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Biomedical subjects

J Raphael

Publications and source records attributed to J Raphael.

11 recordsLinked to original sources

Spinal cord stimulation for relief of abdominal pain in two patients with familial Mediterranean fever.

Familial Mediterranean fever is a hereditary disease characterized by recurrent attacks of fever and serosal inflammation that commonly presents as severe abdominal pain. Though colchicine remains the mainstay of treatment, a significant proportion of patients are partially responsive, unresponsive or intolerant to it. We present two such cases where spinal cord stimulation (SCS) was used to manage the paroxysmal abdominal pain associated with this disease. Abdominal visceral pain pathways and the application of SCS techniques in its management are discussed.

Abdominal Pain↗

Isoflurane does not mimic ischaemic preconditioning in decreasing hydroxyl radical production in the rabbit.

BACKGROUND: Reactive oxygen species are an important mediator in isoflurane-induced myocardial preconditioning. However, hydroxyl radicals are also released during reperfusion after regional ischaemia. The purpose of the present study was to test whether ischaemic preconditioning and isoflurane would influence the production of hydroxyl radicals during reperfusion. METHODS: After i.v. administration of salicylate 100 mg kg(-1) and a 30 min stabilization period, New Zealand White rabbits were subjected to 40 min of regional myocardial ischaemia and 2 h of reperfusion. Ischaemic preconditioning was elicited by 5 min ischaemia followed by 10 min reperfusion (before the 40 min ischaemia). In another group, isoflurane (2.1%) was administered for 30 min, followed by 15 min washout, before the long ischaemia. Area at risk and infarct size were assessed by blue dye injection and tetrazolium chloride staining. We quantified the level of OH-mediated conversion of salicylate to its dihydrobenzoate derivatives (2,3- and 2,5-DHBAs). Normalized values of the DHBAs (ng DHBA per mg salicylate) were calculated. RESULTS: Mean (se) infarct size was 57 (6)% of the risk area in the untreated controls. This was significantly smaller in the ischaemic preconditioning and isoflurane groups: 22 (5) and 23 (6)% respectively. At 10 min of reperfusion, ischaemic preconditioning limited the mean increase in 2,3-DHBA to 24% from baseline, compared with 81% in control and 74% in the isoflurane group. Normalized 2,5-DHBA was maximally increased by 75% in the untreated group, 4 min after reperfusion. Ischaemic preconditioning significantly inhibited this increase (24% increase from baseline, P<0.01). However, the increase observed in the isoflurane group was not different from control (71%). CONCLUSIONS: As already known, ischaemic preconditioning and isoflurane markedly reduced infarct size. However, only ischaemic preconditioning decreased postischaemic production of hydroxyl radicals. These different effects suggest different protective mechanisms at the cellular level.

Anesthetics, Inhalation↗

Isoflurane-induced myocardial preconditioning is dependent on phosphatidylinositol-3-kinase/Akt signalling.

BACKGROUND: Isoflurane and other volatile anaesthetics have a cardioprotective effect and limit myocardial infarct size to the same extent as ischaemic preconditioning. Phosphatidylinositol-3-kinase (PI3K) was found to play a key role in myocardial protection by ischaemic preconditioning. The aim of the present investigation was to evaluate whether isoflurane-induced myocardial preconditioning is dependent on PI3K signalling. METHODS: Using a model of regional myocardial ischaemia and reperfusion, New Zealand White rabbits were subjected to 40 min of regional myocardial ischaemia followed by 120 min of reperfusion. The rabbits were randomly assigned to one of the following six experimental groups: sham-operated controls (n=5); ischaemia and reperfusion controls (n=8); isoflurane preconditioning (n=8); a PI3K inhibitor, wortmannin (0.6 mg kg(-1) i.v.) + isoflurane (n=8); and wortmannin+ischaemia and reperfusion (n=8). An additional control group of sham operation+ wortmannin (n=5) was also included. Myocardial injury was assessed by measuring the serum concentration of the MB fraction of creatine kinase (CK-MB) and infarct size was assessed by 2,3,5-triphenyl tetrazolium chloride staining. Phosphorylation of Akt, a downstream target of PI3K, was assessed by western blotting. RESULTS: Isoflurane preconditioning was seen as reduced infarct size compared with control animals: 24 (4) and 41 (5)% respectively (P<0.05). Wortmannin inhibited this cardioprotective effect with myocardial infarct size at 44 (3)% (not significant). Akt phosphorylation was increased after isoflurane preconditioning, but administration of wortmannin blocked this effect. CONCLUSIONS: Our data demonstrate that isoflurane protects the heart against ischaemia and decreases myocardial infarction by activation of PI3K.

Androstadienes↗

Halofuginone--an inhibitor of collagen type I synthesis--prevents postoperative formation of abdominal adhesions.

OBJECTIVE: To evaluate the effects of halofuginone, a specific inhibitor of collagen type I synthesis, on the postoperative formation of abdominal adhesions in rats. SUMMARY BACKGROUND DATA: Postoperative adhesions remain the leading cause of small bowel obstruction in the Western world. Surgical trauma causes the release of a serosanguineous exudate that forms a fibrinous bridge between two organs. This becomes ingrown with fibroblasts, and subsequent collagen deposition leads to the formation of a permanent adhesion. Most of the drugs used have been clinically ineffective, and none has been specific to a particular extracellular matrix molecule. Therefore, there are serious concerns about the toxic consequences of interfering with the biosynthesis of other collagens, other matrix proteins, or vital collagen-like molecules. METHODS: Adhesions were induced by scraping the cecum until capillary bleeding occurred. The adhesions were scored 21 days later. Halofuginone was either injected intraperitoneally (1 microg/25 g body weight) every day, starting on the day of operation, or added orally at concentrations of 5 or 10 mg/kg, starting 4 days before the operation. Collagen alpha1(I) gene expression was evaluated by in situ hybridization, total collagen was estimated by Sirius red staining, and collagen type III was detected by immunohistochemistry. RESULTS: The adhesions formed between the intestinal walls were composed of collagen and were populated with cells expressing the collagen alpha1(I) gene. Regardless of the administration procedure, halofuginone significantly reduced the number and severity of the adhesions. Halofuginone prevented the increase in collagen alpha1(I) gene expression observed in the operated rats, thus reducing collagen content to the control level. In fibroblasts derived from abdominal adhesions, halofuginone induced dose-dependent inhibition of collagen alpha1(I) gene expression and collagen synthesis. Collagen type III levels were not altered by adhesion induction or by halofuginone treatment. CONCLUSIONS: Upregulation of collagen synthesis appears to have a critical role in the pathophysiology of postoperative adhesions. Halofuginone, an inhibitor of collagen type I synthesis, could be used as an important tool in understanding the role of collagen in adhesion formation, and it may become a novel and promising antifibrotic agent for preventing postoperative adhesion formation.

Abdomen↗

Arthroscopic resection of dorsal ganglion of the wrist.

In summary, arthroscopic resection is a reasonable approach for operative treatment of the dorsal ganglion. Arthroscopy is safe and addresses the key anatomic pathology. Recurrences to date have been equal to or less than with the open technique. Arthroscopic resection minimizes the surgical scar. Arthroscopy also permits evaluation of any intra-articular pathologic condition of either midcarpal or radiocarpal joints. In our series, 42% of patients had intra-articular pathologic conditions. In this study, these findings were recorded but not treated. Symptom resolution, therefore, correlated with ganglion resection and not with intra-articular pathologic conditions. We look forward to publishing our data in full at the completion of our study.

Adult↗

Metaphyseal dissociation fractures of the proximal tibia. An analysis of treatment and complications.

A study was done of 44 metaphyseal dissociation fractures of the proximal tibia in 42 patients (27 men and 15 women, aged 22 to 77 years; mean, 42 years). Follow-up ranged from 6 months to 4 years. There were 2 study groups: a retrospective group (group 1, 22 fractures) given a variety of treatments ranging from casts to dual plates, and a prospective group (group 2, 22 fractures) treated by combining external fixation and optional minimal internal fixation. There were 12 comminuted fractures in group 1 and 20 in group 2 (P < 0.01). All fractures eventually healed, with an average healing time in group 1 of 3.8 months, and 5.3 months in group 2. There was one delayed union in group 2. Results were graded from poor to excellent, based on pain, range-of-motion, and malunion. There were 6 poor and 4 fair results in group 1, and no poor and 3 fair results in group 2. Complications included 6 deep infections, 5 in group 1 (1 requiring a free-flap procedure); and 1 pin-tract infection resulting in septic arthritis in group 2. There were 7 gastrocnemius flaps required in group 1, and 1 in group 2. The results of this study suggest that patients treated with external fixation had better results with less infection and soft-tissue complications than those treated with conventional internal fixation.

Adult↗

Characteristics of alcohol abusers among incidental primary health clinic attenders in an Israeli development town.

BACKGROUND: The belief that alcoholism is rare among Jews appears to be tenable no longer. High rates of alcohol abuse are being reported in subgroups of the population and in socially disadvantageously placed persons. The main objective of this study was to search for etiologic clues for alcohol abuse in different ethnic groups in a development town in southern Israel. METHODS: A structured questionnaire was answered by 152 randomly selected incidental attenders at a primary health care clinic. Alcohol abuse was determined using the CAGE questionnaire. RESULTS: The rate of present-time alcohol abuse was 17% and 20% among male Indian and non-Indian clinic attenders, respectively, while life-time abuse was 37% and 25%, respectively. These findings were considerably higher than the reported national rates of 2-3%. Differences were found between alcohol abusers in the various ethnic groups. Non-Indian life-time abusers were characterized by more frequent use of medical services, more reported physical and mental symptoms, more use of psychotropic drugs, and higher rates of unemployment. CONCLUSIONS: These differences suggest that the non-Indians may include symptomatic drinkers, while the Indians, we propose, may be alcohol abusers for cultural reasons. The extent of the alcohol abuse problem detected in this survey indicates that a major public health issue may exist in development town populations.

Alcoholism↗