Long-term results and complications of preoperative radiation in the treatment of rectal cancer

A retrospective study of 149 patients with rectal cancer diagnosed between 1972 and 1979 was undertaken to compare survival, disease-free survival, recurrence sites, and long-term complications of 40 patients who received 4000 to 4500 rads of preoperative adjuvant radiotherapy (radiation group) with those of 109 patients treated by resection alone (control group). After a mean follow-up of 84 months and 99 months, respectively, survival of the irradiated patients was significantly better than that of controls (68% versus 52%, p less than 0.05). Disease-free survival of those patients rendered free of disease by treatment was also superior for the irradiated group (84% versus 57%, p less than 0.005). Local recurrence without signs of distant metastases developed only one-third as often in irradiated patients (6% versus 18%). Distant metastases, alone or in combination with local recurrence, were also less common after radiation (12% versus 27%). Second primary tumors developed in 15% and 10% of the respective groups, a difference that was not statistically significant. When we consider the survival benefit of preoperative radiation therapy, long-term complications were relatively mild. Delayed healing of the perineum was noted in two irradiated patients. Persistent diarrhea was severe enough to warrant treatment in only one case, and one patient required a colostomy for intestinal obstruction from pelvic fibrosis.     

Inhibition of dapsone-induced methaemoglobinaemia in the rat isolated perfused liver

We have investigated the disposition of dapsone (DDS, 1 mg) in the rat isolated perfused liver in the absence and the presence of cimetidine (3 mg). After the addition of DDS alone to the liver there was a monoexponential decline of parent drug concentrations and rapid formation of DDS-NOH (within 10 min) which coincided with methaemoglobin formation (11.7 +/- 3.0%, mean +/- s.d.) which reached a maximum (22.6 +/- 9.2%) at 1 h. The appearance of monoacetyl DDS (MADDS) was not apparent until 30-45 min. Addition of cimetidine resulted in major changes in the pharmacokinetics of DDS and its metabolites. The AUC of DDS in the presence of cimetidine (1018.8 +/- 267.8 micrograms min mL-1) was almost three-fold higher than control (345.0 +/- 68.1 micrograms min mL-1, P less than 0.01). The half-life of DDS was also prolonged by cimetidine compared with control (117.0 +/- 48.2 min vs 51.2 +/- 22.9, P less than 0.05). The clearance of DDS (3.0 +/- 0.55 mL min-1) was greatly reduced in the presence of cimetidine (1.03 +/- 0.26 mL min-1 P less than 0.01). The AUC0-3h for DDS-NOH (28.3 +/- 21.2 micrograms min mL-1) was significantly reduced by cimetidine (8.1 +/- 3.40 micrograms min mL-1, P less than 0.01). In contrast, there was a marked increase in the AUC0-3h for MADDS (32.7 +/- 25.8 micrograms min mL-1) in the presence of cimetidine (166.0 +/- 26.5 micrograms min mL-1 P less than 0.01). The methaemoglobinaemia associated with DDS was reduced to below 5% by cimetidine. Hence, a shift in hepatic metabolism from bioactivation (N-hydroxylation) to detoxication (N-acetylation) caused by cimetidine, was associated with a fall in methaemoglobinaemia. These data suggest that the combination of DDS with a cytochrome P450 inhibitor might reduce the risk to benefit ratio of DDS.     

Antibacterials. synthesis and structure-activity studies of 3-aryl-2-oxooxazolidines. 4. Multiply-substituted aryl derivatives.

The synthesis and structure-activity relationship (SAR) studies of the effect of different polysubstitution patterns in the aromatic ring of 5-(acetamidomethyl)oxazolidinone antibacterials (I) on antibacterial activity are presented. Compounds I were prepared by the six-step synthesis described previously (Gregory, W. A.; et al. J. Med. Chem. [formula: see text] 1989, 32, 1673), electrophilic aromatic substitution reactions of 3-substituted compounds, and functional-group interchange reactions of 3,4-disubstituted compounds. Antibacterial evaluation of compounds I against Staphylococcus aureus and Enterococcus faecalis gave the following results. The 2,4- and 2,5-disubstituted derivatives have weak or no antibacterial activity. Antibacterial activities of 3,4-disubstituted compounds are comparable to those of the 4-monosubstituted analogues for small 3-substituents (smaller than Br), but decline rapidly for larger 3-substituents. 3,4-Annulated derivatives are comparable in activity to their open-chain analogues. 3,5-Disubstituted and 3,4,5- and 2,4,6-trisubstituted derivatives are devoid of antibacterial activity.     

Reduction of flurazepam's antiseizure efficacy persists after stress.

Twenty-four hours after mice were forced to swim for up to 10 min in cold (6 degrees C) water, the ability of flurazepam to antagonize the electrical precipitation of seizures was reduced. This stress-induced reduction in flurazepam's antiseizure efficacy persisted for at least 72 h; but was absent 1 week after the single session of swim stress. The data may be relevant to stress-related psychiatric disorders and suggest that the therapeutic efficacy of benzodiazepines may be altered after a severe stress.     

Recognition and management of patients with high-risk vesicovaginal fistulas: Implications for teaching and research

Vesicovaginal fistulas (VVFs) occurring as a result of obstetric trauma are a vast problem in Nigeria and Ghana, where at least 20 000 women await repair, and fewer than 50 physicians have the necessary expertise. Through a series of conferences those VVFs that are at high risk and those at low-risk for repair failure, were identified. A clinic was established where repair of low-risk VVFs was done on an ongoing basis in a remote region of Ghana. A visiting surgical team was utilized to repair the difficult, or high-risk, VVFs, which included 4–6 cm VVFs (3), recurrent VVF (1), combined VVF and RVF (rectovaginal fistula), a large 5 cm juxtacervical VVF (1), and a vesicouterine fistula (1). Management of these patients and others with VVF repair complications is discussed.     

Infracture Technique for the zygomatic body and arch reduction

In the Orient, prominent malar regions are considered unaesthetic and the majority of women with a prominent malar want to reduce the zygoma. Various operative procedures such as shaving or chiseling the zygomatic body or the zygomatic arch have been used for reducing malar eminence, but the zygomatic arch cannot be reduced sufficiently by these methods. By combining intraoral shaving of the zygomatic body and a new effect arch infracture technique through a temporopreauricular incision, we have obtained very satisfactory results in 19 cases and notable minimal complications over the last three years.     

The Association of Different Measures of Insulinaemia with Vascular Risk Factors in Healthy Normoglycaemic Normotensive Non-obese Men and Women

Hyperinsulinaemia is said to be a risk factor for cardiovasculardisease, but the extent to which different insulinaemic measuresare associated with vascular risk factors in ostensibly healthyindividuals, and whether they operate independently in men andwomen, remains uncertain. The association between risk factors and various insulinaemicmeasures was examined in 148 men and 118 women who were normoglycaemic,normotensive, and non-obese (body mass index in men <27,in women <25). A 75 g glucose tolerance test was administeredafter blood sampling for fibrinogen, lipids, lipoproteins andinsulin. Insulin was also measured after 1 and 2 hours. Significantunivariate correlations (p<0.01) were most consistently recordedbetween insulinaemic measures and fasting serum triglyceridesin men and women, whilst systolic blood pressure only correlatedwith insulinaemia in women, and diastolic blood pressure correlatedwith fasting and 2 hour insulinaemic measures in men and women.Inconsistent associations were noted with total serum cholesterolin men and women, with high density lipoprotein cholesterol,body mass index, apoprotein B and A1 in men, and with fibrinogenin women. Age was not correlated with any insulinaemic measurein men or women. Differences in vascular risk factors between quintiles of theinsulinaemic measures were examined, after correction for bodymass index. The dominant association with fasting and post-glucoseload insulinaemic measures was with triglycerides, especiallyin women, with less frequent graded differences between quintilesobserved for total cholesterol, and diastolic and systolic bloodpressures in men and women. The incidence of other risk factors often only differed in thelowest or highest quintile in comparison to other quintiles,suggesting a threshold rather than a graded effect. Furthermore,differences in HDL cholesterol and apoprotein B were only recordedfor top quintiles of post-glucose challenge/integrated insulinaemicmeasures in men, whilst serum fibrinogen concentrations onlydiffered significantly in women in the top insulinaemic areaunder the curve quintile. In the absence of additional risk factors such as diabetes,hypertension and obesity, insulinaemic measures are not consistentlyrelated to blood pressure and measures of lipid metabolism andcoagulation, and are thus a weak predictor of other cardiovascularrisk factors. The vascular risk profile associated with insulinappears somewhat different in apparently healthy men and women.     

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.