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Biomedical subjects

M Friedman

Publications and source records attributed to M Friedman.

At least 307 records · Page 17Linked to original sources
PubMed1988

Nuclear magnetic resonance study of an ethyl cellulose sustained-release delivery system. I: Effect of casting solvent on hydration properties.

This study was conducted in order to explore the proton relaxation time and the structural features of films that are cast from different solvents and to be used as sustained-release delivery systems. Protons magnetic resonance measurements were performed on ethyl cellulose (EC) films cast from ethanol or chloroform solutions in the presence of polyethyleneglycol (PEG). Spin-lattice relaxation time (T1) was measured with a Bruker PC-20 Multispec, at 20 MHz and at 37 degrees C, on the dry films and thereafter during gradual, controlled hydration. The prolongation of the rate of relaxation time for the films cast from ethanol and chloroform solutions was found to be drastically different. Water compartmentalization was then calculated according to the Free Induction Decay model. After the addition of similar amounts of water, markedly different hydration fraction (HF) values were derived for the films cast from the different solutions as a function of the amount of embedded PEG. Scanning electron micrographs confirmed that the two types of systems have different film structures that are dictated by the casting solvent and the amount of embedded PEG. From these results it can be concluded that in the presence of PEG, EC films cast from ethanol have more water binding sites and a thicker water multilayer around them than films cast from chloroform. These properties might influence the release rate of an active agent from the sustained-release device.

Cellulose↗
PubMed1988

Nuclear magnetic resonance study of an ethyl cellulose sustained-release delivery system. II: Release rate behavior of tetracycline.

The release rate behavior of tetracycline (TC) from a sustained-release delivery system composed of an ethyl cellulose (EC) film and polyethyleneglycol (PEG) was studied using proton magnetic resonance (PMR) and UV spectroscopy. The optical density (OD) and spin-spin relaxation time (T2) were measured after the films were immersed in di-distilled water. The TC release rate was examined as a function of two variables: gradual changes in the relative amounts (% w/w) of the embedded TC and PEG. A high correlation was found between the fractional changes of T2 relaxation time and the percent release of TC, as measured by means of UV spectroscopy. The results revealed that the TC release profile from EC film is strongly dependent on the amount of embedded TC. On the other hand, the amount of embedded PEG markedly affected the release rate and release time of TC. These changes were reflected in a pronounced shortening of the T2 relaxation time. The improvement in the hydrophilic character of the EC polymer allowed better penetration and contact of water with the whole film matrix and enhanced the dissolution of TC.

Cellulose↗
PubMed1988

The application of a two-stage design for clinical trials in patients with recurrent head and neck cancer.

Cytotoxic chemotherapy produces modest benefits for patients with recurrent and metastatic squamous cell carcinoma of the head and neck (SCCHN). Prospective randomized clinical trials have failed to demonstrate unequivocal superiority of aggressive multidrug regimens over single agents. Despite this, phase II trials frequently result in encouraging preliminary observations that compare favorably to historical single-agent data. While providing for a useful method of screening for anti-tumor activity, phase II studies have limited use in determining the relative value of a new treatment program. Results of phase II studies are considerably influenced by patient selection factors and criteria used to establish therapeutic benefits (responses). Furthermore, estimations of true levels of efficacy (response rates) are dependent on sample sizes, which are usually limited in such trials. We propose that newly developed combinations containing at least one known active agent in this disease should be tested in a controlled setting after their toxicity pattern has been well established. The conduct of the usual phase II study in these situations will probably not provide useful new information, since responses are likely to be observed. We describe a two-stage design applied to terminate a trial if at the first stage there is no evidence of improvement over the control arm. This method allows for early termination of studies involving relatively inefficient treatment regimens and, at the same time, continuation of those with a high likelihood to result in significant therapeutic improvements over a control arm. Loss of power is negligible and sample sizes can be reduced significantly. The rationale behind this method and its simplicity are attractive features for a widespread application for new drug development strategies in this and other diseases.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

Protein reactions with methyl and ethyl vinyl sulfones.

Disulfide bonds of bovine serum albumin and wool were reduced by n-tributylphosphine to sulfhydryl groups that were then modified by methyl or ethyl vinyl sulfone in a nucleophilic addition reaction to S-(beta-ethylsulfonylmethyl)-L-cysteine and S(beta-ethylsulfonylethyl)-L-cysteine, respectively. The reductive alkylation was carried out either simultaneously, with both the reducing and alkylating agents present in the reaction mixture, or sequentially, with the reduced proteins first isolated before alkylation. Amino acid analysis studies showed that authentic, synthetic S-(beta-ethylsulfonylethyl)-L-cysteine eluted as a well-resolved peak after serine but that the peak associated with the corresponding methyl derivative overlapped the corresponding peak due to threonine. The extent of alkylation of the sulfhydryl groups of cysteine, epsilon-NH2 of lysine, and NH groups of the imidazole ring of histidine was also measured by amino acid analysis. The results show that alkyl vinyl sulfones have a strong chemical affinity for protein functional groups.

Alkylating Agents↗
PubMed1988

Papillomaviruses in lesions of the lower genital tract in Israeli patients.

Human papillomaviruses (HPVs) have been strongly associated with benign lesions of the genital tract (condylomata) and with genital cancer of the vulva and cervix. Since the incidence of these lesions in Israel is considered to be low, we have studied the presence of HPV 6, 11, 16 and 18 DNAs in benign, premalignant and malignant tissue samples or gynecological swabs of the lower genital tract. HPV sequences were detected in 48 out of 66 condylomatous lesions (72%), 5/11 grades I-II intraepithelial neoplasia (45%), 4/6 grade III intraepithelial neoplasia (carcinoma in situ) (66.6%) and 8/22 invasive carcinoma (36%). The latter included six cases of vulvar carcinoma which were all negative for HPV sequences. No additional HPV types could be detected in any of the tissue biopsies examined. HPV 18 DNA has been found in one vulvar condyloma where it persisted as an episomal molecule, this being the first report of that specific viral DNA in a condylomatous lesion. In all the benign and premalignant lesions containing HPV, the viral sequences were maintained in an episomal state. In two cases of invasive carcinoma, the HPV 16/18 related sequences were integrated in the cellular genome, but in five cases (three containing HPV 16/18 related DNAs and two containing HPV 6/11 related DNAs) the viral sequences were episomal. HPV 16/18 related sequences detected in one out of three cases of vaginal carcinoma were also found to be episomal. This data indicates that human papillomavirus sequences are indeed found in genital lesions of Israeli patients, although to a lesser extent than in other countries, especially for benign lesions and invasive carcinomas. Although HPVs may have a causative role in the development of genital lesions, also in this low tumor incidence area, other factors should be also considered in the etiology of these lesions.

Condylomata Acuminata↗
PubMed1988

Diagnostic imaging techniques in thyroid cancer.

With the refinement of fine-needle aspiration, the specific applications of thyroid imaging techniques need to be reevaluated for efficiency and cost containment. No thyroid imaging test should be routinely obtained. Radionuclide scanning is most beneficial in evaluating the functional status of thyroid nodules when fine-needle aspiration is inadequate, the findings are benign, or when there is no discrete nodule that is palpated in an enlarged gland. When fine-needle aspiration is unavailable or unreliable, radionuclide scanning becomes a first-line diagnostic tool. Ultrasonography should be used primarily for identifying a solid component of a cystic nodule, determining the size of nodules on thyroxine suppression that are not easily palpable, or for performing guided fine-needle aspiration. Computerized tomography and magnetic resonance imaging both have a definite role in the evaluation of thyroid tumors. Magnetic resonance imaging is superior to computerized tomography for the evaluation of metastatic, retrotracheal, or mediastinal involvement of large thyroid tumors or goiters. Careful selection of the diagnostic techniques will ensure more accurate diagnosis and reduce unnecessary patient costs in the treatment of thyroid cancer.

Biopsy, Needle↗
PubMed1988

Nutritional value and safety of methionine derivatives, isomeric dipeptides and hydroxy analogs in mice.

Weight gains in mice fed amino acid diets containing methionine and 16 methionine derivatives and analogs were compared at graded dietary concentrations. Linear response was closely approximated for concentrations below those yielding maximum growth. Derivatization of L-methionine generally lowered potency, calculated as the ratio of the slopes of the two dose-response curves. However, the three isomeric dipeptides L-L-, L-D- and D-L-methionylmethionine, N-acetyl- and N-formyl-L-methionine, L-methionine sulfoxide and D-methionine were well utilized. The double derivative N-acetyl-L-methionine sulfoxide reduced potency below 60%. D-Methionine sulfoxide, N-acetyl-D-methionine and D-methionyl-D-methionine had potencies between 4 and 40%. The calcium salts of L- and D-alpha-hydroxy analogs of methionine had potencies of 55.4 and 85.7%, respectively. Several of the analogs were less growth-inhibiting or toxic at high concentrations in the diet than was L-methionine. These results imply that some methionine dipeptides or analogs may be better candidates for fortifying foods than L-methionine. Possible biochemical pathways for the utilization of methionine derivatives and analogs are also described.

Amino Acids↗
PubMed1988

Experience with the sternocleidomastoid myoperiosteal flap for reconstruction of subglottic and tracheal defects: modification of technique and report of long-term results.

Subglottic or tracheal reconstruction may be required in cases of subglottic stenosis, invasive thyroid carcinoma, or trauma. The sternocleidomastoid myoperiosteal flap uses clavicular periosteum on a muscle pedicle to provide vascularity. Clavicular periosteum is fibrous, durable, and will conform to the shape of the trachea, forming bone to provide stability to the airway. The procedure is relatively simple and involves single-staged reconstruction. After 4 years' experience with this flap, we present the results from a series of 11 patients who underwent subglottic or tracheal reconstruction with the sternocleidomastoid myoperiosteal flap. Ten of 11 patients were successfully decannulated. The average time from reconstruction to decannulation was 50.3 days. Follow-up ranged from 12 to 40 months. We also describe modifications of the initial technique that have been introduced to improve the flap's versatility and effectiveness.

Adult↗
PubMed1988

The sternocleidomastoid myoperiosteal flap for esophagopharyngeal reconstruction and fistula repair: clinical and experimental study.

Despite advances in head and neck surgery, reconstruction of the pharynx and cervical esophagus continues to be troublesome. Classic pedicled flaps are often too bulky and difficult to position for repair of pharyngeal and esophageal fistulas. An ideal flap would be local, well-vascularized, compact, and capable of being sutured into a tension-free, water-tight seal. In selected cases, the sternocleidomastoid myoperiosteal flap can meet these requirements in a single-stage procedure for repair of fistulas as well as selected cases of primary pharyngeal reconstruction. The use of this flap is described in five patients. Two patients underwent laryngectomy with partial pharyngectomy that left inadequate mucosa for primary closure. A sternocleidomastoid myoperiosteal flap was used to add width to the remaining mucosa. Both patients healed within 3 weeks and remained stricture free. Three other patients who underwent radiation followed by tumor resection and standard primary closure of the pharynx developed fistulas. Two fistulas were repaired successfully with the sternocleidomastoid myoperiosteal flap, and both patients were able to eat a general diet on the eighth postoperative day. Reconstruction was also performed in dogs to histologically evaluate the epithelialization capacity of the periosteum. There was total epithelialization of the flap at 4 weeks after reconstruction.

Aged↗
PubMed1988

Head and neck: high field magnetic resonance imaging versus computed tomography.

A comparative review of head and neck lesions examined with both CT and MRI showed that the location and extent of lesions can be more precisely evaluated with MRI. MRI allows better differentiation of neurogenic tumors from other lesions. Vascular structures are easily visualized on MRI without intravenous contrast and can easily be differentiated from lymph nodes. However, cystic lesions and necrotic nodes sometimes could not be differentiated from solid lesions when using MRI.

Branchioma↗