We introduce and test a classification system designed to assign a cause of death in twin pregnancies (CoDiT). DESIGN: Retrospective cross-sectional study. SETTING: Tertiary maternity unit in England with a perinatal pathology service. POPULATION: Twin pregnancies in the West Midlands affected by fetal or neonatal demise of one or both twins between 1 January 2005 and 31 December 2016 in which postmortem examination was undertaken. METHODS: A multidisciplinary panel designed CoDiT by adapting the most appropriate elements of singleton classification systems. The system was tested by assigning cause of death in 265 fetal and neonatal deaths from 144 twin pregnancies. Cause of death was validated by another obstetrician blinded to the original classification. MAIN OUTCOME MEASURES: Inter-rater, intra-rater, inter-disciplinary agreement and cause of death. RESULTS: Cohen's Kappa demonstrated 'strong' (>0.8) inter-rater, intra-rater and inter-disciplinary agreement (95% CI 0.70-0.91). The commonest cause of death irrespective of chorionicity was the placenta; twin-to-twin transfusion syndrome (TTTS) was the commonest placental cause in monochorionic twins and acute chorioamnionitis in dichorionic twins. CONCLUSIONS: This novel classification system records causes of death in twin pregnancies from postmortem reports with high inter-user agreement. We highlight differences in aetiology of death between monochorionic and dichorionic twins. TWEETABLE ABSTRACT: New classification system for #twin cause of death 'CoDiT' shows high rater agreement.

Neuroimaging in Pediatric Patients with Juvenile Xanthogranuloma of the CNS.

BACKGROUND AND PURPOSE: Juvenile xanthogranuloma is a rare clonal, myeloid, neoplastic disorder. Typically, juvenile xanthogranuloma is a self-limited disorder of infancy, often presenting as a solitary red-brown or yellow skin papule/nodule. A small subset of patients present with extracutaneous, systemic juvenile xanthogranuloma, which may include the CNS. The goal of this retrospective study was to evaluate and categorize the neuroimaging findings in a representative cohort of pediatric patients with CNS juvenile xanthogranuloma. MATERIALS AND METHODS: The brain and/or spine MR imaging data of 14 pediatric patients with pathology-proven juvenile xanthogranuloma were categorized and evaluated for the location; the signal intensity of xanthogranulomas on T1WI, T2WI, DWI, and a matching ADC map for the pattern and degree of contrast enhancement; and the presence of perilesional edema, cysts, or necrosis. RESULTS: Fourteen pediatric patients (8 girls, 6 boys; mean age, 84 months) were included in the study. Patients presented with a wide variety of different symptoms, including headache, seizure, ataxia, strabismus, hearing loss, facial paresis, and diabetes insipidus. Juvenile xanthogranuloma lesions were identified in a number of different sites, including supra- and infratentorial as well as intracranial and spinal leptomeningeal. Five patients were categorized into the neuroradiologic pattern unifocal CNS juvenile xanthogranuloma; 8, into multifocal CNS juvenile xanthogranuloma; and 1, into multifocal CNS juvenile xanthogranuloma with intracranial and spinal leptomeningeal disease. In most cases, xanthogranulomas were small-to-medium intra-axial masses with isointense signal on T1WI (compared with cortical GM), iso- or hyperintense signal on T2WI, had restricted diffusion and perilesional edema. Almost all xanthogranulomas showed avid contrast enhancement. However, we also identified less common patterns with large lesions, nonenhancing lesions, or leptomeningeal disease. Four cases had an additional CT available. On CT, all xanthogranulomas were homogeneously hyperdense (solid component) without evident calcifications. CONCLUSIONS: CNS juvenile xanthogranuloma may demonstrate heterogeneous neuroimaging appearances potentially mimicking other diseases, such as primary brain neoplasms, metastatic disease, lymphoma and leukemia, other histiocytic disorders, infections, or granulomatous diseases.

Differential binding and internalization of Clostridium difficile toxin A by human peripheral blood monocytes, neutrophils and lymphocytes.

Colitis due to Clostridium difficile infection is mediated by secreted toxins A and B and is characterized by infiltration by cells from the systemic circulation. The aim of our study was to investigate interactions between fluorescently labelled toxin A and peripheral blood monocytes, neutrophils and lymphocytes. Purified toxin A was labelled with Alexa Fluor® 488 (toxin A(488)) and incubated with isolated human peripheral blood mononuclear cells or washed whole blood cells for varying time intervals at either 37 or 4 °C/ice. The ability of trypan blue to quench cell surface-associated (but not cytoplasmic) fluorescence was also investigated. At 37 °C, toxin A(488) -associated fluorescence in monocytes peaked at 1 h (majority internalized), with subsequent loss associated with cell death. In contrast to monocytes, binding of toxin A(488) in neutrophils was greater on ice than at 37 °C. Studies using trypan blue suggested that over 3 h at 37 °C, most of the toxin A(488)-associated fluorescence in neutrophils remained at the cell surface. Over 48 h (37 °C and ice/4 °C), there was minimal toxin A(488)-associated fluorescence in lymphocytes. These studies suggest major differences in interactions between toxin A and circulating cells that infiltrate the mucosa during colonic inflammation in C. difficile infection.

Sudden vision loss caused by rhino-orbital zygomycosis in diabetic patients: case series.

Rhino-orbital zygomycosis is a life-threatening fungal infection generally occurring in patients with an underlying disorder, such as diabetes mellitus with ketoacidosis or with immunocompromising factors, although it may rarely appear in healthy individuals. The study has been undertaken to discuss the clinical presentation, pathogenesis, diagnostic work up and management of this rapidly progressive disease. Four male patients having uncontrolled diabetes and presenting with signs and symptoms of rhino-orbital zygomycosis were studied to illustrate the serious nature of the disease. All the four patients had rapidly deteriorating vision loss either unilateral or bilateral along with other nasal and orbital signs and symptoms. All the patients were put on liposomal amphotericin B and underwent orbital exenteration and pansinusectomy. One patient died, while the other three were successfully treated. Early diagnosis is critical in the prevention of morbidity and mortality associated with the disease. There is need for a high index of clinical suspicion in immunocompromised patients. Timely medical-surgical treatment proves extremely important for prognosis.

Subcutaneous phaeohyphomycotic cyst caused by Pyrenochaeta romeroi.

Pyrenochaeta romeroi is a rare agent of chronic, suppurative subcutaneous infections which ultimately lead to mycetoma. It has only rarely been reported from deep, non-mycetomatous infections. We describe a case of a subcutaneous phaeohyphomycotic cyst in a 45-year-old Indian female who suffered from verrucous plaque and a swelling (30 mm in diameter) on the right forearm that gradually increased in size over a period of 3 months. Direct microscopic examination with 10% KOH and histopathological investigation of exudates revealed septate hyphae without granules, the hallmark of mycetoma. The lesion appeared to be a subcutaneous phaeohyphomycotic cyst caused by P. romeroi. The suspected agent was recovered in culture, identified on the basis of morphologic features and its identification confirmed by sequencing of the internal transcribed spacer regions of rDNA. Treatment consisted of surgical excising of the cyst without any antifungal therapy. There was no relapse during a one-year follow-up and the patient was successfully cured. In vitro antifungal susceptibility tests demonstrated that itraconazole (0.5 microg/ml), isavuconazole (0.125 microg/ml) and posaconazole (0.5 microg/ml) had potent activity against this isolate of P. romeroi. High MICs were found with amphotericin B (4 microg/ml), fluconazole (>64 microg/ ml), voriconazole (4 microg/ml) and caspofungin (8 microg/ml). However, their clinical effectiveness in the treatment of P. romeroi infections remains to be evaluated.

Perceptions of Insulin Pen Use and Technique in Black and Hispanic/Latino Patients with Type 2 Diabetes: a Qualitative Study.

OBJECTIVES: Non-Hispanic Blacks (NHB) and Hispanic/Latinos (H/L) are affected disproportionately by type 2 diabetes (T2DM) and its complications due to a myriad of reasons. Lack of diabetes education has been identified as one risk factor for poorly controlled diabetes. For persons using insulin, poor insulin administration technique can be problematic. Previous studies done demonstrating this have not been inclusive of NHB and H/L populations. As a result, this study aimed to use semi-structured interviews to examine insulin pen technique and training experience in NHB and H/L inpatients with T2DM. DESIGN: Semi-structured interviews comprised open- and close-ended questions, and prompts were conducted until reaching saturation in NHB and H/L inpatients with at least 3 months of insulin pen use. Data was analyzed by two researchers who completed a thematic analysis. RESULTS: Twenty semi-structured interviews were completed. Two major themes emerged from analysis included: patients prefer the insulin pen to syringes and vials and most had a lack of formal pen technique teaching. CONCLUSION: Although the insulin pen is a preferred modality of insulin delivery, this sampling of disparity patients demonstrates that insulin pen technique should be continually reassessed by health care providers as majority of the patients never had formal insulin pen teaching. Among those who did have training, they still made errors such as not priming the pen or shortened dwell time.

The in vivo fates of plant viral nanoparticles camouflaged using self-proteins: overcoming immune recognition.

Nanoparticles offer a promising avenue for targeted delivery of therapies. To slow clearance, nanoparticles are frequently stealth-coated to prevent opsonization and immune recognition. Serum albumin (SA) has been used as a bio-inspired stealth coating. To develop this shielding strategy for clinical applications, it is critical to understand the interactions between the immune system and SA-camouflaged nanoparticles. This work investigates the in vivo processing of SA-coated nanoparticles using tobacco mosaic virus (TMV) as a model system. In comparing four different SA-formulations, the particles with high SA coverage conjugated to TMV via a short linker performed the best at preventing antibody recognition. Irrelevant of the coating chemistry, all formulations led to similar levels of TMV-specific antibodies after repeat administration in mice; importantly though, SA-specific antibodies were not detected and the TMV-specific antibodies were unable to recognize shielded SA-coated TMV. Upon uptake in macrophages, the shielding agent and nanoparticle separate, where TMV trafficked to the lysosome and SA appears to recycle. The distinct intracellular fates of the TMV carrier and SA shielding agent explain why anti-TMV but not SA-specific antibodies are generated. This work characterizes the outcomes of SA-camouflaged TMV after immune recognition, and highlights the effectiveness of SA as a nanoparticle shielding agent.

The dispersion of natural oils in de-gassed water.

Recent studies have demonstrated that pure hydrocarbon oils can be dispersed in water as fine droplets without the use of additives. The high interfacial tension between hydrocarbons and water is expected to cause cavitation between oil droplets during separation. This cavitation is aided by dissolved atmospheric gases present in both the oil and water. Their removal allows oil droplets to be readily dispersed in water. In this paper we report on the effect of the de-gassing process on the dispersion of several natural, water immiscible oils. These natural, mixed oils are eucalyptus, lavender and tea tree oil. Although these oils are mixtures and in some cases not as hydrophobic as those used in the earlier studies, the effect of de-gassing substantially enhances their dispersion, producing micron-sized droplets without the need for additives. Dispersions of these natural oils in pure water have a wide range of uses where purity is an advantage, for example, in skin cleaning products and oral sprays.

A rare case of phaeohyphomycosis caused by Fonsecaea pedrosoi in a child with nephrotic syndrome.

Dematiaceous fungi are the etiological agents of phaeohyphomycosis and are now increasingly being recognized for causing disease in humans. A high level of suspicion and routine fungal cultures are required to identify these cases. There is no consensus regarding their management. Here, an unusual presentation of phaeohyphomycosis (secondary to Fonsecaea pedrosoi) presenting as a disseminated infection in a case of nephrotic syndrome is described.

A study of satisfaction with dental services among adults in the United Kingdom.

OBJECTIVES: To determine satisfaction with dental care services among the UK adult population, and to assess their knowledge regarding the dental complaints procedure. METHODS: A national survey involving a multi-stage random sampling procedure with face-to-face home interviews of 5,385 UK residents was conducted in 1999. RESULTS: The response rate was 69% and 3,739 adults took part in this study. Majority of people (89%) were satisfied with the quality of care they received. Only 2% (76) had actually complained, although 10% (388) had felt like complaining in the past. One third (32%, 1,188) did not know to whom to complain if they had a problem. Among those who knew whom to contact, over a third (36%, 1,359) would contact somebody outside the practice, while another third (31%, 1,169) would contact their dentist or dental practice. CONCLUSION: Overall most people are satisfied with the quality of dental care they receive. However, 2% have complained and 10% have felt like complaining about their dentist/ dental care. In general, knowledge of the complaints procedure and whom to contact appears fragmented.

Monoclonal antibodies against human renin. Blood pressure effects in the marmoset.

The in vivo effects of two anti-human renin monoclonal antibodies with a high binding affinity for primate renin were studied in conscious, volume-depleted marmosets. These antibodies, R-3-17-7 and R-3-36-16, both have high binding activity for renin, but only R-3-36-16 inhibits the enzymatic activity of renin in vitro. In vivo, R-3-17-7 did not affect blood pressure after intravenous injection of doses up to 100 micrograms/kg, although plasma renin activity was partially reduced. In contrast, R-3-36-16 induced a reduction in blood pressure and an inhibition of plasma renin activity at a threshold dose of 3 micrograms/kg. The maximum fall in blood pressure and complete inhibition of plasma renin activity were observed after R-3-36-16, 10 micrograms/kg; these effects persisted for up to 2 hours. Pretreatment with a converting enzyme inhibitor or nephrectomy prevented the hypotensive effects of R-3-36-16. Conversely, pretreatment with R-3-36-16 prevented the hypotensive effects of a converting enzyme inhibitor. These findings indicate that the hypotensive response induced by R-3-36-16 is due entirely to blockade of the renin-angiotensin system. Thus, R-3-36-16 appears to be a specific, potent, and long-acting inhibitor of primate renin. Such monoclonal antibodies provide interesting tools for studying the effects of acute and chronic renin blockade.

Increased plasma renin during renin inhibition. Studies with a novel immunoassay.

The response of renin release to the administration of renin inhibitors cannot be studied with conventional enzymatic methods used to measure plasma renin. In the present experiments, a novel multirange enzyme-linked immunosorbent assay for human and primate renin was used to investigate the changes in plasma immunoreactive renin after renin inhibition. A potent and long-acting statine-containing renin inhibitor, CGP 29 287, was injected in conscious marmosets after mild or severe sodium depletion. In mildly sodium-depleted marmosets, CGP 29 287 (0.1 mg/kg i.v.) reduced mean arterial blood pressure and completely inhibited plasma renin activity for up to 30 minutes. This response was associated with a transient increase in plasma immunoreactive renin concentration. After a dose of 1.0 mg/kg i.v., the reduction of mean arterial pressure and the complete inhibition of plasma renin activity persisted for up to 120 minutes. These effects were accompanied by a sustained increase in plasma immunoreactive renin concentration. In severely sodium-depleted marmosets, CGP 29 287 (1.0 mg/kg i.v.) induced a marked fall in systolic blood pressure and complete inhibition of plasma renin activity within 30 minutes of injection. Plasma immunoreactive renin levels increased to 257% of pretreatment values. The converting-enzyme inhibitor enalaprilat (2 mg/kg i.v.) induced a fall in systolic blood pressure of similar magnitude, which was accompanied by an increase in plasma renin activity. Levels of plasma immunoreactive renin increased to 210% of pretreatment values. Hydralazine (0.2 mg/kg i.v.) did not increase plasma renin activity or plasma immunoreactive renin levels despite a comparable hypotensive effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of a specific and long-acting renin inhibitor in the marmoset.

Inhibition of renin was induced in conscious marmosets with CGP 29 287, Z-Arg-Arg-Pro-Phe-His-Sta-Ile-His-Lys (Boc)-OMe, a renin inhibitor with a prolonged duration of action. In vitro, CGP 29 287 is a potent inhibitor of primate plasma renin (inhibitory concentration, 50%: human = 1 X 10(-9) M; marmoset = 5 X 10(-9) M) and less potent against dog (2 X 10(-7) M) or rat (3 X 10(-5) M) plasma renin. CGP 29 287 is a weak inhibitor of other aspartic proteases such as porcine pepsin or bovine cathepsin D (inhibitory concentration, 50% = 4 X 10(-5) M). In furosemide-treated marmosets, CGP 29 287 lowered blood pressure and inhibited plasma renin activity during intravenous infusion and after intravenous bolus injection. The duration of action after intravenous injection was dose dependent and ranged from 1 hour after 0.1 mg/kg to more than 3 hours after 10 mg/kg. High doses of CGP 29 287 (100 mg/kg) were active after oral administration. In all experiments a close relation between inhibition of plasma renin activity and reduction of blood pressure was found. A maximum hypotensive response to CGP 29 287 was associated with complete inhibition of plasma renin activity, and the recovery of blood pressure was accompanied by recovery of plasma renin activity. The hypotensive effects of CGP 29 287 were smaller in untreated than in furosemide-treated marmosets. CGP 29 287 had no influence on blood pressure in marmosets after bilateral nephrectomy or after pretreatment with a converting enzyme inhibitor.(ABSTRACT TRUNCATED AT 250 WORDS)

Two-kidney, one clip renal hypertension in the marmoset.

The purpose of this study was to assess whether two-kidney, one clip (2K1C) renal hypertension can be induced in the marmoset. During the first 3-5 weeks after renal arterial clipping, blood pressure (BP) and plasma renin activity (PRA) increased in approximately one-third of the operated marmosets. However, within 10 weeks after clipping, BP and PRA had returned to control values. There was a significant positive correlation between BP and log PRA 3 and 5 weeks after the operation, but no correlation was observed at 10 weeks. In a selected group of marmosets with the highest values of BP (greater than 140 mmHg; n = 4), the converting enzyme inhibitor, enalapril (2 mg/kg s.c.) lowered BP by 58 +/- 7 (s.e.m.) mmHg when given 3 weeks after clipping. At 18 weeks the response to enalapril was only -17 +/- 6 mmHg. These results demonstrate that unilateral renal arterial clipping in marmosets results in a transient renin-dependent hypertension. Marmosets in this initial hypertensive phase could be useful for investigating the antihypertensive effects of inhibitors of human renin.

Effects of neurokinins on the isolated pig coronary artery.

The actions of substance P (SP), neurokinin A (NKA), neurokinin B (NKB), physalaemin (PHY), kassinin (KAS) and eledoisin (ELE) were investigated on transversally cut strips of pig coronary artery. All tachykinins produced vasodilatation of coronary arteries precontracted with ACh; 10(-5) M. The order of potency was: SP = PHY ELE greater than KAS greater than NKA greater than NKB, with the ED50 values being 0.38, 0.38, 1.2, 2.6, 8.3 and 34.0 nM, respectively. Continued superfusion of SP (7.4 X 10(-9) M) desensitized the coronary arteries which were refractory to the vasodilator action of NKA, NKB, PHY and KAS. The arteries nevertheless dilated upon the addition of noradrenaline (NA) and bradykinin (BK). Endothelium-removed preparations did not respond to any of the tachykinins. However, tissues devoid of endothelium relaxed in response to both NA and vasoactive intestinal polypeptide (VIP). Three octapeptide antagonists, [D-Pro4,Ala6,D-Trp7,9,Nle11]SP-(4-11) (compound I), [D-Pro4,Ser6,D-Trp7,9,Nle11]SP-(4-11) (compound II) and [D-Pro4,D-Trp7,9,10,Phe11]SP-(4-11) (compound III) were examined as potential antagonists of tachykinin-induced vasodilatation. Compounds I and II blocked the actions of SP and NKA but not that of PHY. Compound III effectively blocked the actions of SP and PHY. We conclude that the pig coronary artery possesses a 'NK-P/SP-P' type receptor, and that this receptor is probably localized on the endothelium.

Serum sodium stabilizing effect of enalapril after standard water load in a patient with a history of self-induced water intoxication.

1. A 21 day prospective placebo controlled double blind cross over trial of enalapril was studied in a normonatremic patient with a known history of SIWI. 2. At the end of each prophylactic treatment, the patient was challenged with a water load of 20 ml/kg. 3. The mean serum sodium of 140.111 mmol/L on prophylactic enalapril was significantly higher than the 137.6 mmol/L on placebo (p = 0.0015). 4. After a water load, the mean serum sodium on enalapril was 137.6 mmol/L, compared to 133.833 mmol/L (p = 0.0015) on placebo.

Potential relationship between dengue fever and neural tube defects in a northern district of India.

A sudden increase in number of births of newborns with neural tube defects (NTD) was observed from June, 1989 to September, 1989 in Medical College and Hospital, Rohtak and various other government and private hospitals of the district of Rohtak. Out of a total 4785 deliveries whose records were collected, there were 87 newborns with NTD with an incidence of 18.18/1000 births which was three times higher than the previous incidence of 6.8/1000 births in the preceding 4 years. There was an epidemic of dengue fever in this area from September, 1988 to December, 1988 affecting almost one member from each family. This coincided with the period of their first trimester. Of these, 18 patients suffered clinically from dengue fever, 21 patients had positive dengue fever history in their family members, 21 patients had positive history in their neighbors. The cluster of NTD appears to be due to dengue virus infection.

Spontaneous splenic rupture in early pregnancy.

Spontaneous rupture of a normal spleen is a rare entity. We report a case of spontaneous rupture during early pregnancy. Ruptured ectopic pregnancy was suspected preoperatively, but on exploration a splenic rupture was detected and splenectomy performed.

Maternal and perinatal complications in neurofibromatosis during pregnancy.

A total of ten patients with lesions of neurofibromatosis during pregnancy were followed up for pregnancy complications. Seven cases (70%) had hypertensive disorders of pregnancy; four had severe PET (pre-eclamptic toxemia) including one case of eclampsia, one had mild PET and the other two had only mild gestational hypertension. A total of 60% had preterm labor and in none of these did the baby survive; thus perinatal mortality was 600/1000. Mean gestation was 33.0 weeks and mean birthweight was only 1.924 kg. Thus, neurofibromatosis during pregnancy is associated with poor obstetrical outcome and requires greater care.