Deafferentation hypersensitivity in the rat after dorsal rhizotomy: a possible animal model of chronic pain.

Unilateral dorsal rhizotomies were done at the cervicothoracic and lumbosacral spinal cord levels in rats. In preliminary experiments dermatome maps were determined for the roots to be sectioned. The behavior of 37 rats was observed for many months after the rhizotomies. The rats with the dorsal roots sectioned in the cervicothoracic spinal cord exhibited the following behavior: at the border of the skin adjacent to the zone of deafferentation, the rat scratched vigorously and progressively denuded the skin; self-mutilation of varying degrees occurred in the deafferented limb. In some animals scratching occurred in the contralateral skin dermatome opposite to the partially deafferented zone. The rats with the dorsal roots sectioned at the lumbosacral level exhibited hypersensitivity to cutaneous stimulation but there was no scratching or self-mutilation. These results are discussed in the light of previous similar research.     

The effect of donor factors on human islet yield and their in vivo function

BACKGROUND: A major problem in the islet field is the high selectivity exercised in accepting cadaveric pancreas for islet isolation. This practice is based on experience that indicates that islet yield and posttransplant function are related to donor demographics and injury mechanisms. OBJECTIVE: To examine factors influencing islets recovery and in vivo function with emphasis on donor-related factors. METHODS: Islets were isolated from 99 human donor pancreata, and islet yield was reported as islet equivalent per gram pancreatic tissue. Donor, procurement, and isolation factors were collected for each isolation and correlation statistics were performed between these variables and islet yield. RESULTS: Results indicated a differential effect of enzyme mixes on yield with Collagenase P digestion most suitable for increased ischemic time (R2 = 0.1; P < .08), Liberase with small donor pancreas size and elevated preprocurement glucose (R2 = 0.15; P < .02), and Serva with female donors (R2 = 0.17; P < .06). Islets from 29 isolations were further tested by transplantation under the kidney capsule of immune-deficient NOD-SCID mice. Although all 29 preparations had acceptable in vitro perfusion parameters indicating viability, only 19 functioned in vivo with serum levels of insulin >5 U/mL and C peptide >1.5 ng/mL. No significant differences in donor, procurement, and isolation factors were evident between the islet preparations that functioned in vivo and those that were nonfunctional. CONCLUSIONS: These data demonstrate that although yield is affected by a variety of donor factors and enzyme mixes, these factors do not affect islet in vivo function.     

Radiation dose-volume effects on growth hormone secretion

Growth hormone (GH) deficiency is a known consequence of central nervous system irradiation. The relationship between the dose to the hypothalamus and the time to onset of clinically significant GH deficiency is unknown. Conformal radiotherapy (CRT) techniques allow for a more accurate determination of hypothalamic dosimetry. We correlated the dosimetry of the hypothalamus and the peak GH value after CRT in children with localized primary brain tumors.

The arginine tolerance/ -dopa test was performed before (baseline) and repeated 6 and 12 months after CRT in 25 children (median age 4.8 years) with ependymoma (n = 15) or low-grade (n = 8) or high-grade (n = 2) astrocytoma. None had evidence of GH deficiency (arginine tolerance/ -dopa peak GH level >10 ng/mL [10 μg/L]) at baseline. Peak GH levels were modeled as a function of time after CRT and volume of the hypothalamus receiving a dose within the specified intervals of 0–20 Gy, 20–40 Gy, and 40–60 Gy. The model was used to predict the change in the peak GH levels over time (0–12 months) and fit under the assumption that the integral effect of irradiation was a linear sum of the products of the volume receiving a particular dose and the impact of that dose.

The peak GH level declined during the 0–12 months after CRT (p < 0.0001). GH deficiency was observed in 11 children at 6 months and a total of 20 children at 12 months. As expected, the effect of the dose interval 0–20 Gy was smaller than the 20–40-Gy dose interval; the largest effect was noted with the dose interval 40–60 Gy. The peak GH level may be predicted using the following estimating equation within the time limit of 0–12 months: GH(t)=Exp[ln(bGH)−(0.00058V_{0–20 Gy}+0.00106V_{20–40 Gy}+0.00156V_{40–60 Gy})×t], where bGH is the baseline peak GH level, V_{0–20 Gy}, V_{20–40 Gy}, and V_{40–60 Gy} is the percent-volume of the hypothalamus irradiated from 0 to 20 Gy, 20 to 40 Gy, and 40 to 60 Gy, respectively, and t is time after irradiation. When included in the model, the rate of decline in the peak GH response also was influenced by hydrocephalus and tumor location.

The peak GH response within 12 months after CRT depends on hypothalamic dose-volume effects and may be predicted on the basis of a linear model that sums the effects of the entire distribution of dose. The modeled effects may be used to optimize radiotherapy and minimize and treat GH deficiency.     

Idiopathic "benign" intracranial hypertension: case series and review.

Idiopathic "benign" intracranial hypertension is an uncommon but important cause of headache that can lead to visual loss. This study was undertaken to review our experience in the diagnosis and management of idiopathic intracranial hypertension, giving special attention to treatments used. A retrospective chart review was conducted on 32 patients diagnosed with idiopathic intracranial hypertension between 1984 and 1995. Subjects included 23 females and ranged in age from 2 to 17.5 years. Headache was the most common symptom, followed by nausea and vomiting, double vision, and visual loss. Papilledema was the most common sign. Others were VIth cranial nerve palsy and compromised visual acuity at or within 3 months of presentation. Management included administration of acetazolamide or corticosteroids, lumboperitoneal shunt, optic nerve fenestration, and repeat lumbar puncture. Treatment combinations were used in 40% of cases. During follow-up, headache, papilledema, and decreased visual acuity persisted for longer than 10 months in a significant number of patients. We conclude that idiopathic intracranial hypertension causes significant short- and long-term morbidity with no proven effective treatment available. A prospective study is needed to establish the indications for treatment and the efficacy of the treatments used.