Thomas Pillar

Failure of passive transfer of serum from patients with alopecia areata and alopecia universalis to inhibit hair growth in transplants of human scalp skin grafted on to nude mice

We have previously demonstrated regrowth of hair in scalp skin grafts taken from patients with alopecia areata (AA) and alopecia universalis (AU) following engraftment on to nude mice. This present study was to determine whether serum from patients with AA and AU, has a role in the process of hair loss and the role of antibodies and complement. Forty mice were grafted with transplants obtained from seven patients. One group of the grafted mice was given patients’ serum and another group normal serum. The mice were treated topically with cyclosporin (CyA), or olive oil. Hair growth was noted in most grafts and intravenous injections of serum did not prevent or inhibit this process. Immunofluorescence studies before grafting showed deposition of immunoglobulins and complement in hair follicles in both normal and affected scalp skin, but a more striking deposition was noted in the affected skin. Deposition of immunoreactants after grafting was observed only after the injection of serum from the patients but not with normal serum. Thus the sera from patients with AA or AU, when injected into nude mice with hair transplants from the scalp skin of patients with these disorders, does not alter the hair growth despite deposition of immunoreactants around the hair follicles.

The pathogenesis of lichen planus

The histological features of lichen planus (LP) are characterized by typical epidermal change with dermal lymphocytes that are mostly Ia positive T cells. In order to find out whether the primary event of LP is damage to basal keratinocytes or a delayed hypersensitivity reaction in which an as yet unidentified antigen activates T lymphocytes that destroy keratinocytes, we transplanted skin obtained from six patients with LP. Two millimetre punch and split thickness of grafts were obtained from involved and uninvolved areas from each patient and grafted onto nude mice. Biopsies were taken from the grafts at 14 and 21 days after transplantation for histological and immunofluorescence studies and after 6 weeks for Dopa incubation for melanocyte populations. A complete disappearance of the pathological changes of LP was found 21 days following grafting. An increased number of melanocytes was noted. This indicates that the pathogenesis of LP may not be due to an inherent change in the epidermal cells, but rather to the migration of cellular elements of the immune system.

Vitiligo and idiopathic guttate hypomelanosis. Repigmentation of skin following engraftment onto nude mice.

Several diseases are included in the category of hypomelanosis. Their clinical course as well as the pathogenesis are diverse and in many cases poorly understood. The aim of the present study is to use the nude mice model to determine whether the primary defect in various pigmentary skin disorders is inherent to the tissue itself or is secondary to systemic factors. Split-thickness skin grafts obtained from patients with vitiligo, acquired hypomelanosis guttata, and tyrosinase-negative albinism were grafted onto nude mice. Histologic examination and dopa staining were performed prior to and following the engraftment. The dopa staining was performed on the epidermal sheet following separation from the dermis. The depigmented area of the vitiligo became completely pigmented 6 to 10 weeks after skin transplantation. The dopa reaction that was negative prior to skin engraftment became completely positive after the transplantation. The number of melanocytes (expressed per square millimeter of skin surface) 8 weeks after transplantation was 197 +/- 73 mm2. Dopa reaction in acquired hypomelanosis guttata showed reduction of the number of melanocytes in the depigmented macula as compared with the surrounding area (55.25 +/- 18.00 mm2 vs 220 +/- 28.28 mm2. Twenty days after skin transplantation, repigmentation of the area was observed. The number of melanocytes increased significantly (388.75 +/- 213 mm2). The grafted skin obtained from patients with tyrosinase-negative albinism showed persistence of the depigmentation after skin transplantation. Dopa reaction was negative prior to and 8 weeks after transplantation. The results of the present study suggest that systemic factors may play a role in the pathogenesis of vitiligo and acquired hypomelanosis guttata.

Topical cyclosporine in male pattern alopecia

We previously demonstrated a systemic and topical effect of cyclosporine on hair growth in an experimental model composed of human scalp skin transplanted onto nude mice. The aim of this study was to determine whether topical cyclosporine affects male pattern alopecia. For 4 months in a double-blind study, 10 subjects were treated with cyclosporine and three were treated with olive oil. Hair growth was evaluated by photographs and hair counts. Significant hair growth was observed in two of the eight patients who completed the study. In one the hair growth was cosmetically satisfactory. No systemic or cutaneous side effects were noted.

Automatic and voluntary lateral weight shifts in rehabilitation of hemiparetic patients

One of the main objectives of exercise therapy for hemiparetic patients is the rehabilitation of their impaired ability to accept and bear bodyweight on the involved lower extremity. The purpose of this study was to compare two types of therapeutic exercises, automatic and voluntary weight shifts, used as treatment for this problem. Thirteen hemiparetic patients and nine age-matched healthy controls participated in the study. Criterion variables were four: (1) body sway; (2) location of the centre of pressure; (3) activation pattern of the gluteus medius and medial gastrocnemius muscles; and (4) magnitude of activation of these two muscles. Each subject was tested three times: (1) during static stance; (2) while standing on a moving platform that imposed automatic lateral weight shifts; and (3) while standing on a stationary base and voluntarily shifting bodyweight from one lower limb to the other. Values of sway and location of the centre of pressure on the mediolateral axis were collected by the Chattecx balance system; magnitude and modulation of the muscular activity in both lower extremities were recorded with surface electromyography. The findings showed significant differences between patients and controls in all four variables. Regarding differences between exercise modes, the main finding pointed to larger sways in voluntary as compared to automatic weight shifts. Presumably, body fixation during automatic perturbations was manifested in a decreased body sway. Stance symmetry and the EMG activation profile of the paretic muscles were not improved by either exercise mode.

The effect of topical cyclosporin on the immediate shedding of human scalp hair grafted onto nude mice.

Considerable evidence now exists that cyclosporin (CyA) has a stimulatory effect on hair growth. Previously, we demonstrated the systemic effect of CyA on hair growth using an experimental model of human scalp skin graft transplanted onto nude mice and rats. In the present study we used this model to investigate the effect of topical CyA on human hair growth. One group of 15 mice was treated with topical CyA in olive oil, and a second group of 10 mice with olive oil only. The numbers of grafts with hair and the number of hairs per graft in the different groups were compared. A statistically significant delay in hair shedding appeared from day 24 onwards in the CyA treated group. This pilot study supports the possibility that CyA may be effective in the treatment of alopecia.

ELECTROMYOGRAPHIC ACTIVITY OF THE BICEPS BRACHII MUSCLES AND ELBOW FLEXION DURING ASSOCIATED REACTIONS IN HEMIPARETIC PATIENTS

Dickstein R, Pillar T, Abulaffio N: Electromyographic activity of the biceps brachii muscles and elbow flexion during associated reactions in hemiparetic patients. Am J Phys Med Rehabil 1995;74:427—431 Activity of the biceps brachii muscles and movements of the elbows were studied during associated reactions in hemiparetic patients and in healthy volunteers. Onset time and increase in electromyographic (EMG) activity during associated reactions and onset of elbow flexion and its maximal magnitude were measured. Testing was performed while standing with a footswitch attached to the sole of the nonparetic foot in patients and to the sole of the right foot in controls. Lifting of that foot generated a trigger signal that served to time the dependent variables. Bilateral EMG activity associated with one foot stance appeared in the two upper extremities in both patients and controls. Elbow flexion occurred in the majority of patients bilaterally, whereas in controls it frequently took place on one side only. There was a significant difference between patients and controls in onset of EMG activity and elbow flexion. This difference indicates an earlier preparatory activity to one foot stance in the upper limbs of patients than in healthy controls. The greatest excursion into flexion was measured in the paretic upper extremity of patients; it significantly exceeded both the flexion angle measured in controls and increase in flexion angle on the nonparetic side. Further understanding of the nature of associated reactions seems to be required for their adequate treatment by physical procedures.

Vertical force loaded on walking canes in hemiparetic patients

Abstract This study was designed to measure the amount of force applied by hemiparetic patients to either a 4-point or a 1-point cane during a single measurement session as well as at specific time intervals after the first evaluation. The influence of usage of either cane type on gait symmetry was also tested. Data on vertical forces loaded on a 4-point and a 1-point cane along with temporal gait variables were gathered from 28 hemiparetic patients, residents of a geriatric rehabilitation institution. Patients were tested at least twice with an interval of 7–14 days between measurements. Testing at each session included measurements during 4-point cane ambulation; Whenever possible. measurements during 1-point cane and/or during free ambulation were also performed. It was found that during the same measurement session, peak force as well as mean force loaded on the 4-point cane was not statistically different from the force applied to a 1-point cane. Yet because of a slower cadence adopted during 4-point cane gait, the integrated force applied to it was larger than the integrated force loaded on a 1-point cane. The peak and integrated forces applied to both cane types decreased with the passage of time. Regarding gait symmetry, duration of single-support period of the affected leg remained 0.6 of the equivalent period in the non-paretic leg. Combination of this finding with the fact that cadence increased over time indicates that the increase in weight bearing by the affected leg could be maintained for only a short period of time, yet the capability to repeat this event frequently has improved.

An ultrasonic-operated kinematic measurement system for assessment of stance balance in the clinic

This study describes the application of a kinematic measurement system based on ultrasonic technology to enable the assessment of stance balance in the clinic. The system is composed of 1-8 ultrasonic transducer markers which transmit ultrasonic waves, and three ultrasonic receivers. The spatial position of each marker is monitored by calculation of the time interval between transmission and reception of the wave. Sway data from the waist of 44 healthy subjects and 15 hemiparetic patients were collected during quiet stance. The results distinguished between data collected with and without vision, between patients and controls, and between the two sides of the body. The findings were found to be valid and reliable in repeated measurements. RELEVANCE:--Assessment of stance balance in the clinic is a requisite for quantifying disability and measuring improvement in patients with postural control deficits. Due to high costs and complexity of operation, the use of prevailing equipment for these purposes is mainly confined to research facilities. This paper describes a unique kinematic measurement system whose low price and ease of operation make it feasible for clinical use.

Response of aged versus young skin to intradermal administration of interferon gamma

BACKGROUND Interferon gamma (IFN-gamma) induces the interaction of intercellular adhesion molecule-1 (ICAM-1) and lymphocyte function-associated antigen type 1 expression, and of HLA-DR antigens by keratinocytes. OBJECTIVE The aim of the present study was to determine the potential ability of aged versus young skin to respond to intradermal administration of IFN-gamma, as an in vivo immunologic stimulus. METHODS For 3 consecutive days elderly and young volunteers were injected with 10 micrograms of recombinant IFN-gamma diluted in 0.1 ml of sterile water. On day 5, punch biopsy specimens were obtained from the injected sites. Histologic and immunohistochemical stainings were performed on all sections. RESULTS ICAM-1 was expressed by keratinocytes in both aged and young skin. An impairment was manifested mainly by the reduced accumulation of mononuclear cells throughout the dermis, the absence of HLA-DR expression by keratinocytes in 7 of 10 elderly volunteers, and the absence of an effect on the Langerhans cell population. CONCLUSION This observation shows a diminished immune response in aged skin.