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Biomedical subjects

I Friedman

Publications and source records attributed to I Friedman.

At least 19 recordsLinked to original sources

The role of superoxide dismutation in malaria parasites.

Oxidant stress is associated with the generation of reactive oxygen species that are responsible for the damage of a variety of cellular components. The prevention of such biological damage can be achieved by dismutation of superoxide to H2O2 which in turn is removed by catalase and GSH peroxidase. However, redox-active iron released during the development of plasmodia in the erythrocyte can mediate the conversion of H2O2 to hydroxyl radical which is more reactive. The roles of SOD and the nitroxide SOD mimic 4-OH,2,2,6,6,tetramethyl piperidine-N-oxyl (Tempol) were examined in P. falciparum grown in vitro. Both compounds did not prevent the interference with growth inflicted by various inducers of oxidant stress. Moreover, Tempol inhibited parasite growth, in agreement with previous experiments depicting accelerated mortality in SOD overexpressing mouse model of malaria. Probably, effective defense against ROS requires balanced increments in antioxidant enzymes and is not necessarily improved by an increase in the activity of one enzyme.

Adaptation, Physiological

Transgenic mice with elevated level of CuZnSOD are highly susceptible to malaria infection.

Copper/zinc superoxide dismutase (CuZnSOD) catalyses the conversion of O2.- into H2O2. Constitutive overexpression of CuZnSOD in cells and animals creates an indigenous oxidative stress that predisposes them to added insults. In this study, we used transgenic CuZnSOD (Tg-CuZnSOD) mice with elevated levels of CuZnSOD to determine whether overexpression of CuZnSOD affected the susceptibility of these mice to plasmodium infection. Acute malaria is associated with oxidative stress, mediated by redox-active iron released from the infected RBC. Two independently derived Tg-CuZnSOD lines showed higher sensitivity than control mice to infection by Plasmodium berghei (P. berghei), reflected by an earlier onset and increased rate of mortality. Nevertheless, while Tg-CuZnSOD mice were more vulnerable than control mice, the levels of parasitemia were comparable in both strains. Moreover, treatment of infected red blood cells (RBC) with oxidative stress inducers, such as ascorbate or paraquat, reduced the viability of parasites equally in both transgenic and control RBC. This further confirms that increased CuZnSOD does not support plasmodia development. The data are consistent with the possibility that the combination of increased redox-active iron and elevated H2O2 in the plasmodium-infected Tg-CuZnSOD mice, led to an enhanced Fenton's reaction-mediated HO. production, and the resulting oxidative injury renders the transgenic mice more vulnerable to parasite infection.

Animals

Acute colonic diverticulitis in the young.

BACKGROUND: Colonic diverticulitis in the young has been considered to have a virulent course, high morbidity, and high operative rate. As a result, elective resection of the involved colonic segment after the first clinical episode has been the usual practice. PURPOSE: This study presents our experience with acute diverticulitis in the young. METHODS: In the last nine years, 63 patients younger than 45 years were treated for acute diverticulitis at our institution. A retrospective review was performed to determine the clinical course and outcome of these patients. RESULTS: Clinical presentations, radiographic tests, operative findings, and pathology results revealed that 57 patients had a pericolonic contained disease (Hinchey State I). Two patients had a large pelvic abscess (Hinchey Stage II), and four patients had a diffuse peritonitis (Hinchey Stage III). Forty-one patients (65 percent) were successfully treated medically with antibiotics and bowel rest. Of 22 patients (35 percent) who underwent emergent operations, 12 patients' diseases had been erroneously diagnosed preoperatively (9 "appendicitis"). CONCLUSION: Diverticulitis at a young age does not have a specific aggressive nature. Although, it is associated with a high rate of emergency operations, many of these are performed for a mistaken diagnosis. The recommendation for routine elective resection following the first episode of diverticulitis should be reassessed.

Acute Disease

Treatment of chronic pilonidal disease.

PURPOSE: Pilonidal disease (PD) is a common chronic intermittent disorder of the sacrococcygeal region. Despite surgical therapy dating back more than one century, management remains controversial and recent reports have advocated different surgical approaches. METHODS: A retrospective review was conducted of 129 patients who were treated for chronic PD in our institution during a five-year period, 1990 to 1994. RESULTS: Excision with primary closure was performed in 56 patients; 47 underwent open excision without closure, and 26 had marsupialization procedure. All were performed electively, with only minor complications. Complete healing was fastest in the primary closure group, despite a 14 percent postoperative wound infection rate. Recurrence rates of 11, 13, and 4 percent were found for primary closure, wide resection, and marsupialization procedures, respectively. There was no correlation among recurrence rate, postoperative infection, or prior surgery. CONCLUSION: Considering healing time, morbidity, and recurrence rate, we conclude that surgical treatment should be directed at either excision and primary closure or marsupialization. Wide excision with secondary healing should be performed only for grossly infected and complex cysts.

Adolescent

Colorectal surgery in octogenarians.

BACKGROUND: Elderly patients are often viewed as high-risk surgical candidates. Recent reports, however, have recommended applying the standard surgical approach to this group. Many of these series report mortality rates that are substantially higher than those in the younger population. Therefore, the applicability of these procedures for the elderly may be questionable. STUDY DESIGN: We retrospectively studied 140 patients older than 80 years who underwent colorectal surgery at our institution between January 1990 and January 1995. Of these, 123 underwent colon or rectal resections and 17 had diverting colostomy only. Ninety-seven (79 percent) of the colorectal resections were for carcinoma. In this study, perioperative care, operative results, and survival are analyzed. RESULTS: Elective and emergent colorectal resections totaled 80.5 and 19.5 percent, respectively. The mortality rate for elective resections was 3 percent and for emergency resections it was 21 percent. Postoperative morbidity was 27 percent and the average hospital stay was 13.1 days. Diverting colostomy was associated with a 24 percent mortality rate. The survival rate after colorectal resections for one, two, and five years was 85, 72, and 40 percent, respectively. CONCLUSIONS: The results support the view that elective colorectal resection in the elderly population is worthwhile and should be performed for the same indications as in younger patients. Although emergent operations were associated with a poor outcome, the majority of the patients survived and left the hospital.

Aged

Subgingival irrigation with amine fluoride-stannous fluoride gel in treated periodontal pockets.

PURPOSE: To evaluate the long-term effect of subgingival irrigations with amine fluoride mixed with stannous fluoride on the repopulation of bacteria in deep periodontal pockets (> 5 mm) following the active phase of non-surgical mechanical treatment. MATERIALS AND METHODS: A split-mouth design was utilized in eight periodontal patients and the effect of the treatment was evaluated by microbiological culturing and clinical parameters. RESULTS: Slight reduction in total anaerobe counts were detected in both treated and control sides, up to the first 5 weeks, followed by an increase in the counts reaching a plateau after 30 weeks. In contrast, black-pigmented bacteroides species (BPB) were significantly suppressed in the treated sides as compared to the control sides over the whole study period. The difference between the clinical parameters and between the tested and control sides, although in some points were found to be statistically significant, seem to have no clinical significance. The use of amine fluoride-stannous fluoride gel for irrigations of deep periodontal pockets as an adjunctive to conventional treatment, can prevent the repopulation of the pockets by BPB, which are considered to be a major group of periodontal pathogens.

Amines

Prolonged conductive hearing loss in rat pups causes shorter brainstem transmission time.

A carefully controlled study was conducted in rats to determine whether a reversible conductive hearing loss during the neonatal period could induce changes in central conduction and thereby perhaps contribute to an understanding of learning problems seen in children following conductive hearing loss in infancy. Ear plugs were inserted from post-natal day 9 in rat pups and auditory nerve brainstem evoked responses were recorded in the presence of ear plugs and following their removal on post-natal day 23. The I-IV interpeak latency (brainstem transmission time) was significantly shorter in the experimental rats several days after plug removal (day 28) compared to untreated control rats. This difference was not related to residual conductive loss, nor to different body weights and was present even in response to equal sensation level stimuli, and was not present in adult rats with similarly induced conductive hearing losses. It seems therefore that conductive hearing loss in the young animal (critical period?) can induce changes in central auditory conduction and may be related to the findings of smaller brainstem auditory neurons in sound deprived animals. These results have implications for neonatal hearing loss in humans.

Animals

Initial experience with laparoscopic cholecystectomy at the Beth Israel Medical Center.

Laparoscopic cholecystectomy has changed the treatment of symptomatic gallstones. We present an initial experience with this technique. From March 1990 to March 1991, there were 250 patients who were studied. There were 182 females and 68 males, with most classified as American Society of Anesthesiology Index Class I or II. All procedures were done using electrocautery. There was a definite learning curve for the procedure as evidenced by the duration of the operation. The mean time to perform the procedure was 112 minutes for the first 50 patients and 79 minutes for the last 50 patients. We converted 12 percent of the procedures to an open cholecystectomy for a variety of reasons, the most common being inflammation and adhesions in the triangle of Calot. However, we only had a 4 percent conversion rate in the last 50 patients. There were nine serious complications, with no deaths. The most frequent was a bile leak from the cystic duct stump. Other complications included a pneumothorax, requiring chest tube drainage and an unobserved carcinoma of the stomach. There were no injuries to the common bile duct. The results of our current experience confirm the safety and efficacy of laparoscopic cholecystectomy for the treatment of symptomatic gallstones. The use of electrocautery is safe during laparoscopy and the need for a laser is optional. Laparoscopic cholecystectomy will continue to evolve as more experience is gained and new instruments are introduced.

Adult

Auditory brainstem response (ABR) latency shifts in animal models of various types of conductive and sensori-neural hearing losses.

Clinical ABR studies in patients with peripheral hearing loss have led to conflicting results, some reporting increases in brainstem transmission time (BTT), some decreases, and others no change. In order to study this in a carefully controlled fashion, various types of peripheral hearing losses were induced in experimental animals: conductive hearing loss by occluding auditory meatus (rats) (CHL), noise induced temporary sensori-neural hearing loss (rats) (NI-SNHL), stimulus intensity attenuation (rats), (Atten.), and controlled hypoxemia induced temporary sensori-neural hearing loss (cats) (HI-SNHL). ABR latencies and thresholds were determined in each animal before (control) and during the induced hearing loss (experimental) states. The data in each group in each state were analyzed by calculating group average values for latency of waves 1 and 4, their interpeak latency (BTT), paired t-tests for changes between the control and experimental states and linear regression analysis of latency changes on threshold shift. In each group, there were small decreases in BTT in the experimental state (not significant in the CHL group only). This was caused by the prolongation of latency of wave 1 to a greater extent than that of wave 4. These changes were smaller than the standard deviation of the BTT in the control state. Therefore, in attempting to apply these results to the human clinical situation, these small decreases in BTT would not be considered abnormal. Possible mechanisms of these BTT changes are considered.

Animals

Interactions of cardiac glycosides with cultured cardiac cells. II. Biochemical and electron microscopic studies on the effects of ouabain on muscle and non-muscle cells.

Electron microscopic and biochemical studies revealed a salient difference in the response to toxic doses of ouabain by cultured cardiac muscle and non-muscle cells from neonatal rats. Progressive cellular injury in myocytes incubated with 1 . 10(-4)--1 . 10(-3) M ouabain ultimately leads to swelling and necrosis. The morphological damage in myocytes was accompanied by a drastic decrease in 14CO2 formation from 14C-labeled stearate or acetate but not glucose. Neither morphological nor biochemical impairments were observed in non-muscle cells. The interaction between ouabain and the cultured cells, using therapeutic doses of ouabain (i.e., less than 1 . 10(-7) M), was characterized. Two binding sites were described in both classes of cells, one site is a saturable K+-sensitive site whereas the other is non-saturable and K+-insensitive. The complexes formed between the sarcolemma receptor(s) and ouabain, at low concentrations of the drug (e.g., 7.52 . 10(-9) M), had Kd values of 8.9 . 10(-8) and 2.3 . 10(-8) M for muscle and non-muscle cells, respectively. The formation and dissociation of the complexes were affected by temperature and potassium ions.

Animals

Retrorectal abscess with neurologic involvement of the lower extremities: report of a case.

A case of retrorectal abscess with neurologic involvement of both lower extremities is presented. The authors believe that an adequate description of this entity is necessary for the clinician, insofar as rectal suppurations rarely cause neurologic symptoms. The clinician must be alert for the possibility of the presence of various presacral tumors, whose treatment and prognosis present much graver problems.

Abscess