The Pharmaceutical Journal
Vol 271 No 7279 p818
13 December 2003

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A kink in time more
Caution over nitric oxide more
Dim future more
The art of creation more

A kink in time

In my part of the south-west we are accustomed to strange goings-on for which we cannot find a satisfactory explanation. No doubt we derive our phenomena from many generations of superstitious folk. At the same time, I suspect that we must attribute something to the wicked habits of our ancestors. They were not averse to a little smuggling and piracy now and then and used a cunning scheme of reputed hauntings to scare any would-be nosy parkers away from a sensitive area of operations.

We have numerous haunted paths, cliff-tops and buildings where we claim to see or hear things that by rights should not be there. There are ghostly hunters on stormy nights, packs of whist-hounds tearing past in the clouds. There is Lady Howard driving in the neighbourhood of Tavistock on the wild moor.

On the lonely road near Postbridge there are the notorious hairy hands that on a dark night will reach out for the traveller’s neck. I have never encountered the hands, but on occasion have felt uneasy when travelling that road, and have been worried by a dark figure in the distance that melts into a hedge where there are no gaps that would permit escape.

Most of our hauntings are of old farmhouses, manors or castles that have an uncanny atmosphere about them. One experience that I have never been able to explain came my way on a visit to that old Tudor edifice of Berry Pomeroy, near Totnes, overlooking the Dart river. This is an impressive structure, with mysterious steep stairways within the thickness of the walls, dungeons, and a host of nasty legends. If the weather is rough it can be forbidding.

One wing, the dwelling place of the Seymours, presents an ancient wall that was once rich in stone-mullioned windows but was long ago blocked in, leaving few apertures. I took many photographs of the place, and was astonished to find the old windows apparently in place as in Tudor days.

When I revisited the place I found that I had been right about the blocking in of the mullions, yet in my photograph the apertures were plainly visible. The odd thing I discovered later was that a friend of mine had also taken photographs that showed exactly the same apertures. This was uncanny and neither of us had an explanation. Had we perhaps discovered a kink in time that carried the past into the present?

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Caution over nitric oxide

In the 27 November issue of The New England Journal of Medicine a report from the University of Chicago concludes that inhalation of nitric oxide by premature infants suffering from respiratory distress syndrome decreases the incidence of chronic lung disease and death. In addition, inhaled nitric oxide decreased the risk of severe intraventricular haemorrhage and periventricular leukomalacia by 47 per cent compared with placebo treatment.

These complications were not prevented entirely but their severity was reduced substantially.

Concern over the safety of nitric oxide has concentrated on the possibility of its inducing bleeding, methaemoglobinaemia and oxidative stress. However, although high concentrations (80ppm) have produced methaemoglobinaemia in full term infants, low concentrations (less than 20ppm) have not. Nitric oxide, it is argued, is an important mediator of both normal lung development and pulmonary vascular tone.

An editorial note in the same issue of the journal calls for caution in arriving at conclusions about the safety of nitric oxide in premature infants. It is true that therapy commencing with 10ppm of the gas from the first day of life reduced the incidence of death or chronic lung disease from 64 per cent to 49 per cent in infants with mild to moderate respiratory distress syndrome, defined as an oxygenation index of less then 6.9, but brought no benefit with an index of 6.9 or higher.

Whether the therapy is safe for preterm infants with respiratory distress or failure remains in doubt. There is uncertainty over the optimal concentration of inhaled nitric oxide and the timing and duration of therapy. It is possible that the gas could induce intracranial bleeding in fragile preterm infants by mechanisms that include decreased platelet aggregation.

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Dim future

We have been aware for decades of the menace of antibiotic-resistant micro-organisms, but have been half-hearted when it comes to action to prevent future disaster. The main problem has been the too lavish resort to antibiotics for the treatment of minor ailments in humans and threatened losses of farming stock. Now a fresh face of the menace is on the horizon. The situation of adequate supplies of new antibiotics capable of overcoming epidemics of infections by organisms resistant to all available antibiotics is now rendered more worrying by the unwillingness of pharmaceutical manufacturers to pursue expensive research into providing new remedies.

The problem is described in The Lancet for 22 November, where it stated that: “there simply aren’t enough new drugs in the pharmaceutical pipeline to keep pace with these ‘super bugs’.” Just as the resistant organisms are becoming a greater threat, many pharmaceutical companies are curtailing their antibacterial research and development programmes, and even in some cases withdrawing from the market.

The fact that such drugs are administered for limited periods, unlike those used for long-term treatment schedules, has reduced the financial returns of investing in them. Moreover, to make an antibiotic profitable it may be necessary to have it approved for several different indications.

During the flourishing period of antibiotic research and discovery from 1930 to 1970, when the incidence of resistance remained low, a state of complacency developed, but since then infectious diseases have seen a surge in incidence. Streptococci, staphylococci, mycobacteria and vibrios have shown high resistance to available drugs.

Eliminating the misuse of antibiotics in medicine and agriculture can be effective, but we still need to develop new antibiotics against multiresistant organisms. But a major problem is the high cost of drug development. In the United States, in particular, there have been calls to set up new consultation bodies, but what is really needed is action now, not more talk. Meanwhile, of some 400 drugs in the development pipeline, only five are antibacterial agents.

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The art of creation

In the case of man, that which he creates is more expressive of him than that which he begets. The image of the artist and the poet is imprinted more clearly on his works than on his children. — Nicholas Berdyaev: The destiny of man (1931).

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