Surgical technique and pitfalls of breast reconstruction immediately after mastectomy for carcinoma: initial experience

Breast reconstruction immediately after mastectomy is being used with increasing frequency. In a study of the first 100 consecutive patients at our institution who underwent this procedure, with (21 patients) or without (79 patients) later nipple reconstruction, 85% responded affirmatively on a follow-up questionnaire when asked whether they would recommend the procedure to other patients. Moreover, 32% rated their cosmetic results as "perfect." No deaths occurred in the immediate postoperative period, but 13 patients had major complications--most commonly, wound infection or displacement or partial extrusion of the implant. All infections, however, occurred early in the study, and with increasing experience and improved selection of patients, the associated morbidity decreased. For the entire group, the mean duration of hospitalization was 7.8 days, similar to that for patients who undergo mastectomy without reconstruction (7.5 days). The high patient acceptance and the overall good results in this preliminary study support the use of breast reconstruction immediately after mastectomy.     

Affinities of barbiturates for the GABA-receptor complex and A1 adenosine receptors: a possible explanation of their excitatory effects

Summary The effects of barbiturates on the GABA-receptor complex and the A₁ adenosine receptor were studied. At the GABA-receptor complex the barbiturates inhibited the binding of [³⁵S]t-butylbicyclophosphorothionate ([³⁵S]TBPT) and enhanced the binding of [³H]diazepam. Kinetic and saturation experiments showed that both effects were allosteric. Whereas all barbiturates caused complete inhibition of [³⁵S]TBPT binding, they showed varying degrees of maximal enhancement of [3H]diazepam binding; (±)methohexital was identified as the most efficacious compound for this enhancement. At the A₁ adenosine receptor all barbiturates inhibited the binding of [³H]N⁶-phenylisopropyladenosine ([³H]PIA) in a competitive manner. The comparison of the effects on [³H]diazepam and [³H]PIA binding showed that excitatory barbiturates interact preferentially with the A₁ adenosine receptor, and sedative/anaesthetic barbiturates with the GABA-receptor complex. It is speculated that the interaction with these two receptors might be the basis of the excitatory versus sedative/anaesthetic properties of barbiturates.Abbreviations GABA -aminobutyric acid - TBPT t-butylbicyclophosphorothionate 1073 - DMBB 5-(1,3-dimethyl)butyl-5-ethylbarbituric acid - MCB N-methyl-5-(1-cyclohexen-1-yl)-5-ethylbarbituric acid - MPPB N-methyl-5-phenyl-5-propylbarbituric acid - PIA N⁶-phenylisopropyladenosine Send offprint requests to M. J. Lohse at the above address     

Pharmacological characterization of A1 adenosine receptors in isolated rat ventricular myocytes

Summary The aim of the present study was the characterization of adenosine receptors in isolated rat ventricular myocytes. The CAMP-levels of rat ventricular myocytes in the presence of 1 mol/l isoprenaline were reduced by up to 48% by adenosine analogues; the rank order of potency was: R-N⁶-phenylisopropyladenosine (IC₅₀ 60 nmol/1), 5-N-ethylcarboxamidoadenosine (IC₅₀ 360 nmol/l) and S-N⁶-phenylisopropyladenosine (IC₅₀ 16 ol/l). The adenosine receptor antagonist XAC (xanthine amine congener) antagonized the effect of R-N⁶-phenylisopropyladenosine in a concentration-dependent manner with a K_i-value of 20 nmol/l. The A₁ receptor-selective radioligand R-N⁶-¹²⁵I-p-hydroxyphenylisopropyladenosine bound to membranes prepared from rat ventricular myocytes in a saturable manner with a B _max of 17.7 fmol/mg protein and a K _D-value of 1.1 nmol/l. Adenosine analogues competed for the binding with the same rank order of potency as for the inhibition of the isoprenaline-induced cAMP-increase. GTP inhibited radioligand binding with an IC₅₀-value of 73 ol/l. These results suggest the presence of A₁ adenosine receptors on rat ventricular myocytes, which mediate an inhibition of adenylate cyclase. The receptors may be responsible for the effects of adenosine and its analogues on the heart.Abbreviations ¹²⁵I-HPIA R-N⁶-¹²⁵I-p-hydroxyphenylisopropyladenosine - PIA N⁶-phenylisopropyladenosine - NECA 5-N-ethyl-carboxamidoadenosine - XAC 8-4-[([(2-aminoethyl)aminocarbonyl]methyl)oxy]phenyl-1,3-dipropylxanthine (xanthine amine congener) - Ro 20-1724 4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone - ScAMPTME 2-O-monosuccinyladenosine-3,5-cyclic monophosphate tyrosyl methyl ester - HEPES N-2-hydroxyethylpiperazine-N-2-ethanesulfonic acid - GTP guanosine-5-tri-phosphate Send offprint requests to D. Martens     

Studies on the mammary tumor-inhibiting effects of diethylstilbestrol and its mono- and diphosphate

Summary Diethylstilbestrol (DES), diethylstilbestrol monophosphate (DES-MP) and diethylstilbestrol diphosphate (DES-DP) were tested for their estrogen receptor affinity, estrogenic potency and mammary tumor-inhibiting activity in vitro and in vivo. DES had a much higher receptor binding affinity than its mono-or diphosphate. All three compounds inhibited the growth of the hormone-dependent MCF-7 and hormone-independent MDA-MB 231 breast cancer line only at relatively high concentrations. The estrogenic potency in the immature mouse uterine weight test decreased in the order DES>DES-MPDES-DP. The hormone-dependent MXT mammary tumor of the mouse was inhibited by all three compounds at a dosage of 1.0 mg/kg per week. At a dose of 0.01 mg/kg, DES, DES-MP, and DES-DP stimulated the tumor growth. Thus, for the first time, a biphasic effect on tumor growth was demonstrated in intact mature animals. As the effects of all three compounds were similar in this assay, a cleavage of the phosphate groups is likely. A decrease in estrogenic potency concomitant with a retained antitumor effect of DES-MP and DES-DP compared to DES was not demonstrable in the mature mouse using the MXT assay, only in the uterotrophic test in the immature mouse.Dedicated to Professor Dietrich Schmähl on occasion of his 60th birthdaySupported by the Deutsche Forschungsgemeinschaft and by the Verband der Chemischen Industrie, Fonds der Chemischen Industrie. The authors thank Dr. Weigert, Asta-Werke AG, Degussa Pharma Gruppe, Bielefeld, FRG, for the analysis of DES-MP and DP     

Percutaneous removal of large gallstones

Two patients are described in whom large gallstones, up to 4 cm in diameter, were removed percutaneously. The technique has some relevance to high risk patients with surgical cholecystotomies in whom elective cholecystectomy may be deferred if all the calculi can be removed. It may also be relevant if "percutaneous cholecystectomy" is ever developed clinically.     

Alternate therapy for traumatic pneumothorax in "pocket shooters"

Traumatic pneumothorax is a common complication of the IV drug abusers in Detroit who utilize the "pocket shot" (the central approach to the internal jugular vein). Fourteen patients who sustained a total of 16 pneumothoraces (two with bilateral collapse) and who underwent catheter aspiration of a simple pneumothorax (CASP) were studied prospectively. The sizes ranged from less than 10% to 100%. In addition, there was one tension pneumothorax and one pneumomediastinum. The 16 CASP procedures produced 13 successful lung expansions (82%). The remaining three were treated with tube thoracostomy and admission. Twelve of the 13 patients in whom the procedure was successful returned for followup, and all of these had 100% continued full expansion. CASP appears to be a safe, efficacious, and cost-effective treatment for the drug abuser with simple traumatic pneumothorax. With the current pressures of cost containment, this less-invasive approach with outpatient management should be studied as initial potential treatment for any simple pneumothorax.     

Evaluation of mathematic models to assess platelet kinetics

Twelve mathematic methods used to calculate the mean platelet survival time were compared by determining the "goodness of fit" of the models to the platelet survival curves of 15 reference subjects and 54 patients. Platelets were labeled with [111In]oxine. The linear (LN), exponential, weighted mean, multiple hit (MH), Dornhorst (DH), Meuleman (ML), alpha order (AO), and polynomial (PO) mathematic models were investigated. The goodness of fit for the exponential model was determined by the nonlinear least squares method (EP), and also by the linear least squares method on logarithmically transformed data (EX) as is recommended. The modified weighted mean (MWM) and the usual weighted mean method (WM) obtained with these exponential models were tested. The Dornhorst (DH10) and Meuleman (ML10) models, where the potential age-dependent platelet survival times were kept constant at 10 days, were also evaluated. The goodness of fit results, expressed as % s.d. indicated that the LN (5.2%), EX (5.0%), EP (4.4%), WM (3.7%), DH10 (3.7%), and ML10 (3.7%) models all fitted the data significantly worse than the MWM, MH, DH, ML, AO, and PO models (range 3.2-3.3%). The mean platelet survival time determined with the MH model differed significantly from the results with the DH, ML, and AO models. The results of mean platelet survival time calculated with different mathematic models cannot, therefore, be compared directly. The models that fitted the platelet survival curve well varied slightly in sensitivity to noise as is indicated by the coefficient of variation of the mean platelet survival time estimates for the reference subjects (range 7.9-12.0%). Fitting data to at least two mathematic models has definite advantages. Data on which the calculations are based are probably invalid if the following are true: (a) if the mean platelet survival time estimated with the alpha order model is shorter than that estimated with the EP, MWM, or MH models, or (b) the mean platelet survival time estimated with either the DH, ML, AO, or PO models, is longer than the LN, MWM, or MH estimate of the mean platelet survival time. We conclude that the mean platelet survival time can be reliably estimated by fitting the data to either the MWM method (if limited computing facilities are available) or the MH model. Confidence in the result will be increased if considered in conjunction with the finding obtained with one other model; in those cases where the platelet survival time is very short, the alpha order model is recommended.(ABSTRACT TRUNCATED AT 400 WORDS)     

L-654,284 a new potent and selective α2-adrenoceptor antagonist

Summary L-654,284 ((2R, 12bS)-N-(1,3,4,6,7,12b-hexahydro-2H-benzo[b]-furo[2,3-a] quinolizine-2-yl)-N-methyl-2-hydroxyethanesulfonamide) was tested in several in vitro and in vivo models for ₂-adrenoceptor antagonist activity and compared to several reference agents. In vitro L-654,284 competed for the binding of ³H-clonidine or ³H-rauwolscine (K _i's 0.8 nM, 1.1 nM) and blocked the presynaptic effects of clonidine in the rat isolated vas deferens (pA₂, 9.1). L-654,284 exhibited marked ₂- vs. ₁-adrenoceptor selectivity in vitro, inhibiting ³H-prazosin binding with a K _i of 110 nM and blocking the effects of methoxamine on the vas deferens with a pA₂ of 7.5. In vivo L-654,284 at 22 nmoles/kg i.v. doubled the ED₅₀ of clonidine to produce mydriasis in rats. Given orally, the potency of L-654,284 in this test was reduced by a factor of 5.5. L-654,284 also potently increased cerebrocortical NE turnover in the rat, another in vivo index of ₂-adrenoceptor blockade in the central nervous system. In the periphery, L-654,284 demonstrated ₂-adrenoceptor selectivity by preferentially blocking the pressor effects of UK 14304 versus those of methoxamine in the pithed rat. Overall, L-654,284 was generally a more potent ₂-adrenoceptor antagonist than RX 781094 with comparable ₂/₁ selectivity and was several times more potent and ₂-selective than WY 26703 or yohimbine. In addition, L-654,284 had better (5–6 times) oral bioavailability than RX 781094 or WY 26703.     

Biochemical and morphologic studies of heterogeneous lobe responses in hepatocarcinogenesis

Experiments have demonstrated interlobe differences in the incidenceof diethylnitrosamine (DEN)-induced hepatocellular carcinoma(HCCA), with a 100% incidence in the left and right median lobesand a 30% incidence in the right anterior lobe 20 weeks afterexposure began. These tumor data provide a model to test thehypothesis that chemically induced neoplasia can be qualitativelyand quantitatively related to promutagenic DNA damage and concurrentcell replication. Experiments were performed to measure O⁴-ethyldeoxythymidine(O⁴-EtdT) (a major pro-mutagenic lesion in hepatic DNA of ratsexposed to DEN), N7-ethylguanine, cell replication and hepatocyteinitiation using the induction of growthselected -glutamyl transferase-positive(GGT+) foci in the left and right median and right anteriorhepatic lobes following 0, 3, 7, 14 or 28 days of DEN administration.Results demonstrated that O⁴-EtdT concentrations were consistentlyhigher in the left and right median versus the right anteriorhepatic lobes, while cell replication was transiently higherin the right median and right anterior lobes. Likewise, highnumbers of GGT+ foci were observed in the left and right medianlobes in DEN-exposed rats subjected to a Cayama-Farber growthselection protocol. Following administration of [¹⁴C]DEN, thedistribution of radioactivity showed a marked left lobe preferencein 4-week-old rats that had no prior exposure to DEN and in8-week-old rats exposed to DEN for 4 weeks. This study suggeststhat interlobe differences in hepatocyte initiation and theincidence of HCCA may be due in part to differences in cellreplication and in DNA alkylation resulting from differentialDEN distribution and/or metabolism.     

Ruthenium nitrosyl complexes: Toxicity toEscherichia coli and yeasts and uptake by marine bacteria

The toxicity and possible accumulation of ruthenium nitrosyl complexes by marine bacteria and test organisms have been studied, A range of these complexes show no toxic effects towardsEscherichia coli K12 at concentrations of mM and below. Yeasts are more sensitive, showing effects on growth at 10 M. The ruthenium nitrosyl complexes tested are unable to permeate the cytoplasmic membrane ofE. coli. This may account for their lack of toxicity. However, these compounds did not have significant inhibitory effects on Mg²⁺-ATPase activity in cell-extracts, I₅₀ values lying in the range 2 to 125 mol(mg protein)^–1. Marine bacteria are capable of taking up ruthenium complexes from simulated effluent, but this cannot be demonstrated in the presence of sediment which competes effectively for binding of complexes. There is minimal likelihood of concentration of ruthenium compounds from effluents by marine bacteria.