The Tribune, Chandigarh, India

The infertile man — a scientific profile
By Dr R.J. Dash

Men often disbelieve that they could be infertile particularly when they look like other men of accomplished fertility and conduct themselves like other married men. For this assumed disbelief, their legal female partners bear the social taboo and sometimes receive continuous harassment from many quarters, threatening marital harmony.

While women with fertility problems conveniently consult a gynaecologist, infertile men do not know where exactly to go. They consult general practitioners, internists, urologists, sex therapists and even faith healers. By the time they seek advice from an andrologist or an endocrinologist, it is often as late as five to 15 years.

In the general population 70 to 90 per cent of the pregnancies are noted within a year of unprotected conjugal life. If this does not happen in a year or two, medical consultation should begin to identify the problem in one partner or the other.

Like infertile women, infertile men need thorough investigations. These should begin with the analysis of their cohabitation practices including the frequency and timing of intercourse, possible environmental exposure to toxins, consumption of drugs including sulphasalazine, cimetidine, anti-epileptics, marihuana, alcohol and heavy smoking. A medical doctor once told me about his carrying a pack of radio-needles in his trousers, pockets, letting his hands carry books and a cigarette. Obviously, his infertility could be linked to radiation damage.

Over-indulgence in sauna baths, repeated testicular traumas and smallpox and mumps virus infections without the classical features of testicular involvement are well- known causes of infertility.

Repeated blood transfusions to thalassaemia boys invariably lead to infertility in adult life for heavy iron deposits in the testis.

Accidental ligation of the sperm-carrying duct or vascular connections to the testis during hernia repair or transfixation of the testis into the scrotum in older children are important causes of infertility. In fact, the history of maldescended testis amongst infertile men (6-10%) who had undergone appropriate surgical procedures in childhood is frequent while in a few abnormally located testis could still be found.

A good physical examination is essential. Long-leggedness, an increase in the span length more than in height, the loss of the sense of smell, the enlargement of breasts, sparse body and facial hair, small testicles and poorly developed scrotal sac that lack dark pigmentation and rugosity are indicators of inadequate testicular function.

Laboratory investigations should aim at determining spermatogenesis, the potency of the sperm passage and the sperm function. Spermatogenesis is assessable by fine-needle aspiration cytology of testes, together with hormone studies, LH, FSH, PRL and testosterone. Of them FSH correlates well with the spermatogenetic process while LH and testosterone correlates with the Leydig cell function. High prolactin from a prolactin producing pituitary tumour is a rare but effectively treatable cause of male infertility.

Abnormalities in sperm carriage is assessable by the seminal plasma fructose estimation and vasography. Sperm function studies aim at demonstrating the sperm penetrating the ovum ( using hamster ova) in vitro, the determination of oxygen free radicals in semen and zona binding assays. These test procedures are still considered research methods, and are not within the reach of many infertile men.

Laboratory evaluation should commence with the most important process — a semen analysis. Although a three-day period of abstinence from sexual activity has been a time honoured practice for obtaining the semen sample, most of us today do not insist on the abstinence period. The couple may maintain their scheduled sex habit and provide the sample for analysis when asked for.

The examination of freshly collected masturbated sample in a clean container should be done by a competent technician in an established andrology laboratory. A flow cytometer for a sperm count, a computer-assisted sperm analysis (CASA), equipment for sperm motility and a binocular microscope for sperm morphology are essential. But these are not available in most of the governmental institutes or research organisations in the country. We mostly depend on the properly conducted conventional procedure for a semen analysis. In the absence of information on a sperm count in men of proven paternity, counts of 60-100 million/ml are considered normal.

There are reports of the progressive lowering of the average sperm count in the male population of reproductive age in many countries. The cause of this fall is ill-defined but is considered a change from environmental influence.

Genital tract infection and its sequalae account for low sperm counts in up to 50 per cent of the infertile men in African countries. Our own study reveals this as a possible cause in over 20 per cent of the patients with mycoplasma infection.

Varicocele is a recognised but controversial cause of infertility. These dilated testicular veins make the testes warmer and drain out testicular testosterone, thus creating unfavourable situations for spermatogenesis. The ligation of varicocele sometimes improves sperm counts.

The treatment of infertile men centres around in-vitro fertilisation (IVF), using sperm concentration and epidedymal aspirate, micro-assisted fertilisation and GIFT (in vitro gamet transfer and fertilisation). The results of IVF for the male factor defects carries a lower success rate than those for tubal infertility in women. Artificial insemination, because of several ethical and legal issues, has become very controversial. Hormone therapy for the initiation and maintenance of spermatogenesis in hypogonadotropic hypogonadism is challenging with success in about 30 per cent of the cases. Similarly hormone modulation therapy for patients with ideopathic oligospermia is promising in certain instances.

Prof R.J. Dash is the Head of the Department of Endocrinology at the PGI, Chandigarh.

Healthy hospitals
By Maj-Gen Dr Jaswant Singh AVSM

I had the good fortune of almost 35 years of commissioned service in the prestigious Army Medical Corps. But I will try to be objective in my assessment of the Indian military hospitals. I have been mostly either working as a specialist or visiting these hospitals as an inspecting officer. But, recently, I had the first hand experience as an in-patient in the intensive care unit (ICU) of the Command Hospital, Chandimandir.

On April 29, at 7.30 a.m, I had to seek admission in the ICU for what could be a disabling disease. The commandant, Maj-Gen. Virendra Singh, was requested and he reached earlier, organised admission, ensured the presence of specialists and medical officers and the nursing staff in advance. Within minutes of my arrival, investigations and treatment were started.

The ICU is meticulously organised, well-equipped with committed medical, nursing and paramedical staff who work with sacred devotion. Spotless cleanliness of every corner of the ward may be the envy even of the gods. The whole staff is fully alive to the assigned duties. No member requires persuasion. Medicines are provided without any hassle. Visitors are strictly restricted — during the visiting hours — minus their shoes and one at a time for each patient. The atmosphere is serene except for voices sometimes of the nursing staff and is ideal for meditation.

The ward staff and the specialists come sharp at 7.30 a.m and go around their patients. Soon the commandant arrives who, incidentally being a specialist in ICU care, has always a word of advice for the patients.

He is held in revered awe and the ward is in ship-shape condition. The beds are freshly made and the patients are washed and spruced up.

I had only a four-day stay. During one midnight an elderly retired officer was brought in by his tenant with no pulse and laboured breathing. The cardiologist and the anaesthetist came within minutes and with frantic efforts revived him. The nursing staff did a splendid job. Otherwise it would have been one of those "brought in dead" stories. This is a measure of professional excellence and dedication. A senior officer with a heart attack was revived; a moribund patient was successfully operated upon with a dextrous team. I do not intend cataloguing the patients!

Nursing care deserved special mention. The Principal Matron, with her dedicated band of nursing officers who have recently converted to olive green from saintly white Nightingale's apparel, provides a dedicated complimentary service to the doctors. Without this background, medical care would be hollow and hoarse. They are seen darting about round the clock with a smile — and full of humour. Their role is exacting and demanding. The Military Nursing Service is a corps within the Army Medical Corps with extremely well paid and highly skilled officers. They are the envy of the nursing fraternity of the country.

The ward is kept clean—dust-free, sparkling white with creaseless beds. I do not intend inviting you to be an inpatient. The hallmark of cleanliness can be seen in the shining bathrooms and annexes of the ward.

The dietary service is a specialised field with a senior qualified lady dietician who caters a variety of delicious diet suited to the individual patient's needs. The food is served hot in a hygienic and modern manner.

The ICU forms a mirror image of the Command Hospital and other military hospitals of the Armed Forces. All hospital services are computerised with an arrangement for video conferencing and the Internet facility for specialist advice from anywhere in the world.

There is a lot of misconceptions among some officers about the military hospitals and the professional competence of the specialists. My only counsel to them is to look around and visit other hospitals, including the prestigious nursing homes, and then compare and comment.

I would humbly suggest that more funds should be provided to these hospitals so that we do not suffer because of the lack of the latest equipment like CT-scan, MRI and Cardiac Dopplers.

This documentation of experience has been inspired by Tavleen Singh's "On the spot" impressions of Indian hospitals in The Tribune of May 6.

General Jaswant Singh has been a consultant surgeon in the Armed Forces and has retired as Director, Medical Services, Western Command. He is a practising surgeon based in Chandigarh.

Breakthrough in organ transplant

In France, a man will again feel the warmth of his children's hands in his. A simple act, but only possible now that surgeons have given him the limbs of a dead man. More transplants are planned. Do they offer real hope or future horror? William Peakin explains:

Unlike many transplants, there was no helicopter or ambulance dash through the night with the organs; the donor was close by. In the early hours of Thursday, January 13, along with his kidneys, liver and heart, the young man's hands and forearms were removed. Prosthetics were fitted just below the elbow to provide a normal appearance for his funeral. The limbs were perfused with preservation fluid, placed in dry plastic bags and carried in a cool box.

Earl Owen had led the first transplant; this time Dubernard would be in charge. Gowns were tied, rubber gloves snapped on. In theatre, there was the occasional glare of a camera flash; an intricate network of lenses, some high above the operating table, others connected to microscopes, had been set up to record the operation.

They began at 6 a.m. Fifty surgeons, specialists and nurses would work on Chatelier, lying with arms outstretched as if crucified, a separate team of four surgeons for each donor hand and each host arm. He had been sedated and then anaesthetised. Tourniquests were applied to his arms and two incisions were made on each to expose the deeper structures. The nerves, arteries, veins and muscles were dissected and tagged and the forearm bones transversely cut with an electric saw so that the grafted limbs would be the same length. At the same time, in an adjoining theatre, the donor hands were similarly dissected and tagged. About 10 cm of the donor arm would also be used.

First the two forearm bones, the radius and ulna, were joined, using small titanium plates with holes for 4.5 mm stainless steel screws to go through; then the arteries and cephalic veins were connected and the first arterial clamps were removed. The tourniquets were loosened and the hands' cool white turned pink. The surgeons left them undisturbed for 20 minutes covered with warm, wet sponges. Then the ulnar, median and radial nerves were microstitched. It took hours. Next were the muscles, then the tendors, interwoven with the muscles where possible, and finally, the skin. It took until 11 pm.

The surgeons had been nervous: not of attaching the hands, but of an unforeseen complication. Patients can lose a lot of blood when two wound sites are opened. If Chatelier had died it would have meant calling a halt to any further such transplants. But, close to midnight, they could relax and watch as nurses wrapped thick bandages around his arms. In the days the followed, Chatelier's progress was good.

A cocktail of four immunosuppressants and steroids was given, the same mix used in the first transplant 15 months ago, one that had proved very effective. It included an ingredient that has greatly advanced immunosuppression; tacrolimus, derived from a fungus found in soil dug near the manufacturer's laboratory in Japan. An unexpected side effect is that it encourages faster nerve regeneration and reduces scarring.

The patient was told not to give in to temptation and try and move his fingers. That would come in time, first with thin rubber bands attached to provide gentle resistance and then later, over the next three months, with intensive physiotherapy.

Chatelier's operation was the first in a series of five double hand transplants that France will use to decide whether the transplantation of limbs and other external multi-tissue organs will become commonplace there. The US team in Louisville, Kentuchky, has a double hand patient standing by. Nadey Hakim is trying to organise Britain's first single transplant later this year. In Austria and Italy, other operations are being planned. Although the expertise and the antirejection drugs to undertake this surgery have existed for some time, the significance of the hand's visibility as prevented the procedure from being attempted until now. "The hand is still a special symbol, like the heart was 30 years ago," Dubernand says.

The story of how this taboo was broken combines surgical brilliance with naked medical one-upmanship. It questions why most scientific advances are made in secret. And it points to an extraordinary future where arms and legs lost in accidents or war could be routinely replaced; congenital defects corrected; where a balding man could receive a new head of hair. Perhaps most starling of all, it will be possible for someone terribly scarred or burnt to have a face transplant. It's a story littered with extraordinary, and often flawed, characters.

At school in Sydney 55 years ago, as Australian troops fought the Japanese in Borneo, Earl Owen grew increasingly bored. Sitting near the back of his class, he was able to rest a book on the top of his desk, to give the impression that he was reading, while his hands reached inside and carved small toys from balsa would blocks, tiny soldiers, tanks and aeroplanes about 1 cm long; all the time wondering when his father and uncles would return from the war.

His arms were still, his hands barely moved. The carving came from the thumb, index finger and a tiny parch on the middle finger. An entire army was created that so impressed the headmaster when Owen was caught that the chosen punishment for not paying attention in class was suitably benign; to carve the school's crest. Owen was predestined to go into medicine — his father and eight uncles were all doctors or surgeons — but perhaps we have that carving to thank for helping to create a new field, microsurgery.

Without it, 35 years ago a baby whose oesophagus was connected to his lung and his trachea to his stomach, the kind of baby Owen was advised by his tutors to "put aside", would not have been saved. And 30 years ago, a little boy whose finger had been cut off with an axe by an over-enthusiastic playmate would not have had it reattached — a first for which Owen was sacked. He had refused to obey a superior who, over the phone late at night, told him to simply stitch the stump and be done with it. There would be more firsts — including the first successful vasectomy reversal — and when most eminent surgeons in their 60s would have had one eye on the gold course, he contemplated another milestone: the first transplant of a limb from a braindead donor.

"We are extraordinarily privileged", he says. "We see down the microscope, with awe and with wonder, human tissues that are alive in extraordinary detail, and it is just mind-boggling. And we have the privilege of being able to reassemble, nowhere near as good as God did, but as close as we can get with the full benefit of modern scientific development. That puts you in a very humble position. And people accuse us of doing this for publicity, which is really very unfair".

Owen first floated the idea of a hand transplant 32 years ago, in a speech at Edinburgh University, but it was not until the mid-1990s that he decided it was possible. As president of the International College of Surgeons, he was friendly with his European counterpart, Nadey Hakim. Over dinner after a conference in Bolivia in November 1996, Owen told Hakim he wanted his help in performing the operation. "But don't tell anyone," he cautioned, "not even your wife.

This will be a world first." Owen had a great love of London, where he trained and practised for many years, and wanted to perform it there; Hakim got to work immediately, contacting the Royal College of Surgeons and the UK's transplant service authority, but when it came to the ethics, the St Mary's authorities were unconvinced. Putting a healthy patient on potentially dangerous immunosuppressants could not be justified, they said.

"Look," Owen told Hakim during one of their many telephone conversations, trying to find a way through the impasse in London, "we really have to get a move on with this." In July 1998, the Louisville team announced it had approval to perform the operation and Owen became gripped by a sense of urgency.

(To be continued)

Sleep: it's all in the mind

Falling asleep or waking up is the outcome of a hormone battle, according to scientists who have established that a small part of the front of the brain will determine whether you will sleep soundly or toss and turn.

A Franco-Swiss team says it has proved for the first time that a brain region called the ventrolateral preoptic nucleus (VLPO) holds the key to sleep.

Their research, conducted on rats, shows that the triangular-shaped cells in the VLPO are inhibited by hormones such as noradrenaline and serotonin when we are awake.

When we nod off, it is because the VLPO cells are switched on by the onset of darkness, alcohol, warmer temperature and other factors, according to this theory.

The VLPO cells, in a burst of activity, stop other regions of the brain from releasing the "wakeful" hormones. That, in turn, allows more VLPO cells to become active, winning the war of the hormones and bringing the onset of sleep.

The VLPO neurons are also highly active during the deepest sleep — the period of so-called rapid-eye movement in which the eyeballs twitch and move under the eyelids and there are powerful dreams.

The work was conducted by scientists from the University Medical Centre in Geneva; the Neurobiological Laboratory for Sleeping and Wakefulness in Lyon, France; and the Laboratory for Neurobiology and Cellular Diversity at France's National Centre for Scientific Research (CNRS) in Paris.

It has been published in the British scientific weekly, Nature.
— (AFP)