Partial mastectomy with axillary lymph node dissection and radiotherapy as a new treatment modality of breast cancer (I).

This is the first preliminary report among two consecutive papers. Partial mastectomy(PM), axillary lymph node dissection(AD) and radiotherapy (RT) were performed on seventeen operable breast cancer patients who had been admitted from April 1991 to March 1992 to the department of surgery, Yongdong Severance Hospital for improved cosmetic appearance and better survival rate. Of seventeen patients, 47% were T1 lesion and 76% were stage I and II. Extensive intraductal component(EIC) within or around the tumor was also analyzed. Twenty nine per cent of the patients were EIC positive. The mean number of axillary lymph nodes was 21.5 after PM with AD and 20.5 after mastectomy. For radiotherapy, 4,500 rad was delivered to the breast parenchyma and 1,600 rad of boost to the primary tumor site using the electron beam method after surgery. All patients have since been living well without any local recurrence and were satisfied with breast preservation for the one-year follow-up period. We concluded that the PM, AD and RT can be another surgical treatment modality of breast cancer. A longer follow-up data will be followed on the second paper.     

Double-bundle technique: Endoscopic posterior cruciate ligament reconstruction using tibialis posterior allograft

Recently, attention has been given to the double-bundle technique for treating the posterior cruciate ligament (PCL)-deficient knee. We present an arthroscopic PCL reconstruction using a double-bundle technique with 3-stranded tibialis posterior (TP) allograft that has not been described before. The anterolateral bundle of the PCL is reconstructed using 2-stranded TP allograft and the posteromedial bundle using 1-stranded TP allograft. Three-stranded TP allograft will be an alternative graft choice for PCL reconstruction.     

The mechanism of bioactivation and antigen formation of amodiaquine in the rat.

A glutathione conjugate of amodiaquine has been isolated and characterized from rat bile after administration of [14C]amodiaquine (50 mumol/kg, 5.0 muCi/rat) to anaesthetized male Wistar rats. Thioether conjugates of amodiaquine in rat bile accounted for a total of 12% of the dose, 5 hr after administration of the drug. In addition, 1% of the dose remained in the liver covalently bound to tissue proteins after 5 hr. These findings provide direct evidence that a chemically reactive metabolite, amodiaquine quinoneimine, has been formed from the drug in vivo. A second major metabolite, desethylamodiaquine, accounting for 14% of the given dose, was present in the liver after 5 hr. Enzyme inhibition studies with ketoconazole-pretreated rats showed that both amodiaquine quinoneimine and desethylamodiaquine formation can be catalysed by cytochrome P450. The demonstration that amodiaquine readily and extensively forms a metabolite in vivo, with strong reactivity towards protein and non-protein thiol groups, may help to explain the idiosyncratic toxicity observed in man.     

Ictal brain imaging in presurgical evaluation of patients with medically intractable complex partial seizures

At the Indiana University Medical Center, 99 patients with medically intractable complex partial seizures (MI-CPS) had presurgical evaluation with subsequent anterior temporal lobectomy. The majority of the patients had single photon emission tomography (SPECT) performed interictally as well as during an actual epileptic seizure (ictal scan). Decreased regional cerebral perfusion (rCP) was seen in 54/94 (57%) of the interictal scans corresponding to the eventual site of the surgery. However, ictal scans provided a higher yield; increased rCP in the temporal lobe during an actual seizure was observed in 60/82 (73%) concordant to the side of surgery. SPECT is a useful, noninvasive method of localizing the epilepti-form focus in patients with MI-CPS considered for resective surgery. Both interictal and ictal SPECT need to be performed; combined interictal hypo-perfusion and ictal hyperperfusion in the same focal area are unique to epileptogenic lesions. Ictal SPECT studies can be performed in the majority of patients during the period of continuous video/EEG monitoring with only a little additional effort. Combining the results of functional brain imaging (interictal and ictal SPECT, PET) with clinical semiology of seizures, surface and sphenoidal EEG, magnetic resonance imaging and other non-invasive tests, anterior temporal lobectomy can be recommended in approximately two-thirds of the patients without resorting to potentially dangerous intracranial EEG monitoring.     

An Unusual Form of Skin Tuberculosis Following B.C.G. Vaccination

A 25-year-old female has had brown to erythematous telangiectatic patches and grouped papules on her face, neck, arm, and trunk since childhood following B.C.G. vaccination. Histopathologically, the lesions consisted of hyperkeratosis, slight acanthosis, tuberculoid granulomas with some Langerhans type giant cells in the mid-dermis. Although various forms of cutaneous tuberculosis after B.C.G. vaccination have been reported, it was difficult for us to assign the patient's skin lesion to any specific disease entity. Remission of her cutaneous lesions occurred clinically and histopathologically after treatment with isoniazid and rifampin.     

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.