Mucocele of maxillary sinus]

The effect of heat on double-strand breaks (dsb) repair was compared with thermal radiosensitization using HeLa S3 cells. Cells were exposed to a combined treatment of X-irradiation followed by heat (44 degrees C, 0.5 h) separated by time intervals up to 8 h. DNA dsb were measured by PFGE and survival by the colony forming assay. In non-heated HeLa S3 cells repair of dsb was biphasic with the majority of breaks being repaired fast with a half-time of 14 min and only a minority were repaired slowly with a half-time of 130 min. Heat applied immediately after irradiation was found to cause an increase in both half-times but mainly to result in an increased fraction of slowly repairable dsb. The latter effect was shown to result from the formation of additional dsb. The number of additional dsb declined when irradiation and heat were separated by an interval at 37 degrees C with a half-time of 120 +/- 30 min. This half-time was similar to the half-time of 100 +/- 20 min found for the loss of thermal radiosensitization studied for the same protocol. Both processes were recently found also to correlate in CHO cells but occurred much faster in rodent cells than in the human HeLa S3 cells used in the current study. These results show that in human cells, unlike previously suggested on the basis of rodent cells, thermal radiosensitization is still a substantial contributor to the killing efficacy of a combined treatment even when irradiation and heat are separated by a time internal of 4 h.     

Randomised trial of coronary intervention with antibody against platelet IIb/IIIa integrin for reduction of clinical restenosis: results at six months. The EPIC Investigators

Restenosis after coronary angioplasty occurs in at least 30% of patients in the first six months and, as yet, there is no known treatment to decrease this event. We tested a monoclonal antibody Fab fragment (c7E3) directed against the platelet glycoprotein IIb/IIIa integrin, the receptor mediating the final common pathway of platelet aggregation, to see whether it reduced the frequency of clinical restenosis. Patients who had unstable angina, recent or evolving myocardial infarction, or high-risk angiographic morphology, were randomised to receive c7E3 bolus and a 12 hour infusion of c7E3 (708 patients), c7E3 bolus and placebo infusion (695 patients), or placebo bolus and placebo infusion (696 patients). With maintenance of the double-blind state, patients were followed-up for at least 6 months to determine the need for repeat angioplasty or surgical coronary revascularisation and the occurrence of ischaemic events. By 30 days, 12.8% of placebo bolus/placebo infusion patients had had a major ischaemic event (death, myocardial infarction, urgent revascularisation), compared with 8.3% of c7E3 bolus/c7E3 infusion patients, yielding a 4.5% difference (35% reduction, p = 0.008). At 6 months, the absolute difference in patients with major ischaemic event or elective revascularisation was 8.1% between placebo bolus/placebo infusion and c7E3 bolus/c7E3 infusion patients (35.1% vs 27.0%; 23% reduction p = 0.001). The favourable long-term effect was mainly due to less need for bypass surgery or repeat angioplasty in patients with an initial successful procedure, since need for repeat target vessel revascularisation was 26% less for c7E3 bolus/c7E3 infusion than for placebo treatment (16.5% vs 22.3%; p = 0.007). The c7E3 bolus/placebo infusion group had an intermediate outcome which was not significantly better than that of the placebo bolus/placebo infusion group. These results extend the benefit of c7E3 bolus/c7E3 infusion from reducing abrupt closure and acute-phase adverse outcomes to a diminished need for subsequent coronary revascularisation procedures. Because this therapy carries a risk of bleeding complications and has been studied only in high-risk angioplasty patients, further evaluation is needed before it can be applied to other patient groups.     

Evaluation of alternative methods for establishing safe levels of occupational exposure to vinyl halides

The facts that reduction of occupational vinyl chloride exposures to levels within or below the 0.5-5 ppm range has so far been successful in eliminating vinyl chloride-induced liver angiosarcoma and that humans appear to be less sensitive to the carcinogenic effect of vinyl chloride than rats offered an opportunity to verify or dispute risk assessment extrapolation models used, and proposed, by the U.S. EPA. Safe occupational vinyl chloride exposures were defined as levels associated with an incidence of one angiosarcoma in 100,000 exposed workers, determined from rat bioassay data using default no-threshold (linearized multistage model and benchmark dose approach with linear extrapolation) and threshold (NOEL/LOEL and benchmark dose uncertainty factor approaches) models, and then compared against the likely protective range of 0.5-5 ppm. Safe levels derived using either no-threshold model are equivalent and are two to three orders of magnitude below the 0.5-5 ppm range. Safe levels derived using either threshold model, when applying uncertainty factors which reflect equal or less sensitivity in humans compared to rats, fall within the 0.5-5 ppm range. Similar results were obtained for vinyl bromide and vinyl fluoride. These results undermine the U.S. EPA default assumption of no-threshold for vinyl halides as well as for other DNA-reactive carcinogens while simultaneously supporting the notion that a practical threshold exists. They further suggest that when threshold models are appropriate, the default assumption of greater sensitivity in humans compared to rats should be carefully evaluated.     

The question cube: a model for developing question repertoire in training couple and family therapists

This paper presents a three-dimensional model for teaching questioning to those wishing to develop skills in couple and family therapy. The model breaks questions into their component parts of format (the style of the question: open, closed, forced choice, rating, or ranking); orientation (the person who is being inquired about: self or other), and subject (the content of the question: behavior, feelings, beliefs, meaning, or relationship). The model is presented in the context of our post-Milan version of couple and family therapy training. The model is useful in that it allows students gradually to increase their repertoire of questions in a way that offers step-wise learning and integrates with their existing skills.     

Quality of life in children with congenital heart defects

PURPOSE: The antiepileptic effects of zonisamide (ZNS) have been well documented experimentally and clinically. The purpose of this study was to examine whether ZNS reduces cerebral damage after transient focal ischemia in rats. METHODS: Ischemia was induced by a transient occlusion of the left middle cerebral artery (MCA) with a 3-0 nylon monofilament for 90 min. Neurological evaluation was performed by measuring the event of neurological deficit of the contralateral forepaw and hindpaw at 10 min and 1 day after MCA occlusion (MCAo). Brain infarct size was determined by measuring triphenyltetrazonium chloride-negative stained area of the serial brain sections 1 day after MCAo. RESULTS: The pre- or postischemic treatment with ZNS [(10-100 mg/kg p.o.), 30 min before and 4 h after or 15 min and 4 h after the occlusion] markedly reduced cerebral damage in the ipsilateral hemisphere and the neurological deficit induced by transient ischemia. The reducing effect on the damage was observed in the cortical and subcortical regions. Preischemic treatment with carbamazepine (CBZ 60 mg/kg p.o. twice 30 min before and 4 h after MCAo) tended to reduce the cerebral damage and neurological deficit, but the lower dose (20 mg/kg p.o. twice) did not. Valproate (VPA 1,000 mg/kg p.o. twice) also had no effect. CONCLUSIONS: ZNS at the anticonvulsant dose, unlike CBZ and VPA, ameliorated the brain infarction and the event of neurological deficit after transient focal cerebral ischemia. These data suggest that ZNS has therapeutic potential in protecting against ischemic cerebral damage, such as stroke.     

The practice of obstetrics in Mongolia

Sponsored by the US Department of State and the US Army Pacific as part of a Medical Readiness Training Exercise, 17 physicians from Tripler Army Medical Center traveled to Outer Mongolia during September 1995 to examine the practice of medicine in the country. The obstetrical care observed was delivered at Third Women's Hospital in Ulanbataar. Prenatal care in Mongolia is provided mainly by family physicians, with the family doctor visiting each pregnant patient every month for the first 5 months, increasing to weekly visits at 7 months. The patient is taken to an obstetrical or women's and children's hospital when she reaches term or goes into labor. The staff at Third Women's Hospital deliver approximately 2000 babies annually and perform approximately 1000 pregnancy terminations through sharp curettage. The cesarean section rate is reported to be 10%. The hospital has no laboratory or X-ray capability, but can send out for such tests on rare occasions. During labor, patients are fully ambulatory on an as-needed basis. Fetal monitoring is not routinely available, except for occasional auscultation, patients in labor were not given IV fluid, delivery rooms were bleak and with only antiquated equipment, lighting was poor, and gloves were reused until they were too tattered for reuse. The authors discuss their experience with 3 cesarean sections and 1 ectopic pregnancy performed while in the country.     

Aip3p/Bud6p, a yeast actin-interacting protein that is involved in morphogenesis and the selection of bipolar budding sites

A search for Saccharomyces cerevisiae proteins that interact with actin in the two-hybrid system and a screen for mutants that affect the bipolar budding pattern identified the same gene, AIP3/BUD6. This gene is not essential for mitotic growth but is necessary for normal morphogenesis. MATa/alpha daughter cells lacking Aip3p place their first buds normally at their distal poles but choose random sites for budding in subsequent cell cycles. This suggests that actin and associated proteins are involved in placing the bipolar positional marker at the division site but not at the distal tip of the daughter cell. In addition, although aip3 mutant cells are not obviously defective in the initial polarization of the cytoskeleton at the time of bud emergence, they appear to lose cytoskeletal polarity as the bud enlarges, resulting in the formation of cells that are larger and rounder than normal. aip3 mutant cells also show inefficient nuclear migration and nuclear division, defects in the organization of the secretory system, and abnormal septation, all defects that presumably reflect the involvement of Aip3p in the organization and/or function of the actin cytoskeleton. The sequence of Aip3p is novel but contains a predicted coiled-coil domain near its C terminus that may mediate the observed homo-oligomerization of the protein. Aip3p shows a distinctive localization pattern that correlates well with its likely sites of action: it appears at the presumptive bud site prior to bud emergence, remains near the tips of small bund, and forms a ring (or pair of rings) in the mother-bud neck that is detectable early in the cell cycle but becomes more prominent prior to cytokinesis. Surprisingly, the localization of Aip3p does not appear to require either polarized actin or the septin proteins of the neck filaments.     

Differences in myocardial velocity gradient measured throughout the cardiac cycle in patients with hypertrophic cardiomyopathy, athletes and patients with left ventricular hypertrophy due to hypertension

OBJECTIVES: We sought to compare the myocardial velocity gradient (MVG) measured across the left ventricular (LV) posterior wall during the cardiac cycle between patients with hypertrophic cardiomyopathy (HCM), athletes and patients with LV hypertrophy due to systemic hypertension and to determine whether it might be used to discriminate these groups. BACKGROUND: The MVG is a new ultrasound variable, based on the color Doppler technique, that quantifies the spatial distribution of transmyocardial velocities. METHODS: A cohort of 158 subjects was subdivided by age into two groups: Group I (mean [+/-SD] 30 +/- 7 years) and Group II (58 +/- 8 years). Within each group there were three categories of subjects: Group Ia consisted of patients with HCM (n = 25), Group Ib consisted of athletes (n = 21), and Group Ic consisted of normal subjects; Group IIa consisted of patients with HCM (n = 19), Group IIb consisted of hypertensive patients (n = 27), and Group IIc consisted of normal subjects (n = 33). RESULTS: The MVG (mean [+/-SD] s-1) measured in systole was lower (p < 0.01) in patients with HCM (Group Ia 3.2 +/- 1.1; Group IIa 2.9 +/- 1.2) compared with athletes (Group Ib 4.6 +/- 1.1), hypertensive patients (Group IIb 4.2 +/- 1.8) and normal subjects (Group Ic 4.4 +/- 0.8; Group IIc 4.8 +/- 0.8). In early diastole, the MVG was lower (p < 0.05) in patients with HCM (Group Ia 3.7 +/- 1.5; Group IIa 2.6 +/- 0.9) than in athletes (Group Ib 9.9 +/- 1.9) and normal subjects (Group Ic 9.2 +/- 2.0; Group IIc 3.6 +/- 1.5), but not hypertensive patients (Group IIb 3.3 +/- 1.3). In late diastole, the MVG in patients with HCM (Group Ia 1.3 +/- 0.8; Group IIa 1.4 +/- 0.8) was lower (p < 0.01) than that in hypertensive patients (Group IIb 4.3 +/- 1.7) and normal subjects (Group IIc 3.8 +/- 0.9). An MVG < or = 7 s-1, as a single diagnostic approach, differentiated accurately (0.96 positive and 0.94 negative predictive value) between patients with HCM and athletes when the measurements were taken during early diastole. CONCLUSIONS: In both age groups, the MVG was lower in both systole and diastole in patients with HCM than in athletes, hypertensive patients or normal subjects. The MVG measured in early diastole in a group of subjects 18 to 45 years old would appear to be an accurate variable used to discriminate between HCM and hypertrophy in athletes.