Cutaneous habronemosis in horses: First molecular characterization of Habronema muscae in Israel.

Draschia megastoma, Habronema microstoma, and Habronema muscae are the etiological agents of cutaneous habronemosis, commonly known as summer sores, an inflammatory cutaneous and ocular parasitic disease of horses and other equids transmitted by flies. Here, we describe a cluster of cutaneous habronemosis in five horses that showed single or multiple typical cutaneous ulcerative wounds located on the face, lower forelegs or hindquarters in Israel with the presence of typical "sulphur granules." All affected animals were confirmed by histopathological and/or molecular methods to be infected by H. muscae. This constitutes the first report of cutaneous habronemosis in Israel in which the causative nematode, H. muscae, was identified by molecular means. Cutaneous habronemosis should be considered as a differential diagnosis in equids with cutaneous ulcerative lesions during the summer months, especially when affected animals are refractive to antibiotic treatment alone.

Evaluation of hemostatic abnormalities in canine spirocercosis and its association with systemic inflammation.

BACKGROUND: Canine spirocercosis is caused by the nematode Spirocerca lupi and is characterized by esophageal fibro-inflammatory nodules that may undergo neoplastic transformation. No sensitive and specific laboratory assays other than histopathology have been reported to differentiate non-neoplastic from neoplastic disease. HYPOTHESIS/OBJECTIVES: Dogs with spirocercosis will have evidence of hypercoagulability based on thromboelastography (TEG)-derived maximal amplitude (MA); increased MA will be correlated with increased acute phase protein (APP) concentrations (C-reactive protein [CRP] and fibrinogen); increased MA and APPs will be exacerbated with neoplastic spirocercosis. ANIMALS: Thirty-nine client-owned dogs with naturally occurring spirocercosis and 15 sex-matched healthy controls. METHODS: A prospective comparative study evaluating TEG, activated partial thromboplastin time, prothrombin time, antithrombin (AT) activity, platelet count and D-dimer concentration, and APPs of dogs with non-neoplastic (n = 24) and neoplastic (n = 15) spirocercosis compared to control dogs. RESULTS: Median MA was significantly increased in the non-neoplastic group (P < .01) and neoplastic group (P < .01) compared to the controls. Both APPs were significantly increased in the neoplastic group compared to the non-neoplastic and control groups. MA was strongly correlated with fibrinogen (r = 0.85, P < .001) and CRP (r = 0.73, P < .001). An MA >76 mm provided 96% specificity and 73% sensitivity for differentiation of disease state. CONCLUSIONS AND CLINICAL IMPORTANCE: Canine spirocercosis is associated with increased TEG variables, MA and α, and decreased AT activity, which may indicate a hypercoagulable state seemingly more severe with neoplastic transformation. MA was correlated with APP in dogs with spirocercosis and can be used as an adjunctive test to support the suspicion of neoplastic transformation.

Vascular endothelial growth factor concentrations in dogs with spirocercosis.

BACKGROUND: Vascular endothelial growth factor (VEGF) is a potent proangiogenic factor associated with tumor development. Spirocerca lupi is a nematode of canids that induces an esophageal nodule that progresses to a sarcoma in 25% of cases. Determination of neoplastic transformation is challenging and usually based on endoscopy-guided biopsies under general anesthesia, an expensive procedure that often yields nondiagnostic, necrotic samples. HYPOTHESIS: Circulatory VEGF concentrations are increased in dogs with neoplastic spirocercosis and can distinguish between dogs with neoplastic and nonneoplastic disease. ANIMALS: A total of 24 client-owned dogs, 9 nonneoplastic, 9 neoplastic, and 6 controls. METHODS: Case-control study. Plasma and serum VEGF concentrations at the time of diagnosis were compared with those of healthy controls. Measurement of VEGF was performed using a canine-specific ELISA. Kruskal-Wallis and Dunn's tests were used for statistical analysis with significance set at P < .05. RESULTS: The median plasma VEGF concentrations of dogs with neoplastic spirocercosis were 629 pg/mL (range, 282-2,366) higher than both the nonneoplastic (<39.5 pg/mL; range, <39.5-716) and control dogs (<39.5 pg/mL; all values, <39.5; P = .0003). The median serum VEGF concentration of the neoplastic dogs was 69 pg/mL (range, <39.5-212) higher than the nonneoplastic (<39.5 pg/mL; range, <39.5-44.13) and control dogs (<39.5 pg/mL; all values, <39.5; P = .001). CONCLUSIONS AND CLINICAL IMPORTANCE: Both plasma and serum VEGF concentrations can be used to differentiate nonneoplastic and neoplastic spirocercosis. The role of VEGF in neoplastic transformation of S. lupi-induced nodules and the potential utility of anti-VEGF drugs in spirocercosis-induced sarcoma warrant further investigation.

Hypovitaminosis D in dogs with spirocercosis.

BACKGROUND: Spirocercosis in dogs is characterized by esophageal nodules that can undergo neoplastic transformation. Hypovitaminosis D has been associated with neoplasia formation. We hypothesized hypovitaminosis D in neoplastic spirocercosis and that it could be a risk factor for neoplastic transformation. OBJECTIVE: To measure and compare vitamin D status, assessed by serum 25-hydroxyvitamin D [25(OH)D] concentrations in non-neoplastic (n = 25) and neoplastic (n = 26) spirocercosis client-owned dogs and healthy dogs (n = 24). ANIMALS: Twenty-five non-neoplastic dogs, 26 neoplastic dogs, and 24 healthy dogs. METHODS: Fifty-one dogs were randomly selected from 119 dogs diagnosed with spirocercosis presenting to our hospital, and further divided into non-neoplastic or neoplastic groups. Exclusion criteria included dogs less than 1 year old, with concurrent diseases, received corticosteroids, or treated prophylactically for spirocercosis. Serum 25(OH)D concentration was measured by high-performance liquid chromatography. Spirocercosis dogs' appetites were graded and compared. RESULTS: Serum 25(OH)D concentrations were significantly different among all groups (P < .001). 25-Hydroxyvitamin D concentrations were significantly lower in neoplastic group (median 30.7 nmol/L [range 14.7-62.2]) compared to non-neoplastic (median 52.7 nmol/L [range 19.1-129.7, P < .05]) and healthy groups (median 74.6 nmol/L [range 37.4-130.5, P < .005]). 25-hydroxyvitamin D concentrations were significantly lower in non-neoplastic spirocercosis dogs compared to healthy ones (P < .05). Neoplastic and non-neoplastic spirocercosis dogs had similar appetite scores (P = 1.0). 25-Hydroxyvitamin D concentrations were not significantly different between dogs with normal (P = .087) and abnormal (P = .125) appetites within neoplastic and non-neoplastic spirocercosis groups. CONCLUSIONS AND CLINICAL IMPORTANCE: Further studies are warranted to determine potential use of vitamin D treatment in spirocercosis and explore role of hypovitaminosis D in pathogenesis of malignant transformation.

Plasma IL-8 concentrations are increased in dogs with spirocercosis.

The nematode Spirocerca lupi (S. lupi) induces sarcoma in the dog oesophagus in about 25% of cases. The aim of this study was to compare the differences in the cytokine milieu between dogs with neoplastic (n=29) and non-neoplastic disease (n=49) and age- and gender-matched healthy controls (n=25). We measured IL-2, IL-4, IL-6, IL-8, IL-10, IL-18, GM-CSF and MCP-1 in a specific canine multiplex immunoassay kit. Cytokine concentrations were compared between the different groups using the Kruskal-Wallis test followed by Dunn's test. Only IL-8 and IL-18 showed significant differences in their plasma concentration among the three groups. Kruskal-Wallis test revealed a significant (p=0.001) difference in IL-8 concentration between the neoplastic group (634pg/ml), the non-neoplastic (429 pg/ml) and the control groups (150 pg/ml). Post-test analysis revealed a significance difference between the two S. lupi groups and the control group (p<0.01). The highest IL-18 concentration was found in the non-neoplastic group (53 pg/ml), followed by the control group (46 pg/ml) and finally the neoplastic group (33 pg/ml). IL-18 concentrations were significantly higher in the non-neoplastic group than in the neoplastic group (p=0.05). The increased IL-8 in the spirocercosis groups is consistent with the neutrophilic infiltrate in spirocercosis lesions and in those of other inflammatory-induced neoplasias such as Barret's oesophagus and Helicobacter gastritis. IL-18 showed negative regulatory effect in several worm infections and it is possible that it plays the same role in spirocercosis, allowing the worm to evade the host response and to induce neoplastic transformation.

Immunohistochemical characterization of lymphocyte and myeloid cell infiltrates in spirocercosis-induced oesophageal nodules.

Spirocerca lupi is a nematode that infects the dog's oesophagus and promotes the formation of an inflammatory fibroblastic nodule that progresses to sarcoma in approximately 25% of cases. Spirocercosis-associated oesophageal sarcoma is an excellent and under-utilized spontaneous model of parasite-associated malignancy. The inflammatory infiltrate of paraffin-embedded, non-neoplastic oesophageal nodules (n = 46), neoplastic nodules (n = 25) and normal oesophagus (n = 14) was examined by immunohistochemistry using MAC387 (myeloid cells), CD3 (T cells), Pax5 (B cells) and FoxP3 (T regulatory cells) antibodies. Myeloid cells predominated in 70% of nodules, in pockets around the worms' migratory tracts and in necro-ulcerative areas in neoplastic cases. T cells predominated in 23% of cases with a focal or diffuse distribution, in the nodule periphery. No significant differences were observed between neoplastic and non-neoplastic stages. FoxP3+ cells were observed in low numbers, not significantly different from the controls. The inflammation in spirocercosis is characterized by pockets of pus surrounded by organized lymphoid foci. There was no evidence of a local accumulation of FoxP3+ cells, unlike many previous studies that have reported an increase in FoxP3+ T cells in both malignancies and parasite infections. The triggering factor(s) driving the malignant transformation of the spirocercosis-associated chronic inflammatory nodule warrants further investigation.

Serum C-reactive protein concentration in benign and malignant canine spirocercosis.

BACKGROUND: Spirocerca lupi is a nematode of canids that forms a nodule in the esophagus that can undergo neoplastic transformation. C-reactive protein (CRP) is a major acute phase protein in the dog that has been used for treatment, monitoring, and prognostication in inflammatory and neoplastic disease. HYPOTHESIS/OBJECTIVES: The objectives of this study were to determine if serum CRP concentration (1) is increased in canine spirocercosis, (2) can be used to determine neoplastic transformation, and (3) can be used to monitor response to treatment in benign spirocercosis. ANIMALS: Forty-two dogs naturally infected with S. lupi and 21 control dogs. METHODS: A retrospective study was performed. The infected cases were divided into benign (n = 28) or malignant (n = 14) spirocercosis. CRP was performed on all of the spirocercosis and control cases at presentation. Statistical analysis was done by the one-way analysis of variance and Student's t-test. RESULTS: The mean CRP concentration in the benign cases was 60.4 ± 48.0 mg/L and that of the malignant cases was 76.5 ± 44.8 mg/L; both values were significantly higher (P < .001) than those of the control group where the mean was 13.4 ± 17.9 mg/L. The mean CRP concentration for the convalescent sera in the benign group was lower than the pretreatment concentrations (P= .01). CONCLUSION AND CLINICAL IMPORTANCE: CRP cannot be used to differentiate between benign and malignant spirocercosis. There is a decrease in CRP concentration in dogs with benign spirocercosis once treatment has commenced. Serial CRP measurement can be used to monitor response to treatment in benign spirocercosis.

Proposed histological progression of the Spirocerca lupi-induced oesophageal lesion in dogs.

This study aims to outline the histological progression of the Spirocerca lupi nodule from infection to neoplastic transformation. Sixty-two spirocercosis-induced nodules, 42 non-neoplastic and 20 neoplastic, were stained with HE. Ten non-overlapping high power fields per nodule were examined and non-neoplastic and neoplastic nodules were compared. Inflammation was scored 0-3 and revealed a score of 1.91+/-0.52 in the non-neoplastic and 0.97+/-0.5 in the neoplastic cases (p<0.01). In most non-neoplastic cases the inflammatory infiltrate was lymphoplasmacytic and in the neoplastic cases neutrophils predominated. Necrosis was scored 0-3 and revealed a score of 0.88+/-0.41 in the non-neoplastic and 1.47+/-0.5 in the neoplastic cases (p<0.01). The average number of mitoses over 10 high power fields per nodule was 1.31+/-1.55 in the non-neoplastic compared to 42.85+/-30.79 in the neoplastic cases (p<0.01). The average number of multinucleated giant cells over 10 high power fields per nodule was 0.9+/-1.45 in the non-neoplastic compared to 13.9+/-14.66 in the neoplastic cases (p<0.01). In the non-neoplastic cases, collagen, immature fibroblasts and fibroblast activation (excessively plump euchromatic nuclei with single or multiple prominent nucleoli) were scored 0-3 and a combined score, fibroblasts+activation score-collagen was calculated. The non-neoplastic cases were divided into a combined score of 1 (n=27). The 2 groups had similar scores for inflammation and necrosis, but were significantly different (p<0.01) in mitotic index (0.26+/-0.46 vs. 1.89+/-1.65) and number of multinucleated cells (0 vs. 1.4+/-1.6). These results indicate 2 stages in the non-neoplastic nodules: early inflammation, characterized by fibrocytes and abundant collagen, and a pre-neoplastic stage, characterized by activated fibroblasts and reduced collagen.

A novel phospholipid derivative of indomethacin, DP-155 [mixture of 1-steroyl and 1-palmitoyl-2-{6-[1-(p-chlorobenzoyl)-5-methoxy-2-methyl-3-indolyl acetamido]hexanoyl}-sn-glycero-3-phosophatidyl [corrected] choline], shows superior safety and similar efficacy in reducing brain amyloid beta in an Alzheimer's disease model.

Indomethacin has been suggested for the treatment of Alzheimer's disease (AD), but its use is limited by gastrointestinal and renal toxicity. To overcome this limitation, D-Pharm Ltd. (Rehovot, Israel) developed DP-155 (mixture of 1-steroyl and 1-palmitoyl-2-{6-[1-(p-chlorobenzoyl)-5-methoxy-2-methyl-3-indolyl acetamido] hexanoyl}-Sn-glycero-3-phosophatidyl [corrected] choline), a lecithin derivative of indomethacin. Safety was tested by daily oral administration of DP-155 or indomethacin to rats in a dose range of 0.007 to 0.28 mmol/kg. The prevalence of gastrointestinal ulceration was significantly lower (10-fold) for DP-155 than for indomethacin, and the ulcerations were delayed. Signs of renal toxicity, namely reduced urine output and increased urine N-acetyl glycosaminidase to creatinine ratio, were 5-fold lower for DP-155. Indomethacin, but not an equimolar dose of DP-155, reduced urine bicyclo-prostaglandin E(2). An equimolar oral dose of DP-155 or indomethacin, administered every 4 h for 3 days, was equally efficacious in reducing the levels of Abeta42 in the brains of Tg2576 mice. Indomethacin was the principal metabolite of DP-155 in the serum. After DP-155 oral administration, indomethacin's half-life in the serum and the brain was 22 and 93 h, respectively, compared with 10 and 24 h following indomethacin oral administration. The brain to serum ratio was 3.5 times higher for DP-155 than indomethacin. This finding explains the efficacy of DP-155 in reducing Abeta42 brain levels, despite the low systemic blood concentrations of indomethacin derived from DP-155. In conclusion, compared with indomethacin, DP-155 has significantly lower toxicity in the gut and kidney while maintaining similar efficacy to indomethacin in lowering Abeta42 in the brains of Tg2576 mice. This superior safety profile highlights DP-155's potential as an improved indomethacin-based therapy for AD.

Congenital narrowing of the intrapharyngeal opening in a dog with concurrent oesophageal hiatal hernia.

A one-year-old, male, smooth-haired standard dachshund was presented with a history of chronic hypersalivation, dysphagia, puffing of the cheeks on expiration, and inspiratory stridor. Oral examination revealed a moderately thickened tongue radix and that the normal intrapharyngeal opening was obliterated. A 7 mm long, midline palatal slit was the only communication between the naso- and oropharynx. The soft palate was fused to the caudal pharyngeal wall. A concurrent hiatal hernia was diagnosed on thoracic radiographs. The soft palate abnormality was surgically corrected and the hiatal hernia was managed medically. On follow-up evaluations, the clinical signs had markedly improved, and the hiatal hernia was no longer visible on survey thoracic radiographs.

Effect of electrocardiographic filters on the R-amplitude of canine electrocardiograms.

Lead II electrocardiograms (ECGs) were recorded in 88 dogs ranging in weight from 3 to 50 kg. A commercial direct-writing electrocardiograph was used to record the ECGs, first with manual HUM filter (notch filter at 50/60 Hz) and EMG filter (cut-off frequency of -3 dB at 35 Hz) on, immediately followed by a recording with both filters off. The mean (sd) reduction in R-amplitude with the filters on was 53(18) per cent with a range from 22 to 100 per cent and a median value of 51 per cent. The R-amplitude with the filters off was related to the R-amplitude with the filters on, making it possible to correct for the effect of the filters. The reduction in R-amplitude was inversely correlated with the weight of the dog and with the duration of the QRS-complex. Other known changes induced by filters, such as the elimination of notches and the slurring of the junction between the QRS-complex and the ST-interval were also observed. The inverse relationship between the weight of the dog and the magnitude of the reduction in R-amplitude by the filters indicates that ECG machines with different characteristics should ideally be used to record ECGs in dogs of different sizes.

Radiographic and computed tomographic changes and clinical presentation of spirocercosis in the dog.

A retrospective study of 39 dogs with spirocercosis is described, emphasizing radiographic and computed tomographic aspects and clinical presentation. Dogs were classified as complicated or uncomplicated, both clinically and radiographically. Besides the expected upper gastrointestinal signs, a high incidence of respiratory (77%) and locomotor (23%) complications were present. All dogs had thoracic radiographs. Esophageal masses were radiographically classified as typical or atypical according to their location. Twenty-seven dogs had a typical caudal esophageal mass. Six dogs had a mass atypically located in the hilar region. These masses were smaller and more difficult to visualize radiographically. The remaining 6 dogs did not have a radiographically detectable esophageal mass. Radiology as an initial diagnostic tool was effective in detecting and localizing the mass and to detect early respiratory abnormalities such as pleuritis, mediastinitis, pneumonia, and bronchial displacement. Endoscopy was the modality of choice to confirm antemortem esophageal masses. In dogs where the mass filled the whole esophageal lumen, endoscopy failed to give essential information necessary for surgical excision of neoplastic masses, such as the extent of esophageal wall attachment. Caudal esophageal sphincter involvement was difficult to determine endoscopically with large caudal esophageal masses. Computed tomography was performed on 3 dogs and did not address the latter problems completely, but was found to be a sensitive tool to detect focal aortic mineralization and early spondylitis, both typical for the disease, and essential in the diagnosis of non- or extramural esophageal abnormalities.

Chronic idiopathic intestinal pseudo-obstruction in an English bulldog.

A case of chronic idiopathic intestinal pseudo-obstruction in an English bulldog is described. The dog was presented with chronic weight loss and vomiting. An intestinal obstruction was suspected based on clinical and radiological findings. A diagnosis of chronic idiopathic intestinal pseudo-obstruction was made on the basis of full thickness intestinal biopsies. The dog was refractory to any antiemetic therapy. Necropsy revealed marked atrophy and fibrosis of the tunica muscularis, together with a mononuclear cell infiltrate extending from the duodenum to the colon. This case was presented with clinical findings consistent with visceral myopathy in humans--namely, atony and dilatation of the whole gut--but the histological findings resembled sclerosis limited to the gastrointestinal tract.

Magnetic resonance imaging of otitis media in a dog.

Otitis media/interna was diagnosed in a 20-month-old German shepherd with the assistance of magnetic resonance (MR) imaging. The MR images were acquired primarily to exclude a brain lesion responsible for vestibular signs. No brain lesion was detected, but obvious signs of chronic changes in the left bulla and external ear canal were confirmed. Thickening of the epithelium and soft tissue surrounding the external ear canal and a laminated appearance of high and low T2 intensities in the tympanic bulla's mucosa were present. The hypointense lines were suspected to be fibrous tissue, indicating chronic changes. This report suggests that MR imaging may serve as a useful imaging tool for otitis media and that it supplies information not obtained with radiography or computed tomography.

A histological and carbon perfusion study of cephalic and saphenous venous flaps in the dog.

A histological and carbon-infusion study of cephalic and saphenous venous flaps in the dog shows that cephalic flaps survive significantly better than saphenous flaps, their mean viability at 5-14 days being 50-60% compared to 23.8% for saphenous flaps. Venous drainage is essential for flap survival but perfusion of the cephalic vein with arterial blood does not alter flap viability. The findings indicate that cephalic flaps survive better because they are thinner and contain a more extensive venous plexus. A cephalic flap is a suitable model for in vivo study of the circulation within a venous flap.

Biochemical analysis of the venous flap in the dog.

There has been great interest stimulated by reports on factors influencing the survival of skin flaps which possess only venous inflow and outflow, i.e., venous flaps. The present study serially (Days 1, 2, and 4 postoperatively) observed several biochemical factors which might affect flap survival. ATP levels were measured to assess endogenous energy stores, malonyldialdehyde (MDA) and xanthine oxidase (XO) to estimate free radical production, superoxide dismutase (SOD) to quantify antioxidant defenses, and edema to measure inflammatory changes. Eighteen thighs on nine dogs were assigned randomly to one of three groups: full-thickness skin grafts, flaps based solely on the saphenous artery and vein (AV flaps), or flaps based solely on the saphenous vein (venous flaps). These were regarded as being mostly ischemic, totally perfused, and partially ischemic, respectively. Control skin biopsies were obtained adjacent to surgical sites. AV flaps and control skin were similar in all respects. Venous flaps compared with skin grafts were significantly less edematous (P less than 0.01) had less MDA and XO (P less than 0.05), but no significant differences in SOD and ATP levels. However venous flaps had significantly less ATP than AV flaps (P less than 0.01). Thus venous flaps survive despite depletion of ATP levels. These results suggest that decreased free radical production and lessened edema may be important factors in promoting ultimate survival of venous flaps.

Prefabrication of thin transferable axial-pattern skin flaps: an experimental study in rabbits.

The arteriovenous pedicle of all known axial-pattern skin flaps enters from the deep aspect and consequently the flap must contain fat and/or muscle and be of considerable thickness. In an attempt to fabricate a thinner axial-pattern flap the femoral artery and vein of rabbits were implanted, in various vascular configurations, directly into the subdermal layer of the skin. Implantation was found to provoke an extensive outgrowth of new vessels from the implanted artery and vein, and the progress and pattern of this neovascularisation was studied by carbon gelatine perfusion and histology. Neovascularisation begins within a few days of implantation and progresses rapidly. By 8 to 12 weeks it is possible to elevate regularly a viable, large skin flap based on the implanted pedicle.

Microsurgical transfer of the greater omentum in the treatment of canine obstructive lymphoedema.

In 13 dogs, experimental obstructive lymphoedema of the lower limb was created by combined radiotherapy and radical groin dissection. Six months later, when the degree of lymphoedema was stable, the lymphatic obstruction was bridged by microvascular insertion of a free omental graft. Six months after grafting, circumferential measurements indicated a statistically significant 38% reduction in the magnitude of lymphoedema. Biopsies showed the omental grafts were alive but contained much fibrous tissue. Lymphatic vessels were identified in 10 of 11 biopsies but connections between these lymphatics and lymphatics proximal to the graft could not be demonstrated by either lymphangiography or dye-injection techniques. The findings indicate that experimental obstructive lymphoedema in the dog can be reduced significantly by insertion of a vascularised omental graft. However, it could not be established that improvement was due to union of graft lymphatics with those of the lymphoedematous limb, although this union may have consisted of lymphatics too small to be demonstrated.

Long-term results after microlymphaticovenous anastomoses for the treatment of obstructive lymphedema.

Over the last 14 years, 134 patients with obstructive lymphedema have been treated with microlymphaticovenous anastomoses. Ninety patients were available for long-term follow-up study. Of these, 52 patients were treated by microlymphatic surgery only and 38 of them also had segmental or radical reduction surgery, either at the same time or secondarily. Objective assessment was undertaken by volume and circumferential measurements. Initially, lymphangiography was used, but a study demonstrated increased edema immediately following the investigation in one-third of the patients and it was abandoned, both preoperatively and postoperatively. In the microlymphaticovenous anastomoses only group (N = 52), subjective improvement occurred in 38 patients (73 percent). Objectively, volume changes showed a significant improvement in 22 patients (42 percent), with an average reduction of 44 percent of the excess volume. In the microlymphaticovenous anastomoses and reduction surgery, usually segmental, group (N = 38), subjective improvement occurred in 30 patients (78 percent) and objective improvement occurred in 23 patients (60 percent), with an average reduction of 44 percent of the excess volume. Of those followed up, 67 patients (74 percent) have been able to discontinue the use of conservative measures, with an average follow-up of 4.0 years and average reduction in excess volume of 26 percent. There was a 58 percent reduction in the incidence of cellulitis following surgery. In those patients who were improved, drainage resulted in increased softness of the limbs. Edema of the hand diminished considerably in most patients, although this was difficult to measure. These long-term results indicate that microlymphaticovenous anastomoses have a valuable place in the treatment of obstructive lymphedema and should be the treatment of choice in these patients. Reduction surgery can be used as an adjunct in some of these patients, especially in the posteromedial aspect of the upper arm. Liposuction has been used in failed cases or in patients in whom no lymphatics could be found. Improved results can be expected with earlier operations because patients referred earlier usually have less lymphatic disruption.