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Biomedical subjects

J Gross

Publications and source records attributed to J Gross.

At least 19 recordsLinked to original sources

Comparative study of doxorubicin, mitoxantrone, and epirubicin in combination with ICRF-187 (ADR-529) in a chronic cardiotoxicity animal model.

In this study doxorubicin, epirubicin, and mitoxantrone were compared for their cardiotoxic potential in a chronic mouse model in an effort to identify and compare their mechanism(s) of toxicity. In addition, the cardioprotective ability of ICRF-187 [(+/-)-1,2-bis(3,5-dioxopiperazinyl-1-yl)propane] with each anticancer drug was evaluated in this model. The antioxidant capacity (superoxide dismutase, reduced glutathione, catalase, and glutathione peroxidase) was assessed following drug treatment. Five-week-old BALB/c mice received weekly i.p. injections of each drug or the drug and ICRF-187 over a 3-month period. ICRF-187 was administered 30 min prior to the anticancer drug. The hearts were examined by electron and light microscopy to assess subcellular changes, and the cardiac and hepatic antioxidant levels were measured concurrently. Chronic treatment with these drugs or each combined with ICRF-187 did not change the antioxidant levels relative to the control values. However, all three drugs caused cardiac damage during chronic exposure. Both epirubicin and mitoxantrone caused less severe damage than doxorubicin, and epirubicin was the least cardiotoxic of the three. ICRF-187 was cardioprotective for epirubicin and doxorubicin but not for mitoxantrone. These results suggest epirubicin acts by a mechanism similar to that of doxorubicin that is probably mediated by oxygen-free radicals, while mitoxantrone acts by a different mechanism to cause cardiotoxicity.

Animals

Effects of postnatal ganglioside administration and hypoxia-exposure on the dopamine release from striatal slices, the behaviour and the ganglioside pattern of 2-3 months old rats.

Neonatal rats were injected with a mixture of bovine brain gangliosides (30 mg/kg body weight, s.c.) immediately before the exposure to hypoxia (pO2 = 10 kPa, 10 hrs daily) from the 2nd to the 11th day of life. At the age of 2-3 months the potential protective or restitutive effect of gangliosides on the radiolabelled dopamine release from striatal slices and on the conditioned avoidance learning was studied. No change in the content and the pattern of gangliosides of the rat striata was found after exposure to hypoxia and ganglioside administration, respectively. Both hypoxia exposure and ganglioside treatment of controls increased the dopamine release whereas hypoxic animals treated with gangliosides showed a diminished release. Hypoxia-induced impaired conditioned avoidance learning was improved by ganglioside treatment. The changed release of dopamine and the altered behavioural performance after ganglioside treatment alone indicate the necessity of a very cautious application of gangliosides to the developing brain.

Aging

Experimental model of smoking re-exposure: effects on relapse.

This study used a short-term laboratory model of smoking cessation and relapse to prospectively examine the effects of programmed self-administered smoking re-exposure during early abstinence. Sixty-seven subjects who had quit smoking for 3 days were randomly assigned either to smoke five cigarettes in their natural environment or to remain abstinent during the exposure period. The main hypothesis, that relapse to regular smoking would be quicker and more prevalent in exposed subjects, was supported. All exposed subjects had relapsed by 2 days post-exposure while 16% of unexposed subjects remained continuously abstinent throughout the 8 day study. This behavioral effect was seen in spite of acute decreases in reported desire to smoke and increases in guilt measured just after exposure. The study supports a role for stimulus re-exposure effects in the relapse process and suggests that additional research on experimental re-exposure is warranted.

Adult

Combined maze procedure and septal myectomy in a septuagenarian.

A 75-year-old woman with refractory paroxysmal atrial fibrillation and hypertrophic obstructive cardiomyopathy underwent a successful combined maze procedure and septal myectomy. Postoperative episodes of atrial fibrillation and flutter occurred only during periods of bradyarrhythmia and did not recur with atrial inhibited pacing.

Aged

Lasting effects of postnatal hypoxia and saline injection on the striatal dopamine transport and their modification by gangliosides.

Hypobaric hypoxia (10 h daily, pO2 10 kPa) and saline administration (2.5 microliters/g body wt) from the 2nd till the 11th day of life both induced a long-lasting increase of the low-affinity dopamine (DA) uptake capacity in S1-fractions of the rat striatum. Additionally, the potassium-stimulated DA release was enhanced in adult control rats postnatally injected with saline. The administration of a mixture of bovine brain gangliosides (30 micrograms/g body wt) was found to prevent these effects. However, the kinetic constants of the DA uptake of hypoxic rats treated with gangliosides were reduced in comparison to untreated controls. Thus, the effects of gangliosides appear to differ between hypoxic and control conditions. The modification of the dopaminergic activity during brain development is discussed as a possible mechanism of the preventive effects of gangliosides against long-term cerebral dysfunctions following hypoxia or stress.

Animals

Craniofacial applications for the Medpor porous polyethylene flexblock implant.

We describe use of flexblock, a newly designed Medpor porous polyethylene implant. This implant is ideally suited for repair of small to medium-sized cranial defects and correction of contour deformities. Medpor is used for a wide variety of maxillofacial procedures, and its properties make it an excellent choice for the cranium. It is a highly stable and somewhat flexible porous alloplast that has been shown to exhibit rapid soft-tissue and bone ingrowth. Flexblock, which was designed as an onlay for calvarial bone graft donor sites, has a smooth exterior surface and a series of conical ridges on its undersurface that enable easy bending, good contour adaptability, and suitable strength. We used the Medpor flexblock implant in 12 patients over 2 years for correction of contour deformities, cranial defects, and reconstruction of the supraorbital rim. There were no complications. Larger cranial defects and complex reconstructions can be performed using customized Medpor implants. The properties of Medpor and the flexblock design make this implant an excellent alternative to the existing methods of cranioplasty and cranial contour correction.

Adult

Clinical evaluation of the safety of repetitive intraoperative defibrillation threshold testing.

One goal of the initial implantation procedure for a cardioverter defibrillator is determination of the configuration and patch location with the lowest defibrillation threshold (DFT). To determine the safety of multiple defibrillation tests, an analysis of the intraoperative defibrillation threshold tests (DFTT) in our patients was performed. In 84 patients, the mean number of DFT trials was 5.27; the mean number of joules received was 275.0. The maximum number of shocks in one implant procedure was 50 for a total of 4,895 joules without complications. Four patients received 30 or more DFT shocks without complication. There were two complications related directly to the DFTT: one patient with severe noninflammatory cardiomyopathy developed electromechanical dissociation and was subsequently resuscitated and survived; the second patient with severe triple vessel coronary artery disease suffered an intraoperative myocardial infarction during testing and eventually died 22 days postoperatively. All patients received an ICD unit; six patients had DFTs of greater than 20 joules. Based on our experience, we followed the clinical status (heart rate, blood pressure, ECG changes, fluid status, total anesthesia time) during the DFTT to determine the extent and duration of our testing protocol. Multiple shocks due to repositioning of the leads in a stable patient should not prohibit extensive testing as adverse consequences do not appear to be cumulative.

Electric Countershock

Influence of left ventricular function on outcome of patients treated with implantable defibrillators.

BACKGROUND: The outcomes of patients treated with implantable defibrillators were compared between patients with left ventricular ejection fraction greater than or equal to 30% and less than 30%. METHODS AND RESULTS: Of 68 consecutive patients treated with implantable defibrillators, 40 patients (group 1) had left ventricular ejection fraction greater than or equal to 30%, and 28 patients (group 2) had left ventricular ejection fraction less than 30%. Sudden death, surgical mortality, nonsudden arrhythmia-related death (death within 24 hours after an arrhythmic event despite initial termination of the arrhythmia by the implantable defibrillator), total arrhythmia-related death (including sudden death, surgical death, and nonsudden arrhythmia-related death), and total cardiac death were compared between the two groups. Surgical mortality was 4.4% (0% in group 1, 11% in group 2). During the follow-up of 31 +/- 27 months, actuarial survival rates free of events were 97%, 97%, and 97% in group 1 and 96%, 91%, and 82% in group 2 at 12, 24, and 36 months, respectively, for sudden death (p = NS); 97%, 97%, and 97% in group 1 and 85%, 81%, and 72% in group 2 at 12, 24, and 36 months, respectively, for sudden death and surgical mortality (p less than 0.05); 97%, 97%, and 97% in group 1 and 82%, 78%, and 70% in group 2 at 12, 24, and 36 months, respectively, for total arrhythmia-related death (p less than 0.05); and 95%, 95%, and 95% in group 1 and 82%, 69%, and 57% in group 2 at 12, 24, and 36 months, respectively, for total cardiac death (p less than 0.05). Four (57%) of seven nonsudden cardiac deaths during the initial 36-month follow-up period were causally related to arrhythmia (three surgical deaths and one arrhythmia-related nonsudden death). CONCLUSIONS: The outcome of patients treated with implantable defibrillators is strongly influenced by the degree of left ventricular dysfunction. In group 1 patients, surgical mortality, sudden death, and total cardiac death are rare. In group 2, sudden death rate may not be markedly different from that of group 1 patients. However, the risk of therapy (surgical mortality) is high. Many nonsudden cardiac deaths are causally related to arrhythmia (surgical mortality or nonsudden arrhythmia-related death). Therefore, the survival rate free of total arrhythmia-related death is significantly lower in group 2 (70% versus 97% in group 1 at 3 years). Further studies are needed to determine the roles of defibrillator therapy and other therapies in various clinical settings.

Actuarial Analysis

The appearance in thyroidectomized mice of immunoglobulins that bind TSH and stimulate FRTL-5 thyrocytes.

The purpose of these studies was to examine whether thyroid stimulating antibodies in Graves' patients could arise as auto-antiidiotypic antibodies to endogenous anti-TSH antibodies. The model system chosen was the thyroidectomized mouse, exhibiting an elevated level of endogenous, circulating TSH. Mice were thyroidectomized by 131I administration. Sera samples were drawn 1 to 14 months later. The following activities were measured in the immunoglobulin (Ig) fractions prepared: (a) TSH binding by elisa techniques, (b) iodide pump activity (as measured by 99mTcO4 uptake) and (c) increased [3H]thymidine incorporation into the DNA of FRTL-5 cells. TSH binding Igs were detected in 29/98 mice thyroidectomized for 7-14 months. Stimulation of technetium uptake was observed in 59/110 mice and stimulated labeled thymidine uptake in 37/102 mice, beginning eight and nine months after thyroidectomy, respectively. Of the positive animals, 51 showed a single stimulating activity. The incidence and the serum titers of Igs that stimulate technetium uptake increased significantly with time. Indeed, in the group tested 14 months post-thyroidectomy, 75% of the sera were positive for this antibody with a mean titer eightfold higher than the controls. Hybridomas were prepared from the spleen lymphocytes of thyroidectomized mice. Of these, 18 produced 99mTcO4 uptake stimulating Igs, 12 [3H]thymidine-uptake stimulating Igs and 18 TSH binding Igs. Most of the hybridomas secreted Igs with a single bioactivity. One monoclonal antibody was isolated which neutralized the bioactivity of bTSH on FRTL-5 cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Glycosylated serum protein levels assayed with highly sensitive immunoradiometric assay accurately reflect glycemic control of diabetic patients.

OBJECTIVE: To develop a sensitive and reliable immunoreadiometric assay to measure glycosylated lysine residues on serum proteins (GSP) and to evaluate its efficacy in monitoring glycemic control. RESEARCH DESIGN: The effect of acute and chronic in vitro and in vivo changes in glucose levels on GSP concentration was evaluated. GSP determinations from insulin-dependent diabetic (IDDM) patients, non-insulin-dependent diabetic (NIDDM) patients, and control subjects were correlated with other indices of glycemic control. RESULTS: The GSP levels were unaffected by acute glucose changes after food or intravenous glucose administration but increased during storage at -20 degrees C due to in vitro glycosylation by endogenous glucose. Immediate acidification of the serum prevented this, permitting long-term storage despite high ambient glucose levels. In randomly selected diabetic patients, 96% of GSP values were greater than the mean +3SD of nondiabetic control subjects. In diabetic patients, GSP levels correlated with mean plasma glucose concentrations (Kendall correlation statistics 0.47, P less than 0.001), fasting plasma glucose levels (Kendall statistics 0.42, P less than 0.001), and glycosylated hemoglobin (GHb, Kendall statistics 0.30, P less than 0.005). Induction of near-normal glycemia in poorly controlled NIDDM patients reduced GSP levels with a slope consistent with a half time of disappearance of 4.7 +/- 0.4 days. GSP levels remained elevated in 6 of 10 well-controlled NIDDM patients, despite normal GHb concentrations. Chronic hypoglycemic states, like pregnancy and hyperinsulinemic hypoglycemia, were associated with significantly low GSP levels. CONCLUSION: We describe a reproducible and sensitive immunoradiometric assay for GSP that closely reflects the degree of glycemic control in diabetic patients. Further studies are needed to determine whether this assay may be useful in screening for glucose intolerance or gestational diabetes.

Blood Glucose

[The modified Magill forceps].

The Magill forceps are used for nasotracheal intubation, endotracheal suctioning, passing gastric tubes, placement of tampons in the nasopharynx and extraction of foreign material from the pharynx. There are several disadvantages of the standard Magill forceps; however: the danger of cuff perforation, the necessity of readjusting the forceps when placing a tube or catheter, and the risk of injury to the mucous membrane. For these reasons the standard Magill forceps have been modified: the jaws of the forceps have been changed to give curved atraumatic parts without any serrations or sharp edges. RESULTS. The resulting benefits are as follows: Reduced risk of injuring the mucous membrane and perforating the cuff. Tubes and catheter are safely guided between the semiround jaws, making it unnecessary to open the forceps repeatedly to advance the tube. Tampons being placed in the throat no longer get caught between the serrations, and even small foreign objects can easily be extracted from the pharynx.

Anesthesiology

Exacerbation of ventricular arrhythmias during the postoperative period after implantation of an automatic defibrillator.

The postoperative course of 68 consecutive patients treated with an implantable defibrillator during the period from 1982 through 1990 was studied. In 46 patients (group 1), no concomitant surgery was performed during the implantation. In 22 patients (group 2), concomitant surgery (coronary artery bypass [n = 12], valve replacement [n = 3] or arrhythmia surgery [n = 7]) was performed. All patients in group 1 were clinically stable before surgery, receiving an antiarrhythmic regimen chosen by serial drug testings. The same regimen was continued postoperatively. Eight of the 46 patients in group 1 whose condition had been stable in the hospital for 19 +/- 25 days preoperatively developed multiple episodes of sustained ventricular tachycardia 4 +/- 9 days after implantation while receiving the same antiarrhythmic regimen. Although the exacerbation was transient in some patients, six required different antiarrhythmic therapy and one eventually died. Two additional patients had frequent and prolonged episodes of nonsustained ventricular tachycardia that could trigger the defibrillator, requiring changes in the antiarrhythmic regimen. Another patient had progressive cardiac failure and died on day 5. A marked (sevenfold) increase in asymptomatic ventricular arrhythmias was noted in 42% of the remaining 35 patients. In group 2 (combined surgery), one patient developed refractory ventricular tachycardia 3 days postoperatively and died on that day. Three patients developed frequent nonsustained ventricular tachycardia postoperatively, requiring changes in the antiarrhythmic regimen. The overall surgical mortality rate was 4.4% (4.3% in group 1 and 4.5% in group 2) and was due to refractory ventricular tachycardia in two patients and cardiac failure in one.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

HIV-1 proteinase is required for synthesis of pro-viral DNA.

HIV-1 proteinase activity is thought to occur primarily post-integration by cleaving the viral Gag and Gag-Pol polyproteins. Its role in the pre-integration stages of viral replication, however, has not been studied in detail. Here we report that a synthetic peptide analogue, UK-88,947, which is a specific inhibitor of purified HIV-1 proteinase, inhibits the processing of the viral polyproteins in cultures of HIV-1 infected cells and prevents the formation of mature, infectious virions. Analysis of DNA from HIV-1 infected cells treated with UK-88,947 showed that viral DNA synthesis was inhibited when the compound was added to cultures one hour before infection. Similar results were obtained when AZT was used. Neither HIV-1 reverse transcriptase or the replication of FIV are inhibited by UK-88,947.

Amino Acid Sequence

Benefits of implantable defibrillators are overestimated by sudden death rates and better represented by the total arrhythmic death rate.

Benefits of the implantable defibrillator on survival were studied in 56 consecutive patients (concomitant coronary bypass or arrythmia surgery in 15) during an 8 year period between 1982 and 1990. During a follow-up period of 29 +/- 25 months, six patients had a sudden death and eight patients had a nonsudden cardiac death. Nonsudden cardiac deaths included three surgical deaths (death within 30 days after the surgery; two in patients without and one in a patient with concomitant cardiac surgery), one arrhythmia-related nonsudden death (death within 24 h after an arrhythmic event despite initial termination of the arrhythmia by the implantable defibrillators) and four nonarrhythmic cardiac deaths. The actuarial survival rate free of events at 1, 2 and 3 years was 96%, 96% and 92%, respectively, for sudden death, 91%, 91% and 87% for sudden death and surgical mortality and 89%, 89% and 85% for total arrhythmic death (sudden death, surgical mortality and arrhythmia-related nonsudden death). Thus, in patients treated with an implantable defibrillator, 1) the rate of sudden death is low (8% at 3 years); 2) 50% of nonsudden cardiac deaths are causally related to arrhythmia (surgical mortality or arrhythmia-related nonsudden death); 3) the total arrhythmic death rate is substantially higher than the sudden death rate; and 4) benefits of an implantable defibrillator are overestimated by reported sudden death and nonsudden cardiac death rates. The benefits may be better represented by the total arrhythmic death and nonarrhythmic cardiac death rates.

Actuarial Analysis

Spatial variation of sequestered calcium in the multicellular stage of Dictyostelium discoideum as assayed by chlortetracycline fluorescence.

We have used chlortetracycline (CTC) as a fluorescent probe to detect the distribution of sequestered calcium in multicellular stages of Dictyostelium discoideum. Tips of late aggregates, slugs and early culminating masses fluoresce very strongly. Most of the fluorescence is intracellular in origin and emanates from a small number of intense punctate sources. The sources correspond in part to autophagic vacuoles vis. neutral-red staining, acidic digestive vesicles, and may also include intracellular organelles; cytoplasmic fluorescence is much weaker in comparison. The level of fluorescence drops in the middle portion of slugs and rises again in the posteriormost region, though not to as high a level as in the tip. This holds good irrespective of whether CTC is applied only in the neighbourhood of the aggregate centre, only in the aggregate periphery, or to the whole aggregate. We infer that there must be a good deal of mixing in the stages leading from aggregation to slug formation; thus the serial order in which cells enter an aggregate does not bear any relation to their ultimate fates. The other implication of our study is that calcium sequestration is much more extensive in prestalk and anterior-like cells than in prespore cells. These findings are discussed with regard to possible implications for pattern formation.

Animals

Pacemaker infection with Mycobacterium avium complex.

A 21-year-old. HIV negative, malnourished, homeless woman with congenital heart block had a pacemaker implanted at 7 years of age and multiple procedures thereafter. The most recent of these procedures was replacement of a pulse generator in the right pectoral region. Four months later she had fever, pain, and swelling over the implant site resulting from infection with mixed flora and Mycobacterium avium complex. The pacemaker system was removed by thoracotomy via a median sternotomy and a new DDD pacemaker simultaneously implanted. She was treated with systemic antibiotics--isoniazid, rifampin, ethambutol--for 2 weeks. Six months later she was healthy, pacing well, and apparently free of infection, off all medications.

Adult