Month: April 2011

Distribution pattern of HCV genotypes & its association with viral load

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Hepatitis C virus (HCV) has emerged as a leading cause of chronic hepatitis, liver cirrhosis and hepatocellular carcinoma worldwide. Genotyping and assessment of the viral load in HCV patients is important for designing the therapeutic strategies. Thus the present study was designed to determine the distribution pattern of HCV genotypes in chronic hepatitis patients and their association with the viral load and biochemical profiles.
Methods: Seventy one HCV RNA positive patients were included in the study. HCV genotyping was carried out by restriction fragment length polymorphism (RFLP) followed by the direct sequencing of the core region. Viral load estimation was carried out by Taqman real time PCR system.
Results: Sixty three per cent (45/71) of cases were infected with genotype 3 followed by genotype 1 in 30.98 per cent (22/71) and genotype 2 in 5.63 per cent (4/71) of cases. Genotype 1 was associated with a significantly (P<0.001) higher viral load as compared to genotypes 3 and 2. There was no significant difference seen in the biochemical profile between the three groups of genotypes except in the levels of SGOT. The commonest mode of transmission was parenteral which accounted for 68 per cent of all the infected cases.
Interpretation & conclusions: The present study revealed that HCV genotype 3 and 1 accounted for approximately 95 per cent of the HCV infection in Delhi and surrounding areas. Also two atypical subtypes like 3i and 3f were identified. Genotype 1 was associated with more severity of liver disease as compared to genotypes 3 and 2 as assessed by viral load.

source: IJMR

Vitamin D deficiency in healthy breastfed term infants at 3 months & their mothers in India: Seasonal variation & determinants

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Vitamin D deficiency with a resurgence of rickets and tetany are increasingly being reported in young infants from temperate regions, African Americans and also from India. The data on vitamin D status of healthy term breastfed Indian infants and mothers are scant. Therefore, we undertook this study to determine the prevalence of vitamin D deficiency and insufficiency [serum 25 hydroxyvitamin D (25OHD) < 15 ng/ml and 15-20 ng/ml, respectively] among healthy term breastfed 3 month old infants and their mothers, evaluate for clinical and radiological rickets in those infants having 25OHD
< 10 ng/ml, and check for seasonal variation and predictors of infants’ vitamin D status.
Methods: A total of 98 infants aged 2.5 to 3.5 months, born at term with appropriate weight and their mothers were enrolled; 47 in winter (November- January) and 51 in summer (April-June). Details of infants’ feeding, vitamin D supplementation, sunlight exposure and mothers’ calcium and vitamin D intake were recorded. Serum calcium, phosphate, alkaline phosphatase, 25 hydroxyvitamin D (25OHD) and parathormone were estimated.
Results: Vitamin D deficiency was found in 66.7 per cent of infants and 81.1 per cent of mothers; and insufficiency in an additional 19.8 per cent of infants and 11.6 per cent of mothers. Radiological rickets was present in 30.3 per cent of infants with 25OHD < 10 ng/ml. 25OHD did not show seasonal variation in infants but maternal concentrations were higher in summer [11.3 (2.5 – 31) ng/ml] compared to winter [5.9 (2.5-25) ng/ml, P=0.003]. Intake of vitamin supplement, sunlight exposure and mother’s 25OHD were predictors of infants’ 25OHD levels.
Interpretation & conclusions: Prevalence of vitamin D deficiency and insufficiency was found to be high in breastfed infants and their mothers, with radiological rickets in a third of infants with 25OHD < 10 ng/ml in this study. Studies with large sample need to be done in different parts of the country to confirm these findings.

source: IJMR

Recent developments in treatment of latent tuberculosis infection

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Latent tuberculosis infection (LTBI) can be detected with immune based tests such as the tuberculin skin test (TST) or interferon gamma release assays (IGRA). Therapy for those with positive tests can reduce the subsequent risk of re-activation and development of active TB. Current standard therapy is isoniazid (INH) which reduce the risk of active TB by as much as 90 per cent if taken daily for 9 months. However, this lengthy duration of therapy discourages patients, and the risk of serious adverse events such as hepatotoxicity, discourages both patients and providers. As a result completion of INH therapy is less than 50 per cent in many programmes. However, programmes that offer close follow up with supportive staff who emphasize patient education, have reported much better results. The problems with INH have stimulated development and evaluation of several shorter regimens. One alternative was two months daily rifampin and pyrazinamide; this regimen has been largely abandoned due to unacceptably high rates of hepatotoxicity and poor tolerability. The combination of INH and rifampin, taken for 3 or 4 months, has efficacy equivalent to 6 months INH albeit with somewhat increased hepatotoxicity. Four months rifampin has efficacy at least equivalent to 6 months INH but there are inadequate trial data on efficacy. The safety of this regimen has been demonstrated repeatedly. Most recently, a regimen of 3 months INH rifapentine taken once weekly under direct observation has been evaluated in a large scale trial. Results have not yet been published, but if this regimen is as effective as INH, this may be a very good alternative. However, close monitoring and surveillance is strongly suggested for the first few years after its introduction. Evidence from several randomized trials has shown that the benefits of LTBI therapy is only in individuals who are tuberculin skin test (TST) positive even among those with HIV infection. Hence, LTBI therapy should be given only to those with positive tests for LTBI. We conclude that LTBI therapy is considerably underutilized in many settings, particularly in low and middle income countries.

source: IJMR

Mortality in HIV infected individuals in Pune, India

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With the presence of HIV epidemic for more than two decades in India, rise in the number of HIV related deaths is expected. Data on mortality in HIV infected individuals from prospective studies are scanty in India. We report here data on mortality in a systematically followed cohort of HIV infected individuals at Pune, Maharashtra, India
Methods: A total of 457 HIV infected individuals were enrolled in a prospective study in Pune between September 2002 and November 2004. They were evaluated clinically and monitored for CD4 counts at every quarterly visit. Mortality data were collected from the records of hospital facilities provided by the study. If the death occurred outside such hospitals; relatives of the participants were requested to inform about the death.
Results: Median CD4 count in study participants was 218 cells/μl (95% CI: 107-373) at baseline. The median duration of follow up was 15 months (IQR: 12, 22). Mortality was higher in antiretroviral therapy (ART) naive patients compared to those who received treatment (16.59 vs. 7.25 per 100 person years). Participants above 35 yr of age, CD4 count less than or equal to 100 cells/μl at baseline, tuberculosis at any study time point and ART status were independently associated with high mortality [(RR=1.97; 95% CI: (1.23, 3.14), P=0.005, (RR=33.20, 95%CI (7.59, 145.29), P<0.001, (RR=2.38, 95% CI (1.38, 4.09),
P= 0.002 and RR=5.60, 95% CI (3.18, 9.86), P<0.001, respectively].
Interpretation & conclusions: High mortality at advanced immunosuppression highlights the importance of early detection of HIV infection. Emphasis needs to be given at timely diagnosis and management of tuberculosis and ART initiation. It is important to create awareness about availability of free antiretroviral drugs in the government ART roll out programme.

source: IJMR

How long does postpartum thyroiditis usually last?

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Postpartum thyroiditis — a painless inflammation of the thyroid gland that develops within the first year after childbirth — often lasts from several weeks to several months. For some women, postpartum thyroiditis leads to long-term underactive thyroid (hypothyroidism).

The cause of this uncommon condition isn’t known. You may be at increased risk of postpartum thyroiditis if you have an immune system disorder, type 1 diabetes or a history of thyroiditis.

At first, the release of thyroid hormone and the related inflammation may cause signs and symptoms similar to those of an overactive thyroid (hyperthyroidism), including:

  • Anxiety
  • Irritability
  • Rapid heartbeat or palpitations
  • Unexplained weight loss
  • Increased sensitivity to heat

A diagnosis of hyperthyroidism can be confirmed with blood tests. Treatment generally isn’t needed for mild signs and symptoms. If necessary, beta blockers may help reduce signs and symptoms — although beta blockers aren’t recommended for women who are breast-feeding.

Later, as thyroid cells become impaired by the inflammation, signs and symptoms of hypothyroidism may develop, including:

  • Fatigue
  • Weakness
  • Unexplained weight gain
  • Increased sensitivity to cold

As with hyperthyroidism, a diagnosis of hypothyroidism can be confirmed with blood tests. Treatment generally isn’t needed for mild signs and symptoms. If signs and symptoms are severe, thyroid hormone replacement therapy may be prescribed.

For the majority of women, thyroid function eventually returns to normal. However, some women who develop postpartum thyroiditis develop hypothyroidism and require lifelong thyroid hormone replacement therapy. Because hypothyroidism presents a significant risk to developing babies, it’s important to make sure the condition is under control before attempting another pregnancy.

source: mayo clinic

Virus-specific mechanisms of carcinogenesis in hepatitis C virus associated liver cancer

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The development of hepatocellular carcinoma (HCC) in persons who are persistently infected with hepatitis C virus (HCV) is a growing problem worldwide. Current antiviral therapies are not effective in many patients with chronic hepatitis C, and a greater understanding of the factors leading to progression of HCC will be necessary to design novel approaches to prevention of HCV-associated HCC. The lack of a small animal model of chronic HCV infection has hampered understanding of these factors. As HCV is an RNA virus with little potential for integration of its genetic material into the host genome, the mechanisms underlying HCV promotion of cancer are likely to differ from other models of viral carcinogenesis. In patients persistently infected with HCV, chronic inflammation resulting from immune responses against infected hepatocytes is associated with progressive fibrosis and cirrhosis. Cirrhosis is an important risk factor for HCC independent of HCV infection, and a majority of HCV-associated HCC arises in the setting of cirrhosis. However, a significant minority arises in the absence of cirrhosis, indicating that cirrhosis is not a prerequisite for cancer. Other lines of evidence suggest that direct, virus-specific mechanisms may be involved. Transgenic mice expressing HCV proteins develop cancer in the absence of inflammation or immune recognition of the transgene. In vitro studies have revealed multiple interactions of HCV-encoded proteins with cell cycle regulators and tumor suppressor proteins, raising the possibility that HCV can disrupt control of cellular proliferation, or impair the cell’s response to DNA damage. A combination of virus-specific, host genetic, environmental and immune-related factors are likely to determine the progression to HCC in patients who are chronically infected with HCV. Here, we summarize current knowledge of the virus-specific mechanisms that may contribute to HCV-associated HCC.

source: oncogene nature

FDA: Hand Sanitizers Make False Claims

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Sanitizers Overstate Germ-Killing Claims; Don’t Kill MRSA, E. coli, Flu

Hand sanitizers protect us from germs, don’t they? A new FDA initiative has consumers confused.

The FDA yesterday warned consumers not to buy hand sanitizers “that claim to prevent infection from MRSA, E. coli, salmonella, flu, or other bacteria or viruses.” But isn’t that why we use them?

An FDA spokesperson tells WebMD that consumers should continue to follow CDC advice to use hand sanitizers when water is not available.

The CDC advice specifically says alcohol-based hand sanitizers help protect against MRSA and other germs. During flu season, the CDC continually warns Americans to prevent flu by using hand sanitizers when soap and water aren’t around.

So what’s the FDA’s problem with hand sanitizers?

The FDA points to four companies whose products, it says, are in violation of FDA regulations. Each of these products specifically claims to kill MRSA, staph, or other bacteria or viruses:

  • Staphaseptic First Aid Antiseptic/Pain Relieving Gel from Tec Laboratories
  • Safe4Hours Hand Sanitizing Lotion and Safe4Hours First Aid Antiseptic Skin Protectant from JD Nelson and Associates
  • Dr. Tichenor’s Antiseptic Gel from Dr. G.H. Tichenor Antiseptic Co.
  • CleanWell All-Natural Foaming Hand Sanitizer, CleanWell All-Natural Hand Sanitizer, CleanWell All-Natural Hand Sanitizing Wipes, and CleanWell All-Natural Antibacterial Foaming Handsoap from Oh So Clean Inc. (doing business as CleanWell Company).

But what about other products? The label of a very popular 62% ethyl alcohol hand sanitizer says “Kills 99.99% of Germs.” The product web site stresses that it “kills” the bad germs on your hands.

The FDA’s rule on the question is a “tentative final monograph” (a confusing term itself) published in June 1994. It says that makers of over-the-counter antiseptic products may claim only that they “help reduce bacteria that potentially can cause disease.” They may not claim a product “kills micro-organisms.”

FDA spokesperson Shelly Burgess tells WebMD that the FDA is sending warning letters only to the four firms listed above.

“FDA has not approved any products claiming to prevent infection from MRSA, E. coli, Salmonella, or H1N1 flu, which a consumer can just walk into a store and buy,” Deborah Autor, FDA compliance director, says in a news release. “These products give consumers a false sense of protection.”

Here’s the bottom line: Don’t count on hand sanitizers for 100% protection from anything. Do wash your hands often. And when you can’t wash your hands, do use hand sanitizers. Even the FDA agrees they get rid of a lot of the germs that are on your hands.

source: FDA

Turning stem cells into neurons without tumors growing

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Scientists have created stem cells that could turn into many types of neuron, without the risk of tumors developing in laboratory mice. University of California at San Diego professor Kang Zhang created self-renewing neural stem cells that can produce a steady supply of stem cells – which could one day be used to treat a number of diseases ranging from eye diseases to Parkinson’s disease.

While human embryonic stem cells can grow into any cell and regenerate damaged cells and tissue, stem cell therapy hasn’t exactly lived up to its promise. One of the major setbacks, as seen in animal models, occurs when stem cell injections result in tumor growth. The problem here is this: What is the purpose of curing one disease to replace it with another, more serious ailment?

With the right mix of chemicals, the stem cells were able to grow into precursor cells and remained in limbo in an intermediate stage until they were directed to grow into mature neurons. What’s more, growing the stem cells this way enabled Zhang to create millions of neural stem cells in less than a week.

Since the cultures didn’t require any animal products or gene transfer, the stem cells remained rather pure. According to 10News.com:

Two years ago, 40 mice were injected with stem cells at the laboratory. Six months later, all 40 mice developed some sort of tumor.

But after using the research from UC San Diego, 40 additional mice were recently injected with stem cells. Now, six months and even a year later, none of the mice developed a single tumor.

Zhang told SmartPlanet that he is interested in creating eye-specific neurons to repair the ones lost in degenerative diseases like macular degeneration. But he adds that it might be possible to regenerate motor neurons lost in spinal cord injuries, and repair those lost in Lou Gehrig’s disease and Parkinson’s disease.

In the future, Zhang will see if stem cells can treat neurodegenerative diseases, such as macular degeneration or glaucoma.

source: IBM smart planet

Japanese researchers devise laser ’spark plugs’

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The  new laser system invented by Japanese researchers could displace the venerable design of spark plugs, which has stood virtually unchanged for the past 150 years.

An inter-university team of researchers at Japan’s National Institutes of Natural Sciences, or (NINS), will be demonstrating a multi-beam laser system at the Conference on Lasers and Electro-Optics next week in Baltimore.

The system promises to improve fuel economy and reduce emissions of smog causing nitrogen oxides. It ignites an engine’s air-fuel mixture more efficiently and further down within the cylinder, burning more air and less fuel.

“Timing–quick combustion–is very important. The more precise the timing, the more efficient the combustion and the better the fuel economy,” NINS researcher Takunori Taira said in a prepared release.

Traditional spark plugs are an electrical device that works by igniting the compressed fuel nearest to the cylinder head with jolts of high voltage electricity. They are also a proven technology that doesn’t cost much to produce.

Taira said that the team’s system could be inexpensively mass-produced, having overcome the size limitations of traditional laser designs by making composite lasers from ceramic powders.

“Ceramics are easier to tune optically than conventional crystals. They are also much stronger, more durable, and thermally conductive, so they can dissipate the heat from an engine without breaking down,” a NINS press release stated.

I’m wondering how much more incremental cost this will add to vehicles, and whether existing engines could be retrofitted. It would also be interesting to see how much more reliable lasers will be in extremely cold weather.

There is room for innovation in the design of internal combustion engines, because they aren’t going to be phased out any time soon. If Edison’s lightbulb can become outmoded, so can the spark plug. It’s technology – not a religious relic.

Some automotive blogs appear to be skeptical of the technology, but if new thinking can reduce emissions at a reasonable cost, it should be taken seriously – even if it means bidding farewell to a 150 year old design.

source: IBM smart planet

Zoonotic Leprosy in the U.S.

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Detailed genetic analysis of Mycobacterium leprae isolates from wild armadillos and human patients suggests that leprosy may be a zoonosis in the southern U.S.

Despite suspicion that some leprosy patients in the U.S. might have acquired their disease from armadillos, causality has not been proven. To further explore this possibility, investigators performed an ecologic cohort study that involved skin-biopsy specimens from 50 leprosy patients who lived in the southern U.S. and tissue samples from 33 wild armadillos from the same geographic region.

Whole-genome sequencing, single nucleotide polymorphism typing, and variable-number tandem-repeat analysis were used to molecularly characterize the Mycobacterium leprae strains isolated from these samples.

One genotype, labeled 31-2-v1, appeared to be unique and highly distinctive and was significantly associated with a history of residence in regions where infected wild armadillos have been found (P<0.001). This genotype was recovered from 28 of 33 armadillos and from 25 of the 39 patients who lived in regions where exposure to infected armadillos was possible; the genotype has not been reported from anywhere else in the world. There was some suggestion that contact with an armadillo might increase the likelihood of infection with this unique strain (odds ratio, 4.0; 95% confidence interval, 0.5–35.8).

Comment: The results of this in-depth strain analysis are intriguing and should encourage additional activities to confirm the impression that zoonotic leprosy occurs in the southern U.S.

Source: Journal Watch Infectious Diseases