The extraction problem is still with us.
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Biomedical subjects
Publications and source records attributed to M Goldberg.
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Surgical treatment of extensive hypopharyngeal carcinoma often includes total thyroidectomy together with resection of the primary disease. The risk of removing or damaging the parathyroid glands is considerable; this may render the patient permanently hypoparathyroid with all the problems of management. These patients must be on lifelong supplementation and at times, due to failure to take the medication, hypocalcemic crises are precipitated. To avoid this problem, we have been identifying the parathyroid glands intraoperatively and, after pathological confirmation, have transplanted them to the forearm. Three patients who underwent this procedure are presented. All are normocalcemic without supplementation and parathyroid hormone assays on serum from the transplanted forearm show significantly elevated levels.
In order to determine the effects of guanabenz upon renal function, clearance studies were performed on hypertensive volunteers during sustained steady-state water diuresis. The data reveal an acute fall in renal hemodynamics and a marked reduction in sodium excretion during the 3rd and 4th hour after administration. Tha antinatriuresis was due to decreased filtration and enhanced distal nephron reabsorption of sodium, principally in association with secretion of potassium. Chronic administration of guanabenz for one week produced a sustained reduction in blood pressure, but there was no change in either body weight or 24-hour urinary sodium excretion. Repeat clearance studies revealed no change with either renal hemodynamics or sodium clearance. The data suggest that the acute antinatriuresis is a transient hemodynamic event and chronic therapy with guanabenz will not be complicated by sodium retention, a feature characteristic of other antihypertensive agents.
Statistical methods for characterizing risks are now well-developed, although little attention has focussed on the problem of risk identification, as in the surveillance of adverse drug reactions or occupational cancers. In this paper we consider the analysis of studies in which one ascertains and compares cases of several disease groups in terms of exposure histories. We address the problem of adjusting each risk for the confounding effects of all the other risks in the data. Data analysis consists of multidimensional contingency tables or polychotomous logistic regression. The latter approach focuses attention on the exposure-disease relations of primary interest rather than on those among the exposure factors and higher-order interactions, and applies easily to many exposure variables and to continuous exposure variables. We describe a stepwise approach to selecting effects for inclusion in the model. Application to preliminary data from a study aimed at identification of hitherto unsuspected occupational carcinogens illustrates the general approach.
Thirty-nine patients with mediastinoscopy stage IIIA, N2 non-small cell lung cancer received two cycles of MVP (mitomycin C, vindesine, cisplatin). Responders underwent thoracotomy for resection and two further courses of MVP. Overall response rate was 64% (25/39) with three complete and 22 partial responses. Twenty-two patients were resected, which included radical mediastinal node dissection. Eighteen resections were complete and four were incomplete. Pathologically, three patients (7.7%) had no remaining tumor. Toxicity included two postoperative deaths with B-P fistula, mitomycin pulmonary toxicity in two patients, and four septic deaths. Twenty-eight patients have died, 20 with recurrent or progressive disease. Of the 18 patients completely resected, eight have recurred with a median time to recurrence of 20.6 months. Sites of recurrence include two locoregional, five distant (two in brain) and one in both. Median survival of the entire 39 patients is 18.6 months, with a three year survival of 26%. The median survival for those patients completely resected was 29.7 months with a 3-year survival of 40%.
The in vitro activity of cefpirome was evaluated against strains that showed conflicting results for third generation cephalosporins. Against isolates with derepressed inducible chromosomal cephalosporinase (n = 40) cefpirome was the sole cephalosporin with an MIC90 in the susceptible range; Klebsiella spp. with plasmid-mediated beta-lactamases (broad spectrum SHV-2 or SHV-2 type) (n = 40) remained most susceptible to ceftizoxime and cefpirome; against aminoglycoside-resistant Pseudomonas aeruginosa (n = 50), cefpirome was as active as ceftazidime and cefoperazone; against oxacillin-susceptible and oxacillin-resistant Staphylococcus spp., (n = 40), cefpirome was more active than other third generation cephalosporins but killing was inadequate against both oxacillin-resistant staphylococci and enterococci.
The incidence of strains producing transferable beta-lactamases capable of hydrolyzing third generation cephalosporins or aminothiazole-oximino substituted monobactams in five Buenos Aires hospitals during a four month period was studied. These enzymes were categorized by 1) MIC greater than or equal to 1 mg/l for third generation cephalosporins; 2) MIC less than 0.06 mg/l for third generation cephalosporins combined with clavulanic acid or sulbactam; 3) sensitivity to imipenem or cephamycins (excluding permeability mutants); and 4) transferable resistance by conjugation. Beta-lactamases hydrolyzing aminothiazole-oximino substituted monobactams were produced by 17.2% of Enterobacteriaceae from intensive care unit patients; 3.6% from inpatients of other units and 1.2% from outpatients. Producers were mainly Klebsiella spp. (45/46) resistant to aminoglycosides (most of them AAC 3'-AAC 6' producers). Three strains had a an isoelectric point of 6.0, two of 6.5 and three of 7.7. TEM-1 beta-lactamase (isoelectric point 5.4) was detected in 6/8 strains. An inocolum effect was observed in 40/46 strains. A Klebsiella pneumoniae strain preserved since 1982 also produced a transferable beta-lactamase hydrolyzing aminothiazole-oximino substituted monobactams.
Salmonella typhimurium strains resistant to most beta-lactams, co-trimoxazole, tobramycin and gentamicin were isolated from patients in two hospitals in Buenos Aires, Argentina, beginning in August 1990. The patients were suffering from meningitis, septicaemia or enteritis. Therapy including ampicillin, ceftriaxone and gentamicin failed. The strains produced a plasmidic (pMVP-4) extended broad-spectrum beta-lactamase which is more active against cefotaxime than against ceftazidime (Vmax for cefotaxime 350 times higher than for ceftazidime). This cefotaximase demonstrates similarity to the previously described CTX-ase-M-1 from Escherichia coli, but it is distinctly different from CTX-ase-M-1 by its isoelectric point (7.9 for CTX-ase-M-2 in comparison with 8.9 for CTX-ase-M-1) as well as in its lower susceptibility to the beta-lactamase inhibitors sulbactam, clavulanic acid, tazobactam and BRL 42715. Thus, the beta-lactamase produced by S. typhimurium strains from Argentina appears to represent a new member (CTX-ase-M-2) of a novel group of plasmidic extended broad-spectrum beta-lactamases designated as cefotaximases.
Ethanol dependence was achieved in male, Long-Evans rats after 8 days on a balanced liquid diet that supplied 4.5% ethanol. After 1-h access to a solution of 10% ethanol (95%)/5% sucrose, the rats were deprived of food, water, and ethanol for 9 h. Following 30-s key jingling, about 80% of the animals exposed to ethanol experienced tonic-clonic seizures. Neurochemical analyses of striatal tissues revealed a significant (p < 0.05) increase in dopamine (DA) and a significant decrease in serotonin (5-HT) in the ethanol-exposed rats that had seizures compared to control rats. Homovanillic acid concentrations of the ethanol-treated rats with seizures were significantly higher than the levels found in ethanol-treated animals that had experienced no seizures. Daily average ethanol intake of the rats that had seizures vs. those that did not was almost the same at 16 g/kg/day. The findings indicate that rats experiencing ethanol withdrawal-induced seizures manifest opposite alterations in dopaminergic and serotoninergic activity compared to controls. The present results do not reveal if the striatal changes are caused by ethanol rather than by the seizures.
For a number of years now, we have argued that current models for the control of initiation of DNA synthesis, chromosomal partitioning and septum formation in Escherichia coli are unsatisfactory. Indeed, we could argue that despite considerable efforts, with the possible exception of dnaA and ftsZ, no genes specifically implicated in these control processes have been identified. In the cases of DnaA and FtsZ, no evidence has appeared to indicate how such molecules might be regulated to act once per cycle. In 1988, we formulated a specific proposal that the timing of cell cycle events in E. coli might be determined by a Ca++ flux, mediated by calcium-binding proteins and protein kinases and culminating, in the case of chromosome segregation and division, in the action of force-generating proteins such as myosin (Norris et al., 1988). In formulating this proposal, we took the view that the fundamental elements of cell cycle regulation are likely to be highly conserved across all species including prokaryotes. In this presentation, we shall describe the approaches we have been taking in order to test this hypothesis and to summarize the data obtained, in particular in relation to new genes identified which may play a role in the E. coli cell cycle. We shall also briefly indicate recent data from other laboratories consistent with our general hypothesis.
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