Recurrent Takotsubo cardiomyopathy in a postmenopausal Indian lady: Is there a pattern?

Takotsubo cardiomyopathy (TTC) is a syndrome of acute left ventricular dysfunction with a clinical presentation often mimicking acute coronary syndrome. Without a high index of suspicion, this clinical entity often goes unrecognized. Although initially categorized as a benign completely reversible condition, it is no longer considered to be so. Recurrence of this condition, though rare, has been reported in a non-Indian population. We present a case of recurrent TTC in a postmenopausal Indian lady who had a similar clinical presentation both at the index event and at recurrence.

Mapping unmet supportive care needs, quality-of-life perceptions and current symptoms in cancer survivors across the Asia-Pacific region: results from the International STEP Study.

Background: To assess the supportive care needs, quality of life (QoL) and symptoms of patients with cancer after the end of first-line treatments and into survivorship in Asian countries using Australian data as benchmark. Patients and methods: A cross-sectional survey was carried out in Australia and eight high-income (HICs) and low-/middle-income (LMICs) Asian countries (China, Japan, Hong Kong SAR, South Korea, Myanmar, Thailand, India, Philippines) using validated scales (Cancer Survivors Unmet Needs scale), physical-symptom concerns (Cancer Survivors Survey of Needs subscale) and a single-item measure of global QoL perception. Results: Data were collected from 1873 patients. QoL was highest in Australia and all other countries had significantly lower QoL than Australia (all P < 0.001). One-quarter of the patients reported low QoL (scores 1-3/10). The most frequently reported symptoms were fatigue (66.6%), loss of strength (61.8%), pain (61.6%), sleep disturbance (60.1%), and weight changes (57.7%), with no difference in symptom experience between Australian data and all other countries, or between HICs and LMICs. Unmet needs of moderate/strong level were particularly high in all aspects assessed, particularly in the area of existential survivorship (psychosocial care) and receiving comprehensive cancer care. Australia and HICs were similar in terms of unmet needs (all low), but LMICs had a significantly higher number of needs both compared with Australia and HICs (all P < 0.001). Conclusion: Health care systems in Asian countries need to re-think and prioritize survivorship cancer care and put action plans in place to overcome some of the challenges surrounding the delivery of optimal supportive cancer care, use available resource-stratified guidelines for supportive care and test efficient and cost-effective models of survivorship care.

Milk glucosidase activity enables suckled pup starch digestion.

UNLABELLED: ᅟ: Starch requires six enzymes for digestion to free glucose: two amylases (salivary and pancreatic) and four mucosal maltase activities; sucrase-isomaltase and maltase-glucoamylase. All are deficient in suckling rodents. OBJECTIVE: The objective of this study is to test (13)C-starch digestion before weaning by measuring enrichment of blood (13)C-glucose in maltase-glucoamylase-null and wild-type mice. METHODS: Maltase-glucoamylase gene was ablated at the N-terminal. Dams were fed low (13)C-diet and litters kept on low (13)C-diet. Pups were weaned at 21 days. Digestion was tested at 13 and 25 days by intragastric feeding of amylase predigested (13)C-α-limit dextrins. Blood (13)C-glucose enrichment was measured by gas chromatography combustion isotope ratio mass spectrometry (GCRMS) using penta-acetate derivatives. RESULTS: Four hours after feeding, blood (13)C-glucose was enriched by 26 × 10(3) in null and 18 × 10(3) in wild-type mice at 13 days and 0.3 × 10(3) and 0.2 × 103 at 25 days (vs. fasting p = 0.045 and p = 0.045). By jejunal enzyme assay, immunohistochemistry, or Western blots, there was no maltase activity or brush border staining with maltase-glucoamylase antibodies at 13 days, but these were fully developed in the wild-type mice by 25 days. In 13-day null mice, luminal contents were stained by maltase-glucoamylase antibodies. Lactating the mammary gland revealed maltase-glucoamylase antibody staining of alveolar cells. Reverse transcription/polymerase chain reaction (RT/PCR) of lactating glands revealed a secreted form of maltase-glucoamylase. CONCLUSIONS: (1) (13)C-α-limit dextrins were rapidly digested to (13)C-glucose in 13-day mice independent of maltase-glucoamylase genotype or mucosal maltase activity. (2) This experiment demonstrates that a soluble maltase activity is secreted in mouse mother's milk which enables suckling pup starch digestion well before brush border enzyme development. (3) This experiment with (13)C-α-limit dextrins needs to be repeated in human breast fed infants.

Compression syndrome as a complication of percutaneous coronary intervention.

Coronary artery perforation is a rare complication of percutaneous coronary intervention with potentially fatal consequences. A case of perforation occurring during percutaneous coronary intervention to a saphenous vein graft, complicated by the subsequent development of a compressive right atrial hematoma, is reported. The management of the case is described, and similar case reports in the literature are reviewed. The role of imaging in making the initial diagnosis and formulating an appropriate management strategy is emphasized.

Increased ceruloplasmin and fibrinogen in type 2 diabetes corresponds to decreased anti-oxidant activity in a preliminary tertiary South Indian hospital study.

The relationship between type 2 diabetes, antioxidant-enzyme serum ceruloplasmin, pro-inflammatory blood fibrinogen and antioxidant activity (AOA) was investigated in 40 diabetics and 47 non-diabetics hailing from South India as a preliminary study aspiring to be a crucial stepping stone for a large study. Serum AOA was lower (p<0.01) in diabetics (0.68+/-0.03 mmol/L) than controls (0.92+/-0.07 mmol/L) and ceruloplasmin more (p<0.001) in diabetics (983.20+/-52.18 mg/L) than controls (470.79+/-39.20 mg/L). Plasma fibrinogen was higher (p<0.001) in diabetics (480.23+/-19.52 mg/dl) than controls (313.94+/-13.42 mg/dl). Males had more AOA. Fibrinogen increased with age. These significant findings point strongly to augmented oxidative stress and inflammatory states in South Indian diabetics.

Treatment of hyper-IgG4 disease with sequential corticosteroids and tamoxifen - case report and review of the literature.

We report a patient with multifocal fibrosclerosis presenting as sialadenitis, hepatic fibrosis, and retroperitoneal fibrosis with renal failure. His medical management consisted of prednisone (4 months at 40 mg daily, then tapered down to 5 mg daily for another 14 months) and 18 months of tamoxifen. He responded clinically and radiographically to this regimen, and remains in clinical remission 10 months after discontinuing medical therapy. Subsequent histologic examination of submandibular gland tissue revealed strong staining for IgG4-positive plasma cells. To our knowledge, this is the first case of confirmed multifocal hyper-IgG4 disease to be successfully treated with sequential corticosteroids and tamoxifen.

Gateway cloning for protein expression.

The rate-limiting step in protein production is usually the generation of an expression clone that is capable of producing the protein of interest in soluble form at high levels. Although cloning of genes for protein expression has been possible for some time, efficient generation of functional expression clones, particularly for human proteins, remains a serious bottleneck. Often, such proteins are hard to produce in heterologous systems because they fail to express, are expressed as insoluble aggregates, or cannot be purified by standard methods. In many cases, researchers are forced to return to the cloning stages to make a new construct with a different purification tag, or perhaps to express the protein in a different host altogether. This usually requires identifying new cloning schemes to move a gene from one vector to another, and frequently requires multistep, inefficient cloning processes, as well as lengthy verification and sequence analysis. Thus, most researchers view this as a linear pathway - make an expression clone, try it out, and if it fails, go back to the beginning and start over. Because of this, protein expression pipelines can be extremely expensive and time consuming.The advent of recombinational cloning has dramatically changed the way protein expression can be handled. Rapid production of parallel expression clones is now possible at relatively low cost, opening up many possibilities for both low- and high-throughput protein expression, and increasing the flexibility of expression systems that researchers have available to them. While many different recombinational cloning systems are available, the one with the highest level of flexibility remains the Gateway system. Gateway cloning is rapid, robust, and highly amenable to high-throughput parallel generation of expression clones for protein production.

Improved recombinational stability of lentiviral expression vectors using reduced-genome Escherichia coli.

Lentiviral expression clones, which contain long direct repeats, often show dramatic instability in Escherichia coli, leading to difficulties in obtaining valid clones. We show that the reduced-genome E. coli strain MDS42 is capable of stabilizing lentiviral expression clones containing direct repeats, and outperforms many commonly used cloning strains for this purpose. In addition, the strain has several characteristics that make it highly amenable for use in recombinational cloning systems.

Multiprobe laser reflectometry in imaging and characterization of biological tissues.

Laser backscattered radiation from human forearm and foot were measured by multi-probe reflectometer, which consisted of one input probe and three output probes placed at distances of 2, 4 and 6 mm from the input probe. The normalized backscattered intensity (NBI) signals from the tissue surface, measured by the output probes, after digitization, were used to reconstruct the reflectance images of tissues in various layers below the skin surface. From NBI profiles measured at various locations of the tissues on the forearm the corresponding optical parameters, the scattering (mu(s)) and absorption (mu(a)) coefficients and the anisotropy parameter g, by matching these with profiles as simulated by Monte Carlo procedure were determined. From these data the optical parametric images of forearm were reconstructed which show the variation of these parameters at various locations. Similarly, the NBI data were collected from the foot sole region of healthy and diabetes subjects and their images reconstructed. These images showed the variation in the NBI in the diabetic foot sole compared to that of healthy subject, indicating the tissue structural changes. These procedures could be useful for diagnostic and therapeutic applications of lasers.

First-principles investigation of finite-temperature behavior in small sodium clusters.

A systematic and detailed investigation of the finite-temperature behavior of small sodium clusters, Na(n), in the size range of n=8-50 are carried out. The simulations are performed using density-functional molecular dynamics with ultrasoft pseudopotentials. A number of thermodynamic indicators such as specific heat, caloric curve, root-mean-square bond-length fluctuation, deviation energy, etc., are calculated for each of the clusters. Size dependence of these indicators reveals several interesting features. The smallest clusters with n=8 and 10 do not show any signature of melting transition. With the increase in size, broad peak in the specific heat is developed, which alternately for larger clusters evolves into a sharper one, indicating a solidlike to liquidlike transition. The melting temperatures show an irregular pattern similar to the experimentally observed one for larger clusters [Schmidt et al., Nature (London) 393, 238 (1998)]. The present calculations also reveal a remarkable size-sensitive effect in the size range of n=40-55. While Na(40) and Na(55) show well-developed peaks in the specific-heat curve, Na(50) cluster exhibits a rather broad peak, indicating a poorly defined melting transition. Such a feature has been experimentally observed for gallium and aluminum clusters [Breaux et al., J. Am. Chem. Soc. 126, 8628 (2004); Breaux et al., Phys. Rev. Lett. 94, 173401 (2005)].

Why do gallium clusters have a higher melting point than the bulk?

Density functional molecular dynamical simulations have been performed on Ga17 and Ga13 clusters to understand the recently observed higher-than-bulk melting temperatures in small gallium clusters [Phys. Rev. Lett. 91, 215508 (2003)]]. The specific-heat curve, calculated with the multiple-histogram technique, shows the melting temperature to be well above the bulk melting point of 303 K, viz., around 650 and 1400 K for Ga17 and Ga13, respectively. The higher-than-bulk melting temperatures are attributed mainly to the covalent bonding in these clusters, in contrast with the covalent-metallic bonding in the bulk.

Desensitization of the adrenocorticotrophin responses to arginine vasopressin and corticotrophin-releasing hormone in ovine anterior pituitary cells.

Following repeated or prolonged exposure to either corticotrophin-releasing hormone (CRH) or arginine vasopressin (AVP), pituitary adrenocorticotrophin (ACTH) responsiveness is reduced. This study compared the characteristics of desensitization to CRH and AVP in perifused ovine anterior pituitary cells. Desensitization to AVP occurred at relatively low AVP concentrations and was both rapid and readily reversible. Treatment for 25 min with AVP at concentrations greater than 2 nM caused significant reductions in the response to a subsequent 5 min 100 nM AVP pulse (IC(50)=6.54 nM). Significant desensitization was observed following pretreatment with 5 nM AVP for as briefly as 5 min. Desensitization was greater following a 10 min pretreatment, but longer exposures caused no further increase. Resensitization was complete within 40 min following 15 min treatment with 10 nM AVP. Continuous perifusion with 0.01 nM CRH had no effect on AVP-induced desensitization. Treatment with 0.1 nM CRH for either 25 or 50 min caused no reduction in the response to a subsequent 5 min stimulation with 10 nM CRH. When the pretreatment concentration was increased to 1 nM significant desensitization was observed, with a greater reduction in response occurring after 50 min treatment. Recovery of responsiveness was progressive following 50 min treatment with 1 nM CRH and was complete after 100 min. Our data show that in the sheep AVP desensitization can occur at concentrations and durations of AVP exposure within the endogenous ranges. This suggests that desensitization may play a key role in regulating ACTH secretion in vivo. If, as has been suggested, CRH acts to set corticotroph gain while AVP is the main dynamic regulator, any change in responsiveness to CRH may significantly influence the overall control of ACTH secretion.

Increased contractility of diabetic rabbit corpora smooth muscle in response to endothelin is mediated via Rho-kinase beta.

Corpus cavernosum smooth muscle (CCSM) from rabbits made diabetic for 6 months as a result of alloxan injection exhibited increased sensitivity (3vs 9 nM EC(50)) and generated 20-50% greater force to endothelin-1 (ET-1) compared to CCSM from normal rabbits. In contrast, the force produced by the CCSM in response to KCl and phenylephrine was not significantly altered in diabetic CCSM. The increased ET-1 sensitivity is associated with a two to three-fold upregulation of ET receptor A at both mRNA and protein levels in diabetic CCSM. ET-1-induced CCSM contraction is largely dependent upon Rho-kinase (ROK), since it is almost completely blocked by Y-27632 (a highly selective ROK inhibitor). Furthermore, expression of ROKbeta isoform is selectively upregulated in CCSM from diabetic rabbits. Thus, an increased CCSM tone, modulated by sensitization of the endothelin-mediated contractile pathway via ROK, may be a key component of the molecular mechanism of diabetes-induced erectile dysfunction.

Pacemaker endocarditis caused by Pseudomonas aeruginosa treated successfully.

Infective endocarditis (IE) is a rare but serious complication of permanent cardiac pacemaker placement. Endocarditis in the presence of prosthetic valves and pacemakers is usually due to staphylococci. We present a case of pacemaker endocarditis caused by Pseudomonas aeruginosa that was successfully treated with a combination of antimicrobial therapy and percutaneous removal of the colonized lead.

An indigenously developed method for sweat collection and estimation of chloride for diagnosis of cystic fibrosis.

An indigenously developed method for sweat collection and titration method for estimation of chloride was validated. The mean difference in estimated chloride value from the known strength of saline in 50 samples was -1.04 +/- 4.13 mEq/L (95% CI: -0.07 to 2.28). The mean difference in the estimated chloride values between two observers when the test was performed on known strengths of saline solution was -2.5 +/- 4.24 mEq/L (95% CI: -3.67 to 1.33). The inter observer variability between two observers when the test was performed on sweat samples obtained from 50 individuals was -1.12 +/- 4.34 mEq/L (95% CI: -2.23 to 0.8 ). Sweat weight of more than 100 mg could be collected in first attempt in 602 of 757 (80%) patient with an average sweat weight of 230 mg. This inexpensive method of sweat collection and chloride estimation has acceptable accuracy and repeatability and can be used in resource poor setting for making a diagnosis of cystic fibrosis.

Acute and chronic regulation of pituitary receptors for vasopressin and corticotropin releasing hormone.

At least two hypothalamic peptides, corticotropin releasing hormone (CRH) and vasopressin (VP), are important in regulating adrenocorticotropin (ACTH) release from the anterior pituitary. Both are secreted in a pulsatile manner and stimulate ACTH secretion by interacting with G protein-coupled receptors (GPCRs), namely the type 1 CRH receptor and V1b receptor, respectively. Repeated or prolonged stimulation with either peptide can cause reduced ACTH responsiveness or desensitisation, both in vivo and in vitro. Desensitisation of perifused sheep anterior pituitary cells to VP was found to be rapid and occurred following treatment with 5 nM VP for 5 min. This is within the range of concentrations and durations of VP pulses seen in sheep portal blood during acute stress. In contrast, significant desensitisation of the ACTH response to CRH required pre-treatment for longer than 25 min with a CRH concentration of 1 nM, suggesting that endogenous pulses may not elicit desensitisation. Although rapid GPCR desensitisation involves uncoupling of receptors from their G proteins, commonly mediated by receptor phosphorylation, and internalisation of receptors, desensitisation of neither the CRH nor VP receptor was mediated by PKA or PKC, respectively. Desensitisation of the response to VP was found to be dependent upon receptor internalisation, and resensitisation could be delayed by treatment with a protein phosphatase 2B inhibitor. The rapid kinetics of desensitisation of the ACTH response to VP suggest that this process is important in regulating the response to acute rather than chronic stress. If, as has been suggested, CRH acts in a permissive way to set corticotrope gain, desensitisation to CRH could also be important in long term regulation of ACTH secretion.