Metabolic effects of sapropterin treatment in autism spectrum disorder: a preliminary study.

Sapropterin, a synthetic form of tetrahydrobiopterin (BH4), has been reported to improve symptoms in children with autism spectrum disorder (ASD). However, as BH4 is involved in multiple metabolic pathway that have been found to be dysregulated in ASD, including redox, pterin, monoamine neurotransmitter, nitric oxide (NO) and immune metabolism, the metabolic pathway by which sapropterin exerts its therapeutic effect in ASD effect remains unclear. This study investigated which metabolic pathways were associated with symptomatic improvement during sapropterin treatment. Ten participants (ages 2-6 years old) with current social and/or language delays, ASD and a central BH4 concentration 30 nM l(-1) were treated with a daily morning 20 mg kg(-1) dose of sapropterin for 16 weeks in an open-label fashion. At baseline, 8 weeks and 16 weeks after starting the treatment, measures of language, social function and behavior and biomarkers of redox, pterin, monoamine neurotransmitter, NO and immune metabolism were obtained. Two participants discontinued the study, one from mild adverse effects and another due to noncompliance. Overall, improvements in subscales of the Preschool Language Scale (PLS), Vineland Adaptive Behavior Scale (VABS), Aberrant Behavior Checklist (ABC) and autism symptoms questionnaire (ASQ) were seen. Significant changes in biomarkers of pterin, redox and NO were found. Improvement on several subscales of the PLS, VABS, ABC and ASQ were moderated by baseline and changes in biomarkers of NO and pterin metabolism, particularly baseline NO metabolism. These data suggest that behavioral improvement associated with daily 20 mg kg(-1) sapropterin treatment may involve NO metabolism, particularly the status of pretreatment NO metabolism.

Ultrastructural observations in pleomorphic liposarcoma.

An ultrastructural study of pleomorphic liposarcoma with an unusual clinical presentation is described. A 69-year-old Caucasian female presented with recurrent superficial phlebitis of left leg, which responded only partially to conventional therapy. Following investigations, a mass was excised. Diagnosis of pleomorphic liposarcoma was made on microscopic examination. Numerous lipid droplets in the cytoplasm and often within intranuclear extensions of cytoplasm were seen on oil red O stain of frozen sections. Ultrastructural features are quite distinctive. The cells varied from small to often large pleomorphic cells with numerous lipid spaces without limiting membrane, large pleomorphic nuclei, and an abundance of cytoplasmic organelles. Centrioles were very prominent, in close proximity to nuclei, and collections of autophagocytic inclusions. Intercellular collagen was immature and scant. These features are compared to ultrastructural features of malignant fibrous histiocytoma, pleomorphic rhabdomyosarcoma, and cardiac myxoma, indicating that ultrastructural features are distinctive and help differentiate similar soft tissue tumors.

Primary Kaposi's sarcoma of lymph nods.

An example of Kaposi's sarcoma with primary involvement of lymph nodes is reported. The patient, a woman, was admitted because of generalized lymphadenopathy and anemia. She was also known to have congestive heart failure of rheumatic origin. SMA-12 screening disclosed hypercalcemia on several occasions during her hospitalization. Levels of circulating parathormone and prostaglandins E2 and F were markedly increased. Total bone scan was negative for involvement by tumor. Electronmicroscopic examination of an involved lymph node disclosed secretory bodies in the cytoplasm of malignant cells and other cells, with clear indication of endothelial origin. The rarity of Kaposi's sarcoma with primary lymph nodal involvement in the United States is discussed. So far as is known by the authors, no example of Kaposi's sarcoma has been associated with hypercalcemia due to ectopic endocrine production.

Carcinosarcoma and mixed müllerian tumors of the fallopian tube: report of four cases.

We report a 74-year-old woman with malignant mixed müllerian tumor and three women, aged 47, 58, and 76 years, with carcinosarcomas, all primary in the fallopian tube. The tumors grew predominantly intraluminally and were associated with hydrosalpinx. All four patients underwent salpingectomy. Two of them received radiation therapy; one died within 9 months because of the tumor and the second is well 2 years after diagnosis. Of the two women without additional therapy, one is alive with tumor 53 months postoperatively and the other is well 1 year after surgery. Available data suggest that these neoplasms are relatively radioresistant and that their prognosis correlates best with local invasiveness.

Comparison of colposcopy directed biopsies and cold knife conization in patients with abnormal cytology.

One hundred patients with abnormal cytology were evaluated by colposcopy, and histologic material was obtained by directed biopsies, cold knife conization and endocervical curettage. The colposcopy directed biopsies provided the diagnosis in 94 per cent of the patients, and the colposcopic impression was accurate in 89 per cent of the patients. Cold knife conization was performed in 98 patients, since two patients had invasive carcinoma on colposcopic directed biopsy. In 75 patients, the histopathologic finding on cone biopsy was in complete agreement with the directed biopsies. In 11 patients, the directed biopsies were a degree higher than on cone biopsy, and in six patients the histopathologic findings were a degree lower. In six patients the colposcopic directed biopsies missed the diagnosis of dysplasia. No patients with carcinoma in situ or invasive carcinoma were missed by the colposcopic directed biopsies.

Relationship between hepatic morphology and clinical and biochemical findings in morbidly obese patients.

This study was undertaken to determine the interrelations between clinico-biochemical parameters and hepatic morphology in markedly obese patients. One hundred and sixty-six women and 52 men comprise this series. There was a statistically significant association of carbohydrate metabolism disturbance with increasing age and corpulence and, in women, with hyperuricaemia and morphological alterations of the liver. Menstrual irregularities also correlated well with hepatic morphology. The livers frequently exhibited steatosis, but other morphological changes were mild. Compared with women, men had higher triglyceride values, more severe hepatic involvement, and poorer correlation of carbohydrate disturbances with hepatic histology. The results indicate a central role of the impaired carbohydrate utilization in the biochemical and hepatic alterations of obesity.