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Biomedical subjects

Michael Friedman

Publications and source records attributed to Michael Friedman.

At least 55 records · Page 3Linked to original sources
PubMed2003

Expandable gastroretentive dosage forms.

Expandable gastroretentive dosage forms (GRDFs) have been designed for the past 3 decades. They were originally created for possible veterinary use, but later the design was modified for enhanced drug therapy in humans. These GRDFs are easily swallowed and reach a significantly larger size in the stomach due to swelling or unfolding processes that prolong their gastric retention time (GRT). After drug release, their dimensions are minimized with subsequent evacuation from the stomach. Gastroretentivity is enhanced by the combination of substantial dimensions with high rigidity of the dosage form to withstand the peristalsis and mechanical contractility of the stomach. Positive results were obtained in preclinical and clinical studies evaluating GRT of expandable GRDFs. Narrow absorption window drugs compounded in such systems have improved in vivo absorption properties. These findings are an important step towards the implementation of expandable GRDFs in the clinical setting. The current review deals with expandable GRDFs reported in articles and patents, and describes the physiological basis of their design. Using the dog as a preclinical screening model prior to human studies, relevant imaging techniques and pharmacokinetic-pharmacodynamic aspects of such delivery systems are also discussed.

Animals↗
PubMed2003

Novel levodopa gastroretentive dosage form: in-vivo evaluation in dogs.

Due to its narrow absorption window, levodopa has to be administered continuously to the upper parts of the intestine in order to maintain sustained therapeutic levels. This may be achieved by a controlled release (CR) gastroretentive dosage form (GRDF). The aim of this work was to develop a novel GRDF, based on unfolding polymeric membranes, that combines extended dimensions with high rigidity, and to examine the pharmacokinetics of levodopa compounded in the GRDF. Levodopa CR-GRDFs were administered to beagle dogs pretreated with carbidopa. The CR-GRDF location in the gastrointestinal tract was determined by X-ray, and serial blood samples were collected and assayed for levodopa. Optimization of the pharmacokinetic profile of levodopa from the CR-GRDFs was carried out based on the in-vitro in-vivo correlation following modifications of the release rates (adjusted by various membrane thicknesses) and drug loads. The successful CR-GRDF maintained therapeutic levodopa concentrations (>500 ng ml(-1)) over 9 h. In comparison to non-gastroretentive CR-particles and oral solution, mean absorption time was significantly extended. These outcomes demonstrate that the CR-GRDF may be used to improve levodopa therapy and can be applied to extend the absorption of other narrow absorption window drugs that require continuous input.

Administration, Oral↗
PubMed2003

Combined uvulopalatopharyngoplasty and radiofrequency tongue base reduction for treatment of obstructive sleep apnea/hypopnea syndrome.

OBJECTIVE: In this study, we compare the objective results of uvulopalatopharyngoplasty (UPPP) combined with tongue base radiofrequency reduction (TBRF) with standard UPPP treatment of obstructive sleep apnea/hypopnea syndrome (OSAHS). STUDY DESIGN: We conducted a retrospective study of 277 patients who had stage I, II, or III OSAHS based on the Friedman staging system previously presented. METHODS: One hundred thirty-four patients who had treatment with UPPP only were used as a control group. This included 31 patients with stage I, 29 patients with stage II, and 74 patients with stage III OSAHS. An additional 143 patients with Stage II (n = 52) and III (n = 91) OSAHS were treated with combined UPPP and TBRF, initially and followed by additional TBRF treatments (up to 9000 J) as necessary. Subjective results were collected based on questionnaires and the Epworth Sleepiness Scale score for the experimental group, but these subjective measures were not available for the control group. Objective results were compared based on the polysomnographic findings before and after surgery. RESULTS: Subjectively, the study group did extremely well. Based on objective measures of successful treatment, UPPP plus TBRF resulted in a significantly higher percentage of patients who were "cured" of OSAHS compared with the control group. CONCLUSIONS: Stage I patients were usually successfully treated with UPPP only. However, patients allocated to stage II or III will benefit from the addition of TBRF to standard UPPP. Many UPPP-plus-TBRF patients in this study aborted further recommended TBRF treatments after subjective improvement and therefore objective results for this group, although improved in comparison to stage II and III patients treated with UPPP only, may not represent maximal potential improvement.

Adult↗
PubMed2003

Novel gastroretentive dosage forms: evaluation of gastroretentivity and its effect on levodopa absorption in humans.

PURPOSE: To design novel expandable gastroretentive dosage form (GRDFs) and evaluate their gastroretentive properties. Then, to assess the pharmacokinetics of levodopa compounded in such a GRDF in healthy volunteers. METHODS: Thin (<0.07 cm), large-dimensioned (> or = 5 x 2.1 cm), multi layer dosage forms (DFs) with different rigid polymeric matrices an mechanical properties were folded into gelatin capsules and wer administered to healthy volunteers with a light breakfast. GRDF unfolding and physical integrity were evaluated in vitro and in vivo (by gastroscopy and radiology). The pharmacokinetics of levodopa GRDF were compared to Sinemet CR in a crossover design. RESULTS: The combination of rigidity and large dimension of the GRDFs was a decisive parameter to ensure prolonged gastroretentivity (> or = 5 h). Large-dimension DFs lacking rigidity had similar gastroretentivity as a nondisintegrating tablet (10 mm). The GRDF rapidly unfolded and maintained their mechanical integrity. The absorption phase of levodopa was significantly prolonged following GRDF administration in comparison to Sinemet CR. CONCLUSIONS: The combination of size and rigidity of the novel GRDF enables a significant extension of the absorption phase of a narrow absorption window drug such as levodopa. This approach is an important step toward the implementation of such GRDFs in the clinical setting.

Administration, Oral↗
PubMed2003

Effect of sustained-release chlorhexidine varnish on Streptococcus mutans and Actinomyces viscosus in orthodontic patients.

This study evaluated the effect of sustained-release chlorhexidine varnish on orthodontic patients. Ten children, ages 10 to 16 years, participated. Bacterial levels of Streptococcus mutans and Actinomyces viscosus and total counts were evaluated in sputum samples. These counts were evaluated at 4 stages: before orthodontic treatment, at least 2 weeks after bonding of the brackets, 1 week after application of chlorhexidine varnish, and 3 weeks after application of chlorhexidine varnish. Increases in bacterial levels of S mutans and in the total bacterial count were detected after the brackets were bonded. One week after the sustained-release chlorhexidine varnish was applied, a significant decrease of total bacterial levels and S mutans was observed. This decrease persisted for 3 weeks after the first application. No significant change in A viscosus levels occurred during that period. The results provide additional evidence that sustained-release chlorhexidine varnish decreases S mutans levels in orthodontic patients with fixed appliances and therefore might be useful in preventing caries lesions.

Actinomyces viscosus↗
PubMed2003

Radiofrequency tonsil reduction: safety, morbidity, and efficacy.

OBJECTIVES: To evaluate the safety, morbidity, and efficacy of radiofrequency tissue volume reduction of tonsils using two different surgical techniques and to compare these two techniques with each other and with classic tonsillectomy. STUDY DESIGN: A nonrandomized retrospective review of tonsil reductions was made between 2000 and 2002 using in vivo studies associated with tonsil reduction and tonsillectomy performed either in the hospital operating room or in the outpatient treatment area. METHODS: We studied 150 patients and divided them into three main groups based on surgical technique. Group A consisted of 50 consecutive patients who underwent tonsil "ablation," Group B contained another 50 consecutive individuals who received tonsil "coblation," and Group C consisted of 50 patients who underwent classic tonsillectomy (cold dissection). Each group consisted of two subcategories of children (age range, 1-12 y) and adults (age range, 12-60 y) with chronic tonsillar hypertrophy. Most of the pediatric patients underwent adenoidectomy during the same surgical procedure. Indications for tonsillectomy were those listed by the American Academy of Otolaryngology-Head and Neck Surgery. A retrospective chart review was used to assess procedures, safety, morbidity, and efficacy of tonsil reduction and tonsillectomy. Four specific end points of morbidity were investigated: pain, return to normal diet, return to normal activity, and use of pain medication. Efficacy of tonsillectomy was determined by the clinical observation of the remaining tonsillar tissue and compared with pretreatment photographs of the tonsils. RESULTS: There were no complications in any of the groups. Efficacy was assessed based on the mean tonsil reduction and was found to be 100% for tonsillectomy, 86% for the tonsil coblation technique, but only 53.6% for the ablation technique. Morbidity was minimal in groups A and B and significantly greater in Group C. The number of pain days, narcotic-use days, and days before return to normal diet and activity were greatly reduced in groups A and B when compared with classic tonsillectomy (group C). Pain levels on day 1 were less than 3 (on a scale of 1-10) in groups A and B. The number of pain days and narcotic-use days was less than 4 days in groups A and B. Similarly, most patients returned to solid diet and normal activity by day 4. Pain levels, number of narcotic-use days, and number of days to return to normal diet and activity were significantly higher for classic tonsillectomy. CONCLUSIONS: Tonsil coblation has distinct advantages when compared with tonsil ablation and standard tonsillectomy. Tonsil coblation resulted in greater than 86% elimination of tonsillar tissue in both children and adults. In most patients, pain levels were minimal and limited to the first 48 hours after surgery. Return to normal diet and activity was much earlier in the coblation group versus classic tonsillectomy.

Adolescent↗
PubMed2003

Quantification of guided regeneration of weight-bearing bones.

An accurate histological evaluation system was established to improve and quantify the compatibility of membranes to provide bone regeneration in a large mid-diaphyseal bone defect, complementing radiographic evaluation. New bone formation obtained in critical segmental defects covered with tubular ethyl cellulose membranes was examined. Computerized radiography showed gradual new bone formation, which slows after 6 weeks. In a parallel histomorphological assessment, a characteristic process of new bone formation occurs inside the confined space and surrounding tissues. Histological findings are summarized according to the new scoring system, which clarifies the mechanism and provides complementary quantification of guided bone regeneration.

Animals↗
PubMed2003

Furosemide pharmacokinetics and pharmacodynamics following gastroretentive dosage form administration to healthy volunteers.

The objective of this study was to evaluate the pharmacokinetic and pharmacodynamic properties of furosemide following gastroretentive dosage from (GRDF) administration. A furosemide (60 mg) GRDF, releasing the drug during 6 hours in vitro, or an immediate-release tablet was administered to healthy male volunteers (N = 14) in a crossover design. Food and liquid intake were standardized; urine was collected, weighed, and assayed for furosemide and sodium concentrations. Pharmacokinetics of furosemide following the GRDF administration, as compared to the tablet, showed lower Cmax and indicated a prolonged absorption phase leading to longer mean residence time in the stomach. The sustained input of the drug significantly improved diuretic and natriuretic efficiencies during the first 5 hours and thereby increased the total effects measured over 24 hours. The unfolding controlled-release GRDF of furosemide improved the pharmacodynamic actions due to the sustained absorption in the stomach and jejunum, which delayed the body's counteractivity to the drug effect.

Adult↗
PubMed2002

Superior laryngeal nerve identification and preservation in thyroidectomy.

BACKGROUND: Injury to the external branch of the superior laryngeal nerve (EBSLN) can result in detrimental voice changes, the severity of which varies according to the voice demands of the patient. Variations in its anatomic patterns and in the rates of identification reported in the literature have discouraged thyroid surgeons from routine exploration and identification of this nerve. Inconsistent with the surgical principle of preservation of critical structures through identification, modern-day thyroidectomy surgeons still avoid the EBSLN rather than identifying and preserving it. OBJECTIVES: To describe the anatomic variations of the EBSLN, particularly at the junction of the inferior constrictor and cricothyroid muscles; to propose a systematic approach to identification and preservation of this nerve; and to define the identification rate of this nerve during thyroidectomy. MATERIALS AND METHODS: A retrospective review of thyroid lobectomies and total thyroidectomies performed between 1978 and 1997 was carried out. A total of 884 patients were included, with 1057 EBSLNs explored. Intraoperative findings of identification of the EBSLN were recorded and compared on an annual basis for both benign and malignant disease. Overall results were also compared with those found in previous series identified through a 50-year literature review. RESULTS: The 3 anatomic variations of the distal aspect of the EBSLN as it enters the cricothyroid were encountered and are described. The total identification rate over the 20-year period was 900 (85.1%) of 1057 nerves. Operations performed for benign disease were associated with higher identification rates (599 [86.1%] of 696) as opposed to those performed for malignant disease (301 [83.4%] of 361). Operations performed in recent years have a higher identification rate (over 90%). CONCLUSIONS: Understanding the 3 anatomic variations of the distal portion of the EBSLN and its relation to the inferior constrictor muscle allows for high rates of identification of this nerve. The EBSLN should be explored during thyroid surgery and identification is possible in most cases. Preservation of the EBSLN maintains optimal function of the larynx.

Humans↗
PubMed2002

Novel gastroretentive dosage forms: evaluation of gastroretentivity and its effect on riboflavin absorption in dogs.

PURPOSE: [corrected] The purpose of this study was to design novel gastroretentive dosage forms (GRDFs) based on unfolding multilayer polymeric films, to investigate the mechanism of their gastroretentivity in dogs, and to assess the effect of compounding a narrow absorption window drug in a GRDF on the drug's absorption properties. METHODS: Dosage forms (DFs) with different dimensions and mechanical properties were administered to beagle dogs with acidic buffer (pH = 1.5), whose gastric retention time (GRT) was then determined by X-ray pictures. Concurrent administration of radiopaque markers was used to assess the effect of the GRDF and/or acidic buffer on GRT. The absorption of riboflavin from a prototype GRDF was compared with a nongastroretentive controlled-release DF and to an oral solution of the drug. RESULTS: Large DFs (> or = 2.5 x 2.5 cm) containing rigid frame had prolonged GRT (>4 h). Administration of 400 mL of acidic buffer (or water) prolonged GRT whereas the GRDF did not cause additional prolongation. The extended absorption phase (>48 h) of riboflavin administered in a GRDF led to 4-fold increased bioavailability. CONCLUSION: The combination of large dimensions with rigidity produce gastroretentivity that can be used to improve absorption properties of a model of narrow absorption window drugs in the gastrointestinal tract.

Animals↗
PubMed2002

Melanoma growth stimulatory activity in primary malignant melanoma: prognostic significance.

Malignant melanoma (MM) cells do not require all exogenous growth factors of normal melanocytes. It is hypothesized that they make their own growth factors including melanoma growth stimulatory activity (MGSA). Cultured melanoma cells respond to MGSA with increased growth and angiogenesis suggesting a role for MGSA in MM proliferation, differentiation, and progression. We assessed the prognostic significance of MGSA expression in 37 primary MM immunostained for MGSA. Immunostains were graded for intensity (0-3+), percentage of cells immunostained, and location of immunostain (intraepidermal, junctional, or dermal). In addition, 31 melanocytic and 23 dysplastic nevi were similarly studied for MGSA expression. All MM showed the presence of immunostain, 6 (16%) 1+, 12 (32%) 2+, and 19 (51%) 3+. Six (16%) had immunostain in < or = 50% tumor cells, 31 (84%) in >50%. A significant number of MM showed >50% tumor cells staining at the dermal-epidermal junction compared with intraepidermal staining (P <.0001). Intensity and amount of immunostain did not correlate with Clark's or Breslow's level. During a mean follow-up of 60 months (range: 5-101) on 27 patients, there were 4 local recurrences, 6 distant metastases, and 10 deaths. MGSA expression was not of prognostic significance with regard to survival (overall, disease free), or local recurrence or distant metastasis in primary MM. MGSA expression was similar in benign melanocytic and dysplastic nevi. Strong diffuse expression was noted in the junctional component of all junctional and most compound nevi. The dermal component consistently expressed less or no (in 45% of intradermal nevi) MGSA. MGSA expression does not correlate with prognosis in MM. Increased expression of MGSA at the dermal-epidermal junction in nevi and MM may indicate a role for MGSA in early local growth, before development of atypia.

Adolescent↗
PubMed2002

Clinical staging for sleep-disordered breathing.

OBJECTIVE: The purpose of this study was to identify prognostic indicators that would lead to stratification of patients likely to have successful surgery for sleep-disordered breathing (SDB) versus those destined to fail. STUDY DESIGN: We retrospectively reviewed 134 patients to correlate palate position and tonsil size to the success of the UPPP as based on postoperative polysomnography results. Similar to our previously published data on the Friedman Score as a predictor of the presence and severity of SDB, the palate position was determined on physical examination of the oral cavity and was graded for each patient. This grade combined with tonsil size was used to stage the patients. Stage I was defined as having palate position 1 or 2 combined with tonsil size 3 or 4. Stage II was defined as having palate position 3 or 4 and tonsil size 3 or 4. Stage III patients had palate position 3 or 4 and tonsil size 0, 1, or 2. Any patient with body mass index of greater than 40 was placed in the stage III group. The results of uvulopalatopharyngoplasty (UPPP) were then graded as success or failure and success rates were compared by stage. SETTING: Academically affiliated tertiary care referral center. RESULTS: Stage I patients who underwent UPPP had a success rate of 80.6%, stage II patients had a success rate of 37.9%, and stage III patients had a success rate of 8.1%. CONCLUSION: A clinical staging system for SDB based on palate position, tonsil size, and body mass index is presented. It appears to be a valuable predictor of the success of UPPP. Additional studies and wider use of the staging system will ultimately define its role in the treatment of SDB.

Adult↗
PubMed2002

Enhancement of the perception of systemic pain in women with vulvar vestibulitis.

OBJECTIVE: The aim of this study was to determine whether the characteristics of systemic pain perception and anxiety differ between women with vulvar vestibulitis and healthy women. DESIGN: Case control study. SETTING: Tertiary care hospital. POPULATION: Forty-four women with vulvar vestibulitis and 41 healthy women participated in the study. METHODS: First, the women's state and trait anxiety was evaluated. Thereafer, heat pain stimuli were applied to the women's forearm and the pain and unpleasantness thresholds, as well as magnitude estimation of perceived intensity and unpleasantness of suprathreshold stimuli, were assessed. Finally, blood pressure was measured before, during and after a heat stimulus of 46 degrees C. MAIN OUTCOME MEASURES: Pain threshold and suprathreshold, and anxiety levels of women with vulvar vestibulitis. RESULTS: Women with vulvar vestibulitis had a higher anxiety state (40.0 [12.8] vs 34.1 [10.8], P = 0.044), a higher anxiety trait (42.1 [10.2] vs 35.6 [7.5], P = 0.005), a lower pain threshold (42.2 degrees C [2.5] vs 43.6 degrees C [1.9], P = 0.006), a lower unpleasantness threshold (40.2 degrees C [2.9] vs 41.7 degrees C [2.3], P = 0.023), a higher magnitude estimation of suprathreshold pain at 47 degrees C (88.3 [14.9] vs 70.8 [14.9], P = 0.0001) and at 48 degrees C (96.1 [7.3] vs 84.6 [14.8], P < 0.0001), a higher scoring of tonic pain perception (65.2 [17.3] vs 53.0 [18.6], P = 0.006) and a higher increase in systolic blood pressure during tonic pain stimuli (4.6 [9.6] vs -2.1 [8.7] mmHg, P = 0.005). CONCLUSION: Women with vulvar vestibulitis have an enhanced systemic pain perception and are more anxious.

Adult↗
PubMed2002

Pharmacokinetic-pharmacodynamic analysis of the glucose-lowering effect of metformin in diabetic rats reveals first-pass pharmacodynamic effect.

Metformin, a commonly used antidiabetic drug, exerts its glucose-lowering effect due to metabolic activities at several sites of action (biophases), including liver, intestine, muscle cells, and adipocytes. The relative contribution of the individual biophases to the overall glucose-lowering effect is not known. Thus, the aims of this investigation were to study the influence of mode of drug administration on the kinetics of glucose-lowering action of metformin in diabetic rats and identify the contribution of different sites of action to the overall response. Streptozotocin diabetic rats received metformin in crossover fashion via intraduodenal, intravenous, and intraportal routes as bolus dose or infusion regimens designed to yield similar pharmacokinetic profiles. Metformin plasma concentrations and blood glucose levels were measured following each mode of administration. Despite the similarity in the concentration-time profiles obtained for different routes of metformin administration, intraduodenal administration produced larger response than intraportal metformin infusion, and lowest response was observed following intravenous administration. This finding indicates that a significant "first-pass" pharmacodynamic effect, which occurs in the presystemic sites of action (liver and the gastrointestinal wall), contributes to the overall glucose-lowering response of metformin. We applied a combined pharmacokinetic-pharmacodynamic modeling approach to study the nature of the first-pass pharmacodynamic effect. The observed data were successfully described by a novel integrated indirect response pharmacokinetic-pharmacodynamic model that revealed a correlation between the temporal metformin concentrations that transit the portal vein and through the gut wall rather than with drug concentrations that accumulated in the liver and the intestinal wall.

Animals↗
PubMedDate not supplied

Validity of a self-report depression symptom scale for identifying remission in depressed outpatients.

In treatment studies of depression, remission is usually defined by scoring less than a threshold value on an interview-based measure of depression severity such as the Hamilton Rating Scale for Depression (HRSD). Although it has been recommended that measures such as the HRSD be used by clinicians in clinical practice to evaluate remission status, the time demands of clinical practice limit the feasibility of this suggestion. Self-report questionnaires are a cost-effective option to thoroughly, systematically, reliably, and validly evaluate clinical status because they are inexpensive in terms of professional time needed for administration and do not require special training for administration. In a previous report from the Rhode Island Methods to Improve Diagnostic Assessment and Services project, we derived a cutoff on a self-report depression questionnaire corresponding to the widely used definition of remission on the HRSD (ie, < or = 7). In the present report, we examined the validity of this questionnaire as an indicator of remission among patients who responded to antidepressant treatment. Specifically, we examined psychosocial functioning in treatment responders who were and were not in remission according to the self-report symptom scale. In a sample of 371 depressed outpatients who were judged by their treating psychiatrists as having responded to treatment, 250 scored in the remission range on the symptom scale. Compared with treatment responders whose depression was not in remission, the patients who were in remission reported significantly less psychosocial impairment and significantly better quality of life and were significantly more likely to assert that they are in remission from their depression. These findings support the validity of a self-report depression questionnaire as an index of remission status among treatment responders.

Adult↗