Decreased intraocular pressure in the hypertensive human eye with betaxolol, a beta 1-adrenergic antagonist

In a double-masked randomized prospective study, 19 adult white subjects with primary open-angle glaucoma or ocular hypertension were treated twice daily with drops of 0.25% betaxolol (a relatively selective beta 1-adenoceptor antagonist) or placebo for six weeks. The nine betaxolol-treated subjects demonstrated a statistically significant average decrease in intraocular pressure of 3.8 +/- 5 mm Hg, evident after one week and persisting throughout the entire six-week treatment period. The ten placebo-treated subjects exhibited a statistically nonsignificant increase in intraocular pressure of 0.4 +/- 2.4 mm Hg. Mean systemic arterial blood pressure, pulse rate, corneal sensitivity, pupil diameter, and basal tear secretion remained unchanged in both groups. Transient stinging upon instillation of the eyedrops was the only side effect in the betaxolol-treated subjects but in no case did it necessitate cessation of therapy.     

Phenobarbital-dependent proliferation of putative initiated rat hepatocytes

The mitogenic effects of phenobarbital (PB) were examined usingcultures of putative initiated hepatocytes that proliferateand form colonies under conditions in which normal hepatocytessenesce and die. The frequencies of colony-forming hepatocytesin primary cultures isolated 2 weeks after initiation with methyl(acetoxymethyl)nitrosamineor benzo-[a]pyrene-7, 8-diol-9, 10-epoxide(anti) were in therange of 2–38 per million in the presence of PB. Colony-formationfrequencies were 0.1 per million in the absence of PB. Proliferativehepatocyte colonies were not observed in cultures grown in serum-freemedium containing PB, epidermal growth factor, nor-epinephrineand insulin. The requirement for PB was characterized furtherusing secondary cultures of hepatocytes that had been isolatedfrom a liver 5 weeks after initiation. The colony-fonning efficiencyof these hepatocytes was about 10% in the presence of 2 mM PBand less than 0.2% in its absence. Colony formation displayeda linear response to concentrations of PB in the range of 0.5–2mM and a decline above the optimal 2 mM concentration. Autoradiographywas used to determine the percentages of hepatocytes in secondarycultures that synthesized DNA in the presence or absence ofPB. By the third day after seeding as single cells, hepatocytesexhibited a labeling index of about 50% and this level of labelingwas preserved for up to 2 weeks after seeding. Very few hepatocyteswere found to synthesize DNA In the absence of PB and most senesced.A small fraction of the colony-forming hepatocytes continuedto proliferate in the absence of PB and formed colonies witha high labeling index. These results suggest that the proliferationof initiated hepatocytes in vivo may be conditional upon thepresence of the hepatic tumor promoter, PB.     

Analysis of isoenzymes in normal and carcinogen-treated human endometrial stromal cells in culture

The isoenzyme patterns of lactate dehydrogenase (LDH), hexokinase,phosphofructokinase, and aldolase were investigated in culturednormal and carcinogen-treated human endometrial stromal cells.Both normal and carcinogen-treated cells had similar phosphofructokinaseand aldolase isoenzymes. Distinctive changes in hexokinase andLDH isoenzyme patterns were found in the carcinogen-treatedstromal cells. The LDH isoenzyme patterns of the carcinogen-treatedstromal cells were shifted toward the muscle LDH forms. Thisis comparable to the alteration of LDH isoenzyme profiles observedin cell lines established from human uterine sarcomas. The twotissue culture media used affected the LDH isoenzyme patternsof endometrial stromal cells but differences between the LDHisoenzyme patterns of control and carcinogen-treated cells weredetected regardless of the growth medium used. Total LDH activitywas not significantly different in control and carcinogen-treatedstromal cells. The hexokinase isoenzyme patterns expressed bythe carcinogen-treated stromal cells were distinctly differentfrom the normal hexokinase patterns. The treated stromal cellscontained both hexokinase I and II, whereas the normal cellscontained only hexokinase I. Hexokinase and LDH isoenzyme patternsmay serve as markers with which to evaluate carcinogen-inducedneoplastic changes in cultured endometrial stromal cells.     

Virus proteins in herpetic keratitis

We examined the differences in protein expression among several strains of herpes simplex virus that cause epithelial and stromal keratitis in the rabbit eye. The isolates were grown in HEp-2 cells in the presence of various radioactive isotopes and were analyzed by SDS-PAGE. The in vitro expression of viral specified proteins was studied with antiserum to the purified virion (heterologous) and with the strain's homologous antiserum made during herpetic ocular disease.We found: (1) similarity among the strains in their in vitro expression of viral proteins; (2) polypeptide differences in the areas of ICP 9/10-ICP 14 and ICP28/29 and 30, when these proteins were immune precipitated with their homologous antisera; (3) more abundant glycosylated polypeptides in the RE (stromal disease-producing) strain than in the F (epithelial disease-producing) strain; (4) secretion of the major glycoproteins (gC, gD and gA, gB) into the extracellular fluid by all tested strains. However, the amounts of the glycoproteins secreted seemed to be characteristic of the individual strain. Those strains that secreted the larger amounts of glycoproteins were the strains that are known to produce stromal disease in the rabbit eye, which suggests that one determinant in the induction of stromal disease may be the number of glycosylated polypeptides as well as the secretion of glycoproteins in a soluble antigenic form.     

Combined modality treatment of gastric cancer

In a series of 46 patients with localized gastric cancer treated at Massachusetts General Hospital, problems with excessive acute or chronic toxicity due to combination treatment with irradiation (XRT) and chemotherapy (CT) were not seen. Forty of the 46 received combined treatment with 2 regimens: 1) Irradiation plus concomitant 3 days of 5-FU followed by maintenance 5-FU or combined drugs--26 patients; 2) In the other 14 patients, the sequence of irradiation and chemotherapy was altered. A single course of combined drug chemotherapy was given prior to irradiation and 5-6 additional courses were administered after completion of XRT (CT-XRT-CT). The drug combination was initially 5-FU-BCNU but this was changed to FAM (5-FU, Adriamycin, Mitomycin C). Irradiation was delivered to tightly contoured portals using shaped blocks to spare as much small bowel, kidney and marrow as possible while giving 4500-5200 rad in 25 to 29 fractions over 5 to 6 weeks. In this series, there were no cases of septicemia or any deaths related to treatment. A 3 year survival rate of about 20% was achieved for the total group of patients and 43% in the group with resection but at high risk for later failure. Our inability to improve these numbers is undoubtedly a result of dose limitations with external beam irradiation combined with a systemic failure problem. When irradiation is combined with surgical resection of all or a majority of tumor, both survival and local control appear to be better than in the unresected patient group. Only 4 of 29 patients (14%) with curative resection, or resection but residual disease, had later evidence of failure within the irradiation field as opposed to 6 of 9 or 66% in the group with unresectable disease.     

'Sneeze syncope', basilar invagination and Arnold-Chiari type I malformation.

Syncope precipitated by sneezing in an adult male associated with an Arnold-Chiari type I malformation and basilar invagination presents a clinical problem in the differential diagnosis and pathological anatomy of Valsalva-related syncope. An abnormally acute clivoaxial angle, small foramen magnum, and type I Arnold-Chiari malformation appear to be a combination of features intolerant of Valsalva-induced changes in cerebral volume, brain-stem position, CSF fluid dynamics, or blood vessel relationships. Proposed mechanisms of pressure transmission to the area of intracranial pathology are discussed.