Chronic infections & coronary artery disease with special reference to Chalmydia pneumoniae.

BACKGROUND & OBJECTIVES: Studies on cardiovascular diseases (CVD) in India have shown about 10-20 per cent of cases with no obvious risk factors, raising a suspicion of infections as a cause. There is a paucity of data on this possible role of infections. This study was, therefore, undertaken to find out the association between infection due to Chlamydia pneumoniae and other organisms and coronary artery disease (CAD). METHODS: Patients with CAD were selected in group I (acute myocardial infarction, AMI) and group III (patients undergoing coronary artery bypass graft (CABG) surgery), and normal controls in group II. Routine biochemical, haematological and inflammatory tests [C-reactive protein (CRP), total leucocyte count (TLC), fibrinogen, ESR], serodiagnostic tests for IgA and IgG antibodies to C. pneumoniae, Helicobacter pylori, cytomegalovirus (CMV), Mycoplasma pneumoniae and Parvovirus B-19 by ELISA kits, C. pneumoniae antigen by microimmunofluorescence and PCR from endothelial tissue obtained at CABG were carried out. Aortic punch biopsies were done in patients who underwent CABG. RESULTS: Acute MI patients had a significantly higher association with accepted cardiac risk factors, lipid profile, inflammatory and thrombogenic tests. IgG and IgA antibodies levels against C. pneumoniae were not significantly different in the controls as against the AMI group. However, C. pneumoniae antigen seropositive group had significant association with HDL cholesterol, lipid tetrad index (P<0.001) and with triglycerides. Parvovirus B antigen was detected in 8.3 per cent of tissue specimens by PCR and of 44 patients with AMI (6.8%) were also positive for parvovirus B-19 IgG antibodies. INTERPRETATION & CONCLUSIONS: There was no direct evidence of the involvement of C. pneumoniae and other infective agents and viruses in CAD. It is possible that such infections produce an indirect adverse effect on the lipid profile.

Risk factors for ischemic heart disease in Delhi. (A prospective study of 7000 cases).

BACKGROUND: A prospective study of 7000 consecutive patients with IHD was carried out for "traditional" risk factors at the National Heart Institute (NHI) of the All India Heart Foundation (AIHF) and compared with 1000 "normal" controls. A specially designed proforma was used. STUDY GROUP: There were 5334 men (76%) and 1666 women (24%). The ages ranged from 24 to 92 years; above 60 (35%), between 51-60 (23%), 41-50 (22%) and below 40 (21.7%). The risk factor profile for the whole group was positive family history 38%, sedentary lifestyle 56%, overweight & obesity 21%, hypertension 64%, smoking 43% diabetes 39%, hypercholesterolemia 21% with no obvious risk factor in 15%. Those with no obvious risk factors could have had some of the "new" ones, which were not addressed. 2 & 3 risk factors were present in the majority (5618 patients 80%) and multiple risk factors in 96%. Hypertension was dominant in all groups. WOMEN: Significant differences were more, sedentary lifestyle, little or no smoking, higher cholesterol and more with no obvious risk factors. PRECOCIOUS IHD: In the 22% below 40 years, there was a significantly higher family history and smoking with significant prevalence of smoking, hypertension and diabetes. EXECUTIVE GROUP: The ages ranged from 24 to 59 with none above 60. There was no obvious risk factor in 55%. Here was a positive family history in 30.8%, sedentary lifestyle in 34%, smoking in 24.7%, hypertension in 16.5%, diabetes 11.8% and high cholesterol only in 5.6%. CONCLUSION: Multiple traditional risk factors were dominant in all the groups, with hypertension heading the list. Control of these, should be the target for all preventive programmes, targeting the general population and high risk groups.

Extra corporeal membrane oxygenation support for neonatal vein of Galen aneurysmal malformation: Case report.

BACKGROUND: The vein of Galen aneurysm (VGAM) is the most common type of arteriovenous malformation in the neonate. These neonates commonly present with high output cardiac failure that may be associated with pulmonary hypertension. The medical management and stabilization of these neonates can be challenging before staged transarterial embolization of the aneurysm is undertaken. CASE: A 2.34 kilogram neonate, antenatally diagnosed to have VGAM, was born at 36 weeks of gestation for fetal distress. The neonate failed to respond to medical management including inotropes, high frequency mechanical ventilation and inhaled nitric oxide. The patient's high-output heart failure and persistent pulmonary hypertension were stabilized with veno-arterial extra-corporeal membrane oxygenation (VA-ECMO) using central cannulation. Further transarterial staged embolization of the VGAM was undertaken on VA-ECMO support. CONCLUSION: There may be a role of VA-ECMO using central cannulation to optimize management of high output cardiac failure and persistent pulmonary hypertension in neonatal VGAM patients who fail medical management to facilitate staged transarterial embolization of the VGAM.

Synthesis of nucleoside 5'-O-alpha,beta-methylene-beta-triphosphates and evaluation of their potency towards inhibition of HIV-1 reverse transcriptase.

A polymer-bound alpha,beta-methylene-beta-triphosphitylating reagent was synthesized and subjected to reactions with unprotected nucleosides, followed by oxidation, deprotection of cyanoethoxy groups, and acidic cleavage to afford nucleoside 5'-O-alpha,beta-methylene-beta-triphosphates. Among all the compounds, cytidine 5'-O-alpha,beta-methylene-beta-triphosphate inhibited RNase H activity of HIV-1 reverse transcriptase with a K(i) value of 225 microM.

Type 1 Papillary Renal Cell Carcinoma Presenting as an Infected Benign Renal Cyst: an Uncommon Presentation.

We describe an unusual presentation of papillary renal cell carcinoma in a 40-year old male where radiological evaluation revealed a Bosniak type 2 cyst (probably benign), and clinical signs as well as symptoms also suggested an infected cyst l. However, on histopathological examination, an intra cystic type 1 papillary renal cell carcinoma was diagnosed. This is an extremely rare presentation of papillary renal cell carcinoma because it usually present as a heterogenous mass. Hence, even the radiologically benign cyst should be evaluated and managed cautiously.

Analysis of silver binding nucleolar organizer regions in exfoliative cytology smears of potentially malignant and malignant oral lesions.

Nucleolar organizer regions are nucleolar components that contain proteins that are stained selectively by silver methods; they can be identified as black dots throughout the nucleolus and are known as silver binding nucleolar organizer regions (AgNOR). The number of AgNOR is related to the cell cycle and the proliferative activity of the cells. We investigated AgNOR using exfoliative cytology smears of potentially malignant oral lesions. Eighty individuals were divided into four equal groups: healthy controls, oral leukoplakia, oral submucous fibrosis and oral squamous cell carcinoma. The mean number of AgNOR in each study group gradually increased from control to oral leukoplakia to oral submucous fibrosis to oral squamous cell carcinoma. The proliferative index was increased in the oral premalignant and malignant patients compared to normal subjects. The mean AgNOR size gradually increased from control to oral leukoplakia to oral submucous fibrosis to oral squamous cell carcinoma. Spherical shaped AgNOR were most common in controls, whereas large, clustered and kidney shapes were most common in oral squamous cell carcinoma. Multiparameter analysis of AgNOR in oral exfoliative smears is a simple, sensitive and cost-effective method for differentiating premalignant from malignant lesions and can be used in conjunction with routine cytomorphological evaluation.

Anasarca-mediated attenuation of the amplitude of electrocardiogram complexes: a description of a heretofore unrecognized phenomenon.

OBJECTIVES: The relationship between the changes of weight (WT) and electrocardiogram (ECG) QRS amplitude in patients with anasarca (AN) was evaluated. BACKGROUND: Attenuation of the ECG voltage occurs as the electrical current spreads from the epicardium to the body surface. The voltage registered is a function of the cardiac potentials, the electrical resistivities of the intervening tissues and the orientation of the ECG leads with respect to the direction of propagation of excitation. Lung congestion and pericardial and pleural effusions can cause attenuation in the ECG potentials; additionally, a similar change was recently observed in patients with AN. METHODS: A prospective study of this phenomenon in 28 patients with a critical illness was carried out. Electrocardiograms and patients' WTs were recorded daily. Pericardial effusions were excluded by serial echocardiograms. The sums of the amplitude of QRS complexes from the 12 ECG leads (Sigma QRS) were correlated with the corresponding WTs. Intracardiac ECGs, done in three patients, were correlated with surface ECGs. RESULTS: Admission WT was 148.9 +/- 37.8 lbs, and it peaked to 197.8 +/- 52.3 lbs (p = 0.0005). Admission Sigma QRS was 120.2 +/- 41.6 mm and dropped to 54.8 +/- 26.9 mm at time of peak WT (p = 0.0005). Regression of Sigma QRS on WT revealed an r = 0.61 and a p = 0.0005. Subsequent WT loss in 13 patients (from 219.0 +/- 40.7 lbs to 179.5 +/- 41.7 lbs, p = 0.001) led to an increase of Sigma QRS from 53.5 +/- 24.5 mm to 86.8 +/- 38.2 mm (p = 0.001). Intracardiac ECGs remained stable, while surface ECGs changed with perturbations of WT. CONCLUSIONS: Attenuation of ECG voltage in patients with AN correlates with WT gain, and it can be attributed to a shunting of the cardiac potentials due to the low resistance of the AN fluid.

Role of COX-2 selective inhibitors for prevention and treatment of cancer.

Cyclooxygenase-2 (COX-2) is an enzyme induced by inflammatory and mitogenic stimuli and results in enhanced synthesis of PGs in inflamed and neoplastic tissues. It is associated with cell proliferation and growth, in various cancerous conditions. We review the potential mechanisms of cancer reduction with COX-2 inhibitors and the preclinical evidence suggesting their effectiveness. Results of our study show that COX-2 is a regulatory factor for a number of pathways that can result in cancer. COX-2 makes cells resistant to apoptosis and promote angiogenesis, metastasis and cancer cell cycle by controlling number of targets. We found that, COX-2 selective inhibitors (like celecoxib and NS-398) can suppress the cancer both by COX-2 dependent and COX-2 independent pathways. COX-2 inhibitors can also produce synergic effects when used with other anti-cancer therapies. Thus, it is concluded that COX-2 selective inhibitors may be promising agents for prevention and treatment of cancer.

Comparing nonrigid registration techniques for motion corrected MR prostate diffusion imaging.

PURPOSE: T2-weighted magnetic resonance imaging (MRI) is commonly used for anatomical visualization in the pelvis area, such as the prostate, with high soft-tissue contrast. MRI can also provide functional information such as diffusion-weighted imaging (DWI) which depicts the molecular diffusion processes in biological tissues. The combination of anatomical and functional imaging techniques is widely used in oncology, e.g., for prostate cancer diagnosis and staging. However, acquisition-specific distortions as well as physiological motion lead to misalignments between T2 and DWI and consequently to a reduced diagnostic value. Image registration algorithms are commonly employed to correct for such misalignment. METHODS: The authors compare the performance of five state-of-the-art nonrigid image registration techniques for accurate image fusion of DWI with T2. RESULTS: Image data of 20 prostate patients with cancerous lesions or cysts were acquired. All registration algorithms were validated using intensity-based as well as landmark-based techniques. CONCLUSIONS: The authors' results show that the "fast elastic image registration" provides most accurate results with a target registration error of 1.07 ± 0.41 mm at minimum execution times of 11 ± 1 s.

Crossover comparison of timolol and latanoprost in chronic primary angle-closure glaucoma.

OBJECTIVE: To compare latanoprost and timolol maleate as primary therapy in 60 eyes with chronic primary angle-closure glaucoma after a laser iridotomy. METHODS: We performed a prospective, randomized, crossover study of 60 eyes of 30 patients with chronic primary angle-closure glaucoma after laser iridotomy. Patients were randomized to 2 groups: those taking latanoprost once daily or those taking timolol twice daily. Three months after treatment with the first drug, the second drug was substituted. The circadian rhythm of intraocular pressure (IOP) was recorded before the start of therapy, at 3 months, and at 7 months. The fourth month was the washout period for the first drug. RESULTS: The mean baseline IOP was 23.5 +/- 2.1 mm Hg, which decreased by 8.2 +/- 2.0 mm Hg with latanoprost (P<.001) and by 6.1 +/- 1.7 mm Hg with timolol (P =.01). The decrease in IOP was greater for patients taking latanoprost (P<.001). Latanoprost was significantly more effective in eyes having morning and afternoon peaks of IOP. A total of 43 eyes (72%) of patients taking latanoprost and 26 (43%) on timolol achieved a reduction of more than 30% from baseline IOP. CONCLUSION: There were greater mean and peak IOP reductions achieved with 0.005% latanoprost once daily compared with 0.5% timolol twice daily.

Aspergillus endophthalmitis.

A case is reported of bilateral aspergillus endophthalmitis in an infant without any detectable systemic predisposition or focus of infection. The patient is the youngest recorded case of endogenous aspergillus endophthalmitis so far, with an onset of symptoms at the age of 15 days. After histopathological confirmation of the aetiology by enucleation of the atrophic eye, systemic amphotericin B therapy was instituted with excellent results in the fellow eye. This is the first recorded instance of a complete clinical cure in aspergillus ocular disease on systemic amphotericin B therapy alone.

Role of argon laser trabeculoplasty as primary and secondary therapy in open angle glaucoma in Indian patients.

AIMS: To study the efficacy of argon laser trabeculoplasty (ALT) as a primary and secondary therapy in Indian patients with primary open angle glaucoma (POAG). METHODS: ALT was performed as a primary therapy in 40 eyes of 21 patients newly diagnosed with POAG (group I) and as a secondary therapy in 39 eyes of 21 patients who had been taking topical antiglaucoma medications for more than 1 year. The best corrected visual acuity, baseline intraocular pressure (IOP), diurnal variation of IOP, anterior chamber angles, and visual fields were the various parameters evaluated before and after performing ALT. Follow up visits were scheduled at 24 hours, 1 week, 1 month, 3 months, 6 months, and 1 year after the surgery. The patients were recalled at the end of 5 years for the final follow up examination. Success of ALT was defined as IOP

Conjunctival dysfunction and mitomycin C-induced hypotony.

PURPOSE: To determine the role of a physically intact conjunctiva in the development of chronic hypotony after mitomycin C-enhanced trabeculectomy. METHOD: Three patients with mitomycin C-related hypotonic maculopathy, but without a leak on Siedel test, had a thorough evaluation of the bleb area and an anterior segment fluorescein angiography. The bleb was excised and a pedicle flap, rotated from the temporal conjunctiva, was sutured to cover the defect superiorly. The scleral flap and its sutures were not disturbed. The excised bleb was subjected to light and electron microscopy. RESULTS: The Seidel test result was negative in all patients, but late phases of the anterior segment angiography showed a generalized seepage of aqueous from the bleb. After revision of the bleb, there was a gradual increase in the intraocular pressure, a reversal of the hypotonic maculopathy, and consequent improvement in visual acuity in all three patients, stable up to a minimum follow-up of 18 months. On histopathologic examination, the basement membrane was thickest under thin areas of the epithelium and thinnest below thicker epithelial layers. CONCLUSION: A dysfunctional conjunctival barrier, as evidenced by the "sweating" of the bleb and histopathologic alterations in the epithelial barrier, could be responsible for the hypotonic maculopathy in these patients. Excision of the conjunctiva alone and replacement by a pedicle conjunctival graft offers a safe and effective method of treating chronic hypotony after mitomycin C-augmented trabeculectomy in such patients.

Comparison of symptomatic and asymptomatic, chronic, primary angle-closure glaucoma, open-angle glaucoma, and controls.

PURPOSE: To determine the clinical features and anatomic parameters in asymptomatic (creeping) and symptomatic, chronic, primary angle-closure glaucoma (PACG) as compared with open-angle glaucoma (OAG) and with control subjects with normal eyes. METHODS: Forty consecutive patients with each of the following four types of eyes were studied (N = 160): eyes with symptomatic PACG, eyes with asymptomatic PACG, eyes with OAG, and the eyes of age-, sex-, and refraction-matched control subjects. The refractive status, keratometry, pachymetry, corneal diameter, anterior chamber depth, lens thickness, axial length, and relative lens position were noted. The groups were compared using a paired t test and analysis of variance. RESULTS: Patients with asymptomatic chronic PACG were older than patients in the symptomatic group, were more often men, and were more likely to have either diabetes mellitus or hypertension. Symptomatic chronic PACG eyes were more hypermetropic. Asymptomatic eyes had more iridotrabecular synechiae and minimal pupillary ruff atrophy as compared with the symptomatic eyes that had largely iridocorneal synechiae and large areas where the ruff was absent. All other clinical and anatomic parameters were statistically similar in the two groups, but differed significantly from OAG and control eyes. CONCLUSIONS: The ocular parameters of asymptomatic or creeping angle closure eyes show that these are significantly different from eyes having POAG. Asymptomatic and symptomatic chronic PACG eyes are structurally similar. Open-angle glaucoma eyes and normal eyes were comparable, but differed from both the chronic angle-closure glaucoma groups in having a larger corneal diameter, deeper anterior chamber, thinner lens, and a longer axial length. The symptomatic chronic PACG eyes showed more evidence of ischemic damage to the iris, and this could account for the symptoms reported by these patients.

A critique of the new ST-segment criteria for the diagnosis of acute myocardial infarction in patients with left bundle-branch block.

BACKGROUND: Recently, electrocardiogram (ECG) criteria have been proposed for the diagnosis of acute myocardial infarction (AMI) in the presence of left bundle-branch block (LBBB). However, clinical experience indicates that such ECG changes indicative of AMI are occasionally noted in clinically stable patients with LBBB, raising concerns about the specificity of the proposed criteria. HYPOTHESIS: The aim of this study was to evaluate the frequency of ST-segment abnormalities suggestive of AMI in ambulatory patients with cardiovascular disease and chronic LBBB, who did not have an AMI. In addition, the ECG determinants of such ST-segment abnormalities were sought. METHODS: The files of all (4,193) patients followed in the outpatient cardiology clinic were reviewed to identify patients with LBBB. Electrocardiograms of these patients were evaluated as to the duration of the QRS complex, frontal QRS axis, amplitude of QRS in leads V1-V3, and the presence and magnitude of ST-segment depression (-ST) in leads V1-V3, and ST-segment elevation (+ST) in leads with predominantly positive or negative QRS complexes. Correlations of these ECG variables were carried out. RESULTS: In 124 patients with LBBB only 1 patient with -ST of 1 mm in leads V1-V3, and 1 patient with +ST of 1 mm in a predominantly positive ECG lead were found; the latter patient also had +ST of 6 mm in V3. Nine patients were detected with > or = 5 mm +ST in at least one ECG lead with predominantly negative QRS complex. Regression analysis of amplitude of +STs on corresponding QRS amplitudes in leads V1-V3 yielded Rs of 0.69, 0.68, and 0.69, all with a p value of 0.00005. A similar analysis of the amplitudes of +STs > or = 5 mm with the corresponding QRSs yielded an R = 0.76 and a p value of 0.0018. CONCLUSIONS: Thus, recently proposed ST-segment criteria for the diagnosis of AMI in patients with LBBB are appropriate. However, stable > or = 5 mm +STs are occasionally found in leads with predominantly negative QRS complexes, particularly of large amplitude (mean value 46.0, range [28.0-71.0] mm) in the absence of AMI. In such patients presenting with symptoms suggestive of AMI, further non-ECG confirmation of probable underlying AMI should be sought.

Dry aerial fallout of organochlorine insecticide residues in Delhi, India.

Monitoring of airborne dust in Delhi during May to July 1985 revealed residues of DDT varying from 1.3 to 7.14 ng mg(-1) (4.06-22.31 ng m(-2) day(-1)) with an average of 3.32 ng mg(-1) (10.38 ng m(-2) day(-1)), and HCH which ranged from 0.46 to 2.35 ng mg(-1) (1.44-7.34 ng m(-2) day(-1)) with a mean of 1.16 ng mg(-1) (3.63 ng m(-2) day(-1)). The concentration of total DDT was almost 3 times greater than that of HCH.

Comparative studies on topical lomefloxacin and ciprofloxacin on ocular kinetic and experimental corneal ulcer.

Fluoroquinolones are antimicrobial agents that have a broad spectrum of activity and that are widely used against many of the ocular pathogens responsible for conjunctivitis, blepharitis, corneal ulcers, etc. The aim of our study was to compare the ocular pharmacokinetics of ciprofloxacin (0.3% w/v) and lomefloxacin (0.3% w/v) by HPLC after a single application of 50 microl topically. The study was also extended to compare their efficacy in experimentally-induced corneal ulcers. In ocular kinetic studies, lomefloxacin showed nearly 10 times more ocular bioavailability in aqueous humor as compared to ciprofloxacin. Lomefloxacin showed a Cmax of 1.62 microg/ml at the Tmax of 1 hr whereas ciprofloxacin showed a Cmax of 102.8 ngs/ml at the Tmax of 1 hr. Lomefloxacin was found to have significant efficacy in the healing of Staphylococcus aureus-induced corneal ulcers and associated lesions. Moreover, aqueous formulation oflomefloxacin showed a good compatibility at neutral pH. The results of our study indicate that a suitable treatment regimen with lomefloxacin (0.3%) therapy could be an excellent therapeutic alternative over ciprofloxacin in bacterial keratitis.

Entropion uveae: early sphincter atrophy, signposting primary angle closure glaucoma?

PURPOSE: An easily recognized clinical marker for early changes of primary angle closure glaucoma (PACG) or eyes predisposed to angle closure is important so that timely laser iridotomy can prevent morbidity. Pupillary ruff changes, specifically appearance of entropion uveae (EU), are frequent in eyes with PACG. METHODS: Pupillary ruff was examined under magnification and EU, if present, was graded and correlated with gonioscopic grading and presence of peripheral anterior synechiae (PAS) in consecutive patients with primary open angle glaucoma (POAG), non-glaucomatous controls, and PACG of the subacute, acute, chronic symptomatic, and creeping angle closure glaucoma subgroups. RESULTS: No POAG eye had an abnormal pupillary ruff. A total of 86.7% of subacute PACG eyes and all eyes with acute and chronic PACG showed some grade of EU. Iridocorneal synechiae were more significantly correlated with EU than goniosynechiae (p<0.001). Meridian of iridocorneal but not iridotrabecular synechiae could be correlated with the meridian of EU. In age-matched patients EU was only present in eyes with steep iris configuration, with significant correlation with narrow angles and goniosynechiae. In the detection of PACG the presence of EU Grade I was 94.9% sensitive and 98.2% specific for PACG eyes compared to the gonioscopic picture of angle closure in occludable angles. Its positive predictive value was 91.4%. CONCLUSIONS: EU shows significant correlation with narrow angles, steep iris configuration, and PAS. Kinking of radial iris arteries during angle closure probably causes temporary ischemia, especially of end arteries supplying area of the pupil and sphincter pupillae. EU emerges as an easily observed, objective marker for PACG.

Correlation between confocal scanning laser ophthalmoscopy and scanning laser polarimetry in open angle glaucoma.

PURPOSE: To correlate the findings of confocal scanning laser ophthalmoscopy and scanning laser polarimetry in diagnosed cases of glaucoma with established visual field defects. METHODS: A total of 53 diagnosed cases of primary open angle glaucoma that had at least two recorded of IOP more than 21 mm Hg on Goldmann applanation tonometry, open angles on gonioscopy and glaucomatous visual field defects on automated perimetry, were examined by confocal scanning laser ophthalmoscopy (HRT-II) and scanning laser polarimetry (GDx-NFA), in random order. RESULTS: The number on GDx advanced analysis had a significant (p < 0.05) correlation with the rim area (r = -0.279; p = 0.043), cup area (r = 0.311; p = 0.023) and the vertical cup: disc ratio (r = 0.376; p = 0.006). The correlation between HRT-II stereometric parameters and GDx advanced analysis parameters was significant (p < 0.05) for more parameters targeting the inferior pole of the disc than the superior pole. Numerically, the worst values of GDx parameters were associated with a worse result on Moorfields regression analysis, but there was poor agreement between the diagnostic labels like within or outside normal limits as obtained on GDx and HRT-II. CONCLUSIONS: Nerve fiber loss as detected on GDx correlates well with topographic optic nerve head changes as measured with the HRT-II. However, automated diagnosis on the two machines showed poor agreement.