Monday, June 11, 2012

Baldness is probably the one thing that causes men more anxiety than anything else in their life. Now, scientists believe they may have found a new way to reverse baldness and treat conditions like alopecia. Scientists have identified stem cells or master cells in the hair follicles of mice. They found that these cells grow into hair follicles and produce hair when transplanted into skin. George Cotsarelis, Assistant Professor of dermatology from the University of Pennsylvania, said that the study could lead to new ways of treating hair loss in humans through drugs or surgery. "This may lead to a new type of tissue engineering for treating baldness - for example, isolating hair follicle stem cells from the scalp and reconstituting hair follicles in bald areas," Dr Cotsarelis said. "I can't predict the future but this type of research certainly opens new avenues for developing new treatments for baldness." The study, published in the journal Nature Biotechnology, isolated the stem cells within the bulbous follicle at the base of a hair shaft. Sometimes these follicles go into a permanent resting phase, halting hair regeneration. When the researchers transplanted the stem cells into the skin of other mice, hair follicles began to re-grow within four weeks. "Now that we can isolate stem cells involved in hair growth, we can develop targets for manipulating hair growth," Dr Cotsarelis said. Receding hairlines and the arrival of the bald patch are feared by men around the globe. Hair may start to disappear from the temples and the crown of the head at any time. For some men this process starts as early as the later teenage years, for most it happens in the late 20s and early 30s. Initially it may just be a little thinning that's noticed. Then, the absence of hair allows more of the scalp to become visible. Some men are not troubled by this process at all. Others, however, suffer great emotional distress associated with a lack of self-confidence and sometimes depression. In male pattern baldness, which is hereditary, the hair is usually lost at the temples and the crown. This happens because an over-sensitivity of the hair follicle to normal levels of testosterone switches the hair loss gene on. Not every hair follicle has this gene which is why some hair falls out whilst other hair doesn't. Other causes of hair-loss that are usually reversible include; iron deficiency anaemia; under-active thyroid; fungal scalp infection; some prescribed medicines; and stress. Scientists have long-suspected that hair follicles contained stem cells. However, it has proved difficult to isolate these cells in humans. This latest study raises hopes that they can now track these genes and identify stem cells in human hair follicles. "Ultimately, these findings provide potential targets for the treatment of hair loss and other disorders of skin and hair," the researchers wrote. While the discovery could lead to new treatments for baldness and conditions like alopecia, the researchers believe it may also help burn victims. "One problem with a burn is that the wound is never covered with hair follicles," said Dr Cotsarelis. "These cells have that capability so if we can isolate them and seed them onto a wound we can constitute skin that is more normal than currently possible."

Evidences of spinal tuberculosis have been found in Egyptian mummies and the disease is one of the oldest diseases afflicting humans. The demography, diagnosis, medical and surgical treatment, as advocated currently, have been reviewed with a brief discussion of the literature. Early diagnosis and comprehensive treatment are needed to control this public health problem.

Tuberculosis of the spine is one of the oldest diseases afflicting humans. Evidences of spinal tuberculosis have been found in Egyptian mummies dating back to 3400 BC1. The descriptions in Rigveda, Atharvaveda and Charak Samhita are the oldest known texts in the world literature relating to this disease2. The association of paraplegia and kyphotic deformity of the spine was first noticed by Sir Percival Pott3.

Tuberculosis was a leading cause of mortality in the beginning of the twentieth century4. Improvement in the socio-economic status led to a major decline in the prevalence even before the introduction of antituberculous drugs.

However, it continues to be a major public health problem in developing countries. Malnutrition, poor sanitation, and exanthematous fever are the factors contributing to the spread of the disease.

In the United States, there has been a steady increase in the prevalence of pulmonary as well as extrapulmonary tuberculosis5. This is largely due to impairment of immune system by the human immunodeficiency virus leading to reactivation of latent infection and a likelihood of progression to active disease6.

The commonest causative organism for spinal tuberculosis is Mycobacterium tuberculosis, an acid-fast bacillus growing only on media enriched with egg and potato base or serum. The practice of boiling of milk before consumption has limited the Myco bovis-caused disease and the Myco africanum is geographically limited to Northwest Africa7.

Topographically, spinal tuberculosis constitutes about half the cases of skeletal tuberculosis8. The dorsal spine is involved in half the cases of spinal tuberculosis. The disease is always secondary to a primary visceral focus which may be in the lungs, lymph nodes or kidneys.

Extrapulmonary tuberculosis is more common in children than in adults, the commonest site being the superficial lymph nodes9. A minimum time lag of 2 to 3 years is present between the development of primary focus and manifestation of the disease in the spine.

The bacteria may reach the spine through the arterial circulation or the Batson's plexus of veins. Initially, two contiguous vertebral bodies are involved due to a common vascular supply.

Destruction of vertebral bodies compromises the nutrition of the intervertebral disc and leads to progressive disc destruction10 and vertebral collapse.

Demography of Spinal Tuberculosis

In the Indian population, spinal tuberculosis is predominantly a disease of the young, the usual age of presentation being the first three decades of life. Reports from developed countries indicate a much older patient population, the median age at diagnosis being sixty-one years11. In most series, the disease has been found to affect males and females in equal proportions12,13.

Diagnosis of Spinal Tuberculosis

Clinical presentation - The clinical features of tuberculosis of the spine include insidious onset of localised pain in the spine. This is usually accompanied by fever, malaise, anorexia and weight loss.

Clumsiness in walking and weakness in lower limbs may be present. There may be evidences of associated extraskeletal tuberculosis like cough, expectoration, lymphadenopathy, diarrhoea and abdominal distension. Presence of hoarseness, dysphagia, respiratory stridor or torticollis indicate cervical involvement.

Physical examination of the spine reveals localised tenderness and paravertebral muscle spasm. A kyphotic deformity due to prominence of spinous process may be evident due to collapse and anterior wedging of vertebral bodies.

Tuberculous necrotic material from the cervical spine may collect in the form of a cold abscess in the retropharyngeal region; at the posterior border of sternomastoid; in the back of neck along spinal nerves and in the axilla along axillary sheath.

Involvement of the dorsolumbar spine may lead to cold abscess in the rectus sheath and lower abdominal wall along the intercostal, ilioinguinal and iliohypogastric nerves; in the thigh along the psoas sheath; in the back along the posterior spinal nerves; in the buttock along superior gluteal nerve; in the Petit's triangle along the flat muscles of abdominal wall or, in the ischiorectal fossa along the internal pudendal nerve. The presence of a sinus in the back with a thin watery discharge is a strong evidence of tuberculous involvement of the posterior arch of vertebral bodies.

Rarely, tuberculous spondylitis may present as synovitis of posterior vertebral articulations, atlanto-occipital or atlanto-axial joints or as spinal tumour syndrome.

Radiographs - Radiographs are the first line of investigations to substantiate or refute a clinical diagnosis of tuberculosis of the spine. The commonest radiological presentation is the paradiscal lesion. The earliest signs are narrowing of the joint space and loss of definition of the paradiscal margin of vertebral bodies.

The narrowing may be due to atrophy of the disc or herniation of nucleus pulposus into the vertebral bodies. The collection of tuberculous granulation tissue and necrotic material leads to formation of paravertebral abscess.

It is evident on plain radiographs as a fusiform or globular radiodense shadow or a bulging of the lateral border of psoas shadow. Long standing abscesses may erode the anterior margins of the vertebral bodies producing a scalloped appearance. Wedging of vertebral bodies leads to a kyphotic deformity.

Rare radiological presentations of tuberculosis of the spine include central type, anterior type and appendiceal type. Central disease presents as areas of destruction, ballooning of vertebral bodies and later as concentric collapse. Anterior type is more common in the paediatric dorsal spine and appears as erosion of anterior margin of vertebral bodies.

Appendiceal disease is involvement of the posterior arches. Isolated posterior arch disease is difficult to diagnose with conventional radiography but may be suspected by the presence of erosive lesions and paraspinal shadows. CT scan examination and MR scanning are increasingly being used to diagnose posterior arch disease. Presence of lateral shift indicates panvertebral disease14.

Haematological investigations - The erythrocyte sedimentation rate is usually elevated but is neither specific nor reliable in the diagnosis of spinal tuberculosis. The enzyme-linked immunosorbent assay (ELISA) has a reported sensitivity of 60 to 80 per cent15.

Stroebel et al16 have reported a sensitivity of 94 per cent and a specificity of 100 per cent for osteoarticular tuberculosis by ELISA using antibody to mycobacterial antigen6. The polymerase chain reaction is being tested for the diagnosis but is currently not available in all clinical settings15. A brucella complement fixation test may be useful in endemic areas as brucella can clinically mimic tuberculosis.

CT/MR scanning - The wide availability of CT scanning and MR scanning has increased the use of these modalities in the management of tuberculosis of the spine. CT scanning can determine posterior extension and encroachment of inflammatory tissue, bone or disc material17, and diagnose posterior spinal disease and involvement of sacroiliac joints and sacrum. It helps in guiding biopsies and planning operative interventions.

MR scanning is done to detect soft tissue masses, appendicular tuberculosis, extent of disease and the subligamentous spread of tuberculous debris.

This spread under the anterior and posterior ligaments is strongly suggestive of tuberculosis of the spine but is not pathognomonic18. MR is also useful in evaluation of intramedullary lesions and extradural spread and to differentiate between cord compression by granulation from that by bone and disc.

Skin tests - A positive Mantoux test can be observed, one to 3 months after infection. The test may be negative in almost 20 per cent patients with active disease if the disease is disseminated, or if the patient is immunocompromised or suffering from exanthematous fevers19. Co-existent infection by human immunodeficiency virus may also give a false negative skin test20.

Bone scan - Technitium (Tc) - 99 m bone scan showed increased uptake in 63 per cent patients with active tuberculosis in the series reported by Weaver and Lifeso21. The remaining patients showed a cold spot due to formation of avascular segments and abscesses. The Tc-99m scan is considered to be highly sensitive but nonspecific. It may only aid to localise the site of active disease and to detect multilevel involvement.

Smear and culture - Acid-fast bacilli may be demonstrated on smear examination. The Ziehl-Neelsen staining is a quick and inexpensive method but has a low positivity. Stains require a minimum of 104 bacilli per ml19 while culture shows a growth with only 103 bacilli per ml22. Moreover, cultures can be employed to determine drug susceptibility but the results are available only after a few weeks.

Biopsy - The high prevalence of tuberculosis in India precludes the need of histopathological diagnosis prior to starting chemotherapy. However, a biopsy may be needed in cases of equivocal clinicoradiologic findings, lack of proper response to drug therapy and suspicion of drug-resistant strains.

The method most widely used for the histopathologic diagnosis of spinal tuberculosis is computed tomography guided needle biopsy23. Alternatively, core needle biopsy may be used. The tissue obtained should be sent for culture and antibiotic sensitivity as well as histopathology. 

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