Therapeutic uses of autologous endothelial cells for vascular disease

Endothelial cells play important structural and functional roles in vascular homoeostasis. Perturbations in endothelial cell number and function are directly involved with the initiation and progression of multiple cardiovascular diseases, including atherosclerosis, hypertension and congestive heart failure. Attempts to modify these disorders have included pharmacological strategies to improve vascular and thus endothelial function. A goal of biological approaches to these disorders is the delivery of endothelial cells that might act to provide beneficial endothelial-derived factors. However, this approach has generally been limited by the lack of readily available autologous endothelial cells for delivery. The isolation of circulation-derived endothelial progenitor cells allows for direct access to autologous endothelial cells for preclinical and clinical studies. Preclinical studies using autologous endothelial cells have demonstrated beneficial effects when delivered in animal models of vascular injury and grafting. These effects are related to the endothelial nature of the cells and may be paracrine in nature. Ongoing studies are aimed at defining the nature of these effects and optimizing delivery strategies cognizant of these mechanisms.     

Nephrogenic diabetes insipidus presenting with developmental delay and intracranial calcification

A one-year-boy presented with constipation, fever, failure to thrive and developmental delay from the neonatal period. Investigations revealed persistent hypernatremia and deranged renal functions. Diagnostic work-up was suggestive of nephrogenic diabetes insipidus (NDI). Computerized tomography of head revealed calcification in the frontal, thalamic and basal ganglia region. The rare association of NDI and intracranial calcification is discussed     

Morphine tolerance does not develop in mice treated with endothelin-A receptor antagonists

Long-term use of morphine leads to development of antinociceptive tolerance. We provide evidence that central endothelin (ET) mechanisms are involved in development of morphine tolerance. In the present study, we investigated the effect of ET(A) receptor antagonists, BQ123 and BMS182874, on morphine antinociception and tolerance in mice. Mechanism of interaction of ET(A) receptor antagonists with morphine was investigated. BQ123 (3 microg, i.c.v.) and BMS182874 (50 microg, i.c.v.) significantly enhanced antinociceptive effect of morphine (P < 0.05), through an opioid-mediated effect. Treatment with a single dose of BQ123 (3 microg, i.c.v.) reversed tolerance to morphine antinociception in morphine-tolerant mice. BQ123 or BMS182874 did not affect naloxone binding in the brain. Therefore, ET(A) receptor antagonists did not bind directly to opioid receptors. [35S]GTPgammaS binding was stimulated by morphine and ET-1 in non-tolerant mice. Morphine- and ET-1-induced GTP stimulation was significantly lower (P < 0.05) in morphine-tolerant group (33% and 42%, respectively) compared to control group. BQ123 and BMS182874 did not activate binding in non-tolerant mice. BQ123 and BMS182874 significantly increased G protein activation in morphine-tolerant mice (96% and 86%, respectively; P < 0.05). These results provide evidence that uncoupling of G protein occurs in morphine-tolerant mice, and ET(A) antagonists promote coupling of G protein to its receptors, thereby restoring antinociceptive effect. These findings indicate that ET(A) receptor antagonists potentiate morphine antinociception and reverse antinociceptive tolerance in mice, through their ability to couple G proteins to opioid receptors.     

Diagnostic dilemmas in fulminant subacute sclerosing panencephalitis (SSPE)

This report describes an eleven-year-old boy with atypical features of subacute sclerosing panencephalitis (SSPE), a rare complication of measles. He had only visual symptoms for 2 months followed by rapid neurological worsening to a vegetative state in 10 days. A diagnosis of SSPE was made based on the history of measles, characteristic ocular findings, compatible magnetic resonance imaging and electroencephalographic changes, and elevated ratio of cerebrospinal fluid to serum anti-measles antibody titers     

Evaluation of endometrial steroid receptors and cell mitotic activity in women using copper intrauterine device: Can Cu-T prevent endometrial cancer?

AIMS: To study changes in endometrial proliferative indices (i.e. cell mitosis and Ki67), endometrial steroid (estrogen and progesterone) receptors, and serum estradiol and progesterone level in women using copper intrauterine device (IUD) after 6 months of use. METHODS: Fifteen healthy women were recruited having no contra indication to IUD or endometrial biopsy. Endometrial biopsies and serum samples were taken on 10/11th day of menstrual cycle at recruitment and after six months. The endometrial samples were subjected to: (i) steroid receptor estimation by immunohistochemistry; (ii) cell mitosis and Ki67 estimation by morphology and proliferative indices. RESULTS: The mean glandular mitotic index was 1.69 +/- (0.39) at first visit and 0.35 +/- (0.15) at second visit after 6 months. Similarly, Ki-67 count in glands was 11.79 +/- (1.59) at first visit and 2.40 +/- (0.54) at second visit. In the stroma, Ki67 decreased from a mean of 0.85 to 0.01 in six months. This suggested statistically significant reduction in proliferation and mitotic activity in endometrial glands and the stroma of women who used Cu-T continuously for a long period.There was a significant reduction of estrogen receptor concentration in glands (from a mean of 51.67 down to 11.67) and the stroma (from a mean of 33.00 to 8.00) over this 6-month period. The observed fall in progesterone receptor counts was less compared to other parameters studied, being marginally significant in stroma (from a mean of 32.00 down to 14.33), but not significant enough in glands (from a mean of 45.00 down to 25.00). No changes were observed in serum hormone levels in these two visits. CONCLUSION: Continuous use of copper intrauterine device causes significant reduction in endometrial mitotic activity as well as estrogen receptor concentration without affecting serum estradiol or progesterone levels. This finding infers that Cu-T may have a protective role against endometrial cancer.     

Balloon cell nevus of the pharynx

BACKGROUND: Mucosal melanotic lesions are rare, and the still rarer balloon cell variant has not been reported in the upper aerodigestive tract mucosa. We report a case of balloon cell nevus of the pharynx. METHODS: A 35-year-old woman was seen with complaints of a black color in her mouth. Physical examination revealed a diffusely pigmented posterior pharyngeal wall. The pigmentation extended superiorly to the posterior edge of the palate, and laterally, it stopped short of the posterior tonsillar pillars. The overlying mucosa was smooth, with no swelling. Flexible endoscopy showed that the lesion extended to the cricopharynx. Findings on histopathologic examination were consistent with balloon cell nevus of the pharynx. Complete excision was not possible, because the lesion was very diffuse. RESULTS: After 2 years of conservative management and regular follow-up examinations, no change in the symptoms and no increase in the lesion have been seen. CONCLUSION: Melanotic lesions in the upper aerodigestive tract mucosa are rare. This case is reported for its rarity, unusual presentation, and characteristic histopathologic features.     

Use of Joshi External Stabilizing System in postburn contractures of the hand and wrist: a 20-year experience

Postburn contractures of the hand and wrist can range from a minor cosmetic problem to a crippling condition. The contractures, initially limited to the skin, extend to all the soft-tissue structures over time, often necessitating capsulotomies and tendon lengthening, although they still may not be amenable to total correction. The Joshi External Stabilizing System (JESS) is a versatile, lightweight external fixator consisting of K wires, distractors, and connecting rods (both hinged and nonhinged) along with various link joints. JESS is a dynamic system that allows the lengthening of the contracted tissues via slow distraction, causing minimal surgical insult. This is a retrospective review of 218 cases of postburn contractures of the hand treated with JESS during the last 20 years. Deformities varied from finger contractures to metacarpophalangeal joint and wrist contractures. All cases were of long duration at the time of presentation with the original injury being 4 months to 20 years old. All were assessed for the degree of function and deformity. The patients' activities of daily living were recorded and x-rays taken to evaluate joint configuration. The patients underwent a conservative surgical release followed by application of the appropriate JESS frame for the correction of the residual deformity. After 6 weeks, the frame was removed and hand therapy continued. An analysis is provided of the outcome. The technique produces functional hands with minimal surgical insult.