Successful pregnancy outcome in a woman with Turner's syndrome.

Women with Turner's syndrome have a high incidence of cardiovascular complications, endocrine and hypertensive disorders. Those with the 45X chromosome complement require oocyte donation and in vitro fertilisation to conceive. Pregnancies in such women are challenging to manage due to the high risk of pregnancy-related hypertensive disorders, impaired glucose tolerance, fetal growth restriction and preterm birth. Women also need to be aware of the significant risk of aortic dilatation, dissection or rupture in pregnancy, which may be fatal. Despite these risks, favourable obstetric outcomes are achievable with careful pre-pregnancy counselling and cardiovascular assessment, intensive multidisciplinary antenatal monitoring and individualised delivery planning. We report the case of a 33-year-old woman with Turner's syndrome, pre-existing hypertension, insulin-dependent diabetes and primary hypoparathyroidism who had a successful pregnancy with good maternal and fetal outcomes despite the complexity of her medical conditions.

Resolution of neonatal hypertrophic cardiomyopathy presumed secondary to acquired maternal ribonucleoprotein and smith autoantibodies.

Severe asymmetrical hypertrophic cardiomyopathy without heart block accompanied by neuromuscular hypotonia and feeding difficulties was evident shortly after birth in the second child of a mother with systemic lupus erythematosus who had no indication of gestational diabetes. High-level anti-ribonucleoprotein (RNP) and Smoth (Sm) antibodies arising from transplacental transfer of maternal antibodies were detected in the child's serum. The cardiac abnormalities improved with a commensurate decline in antibody titers. Previously reported cases of neonatal cardiomyopathy with endocardial fibroelastosis have been ascribed to the transplacental transfer of maternal Sjogrens Syndrome (SS) A (Ro) and Sjogrens Syndrome (SS) B (La) antibodies and have been more severe and persistent compared with our patient. We advocate close monitoring of all babies of mothers with systemic autoimmunity for changes in heart rate during pregnancy and signs of heart failure and neuromuscular weakness after delivery.

Predicting 22q11.2 deletion syndrome: a novel method using the routine full blood count.

BACKGROUND: 22q11.2 deletion syndrome is common affecting nearly 1 in 3000, including many with DiGeorge Syndrome and 5% of individuals with congenital heart disease. Diagnosis is important because affected patients have impaired immune function and may suffer high mortality rates if given non-irradiated blood products from graft versus host disease. Symptomatic hypocalcaemia may also occur. Our objective was to determine whether mean platelet volume (MPV), available from the routine full blood count, may be a useful and rapid indicator of 22q11.2 deletion. METHOD: A retrospective case control cohort study analysing MPV and 22q11.2 deletion status was performed in a paediatric population (n = 166) undergoing cardiac surgery between 1999 and 2005. RESULTS: Twenty children were 22q11.2 positive. The median MPV was significantly larger for the 22q11.2 positive patient group compared to the non-22q11.2 patients (10.9fL versus 8.6fL, p<0.001). The area under the curve of the receiver operating characteristics (ROC) curve of MPV was large enough (0.85) to enable the accurate prediction of 22q11.2 deletion using MPV. CONCLUSIONS: MPV is a useful screening test, involving no extra laboratory work, cost or patient discomfort. MPV>10fL is a positive predictor of the presence of 22q11.2 deletion in children with congenital heart disease (specificity 89.7%). This finding should aid rapid decision-making for ordering irradiated blood products to prevent potentially fatal transfusion-associated graft versus host disease. It will alert clinicians to monitor serum calcium levels closely to prevent hypocalcaemic seizures.

A new formula for blood transfusion volume in the critically ill.

BACKGROUND: Published formulae, frequently used to predict the volume of transfused red cells required to achieve a desired rise in haemoglobin (Hb) or haematocrit (Hct), do not appear to have been validated in clinical practice. AIMS: To examine the relation between transfusion volume and the resulting rise in Hb and Hct in critically ill children. METHODS: Phase 1: Sample of 50% of children admitted during 1997; 237 of these 495 patients received at least one packed red cell transfusion; 82 children were transfused without confounding factors that could influence the Hb/Hct response to transfusion and were analysed further. Actual rise in Hb concentration or haematocrit was compared to that expected from use of existing formulae. A new formula was developed. Phase 2: In 50 children receiving a packed red cell transfusion during 2001, actual rise in Hb concentration was compared to expected rise in Hb with use of the new formula. RESULTS: Phase 1: Existing formulae performed poorly; median ratio of actual/predicted rise in Hb or Hct ranged from 0.61 to 0.85. Using the regression coefficients new formulae were developed for both Hb and Hct. These formulae were applicable across all age and diagnostic groups. Phase 2: Median ratio of actual/predicted rise in Hb improved to 0.95 with use of the new formula. CONCLUSIONS: Existing formulae underestimate the volume of packed red cells required to achieve a target Hb or Hct. Adoption of the new formulae could reduce the number of transfusion episodes in PICU, cutting costs and reducing risk.

The first British illustrated surgical catalogue.

Surgical instrument catalogues are valuable documents, which help in both the identification and dating of instruments. A rare copy of the first British illustrated surgical catalogue was offered for sale in 2003. This paper gives brief details of the catalogue and its author, JH Savigny.

The relationship between perception and production in songbird vocal imitation: what learned calls can teach us.

Songbirds produce calls as well as song. This paper summarizes four studies of the zebra finch long call, used by both sexes in similar behavioral contexts. Female long calls are acoustically simpler than male long calls, which include acoustic features learned during development. Production of these male-typical features requires an intact nucleus robustus archistriatalis, the sexually-dimorphic source of the telencephalic projection to brainstem vocal effectors. In experiments that quantified the long calls produced in response to long call playbacks, intact adult zebra finch males, but not females, show a categorical preference for the long calls of females over those of males. Experiments with synthetic stimuli showed that males classify long call stimuli that they hear by gender, using both spectral and temporal information, but that females use only temporal information. Juvenile males (<45 days) did not show the categorical preference, but it emerged during the same period when the robustus archistriatalis matures anatomically and the first male-typical vocalizations are produced. Adult males with robustus archistriatalis lesions lost the categorical preference for female long calls, suggesting that the robustus archistriatalis plays a role in long call discrimination. These results demonstrate that calls complement song as a potent tool for studying the neurobiology of vocal communication.

Standard cardiac rehabilitation is less effective for diabetics.

To assess clinical outcomes and lifestyle modifications in diabetic patients attending a standard cardiac rehabilitation programme following myocardial infarction (MI), a retrospective longitudinal study was undertaken in a district general hospital in the north west of England. A total of 1804 patients attended the cardiac rehabilitation programme over 10 years, of whom 223 (12.4%) had diabetes mellitus. Drugs were underprescribed in all patients, aspirin and beta-blockers especially in diabetics (75.3% vs 90.3%, p < 0.0001; 38.6% vs 60.8%, p < 0.0001). Smoking cessation was poor in diabetics (54.2% vs 69.1%, p < 0.003) and diabetics were less likely to attend at least one session of physiotherapy (26.9% vs 58.6%, p < 0.0001). Diabetics had higher mortality at one year (15.7% vs 5.6%; p < 0.0001), mostly associated with cardiovascular disease (13.4% vs 5.4%, p < 0.0001). Standard cardiac rehabilitation programmes appear to be less effective for patients with diabetes mellitus. We suggest that patients presenting with an existing chronic condition need specialised programmes of rehabilitation to integrate the care of that condition with their recent MI. Aggressive drug therapy following acute MI should also be prescribed in all patients when not contraindicated by other evidence.

Behavioral discrimination of sexually dimorphic calls by male zebra finches requires an intact vocal motor pathway.

Vocal communication between zebra finches includes the exchange of long calls (LCs) as well as song. By using this natural call behavior and quantifying the LCs emitted in response to playbacks of LCs of other birds, we have previously shown that adult male zebra finches have a categorical preference for the LCs of females over those of males. Female LCs are acoustically simpler than male LCs, which include complex acoustic features that are learned during development. Production of these male-typical features requires an intact nucleus RA, the sexually dimorphic source of the main telencephalic projection to brainstem vocal effectors. We have now made bilateral lesions of RA in 17 adult males and tested their discrimination behavior in the call response situation. Lesioned birds continue to call, but lose the male-typical preference for female LCs. The degree of loss is correlated with the extent of RA damage. Further, the simplified LCs of males with RA lesions have a variable duration that is correlated with stimulus features. In effect, the call response behavior of lesioned males becomes like that of females. Apparently, in the absence of RA, the remaining intact structures receive different call information than RA normally does, and/or process it differently. This suggests that the vocal motor nucleus RA could play a role in the transformation of a signal encoding the salience of stimulus parameters into a control signal that modulates the probability and strength of responding.

Interactions of Cdc4p, a myosin light chain, with IQ-domain containing proteins in Schizosaccharomyces pombe.

The fission yeast Schizosaccharomyces pombe undergoes cell division through a medially placed actomyosin-based contractile ring. One of the key components of this ring is the F-actin based motor protein myosin II. The myosin II heavy chain Myo2p has two light-chain-binding domains, IQl and IQ2, which bind the essential light chain, Cdc4p, and the regulatory light chain, Rlc1p. Previously, we have reported the characterization of cells expressing Myo2p lacking the IQ2 domain that facilitates Myo2p interaction with Rlc1p. In this study, we have created and characterized S. pombe strains carrying precise deletions of IQ1 and the entire neck region encompassing the IQ1 and IQ2 domains. Surprisingly, we found that the entire neck region of Myo2p is dispensable for Myo2p function. Cells deleted for IQ1, IQ2 and the entire neck region of Myo2p do not display any obvious cytoskeletal abnormalities. Immunofluorescence studies indicated that Cdc4p localizes at the ring in early and late mitotic cells in a strain in which interactions of Cdc4p with both the myosin II heavy chains (Myo2p and Myp2p) are abolished. Unlike mutations in Rlc1p that are suppressed by a simultaneous deletion of its binding site on Myo2p, mutations in the essential light chain Cdc4p are not suppressed by deletion of its binding sites on Myo2p, suggesting that Cdc4p may have additional partners essential for cytokinesis. Consistent with this, we provide evidence that two other IQ-domain containing actomyosin ring proteins, Rng2p (an IQGAP-related protein) and Myo51p (a type V myosin heavy chain), physically interact with Cdc4p. We concluded that Cdc4p, a novel myosin light chain, interacts with multiple actomyosin ring components to effect cytokinesis.

Type II myosin regulatory light chain relieves auto-inhibition of myosin-heavy-chain function.

The F-actin based motor protein myosin II has a key role in cytokinesis. Here we show that the Schizosaccharomyces pombe regulatory light chain (RLC) protein Rlc1p binds to Myo2p in manner that is dependent on the IQ sequence motif (the RLC-binding site), and that Rlc1p is a component of the actomyosin ring. Rlc1p is important for cytokinesis at all growth temperatures and is essential for this process at lower temperatures. Interestingly, all deleterious phenotypes associated with the loss of Rlc1p function are suppressed by deletion of the RLC binding site on Myo2p. We conclude that the sole essential function of RLCs in fission yeast is to relieve the auto-inhibition of myosin II function, which is mediated by the RLC-binding site, on the myosin heavy chain (MHC).

Early filtration and mortality in meningococcal septic shock?

Following the introduction of a policy of early therapeutic filtration for presumed meningococcal septicaemic shock, the overall mortality has decreased.

Synthetic oligonucleotides as therapeutics: the coming of age.

Synthetic oligonucleotides (ODNs) are short nucleic acid chains that can act in a sequence specific manner to control gene expression. Significant progress has been made in the development of synthetic ODN therapeutics since the first demonstration of gene inhibition by antisense ODNs in a cell culture system two decades ago. This new class of therapeutic agents can potentially target any abnormally expressed genes in a broad range of diseases from viral infections to psychoneurological disorders. A number of "first" generation synthetic ODNs have entered into human clinical trials in the last few years. The eminent approval of the first ODN for the treatment of cytomaglovirus retinitis by the FDA in USA will provide much excitement that this new class of compounds holds great promise as a therapeutic "magic bullet". However, many obstacles still exist in the development of this technology. In this review, the current status of synthetic ODN chemistry, drug delivery methods, mechanisms of ODN action, potential clinical applications and its limitations in a wide range of human disorders will be described.

Identification of a 26S proteasome-associated UCH in fission yeast.

We have identified a 26S proteasome-associated ubiquitin carboxyl-terminal hydrolase (UCH) in Schizosaccharomyces pombe. The gene (designated uch2+) encodes a protein containing a UCH catalytic domain at its N-terminus and a short extension at its C-terminus. uch2+ is nonessential as the uch2 null mutant strain showed no significant difference from the wild-type strain. The GFP-tagged Uch2p is localized predominantly to the nuclear periphery, which is similar to the 26S proteasome localization. Deletion of the C-terminal extension of Uch2p resulted in a drastic change of its subcellular localization: it showed a generally diffused distribution instead of a perinuclear pattern. Glycerol gradient centrifugation analysis and coimmunoprecipitation studies of fission yeast extracts using anti-Mts4p antiserum suggest that Uch2p is associated with the 26S proteasome and the association of Uch2p with the 26S proteasome is mediated by its C-terminal extension.

Fission yeast Rng3p: an UCS-domain protein that mediates myosin II assembly during cytokinesis.

Cell division in many eukaryotes, including the fission yeast Schizosaccharomyces pombe, utilizes a contractile actomyosin ring. In S. pombe, the actomyosin ring is assembled at the medial cortex upon entry into mitosis and constricts at the end of anaphase to guide the centripetal deposition of the septum. Despite identification of several structural components essential for actomyosin ring assembly, the interdependencies between these gene-products in the process of ring assembly are unknown. This study investigates the role of Rng3p, a member of the UCS-domain containing protein family (Unc-45p, Cro1p, She4p), in actomyosin ring assembly. Null mutants in rng3 resemble deletion mutants in the type II myosin heavy chain (myo2) and rng3(ts) mutants show strong negative interactions with the myo2-E1 mutant, suggesting that Rng3p is involved in modulating aspects of type II myosin function. Interestingly, a green fluorescent protein (GFP) tagged Rng3p fusion is detected at the division site in the myo2-E1 mutant, but not in other myo2-alleles, wild-type cells or in 18 other cytokinesis mutants. Assembly and maintenance of Rng3p at the division site in the myo2-E1 mutant requires F-actin. Rng3p is also required for the proper assembly of Myo2p and F-actin into a functional actomyosin ring but is not necessary for their accumulation at the division site. We conclude that Rng3p is a novel component of the F-actin cytoskeleton essential for a late step in actomyosin ring assembly and that it might monitor some aspect of type II myosin assembly during actomyosin ring construction.

Evidence for F-actin-dependent and -independent mechanisms involved in assembly and stability of the medial actomyosin ring in fission yeast.

Cell division in a number of eukaryotes, including the fission yeast Schizosaccharomyces pombe, is achieved through a medially placed actomyosin-based contractile ring. Although several components of the actomyosin ring have been identified, the mechanisms regulating ring assembly are still not understood. Here, we show by biochemical and mutational studies that the S.pombe actomyosin ring component Cdc4p is a light chain associated with Myo2p, a myosin II heavy chain. Localization of Myo2p to the medial ring depended on Cdc4p function, whereas localization of Cdc4p at the division site was independent of Myo2p. Interestingly, the actin-binding and motor domains of Myo2p are not required for its accumulation at the division site although the motor activity of Myo2p is essential for assembly of a normal actomyosin ring. The initial assembly of Myo2p and Cdc4p at the division site requires a functional F-actin cytoskeleton. Once established, however, F-actin is not required for the maintenance of Cdc4p and Myo2p medial rings, suggesting that the attachment of Cdc4p and Myo2p to the division site involves proteins other than actin itself.

Asymptomatic pituitary apoplexy after aortocoronary bypass surgery.

Pituitary apoplexy usually presents with acute neuro-ophthalmological complications that require urgent neurosurgical intervention. We present a case of pituitary apoplexy following aortocoronary bypass surgery that was asymptomatic until the patient presented with features of hormonal deficiency three months later. Only one case of pituitary apoplexy has been described in the literature following cardiac surgery that did not require operative intervention. We discuss the aetiology of pituitary apoplexy and the possible mechanisms for such an event after cardiac surgery. Although this is rare, any unusual feature after operation such as lethargy or erectile dysfunction should remind us of hypopituitarism.