Effects of alkyl chain length on the inhibition of NNK-induced lung neoplasia in A/J mice by arylalkyl isothiocyanates

Six homologous arylalkyl isothiocyanates were evaluated fortheir abilities to inhibit pulmonary adenomas induced by thetobacco-specific nitrosamine 4-(methylnitrosamino)-l-(3-pyridyl)-1-butanone(NNK) in A/J mice. Four consecutive daily doses (5 µmol/mouse)of phenyl isothiocyanate (PITC), benzyl isothiocyanate (BITC),phenethyl isothiocyanate (PETTC), 3-phenylpropyl isothiocyanate(PPITC), 4-phenylbutyl isothiocyanate (PBITC), 4-oxo-4-(3-pyridyl)-butylisothiocyanate (OPBITC) and corn ofl were administered to miceby gavage. Two hours following the final dosing, mice were administeredsaline or 10 µmol of NNK in saline i.p. Pulmonary adenomaswere counted at 16 weeks after NNK administration. The miceadministered only corn oil prior to NNK developed an averagemultiplicity of 9.2 tumors/ mouse. Pretreatment with PITC, BITCand OPBITC had no significant effects on NNK-induced lung neoplasia.However, PEITC pretreatment resulted in a 64% reduction of lungtumor multiplicity, but did not affect the percentage of micethat developed tumors. Both PPITC and PBITC decreased tumormultiplicity by 96% and the percentage of tumor-bearing animalsby >60%. These results, in conjunction with our previouswork, demonstrate a general trend of increasing inhibition ofNNK-induced lung neoplasia by arylalkyl isothiocyanates withincreasing alkyl chain length. This study also demonstratesthe remarkable inhibitory activities of PPITC and PBITC, twoisothiocyanates that had not previously been tested as chemopreventiveagents.     

Long-term treatment of anxiety and risk of withdrawal. Prospective comparison of clorazepate and buspirone

Risk of withdrawal was investigated in a prospective, double-blind comparison of clorazepate dipotassium, a benzodiazepine with a long half-life, and the nonbenzodiazepine buspirone hydrochloride in the long-term treatment of anxious outpatients. Patients were treated with therapeutic doses of clorazepate dipotassium (15 to 60 mg/d) or buspirone hydrochloride (10 to 40 mg/d) for six continuous months before their tranquilizer therapy was blindly and abruptly stopped. There was a significant increase in symptom severity consistent with a withdrawal reaction for the clorazepate group but not the buspirone group. For the clorazepate group, there was a suggestion that previous discontinuous exposure to benzodiazepines might sensitize patients to subsequent withdrawal effects. For the buspirone group, a higher dropout rate raised questions about patient satisfaction with therapy in this rather chronically anxious population.     

Conservative treatment of neonatal hydronephrosis.

From February 1990 to January 1991, 19 cases of hydronephrosis in children of less than one year of age were managed at Mackay Memorial Hospital. In the majority of these patients, there were evident causes such as ureteropelvic junction stenosis, ureterovesical reflux or a posterior urethral valve for which definite therapeutic measures were performed. However, some cases had no obvious origins and the hydronephrosis was speculated to be from nonobstructive or physiologic dilatation of the kidneys. The conventional tools, such as intravenous pyelogram or renal ultrasound, which comprise the mainstay of diagnosis, provide limited information on renal functional status. Recent introduction of the Tc-99m diethylene triamine penta-acetic acid (DTPA) diuretic renal scan has enabled us to distinguish between obstructive and nonobstructive hydronephrosis and helps us to determine whether or not surgery is necessary. In the past year, eight patients with hydronephrosis of less than one year of age were diagnosed as nonobstructive after a series of evaluations using renal ultrasound, voiding cystourethrography (VCUG) and Tc-99m DTPA diuretic renal scan. Follow-up studies by echography or DTPA renal scan revealed spontaneous resolution of the dilated collecting systems in these cases and confirms our belief that some hydronephrosis in neonates and infants may resolve spontaneously and may just be a manifestation of physiologic change during development. The value of the Tc-99m DTPA diuretic renal scan in the diagnosis of obstructive uropathy is discussed.     

Thiamin and vitamin B6 intakes and erythrocyte transketolase and aminotransferase activities in morbidly obese females before and after gastroplasty.

To assess the need for postoperative vitamin supplements, intakes and nutritional status of thiamin (B1) and vitamin B6 were studied in 18 female gastroplasty patients who received a placebo or different levels of supplemental vitamins. Postoperative erythrocyte transketolase basal (BA) and thiamin pyrophosphate-stimulated (SA) activities and activity coefficients (AC) correlated significantly with B1 intake. Despite a decrease in apotransketolase, low thiamin intakes were associated with increased AC values during the first 3 months. With return to low B1 intakes following repletion during month 4, the AC values remained normal with low total activities. Both alanine (EALT) and aspartate (EAST) aminotransferase apoenzyme levels declined and AC values increased significantly during the first 3 months. Although the EALT-indices were more sensitive to changes in B6 intake than the EAST-indices, the EASTBA and SA correlated most consistently with the intake. Postoperative dietary intakes of both vitamins were inadequate for maintenance of normal activities of these erythrocyte enzymes. Although B1 intake of greater than or equal to 1.0 mg/day was adequate for maintenance of normal thiamin status in most subjects of this study, supplementation with greater than or equal to 1.5 mg/day is prudent even though it may not prevent the early postoperative loss of apotransketolase. Vitamin B6 intake at the current recommended dietary allowance (1.6 mg) was not adequate to maintain coenzyme saturation of the erythrocyte aminotransferases. Marginal intake of other nutrients may have affected the utilization of both thiamin and vitamin B6.     

A Bayesian approach to subvoxel tissue classification in NMR microscopic images of trabecular bone

NMR microscopy is currently being used as an investigational tool for the evaluation of micromorphometric parameters of trabecular bone as a possible means to assess its strength. Since, typically, the image voxel size is not significantly smaller than individual trabecular elements, partial volume blurring can be a major complication for accurate tissue classification. In this paper, a Bayesian segmentation technique is reported that achieves improved subvoxel tissue classification. Each voxel is subdivided either into eight subvoxels twice the original resolution, or up to four subvoxels along the transaxial direction and the subvoxels optimally classified as either bone or marrow. Based on a statistical model for partial volume blurring, the likelihood for the number of marrow subvoxels in each voxel can be computed on the basis of its measured signal. To resolve the ambiguity of the location of the marrow subvoxels, a Gibbs distribution is introduced to model the interaction between the subvoxels. Neighboring subvoxel pairs with the same tissue label are encouraged, and pairs with distinct labels are penalized. The segmentation is achieved by maximizing the a posteriori probability of the label image using the block ICM (iterative conditional mode) algorithm. The potential of the proposed technique is demonstrated in real and synthetic NMR microscopic images.     

Haemostatic changes and thromboembolic risk during tamoxifen therapy in normal women.

Tamoxifen has been implicated as a risk factor for venous thrombosis in advanced breast cancer although the evidence for increased arterial or venous thrombosis with tamoxifen in early breast cancer is less clear. The effect of tamoxifen on haemostasis, and thereby possible thromboembolic risk, was investigated in normal women enrolled in a placebo controlled trial of tamoxifen as a chemopreventative agent for breast cancer. There was an initial reduction in fibrinogen levels in all women on tamoxifen over the first year of follow-up and a marginal reduction in antithrombin III and Protein S in postmenopausal women at 6 months. There were no changes in cross linked fibrinogen degradation products or Protein C for pre or post-menopausal women. There was no increase in the incidence of thromboembolic events on tamoxifen. This study demonstrates that tamoxifen has only marginal effects on factors involved in haemostasis reported to affect the incidence of arterial or venous thromboembolic disease. The follow-up time is relatively short (maximum 36 months) and careful long term follow-up is necessary to detect clinically significant morbidity.     

Pancreatoblastoma--histopathological and ultrastructural analysis of two cases.

Pancreatoblastoma has been described in children and characterized by unique histologic features and excellent clinical course. Ultrastructural and immunohistochemical studies of pancreatoblastoma reveal either exocrine alone or both endocrine and exocrine differentiation. We present two cases of pancreatoblastoma in children in which immunohistochemical and ultrastructural examination failed to demonstrate features of either enzyme or hormone production and which became worse in clinical course. We assume that pancreatoblastomas are tumors which differentiate more toward acinar or ductal elements than toward islet cell.     

Should all the N3 lymph nodes group metastasis be regarded as distant metastasis (M1) in curatively resected gastric cancer?

Recently, metastasis to N3 lymph nodes group was regarded as distant metastasis by the new TNM staging system due to poor overall survival. However, the 5-year overall survival rate of patients with metastasis to N3 groups was 34.5% after curative surgery. Moreover, in patients with metastasis to lymph node subgroups of #12, #13, #14, the overall 5-year survival rate increased upto 47.2% after curative resection and adjuvant chemotherapy. This was similar to that of the patients with metastasis to N1 and N2 lymph nodes groups. But in these highly tumor burden states, no survival benefit was found with the addition of immunotherapy to chemotherapy as we achieved in stage II and III. Therefore, we suggest that, at least, metastasis to #12, #13, #14 lymph nodes subgroups should not be categorized as a distant metastasis. And in these situations, active curative radical surgery with extended lymphadenectomy and adjuvant chemotherapy are recommended.     

The path to care in autism: Is it better now?

Parents of children with autism often report problems associated with obtaining a diagnosis of their child's condition, family support, information, and appropriate services. To evaluate any changes in the situation over the last two decades, the families of all members of the West Midlands Autistic Society, age 19 years and below, were asked to fill in a questionnaire that covered aspects of detection, diagnosis, help and information received, and educational provision. Responses were obtained from 127 families, the children of whom formed an older group ages 10 years and above (n=67) and a younger group ages 9 years and below (n=61). Findings show that there have been improvements for the younger group in some areas, such as earlier referral, diagnosis, and statementing. However, the situation with respect to advice given by professionals and the support and provision available after referral is still much the same as that experienced by families of the older group of children. Many difficulties and hurdles remain which hinder parents and children on the path to care in autism.     

Bilateral internuclear ophthalmoplegia in a patient with Wernicke's encephalopathy.

The most common cause of bilateral internuclear ophthalmoplegia is multiple sclerosis. Wernicke's encephalopathy has been reported as a cause of unilateral internuclear ophthalmoplegia but not of bilateral internuclear ophthalmoplegia. In this report, we present the case of a patient with a history of alcohol abuse and acute onset of bilateral internuclear ophthalmoplegia whose clinical course and diagnostic studies are most consistent with a diagnosis of Wernicke's encephalopathy.