Route of nutrition influences intercellular adhesion molecule-1 expression and neutrophil accumulation in intestine.

HYPOTHESIS: The levels of intestinal interleukin 10 and interleukin 4, inhibitors of intercellular adhesion molecule-1 (ICAM-1) expression, decline with total parenteral nutrition (TPN). These cytokine changes induced by lack of enteral nutrition may increase ICAM-1 expression, resulting in polymorphonuclear neutrophil accumulation in intestine. DESIGN: Prospective randomized experimental trials. SETTING: Laboratory. MATERIALS: Male mice. INTERVENTIONS: Sixty-three mice were randomized to chow, intravenous TPN, or intragastric TPN. MAIN OUTCOME MEASURES: Experiment 1: After diet manipulation, iodine 125-labeled anti-ICAM-1 antibody and iodine 131-labeled nonbinding antibody were injected to quantify ICAM-1 expression on endothelial cells in the lung, liver, kidney, and small intestine. Measurement of myeloperoxidase was used to quantify polymorphonuclear neutrophil accumulation in the organs. Experiment 2: Intestine was harvested for both ICAM-1 and myeloperoxidase levels after chow refeeding of mice in the intravenous TPN group. RESULTS: In experiment 1, uninjured mice fed intravenous TPN showed significantly increased intestinal ICAM-1 expression and polymorphonuclear neutrophil accumulation with no significant changes in the lung, liver, or kidney. No changes occurred in mice fed chow or intragastric TPN. In experiment 2, reinstitution of enteral feeding returned intestinal ICAM-1 and myeloperoxidase levels to normal. CONCLUSION: Gut changes associated with lack of enteral feeding induce endothelial changes and an immunologic response, which may influence subsequent responses to injury.     

Assessment of ocular perfusion after carotid endarterectomy with color-flow duplex scanning

PURPOSE: The purpose of this study was to assess the effect of carotid endarterectomy (CEA) on ocular perfusion with the measurement of the ophthalmic artery (OA) and the central retinal artery (CRA) flow velocities with color-flow ocular duplex scanning (ODS). Ocular hemodynamics also were examined in a subset of patients with visual symptoms in an attempt to characterize the origin of the ocular symptoms and their response to surgery. METHODS: Twenty-five patients with internal carotid artery stenoses (>/=70%) underwent 29 CEAs. All the patients underwent ODS for the measurement of the peak systolic velocity (PSV) in the OA and the CRA of the ipsilateral eye before and after CEA. The preoperative and postoperative flow velocities were compared in all the patients and in the patients with and without visual symptoms. RESULTS: The preoperative PSV in the OA was 21.6 +/- 2.2 cm/s and in the CRA was 7.7 +/- 0.7 cm/s. These values were reduced as compared with normative values (OA, 37.8 cm/s; CRA, 10.7 cm/s). After CEA, the PSV increased significantly in both vessels (postoperative OA, 38.6 +/- 2.5 cm/s, P <.0001; postoperative CRA, 12.1 +/- 0.9 cm/s, P =.0008). Fifteen of the 29 CEAs were performed for visual symptoms. The patients with ocular symptoms had significantly lower preoperative PSVs in the CRA as compared with those patients without visual symptoms (CRA with ocular symptoms, 6.5 +/- 0.8 cm/s; CRA with no ocular symptoms, 9.4 +/- 0.9 cm/s; P =.02). The PSV in the OA was not significantly lower in the patients with ocular symptoms. Eight patients (28%) were found to have reversed OA flow before surgery, but only three patients had ocular symptoms. All eight patients had normal antegrade flow in the OA after surgery. CONCLUSION: Severe carotid stenosis may be associated with reduced ocular perfusion, which can be quantitatively evaluated with ODS. Reduced OA and CRA flow velocities are corrected with successful CEA. The patients with ocular symptoms were observed to have significant reductions in CRA flow velocities. Reversed flow in the OA was not a marker for ocular symptoms in this study. ODS can identify global ocular ischemia and may be helpful in the evaluation of patients with atypical visual symptoms or with amaurosis fugax and no evidence of retinal emboli.     

Patterns of success and failure with laparoscopic Toupet fundoplication

Background: Advocates of the Toupet partial fundoplication claim that the procedure has a lower rate of the side effects of dysphagia and gas bloat than a complete Nissen fundoplication. However, there is increasing recognition that reflux control is not always as good with the Toupet procedure as with the Nissen. Therefore, we set out to evaluate the factors contributing to success and failure in patients who underwent laparoscopic modified Toupet fundoplication (LTF). Methods: A total of 143 patients undergoing LTF for documented gastroesophageal reflux disease (GERD) were evaluated prospectively in regard to their outcomes over a 4-year period. All patients had preoperative esophagogastroduodenoscopy (EGD) and manometry; 24-h pH testing was used selectively. Esophageal manometry was requested of all patients 6 weeks postoperatively. Clinical follow-up was by office visit or questionnaire every 6 months after surgery; patients with significant problems were investigated further. Failure was defined as the development of recurrent reflux documented by endoscopy, 24-h pH test, or wrap disruption on barium swallow, or severe dysphagia persisting >3 months and requiring surgical revision. Results: At a mean follow-up of 30 months (range, 3–51), 21 of 143 patients failed LTF; two had dysphagia and 19 had recurrent reflux. Failure was associated with preoperative findings of a defective lower esophageal sphincter (LES) (14/21), complicated esophagitis (13/21), and failure to divide short gastric vessels (12/19) (chi-square p < 0.05). Defective esophageal body peristalsis, present in 14 patients, resulted in failure in six cases. Presence of either complicated esophagitis or a defective LES was associated with a 3-year 50% success rate, whereas presence of mild esophagitis and a normal LES was reflected in a 96% 3-year success rate. Conclusion: Laparoscopic Toupet fundoplication should be reserved for milder cases of GERD, as assessed by manometry and endoscopy. Received: 29 June 1998/Accepted: 2 July 1999     

The contribution of inner and outer retinal photoreceptors to infra‐slow oscillations in the rat olivary pretectal nucleus

A subpopulation of olivary pretectal nucleus (OPN) neurons discharges action potentials in an oscillatory manner, with a period of approximately two minutes. This ‘infra‐slow’ oscillatory activity depends on synaptic excitation originating in the retina. Signals from rod‐cone photoreceptors reach the OPN via the axons of either classic retinal ganglion cells or intrinsically photosensitive retinal ganglion cells (ipRGCs), which use melanopsin for photon capturing. Although both cell types convey light information, their physiological functions differ considerably. The aim of the present study was to disentangle how rod‐cone and melanopsin photoresponses contribute to generation of oscillatory activity. Pharmacological manipulations of specific phototransduction cascades were used whilst recording extracellular single‐unit activity in the OPN of anaesthetized rats. The results show that under photopic conditions (bright light), ipRGCs play a major role in driving infra‐slow oscillations, as blocking melanopsin phototransmission abolishes or transiently disturbs oscillatory firing of the OPN neurons. On the other hand, blocking rod‐cone phototransmission does not change firing patterns in photopic conditions. However, under mesopic conditions (moderate light), when melanopsin phototransmission is absent, blocking rod‐cone signalling causes disturbances or even the disappearance of oscillations implying that classic photoreceptors are of greater importance under moderate light. Evidence is provided that all photoreceptors are required for the generation of oscillations in the OPN, although their roles in driving the rhythm are determined by the lighting conditions, consistent with their relative sensitivities. The results further suggest that maintained retinal activity is crucial to observe infra‐slow oscillatory activity in the OPN.     

Elevated plasma levels of TIMP-1 in patients with rotator cuff tear

Background and purpose

Extracellular matrix remodeling is altered in rotator cuff tears, partly due to altered expression of matrix metalloproteinases (MMPs) and their inhibitors. It is unclear whether this altered expression can be traced as changes in plasma protein levels. We measured the plasma levels of MMPs and their tissue inhibitors (TIMPs) in patients with rotator cuff tears and related changes in the pattern of MMP and TIMP levels to the extent of the rotator cuff tear.

Methods

Blood samples were collected from 17 patients, median age 61 (39–77) years, with sonographically verified rotator cuff tears (partial- or full-thickness). These were compared with 16 age- and sex-matched control individuals with sonographically intact rotator cuffs. Plasma levels of MMPs and TIMPs were measured simultaneously using Luminex technology and ELISA.

Results

The plasma levels of TIMP-1 were elevated in patients with rotator cuff tears, especially in those with full-thickness tears. The levels of TIMP-1, TIMP-3, and MMP-9 were higher in patients with full-thickness tears than in those with partial-thickness tears, but only the TIMP-1 levels were significantly different from those in the controls.

Interpretation

The observed elevation of TIMP-1 in plasma might reflect local pathological processes in or around the rotator cuff, or a genetic predisposition in these patients. That the levels of TIMP-1 and of certain MMPs were found to differ significantly between partial and full-thickness tears may reflect the extent of the lesion or different etiology and pathomechanisms.The subacromial pain syndrome includes a range of disorders from reversible inflammation to massive rotator cuff tearing (Shindle et al. 2011). The etiology appears to be multifactorial, and several anatomic structures may be involved. Repetitive damage of the supraspinatus tendon by mechanical wear from the coraco-acromial ligament and the anterior acromion was described by Neer 1972, and for a long time it was considered the major cause of cuff tearing (Neer 1983). Others have reported age-related tendon degeneration, associated with alterations in extracellular matrix remodeling as a contributing factor (Lo et al. 2004, Millar et al. 2009, Pasternak and Aspenberg 2009, Shindle et al. 2011). Histopathological changes associated with rotator cuff tendinosis have been documented, but it is unclear whether they are a result of a subacromial impingement or an endogenous process, and whether tendinosis might predispose to tendon tears (Lo et al. 2004).Regardless of whether mechanical or degenerative factors initiates tearing, there are alterations in the cellular and extracellular matrix (Gwilym et al. 2009). It has been suggested that genetic factors may influence apoptosis or regeneration (Gwilym et al. 2009, Shindle et al. 2011). Still, the molecular changes associated with rotator cuff tearing are largely unknown (Lo et al. 2004, Garofalo et al. 2011). Turnover of the extracellular matrix (ECM) is mediated by matrix metalloproteinases (MMPs), a family of at least 24 zinc-dependent endopeptidases. The MMPs are classified according to their main degradative activity, into for example collagenases, gelatinases, and stromelysins (Pasternak and Aspenberg 2009). Their activity is regulated by endogenous inhibitors: tissue inhibitors of metalloproteinases (TIMPs). There are 4 known TIMPs, which reversibly inhibit all MMPs by 1:1 interaction with the zinc-binding site (Lo et al. 2004, Pasternak and Aspenberg 2009). MMP production is induced by factors such as cytokines and tumor necrosis factor-α. MMPs are secreted by connective tissue and inflammatory cells and then activated in the extracellular space (Garofalo et al. 2011). The composition of the ECM is dependent on the balance between MMPs and TIMPs (Lo et al. 2004, Pasternak and Aspenberg 2009, Garofalo et al. 2011). Levels of MMP mRNA and TIMP mRNA were found to be altered in biopsies from torn rotator cuff tendon (Lo et al. 2004). It is not known, however, whether these changes are causative or whether they are secondary to tendon tearing.Studies on MMP and TIMP levels in patients with rotator cuff syndrome and cuff tears have used samples collected at surgery from the subacromial bursa, synovial fluid, or the tendons (Lo et al. 2004, Lakemeier et al. 2010, Shindle et al. 2011). To date, there have been no data on systemic levels. Alterations in MMP and TIMP levels in systemic blood samples have been identified in other musculoskeletal diseases such as Dupuytren’s disease, ankylosing spondylitis, and fracture non-union, suggesting that alterations associated with rotator cuff disease may also be measurable systemically (Ulrich et al. 2003, Henle et al. 2005, Pasternak and Aspenberg 2009). In osteoarthritis, circulating MMP-3 has been suggested to be a marker of disease severity and has been used as a prognostic tool (Lohmander et al. 2005).We measured plasma levels of MMPs and TIMPs in patients with rotator cuff tears and compared partial- and full-thickness tears, in order to find disease-associated changes in the expression patterns of MMP and TIMP.     

The Use of Stereotactic Excisional Biopsy in the Management of Invasive Breast Cancer

Stereotactic breast biopsy techniques minimize the surgical trauma associated with conventional wire-guided open breast biopsy for non-palpable breast lesions (NPBLs). Advanced breast biopsy instrumentation (ABBI) allows for a 2-cm core of breast tissue to be excised under stereotactic guidance in an outpatient setting. We report our initial experience with ABBI. Hospital charts from 89 ABBI procedures between 10/1996 and 07/2002 were retrospectively reviewed for patient characteristics, ABBI parameters, radiographic appearance, pathology, complications, and clinical follow-up. Data are presented as percentage/median (range). Median age was 59 years (range: 39–80 years), mammographic lesions were classified as calcifications 49% (44/89), soft tissue 39% (35/89), or mixed 11% (10/89). Median radiographic size was 7 mm (1–60 mm). Final pathology revealed ductal carcinoma in situ (DCIS) in 7% (6/89) and invasive cancer in 22% (20/89). Microscopically clear margins were obtained in 55% (11/20) of patients with invasive cancer. Of these, 82% (9/11) chose not to undergo further local surgical therapy. Eight patients remain disease free at 56 months (range: 41–95 months) follow-up. The ninth patient was deceased at 6 months from an unrelated cause. The overall complication rate was 3% (3/89). A definitive diagnosis was obtained in 100% of malignant and 87% of benign cases. Median waiting time was 19 days (range: 0–90 days). Our experience demonstrates that ABBI is an effective diagnostic tool for NPBLs. It is associated with minimal complications, and provides negative margins in over half of malignant cases. In selected patients with invasive cancer and negative margins, ABBI may obviate the need for further local surgical treatment. ABBI merits additional investigation as a therapeutic modality for early breast cancer.     

Laparoscopic nephron sparing surgery: evolution in a decade

OBJECTIVE: To present our experience with laparoscopic nephron sparing surgery (NSS) over a decade. METHODS: Seventy-eight patients underwent NSS since 1994. Two techniques were used-partial nephrectomy without ischemia (group 1) in 29 patients, and with ischemia (group 2) which was in cold or warm ischemia in 24 and 25 patients respectively. The mean tumour size was 1.97 and 2.2 cm in groups 1 and 2 respectively. Renal reconstruction evolved in our hands during this period. We changed many technical details and now we depend more on clips for securing the sutures rather than free hand knotting. RESULTS: The mean operative time was 162 and 216 minutes in groups 1 and 2 respectively. Mean ischemia time for patients with cold and warm ischemia was 44.9 and 33.8 minutes respectively. 3 patients in group 2 were converted to open surgery. Mean blood loss was 254 and 212 ml for group 1 and 2 respectively with two major bleedings in group 2. Minor intra-operative complication occurred in 3 patients, and major and minor postoperative complication in 15 patients. At a mean follow-up of 23.9 and 12.2 months for groups 1 and 2 respectively there was no recurrence. CONCLUSION: Warm and cold ischemia have widened the indications for laparoscopic NSS to more complex tumours and allow renal reconstruction with acceptable complication rate.