Exploratory Multisite MR Spectroscopic Imaging Shows White Matter Neuroaxonal Loss Associated with Complications of Type 1 Diabetes in Children.

BACKGROUND AND PURPOSE: Type 1 diabetes affects over 200,000 children in the United States and is associated with an increased risk of cognitive dysfunction. Prior single-site, single-voxel MRS case reports and studies have identified associations between reduced NAA/Cr, a marker of neuroaxonal loss, and type 1 diabetes. However, NAA/Cr differences among children with various disease complications or across different brain tissues remain unclear. To better understand this phenomenon and the role of MRS in characterizing it, we conducted a multisite pilot study. MATERIALS AND METHODS: In 25 children, 6-14 years of age, with type 1 diabetes across 3 sites, we acquired T1WI and axial 2D MRSI along with phantom studies to calibrate scanner effects. We quantified tissue-weighted NAA/Cr in WM and deep GM and modeled them against study covariates. RESULTS: We found that MRSI differentiated WM and deep GM by NAA/Cr on the individual level. On the population level, we found significant negative associations of WM NAA/Cr with chronic hyperglycemia quantified by hemoglobin A1c (P < .005) and a history of diabetic ketoacidosis at disease onset (P < .05). We found a statistical interaction (P < .05) between A1c and ketoacidosis, suggesting that neuroaxonal loss from ketoacidosis may outweigh that from poor glucose control. These associations were not present in deep GM. CONCLUSIONS: Our pilot study suggests that MRSI differentiates GM and WM by NAA/Cr in this population, disease complications may lead to neuroaxonal loss in WM in children, and deeper investigation is warranted to further untangle how diabetic ketoacidosis and chronic hyperglycemia affect brain health and cognition in type 1 diabetes.

[Quantification of brain metabolites by 1H spectroscopy using cyclohexane as an external reference].

We tested the reliability of quantifying brain metabolite concentrations by MR spectroscopy. We employed a PRESS sequence and used a cyclohexane sample as an external standard. The signal intensity ratios of water and cyclohexane were measured by changing the geometrical arrangement of the cyclohexane sample and water phantom with various loading factors of the coil. Choline (Cho) concentrations were calculated from the signal intensity ratios of Cho and water and compared with actual Cho concentrations (1.0 to 2.6 mmol/L). The brain metabolites Cho, creatine/phosphocreatine (Cr/PCr) and N-acetylaspartate (NAA) were evaluated in five normal volunteers and six patients with metastatic brain cancer before (0 Gy), after 20 Gy and after 40 Gy of whole brain radiotherapy. Variation in the ratio of spectrum intensity between water and cyclohexane was less than 1.5% for various geometrical arrangements and loading factors. The error in quantification of Cho concentrations in the phantom study was 0.05 +/- 0.10 mmol/L. The concentrations measured in the volunteers were: Cho 1.6 +/- 0.4 mmol/L, Cr/PCr 6.4 +/- 1.1 mmol/L and NAA 8.2 +/- 0.1 mmol/L. There was no significant difference (p > 0.05) in these concentrations between the control group and the patients before, during, or after radiotherapy.

An external reference for in vivo quantification of 1H spectroscopy.

We studied the validity of using an external signal reference for absolute quantification of brain metabolites. We chose cyclohexane as the signal standard. An expression of a perturbed magnetic field in diamagnetic cylindrical materials was first obtained by using a method of equivalent magnetic charges. Broadening of the spectrum in this perturbed magnetic field was then computed. We performed phantom studies. We measured the full width at half maximum (FWHM) of the cyclohexane and the signal ratio (SR) between water and cyclohexane in spheres of two different diameters, and in cylinders of various diameters and lengths. The observed FWHM and SR in the small cylinders had large variations in distribution, whereas those in the spheres and in the large cylinders had small variations. Specifically, in a cylinder with a diameter > 5 cm and with a length > 10 cm, the variation of the SR was < 1.0%. The diameter and the length of the cylinder preferably are large when a cylindrical material is adopted as an external signal standard.

Comparative study of combination chemotherapy of ovarian cancer: cyclophosphamide, adriamycin and cisplatin versus 5-fluorouracil, cyclophosphamide and mitomycin C.

CAP, a multiple-drug combination therapy using cyclophosphamide (750 mg/m2), adriamycin (20-30 mg/m2) and cisplatin (50-75 mg/m2), was applied to 69 cases of epithelial ovarian cancer. The results of this therapy were compared with those of FAM (involving 5-fluorouracil, cyclophosphamide and mitomycin C) in 47 cases of the same cancer, retrospectively. The 5-year survival rate was 61.6% for cases treated with CAP and 56.3% for cases treated with FAM. All 9 patients at stage Ia treated with CAP are free of disease, however, 3 patients out of 13 at stage Ia treated with FAM experienced a recurrence of the disease and died. In stage III and IV cases with detectable lesions, a response was observed in 61.3% (19/31) treated with CAP and in 10.5% (2/19) treated with FAM.

[Cisplatin, adriamycin and cyclophosphamide combination chemotherapy of epithelial ovarian cancer].

The chemotherapeutic effects of cisplatin + adriamycin + cyclophosphamide (PAC) on 50 epithelial ovarian cancers were compared with the effects of 5-fluorouracil + cyclophosphamide + mitomycin C (FAM) in 17 patients. The cumulative survival at 5 years was 61.1% in all patients, 62.5% in patients treated with PAC and 54.7% in patients treated with FAM. The 5-year survival rate was 100% in Stage I, 63.5% in Stage II, 40.1% in Stage III and 22.2% in Stage IV. Of 22 patients with Stage III and IV treated with PAC, 16 patients responded (8CRs + 8PRs). The median survival duration of the treated patients was 19 months. On the other hand, of 8 patients treated with FAM, only one patient responded (PR). The median survival duration was 7 months. These results indicated the effectiveness of PAC chemotherapy against advanced ovarian cancer. No severe toxicity was observed during treatment with PAC or FAM.

Malignant lymphoma of the uterine cervix. Cytologic diagnosis of a case with immunocytochemical corroboration.

The cytologic findings in a case of primary malignant lymphoma of the uterine cervix initially suggested the presence of a malignant neoplasm. By the use of immunologic methods, the lymphoma cells were shown to possess the nature of B lymphocytes. The need for cytochemical study to make a definitive diagnosis of this rare condition is emphasized. The cytologic findings are compared with those of cytologically similar conditions in the cervix: reticulum-cell sarcoma, chloroma and endometrial stromal sarcoma.

Verrucous carcinoma of the uterine cervix: report of a case with follow-up of 6 1/2 years.

A case of verrucous carcinoma of the uterine cervix was reported with a long-term follow-up and close observation. The patient was a 73-year-old, Japanese female, who had a suspicious Papanicolaou smear on routine examination. The cervix was replaced by a papillary mass, which was diagnosed as benign papilloma. The patient was followed every 6 months with cytology, colposcopy, and punch biopsy. No cytologic or microscopic diagnosis of invasive squamous cell carcinoma was made during the entire follow-up period. Total abdominal hysterectomy and partial vaginectomy were performed after 6 1/2 years' follow-up, and the tumor was finally diagnosed as verrucous carcinoma. The patient is alive and well 4 years after the operation.

Cytologic findings of ascites from patients with ovarian dysgerminoma.

The cytomorphologic observations of ascites from three patients with ovarian dysgerminomas are presented. As compared with those in adenocarcinoma, the cytologic findings in this rare malignant ovarian tumor showed more cells lying isolated or in sheetlike arrangements, fewer cells with discrete cytoplasmic vacuoles, less frequent thickening of the nuclear membrane and more frequent multinucleolation.

Adenocarcinoma of the uterine cervix metastatic from primary stomach cancer. Cytologic findings in six cases.

The cytologic features of six cases of stomach cancer metastatic to the uterine cervix are presented. Atypical cells were found in cytology samples from four patients. Fewer atypical cells, larger cellular and nuclear areas, more discrete vacuoles, increased frequencies of thickening of the nuclear membrane and more coarsely granular chromatin patterns were the characteristic cytologic findings of metastatic cervical adenocarcinoma as compared with primary endocervical adenocarcinoma.

Abortifacient effect and uterine cervix-dilating action of 16, 16-dimethyl trans delta 2 PGE1 methyl ester (ONO 802) in the form of a vaginal suppository (a randomized, double-blind, controlled study in the second trimester of pregnancy).

A newly synthesized 16, 16-dimethyl trans delta 2 PGE1 methyl ester (ONO 802) was clinically applied in the form of a vaginal suppository for therapeutic abortion of second trimester pregnancies. Its effects were studied in a double-blind test comparing it with an inactive placebo suppository. The study was conducted at 12 Japanese university hospitals. The number of patients was 125 in total, i.e. 63 receiving ONO 802 vaginal suppository (containing 1.0 mg ONO 802) and 62 receiving inactive placebo suppository. ONO 802 was more effective than placebo with a success rate of 87% (complete (71%) and incomplete (16%) abortions). The onset of uterine contractions was observed in 154.3+/-18.1 min. and the onset of uterine bleeding in 323.6+/-41.0 min. The expulsion of the fetus and placenta was observed in 955.4+/-97.0 and 961.6+/-97.0 min., respectively. The cervix dilating effect of ONO 802 was observed in 63.5% of the patients at 3 hours after the start of administration. Nausea, vomiting, abdominal cramps, diarrhea and pyrexia were noticed. However, all these side effects were transient and mild, requiring no treatment. No abnormality was observed in the puerperal course, duration of uterine bleeding or onset of subsequent menstruation following the therapeutic abortion. Therefore, the present study demonstrated that ONO 802 vaginal suppository was an effective and valuable drug for therapeutic abortion of second trimester pregnancies.

Teratoma of the neck in a newborn infant--a case report.

A case of teratoma of the neck in a newborn is presented. Teratoma of the neck is a rare lesion and is mostly found in the newborn, but in some cases in the fetus and stillborn infant. Although in this case prenatal diagnosis was possible via ultrasonography, the infant did not survive because of respiratory distress. Hence, urgent surgery is imperative in such cases.

Teratoma of the neck in a newborn infant - a case report.

A case of teratoma of the neck in a newborn baby is presented. Teratoma of the neck is a rare lesion and almost always found in the newborn, but also in the fetus and stillborn infant. Although the mass was found prenatally by ultrasonography in the present case, the patient could not be saved because of respiratory distress. Urgent surgical management is the only way to save life in this kind of neonate.