Parasympathetic nervous system dysfunction in Gulf War syndrome

Epidemiology

Gulf War Syndrome

This refers to a wide range of illnesses and symptoms, from asthma to sexual dysfunction, reported by and among U.S. allied soldiers who served in the Persian Gulf War in 1990-1991 (Encyclopedia of Alternative Medicine 2001). Researchers at the University of Texas Southwestern Medical Center investigated a sampling of these veterans with the syndrome (Nutrition Health Review 2004). The researchers found that a primitive portion of the nervous system of these veterans was damaged. This damage to the parasympathetic nervous system appeared to account for almost 50% of the typical symptoms. These symptoms included gallbladder disease, un-refreshing sleep, depression, joint pain, chronic diarrhea, and sexual dysfunction. The parasympathetic system regulates the body's primitive and automatic functions, like digestion and sleep. The sympathetic nervous system, on the other hand, controls the "flight-of-fight" instinct (Nutrition Health Review).

Isolating pure parasympathetic brain function was previously difficult to perform (Nutrition Health Review 2004). Dr. Robert Haley, chief of epidemiology at the University and leading author of this new study, and his team used a new mathematical technique called spectral analysis. It monitored changes in approximately 100,000 heartbeats over 24-hour and measured changes in high-frequency heart rate variability. Only the parasympathetic nervous system regulates this function. Through the method, the team found that parasympathetic brain function, which usually reaches a peak during sleep, barely changed in the veterans, even though they appeared to be sleeping. A similar investigation of a group of healthy veterans, tested for comparison, revealed normal increased brain functions. Dr. Haley explained that the parasympathetic nervous system restores the functions of the body through sleep, Hence, the refreshed feeling upon waking up. When brain functions do not increase during night sleep, illness can occur. This was the position taken by the team to explain the lack of refreshing sleep among the Gulf War veterans. The investigation involved 40 members of a naval reserve construction battalion, the Seabees, some of whom were ill and the rest, healthy (Nutrition Health Review).

Dr. Haley first described the syndrome in a series of papers published in the January 1997 issue of the Journal of the American Medical Association (Nutrition Health Review 2004). He previously ascribed the condition to the veterans' low-level exposure to sarin gas. This was a potent nerve toxin, which was said to have reached thousands of soldiers when American forces detonated Irqi chemical stores during and after the Persian Gulf War in 1991. This occurrence was confirmed by the Government Accountability Office. Succeeding studies performed by Dr. Haley's team suggested that these veterans were also born with lower levels of a protective blood enzyme, called paraoxonase. The enzyme counteracts toxins found in sarin. The team then concluded that veterans who were in the same area and did not get sick were likely to have higher levels of this enzyme (Nutrition Health Review).

Dr. Haley and his team were also the first to use the method of factor analysis in investigating the Gulf War syndrome (Kang 2002). It involved the exploratory analysis of 62 symptoms in 249 of such veterans. These 62 symptoms accounted for 71% of the total variance of the observed variables. Dr. Haley's team presented these as evidence of the syndrome. But the team's observation was derived from just one naval unit of Gulf war veterans and which was not compared with a non-deployed veterans' group. Moreover, the participation rate at 41% could not make generalizations on the syndrome. In comparison with those conducted by Dr. Haley's team and Fukuda's, this current study was population-based and included a comparison group of non-Gulf war veterans. Further differences existed. Dr. Haley's sampling was limited to a small number and from just one naval reserve unit. Fukuda's study was confined to members of a U.S. Air Force, Air Force Reserve or Air National Guard unit. These members were substantially different from those who served in the Army and the Marine Corps, who accounted for 2.3 of deployed troops. In contrast, the current study included a large group of respondent-troops from all of the four branches of the service and who were then on active as well as those who were already separated from the military. The study conducted by Ismail and his team approximated this current one as regards study design but differed in statistical analyses (Kang). It first used four-factor analysis but changed to six-factor when the four-factor methods did not produce interpretable results. The current study eventually concluded that a unique factor, consisting of blurred vision, loss of balance or dizziness, speech difficulty, and tremor or shaking, was found among the veterans. A group of 299 with all the four established symptoms also claimed to have been exposed to many putative risk factors many more times higher than that of other Gulf war veterans. Many associated medical conditions were also reported to have occurred more often among these Gulf war veterans than among other Gulf war veterans. Finding of this current study suggested a possible syndrome related to Gulf War deployment. It also required a strong, objective, supporting clinical evidence. Factor analysis was viewed as a method, which was not completely objective. There were no definite rules in the selection of the appropriate number of factors or from among the many possible methods of rotation. Factor analysis is an empirical method, which provides necessary details, from which the reader can make his own conclusions and interpretation of given data (Kang et al.).

Male Infertility

David Dix of the U.S. Environmental Protection Agency or EPA, Stephen Karwetz of Wayne State University and David Miller of the University of Leeds in England surprised other biologist with their recent finding on male infertility (Travis 2002). They discovered that mature human sperms contain several thousand different strands of RNA, which are the cells' directives for protein manufacturing. The presence of RNA inside mature human sperm was unexpected, as scientists had assumed that newly formed sperm cells shed almost everything as they mature and had little need for RNA. This discovery is significant to many areas of biology and medicine. By establishing an RNA fingerprinting of sperms from fertile men, the scientists could compare them with sperms of infertile men. Further uses can be the development of male contraceptives by identifying the genes used by sperm cells for their development. And sperm RNAs may also help evaluate the safety of environmental chemicals (Travis).

The previous consensus among biologists was that, as a sperm cell matures, it eliminates almost all of its cytoplasm, which is the fluid where the RNA resides (Travis 2002). Krawetz also said that reports of RNA-containing sperm in the past few decades were also disregarded or attributed to contamination by other cells. But about a decade ago, Miller and Krawetz found in joint experiments that RNA was present in spermatozoa. This led them to assume that RNA provides a history of spermatogenesis. They were joined by Dix in exploring the new discovery through a powerful method, which relied on microarrays, in order to scan cells for thousands of RNAs at one time. Microarrays are glass chips, nylon filters or other platforms, which are dotted with thousands of different strands of RNA or DNA. They used a form of DNA known as expressed sequence tag or EST. The microarrays held ESTs of roughly 30,000 different human genes. The scientists obtained semen samples from 10 healthy volunteers with normal-looking sperms and had fathered children. The scientists separated the samples from other kinds of cells and eliminated genetic material from their surface. Then they extracted RNA and converted it into a DNA form they called cDNA. When these cDNAs were applied to the microarrays, the cDNAs stuck to corresponding ESTs. This ultimately identified the genes at the sperms' RNA. The scientists later compared the RNA in the sperms of one fertile man with those of other fertile men. The 2,780 RNAs shared by the samples became representative of the spermatozoal fingerprint for a normal fertile man. Their next step was to find out what RNAs would be missing in the sperms of infertile men. But on the whole, Krawetz, Miller and Dix endeavored to convince their peers that sperms contain RNA through the results of their microarray experiments. Sperm biologist W. Steven Ward of the University of Hawaii at Manoa felt that the idea of spermatozoa having any RNA would be "counterintuitive." But he said he would be willing to give credit to the proof provided by the three scientists. Sergio Oehninger of the Jones Institute of Reproductive Medicine in Norfolk Virginia expressed agreement, but also cautioned that it would take years before microarrays could be cheap enough. The science itself would take time to mature and for the procedure to become routine clinical practice (Travis).

When the role played by sperm RNA in human development becomes accepted as a scientific fact, it may explain why human females cannot reproduce parthenogenetically as frogs and other non-mammalians can (Travis 2002). In parthenogeneris, an unfertilized egg can start dividing and still be capable of reproducing a normal offspring. In some mammals with this capability, an unfertilized egg may begin developing into an embryo or the development can just stop. Investigators even suspected that the difficulties experienced by teams in mammal-cloning experiments were due to the absence of RNAs in the sperm. In cloning, scientists would take the DNA from a non-germ cell, add it to an egg denuded of its DNA and trick it into developing as though it were fertilized by a sperm. The procedure would work only a few times. Most of the time, it would develop gross defects, which often delayed further development. John Eppig, a reproductive biologist at Jackson Laboratory in Bar Harbor, Maine, suggested that the success of cloning was a strong argument against the supposed key biological role of apparently large numbers of RNAs being delivered by the sperm (Travis).

It has been estimated that infertility occurs in 2 million couples in the United States (American Family Physician 1993). About a third of these are attributed to male factors, including primary testicular failure, secondary testicular failure and post-testicular obstruction.

Greendale and his colleagues conducted a study on the possibility of Chlamydia trachomatis as another cause of unexplained infertility. In the study, the team utilized 52 men who were diagnosed with explicitly defined idiopathic infertility and were enrolled in two infertility practices as one group. The other group consisted of 79 men who were enrolled in prenatal classes their partners. Those couples who had unprotected intercourse were placed in a group, which was subjected to two semen analyses. These respondents were not hypogonadal or azoospermic and their partners had idiopathic primary or secondary infertility. When their serum IgG anti-Chlamydia antibodies were measured, infertile men were found to be 3.4 times more likely than fertile men to have a higher titer. About 50% of patients in both groups with anti-Chlamydia antibody titers of 1:64 or higher had no symptoms of infection. Among asymptomatic patients, 20% exhibited abnormal penile discharge, 205 with non-traumatic testicular swelling or pain, and 40% with dysuria. However, these findings by Greenpeace and his team were later found to be inconclusive (American Family Physician).

Review of Methods

Studies on the Gulf War syndrome used the spectral analysis method and the factor analysis method. Spectral analysis focused on the changes in function of the parasympathetic nervous system, mainly sleep. The factor analysis method derived from the symptoms of the syndrome.

Studies on male infertility utilized a method, which relied on microarrays, which, in turn, traced the presence of RNAs in the sperm cell. The absence of RNAs, those researchers suggested, could explain male infertility. Another study suggested that infection with Chlamydia trachomatis could be a cause of the condition.

Mayo Clinic's study supported the effectiveness of acupuncture in managing headaches and chronic neck pain in a substantial number of patients. The method consisted of a three-month treatment of acupuncture with conventional analgesics on three different groups. They mostly reported experiencing reduction of their painful conditions.

Acupuncture involves the insertion of very fine needles into the 12 body meridians to balance the flow of energy, called chi. The imbalance or disruption of the chi leads to illness. Acupuncture restores that balance by triggering the release of natural painkillers and stimulating the release of pain-suppressing neurotransmitters. The practitioner conducts some diagnosis before inserting the needles. These needles are kept in place for a few minutes. Treatment is often for an hour every week for a few weeks. The practitioner advises the patient to seek other treatment options if no improvement results.

Conclusion

The two methods used by epidemiological studies on the Gulf War syndrome on the dysfunction of the parasympathetic nervous system and the signs of physical and emotional disturbance were not contradictory. Rather, they were complementary and should be considered thus. The absence or lack of RNAs, as determined by the microarrays method, can be a breakthrough in establishing the cause of male infertility. Infection by Chlamydial trachomatis through semen analysis was regarded as inconclusive. And the value of acupuncture as an adjunct to conventional pain management has been significantly proven by the study undertaken by Mayo Clinic on a substantial group of volunteer-patients. All other studies support its effectiveness and safety.