Unexpected, transesophageal echocardiography-detected left ventricular microbubbles during off-pump coronary artery bypass graft surgery.
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Coronary Artery Bypass↗
Biomedical subjects
S Akhtar
Publications and source records attributed to S Akhtar.
Ion-dependence of Z-line and M-line response to calcium in striated muscle fibres in rigor.
The calcium-dependent contraction of vertebrate skeletal muscle is thought to be primarily controlled through the interaction of the thick and thin filaments. Through measurement of the Donnan potential, we have shown that an electrical switching mechanism (sensitive to both anions and cations) is present in both A- and I-bands [1]. Here we show that this mechanism is not confined to the contractile apparatus and report for the first time the presence of M-line potentials. The Z-line responds to Ca2+ ions in a similar manner to the A-band under the same solution conditions (phosphate-chloride and imidazole buffers), even though it has no reported Ca2+ binding sites. Z-line potentials were not observed in tris-acetate buffer. The M-line has a markedly different response to any of the other subsarcomeric regions, however, and can only be detected in the phosphate-chloride buffer. Preliminary observations of the M-line potential in creatine kinase-deficient mouse muscle (phosphate-chloride buffer) reveal significant differences in the calcium-induced transitions between two of the genotypes and demonstrate definitively that it is the M-line potential that is being recorded. From these results, it seems likely that the charge response of the Z-line and M-line is being mediated by titin in an anion-dependent manner. Our evidence comes from several observations. First, the similarity between the response of the Z-line potentials to the A-band potentials, where titin is the only link between these structures and second, the differential observation of M-line and Z-line potentials in a range of buffers containing different anion(s). Both Z-line and M-line potentials were seen in phosphate-chloride buffer, but only the Z-line potentials could be detected in chloride-only (imidazole) buffer and neither was observed in the acetate buffer. The latter observations can be attributed to two sources. The first is the effect of acetate buffer on the conformation of myosin [2]; the second is the absence of binding of the M-line protein, myomesin, to titin in the absence of phosphate ions [3].
Acetates↗
Hypotensive effect of chemical constituents from Aloe barbadensis.
Hypotensive effects of aloeemodin, aloin A, elgonica dimer A and bisbenzopyran from Aloe barbadensis have been studied. Aloeemodin has emerged as a potent hypotensive agent in current pharmacological investigations and caused 26 %, 52 %, and 79 % falls in mean arterial blood pressure at the corresponding doses of 0.5, 1, and 3 mg/kg in rats. The paper also describes the absolute configuration of elgonica dimer A (1).
Aloe↗
Congenital hereditary endothelial dystrophy and band keratopathy in an infant with corpus callosum agenesis.
PURPOSE: To report the features of a syndrome of endothelial failure and band-shaped keratopathy in an infant with corpus callosum agenesis. METHODS: The clinical and histopathologic features of an infant presenting with bilateral corneal clouding and corpus callosum agenesis are reported. The patient underwent bilateral penetrating keratoplasty at ages 28 months and 4 years. Light and electron microscopy were used to characterize the structural changes. RESULTS: The epithelium was thin and degenerate. Bowman's membrane contained spherical aggregates that were present also within a connective tissue pannus. The midstroma was normal, but there were floral and rope-like aggregations of collagen in the pre-Descemet's membrane region. Under electron microscopy, the spherules formed target-shaped lesions with a central focus of alternating electron-dense and lucent material. Numerous microfilaments in the pannus and anterior stroma labeled with fibrillin-1 antibody. Microfilaments within fibroblasts were stained with vimentin antibody. Posteriorly, the endothelium was mainly absent and Descemet's membrane showed a fetal layer and a posterior collagenous layer. CONCLUSION: Corneal appearances in this patient were in keeping with those of congenital hereditary endothelial corneal dystrophy. However, there was no family history and neither parent showed a clinical endothelial abnormality. The presence of fetal, banded material in Descemet's membrane suggested that endothelial loss began at or near the time of birth. The band keratopathy was regarded as a secondary change. The association with corpus callosum agenesis does not appear to have been described previously.
Agenesis of Corpus Callosum↗
Primary and booster mucosal immune responses to meningococcal group A and C conjugate and polysaccharide vaccines administered to university students in the United Kingdom.
Meningococcal group A+C capsular polysaccharide (PS) conjugate vaccines may prime for serum immunoglobulin G (IgG) memory responses to meningococcal capsular PS. It is not known whether these vaccines induce immunological memory at the mucosal level, which may be important in reducing nasopharyngeal carriage. Mucosal immune responses to meningococcal conjugate and PS vaccines in young adults were investigated. Healthy university students were randomized to receive either a groups A+C meningococcal conjugate vaccine (MACconj, n = 100) or a group A+C meningococcal PS vaccine (MACPS, n = 95). One year after the primary immunization, both groups were randomized again to receive a MACconj or a MACPS booster vaccination. Saliva samples were collected before and 1 month after the primary and booster vaccinations. Anti-meningococcal A (MenA) and C (MenC) PS IgA and IgG antibody levels were measured by a standard enzyme-linked immunosorbent assay. After the primary vaccination, salivary MenA and MenC IgG and MenA IgA concentrations were significantly increased after immunization with both MACconj and MACPS vaccines, but the salivary Men C IgA level was increased only after MACPS vaccine (P < 0.01). IgA responses to both serogroups were greater for MACPS than MACconj vaccine (P < 0.05), whereas no significant differences were seen for IgG responses. MenA IgG titers were higher after the MACPS booster in MACconj-primed subjects than after the MACPS primary vaccination, suggesting the presence of IgG memory. Antibody responses to a dose of either MACPS or MACconj were not significantly reduced in those previously given MACPS compared to the primary responses to those vaccines. Meningococcal A+C conjugate and PS vaccines induce significant mucosal responses in young adults. MACconj priming may induce IgG memory at the mucosal level, which is likely to be a reflection of an anamnestic serum IgG response. No evidence of mucosal hyporesponsiveness was observed after MACPS priming in this study.
Adolescent↗
Ultrastructural morphology and expression of proteoglycans, betaig-h3, tenascin-C, fibrillin-1, and fibronectin in bullous keratopathy.
AIMS: To investigate the ultrastructural localisation of proteoglycans (PG), betaig-h3 (keratoepithelin), tenascin-C (TN-C)), fibrillin, and fibronectin in bullous keratopathy (BK) corneas. METHODS: Five corneas from cases of pseudophakic bullous keratopathy (BK) were examined by electron microscopy. PG were demonstrated using cuprolinic blue, and the proteins betaig-h3, TN-C, fibrillin, and fibronectin were immunolocalised with rabbit anti-betaig-h3, mouse anti-TN-C (BC10 and TN2), mouse anti-fibrillin-1 (MAB2502), mouse anti-fibrillin (MAB1919), and rabbit anti-fibronectin by using a standard immunogold technique. RESULTS: Epithelial cells contained numerous vacuoles. Epithelial folds and large, electron lucent subepithelial bullae were present. Basal lamina was thickened and traversed by disrupted anchoring filaments. In the stroma, interfibrillar collagen spacing was increased and abnormally large PG were present. Descemet's membrane (DM) contained lucent spaces in which there were small filaments. Keratocyte and endothelial cells contained melanin granules. A posterior collagenous layer (PCL) contained numerous microfilaments and wide spacing collagen fibres with a periodicity of 100 nm. Large quantities of abnormal PG were observed at the endothelial face of the PCL. Very strong labelling with betaig-h3 antibody was observed in the basement membrane, Bowman's layer, stroma, DM, and PCL, but not in keratocytes and endothelial cells. Strong labelling with BC10 and TN2 was seen below the epithelium, in electron lucent spaces where the hemidesmosomes were absent, in the fibrotic pannus, in parts of Bowman's layer, the stroma, and Descemet's membrane. Labelling with BC10 was stronger and more evenly distributed than with TN2. Fibrillin-1 (MAB2502) and fibrillin (MAB1919) labelling was similar to TN-C labelling. Fibrillin (MAB1919) labelling was stronger than fibrillin-1 (MAB2502) labelling. CONCLUSIONS: Immunoelectron microscopy showed precise labelling of proteins at both the cellular and the subcellular level. Expression of proteins betaig-h3, TN-C, fibrillin, and fibronectin was highly increased compared with normal cornea. In the oedematous stroma, increased collagen fibril separation may facilitate a wider distribution of some soluble proteins, such as betaig-h3, throughout stroma. The modified expression of the proteins studied in these cases of BK may be regarded as part of an injury response.
Aged↗
HIV/AIDS knowledge, attitudes and beliefs based prediction models for practices in prison inmates, Sindh, Pakistan.
This study was conducted on prison inmates in Sindh to determine whether HIV/AIDS related knowledge, attitudes and beliefs can predict their practices which risk HIV infection. A pre-designed questionnaire was administered in this cross-sectional study to collect the data on HIV/AIDS related knowledge, attitudes, beliefs, practices and demographic variables in a systematic sample of 3,395 prison inmates during July 1994. The data on responses of inmates to HIV/AIDS related knowledge, attitudes, and beliefs were analyzed and a clear interpretable factor structure emerged for each set of questions labeled as knowledge, attitude and beliefs. Similarly based on responses of inmates to practice questions, three factors emerged and were labeled as heterosexuality, homosexuality and drugs. The standardized factor scores of inmates for each of these six factors were computed and used in further analyses. Multiple linear regression analyses were carried out separately using heterosexuality, homosexuality and drugs factors score as dependent variables to identify if any of the independent variables (demographic variables, knowledge beliefs and attitude) predict these practice factors. The model for heterosexuality explained 23% of the variance and included HIV/AIDS related knowledge, beliefs, age, ethnicity and marital status and duration of imprisonment (F = 84.33, p < 0.001; R2= 23.0). The predictors in the model for homosexuality together explained 10% of the variance and included significant contribution by belief, martial status, ethnicity, education, age and duration of imprisonment (F = 24.76, p < 0.001; R2= 0.10). The model for drugs had significant contributions from HIV/AIDS related beliefs, marital status and ethnicity (F = 20.10, p < 0.001; R2= 0.03). Implications of prevention program based on these results are considered.
Adult↗
Induction of Alzheimer phenotype in mouse skin fibroblasts.
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Alzheimer Disease↗
Comparative studies on nicotinic acid derivatives as hypolipoproteinemic agents.
Nicotinic acid and its related compounds are well known lipid lowering agents but the use of nicotinic acid in clinical practice is limited because of its side effects. To reduce the unwanted effects, new derivatives of nicotinic acid have been synthesized and tested in control and pathological animals for their antilipoproteinemic effects. Two newly synthesized derivatives of nicotinic acid i.e. 3-methoxy phenacyl nicotinium bromide (T1) and 2-methoxy phenacyl nicotinium bromide (T2) have been screened for their hypolipoproteinemic effects in white male rabbits. The compounds were administered in the doses of 30 mg/day and the results were compared with aspirin taken as the reference drug. The present work revealed that both of these synthesize compounds exhibited marked effects on plasma lipoproteins assuming that these compounds exerted their action by inhibiting hepatic production of very low density lipoprotins (VLDL), ultimately leading to reduction in low density lipoprotein. Clofibrate and aspirin are taken as standards to evaluate the potentials of these agents for their effects on lipid.
Journal Article↗
The delivery of antisense therapeutics.
Antisense oligonucleotides, ribozymes and DNAzymes have emerged as novel, highly selective inhibitors or modulators of gene expression. Indeed, their use in the treatment of diseases arising from genetic abnormalities has become a real possibility over the past few years. The first antisense drug molecule is now available for clinical use in Europe and USA. However, their successful application in the clinic will require improvements in cellular targeting and intracellular delivery. This review aims to look at recent advances in the in vitro and in vivo delivery of antisense oligodeoxynucleotides and ribozymes.
Animals↗
Primary and booster salivary antibody responses to a 7-valent pneumococcal conjugate vaccine in infants.
Salivary anticapsular antibody responses to a 7-valent pneumococcal conjugate vaccine (7VPnC) were measured in healthy infants. Infants received diphtheria-tetanus-pertussis/Haemophilus influenzae type b (DTP/Hib; group 1), DTP/Hib and 7VPnC (group 2), or DTP and 7VPnC/Hib (group 3) at ages 2, 3 and 4 months. All children received 23-valent pneumococcal polysaccharide vaccine at age 13 months. Salivary IgA and IgG responses to primary immunizations were generally poor. IgA mean concentrations at age 5 months were higher in the treatment groups than in control subjects for serotype 14 only (P<.001). At age 13-14 months, there were marked increases in IgA (mean fold difference, 3.7-4.9) and IgG (mean fold difference, 4. 1-11.7) levels for serotypes 4, 9V, 14, and 19F and serotypes 4, 18C, 19F, and 23F, respectively, in the treatment groups. This contrasts with low IgA (1.2 and 1.4) and IgG (1.3 and 2.2) mean fold differences for non-7VPnC serotypes 1 and 5. The results suggest that 7VPnC primes for mucosal memory responses in infants.
Antibodies, Bacterial↗
From schisms through synthesis to informed oscillation: an attempt at integrating some diverse aspects of psychoanalytic technique.
There exists a conceptual bifurcation at the core of psycho-analysis. It has been viewed from differing vantage points and portrayed as subsuming various dichotomies (oedipal-preoedipal, conflict-deficit, one person-two person, classic-romantic, and so on). While each such conceptual pair has its own heuristic accompaniments, these dichotomies share a profoundly important element. They have divergent effects upon the analyst's mode of listening and the nature of his or her interventions. These and other related technical implications are the topic of this paper. With the help of three clinical vignettes and by coalescing the isolated voices of many distinguished theoreticians, the author attempts to elucidate and heal this split. This paper proposes three levels of increasingly sophisticated resolution of the technical divergence resulting from this schism. The paper recommends an informed oscillation between the two polarities of psychoanalytic technique, an oscillation that must remain in consonance with the patient's shifting ego organization. The paper concludes by highlighting the developmental bases for the proposed technical conceptualizations.
Adult↗
The effect of hydration and matrix composition on solute diffusion in rabbit sclera.
There is increasing interest in the possibility for drug delivery into the vitreous humor across the conjunctiva and sclera as an alternative route to the conjunctiva-cornea pathway. As a preliminary to human studies we have investigated the influence of scleral composition and hydration on solute transport in the rabbit sclera. Intermuscular sclera was excised from adult New Zealand rabbits. Tissue samples were either examined directly (controls), digested using chondroitinase ABC or crosslinked using glutaraldehyde. The effect of these treatments on the ultrastructural appearance of the sclera was assessed. Diffusion and partition coefficients for solutes of different molecular weights [sodium chloride (23 MW),(14)C sucrose (342 MW) and dextran-fluoresceins (3, 10, 40 and 70 kDa)] were measured in relation to tissue treatment. The results were used to determine the effect of tissue structure and composition on solute movement. We have found that: (1) diffusion and partition coefficients are sensitive to solute MW, decreasing as MW increases; (2) diffusion and partition coefficients are sensitive to tissue hydration, increasing as hydration increases; (3) crosslinking of the sclera by glutaraldehyde reduced the partition coefficients significantly for solutes with MW over 3 kDa; and (4) removal of glycosaminoglycans has only a small effect on either diffusion or the partition coefficient.
Animals↗
Pretreatment with ranitidine does not reduce the bioavailability of orally administered topotecan.
PURPOSE: The purpose of this randomized, two-period crossover study was to determine the pharmacokinetics of orally administered topotecan in the presence and absence of oral ranitidine. METHODS: Patients with solid malignant tumors refractory to standard treatment were given topotecan orally on a daily times five schedule repeated every 21 days. Topotecan was given initially at 2.3 mg/m2 per day; dose adjustments were permitted after the first dose of course 2 if necessary. Blood samples for pharmacokinetic assessments were drawn at protocol-specified times for up to 10 h following oral administration of topotecan on day 1 of courses 1 and 2. Patients were randomly assigned to receive a total of nine doses of ranitidine: 150 mg twice daily for 4 days before day 1 of one of the first two courses and 150 mg given 2 h before the first topotecan dose. Plasma samples were assayed for concentrations of active topotecan lactone (TPT-L) and total topotecan (TPT-T, lactone plus open-ring carboxylate form) using high-performance liquid chromatography with fluorescence detection. After completion of courses 1 and 2, patients could continue on therapy for days 1-5 of every 21 days if not withdrawn due to unacceptable toxicity, disease progression, protocol violation, or by request. Patients continued on treatment for a maximum of six courses. RESULTS: No pharmacokinetic parameter for either TPT-L or TPT-T differed significantly during administration of topotecan with ranitidine compared with topotecan alone (n = 13). Geometric mean ratios (95% confidence intervals, CIs) of areas under the curve in the presence and absence of ranitidine were 0.94 (0.80, 1.10) for TPT-L and 0.97 (0.80, 1.16) for TPT-T. Corresponding ratios (CIs) of peak plasma concentrations in the presence and absence of ranitidine were 1.06 (0.78, 1.44) for TPT-L and 1.07 (0.84, 1.38) for TPT-T. The median difference in time to peak plasma concentration was 0.0 h for TPT-L and -0.5 h for TPT-T (i.e. slightly faster in the presence of ranitidine). CONCLUSIONS: Administration of ranitidine prior to oral topotecan resulted in a similar extent of absorption. A slightly faster rate of absorption of topotecan was also observed, which is unlikely to be of clinical significance. Dosage adjustments of orally administered topotecan should not be necessary in patients who are pretreated with ranitidine, an H2 antagonist, or another agent that comparably raises gastric pH.
Administration, Oral↗
Con: Preoperative thallium testing should not be performed routinely before vascular surgery.
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Coronary Disease↗
Quality of life issues in recurrent respiratory papillomatosis.
Twenty-six adult patients attending the Royal National Throat, Nose, and Ear Hospital with Recurrent Respiratory Papillomatosis completed two postal questionnaires. One was the generic Short Form-36 (SF-36) quality of life instrument. Severely affected patients had lower scores in all dimensions of this instrument, with large differences from normal controls in dimensions of pain, physical limitation, and energy/vitality. The second questionnaire was newly devised, and designed to ask about a wide variety of larynx-specific symptoms. Answers by patients were compared with those of normal controls, and symptoms selected as significantly more likely to be reported by patients were studied further. Correlation was seen with clinical parameters, and questions likely to be responsive to clinical change in disease burden were identified.
Adolescent↗
Merkel cell carcinoma: report of 10 cases and review of the literature.
BACKGROUND: Merkel cell carcinoma (MCC) is a rare primary neuroendocrine skin tumor that usually arises in the head and neck or the extremities of elderly patients. Because of the limitation of retrospective data, optimal treatment is not well defined. OBJECTIVE: Our purpose was to present the clinical course and treatment of 10 patients with MCC and review the published literature on MCC. METHOD: We conducted a retrospective analysis and obtained detailed clinical information for all 10 patients treated for MCC at our institution from 1986 through 1998. The medical literature was also reviewed for natural history and treatment recommendations using MEDLINE search. RESULTS: Five men and 5 women received their treatment between 1986 and 1998 for MCC (5 had stage IA disease, 4 stage IB, 1 stage II). The mean age was 70.3 years (range, 47-86 years). Seven tumors were located on the head and neck and 3 on extremities. Five of 10 patients had a relapse (mean time before recurrence, 5.7 months) (range, 2 weeks-20 months); one patient had local recurrence, one had regional lymph node recurrence, and 3 had both local and regional lymph node recurrence. In 4 patients systemic metastases developed. Long survival is also noted (6 to > 164 months); 4 patients died of MCC. After initial surgery, 9 patients received radiotherapy at some point and 3 patients also received chemotherapy. Five of 10 patients had 13 previously treated or coexisting malignant neoplasms. In one patient MCC developed in a previously irradiated field. Review of 875 cases showed a male/female ratio of 1.5:1; location of tumors was as follows: head and neck, 47%; extremities, 40%; trunk, 8%; unknown primary site, 5%. Local recurrence was observed in 25%, regional lymph node involvement in 52%, distant metastasis in 34%, and MCC was a cause of death in 34%. CONCLUSION: MCC has a high incidence of locoregional recurrence with distant metastases that is more common with higher stage lesions. Early local management of smaller lesions results in good long-term survival. It is not known whether prophylactic lymph node dissection and/or radiation and adjuvant radiation increases survival. Long survival can be achieved after treating locoregional recurrence. The role of chemotherapy is still controversial and should be considered in patients with advanced disease and those not thought to be candidates for surgery.
Aged↗