Day: 08/14/2010

David Payne on Florence Nightingale

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David Payne Today, 100 years ago, Florence Nightingale died aged 90. Much has been written about the Lady with the Lamp, who left behind her aristocratic life to nurse wounded soldiers in the Crimea, returning to London to help found the modern nursing profession, campaign for sanitary reform and hospital design, and hone her skills as a statistician, before retiring to her bed with brucellosis.

Sixteen years ago I met Sybylla Bonham Carter, a cousin of Nightingale’s and the last person alive to have met her. Then in her 90s and up in London for the day from her home in Sonning Common, Berkshire, she vividly remembered a childhood walk with her father across Hyde Park to her cousin’s home in South Street, Mayfair. It was the briefest of meetings and cousin Florence by that stage was very deaf, but it inspired Sybylla to become a wartime nurse, as many upper class women then did.

Bloombsuryite Lytton Strachey was the first Nightingale biography to debunk the Lady with the Lamp myth in Eminent Victorians and detect something “less agreeable” in her character. I once read a history of the St Thomas’ Hospital Nighintgale Nursing School where she described the Nightingale nurses as “loud and nasty.” Nightingale wrote for the BMJ twice. The last time was an editorial about the late Mrs Wardroper, matron of St Thomas’ Hospital, in 1893.  A colleague who located it last year was struck by its pompous tone. Florence also graced the BMJ’s front cover in its 2008 Christmas edition.

In May this year the newly refurbished Nightingale Museum hosted an exhibition which highlights the role of Edinburgh surgeon John Sutherland, who worked with her in the Crimea but whose role has gone largely unrecorded. Sutherland had an uneasy relationship with the Lady with the Lamp, urged her to be “more perceptive and less doctrinal” when he offered feedback on an early version of her Notes on Nursing, and once described himself as overworked and abused…one of your wives.” He also advised her on how to win over Queen Victoria.

But when he died in 1891, Nightingale said of him in a letter to The Times: “I was his pupil both in sanitary administration and practice and am anxious for my master’s fame.”

Nightingale’s single minded determination is understandable. She resisted family and society’s presure to marry and incurred the anger of her family by wanting to become a nurse, but she followed God’s calling (he spoke to her four times, she claimed) and transformed the profession’s reputation. In 1907 became the first woman to be awarded the Order of Merit.

In recent times her life and reputation have been subject to constant comparisons with Mary Seacole, who nursed soldiers also during the Crimea, but whose “forgotten” status is attributed to racism. Seacole’s contribution pales in comparison to Nightnigale’s who utlimately used her superior social position and family connections to grab the attention of government ministers.

I think Mark Bostridge, Nightingale’s most recent biographer, was right to explain why she took steps to distance herself from Seacole’s legacy.  This isn’t to downplay Seacole’s role. Nightingale didn’t need to trade on her connections. She could have returned to a life of tranquility following the Crimea, but chose not to. She was an inveterate letter writer, even from her sickbed.

David Payne is editor, bmj.com and doc2doc.bmj.com

Direct deposition of micro- and nanoscale hydrogels using Dip Pen Nanolithography (DPN)

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Dip Pen Nanolithography® (DPN™) is the controlled delivery of material from nanoscale tips to a surface. Its advantages over other lithography techniques include low operating costs, high resolution, nanoscale registry and multiplexed deposition capabilities. With NanoInk’s latest nanolithography tools and new biocompatible patterning protocols, any scientist can easily and rapidly create arbitrary hydrogel patterns with subcellular feature sizes to be used for cell adhesion, cell migration and drug delivery studies.

DPN is a technique in which multiple materials are patterned onto a surface using nanoscale tips1. NanoInk’s nanolithography tools offer several important advantages over other instruments that rely on more conventional lithography techniques. DPN instruments can reproduce virtually any feature that can be created using high-cost clean-room equipment, all at ambient temperature and pressure. Such conditions are essential for creating substrates that are permissive to cell culture. With tip-based nanolithography, biocompatibility need not be sacrificed to achieve nanoscale precision and registry2.

The NLP 2000 System is NanoInk’s latest DPN instrument (Fig. 1a). It is designed specifically for researchers interested in creating complex, multicomponent substrates for use in biological experiments. The system is designed to control the leveling and translational positioning of multiple nanoscale tips. The tips are loaded with printing materials using NanoInk’s microfluidic chips, or ‘Inkwells’, as shown in Figure 1b. The figure is a combination of two images, one of an Inkwell filled with four different dye-labeled protein solutions and the other a top-down view of NanoInk M-type cantilever tip arrays. They are shown together to demonstrate how each tip lines up with a microchannel, enabling simultaneous loading of separate materials on each tip. After dipping into the Inkwells, the tips can be moved over to a surface, where they will transfer controlled amounts of the desired material, creating features as small as 50 nm and as large as 5 μm. The technique is analogous to multiple pens being used in a printing process—hence the name ‘dip pen nanolithography’. Figure 1c is a fluorescence image showing the multiplexed deposition of four different proteins. The figure demonstrates that even when submicron feature size is not required (the scale bar is 10 μm), the nanoscale precision of the NLP 2000 System’s translation stages is essential for the creation of well-ordered patterns.

Nanoprobes of Cell Potential

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Direct electrical measurements of cell potentials usually face design compromises. Microelectrodes probe within the cytosol of cells but have a minimum size (hundreds of nanometers in width) for obtaining useful signals. Nanoscale field effect transistors (FETs) can have an active probe size of only tens of nanometers but generally allow only the outer cell potential to be measured. Tian et al. (p. 830) fabricated nanowires in which kinks could be introduced to create a sharp probe tip pointing away from the fabrication substrate. Coating the tip with a phospholipid bilayer allowed the probe to be inserted through the membranes of beating cardiac cells, where it could be used to follow temporal changes in cell potential.

Vitiligo: concise evidence based guidelines on diagnosis and management

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Vitiligo is a common disease that causes a great degree of psychological distress. In its classical forms it is easily recognised and diagnosed. This review provides an evidence based outline of the management of vitiligo, particularly with the non-specialist in mind. Treatments for vitiligo are generally unsatisfactory. The initial approach to a patient who is thought to have vitiligo is to make a definite diagnosis, offer psychological support, and suggest supportive treatments such as the use of camouflage cosmetics and sunscreens, or in some cases after discussion the option of no treatment. Active therapies open to the non-specialist, after an explanation of potential side effects, include the topical use of potent or highly potent steroids or calcineurin inhibitors for a defined period of time (usually 2 months), following which an assessment is made to establish whether or not there has been a response. Patients whose condition is difficult to diagnose, unresponsive to straightforward treatments, or is causing psychological distress, are usually referred to a dermatologist. Specialist dermatology units have at their disposal phototherapy, either narrow band ultraviolet B or in some cases photochemotherapy, which is the most effective treatment presently available and can be considered for symmetrical types of vitiligo. Depigmenting treatments and possibly surgical approaches may be appropriate for vitiligo in selected cases. There is no evidence that presently available systemic treatments are helpful and safe in vitiligo. There is a need for further research into the causes of vitiligo, and into discovering better treatments.

How does the FDA use Advisory Committees to make decisions about drugs?

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When FDA faces important and challenging issues, the Agency often consults with one of its 49 technical and scientific Advisory Committees.  FDA’s Advisory Committees supplement the Agency’s internal scientific and medical expertise as well as provide a public forum for participation by other stakeholders (e.g., patients, health care providers, academia and industry).  Congress authorized the use of advisory committees in 1972 in the Federal Advisory Committee Act (FACA).  This law requires open, pre-announced meetings; public access to deliberations, records and documents; opportunity for the public to provide comments; fairly balanced membership; and the evaluation of conflicts of interest for certain members.  In general, the provisions of FACA apply when the government uses an outside group to provide advice and recommendations to a Federal official.

Typically, members of an FDA Advisory Committee are asked to meet with FDA officials to evaluate an FDA issue.  Often, the Committees vote on questions asked to them by FDA.  For instance, if research indicates a drug may be causing unexpected occurrences of liver failure, FDA may ask members of the Advisory Committee to study that research and then offer their views as to whether they believe the drug should be withdrawn from the market, kept on the market with new labeling and/or restrictions, or kept on the market without new restrictions.  Importantly, although FDA values the input of its Advisory Committees, FDA is not obligated to follow the advice of the committees.  Ultimately, all final decisions are the responsibility of FDA.

FDA Says Lamotrigine Poses Risk for Aseptic Meningitis

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Lamotrigine (Lamictal), used to treat seizures in children and bipolar disorder in adults, is associated with an increased risk for aseptic meningitis, the FDA announced on Thursday.

Since the drug’s approval in 1994, the FDA has identified 40 cases of aseptic meningitis out of approximately 46 million lamotrigine prescriptions that were filled (1 case per 1.2 million prescriptions). Meningitis symptoms began between 1 and 42 days after starting the drug. Thirty-five of the 40 patients were hospitalized, and in 15 instances, symptoms quickly returned after patients resumed taking lamotrigine.

The agency recommends that if a patient taking lamotrigine develops meningitis symptoms, clinicians should consider discontinuing the drug if they can identify no other obvious cause of meningitis.

Acetaminophen Linked to Asthma in Adolescents

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Current acetaminophen use seems associated with asthma in adolescents, according to a cross-sectional study in the American Journal of Respiratory and Critical Care Medicine.

Researchers surveyed some 360,000 13- and 14-year-olds in 50 countries about their recent (within 1 year) use of acetaminophen and their experience of symptoms of asthma, rhinoconjunctivitis, and eczema. They found an exposure-dependent risk for current asthma symptoms, with an odds ratio of 1.43 for medium use (at least once yearly) and 2.51 for high use (at least once monthly) compared with no use. Similarly, rhinoconjunctivitis and eczema were associated with recent use.

Oxidant-induced airway inflammation and enhanced Th2 T-cell responses are potential mechanisms to account for these effects.

The authors caution that with their design, “it is not possible” to prove a causal association, and conclude that “randomized controlled trials are now urgently required to investigate this relationship further.”