Combinatorial nanoparticles for cancer diagnosis and therapy.

Nanotechnology when engineered together with biotechnology opens a fascinating field with applications in diverse areas such as drug targeting and delivery, medical imaging, biosensing, biomaterials and nanotechnology. Conjugating nanoparticles with biomolecules like QD-herceptin conjugates or QD-aptamer (Apt)-DOX conjugates provides many opportunities for improving many of the current challenges in cancer diagnosis and therapy. This paper reviews combinatorial nanoparticles designed and formulated for cancer imaging and therapy, including inorganic nanoparticles (quantum dots, iron oxide particles, gold nanoparticles and silica and carbon nanoparticles), polymeric nanoparticles (PLGA, PLGA-PEG, PAMAM), liposomes and lipid nanoparticles. These nanoparticles are multifunctional in nature and combine two or more functions like targeting, imaging and therapy. In this review, we have classified these combinatorial targeted nanoparticles into inorganic, polymeric and liposome based nanosystems.

Análisis fitofarmacológico de los frutos de Luffa acutangula para determinar su actividad antihepatotóxica / Phytopharmacological screening of Luffa acutangula fruits for its antihepatotoxic activity

Se examinó el extracto acuoso y etanólico (100 mg/kg) de Luffa acutangula Linn (frutos) para determinar la actividadantihepatotóxica en ratas druckrey mediante la hepatotoxicidad inducida por tetracloruro de carbono (CCl4)y paracetamol (PCM). Se demostró que el extracto posee un efecto hepatoprotector signifi cativo, ya que reduce losniveles séricos de transaminasas (SGPT y SGOT), fosfatasa alcalina (ALP) y bilirrubina. La signifi cativa actividadhepatoprotectora de Luffa acutangula es comparable a la de la silimarina, agente hepatoprotector estándar, lo quejustifi ca su uso en afecciones del hígado

The ethanolic and aqueous extract (100mg/kg) of Luffa acutangula Linn(fruits) was examined for antihepatotoxic activityin druckrey rats by inducing hepatotoxicity with Carbon tetrachloride(CCl4) and Paracetamol(PCM). The extracthas shown to posses signifi cant hepatoprotective effect by lowering the serum level of transaminases (SGPT & SGOT),Alkaline phosphatase (ALP) and bilirubin. The signifi cant hepatoprotective activity of Luffa acutangula is comparableto that standard hepatoprotective agent silymarin, which justify its use in liver affection

Investigation of an outbreak of Escherichia coli O157 infection caused by environmental exposure at a scout camp.

In May 2000 a scout camp was held on an agricultural showground in New Deer, Aberdeenshire. There were 337 campers at the event, comprising 233 cubs, scouts, and venture scouts, and 104 adults. The event was abandoned early because of heavy rainfall. Twenty campers who became ill between 28 May and 3 June were confirmed as having E. coli O157 infection. Preliminary investigation did not suggest a food vehicle but did indicate environmental exposure at the camp as a risk factor. Subsequent investigations supported the hypothesis that transmission of E. coli O157 was from the environment to cases by contaminated hands, either directly from hand to mouth, or via food. As a result of the investigation the Aberdeenshire Council and the Scout Association jointly prepared interim guidelines to reduce the risk of E. coli O157 infection at scout camps.

Isolated calf vein thrombosis: comparison of MR venography and conventional venography after initial sonography in symptomatic patients.

RATIONALE AND OBJECTIVES: The authors performed this study to compare magnetic resonance (MR) venography and conventional venography in the diagnosis of deep venous thrombosis (DVT) in the calf after sonography. MATERIALS AND METHODS: Sonography was performed in 595 patients who were suspected of having lower-extremity DVT. Patients with positive above-knee duplex sonograms, allergy to iodinated contrast material, renal insufficiency, or cardiac pacemakers and patients who were obese were excluded. The remaining 73 patients were asked to undergo MR venography and conventional venography. All studies were to be performed within 48 hours of the clinical diagnosis and according to standard clinical practice. Images were interpreted by radiologists who were blinded to the results of other modalities. Two separate analyses were performed: one in which conventional venography was used as the standard of reference, and one in which the presence of at least two positive studies for thrombus was considered diagnostic. RESULTS: Although 36 patients agreed to participate in the study, only 14 underwent MR venography and conventional venography within 48 hours of the clinical diagnosis. With use of any two positive studies for confirmation, acute DVT was diagnosed in three patients. Conventional venography depicted two of the three cases, whereas sonography and MR venography each depicted all three. The findings were concordant in only five of the 14 patients. CONCLUSION: Moderate discrepancy among modalities was demonstrated. This suggests radiologists should undertake comparisons among these three modalities for the detection of calf DVT. In patients with a high clinical suspicion, a second modality may be useful if the initial study is negative.

Public health management of an outbreak of group C meningococcal disease in university campus residents.

BACKGROUND: Increasing numbers of outbreaks of Group C meningococcal disease in teenagers and young adults led to a new policy in the UK in 1999 of vaccinating all new college students. The largest of these outbreaks involved seven students in one university, six of whom were from one hall of residence, and two of whom died. METHODS: Control of the outbreak involved close medical surveillance of resident students, mass chemoprophylaxis and vaccination, and wide dissemination of daily information bulletins. Investigation of the epidemiology of the outbreak involved searching for the network of close contacts between cases, a prevalence survey of carriage of meningogocci and a case control study of risk factors for carriage. RESULTS: Clinical cases could be linked by a discrete network of social contacts within the halls of residence, but the Group C epidemic strain (2a P1.5) was not detected in 454 students (upper 95% confidence interval 0.7%). Carriage of any meningococcal strain (19%) was associated with patronage of the campus bar (OR = 3.0, 0.99-9.1). CONCLUSION: Important factors in the control of the outbreak were rapid institution of mass chemopropylaxis and immunisation of residents, and involvement of student organizations in the dissemination of information about the disease and its control. The role of campus bars in dissemination of the carriage of meningogocci deserves further investigation.

Ascertainment of non-respiratory tuberculosis in five boroughs by comparison of multiple data sources.

The incidence of non-respiratory tuberculosis (TB) is known to be rising in many parts of the world. Examination of the ascertainment of non-respiratory TB in five Welsh boroughs by comparing multiple data sources showed that statutory notifications missed nearly half (38/81) of all cases over a period of 10 years, and illustrates an urgent need to improve surveillance.

A community outbreak of food-borne small round-structured virus gastroenteritis caused by a contaminated water supply.

In August 1994, 30 of 135 (23%) bakery plant employees and over 100 people from South Wales and Bristol in the United Kingdom, were affected by an outbreak of gastroenteritis. Epidemiological studies of employees and three community clusters found illness in employees to be associated with drinking cold water at the bakery (relative risk 3.3, 95%, CI 1.6-7.0), and in community cases with eating custard slices (relative risk 19.8, 95%, CI 2.9-135.1) from a variety of stores supplied by one particular bakery. Small round-structured viruses (SRSV) were identified in stool specimens from 4 employees and 7 community cases. Analysis of the polymerase and capsid regions of the SRSV genome by reverse transcription-polymerase chain reaction (RT-PCR) demonstrated viruses of both genogroups (1 and 2) each with several different nucleotide sequences. The heterogeneity of the viruses identified in the outbreak suggests that dried custard mix may have been inadvertently reconstituted with contaminated water. The incident shows how secondary food contamination can cause wide-scale community gastroenteritis outbreaks, and demonstrates the ability of molecular techniques to support classical epidemiological methods in outbreak investigations.

Immunotherapy of lepromin-negative borderline leprosy patients with low-dose Convit vaccine as an adjunct to multidrug therapy; a six-year follow-up study in Calcutta.

The present report, which describes management of lepromin-negative borderline leprosy patients with low-dose Convit vaccine, is an extension of our earlier study on the treatment of lepromatous leprosy patients with low-dose Convit vaccine as an adjunct to multidrug therapy (MDT). The test Group I, consisting of 50 lepromin-negative, borderline leprosy patients, were given low-dose Convit vaccine plus MDT. The control group II consisted of 25 lepromin-negative, borderline leprosy patients given BCG vaccination plus MDT and 25 lepromin-negative, borderline leprosy patients given killed Mycobacterium leprae (human) vaccine plus MDT. The control group III consisted of 50 lepromin-positive, borderline leprosy patients not given any immunostimulation but given only MDT. Depending upon the lepromin unresponsiveness, the patients were given one to four inoculations of the various antileprosy vaccines and were followed up every 3 months for 2 years for clinical, bacteriological and immunological outcome. All patients belonging to the test and control groups showed clinical cure and bacteriological negativity within 2 years. However, immunologic potentiation, assessed by lepromin testing and the leukocyte migration inhibition test (LMIT), was better in the test patients receiving low-dose Convit vaccine plus MDT than in the control patients receiving BCG vaccine plus MDT or killed M. leprae vaccine plus MDT or MDT alone. But the capacity of clearance bacteria (CCB) test from the lepromin granuloma showed poor bacterial clearance in the test patients. However, there was no relapse during 6 years of follow up. Two mid-borderline (BB) patients had severe reversal reactions with lagophthalmos and wrist drop during immunotherapy despite being given low-dose Convit vaccine.

Response to the discovery of two practising surgeons infected with hepatitis B.

Two surgeons (henceforth called A and B) working in neighbouring district general hospitals were found, on routine testing, to carry hepatitis B e antigen and therefore to be at high risk of transmitting infection. Neither surgeon gave a history of injury at work. The only exposure prone operations performed by surgeon A were 16 repairs of uncomplicated inguinal hernias. Two of the 16 patients were found to have acute hepatitis B. In contrast, 15 cases on whom surgeon B performed exposure prone orthopaedic procedures remained free of hepatitis B virus infection. The follow up protocol for the patients of the two surgeons differed in that all surgeon B's patients were immunised using an accelerated course of hepatitis B vaccine, which had not been offered to patients of surgeon A. The detection of two cases of hepatitis B among patients operated on by an infected surgeon illustrates the importance of evaluating the risk of exposure associated with particular procedures when deciding whether to check patients who may have been exposed to a high risk surgeon. Surgeon A had been vaccinated before arriving in the United Kingdom and this incident highlights the need to verify immunity after vaccination against hepatitis B virus.

Factors influencing regional myocardial contractile response to inotropic stimulation. Analysis in humans with stable ischemic heart disease.

BACKGROUND: We hypothesized that the response of a myocardial segment to maximal dobutamine reflects not only maximal blood flow but also tethering, metabolic, and beta-blocker status. METHODS AND RESULTS: Patients with stable ischemic heart disease (n = 27) had positron emission tomographic measurement of blood flow at rest and with adenosine, and echocardiography at rest and with dobutamine. Positron emission tomographic measurement of [18F]fluorodeoxyglucose myocardial distribution also was made. Adenosine blood flow in segments that contracted normally at peak dobutamine was similar to that of segments that became hypokinetic (1.06 +/- 0.72 versus 1.02 +/- 0.77 mL.g-1.min-1). Segments that became akinetic failed to augment blood flow (0.68 +/- 0.30 mL.g-1.min-1). Fluorodeoxyglucose-blood flow mismatch was more common in segments with abnormal wall motion at peak dobutamine (24 of 59, 41%) versus those that contracted normally (63 of 269, 23%; chi 2, 7.40; P < .01). In patients off beta-blockers, segments that contracted normally at peak dobutamine increased blood flow with adenosine (0.70 +/- 0.31 to 0.86 +/- 0.46 mL.g-1.min-1; P < .05), whereas those that became abnormal did not (0.63 +/- 0.24 to 0.65 +/- 0.19 mL.g-1.min-1; P = NS). Segments of patients on beta-blockers that contracted normally at peak dobutamine increased blood flow with adenosine (0.78 +/- 0.31 to 1.10 +/- 0.70 mL.g-1.min-1; P < .05), as did segments that became abnormal (0.74 +/- 0.34 to 1.06 +/- 0.82 mL.g-1.min-1; P = NS). However, segments adjacent to ones with abnormal wall motion at rest had higher frequency of abnormal response at peak dobutamine in groups on (48% versus 16%; chi 2, 14.1; P < .001) and off (51% versus 21%; chi 2, 10.9; P < .01) beta-blockers. CONCLUSIONS: Augmented contraction at maximal dobutamine depends not only on increased myocardial blood flow but also on tethering, metabolic, and beta-blocker status. Furthermore, impaired flow reserve does not preclude a normal response to maximal dobutamine, since blood flow need not increase greatly to meet demand.

Immunotherapy of far-advanced lepromatous leprosy patients with low-dose convit vaccine along with multidrug therapy (Calcutta trial).

This report describes a promising mode of treatment of lepromin-unresponsive, far-advanced, lepromatous (LL) leprosy patients with antileprosy vaccines as an adjunct to multidrug therapy (MDT). The Trial Groups included 50 highly bacilliferous, lepromin-negative, untreated LL patients. They were given MDT for 2 years. Of them, 30 patients were administered a mixed antileprosy vaccine containing killed Mycobacterium leprae of human origin plus M. bovis BCG. The remaining 20 patients were given M. bovis BCG. Depending on the severity of lepromin unresponsiveness, they were given one to six inoculations at 3-month intervals. Another 20 similar LL patients were taken in the Control Group. They were given only MDT for 2 years. From the start of the study, all patients belonging to the Trial and Control Groups were followed every 3 months for clinical, bacteriological and immunological outcomes. Within 2 years all 50 patients of the Trial Groups and 19 of the 20 patients of the Control Group became clinically inactive and bacteriologically negative. However, the clinical cure and the falls of the bacterial and morphological indexes were much faster in those patients receiving the mixed vaccine therapy than in those patients who were given BCG plus MDT or only MDT. The immunological improvements in the patients of the Trial and Control Groups were assessed by: a) lepromin testing at the beginning of the study and at 3-month intervals and also by b) the in vitro leukocyte migration inhibition (LMI) test at both the beginning and end of the study. As the patients were given more and more vaccinations, the incidence of lepromin conversion increased, more so in the patients receiving the mixed vaccine. Thus, 63%, 15% and 5% of the patients became lepromin positive in those patients receiving the mixed vaccine, BCG, and MDT only, respectively. Lamentably, the vaccine-induced lepromin positivity was temporary and faded away within several months. At the beginning of the study, the LMI test against specific M. leprae antigen was negative in all patients of both the Trial and Control Groups. After the end of the chemo-immunotherapy schedule, the LMI test became positive in 50% and 20% of LL patients receiving the mixed vaccine and BCG, respectively. None of the Control Group could show LMI positivity after completion of the MDT schedule. These results show that treatment of LL patients with the mixed vaccine and MDT could quickly reverse the clinical course of the disease, remove immunologic anergy in some patients, and induce a rapid decrease in the bacterial load in them.