Addition of epinephrine to intrathecal tetracaine augments depression of the bispectral index during intraoperative propofol sedation

Purpose Epinephrine added to local anesthetic agents for spinal anesthesia is frequently used to prolong the duration of anesthesia. Epinephrine stimulates the -adrenoceptor, and it is known that the 2-adrenoceptor agonists have a central inhibitory effect. We investigated the effect of intrathecal epinephrine during propofol sedation with spinal anesthesia, using a bispectral index (BIS) monitor.Methods Twenty adult patients, scheduled for spinal anesthesia, were allocated to the control group (n = 10) or epinephrine group (n = 10). Patients in the control group received 14mg of tetracaine, whereas the epinephrine group received 14mg of tetracaine and 0.2mg of epinephrine. Immediately after the pinprick test, propofol was administered at 0.5mg·kg^–1 by infusion for the initial dose, then continuously at 2mg·kg^–1·h^–1 in both groups. BIS scores were recorded before subarachnoid block, and then every 5min for 90min after subarachnoid block.Results There were significant differences in the BIS score between the two groups at 45–55min and at 60–70min after subarachnoid block.Conclusion Intrathecal epinephrine augments the sedative effect of propofol during spinal anesthesia.     

Elective neurectomy during open, “tension free” inguinal hernia repair

Chronic postoperative inguinal pain syndromes are potentially debilitating sequelae following elective inguinal hernia repair. Diagnosis and definitive treatment constitute challenging issues for both the surgeon and the patient. In this prospective trial, we evaluated the impact of elective iliohypogastric and ilioinguinal nerve resection on the incidence of pain, numbness, and sensory loss following anterior, tension-free herniorrhaphy. One hundred ninety-one patients were enrolled and were reviewed 1 month, 6 months, and 1 year postoperatively. Pain, numbness, or any loss of sensation were recorded and categorized on a mild, moderate, or severe scale. No persistent pain syndrome was encountered. Numbness was found in 9.42% of the patients at the first month and in 6.28% of the patients after 1 year. Sensation loss (1.04%) was never bothersome or incapacitating at the end of the follow-up period. Elective neurectomy is safe to perform, well tolerated by patients, and is not associated with chronic postoperative inguinal pain.     

Naloxone and flumazenil fail to antagonize the isoflurane-induced suppression of dorsal horn neurons in cats

Effects of naloxone and flumazenil on isoflurane activities were examined on dorsal horn neurons in cats. Isoflurane suppressed bradykinin-induced nociceptive responses in transected feline spinal cords. The bradykinin-induced neuronal firing rates were significantly suppressed by 60.0%, 35.3% and 32.2% at 10, 20 and 30min after isoflurane administration, respectively. The 32.3% suppression on bradykinin-induced neuronal responses at 30min after isoflurane administration was not reversed 5min after administration of naloxone (36.4% suppression). The suppressive effects of isoflurane were not reversed by naloxone (0.2mg·kg^–1, i.v.). Similarly, the benzodiazepine antagonist, flumazenil (0.2mg·kg^–1, i.v.), did not affect the suppressive effects of isoflurane. Failure of naloxone and flumazenil to reverse the suppressive effects of isoflurane suggests that isoflurane interacts with neither opioid nor benzodiazepine receptors in producing its suppressive action on nociceptive responses in dorsal horn neurons of the feline spinal cord.(Okuda T, Wakita K, Tsuchiya N, et al.: Naloxone and flumazenil fail to antagonize the isoflurane-induced suppression of dorsal horn neurons in cats. J Anesth 7: 462–467, 1993)     

Reducing the pain of open groin hernia repair

Pain after open mesh repair of groin hernia has a multifactorial etiology. Suturing technique for anchoring the mesh is important. Sutures placed too tightly, a common practice, are often the site of pain and point tenderness. These pain points are often precisely felt by patients and may vary in their intensity and duration. We believe that this type of suturing-technique-related pain can be significantly reduced by an air-knotting technique described below. The mesh was anchored with sutures tied in a subtle air-knot. In the event of accidentally incorporating a nerve in the knot, an air knot is less likely to cause the distressing symptoms of entrapment neuralgia. All knots are tied above the mesh and not across the edge of the mesh. Using this technique, we believe a significant reduction in the sharp, well-localized point pain can be achieved.Presented at the meeting of the American Hernia Society, in Orlando, Fla. USA, in February 2004     

Facial pain III. A prospective study of the localization of facial pain in 1052 patients

Summary The study is based on 1052 prospective patients. They have been divided into 3 groups according to the duration of the attack. The purpose of this study is to evaluate the importance of localization of the pain in order to determine its patho-anatomical basis. The right/left ratio was 2/1 in the Neuralgia Patients. There was no difference in patients with Non-neuralgiform Pain. There were extremely few cases of bilateral pain among the Neuralgia Patients, 15% among patients with Non-neuralgiform Pain. In the Neuralgia Patients there was a predominantly deep localization up to 50%, the Non-neuralgiform Pain 74%. Seventeen points of origin of pain have been registered in the face. By far the most frequent is a point of origin with radiation. If the percentage distribution is calculated according to each trigeminal division, the point of origin of pain in 74% is the eyebrow in the area of the 1st division, as regards the 2nd and 3rd divisions more than 30% from the upper gingiva, the area in front of the ear and the lower gingiva and between 11 and 20% from the forehead and the hairline, the upper lip and the nasolabial sulcus, the maxilla and the cheek. Pain radiation is generally most frequent to the division from which the pain originates. Neuralgia hardly radiates outside the boundaries of the face. The pain is localized within the area of one division in 42%. The radiation is not systematic. It is not possible from the localization of the pain to decide any patho-anatomical basis of the pain. Nothing in the localization of pain can be used for classification of facial pain (particularly not the parallelism or the peripheral course).Financial support for this study has been received from the Foundation for the Advancement of Medical Research.     

Ureteral stents — materials and new forms

Summary Three different types of polymers are currently used for self-retained ureteral stents: thermoplastic materials such as polyurethanes, and thermoset elastomers such as silicone and hydrogels. Polyurethane stents are easy to form and have high drainage capacity, whereas silicone shows the best biocompatibility but a lower drainage efficacy than the former. A mock urinary system consisting of a collecting system and a 9-F tube was used to evaluate the flow characteristics of various double-pigtail stents in cases of urinary obstruction. For simulation of an unobstructed urinary system a human urogenital system was used. Inner flow polyurethane stents showed the best drainage as compared with inner flow silicone and outer flow ESWL stents in an obstructed ureter, whereas ESWL stents maintained the best flow in an unobstructed ureter or in respect to conventional stents with obstructed sideports.     

Reduction in late postoperative pain after iliac crest bonegraft harvesting for cervical fusion: a controlled double-blinded study of 100 patients

Summary Background. A randomized prospective double-blinded study was conducted in 100 patients suffering from mono- or bisegmental cervical retrospondylosis or disc herniation.Method. In group I, 50 patients were treated by injection of 10ml Ropivacaine 7,5% at the iliac crest bonegraft donorsite. Local anaesthetic (LA) was injected through the wound drainage after closure of the muscle fascia, the suction drainage was opened after closure of the skin. Group II was treated with 0,9% saline. Operator and patient were blinded to the injected substance. Daily controls of pain intensity were made with the 10cm visual analog scale from 0 (no pain) to 10 (severe pain) for 5 days. All patients were questioned regarding pain character and movement provoking pain. Additional pain medication was standarized.Findings. Statistical analysis of mean pain intensity over the whole hospital stay showed a significant difference in pain intensity between the two groups (p=0,017, Chi-Square test). The comparison between pain intensity with LA and without LA showed a gradual increase in statistical significance from day 1 to day 5 (day 1: p=0,54, not significant; day 2: p=0,026; day 3: p=0,008; day 4: p=0,004; day 5: p=0,002).Interpretation. This data shows that intra-operative blockage of peripheral nociceptive structures results in decreased pain at later time points. We conclude that wound infiltration with 7,5% Ropivacaine after bonegraft removal at the iliac crest is effective in reducing postoperative pain.     

The effect of craniotomy location on postoperative pain and nausea

Purpose.At least one retrospective study has suggested that the need for postoperative control of pain and nausea depends on the location of the cranial surgery. This prospective study was performed to examine the hypothesis that patients who have had infratentorial craniotomy experience more severe pain and more frequent nausea than those with supratentorial procedures. Methods.We compared postoperative outcomes in 28 patients with infratentorial craniotomy, 53 with supratentorial craniotomy, and 47 with complex spinal cord surgery (the control group). Anesthesia was standardized for all three groups and the concentration of isoflurane was titrated to keep mean arterial pressure within 30% of preoperative values. Severity of pain and frequency of nausea and vomiting were recorded for 24h after surgery. Pain was assessed with a verbal pain score scale of 0–10, with 10 being the worst pain imaginable. Data were collected for 24h postoperatively. Results.Because nausea and pain diminish drastically 2h after surgery, pairwise differences were assessed at each point within the first 2h. Within 30min of extubation, median pain scores in the supratentorial and spine groups rose to 2 and in the infratentorial group to 5. The statistical differences between groups were not significant (P > 0.06) by logistic regression. Also, the incidence of nausea was not significantly different (57% supratentorial, 57% spine, 67% infratentorial; P = 0.62) by Dunns procedure. Conclusion.There were no significant differences in the severity of pain or the frequency of nausea based on the craniotomy site.     

Comparison of anesthetic effects of epidural and intravenous administration of buprenorphine during operation

Thirty six patients were received epidural anesthesia with or without buprenorphine (BPN) during upper abdominal surgery. They were divided into three groups of 12 patients as follows; G-I received 20ml of 1% lidocaine epidurally, G-II received 20ml of 1% lidocaine epidurally and 0.6mg BPN intravenously, G-III received 20ml of 1% lidocaine with 0.6mg BPN epidurally. Additional 5ml of 1% lidocaine was given to any patient if systolic blood pressure or heart rate increased 10% compared to control value. Trachea was intubated following anesthetic induction with thiopental. The lungs were ventilated with a mixture of N₂O/O₂ (33%) and pancuronium was used for muscle relaxation. The total required doses of lidocaine in G-II and G-III were decreased 60% compared to control group (G-I) (P 0.05). The mean period of time until the first administration of pentazocine for postoperative pain was 13 ± 10hr (mean ± SD) in G-II and 19 ± 24hr in G-III compared to 5 ± 4hr in G-I (P 0.001). The dose of the administration of pentazocine that was required for pain relief during the first 48 postoperative hr in G-III was 54 ± 10mg (mean ± SD) compared to 150 ± 21mg in G-I (P 0.02) and 106 ± 28mg in G-II (P 0.05). Recovery from anesthesia in G-III was more rapid than that in G-I (P 0.05). The Pa_{CO 2} values in G-II and G-III increased 15% compared to control group at about 4hr and 8hr after administration of BPN, but any clinical treatment was not needed for them. Nonrespiratory side effects, e.g., nausea, vomiting, fatigue and headache, were comparably common in all groups. Mild hematuria associated with acute hypotension occurred in two patients in G-II (17%) immediately after the intravenous injection of 0.6mg of BPN. The results showed that 0.6mg of BPN given epidurally demonstrated better anesthetic and more potent postoperative analgesic effects and lesser side effects than 0.6mg of BPN given intravenously in patients undergoing upper abdominal surgery.(Yonemura E, Fukushima K.: Comparison of anesthetic effects of epidural and intravenous administration of buprenorphine during operation. J Anesth 4: 242–248, 1990)     

Oral etodolac,a COX-2 inhibitor,reduces postoperative pain immediately after fast-track cardiac surgery

Purpose The present study was designed to evaluate the efficacy of a cyclooxygenase (COX)-2 inhibitor, etodolac, on postoperative pain after fast-track cardiac surgery, and to examine the changes in plasma etodolac concentration after oral administration.Methods Thirty patients scheduled for elective coronary artery bypass grafting (CABG) surgery were randomly assigned preoperatively in a double-blind fashion to receive either vehicle (n = 15) or etodolac 400mg (n = 15) via a gastric tube at the end of the surgery. Standardized fast-track cardiac anesthesia was used. In both groups, postoperative pain was treated with buprenorphine suppository. Visual analogue pain scores (VASs) were recorded immediately after extubation and at 24h after surgery. Plasma etodolac concentration was measured at 1, 2, and 6h after administration (n = 8).Results No difference was detected in time to extubation between the etodolac group (209 ± 85min, mean ± SD) and the vehicle group (207 ± 98min). VASs were significantly lower in the etodolac (2.3 ± 2.1) vs the vehicle group (5.8 ± 2.0) immediately after extubation (P = 0.009), but no difference was detected in pain scores at 24h after surgery, or in the amount of buprenorphine administered in the intensive care unit (ICU), or in the incidence of side effects. Plasma etodolac concentration was within the pharmaceutically recommended range at 1h, 2h, and 6h after administration.Conclusion The oral use of etodolac with rectal buprenorphine reduces pain scores immediately after cardiac surgery without an increase in side effects.     

The intercollegiate Basic Surgical Skills Course

Objective: This study was undertaken to establish residents progress in minimal access surgery (MAS) after attending the Intercollegiate Basic Surgical Skills Course (BSSC) by means of the Xitact LS500 laparoscopy simulator assessment program. Methods: Twenty-five surgical residents attended the BSSC in Leiden and Eindhoven, The Netherlands. Before and after the course, participants performed three runs on the Xitact LS500, featuring a standardized laparoscopic cholecystectomy clip-and-cut task. A control group of 25 interns not attending the course also performed two sessions of three runs. Parameters of interest were score and time for completion of task. Results: No significant differences were found within the resident group for the parameters time and score when comparing outcomes pre- and post-BSSC. No significant differences were found comparing time and score between residents and interns on each of the six runs, except for time in run 2. Over six runs, both residents and interns became significantly faster. Conclusions: The Xitact LS500 cholecystectomy simulator did not detect significant improvement in MAS performance among a group of surgical residents attending the BSSC.     

Double-blind study with dipyrone versus tramadol and butylscopolamine in acute renal colic pain

Summary To investigate the combined analgesic and spasmolytic effect of dipyrone, 104 patients suffering from severe or excruciating colic pain due to a confirmed calculus in the upper urinary tract were randomized to receive i.v. either 2.5 g dipyrone (36 patients), 100 mg tramadol (35 patients), or 20 mg butylscopolamine (33 patients) in a multicentre, observer-blind, parallel-group study conducted in 8 German centres. The three treatment groups were homogeneous when analyzed by age, sex, height, and baseline pain intensity. Dipyrone was significantly more effective than tramadol in reducing pain for the primary endpoint, pain intensity differences (PID) at 20, 30, and 50 min after drug administration, and was significantly more effective than butylscopolamine at 30 and 50 min for the secondary efficacy endpoint, pain intensity differences on a categorical scale. Dipyrone had the highest SPID_{0–2 h} of the three drugs (P<0.05). Only 5 patients receiving dipyrone needed rescue medication as compared with 13 patients given tramadol and 11 patients receiving butylscopolamine. Adverse events were observed in 4 patients receiving butylscopolamine and in 1 patient each given dipyrone and tramadol. Distinct pain relief as assessed on a visual analogue scale (VAS) is a reliable method of determining the onset of analgesic action in the colic pain model.     

Absorptiometry and “osteoporosis”: problems

connecting the dots between diverse clinical and other matters and an updated bone physiology reveals relationships that could modify some ideas about the roles and uses of absorptiometry in osteoporosis work. Herein, absorptiometry means that part of clinical densitometry that depends on X-ray absorption by bone and other tissues, thus excluding ultrasound methods and magnetic resonance imaging. The modifications concern, in part, some limitations of bone mineral density data, the kinds of physiological information that absorptiometry can and cannot provide, the relative importance of bone mass and whole-bone strength, how to define and study bone health and osteoporosis, and two kinds of osteoporotic fractures. As those modifications concern important national health care issues, they deserve answers based on hard evidence. Identifying those modifications might help others to evaluate them.     

A study on the critical mobilization length of peripheral nerves

Summary The transverse section of the sciatic, tibial and peroneal nerves in rabbits was followed by mobilization in a proximal and distal direction and a tensionfree end-to-end suture of the cut surfaces. The proximal mobilization was performed up to eight different levels between 60 mm and 200 mm, i. e. 20.3% to 67.7% of the total nerve length. Histological findings and their statistical analysis indicated that the critical mobilization length, beyond which ischaemic parenchymal damages occur, is 70 mm or 24% of the total nerve length. Up to this level, the vascular extrinsic system of the mobilized nerve segments is completely compensated for by the intrinsic system. When the mobilization length is increased, the degeneration distances were more pronounced than those of the ischaemic nerve distances. Some nerves showed no effects from the ischaemia.     

The distribution of extracellular matrix vesicles in healing of rat tibial bone three days after intramedullary injury

Summary The distribution of extracellular matrix vesicles on the third day of bone healing was studied by morphometric analysis of transmission electron micrographs. Detection and grouping of the vesicles was performed according to type, diameter, and distance from the calcified front. The different types were selected as follows: vesicles with electron-lucent contents (empty), vesicles with amorphous electron-opaque contents (amorphic), vesicles containing crystalline depositions (crystal), and vesicles containing crystalline structures with ruptured membranes (rupture). The majority of vesicles were between 0.07 µm and 0.12 m in diameter and were located at less than 3 m from the calcified front. The distribution of the empty, amorphic, crystal, and rupture vesicles was 23.2%, 74%, 2.5%, and 0.3% respectively. Their sequence of arrangement according to diameter was as follows: empty, amorphic, crystal, and rupture, the empty vesicles constituting the smallest and the rupture the largest type. Distances from the calcified front were similar for the empty, amorphic, and crystal vesicles, while the rupture type was located nearest to the front. The present observations support the widely acknowledged hypothesis on the role of extracellular matrix vesicles in mineralization. It is thought that the secretion of empty vesicles from the cell is followed by intravscular accumulation of amorphous Ca and Pi to form a hydroxyapatite crystal that, in turn, ruptures the vesicle's membrane. The maturation process is accompanied by an increase of the vesicular diameter and its approximation to the calcifying front.     

Zur Entwicklung der Hüftluxationsbehandlung im Laufe der Medizingeschichte

Zusammenfassung Die historische Entwicklung der ärztlichen Heilmaßnahmen zur Hüftgelenksreposition bei der typischen angeborenen Verrenkung ist ein interessantes Spiegelbild der gesamten Medizingeschichte und der Orthopädie im besonderen. Schon Hippokrates hat auf Grund recht guter pathologisch-anatomischer Sachkenntnis in seinem bedeutenden Werk i — über die Einrichtung der Gelenke — ein ebenso einfaches wie zweckmäßiges Extensionsverfahren am luxierten Bein dargestellt. Nach einer auffallend langen Zeitspanne resignierter Beschränkung auf rein palliative Therapie folgte eine radikal-aktive Ära der operativ-chirurgischen Reposition der kongenitalen Hüftluxation — vor allem repräsentiert durch die blutige Einrenkungsmethode von Hoffa und Lorenz. Erst die klinischen Mißerfolge dieses heroischen Vorgehens mit seiner Möglichkeit eines genauen bioptischen Studiums der weichgewebigen und artikulären Skeletsituation schufen die Grundlage zur Entwicklung der klassischen unblutigen Repositionsmethode, um deren Primat zwischen dem Italiener Paci und Adolf Lorenz eine heftige Kontroverse entstand. Zur stabilen Retention der eingerenkten Luxationshüfte wurden in der Folgezeit sehr verschiedenartige Gipsfixationen und Spreizapparate empfohlen — am bekanntesten die Lorenzprimärstellung, die weniger forcierte Langeposition und das geniale Schedelaufrad. Die moderne Orthopädie hat für die operative Korrektur unblutig nicht zu reponierender Hüftluxationen, etwa beim Vorliegen eines weichgewebigen Interpositums, oder bei unbefriedigendem Behandlungsergebnis eine ganze Reihe chirurgischer Hilfsoperationen — jeweils mit ganz spezieller Indikation — zur Verfügung: Die blutige Einrenkung, die Pfannendachplastik bei mangelhafter knöcherner Formsicherung des Acetabulums, die Femurosteotomie bei bestehender Oberschenkeldeformität im Sinne einer Coxa valga oder pathologischer Antetorsion des proximalen Femurendes — schließlich die Arthroplastik mit oder ohne Endoprothese bei schmerzhaft-kontrakten Spätzuständen. Als ultima ratio kann in besonders schweren Fällen ein stabiles beschwerdefreies Standbein durch Arthrodese geschaffen werden. Selbstverständlich werden heute auch sämtliche bewährten sonstigen physikalischen Hilfsmittel und Heilverfahren — aktive und passive Gymnastik, temporäre Gamaschenextension und Apparatentlastung, Massage und Bäderbehandlung — zur Verbesserung von Form und Funktion der Luxationshüften in den großen Kreis therapeutischer Möglichkeiten einbezogen.Die Arbeit wurde auf die Initiative und unter der Leitung von Herrn Prof. Dr. Rupprecht Bernbeck, München, verfaßt.     

Hospital Readmissions Following Abdominal Aortic Aneurysm Repair

In-hospital outcomes associated with abdominal aortic aneurysm (AAA) repair are well described. However, little is known about post-discharge readmission rates, lengths of stay, associated mortality, and costs. We examined 206 consecutive patients who underwent AAA repair at two American hospitals between 1998 and 2000. Index hospitalization and 6-month readmission data were extracted from a resource and cost accounting system used by both hospitals. Among the 206 patients, 183 survived until discharge (mortality rate 11.2%). Among the surviving patients, 38 (21.0%) were readmitted within 6 months. Half of the readmissions occurred within two weeks of discharge, with patients presenting with a diverse array of complications. Nonelective repair and diabetes mellitus were independent predictors of hospital readmission (OR=2.83, 95% CI=1.25-6.40, p=0.01; OR=6.60, 95% CI=1.02-42.4, p=0.047, respectively). For each readmission, the mean length of stay was 10.7±2.5 days and the mean cost was $13,397±3,381. The cumulative number of hospital days during the 6 months post-discharge was 17.7±3.5 days for each readmitted patient and the mean per-patient total cost was $23,262±5,478. The mortality rate among readmitted patients was 13.2%. Overall, readmissions following AAA repair accounted for a cost >50% over and above the cost of the readmitted patients index hospitalization. Hospital readmissions are common during the 6 months following AAA repair. Patients who are readmitted experience long lengths of stay and high mortality rates, and their care incurs high costs.Dr. Eisenberg is a Physician-Scientist of the Quebec Foundation for Health Research. Dr. Pilote is a Physician-Scientist of the Canadian Institutes for Health Research.     

Impact of Age on Quality of Life in Patients with Rectal Cancer

Some studies indicate that age at the time of surgery has a general effect on outcomes. The impact of age on the quality of life (QOL) of patients with rectal cancer, however, has not been investigated. The present study was conducted to address this issue. Over a 5-year period the European Organization for Research and Treatment of Cancer (EORTC)-QLQ-C-30 and a tumor-specific module were prospectively administered to patients before surgery, at discharge, and at 3, 6, 12, and 24 months postoperatively. Comparisons were made between age groups. A total of 519 patients participated in the study. QOL data were available for 253 patients. Significant differences were observed only between patients aged 69 years and younger (69 years) (169/253) and those aged 70 years and older (70 years) (85/253). Physical and role functioning was better for patients 69 years; patients 70 years suffered from increased pain and fatigue. Younger patients had more difficulty with sexual enjoyment, and over time sexual strain was worse for patients aged 70 years during the early postoperative period but improved, whereas patients aged 69 years had increasing levels of strain over time. The findings in this study confirmed that QOL is dynamic over time and that age has an impact on QOL and sexuality. Patients aged 70 years are affected by impaired physical functioning, global health, and fatigue, whereas increased treatment strain during the early postoperative period improves over time. Patients aged 69 years experience increased strain because of impaired sexual function.     

ACE inhibition modulates transforming growth factor-β receptors in the young rat

The renin-angiotensin system plays an important role in renal growth and development. Exposure of the neonate to angiotensin converting enzyme (ACE) inhibitors increases mortality and results in growth retardation and abnormal renal development. It has been demonstrated that ACE inhibition in the developing kidney reduces the renal expression of growth factors, which may account for renal growth impairment. This study was designed to investigate the relationship between renal growth impairment and the expression of transforming growth factor-1 (TGF-1), TGF- receptor I [TRI, activin-like kinase (ALK)-1 and ALK-5], and TGF- receptor II (TRII). Newborn rat pups were treated with enalapril (30 mg/kg per day) or vehicle for 7 days, and kidneys were removed for Western blotting of TGF-1, ALK-1, ALK-5, and TRII, and for RT-PCR of ALK-5 and TRII. TGF-1, ALK-1, ALK-5, and TRII were also detected by immunohistochemistry. Enalapril treatment resulted in an increased mortality (30.4%) by day 7, and reduced body weight and kidney weight (P<0.05 versus vehicle). Enalapril decreased renal TGF-1, ALK-1, and ALK-5 protein expression (P<0.05). Also, enalapril decreased ALK-5 mRNA expression (P<0.05). TRII expression was not changed by enalapril treatment. These results indicate that ACE inhibition in the developing kidney decreases TGF-1, ALK-1, and ALK-5 expression, which may account for renal growth impairment. TRII may not be modulated by ACE inhibition in the developing kidney.     

Transforming growth factor-β and prostate cancer

Summary This review focuses on the possible role of transforming growth factor- isoforms 1–3 (TGF) in prostate cancer. TGF1 appears to inhibit the cellular proliferation of normal prostate cells. Surprisingly, TGF1 is overexpressed in prostate cancer. To help explain this apparent paradox, it has been revealed that with tumor progression, prostate cancer cells acquire reduced sensitivity to the growth-inhibitory effects of TGF1. Aberrations of the TGF1 signaling pathway at the prereceptor, receptor, or postreceptor level may lead to prostate cancer cell resistance to TGF1 growth inhibition. Indirectly, elevated levels of TGF1 may induce host effects that may be beneficial to prostate tumor growth by suppressing the immune system, promoting angiogenesis and extracellular matrix formation, and enhancing metastatic potential. Consequently, TGF1 appears to be important in prostate carcinogenesis and tumorigenicity. TGF2 and TGF3 are only briefly presented as very little is known about their role in prostate cancer.