Implications of aldose reductase in cataracts in human diabetes.

Cataracts removed intracapsularly by cryoprobe technique from human diabetics were analyzed for sugars and polyols by gas liquid chromatography. The contents of sorbitol and fructose of lenses followed blood glucose levels at least up to 250 mg/dl. Studies indicate that human lens is capable of synthesizing substantial amounts of polyol pathway metabolites given exposure to high glucose levels such as are prevalent in diabetes. The synthesis of sorbitol was found to be susceptible to quercitrin, an inhibitor of aldose reductase. The implications of these findings in the formation of cataracts in diabetic individuals have been discussed.     

Testicular teratocarcinoma with intracaval metastases to the heart.

We report a case of testicular teratocarcinoma involving the inferior vena cava with extension to the right atrium and metastases to the tricuspid valve. We believe this to be the first such reported case.     

A prospective trial of adrenaline infiltration for controlling bleeding during surgery for gynaecomastia

Twenty patients with gynaecomastia undergoing operations on 33 breasts were entered into a prospective randomised controlled clinical study. The breasts were randomised to receive nothing or adrenaline infiltration prior to mastectomy. Blood loss during surgery and drainage afterwards were compared between the two groups. Statistical analysis using the Wilcoxon rank sum test (two-tailed) showed a statistically significant reduction in operative blood loss (p less than 0.01) but no difference in postoperative drainage. There was no adverse effect on the viability of the skin flaps or the nipple-areola complex.     

Nuclear type II sites and malignant cell proliferation: inhibition by 2,6-bis-benzylidenecyclohexanones.

Methyl-p-hydroxyphenyllactate (MeHPLA) is a bioflavonoid and/or tyrosine metabolite which may regulate cellular growth and proliferation through interactions with nuclear type II sites. Our current studies suggest that type II sites may function as MeHPLA receptors which are localized on the nuclear matrix, and occupancy of this binding site by MeHPLA directly correlates with the inhibition of normal and malignant cell proliferation. This ligand is inactivated by MeHPLA esterase in mammary tumors, resulting in a deficiency in MeHPLA, high quantities of unoccupied type II sites, and uncontrolled cellular proliferation. For these reasons we synthesized 2,6-bis((3,4-dihydroxyphenyl)methylene)-cyclohexanone (BDHPC) and 2,6-bis((3-methoxy-4-hydroxyphenyl)-methylene)cyclohexanone (BMHPC) for assessment as nuclear type II site and cell growth antagonists. These two esterase stable cyclohexanone derivatives, which bind to nuclear type II sites with high affinity (Kd 1-7 nM), mimic MeHPLA as cell growth-regulating agents. Dose-dependent occupancy of type II sites in MCF-7 human cells by BDHPC and BMHPC directly correlated with the inhibition of cell proliferation, and administration of BDHPC by silastic implant inhibited mouse mammary tumor growth in vivo. These findings demonstrate that esterase-stable type II antagonists such as BDHPC and BMHPC inhibit mammary cancer cell proliferation in vitro and in vivo and support earlier studies demonstrating that MeHPLA and functionally related compounds may regulate malignant cell proliferation at the level of this binding site.