We conducted active surveillance for kala-azar and post–kala-azar dermal leishmaniasis (PKDL) in a population of 24,814 individuals. Between 2002 and 2010, 1,002 kala-azar and 185 PKDL cases occurred. Median PKDL patient age was 12 years; 9% had no antecedent kala-azar. Cases per 10,000 person-years peaked at 90 for kala-azar (2005) and 28 for PKDL (2007). Cumulative PKDL incidence among kala-azar patients was 17% by 5 years. Kala-azar patients younger than 15 years were more likely than older patients to develop PKDL; no other risk factors were identified. The most common lesions were hypopigmented macules. Of 98 untreated PKDL patients, 48 (49%) patients had resolution, with median time of 19 months. Kala-azar patients showed elevated interferon-γ (IFNγ), tumor necrosis factor-α (TNFα), and interleukin 10 (IL-10). Matrix metalloproteinase 9 (MMP9) and MMP9/tissue inhibitor of matrix metalloproteinase-1 (TIMP1) ratio were significantly higher in PKDL patients than in other groups. PKDL is frequent in Bangladesh and poses a challenge to the current visceral leishmaniasis elimination initiative in the Indian subcontinent.
The authors present a case of a 44-year-old man who presented with acute onset shortness of breath. He had severe subcutaneous emphysema and his chest x-ray and CT scan confirmed presence of air in mediastinum. Rigid bronchoscopy revealed a bronchial tumour which was proven to be a carcinoid on histology. Patient recovered following the surgical excision of the tumour.
Exposure of cancer cells to anticancer agents in cultures induces detachment of cells that are usually considered dead. These drug-induced detached cells (D-IDCs) may represent a clinical problem for chemotherapy since they may survive anoikis, enter the circulation, invade other tissues and resume proliferation, creating a metastasis, especially in tissues where the bioavailability of anticancer agents is not enough to eliminate all cancer cells. In this study we evaluated the antiproliferative effect of menadione : sodium orthovanadate (M : SO) combination on A549 lung cancer cells as well as the ability of M : SO to induce cell detachment. In addition, we followed the fate and chemosensitivity of M : SO-induced detached cells. Using transwell chambers, we found that a fraction of the M : SO-induced detached cells were viable and, furthermore, were able to migrate, re-attach, and resume proliferation when re-incubated in drug-free media. The total elimination of A549 detachment-resistant cells and M : SO-induced detached cells were successfully eliminated by equivalent M : SO concentration (17.5 μM : 17.5 μM). Thus, M : SO prevented cell migration. Similar results were obtained on DBTRG.05MG human glioma cells. Our data guarantee further studies to evaluate the in vivo occurrence of D-IDCs, their implications for invasiveness and metastasis and their sensitivity to anticancer drugs.
Paroxysmal atrioventricular-block is a poorly-recognized cause of atrioventricular conduction abnormality leading to syncope and can be fatal. Here we report a case of paroxysmal atrioventricular-block presenting as syncope treated effectively with pacemaker implantation and review the current literature on prevalence, known mechanisms and treatment for it. Importantly we provide the diagnostically important differentiating points between vagally mediated block and paroxysmal atrioventricular-block as well as the highlight the vastly varying prognosis between the two.
Paroxysmal AV-block; reverse wenckebach; syncope
Serum complement function was evaluated in 125 affected subjects suffering from drinking water arsenic toxicity. Their mean duration of exposure was 7.4 ± 5.3 yrs, and the levels of arsenic in drinking water and urine samples were 216 ± 211 and 223 ± 302 μg/L, respectively. The mean bactericidal activity of complement from the arsenic patients was 92% and that in the unexposed controls was 99% (P < 0.01), but heat-inactivated serum showed slightly elevated activity than in controls. In patients, the mean complement C3 was 1.56 g/L, and C4 was 0.29 g/L compared to 1.68 g/L and 0.25 g/L, respectively, in the controls. The mean IgG in the arsenic patients was 24.3 g/L that was highly significantly elevated (P < 0.001). Arsenic patients showed a significant direct correlation between C3 and bactericidal activity (P = 0.014). Elevated levels of C4 indicated underutilization and possibly impaired activity of the classical complement pathway. We conclude reduced function of serum complement in drinking water arsenic toxicity.
The operative treatment of displaced intraarticular calcaneal
fractures has been a controversial topic. Soft tissue
conditions and concomitant disease must be considered in
these patients. The minimally invasive sinus tarsi approach is
a valid therapeutic solution that guarantees stability,
anatomic reduction of the fracture and soft tissue
preservation. Twenty-five closed calcaneal fractures in 20
patients were treated with open reduction and internal
fixation using the sinus tarsi approach (including fixation
with cannulated screws). All fractures healed by the time of
final follow-up at 18 months. The time to union judged both
clinically and radiographically, averaged 3 months. Mean
Maryland foot scores were: 95 in type II; 91 in type III; and
83 in type IV fractures. Advantages offered by this new
approach include a less invasive incision while still
permitting good visualization and anatomic reduction of
articular surfaces and with few complications.
Intraarticular calcaneal fractures, sinus tarsi approach, Sanders classification
Ewing's sarcoma (ES) primarily affects bones and commonly presents in adolescents and young adults. This paper reports a rare case of extra osseous ES of the scapular region in a 9 years old girl. She was treated by a multidisciplinary approach including surgery, chemotherapy and radiotherapy. She was followed up for two years and remained well.
Ewing’s sarcoma; Extra-osseous; Chemotherapy
Background & objectives:
Factor causing the elimination of the classical biotype of Vibrio cholerae O1, and its replacement by the El Tor biotype causing the 7th cholera pandemic are unclear. Possible ability of the El Tor strains to adapt better than the classical strains to undefined environmental forces have been largely implicated for the change. Here we describe an environmental bacteriophage designated JSF9 which might have contributed to the range of factors.
Competition assays were conducted in the infant mice model and in microcosms between representative El Tor and classical biotype strains in the absence or in the presence of JSF9 phage.
The JSF9 phage was found to kill classical strains and favour enrichment of El Tor strains, when mixtures containing strains of the two biotypes and JSF9 phage were subjected to alternate passage in infant mice and in samples of environmental water. Spontaneous derivatives of the classical biotype strains, as well as transposon mutants which developed resistance to JSF9 phage were found to be defective in colonization in the infant mouse model.
Interpretation & conclusions:
These results suggest that in addition to other factors, the inherent ability of El Tor biotype strains to evade predation by JSF9 or similar phages which kill classical biotype strains, might have enhanced the emergence of El Tor strains as the predominant pandemic biotype.
Classical biotype; El Tor biotype; toxigenic Vibrio cholerae; vibriophage
Toxigenic Vibrio cholerae, the causative agent of the epidemic diarrheal disease cholera, interacts with diverse environmental bacteriophages. These interactions promote genetic diversity or cause selective enrichment of phage-resistant bacterial clones. To identify bacterial genes involved in mediating the phage-resistant phenotype, we screened a transposon insertion library of V. cholerae O1 El Tor biotype strain C6706 to identify mutants showing altered susceptibility to a panel of phages isolated from surface waters in Bangladesh. Mutants with insertion in cyaA or crp genes encoding adenylate cyclase or cyclic AMP (cAMP) receptor protein (CRP), respectively, were susceptible to a phage designated JSF9 to which the parent strain was completely resistant. Application of the cyaA mutant as an indicator strain in environmental phage monitoring enhanced phage detection, and we identified 3 additional phages to which the parent strain was resistant. Incorporation of the cyaA or crp mutations into other V. cholerae O1 strains caused similar alterations in their phage susceptibility patterns, and the susceptibility correlated with the ability of the bacteria to adsorb these phages. Our results suggest that cAMP-CRP-mediated downregulation of phage adsorption may contribute to a mechanism for the V. cholerae O1 strains to survive predation by multiple environmental phages. Furthermore, the cyaA or crp mutant strains may be used as suitable indicators in monitoring cholera phages in the water.
Menadione (Vitamin K3) has anti-tumoral effects against a wide range of cancer cells. Its potential toxicity to normal cells and narrow therapeutic range limit its use as single agent but in combination with radiation or other anti-neoplastic agents can be of therapeutic use. In this paper, we first evaluated the early (within 3 h) effect of menadione on ongoing DNA replication. In normal rat cerebral cortex mini-units menadione showed an age dependent anti-proliferative effect. In tissue mini-units prepared from newborn rats, menadione inhibited ongoing DNA replication with an IC 50 of approximately 10 μM but 50 μM had no effect on mini-units from prepared adult rat tissue. The effect of short (72 h) and prolonged exposure (1–2 weeks) to menadione alone in the DBTRG.05MG human glioma cells line and in combination with vitamin C was studied. After short period of exposure data show that menadione alone or in combination with vitamin C provided similar concentration-response curves (and IC50 values). Prolonged exposure to these drugs was evaluated by their ability to kill 100% of glioma cells and prevent regrowth when cells are re-incubated in drug-free media. In this long-term assay, menadione:vitamin C at a ratio 1:100 showed higher anti-proliferative activity when compared to each drug alone and allowed to reduce each drug concentration between 2.5 to 5-fold. Similar anti-proliferative effect was demonstrated in 8 patient derived glioblastoma cell cultures. Our data should be able to encourage further advanced studies on animal models to evaluate the potential use of this combination therapy for glioma treatment.
Gliomas; Menadione; Vitamin C; Proliferation; DNA replication
Techniques are being standardized in our department for total body irradiation (TBI) with six MV photons in linear accelerator for preconditioning to bone marrow transplantation (BMT). Individualized shields with low melting point alloy are to be fabricated for shielding critical organs such as lungs, kidneys etc. A method to mount diminished dimension of shields in a tray at 3.75m is designed in the department for a teletreatment distance of four meters with magna field with A simulator image taken with the patient's midplane (MP) at one meter distance is used to mark the dimensions of lung, scaled down by a factor of 3.75/4.0. These lung dimensions are reprinted from the digital simulator image for making the shield. The methodology of the technique using digitized minification in radiography is the first of its kind to be used for shield cutting in magna field radiotherapy.
Magna field radiotherapy; shielding in TBI; total body irradiation
Seasonal epidemics of cholera in Bangladesh are self-limited in nature, presumably due to phage predation of the causative Vibrio cholerae during the late stage of an epidemic, when cholera patients excrete large quantities of phage in their stools. To further understand the mechanisms involved, we studied the effect of phage on the infectivity and survival of V. cholerae shed in stools. The 50% infectious dose of stool vibrios in infant mice was ∼10-fold higher when the stools contained a phage (1.8 × 103 to 5.7 × 106 PFU/ml) than when stools did not contain a detectable phage. In competition assays in mice using a reference strain and phage-negative cholera stools, the infectivity of biofilm-like clumped cells was 3.9- to 115.9-fold higher than that of the corresponding planktonic cells. However, the difference in infectivity of these two cell populations in phage-positive stools was significantly less than that in phage-negative stools (P = 0.0006). Coculture of a phage and V. cholerae or dilutions of phage-positive cholera stools in nutrient medium, but not in environmental water, caused rapid emergence of phage-resistant derivatives of the bacteria, and these derivatives lost their O1 antigen. In cholera stools and in intestinal contents of mice prechallenged with a mixture of V. cholerae and phage, the bacteria remained completely phage susceptible, suggesting that the intestinal environment did not favor the emergence of phage-resistant derivatives that lost the O1 antigen. Our results indicate that phages lead to the collapse of epidemics by modulating the required infectious dose of the bacteria. Furthermore, the dominance of phage-resistant variants due to the bactericidal selective mechanism occurs rarely in natural settings, and the emerging variants are thus unable to sustain the ongoing epidemic.
Rotavirus strains not covered by licensed vaccines are increasing.
Approximately 20,000 stool specimens from patients with diarrhea visiting an urban and a rural hospital in Bangladesh during January 2001–May 2006 were tested for group A rotavirus antigen, and 4,712 (24.0%) were positive. G and P genotyping was performed on a subset of 10% of the positive samples (n = 471). During the 2001–2005 rotavirus seasons, G1P (36.4%) and G9P (27.7%) were the dominant strains, but G2 and G12P were present in 15.4% and 3.1% of the rotavirus-positive patients, respectively. During the 2005–06 rotavirus season, G2P (43.2%) appeared as the most prevalent strain, and G12P became a more prevalent strain (11.1%) during this season. Because recently licensed rotavirus vaccines are specific for only P, these vaccines may not perform well in settings where non-P types are prevalent.
Group A rotavirus; diarrhea; genotype; G12P; G2P; Bangladesh; research