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Biomedical subjects

M J Levy

Publications and source records attributed to M J Levy.

At least 19 recordsLinked to original sources

Expression of the insulin-like growth factor (IGF)-I and -II and the IGF-I and -II receptor genes during postnatal development of the rat ovary.

Solution hybridization/RNase protection assays were used to study the developmental expression of the insulin-like growth factor-I (IGF-I), IGF-II, IGF-I receptor, and IGF-II/mannose-6-phosphate receptor genes in the rat ovary between postnatal days 1-80. Maximal IGF-I mRNA levels occurred during the 15- to 25-day postnatal period, and the level on day 20 represented a 9-fold increase over the baseline at earlier and later stages. IGF-II mRNA levels were maximal during the 1- to 5-day postnatal period and subsequently declined to undetectable levels after day 10. IGF-I receptor mRNA levels increased 10-fold to a maximum in the 20- to 25-day postnatal period. This pattern was similar to the developmental pattern of [125I]IGF-I binding in the ovary. Two apparent peaks of IGF-II/mannose-6-phosphate receptor mRNA levels were seen, on day 20 and between days 50-80. These specific and significant changes in the expression of the genes encoding the IGFs and their receptors suggest a role for the IGF system in postnatal ovarian development.

Aging

Reproductive potential in survivors of childhood malignancy.

The aggressive use of multiple therapeutic modalities has led to a significant increase in the number of survivors of childhood malignancy. These forms of cancer therapy have important effects on multiple organ systems. This review article evaluates the long-term effect of therapy on the reproductive potential of both boys and girls. While alkylating agents have been shown to cause a 50% reduction in the fertility potential of boys, they have almost no adverse effect in girls. Other chemotherapeutic agents and combinations of chemotherapeutic agents have also been shown to cause a greater reduction in the reproductive potential of girls than boys. Radiation produces severe dose-related gonadal damage in both boys and girls. The effect of Hodgkin's disease, leukemia and their therapies are evaluated. Despite the known mutagenic potential of some forms of cancer therapy there has not been an increased frequency of congenital abnormalities in the offspring of survivors of childhood cancer. The use of oophoropexy and other forms of prophylactic therapy to limit toxicity are also considered.

Adult

Rapid percutaneous tracheostomy.

We describe a new method of performing percutaneous tracheostomy rapidly and safely using a specialized instrument kit. The technique permits the safe insertion of a full-sized 7.0 (ID) or 7.5 mm (ID) cuffed cannula into the trachea within 1-2 min, through the membranous second intercartilagenous space. Animal studies have demonstrated a superior healing process compared to that seen after conventional tracheostomy techniques.

Animals

Proton NMR study of the influence on iron oxidation/ligation/spin state on the heme orientational preference in myoglobin.

Proton nuclear magnetic resonance spectroscopy has been utilized to demonstrate that the degree of heme orientational disorder within a given myoglobin protein matrix can be a sensitive function of the oxidation/ligation/spin state of the heme iron. For sperm whale deuterohemin-reconstituted myoglobin, the equilibrium was found to strongly favor (5.7 to 7.8 kJ/mol) the X-ray characterized heme orientation in all six-coordinate states, but with a considerable reduction in preference (to 1.6 kJ/mol) in the five-coordinate deoxy state. In native yellow fin tuna myoglobin, changes in heme orientational preferences of approximately 3 kJ/mol occur even between two six-coordinate ferric states differing solely in spin states.

Animals

Percutaneous tracheostomy--a new method.

A rapid method of definitive low tracheostomy utilizing an original instrument kit and percutaneous approach is described. Through a horizontal, shallow (1.5-cm) skin incision in the neck, a 12-ga needle is introduced into the tracheal lumen. A flexible metal guidewire is gently introduced through the needle, which is then removed. A specially designed percutaneous tracheostomy tool slides over the guidewire into the trachea; by squeezing its handles, the intercartilaginous space is enlarged, securing the placement of a cuffed tracheal cannula. After extensive and successful investigation in both cadaver and animal trials, the procedure was carried out in 80 patients who had a variety of underlying diseases, without serious complications. Of these 80 patients, 33 required airway control after neurosurgical interventions or after severe head trauma, 23 had percutaneous tracheostomy performed before radical excision for head and neck cancer, and the remaining 24 suffered from severe cardiorespiratory problems. Twenty-nine procedures were performed in the operating theater, and 51 procedures were carried out at the patient's bedside in the ICU, ED, or in the ward. There was no infection at the stoma site, and late healing was remarkable. It should be strongly emphasized that in the majority of our patients the procedure was carried out safely at the bedside. This resolved the logistic problem of moving very sick ICU patients (who are sometimes on high PEEP levels) to the OR. Although our experience is totally restricted to elective situations, we do postulate that it could be as effective in a variety of urgent situations.

Adult

Oligonucleotide N-alkylphosphoramidates: synthesis and binding to polynucleotides.

A few different methods for the preparation of oligonucleotide N-alkylphosphoramidates were compared directly. One of these, involving the use of protected nucleoside phosphites as building blocks, provided the requisite N-alkylphosphoramidates via oxidation of the intermediate dinucleoside methyl phosphites with iodine in the presence of the appropriate alkylamine. This method was found to have several attractive features, including the use of building blocks identical with those employed for the synthesis of DNA and compatibility with procedures and instruments employed for the stepwise synthesis of oligonucleotides by solution and solid-phase methods. This procedure was used to make several di-, tri-, and tetranucleotide N-alkylphosphoramidates derived from deoxyadenosine and thymidine; alkyl substituents included N,N-dimethyl, N-butyl, N-octyl, N-dodecyl, and N-(5-aminopentyl). The aminoalkyl derivative of d(TpT) (24) was used to demonstrate the feasibility of introducing an intercalative agent to the alkylphosphoramidate moiety of such derivatives. The oligonucleotide N-alkylphosphoramidates were separated into their component diastereomers and characterized structurally by a number of techniques including circular dichroism, high-field 1H NMR spectroscopy, FAB mass spectrometry, and enzymatic digestion to authentic nucleosides and nucleotides. Physicochemical characterization of several di- and trinucleotide alkyl-phosphoramidates revealed that the adenine nucleotide analogues formed stable complexes with poly-(thymidylic acid). The stabilities of these complexes were found to increase with increasing chain length of the N-alkylphosphoramidate substituents. The finding that N-alkylphosphoramidate substituents can enhance the binding of certain oligonucleotides to their complementary polynucleotides suggests the existence of a novel source of polynucleotide affinity.

Chemical Phenomena

Copper(II) facilitates bleomycin-mediated unwinding of plasmid DNA.

The unwinding of plasmid DNA by bleomycin A2 (BLM A2) was investigated by use of two-dimensional gel electrophoresis. It was found that Cu2+ ions greatly facilitated the unwinding of topoisomers of plasmid DNA by BLM A2 at concentrations where cupric ions alone had no effect on DNA supercoiling. The concentration of BLM A2 required for observable unwinding was reduced at least 100-fold in the presence of equimolar Cu2+. A plot of [Cu2+] vs extent of DNA unwinding in the presence of 10(-4) M BLM A2 gave a curve consistent with the action of cupric ions on BLM in an allosteric fashion, possibly rearranging the drug into a conformation that facilitates DNA unwinding. The participation of the metal center in enhancing DNA unwinding via direct ionic interaction with one or more negatively charged groups on the DNA duplex also seems possible. Further analysis of the structural factors required for BLM-mediated DNA unwinding was carried out with Cu2+ + BLM demethyl A2, the latter of which differs from BLM A2 only in that it lacks a methyl group, and associated positive charge, at the C-terminus. Cu(II).BLM demethyl A2 was found to be much less effective than Cu(II).BLM A2 as a DNA unwinding agent, emphasizing the strong dependence of this process on the presence of positively charged groups within the BLM molecule. These findings constitute the first direct evidence that the metal center of BLM can participate in DNA interaction, as well as in the previously recognized role of oxygen binding and activation.

Bacteriophage phi X 174

Surgical removal of a mobile, pedunculated left ventricular thrombus: report of 4 cases.

During an 11-month period, 4 patients underwent surgical removal of a mobile, pedunculated left ventricular thrombus. All 4 patients had a history of myocardial infarction. Two of the 4 patients had systemic emboli, and in the 2 others, the ventricular thrombi were removed to prevent emboli. The thrombus was removed during the acute phase of myocardial infarction in 2 patients and one and two years, respectively, following the infarct in the remaining 2 patients. Concomitant coronary artery bypass grafting was performed in 3 patients. There were no early or late deaths, and none of the patients had clinical or echocardiographic evidence of recurrent thrombi or emboli at follow-up 3 to 15 months later. These results indicate that left ventricular thrombectomy might be an effective treatment for patients with mobile, pedunculated, left ventricular thrombi. However, additional experience is required to compare surgical and medical treatment.

Aged

Safety precautions in the management of patients with pacemakers when electrocautery operations are performed.

The hazards related to ten patients who underwent 11 urologic surgical procedures during a 36 month period were taken into consideration. Electrocautery was used in all instances and there were no complications. All of the pacemakers were preset for ventricular pacing and sensing inhibited or multiprogrammable and were reprogrammed during the operation to ventricular pacing fixed rate mode or magnet mode, with very satisfactory outcome. To avoid life-threatening situations arising from pacemaker inhibition or ventricular fibrillation during cautery for transuretheral resection, three basic factors were considered: 1, appropriate type of pacemaker; 2, the proper grounding of all medical electronic equipment used during the procedure, and 3, the directing of the complete flow of the electrocautery circuits substantially below the level of the pacemaker unit.

Accident Prevention

Dissecting aortic aneurysm in pregnant women without Marfan disease.

Dissection of the young women without Marfan disease is related, in most instances, to pregnancy. The structural changes in the arterial wall that occur during pregnancy may predispose women to this complication of pregnancy. In this study, two young women, who had none of the characteristics of Marfan's syndrome, were operated upon for dissection of the ascending aorta. The first patient was in the 35th week of gestation and a cesarean section was performed prior to replacement of the ascending aorta. In the second patient, diagnosis of dissection and severe aortic regurgitation occurred in the postpartum period. Knowledge of this albeit relatively rare complication of pregnancy may assist the clinician in diagnosing and referring patients early for surgical treatment that, in most instances, may save the lives of both mother and fetus.

Acute Disease

Closed pericardial drainage for relief of pericardial tamponade.

The method of continuous catheter drainage for pericardial tamponade as used in 108 patients is described. The efficacy of this procedure in relieving tamponade resulting from a variety of diseases is demonstrated. Blood clot in the pericardium probably constitutes a contraindication to catheter drainage.

Cardiac Catheterization

Pneumonectomy in pulmonary mucormycosis complicating Behçet's disease.

A 37 year old man with Behçet's disease who was maintained on prolonged corticosteroid therapy, developed diabetic ketoacidosis and pneumonia. Secondary infection with mucor intervened with abscess formation cured by pneumonectomy. The association of Behçet's disease and mucormycosis has not been previously reported, although diabetes mellitus was almost certainly the predisposing cause. Surgical treatment offers the best chance of survival in similar cases.

Adult

Repair of coarctation of the aorta in the first three months of life.

Coarctation of the aorta was surgically treated in 28 infants (16 male, 12 female) aged 2 days-3 months, with 19 younger than 1 month. Body weight at operation was 1.6-4.2 (mean 2.8) kg. 3 infants had coarctation alone, 10 had a wide patent ductus arteriosus as the only associated anomaly and 15 had a variety of other anomalies. Resection with end-to-end anastomosis was performed in only one case, while 21 underwent subclavian flap aortoplasty and six patch graft aortoplasty. Additional procedures were banding of the pulmonary artery in five cases and open aortic commissurotomy in one case. The early mortality was 10.7% (3 infants) and three more died later. Further cardiac surgery was subsequently performed on four of the infants. Of the 22 survivors, two had significant recurrence of coarctation which, however, was successfully corrected in one case. The blood pressure was within normal limits in all survivors, except those with recoarctation.

Aortic Coarctation