A five to ten year follow-up study of parietal cell vagotomy

Records of 51 consecutive patients who underwent parietal cell vagotomy at the Lahey Clinic Medical Center and who had follow-up studies of five to ten years were reviewed. Operation was performed for intractability in 25 patients, intractability and obstruction in 19 patients and bleeding in seven patients. Patients with pyloroduodenal stenosis underwent digital dilation. No operative deaths occurred. Ulcer recurred in two of 25 patients (8 per cent) treated for intractability, in three of 19 patients with obstruction and in two of seven patients operated upon for bleeding. Ulcers recurring in patients operated upon for obstruction developed in the first two years after operation and were frequently gastric. Recurrences in patients treated for intractability were seen throughout the ten years of follow-up study. Of the seven patients who had a recurrence of an ulceration, five were treated successfully with medical therapy and two required truncal vagotomy with antrectomy. Functional results graded according to the Visick criteria revealed excellent to good results in 27 of 32 (84 per cent) of patients without obstruction and in 11 of 19 patients (58 per cent) with obstruction before operation (p less than 0.05). Fair to poor results were attributed to recurrent ulcers in the group of patients without obstruction and to symptoms of delayed gastric emptying in the group of patients with obstruction. We consider parietal cell vagotomy the procedure of choice to use for patients with intractable duodenal ulcer, but we have abandoned use of pyloroduodenal dilation in the patient with appreciable obstruction from fibrosis.     

MMPI-2 profiles of filicidal, mariticidal, and homicidal women

The present study compared the Minnesota Multiphasic Personality Inventory-2 (MMPI-2) clinical and content scale profiles of a group of adult women (N = 73) charged with either murder of their child (filicide) (n = 30), their partner (mariticide) (n = 19), or an unrelated adult (homicide) (n = 24). No significant differences were seen among the three groups on either the MMPI-2 clinical or content scales. Clinical inspection of the 53 valid MMPI-2 profiles (F < 110T) revealed a 6-8 mean profile for the filicidal women, a 2-6 mean profile for the mariticidal women, and a 4-8 mean profile for the homicidal women. Application of the data for criminal forensic psychological evaluations is discussed.     

Cytostatic anticancer drug development

This review focuses on clinical trials and the approval process in order to understand the discrepancy between vibrant science and the continuing failure of mechanism-based anticancer drugs. CLINICAL TRIALS: Mechanistic trials in cancer require at least three elements: the assurance of tumor definition, knowledge of the natural history, and earlier intervention. Histologic identity is not a reliable surrogate of the functional nature or a predictor of the natural history. cDNA arrays and computational models have promise in improving diagnosis and prediction, and thereby making tailored therapy possible. The latter requires: the incorporation of initial and earlier rational combination therapy, dynamic models of disease progression, and methods to discourage the emergence of resistance. For cytostatics, and in early cancer, a delay in progression may represent a better index of survival than tumor shrinkage. APPROVAL PROCESS: Since mechanistic similarities may outweigh therapeutic predictions based on organ-and histology-defined cancer, there is a need for a revised process that would allow for tailored treatment and initial combination therapy to improve safety, efficacy, and circumvent resistance. CONCLUSION: In order to translate the major and immediate potential of cytostatic drugs, clinical trials and the approval process may need to shift to a mechanism-based framework.     

Cyclin-dependent kinase 5 increases perikaryal neurofilament phosphorylation and inhibits neurofilament axonal transport in response to oxidative stress

Cyclin-dependent kinase 5 (cdk5) phosphorylates the high molecular weight neurofilament (NF) protein. Overexpression of cdk5 inhibits NF axonal transport and induces perikaryal accumulation of disordered phospho-NF cables. Experimental and clinical motor neuron disease is characterized by oxidative stress, increased cdk5 activity, and accumulation of phospho-NFs within perikarya or proximal axons. Because oxidative stress increases cdk5 activity in experimental motor neuron disease, we examined whether oxidative stress induced cdk5-mediated NF phosphorylation. Treatment of cultured neuronal cells with hydrogen peroxide inhibited axonal transport of green fluorescent protein-tagged NF subunits and induced perikaryal accumulation of NF phosphoepitopes normally confined to axons. These effects were prevented by treatment with the cdk5 inhibitor roscovitine or transfection with a construct expressing the endogenous cdk5 inhibitor peptide. These findings indicate that oxidative stress can compromise NF dynamics via hyperactivation of cdk5 and suggest that antioxidants may alleviate multiple aspects of neuropathology in motor neuron disease.     

Breast-conserving therapy (BCT) for early-stage breast cancer

Several patient and tumor factors go into the decision process to determine whether a breast cancer patient is a good candidate for breast-conserving therapy. The patient must be seen by all disciplines before any therapeutic intervention. When used appropriately, breast-conserving therapy produces maximal disease control and improves quality of life in patients with early-stage breast cancer.     

Novel approach for the three-dimensional culture of granulosa cell-oocyte complexes

The in vitro culture of immature ovarian follicles is used to examine the factors that regulate follicle development and may ultimately provide options for reproductive infertility. The objective of this study was to develop a three-dimensional in vitro culture system for the growth and development of individual granulosa cell-oocyte complexes. An alginate hydrogel was used to encapsulate immature mouse granulosa cell-oocyte complexes (GOCs) that were subsequently maintained in a serum-free in vitro culture. An overall incorporation efficiency of 50% was achieved. The complexes were assessed by transmission electron microscopy for changes in ultrastructure during in vitro growth. The architecture of the follicular complex was maintained during the encapsulation and the subsequent culture. The granulosa cells proliferated, and the oocytes also grew in volume and obtained the structural characteristics of mature oocytes including cortical granule formation, a well-developed zona pellucida with microvilli, normal mitochondria, and lattice-like structures in the cytoplasm. Oocytes retrieved and matured were able to resume meiosis, a necessary step for proper development. Thus, this system represents a new in vitro methodology for growth of individual granulosa cell-oocyte complexes.