Cloaking the Arc with a Coat of Many Colors
Despite all the attention being paid to tank flammability reduction via inerting, we shouldn’t forget that TWA800 was a wiring initiated fuel-tank explosion. Could there be a simpler and more cost effective method of preventing aircraft electrical fires and fuel-tank explosions?
TWA800 and Swissair have both focused the attention of aviation authorities, airlines, crew and passengers on serious electrical malfunctions emanating from wiring with a record of in-service deterioration. In the case of the earlier ValuJet Flight 592 crash, the NTSB found that “jostled oxygen canisters” ignited. There’s also been persuasive anecdotal evidence that the fire was caused by faulty wiring. If VJ592 had happened after TWA800, would a finding against wiring have been more likely?
It all begs the question: why this abiding concern over aircraft wiring? What are the causes of the fires, and how do they propagate to cause such horrific accidents? Without delving too deeply into the technical specifications of different aircraft wiring types, because it is a very intricate and technical field, we can generalize. There are complex criteria that dictate the optimum wiring insulation for different applications–e.g., insulation resistance, dielectric strength, vibration resistance, fluid resistance, chemical inertness, smoke generation , weight, manufacturing and installation requirements, ease of handling, min. radius, topcoat flaking, etc.). Environmental conditions differ in certain areas of an aircraft and so wire- types with differing characteristics are required. At this stage of wiring technology no unique wire type meets all the necessary criteria. However, the high frequency vibration of flight can cause wiring to “strum” like a guitar string and so chafing is a major concern for all types. This aspect and insulation cracking are of paramount importance.
After TWA800, all parties agreed that high time aircraft, especially pre- 1992 constructs, were more likely to have a fire due to their aging wire (most 737s and 757s, post-1992, are fitted with Boeing’s designedly safer TKT wiring). Aging wire is susceptible to nicks, cracks and the chafing of its insulations, all of which generate daily smoke emergencies. Aromatic polyimide (DuPont’s Kapton, BMS13-51) and X-linked ETFE Polymers (Tefzel BMS 13-48, Raychem’s wire) were two wire-types that had exhibited age degradation. Cuts, nicks, cracks and chafing could cause the insulation to be breached (cracked into the conductor), raising the possibility of electrical arcs (short circuits) and arc-tracking.
Arcs And Arc-Tracking
An arc will occur when a powered conductor contacts a ground potential. This happens if the insulation has been compromised by rubbing against the airframe (chafing), or by wire-to-wire abrasion. Arcing will result in a high current flow which should actuate the applicable circuit-breaker (CB) or fuse. However, arc-tracking is a phenomenon whereby an electrical arc between two or more damaged wires sustains itself through a conductive path provided by degradation of the insulation for a measurable length. It is produced by leakage current, and the associated heat effect of the arc, which locally decomposes the wire insulation material into carbon residues and gasses. If simultaneous conditions are present , the low resistance carbon path may allow the current to flow between the conductors, sustaining the arcing along the wire . Because the current is flowing and not going to ground, the CB may not trip.
Conditions For Arc-Tracking
To initiate arc-tracking:
* At least two wires separated by a small distance with insulation at least cracked to the bare metal.
* An initial short circuit-condition.
* A high voltage through the wire.
* A current sufficient to sustain an arc. The presence of an electrolyte or conductive fluid on or in the immediate vicinity of the damaged wires can accelerate the carbonization and cause the more explosive flashover of wet arc- tracking.
Arc-Tracking Limitations
A laboratory can easily reproduce the phenomenon. When concurrent conditions are met along a measurable length, the arc will move along the concerned wires towards the power source, until it is stopped–i.e., when one of the concurrent conditions disappears. Or,
*The current value sustaining the arc reaches circuit-breaker tripping threshold.
* The conductors (core) of the wires come into direct contact.
*It encounters a connection ; a bundle attachment; or a bulkhead pressure seal.
* There is a divergence of the affected wires within the bundle layout.
It is not just the actual electrical arc and the possibility of arc- tracking that is the only risk. The insulation can also ignite and while still burning, drip onto thermal-acoustic blankets, leaked hydraulic fluid, dust, etc., and set them alight. This is also true in the case of the actual conductor. Beads of molten metal are an indication that arcing has occurred. In 1999, Tim Dobbyn of Reuters wrote, “All aircraft wiring ages, and it is not uncommon to find five to 10 insulation cracks per 1,000 feet of wire in active aircraft, a congressional subcommittee heard Wednesday”. A Boeing 747 features approximately 140 miles of wiring, which translates into 7,390 wire cracks.
Valeriana wallichii DC, a New Chemotype from Northwestern Himalaya
The major constituents of the oils from roots and rhizomes of Valeriana wallichii DC were separated and characterized by GC, GC/MS and NMR (^sup 1^H- and ^sup 13^C-). The chemical compositions of the oils show two chemotypes within Valeriana wallichii. The type-I was characterized by presence of maaliol (64.3%), viridiflorol (7.2%) and sesquiterpene hydrocarbons (19.2%). The type-II contained patchouli alcohol (40.2%), viridiflorol (5.2%), 8-acetoxy-patchouli alcohol (4.5%) and sesquiterpene hydrocarbons (34.5%). Viridiflorol and 8-acetoxy-patchouli alcohol have been isolated from V. wallichii for the first time. Since the V. wallichii is being commercially used even today in Nepal and India as a substitute for V. officinalis, the sharp chemical differences among V. wallichii materials necessitates their identification before commercial exploitation for phytomedicines and flavor chemicals.
Valeriana wallichii, Valerianaceae, chemotypes, essential oil composition, maaliol, viridiflorol, patchouli alcohol, 8-acetoxy-patchouli alcohol.
Valeriana wallichii DC, Indian Valerian, has been an ingredient of herbal medicines in Indian systems of medicine and is used as a substitute of European Valeriana officinalis in India. Survey and collection of V. wallichii DC from the northwestern Himalayan region showed morphologically similar but chemically distinct essential oil compositions. Valeriana wallichii grows in the northwestern Himalaya and has long been used in Ayurveda and Unani systems of medicine , which describes its use in the treatment of obesity, skin disease, insanity, epilepsy and snake poisoning. The crude drugs from the roots/rhizomes and Valerian derived phytomedicines are used as mild sedatives in pharmaceutical industiy. The roots/rhizome parts are highly aromatic and as a result Valerian oil is in great demand.
The pharmacological activity of Valerian is believed to be due to two major groups of constituents-the valepotriates and sesquiterpenoids. According to the European Pharmacopoeia, the crude drug Valerianae radix must contain not less than 0.5% (v/w) of essential oil. Earlier reports on V. wallichii root oil indicate wide variations in their chemical compositions and the major terpenoids reported include sesquiterpene hydrocarbons , valeranone, cryptomeridiol, maaliol, xanthorrhizzol, patchouli alcohol, etc.
As part of work on Himalayan Valenana species we have reported the chemical composition of the essential oils from the leaves and roots of V. wallichii
(5) and had earlier observed compositional variations (4). We now report herein the existence of two chemically distinct species within V. wallichii with no mixed populations.
Experimental
Plant material: Valeriana wallichii were collected from various natural habitats in Nainital, Pithoragarh, Almora, Chamoli, Rudraprayag districts of northwestern Himalayan region situated at different micro-climatic regions of Uttaranchal at three different stages of growth from March to October. The materials were also collected from different locations of Nepal. Plant materials were identified from Botanical Survey of India, Dehradun. Voucher specimens were deposited in the phytochemistry lab of chemistry department, Kumaun University.
Isolation of oil: Various collections of fresh roots of 2 kg each were steam distilled using copper still fitted with spiral glass condensers for 2 h obtaining 5 L water distillate. The distillate saturated with NaCl was extracted with hexane. The organic phase was dried over anhydrous Na^sub 2^SO^sub 4^ and the solvent was distilled off to yield the essential oil.
GC and GC/MS: The oils were analyzed by using Varian Vista 6000 and Thermoquest Trace GC 2000 interfaced with Finnigan MAT Polaris Q Ion trap Mass spectrometer fitted with RTX-5 MS fused silica capillary column . The column temperature 60°-210°C was programmed at 3°C/min using He as carrier gas at 1.0 mL/min. The injector temperature was 210°C, injection size 0.1 µL, prepared in hexane, split ratio 1:40. MS were taken at 70 eV with mass range of m/z 40-450. Characterization was done on the basis of retention index, Library MS Search, by comparing with the mass spectral literature data (8) and NMR of major isolates.
Fractionation/isolation of major constituents: The oils were fractionated by column chromatography on silica gel packed in hexane and eluted with hexane followed by hexane-Et^sub 2^O mixtures. A total of 50 fractions were collected . Fractions eluted in 15-25% ether in hexane gave four compounds - A, B, C, D - which were purified by HPLC on µ-Porasil column . The specific rotation and ^sup 1^H- and ^sup 13^C-NMR spectra of compounds A, B, C, D were measured. It was observed that there were no qualitative changes in composition except minor variations in the concentration of constituents during different stages of growth of the plant.
Interaction of the excited singlet state of neutral red with aromatic amines
Quenching of neutral red fluorescence by a number of aromatic amines has been investigated in acetonitrile solutions. The bimolecular quenching constants (k^sub q^) obtained from steady-state and time-resolved measurements for a particular donor-acceptor pair are seen to be the same within experimental error. Correlation of the changes in the k^sub q^ values with the oxidation potentials of the donors (amines) indicates that electron transfer (ET) is the mechanism operative in the present systems. Direct evidence for ET has been obtained from picosecond transient absorption studies on a suitable amine-NR pair. Experimentally determined k^sub q^ values are seen to correlate well with the free energy changes for the ET reactions, within the framework of the Marcus outer sphere ET theory. From the correlation between the experimentally determined and theoretically calculated k^sub q^ values, it appears that solvent reorganization plays a major role in governing ET dynamics in the systems investigated.
The importance of electron transfer (ET)^ reactions in chemistry and biology is well established . Normally ET from a ground-state donor (D) to a ground-state acceptor (A) is energetically not favorable. However, photoexcitation of either the D or the A, often makes the ET reaction proceed within reasonable rates, as the energy acquired during the photoexcitation process adds to the overall energy changes for the ET reactions making it energetically favorable . Over the last few decades, significant developments have taken place in both theoretical and experimental aspects of photoinduced electron transfer (PET) processes. This topic has emerged as an exciting area in chemical physics and has a variety of practical applications.
The presence of electron-donating amino or substituted amino groups in a molecule generally makes it a good electron donor. Thus the ET reactions with amines as electron donors are almost always very facile. The ET reactions from aliphatic and aromatic amines to suitable acceptors have been studied by many workers under both diffusive and nondiffusive conditions in a wide range of time scales.
Neutral red (NR) is a phenazine-based dye having applications in biological systems. Due to the nontoxic nature of NR, the dye has been extensively used for staining cellular particles . The dye is also used as an intracellular pH indicator due to its strong pH-dependent color changes . Neutral red is a good photodynamic photosensitizer . The NR-sensitized electron transport in liposome systems has also been the subject of intense investigation . Neumann and coworkers have reported the photoreduction behavior of another phenazine-based dye, Safranine, that is structurally similar to NR. In the recent past we have carried out detailed investigations on the photophysical and photochemical properties of NR in different solvents to understand the role of solvent polarity and other specific interactions, like hydrogen bonding, on the photophysical and photochemical behavior of the dye . Because the phenazine and its derivatives are reasonably good electron acceptors, in the present work our motivation was to investigate the nature of the interaction of the excited (SI) NR with a number of amine donors. We used both steady-state (SS) and time-resolved JR) fluorescence quenching techniques as well as picosecond transient absorption studies to understand the nature and the extent of the interaction of the excited NR with a number of aromatic amines. Chemical structures of NR.
Testing the additivity assumption: chemical mixtures and thyroid function
It is well established that many environmental contaminants can disrupt thyroid hormone (TH) homeostasis, which is vital during fetal development and for a variety of physiological processes in adults. Among known TH disruptors are polychlorinated biphenyls (PCBs), dioxins, and dibenzofurans, all members of the polyhalogenated aromatic hydrocarbon (PHAH) chemical family. Little is known, however, about how mixtures of such chemicals at typical environmental exposure levels may disrupt TH functions. Nor is it clear whether effects are additive, synergistic, or antagonistic–that is, whether there is interaction between constituent chemicals, whether their cumulative influence is more than the sum of its parts, or whether they cancel each other out. With respect to risk assessment, the U.S. Environmental Protection Agency’s default assumption is that the effects of chemicals in mixtures are additive.
Over a four-day period the team exposed young female rats to six different doses of a combination of 18 PHAHs comprising 2 dioxins, 4 dibenzofurans, and 12 PCBs. The team determined dose-response information for each constituent chemical before the mixture was tested. The concentration of each chemical in the mixture reflected typical concentrations measured in breast milk and in fish and other foods. The mixture was also formulated so that even at the highest mixture doses, the rats’ exposure to each constituent chemical was at or below the known no-observed-effect level for that chemical.
The mixture reduced the rats’ serum thyroxine in a dose-dependent manner. At lower doses the effects were additive. At higher doses declined by as much as 50%, and the effects were mildly synergistic–about twice what was predicted by additivity–so that even in the upper range the effects as predicted by the additivity hypothesis came close to actual results.
Significantly, the study also showed that the mixture exerted an effect on [T.sub.4] even though concentrations of its constituent chemicals were at least an order of magnitude below their known effective doses. This indicates that considering individual chemicals in isolation may not predict their effects in mixtures because, even though chemicals may not be potent enough by themselves to cause effects, the cumulative effects of low doses of many chemicals may be enough to do so.
The multiple functions of TH, such as its role in fetal development and its regulation of metabolism and heart rate, make it vulnerable at many points. The team estimates that there could be as many as five distinct mechanisms by which chemicals exert antithyroid effects for which a reduction in circulating [T.sub.4] is the common end point.
Several factors temper the study results. One is that this study was a series of short-term exposures that did not encompass all the chemicals’ varied half-lives. The results therefore cannot be directly extrapolated to the effects of chronic exposures and may be subject to confounding by pharmacokinetic differences. Another is that thyroid disruption mechanisms in rats may not be identical to those in humans. The team is now working on testing how a more complex chemical mixture may interact with dietary iodine insufficiency to produce thyrotoxic effects.
A Burning Dilemma - dangers of aromatic candles
The same health-conscious homeowner who would never dream of allowing cigarette smoke
inside the house might be burning aromatherapy candles with the idea that they promote a
healthy, relaxing atmosphere. But burning candles could actually have the opposite effect:
Scientific testing has shown that candles can emit pollutants such as acetone, benzene,
lead, soot and particulate matter.
Cathy Flanders of Plano, Texas found out the hard way that candles can cause indoor air
pollution. Flanders experienced a phenomenon known as “black soot deposition” after burning
candles sold by a popular retailer. “Things started looking gray to me,” Flanders says.
“There was a dark film around electrical outlets, the refrigerator, the air conditioning
vents and on plastic materials such as computer screens.”
Ron Bailey, vice president of Bailey Engineering Corporation, was commissioned to
investigate the Flanders’ home. Testing revealed that burning aromatic candles were
releasing significant quantities of soot and volatile organic compounds. The core wicks of
the candles were found to be made of lead.
The Flanders aren’t alone in their experience. Testing has implicated candles in a number of
cases of black soot deposition in homes and student dormitories across the country. “We’ve
had at least three people who talked about waking up with a black ring around the nostrils,”
says Bailey. “One was sleeping with a surgical mask because she had noticed the problem, and
didn’t know where it was coming from.”
The National Association of Home Builders (NAHB) has been receiving an increasing number of
reports about black soot deposition. Dan Cautley, an NAHB Research Center engineer, says a
prime suspect is the increased use of candles and other indoor combustible materials
including incense, potpourri and oil lamps.
“Since seven out of 10 homes burn candles on a regular basis, according to a study done by
Smith and Kline, this issue is extremely far-reaching and has the potential for affecting
millions of homes,” states an NAHB bulletin.
According to Ken Giles, spokesman for the U.S. Consumer Products Safety Commission (CPSC),
any product that is combusted indoors can create indoor air quality problems–including
wood-burning stoves, fireplaces, and natural gas or kerosene appliances not properly vented.
Only recently have candles also become a concern. “We hear that many lower-quality candles
being manufactured now produce more soot than 20 years ago,” says Cautley. “This has to do
with different types of waxes, aromatic oils and wick types. If the wick doesn’t burn at the
same rate the wax disappears, the wick will get longer and typically, the candle will
produce more soot.”
Maryanne McDermott, executive vice president of the National Candle Association, says U.S.
candlemakers voluntarily discontinued using lead wicks many years ago. “Most of the U.S.
manufacturers are very careful about the quality of their production,” McDermott adds. “I
would think these candles causing problems were imported, instead of domestically produced.”
But Bailey notes that both domestic and imported candles pose problems. Some, but not all,
of the candles implicated are scented. Other factors to pay attention to include poor candle
design and use of improper materials.
“Candles shouldn’t be burned in drafts,” McDermott claims. “And wicks should be trimmed.”
She adds that candles made with beeswax burn cleaner than those made with paraffin wax, a
petroleum product.
Fragrant Frauds
Jeffrey Schiller, founder of the International Aromatherapy and Herb Association, says a lot
of deception surrounds aromatherapy products–and not just candles. In particular, essential
oils (natural, botanical oils emitting the odor of the plant they were derived from and
commonly used in perfumes) have been left out of the mix in many aromatherapy-labeled
products. Schiller says, “I look at all of the ingredients and check for purity. So if there
are any chemicals in there that I don’t recognize, I don’t buy the product.”
Such suggestions are helpful for buying most aromatherapy products, but candlemakers aren’t
required to list ingredients, making it more difficult for consumers to know which candles
are safe. Schiller adds that candles aren’t the best way to put aromas in the air, anyhow. A
diffuser or nebulizer (atomizer) is a better option, he says.
Aromatherapy sales of all types have boomed in recent years, but industry leaders say that
much of what is being sold as aromatherapy doesn’t contain essential oils, is adulterated or
diluted, or isn’t natural. “A lot of big companies are jumping on the bandwagon and saying
their products are aromatherapeutic, when they’re not,” says Cheryl Hoard, president of the
National Association for Holistic Aromatherapy (NAHA). “They are using synthetic fragrances
instead of essential oils. NAHA is very actively involved with educating the public and
manufacturers about true aromatherapy.” The group is also developing quality standards for a
“True Aromatherapy Product” seal.
Calcium in fortified beverages
I’ve frequently wondered how much calcium is actually in my glass of soymilk since there’s often a layer of sludge left at the bottom of the glass or in the carton. Could this be where most of the calcium ends up? Researchers at Creighton University have raised important concerns about the amount of calcium actually delivered by fortified beverages. They examined four brands of calcium-fortified soymilk and rice milk and eight brands of calcium-fortified orange juice. Beverages were tested and assigned a score based on the amount of calcium in the beverage that did not dissolve (and that probably would not be drunk) and on the likelihood of the calcium in the beverage being absorbed. A score of 100 indicates a source of calcium that would be well absorbed and that would deliver the amount of calcium on the product’s nutrition label. Scores for orange juice ranged from 70 to 99, with most products above 95. Soymilk and rice milk scores ranged from 57.5 to 90. These results suggest that many calcium-fortified beverages do not deliver as much calcium as the label suggests they do. What can consumers do?
* Shake calcium-fortified beverages very well to maximize the amount of calcium in your glass.
* Use other well-absorbed sources of calcium like kale and collard greens in addition to calcium-fortified beverages.
* Contact producers of calcium-fortified beverages and let them know that it is important that their products deliver usable calcium in the amount indicated on the label.
Calcium
From a young age, we’ve been told to drink our milk, whether it was our moms not letting us
leave the dinner table until our glasses were empty, or today, milk-mustachioed celebrities
ballyhooing its benefits.
Well, mom and those celebrities are right. Milk, with its abundance of calcium and
beneficial vitamins, does do a body good. As the most calcium-dense food on Earth, milk
helps build strong bones and maintain immune function, and some think it may aid in weight
loss.
But when dairy and your body don’t agree, getting the recommended 1,000-1,300 mg of calcium
a day becomes a bit more difficult. In fact, since the average American diet contains only
800 mg of calcium, it seems that more than just the lactose-intolerant are neglecting to
follow their mom’s milk advice.
Here’s where supplements can swoop in to the rescue. Simply pop a 500-mg calcium pill
daily, and–presto–you’re halfway to the minimum recommended daily amount of 1,000 mg per
day. Or you are until you find yourself standing in front of the shelves at your local
store, eyes slowly glazing over at the array of calcium varieties. Carbonate … citrate …
lactate … how to choose?
Luckily, the answer is elementary, as in the amount of elemental calcium in each. Since
supplements are not completely made of calcium, it’s good to know how much of the element is
in the supplement you choose. Below are the approximate amounts of elemental calcium each
formula has, according to the Physician’s Desk Reference:
* calcium carbonate: 40%
* calcium phosphate: 40%
* calcium citrate: 21%
* calcium lactate: 13%
* calcium gluconate: 9%
Sure makes shopping easier.
Calcium/vitamin D not effective for secondary prevention of fracture
Grant AM, Avenell A, Campbell MK, et al, for the RECORD Trial Group. Oral vitamin D3 and calcium for secondary prevention of low-trauma fractures in elderly people (Randomised Evaluation Of Calcium OR vitamin D, RECORD): a randomised placebo-controlled trial. Lancet 2005; 365:1621-1628.
Porthouse J, Cockayne S, King C, et al. Randomised controlled trial of supplementation with calcium and cholecalciferol (vitamin D3) for prevention of fractures in primary care. BMJ 2005; 330:1003-1006.
* Clinical Question
In older people who have already experienced an osteoporosis-related fracture, does vitamin D, calcium, or the combination prevent secondary fractures?
* Bottom Line
The combination of calcium 1000 mg and vitamin D3 800 IU was ineffective in preventing fractures in 2 studies enrolling a total of more than 8500 participants, almost all of whom were female and aged at least 70 years who either had a previous osteoporotic fracture or were at high risk. The dose of calcium is lower than the 1500 mg commonly recommended and used. These results conflict with a meta-analysis that found that the combination therapy reduced fracture rate, including hip fracture, in older patients who have not had a previous hip or nonvertebral fracture (JAMA 2005; 293:2257-2264). (LOE=1b)
Study Design
Randomized controlled trial (double-blinded)
Allocation
Concealed
Setting
Population-based
Synopsis
wo studies, both conducted in the United Kingdom, studied the effect of calcium and vitamin D. In the first study, the researchers recruited 5292 participants following treatment for a fracture. Most (85%) were white women, all were at least 70 years old and ambulatory, and all had a previous osteoporotic fracture, on average 1 month before entering the study. Approximately 20% of the participants were taking a thiazide diuretic, which blocks calcium excretion.
Using concealed allocation to avoid selective enrolling of patients into a specific treatment, the researchers randomly assigned patients to receive 800 IU daily oral vitamin D3, 1000 mg calcium, the combination of both, or placebo. The patients took their assigned treatment for at least 2 years. Overall, new fractures occurred in 13.0% of the participants; hip fracture, the more clinically relevant outcome, occurred in 3.4% of participants.
Compliance was not good in the study; by 2 years only half the patients were still taking their assigned treatment, and the 2 groups taking calcium had significantly higher noncompliance, with only 42% still taking their assigned treatment at 2 years. The results were analyzed using intention-to-treat, which leaves patients in their assigned groups even if they dropped out of the study or were not compliant. Neither calcium supplementation, vitamin D, nor the combination was effective in decreasing the rate of overall fractures or hip fractures. Compliant patients also did not have lower fracture rates, though the number of patients (508) taking both vitamin D and calcium may not have been large enough to find a difference if one existed.
In the second study, the researchers surveyed general practices across England to find women aged 70 years or older who had either a previous fracture or at least 1 risk factor: low body weight, maternal history of fracture, smoking, or poor/fair health. The 3314 women were randomized, using concealed allocation, to receive either placebo or the combination of calcium 1000 mg and vitamin D3 800 IU. Over a median follow-up of slightly more than 2 years, 4.3% of women experienced a fracture, and 0.7% experienced a hip fracture. Similar to the first study, there was no difference in fracture rates or hip fracture rates with treatment, either overall or in patients who were compliant.
Do calcium antagonists help patients with angina pectoris?
For several years the treatment of angina has been based on combinations of nitrates, beta blockers, and calcium antagonists. In the mid 1990s, there was concern about the long-term safety of calcium antagonists. Poole-Wilson and colleagues studied the effect of the long-acting calcium agonist nifedipine on patients with stable angina pectoris in the ACTION study.
More than 7,600 patients with stable angina pectoris from 291 treatment facilities in 19 countries were recruited for the study. Patients were 35 years or older and required oral or transdermal therapy to prevent or control symptoms. Reasons for exclusion included left ventricular ejection fraction less than 40 percent, overt cardiac failure, major cardiovascular event or intervention in the previous three months, significant cardiac valvular or pulmonary disease, and unstable insulin-dependent diabetes mellitus.
Nifedipine or placebo was added to current therapy depending on randomization. The initial dose of nifedipine was 30 mg daily. If tolerated, this was increased to 60 mg daily within six weeks. Other medications were continued at the discretion of the treating physician except for calcium antagonists, cardiac glycosides (except for supraventricular arrhythmia), positive inotropic agents, antiarrhythmic agents in classes I or III other than amiodarone (Cordarone) or sotalol (Betapace), cimetidine (Tagamet), antipsychotic agents, antiepileptic drugs, and rifampin (Rifadin). Randomization was made following baseline assessment that included a full medical history, echocardiography, blood pressure assessment, and classification into a New York Heart Association (NYHA) category. At each six-month follow-up, clinical assessment included NYHA status, vital signs, and monitoring for adverse effects. The study assessed survival without a major cardiovascular event. This was measured as time to occurrence of acute myocardial infarction, refractory angina, new overt heart failure, debilitating stroke, peripheral revascularization procedure, or death from any cause. The primary combined endpoint was death from any cause, acute myocardial infarction, and debilitating stroke. Other cardiovascular events were predefined as secondary outcomes.
The 3,825 patients randomized to nifedipine were comparable with the 3,840 randomized to placebo. The average age was 63.5 years, and 79 percent of participants were men. One half of the participants had experienced myocardial infarction, and one fourth had undergone a coronary revascularization procedure. Nearly 70 percent had significant lesions on coronary angiography, and 46 percent had NYHA classification of II or III. By six weeks, 88 percent of patients were taking the full dose of medication. Sixteen percent of patients reduced nifedipine to half-dose. Therapy was discontinued by 34 percent of patients taking nifedipine and 31 percent of those receiving placebo. The most common adverse events leading to discontinuation of nifedipine were peripheral edema and headache.
The mean follow-up achieved was almost five years. Patients taking nifedipine experienced significant increases in heart rate and reductions of blood pressure compared with the placebo group. Cardiovascular and noncardiovascular death rates were similar in the two groups. Patients treated with nifedipine had significant reductions in new overt heart failure, coronary angiography, and bypass surgery. Overall, nifedipine prolonged mean event-free survival by 41 days, mainly because of a reduction in coronary angiography.
The authors conclude that nifedipine is safe in patients with stable angina pectoris already using conventional treatments and is associated with a reduction in coronary procedures and interventions. The death rate in patients assigned to nifedipine was 1.1 per 1,000 patient-years greater than the placebo group, but most of these deaths were not because of cardiovascular causes. No evidence was found indicating that nifedipine induces myocardial infarction or heart failure.
Long-term potassium citrate therapy and bone mineral density in idiopathic calcium stone formers
Several authors have described an association between idiopathic calcium (Ca) stone disease and bone mass reduction. Hypocitraturia is a frequent feature of urolithiasis, and alkaline citrate has been recommended as one of the choice treatments in this disease. Some evidence exists as to the positive effect of potassium (K) citrate therapy on bone mass. The aim of this work was the longitudinal evaluation of bone mineral density (BMD) changes in a group of Ca oxalate stone formers treated with K citrate for two years. Enrolled patients were 120; 109 subjects completed the study (51 males and 58 females). A metabolic study and distal radius BMD measurements were conducted both at baseline (BAS) and at the end of the study (END). BMD (0.451 0.081 vs 0.490 0.080 g/cm2), T-score (-1.43 1.02 vs -0.90 1.04), net gastrointestinal alkali absorption (40.37 50.57 vs 61.26 42.26 mEq/day), urinary citrate (2.53 1.15 vs 3.10 1.44 mmol/day) and K (58.93 22.28 vs 65.45 23.97 mmol/day) excretion significantly increased from BAS to END. Urinary Ca excretion remained unchanged from BAS to END (5.16 2.74 vs 5.57 2.85 mmol/day). Our results indicate that long-term treatment with K citrate increases forearm BMD in idiopathic Ca stone formers. It seems probable that the alkali load provided by this drug reduces bone resorption by a buffering of the endogenous acid production. K citrate appears to be a further therapeutic opportunity for the management of osteoporosis in Ca stone formers.