Behavioral studies following lesions of the mesolimbic and mesostriatal serotonergic pathways.

The behavior of rats with selective lesions of either the dorsal (B7), median (B8), or lateral (B9) raphe nuclei was compared to that of sham-lesioned controls in a variety of experimental situations. As described previously, the extent of damage to the midbrain raphe nuclei was determined by fluorescence histochemistry, and the tryptophan hydroxylase and tyrosine hydroxylase activities of 6 forebrain regions were measured for each rat. None of the lesions affected tyrosine hydroxylase activity. Lesions of B7, which reduced tryptophan hydroxylase in the striatum, thalamus, cortex, and hypothalamus, had no significant effect on any of the behavioral measures. Lesions of B9, although twice as large, neither reduced forebrain tryptophan hydroxylase significantly nor affected any of the behavioral variables. However, B8 lesions, which reduced hippocampal, septal, cortical, and hypothalamic tryptophan hydroxylase, had behavioral effects similar to those reported after combined raphe lesions parachlorophenylalanine. Median raphe-lesioned rats were hyperactive when placed in a novel environment and throughout the dark phase of the light/dark cycle. With respect to locomotor activity, B8-lesioned rats were also hyper-responsive to amphetamine. When placed in a stabilimeter and subjected to repeated air puff stimuli, rats with B8 lesions exhibited larger startle responses. Furthermore, only B8-lesioned animals perseverated when given two unreinforced trials in a Y-maze. All these histologic, biochemical, and behavioral variables were assessed individually for all 39 animals, and a multivariate correlational analysis incorporating the data of this and the preceding paper is presented here. These experiments suggest that the mesolimbic serotonergic pathway originating in B8 subserves some of the inhibition necessary to dampen behavioral responsivity.     

Familial visceral myopathy

We report on a 13-year-old white body with familial visceral myopathy. The abnormalities of the gastrointestinal and urinary tracts are described and the literature regarding urologic implications of this disorder is reviewed.     

Interactions of human neutrophils with leukotoxic streptococci

Most strains of Streptococcus pyogenes contain a toxin which can kill neutrophils. Previous workers failed to show any correlation between leukotoxin content and virulence of animals or humans. We examined the in vitro interactions of a leukotoxic streptococcus and a nonleukotoxic variant with human neutrophils. At ratios of 200 streptococcal colony-forming units per neutrophil, the toxic strain killed 92.8 +/- 2.0% of neutrophils, and the nontoxic strain killed only 9.0 +/- 1.2%. Despite this, ingestion of the two strains was equal. Postphagocytic oxidative metabolism was equivalent with low numbers of either toxic or nontoxic streptococci but depressed with high numbers of leukotoxic streptococci. At 20 min, neutrophils were able to kill leukotoxic (99.6 +/- 0.3% killed) and nonleukotoxic streptococci (99.5 +/- 0.2% killed) equally efficiently (P = 0.42). Thus, leukotoxicity does not interfere with the ability of neutrophils to destroy streptococci. This may explain why leukotoxicity does not appear to be an important factor in streptococcal virulence.     

Danger of urography in hyperuricemic children with Burkitt's lymphoma

During three years, four patients with diffuse abdominal involvement by North American Burkitt's lymphoma presented at Children's Hospital of Philadelphia. In three of these untreated patients, an intravenous urogram showed prolonged nephrograms or tubular stasis secondary to urate nephropathy. Careful attention must be given to uric acid levels and, in some instances, nuclear and ultrasonic scanning may replace the traditional urogram or computerized tomography with contrast in the evaluation of the pediatric patient with an abdominal mass, particularly if serum uric acid levels are elevated.     

The role of intraoperative rapid parathyroid hormone monitoring for predicting thyroidectomy-related hypocalcemia

OBJECTIVE: To determine if the intraoperative rapid parathyroid hormone (PTH) assay can be used to accurately predict postoperative calcium levels following total or completion thyroidectomy. DESIGN: A prospective study. SETTING: Tertiary care referral center. PATIENTS: One hundred four patients following a total or completion thyroidectomy.Intervention Intraoperative rapid plasma PTH levels were determined for patients undergoing a total or completion thyroidectomy. MAIN OUTCOME MEASURES: Parathyroid hormone levels were recorded after the induction of anesthesia, before excision, and 5, 10, and 20 minutes after thyroidectomy. Postoperative calcium levels were monitored every 6 hours until hospital discharge. Intraoperative PTH levels were correlated with postoperative calcium levels and clinical symptoms of hypocalcemia. RESULTS: Twenty-two patients (21.2%) required short-term postoperative calcium supplementation, and 2 (1.9%) required long-term calcium replacement. There was a statistically significant difference between those patients requiring calcium replacement and those who did not require calcium supplementation, for postoperative total calcium level (7.2 vs 8.1 mg/dL [1.8 vs 2.0 mmol/L]; P<.001) and ionized calcium level (3.76 vs 4.36 mg/dL [0.94 vs 1.09 mmol/L]; P<.001). In addition, the PTH changes from baseline demonstrated statistically significant differences at 5, 10, and 20 minutes after the excision between the 2 groups (P<.005). In those patients requiring calcium supplementation, 14 (64%) of 22 demonstrated a change in PTH level at 20 minutes of greater than 75% from baseline, and in those patients who did not require postoperative calcium supplementation, 61 (74%) of 82 demonstrated a change in PTH level of less than 75% from baseline (P<.005). CONCLUSION: Intraoperative PTH monitoring may be a useful tool in identifying patients who will not require postoperative calcium supplementation following total or completion thyroidectomy.     

Intralesional cidofovir for pediatric recurrent respiratory papillomatosis

OBJECTIVE: To compare disease response among children with recurrent respiratory papillomatosis (RRP) who underwent combined surgical debulking and intralesional cidofovir injections vs repeated surgical debulking only. DESIGN: Retrospective medical record review; follow-up range: 16 to 56 months. SETTING: Tertiary care children's hospital. PATIENTS: Seven children with RRP, including 4 subjects treated with cidofovir and 3 controls matched for age and initial papilloma staging score. INTERVENTIONS: Subjects treated with cidofovir underwent combined surgical debulking and intralesional cidofovir injection every 2 months until disease remission. Control subjects underwent repeated surgical debulking at individually determined intervals. MAIN OUTCOME MEASURES: Intraoperative endoscopic photographs were retrospectively assigned papilloma staging scores. Cidofovir and control group comparisons were made using nonparametric 2-sample Wilcoxon rank-sum (Mann-Whitney) testing, and comparisons of initial and final papilloma staging scores were made using nonparametric matched-pair Wilcoxon signed-rank testing. RESULTS: The final cidofovir group scores were significantly lower than the control group scores (P < .05). Within-group differences between initial and final scores were not significant (cidofovir group, P = .07; control group, P = .29). CONCLUSIONS: Four children with RRP were safely and successfully treated with intralesional cidofovir injection. Consideration should be given to using cidofovir more widely for treatment of pediatric RRP. Larger numbers in the cidofovir and control groups are needed in future studies to determine the true impact of cidofovir on management of this disease.     

Genetic counselors: translating genomic science into clinical practice

In a time of emerging genetic tests and technologies, genetic counselors are faced with the challenge of translating complex genomic data into information that will aid their client's ability to learn about, understand, make, and cope with decisions relating to genetic diagnoses. The first of two companion articles in this issue examines the role of the genetic counselor, particularly in counseling individuals at risk for or diagnosed with breast cancer, in an era of high-tech health care and gene patents.