Polyamine inhibitors for treatment of feline oral squamous cell carcinoma: a proof-of-concept study.

This study assessed proof-of-concept for use of polyamine inhibitor 2-diluoromethylornithine (DFMO) as a treatment for oral squamous cell carcinoma (SCC) in client-owned cats. Polyamine levels in tumor tissue and normal oral mucosa were quantified before and after treatment. DFMO was administered orally to 14 client-owned cats with histologically confirmed oral SCC. Patients were monitored for gastrointestinal, dermatologic, auditory, hematological, and biochemical abnormalities. Total polyamine levels in tumor tissue decreased after treatment, as did the specific polyamine putrescine in both tumor tissue and normal mucosa. Ototoxicity was observed in 5 of 6 cats receiving pre- and post-treatment brainstem auditory evoked potential tests. Subclinical thrombocytopenia was observed in 6 of 14 cats. One cat showed mild post-anesthetic tremors that resolved without treatment. Oral administration of DFMO at doses used in this study resulted in significantly decreased tumor polyamine levels without life-threatening clinical or hematological toxicities. Further studies are warranted to explore pathophysiology of polyamine biochemistry and use of polyamine inhibitors in treatment of cats with oral SCC.

Outcome and toxicity associated with a dose-intensified, maintenance-free CHOP-based chemotherapy protocol in canine lymphoma: 130 cases.

A dose-intensified/dose-dense chemotherapy protocol for canine lymphoma was designed and implemented at the Veterinary Hospital of the University of Pennsylvania. In this study, we describe the clinical characteristics, prognostic factors, efficacy and toxicity in 130 dogs treated with this protocol. The majority of the dogs had advanced stage disease (63.1% stage V) and sub-stage b (58.5%). The median time to progression (TTP) and lymphoma-specific survival were 219 and 323 days, respectively. These results are similar to previous less dose-intense protocols. Sub-stage was a significant negative prognostic factor for survival. The incidence of toxicity was high; 53.9 and 45% of the dogs needed dose reductions and treatment delays, respectively. Dogs that required dose reductions and treatment delays had significantly longer TTP and lymphoma-specific survival times. These results suggest that dose density is important, but likely relative, and needs to be adjusted according to the individual patient's toxicity for optimal outcome.

Cystosonographic measurements of canine bladder tumours.

The purpose of this study was to evaluate the variability of cystosonographic bladder tumor measurements with both operator and bladder volume changes. Ten dogs with bladder tumors were included. In each dog, three operators determined tumor dimensions for three different bladder volumes. Intraclass correlation coefficient was used to assess operator reliability. Response Evaluation Criteria in Solid Tumors (RECIST) and greater than or equal to 50% differences in tumor measurements were used as guidelines. Poor to fair correlations between operators were found for the different tumor dimensions (r(I) = 0.4 - 0.7). The percent differences in tumor dimensions with operator and bladder volume changes were significant enough to misclassify the tumors into the categories of partial response (PR) or progressive disease (PD). These results suggest that cystosonographic measurements of bladder tumors are affected by both changes in operator and bladder volume, and the discrepancies are significant enough to change response classification.

Canine mammary gland tumours; a histological continuum from benign to malignant; clinical and histopathological evidence.

This study describes the clinical and histopathological findings in dogs with mammary gland tumours, and compares the histopathological and clinical evidence consistent with progression from benign to malignant to human breast cancer epidemiology. Clinical and histopathological data on 90 female dogs with 236 tumours was included. Dogs with malignant tumours were significantly older than dogs with benign tumours (9.5 versus 8.5 years), P = 0.009. Malignant tumours were significantly larger than benign tumours (4.7 versus 2.1 cm), P = 0.0002. Sixty-six percent had more than one tumour, and evidence of histological progression was noted with increasing tumour size. Dogs with malignant tumours were significantly more likely to develop new primary tumours than dogs with benign tumours, P = 0.015. These findings suggest that canine mammary tumours progress from benign to malignant; malignant tumours may be the end stage of a histological continuum with clinical and histopathological similarities to human breast carcinogenesis.

Dacarbazine as single-agent therapy for relapsed lymphoma in dogs.

BACKGROUND: Multidrug resistance is the most common cause of treatment failure in dogs with multicentric lymphoma. 5-(3,3-Dimethyl-1-triazeno)-imidazole-4-carboxamide (DTIC) is an atypical alkylator used as standard treatment in human Hodgkin's lymphoma, and has been effective in combination treatment to treat resistant lymphoma in dogs. However, no data are available on the use of DTIC as a single agent in the treatment of relapsed canine lymphoma. HYPOTHESIS: Single-agent DTIC is effective and safe in treating dogs with lymphoma that relapsed or failed to respond to previous chemotherapy. ANIMALS: Forty client-owned dogs with relapsed lymphoma. METHODS: Dogs were eligible for the retrospective study if they had a histologically or cytologically confirmed diagnosis of lymphoma and had relapsed. Dogs received DTIC (800-1,000 mg/m(2) every 2-3 weeks as a 4-5-hour IV infusion) and were evaluated for response rate and duration. Hematologic and gastrointestinal toxicity was assessed. RESULTS: The overall response rate for dogs being treated with DTIC was 35% (14 dogs) with a median progression-free interval of 43 days. Thirteen dogs had a partial response and 1 dog had a complete response. Stable disease was achieved in 3 dogs. Mild gastrointestinal toxicity was reported in 3 dogs posttreatment. Thrombocytopenia was the principal toxicity observed 7-14 days after the treatment. Treatments were delayed because of thrombocytopenia. CONCLUSIONS: DTIC, when used alone, is effective in the treatment of dogs with relapsed lymphoma.

Cytological lymph node evaluation in dogs with mast cell tumours: association with grade and survival.

The purpose of this retrospective cohort study is to describe the association of cytological assessment of lymph node metastasis with survival and tumour grade in dogs with mast cell tumours. Regional lymph node aspirates of 152 dogs diagnosed with a mast cell tumour were reviewed and classified according to specific cytological criteria for staging. 97 dogs (63.8%) had stage I tumours, and 55 (36.2%) had stage II tumours. Stage II dogs had a significantly shorter survival time than dogs with stage I disease (0.8 and 6.2 years, respectively; P < 0.0001). Dogs with grade III mast cell tumours were more likely to have stage II disease (P = 0.004). These results suggest that cytological evaluation of lymph nodes in dogs with mast cell tumours provides useful and valuable clinical information, and the results correlate with tumour grade and outcome thus providing a practical and non-invasive method for staging.

Evaluation of adjuvant doxorubicin-based chemotherapy for the treatment of feline mammary carcinoma.

BACKGROUND: Feline mammary carcinomas (FMC) are locally invasive and highly metastatic tumors. Because of the high metastatic potential, patients often are treated with adjuvant doxorubicin-based chemotherapy, but little data exist to evaluate the effect of this strategy. HYPOTHESIS: Adjuvant doxorubicin-based chemotherapy improves outcome for FMC compared with surgery alone. ANIMALS: Cats with naturally occurring, biopsy-confirmed FMC treated with either surgery alone (Sx) or with surgery plus adjuvant doxorubicin-based chemotherapy (Sx + Chemo). METHODS: Retrospective cohort study. Clinical data were collected and compared to identify differences between groups. Outcome results were determined and compared. Prognostic factors for disease-free survival (DFS) and overall survival were evaluated. RESULTS: Seventy-three cats were evaluated, of which 37 were in the Sx group and 36 in the Sx + Chemo group. No differences in clinical data were found between Sx and Sx + Chemo groups. Median DFS times for the Sx and Sx + Chemo groups were 372 and 676 days, respectively (P= .15) and median survival times (ST) were 1,406 and 848 days, respectively (P= .78). For cats that underwent a unilateral radical mastectomy, ST was significantly longer for the Sx + Chemo compared with the Sx group (1,998 versus 414 days, respectively; P= .03). CONCLUSIONS AND CLINICAL IMPORTANCE: This study did not find a benefit to adjuvant doxorubicin-based chemotherapy in cats with FMC. Additional studies are required to determine whether patient subgroups with negative prognostic factors may benefit from adjuvant chemotherapy.

Clinical characterization of cardiovascular abnormalities associated with feline mucopolysaccharidosis I and VI.

OBJECTIVE: The purpose of this study was to define the cardiovascular abnormalities present in young and adult cats affected with the lysosomal storage diseases mucopolysaccharidosis (MPS) I and MPS VI. METHOD: Eighteen cats affected with MPS I and 10 cats affected with MPS VI were evaluated by physical examination, electrocardiography and echocardiography. Electrocardiography (ECG) was performed on all MPS I and 9 of the MPS VI cats. Twelve unaffected cats underwent complete examinations for comparison purposes. RESULTS: No cardiovascular abnormalities were noted on physical examination. Measured ECG intervals were normal in affected cats; however, sinus arrhythmia was noted more frequently than in the unaffected cats. Significant echocardiographic abnormalities included aortic valve thickening, regurgitation and aortic root dilation. Significant mitral valve thickening was also noted. The severity of changes increased in older affected cats. CONCLUSION: As affected animals increased in age, more cardiac abnormalities were found with increasing severity. Significant lesions included the mitral and aortic valves and ascending aorta, but myocardial changes were not recognized. MPS I and MPS VI cats have similar cardiovascular findings to those seen in children and constitute important models for testing new MPS therapies.

Secondary intracranial neoplasia in the dog: 177 cases (1986-2003).

BACKGROUND: This study investigates the frequency, location, and clinical findings associated with 177 secondary brain tumors in dogs. HYPOTHESIS: Secondary intracranial neoplasia is more common than primary intracranial neoplasia in dogs during the time period studied, and hemangiosarcoma (HSA) is the most common secondary intracranial tumor. ANIMALS: One hundred and seventy-seven client-owned dogs presented to the Matthew J. Ryan Veterinary Hospital between 1986 and 2003. METHODS: Medical records were searched for a diagnosis of intracranial neoplasia in dogs who underwent complete postmortem examination. Of these dogs, those with a diagnosis of primary intracranial neoplasia were excluded. RESULTS: Of the 177 secondary brain tumors, 51 (29%) were HSAs, 44 (25%) were pituitary tumors, 21 (12%) were lymphosarcomas, and 21 (12%) were metastatic carcinomas. The average age at diagnosis was 9.6 +/- 3.0 years. Most tumors were located in the cerebrum, and a mentation change was the most common presenting clinical sign. On postmortem examination, the same tumor that was in the brain was also present in the lung in 84 cases (47%), in the kidney in 62 cases (35%), and in the heart in 55 cases (31%). CONCLUSIONS AND CLINICAL IMPORTANCE: Secondary intracranial neoplasia in dogs was more common than primary intracranial neoplasia during the time period studied. Many of these dogs had related disease in other body systems that was apparent on diagnostic tests such as thoracic radiography.

Description of clinical and pathological findings, treatment and outcome of feline large granular lymphocyte lymphoma (1996-2004).

Feline large granular lymphocyte (LGL) lymphoma is an uncommon, morphologically distinct variant of feline lymphoma. Limited information exists in the literature regarding pathological and immunohistochemical descriptions, clinical findings, treatment and survival times. The purpose of this study was to describe clinical features, treatment and outcome in feline LGL lymphoma. Medical records of 45 cats with LGL lymphoma were retrospectively evaluated. Decreased appetite/anorexia, weight loss, lethargy and vomiting were the most commonly reported clinical signs. All cats tested for feline leukaemia virus and feline immunodeficiency virus infection were negative. The mesenteric lymph nodes and small intestine were the most commonly affected organs. One complete response and six partial responses were noted in the 23 cats that received chemotherapy as their initial treatment. Median survival time for cats that were treated was 57 days. Based on these results, feline LGL lymphoma appears to be minimally responsive to chemotherapy and is associated with a grave prognosis.

Cutaneous neoplasms in pet rabbits: a retrospective study.

Over a 16-year period, 190 tumors and tumorlike lesions from 179 pet rabbits were submitted for histopathologic examination. A total of 23 different tumor types and 1 tumorlike lesion were diagnosed. The most common diagnoses were trichoblastoma, collagenous hamartoma, and Shope fibroma. Viral-induced tumors were Shope fibroma (19) and Shope papilloma (2). Common nonviral epithelial tumors included trichoblastoma (59), squamous cell carcinoma (5), squamous papilloma (4), trichoepithelioma (3), and apocrine carcinoma (3). Common mesenchymal tumors were lipoma (10), liposarcoma (3), myxosarcoma (9), malignant peripheral nerve sheath tumor (8), fibrosarcoma (7), and leiomyosarcoma (4). Malignant melanoma was diagnosed in 8 rabbits. Collagenous hamartomas were diagnosed in 26 rabbits. Mesenchymal proliferations occurred significantly more often in male rabbits than in females. Collagenous hamartomas and myxosarcomas occurred exclusively in male animals, and 3 rabbits had multiple collagenous hamartomas. Immunohistochemistry was applied in cases in which a definite diagnosis could not be reached on hematoxylin and eosin slides. Follow-up information was received in 19 cases. Carcinomas recurred (2 of 3) or metastasized (1 of 3), whereas sarcomas frequently recurred (7 of 12). One malignant melanoma (1 of 3) and one poorly differentiated round cell neoplasm recurred (1 of 1). This is the first comprehensive retrospective analysis on skin neoplasia in pet rabbits.

Characterization of the biological behaviour of appendicular osteosarcoma in Rottweilers and a comparison with other breeds: a review of 258 dogs.

The purpose of this retrospective study was to compare Rottweilers diagnosed with osteosarcoma (OSA) with other breeds to determine whether Rottweilers experienced a more aggressive form of the disease. Two hundred and fifty-eight dogs were evaluated (102 clinical and 156 necropsy cases). In the necropsy population, Rottweilers had a younger mean age at death (7.3 versus 9 years, P = 0.006). There were no significant differences between Rottweilers and other breeds in age at diagnosis, median disease-free interval or survival time. However, Rottweilers were more likely to have metastasis to the brain (7 versus 0%, P = 0.03). These results suggest that OSA in Rottweilers may have a different biological behaviour, but this study did not confirm that these differences were associated with a worse outcome.

Complications and radiographic findings following cemented total hip replacement: a retrospective evaluation of 97 dogs.

Cemented total hip replacement (cTHR) is commonly performed to treat intractable coxofemoral pain in dogs. While owners generally perceive a good outcome after the procedure, the longevity of the implant may be limited by complications such as infection and aseptic loosening. The objective of this retrospective study was to identify the prevalence of complications and radiographic changes following cTHR, and to identify factors that may predispose to a need for revision surgery. Medical records and radiographs from 97 dogs that underwent cTHR were evaluated for signalment, preoperative degree of osteoarthritis, technical errors, intra-operative culture results, and the post-operative radiographic appearance of the implant. The complications occurring in the intra-operative and short-term (eight week) time period were recorded. Mean (+/- SD) follow-up time was 1.1 +/- 1.6 years (range: 0-7.7 years). Seven dogs had a short-term complication and a revision surgery was performed in eleven dogs. Osseous or cement changes were radiographically detectable in the majority of cTHR. Eccentric positioning of the femoral stem and the presence of radiolucent lines at the femoral cement-bone interface were positively associated with the occurrence of revision surgery. The clinical significance of the periprosthetic radiographic changes is unclear and further investigation is warranted.

Cyclooxygenase-2 expression is associated with histologic tumor type in canine mammary carcinoma.

Cyclooxygenase-2 (COX-2) is an inducible member of the family of cyclooxygenase enzymes that has been implicated in the genesis of numerous cancers. The role of COX-2 in canine mammary neoplasia remains to be more clearly elucidated. The goal of the study reported here was to determine whether a direct association between levels of COX-2 expression and tumor histologic subtype exists in canine mammary carcinoma. Immunohistochemical analysis was performed using a polyclonal antiprostaglandin G/H synthase 2 IgG COX-2 antibody. Sections from the kidneys of young dogs, which stain positive for COX-2 in the macula densa, served as positive controls. Slides were reviewed by a single pathologist, and were evaluated for COX-2 expression according to previously established scales. Positive-staining tumors were given a COX-2 staining distribution (on the basis of the percentage of positive staining cells in five 400x fields) and intensity score according to previously established scales. The product of the COX-2 staining distribution and intensity scores was calculated to create a COX-2 staining index. COX-2 expression was detected in 28 of 50 (56%) samples evaluated. Anaplastic carcinomas had a significantly higher COX-2 staining distribution, intensity, and index, compared with those for adenocarcinomas (P < 0.0001). The overall percentage of positive tumors (56%) was consistent with that of prior studies. To the authors' knowledge, these results indicate, for the first time, a direct association between COX-2 expression and tumor histologic subtype in canine mammary carcinomas. Future research directed at measuring tumor response in canine mammary carcinoma patients treated with a selective COX-2 inhibitor is indicated.

Humoral measurement of type-1 hypersensitivity reactions to a commercial Malassezia allergen.

Malassezia pachydermatis is considered to be a contributing factor to canine atopic dermatitis (AD). The purpose of this study was to investigate the humoral response to a commercially produced M. pachydermatis extract. Fifteen atopic dogs with Malassezia overgrowth on the skin (MD), 16 atopic dogs without MD, three atopic dogs with overgrowth of Malassezia in the ears only (MO), and 12 normal dogs were intradermally tested with M. pachydermatis extract at 50, 100, 250, 500, 1000, 2000 and 4000 PNU mL(-1). All dogs were evaluated cytologically by cutaneous tape strip and bilateral ear exudate sampling to determine presence of MD or MO. Each had serum evaluated for anti-Malassezia IgE using three Malassezia extracts with an ELISA assay. The irritant threshold concentration at which healthy nonatopic dogs ceased to react was 1000 PNU mL(-1). There was a significant difference in intradermal test reactivity between the atopic groups. At this dilution, 93% (14/15) of the atopic MD group, 31% (5/16) of the atopic group without MD or MO, and 100% (3/3) of the atopic MO only group reacted. There were no significant differences in the serum IgE levels as measured by the Greer ELISA assay, between any groups using any of the three extracts. These results support that Greer's M. pachydermatis extract is useful for intradermal testing of dogs with an allergic phenotype, and that atopics with MD are more likely to have a type-1 Malassezia hypersensitivity than those without. The ELISA assay may require further development in order to be useful for the diagnosis of Malassezia hypersensitivity.

Evaluation of cyclooxygenase-1 and cyclooxygenase-2 expression and the effect of cyclooxygenase inhibitors in canine prostatic carcinoma.

Prostatic carcinoma occurs primarily in older castrated male dogs and is typically a fatal disease (most dogs die within few months after the initial diagnosis). Surgery, i.e., total prostatectomy, or radiation therapy is often not pursued due to risks of complications and a high rate of distant metastasis. Cyclooxygenase-2 (Cox-2) expression has been documented in several malignancies, including canine prostatic carcinoma. Cox-2 inhibition has been reported to have preventative effects on several human malignancies and has therapeutic effects on both laboratory and spontaneous tumour models. The purpose of this retrospective study was to evaluate Cox expression and the effects of Cox inhibitors on survival in dogs with prostatic carcinoma. 94.1 and 88.2% of the tumours expressed Cox-1 and Cox-2, respectively. Furthermore, dogs treated with Cox inhibitors (piroxicam or carprofen) lived significantly longer than untreated dogs, 6.9 versus 0.7 months (P < 0.0001), suggesting that Cox inhibitors may have an important role in canine prostate cancer therapy.

Immunohistochemical characterization of canine prostatic carcinoma and correlation with castration status and castration time.

The purpose of this study was to characterize canine prostate cancer using immunohistochemical staining specific for acinar and urothelial/ductal tissue and correlate these results with the dogs' castration status/castration time. Seventy dogs with prostate cancer were included, 71% were castrated and 29% were intact. Compared with an age-matched control population, castrated dogs were at increased risk of prostate cancer, odds ratio 3.9. Immunohistochemical staining was performed on 58 cases. Forty-six of the 58 stained positive for cytokeratin 7 (CK 7) (ductal/urothelial origin) and one of the 58 stained positive for prostate-specific antigen. Dogs with CK 7-positive tumours were younger when castrated than dogs with CK 7-negative tumours, 2 versus 7 years (P = 0.03); dogs castrated at

Comparison of CT scanograms and cephalometric radiographs in craniofacial imaging.

OBJECTIVE: To compare measurements from human skulls and their images from cephalometric radiographs (CR) and computed tomography (CT) scanograms, in order to gauge the potential clinical use of the latter. DESIGN: Based on specific inclusion criteria, including stable centric occlusion, 13 adult skulls were selected from a larger collection. The mandible was taped to the maxilla after securing the occlusion of teeth and condylar seating in the glenoid fossa. Lateral and posteroanterior cephalographs and CT 'scout views' were taken of each skull by standardized methods. Landmarks were identified on skulls and images. OUTCOME MEASURES: Linear measurements were made on all three records; angular measurements only on CR and CT images. Intraclass correlation coefficients (r) were calculated to assess similarity among records. Paired t-tests were used to compare differences between mean measurements. RESULTS: No statistically significant differences were noted between mean angular values on CR and CT views (P > 0.05). The highest correlations were observed for several vertical midline distances between CT and direct skull measures: 0.82 < r < 0.995-greatest for nasion-menton. For sagittal distances, the highest correlation was between the direct measure of condylion-pogonion and its CR image (r= 0.73). Correlations between CR and skull transverse measures were higher (0.46 < r < 0.80) than the corresponding skull vs. CT measures (0.06 < r < 0.38). CT and CR images are 2D slices and projections, respectively, of 3D structures. Vertical CT and skull measures correspond because the CT projection reflects a 1:1 ratio in the midsagittal plane; CT projected lateral images are smaller than the skull measures. The CR image reflects a distortion (approximately 8%) that brings Co-Pg closer to its anatomic distance, inadvertently contributing to better clinical planning, particularly in orthognathic surgery. The pattern of distortion of PA images was in opposite directions for CR and CT views. CONCLUSIONS: Cephalograms and CT scanograms are close in depicting angular relations of structures, but they differ in the accuracy of imaging linear measurements, because the location and size of an object within the imaged 3D structure varies with both records. Logistic and economic considerations favor the use of cephalographs.

The effect of written informed consent on detection of violence in the home.

UNLABELLED: Studies of programmatic interventions for victims of violence in the home may require the use of informed consent. The use of informed consent may result in ascertainment bias, with victims of violence being less likely to participate. OBJECTIVE: To investigate the effect of written informed consent on the detection of violence in the home during emergency department (ED) screening. METHODS: The authors performed a nonrandomized, controlled trial of 3,466 patients at an urban university ED. On odd days, patients (n = 1,857) were read a brief scripted statement and screened using standardized questions. On even days, patients (n = 1,609) received standard written informed consent prior to the same screening questions (writ-IC). The main outcome was the number of cases of violence in the home detected using each screening protocol. RESULTS: Fewer writ-IC patients participated in screening (82% vs 92%; p < 0.001). Despite a higher refusal rate in the writ-IC group, there was no difference in the number of victims detected by each screening method: choked/kicked/bit/punched? (writ-IC, 7.3 vs routine screen, 6.5%; p = 0.3); slapped/grabbed/shoved? (7.3 vs 6.7%; p = 0.4); threatened/actually used knife/gun to scare/hurt you? (8.3 vs 9.4%; p = 0.3); thrown object to harm you? (5.2 vs 4.6%; p = 0.4); forced sex? (5.8 vs 4.7%; p = 0.15); or afraid current/former intimate partner would hurt you physically? (13.9 vs 11.9%; p = 0.9). CONCLUSIONS: A written informed consent process in screening for violence in the home is associated with a higher refusal rate than routine screening, but use of written informed consent does not result in a lower rate of detection for multiple forms of violence. The authors did not find any support for the hypothesis that the use of written informed consent would decrease detection of violence in the home.

Effect of molar rotation on arch length.

The aim of this study was to evaluate the effect of maxillary first molar rotation on arch length in patients whose Class II, division 1 malocclusion was treated with a straight-pull headgear. The sample included 19 children who represent a subset of a population enrolled for 2 years in a prospective clinical trial of Class II treatment. The inner bow was adjusted at monthly visits and the average distalizing force was 14-16 oz per side. Measurements were made with digital calipers on casts obtained at baseline and at a time point averaging 16 months (SD 3 months) into treatment. Molar movement was related to a coordinate system referenced to the midpalatal raphae and the occlusal plane through a palatal plug that could be transferred to successive casts of the same patient. Distances from the cusp tips were measured to the reference system. The distal and lateral displacement, and the rotation of the molars over time were then computed. High correlations were observed between molar rotation and tooth displacement (that is the net differential movement between the mesiobuccal - MB - and mesiopalatal - MP - cusps): r=0.9, p=0.0001 (left side); r=0.8, p=0.0001 (right side). The average rotation of the molar was 15.4 degrees (SE+/-3.80) on the left side and 10.8 degrees (SE+/-2.20) on the right side. The average differential displacements between the MB and MP cusps were 1.04 mm (SE+/-0.29) (left) and 0.73 mm (SE+/-0.23) (right). The differences between the two sides were not statistically significant. The molar rotation did not correlate with any of the following parameters: initial tooth position; initial distance between the MB and MP cusps as a correlate of molar anatomy; transverse (mostly buccal) movement of the MB and MP cusps; distal movement of the tooth, as measured by the total displacement of the MB and MP cusps. This study qualifies the relationship between molar rotation and increase in arch length. The mean total distal movement of the molar was larger (nearly 3 mm) than the average contribution of molar rotation to space gain (about 1 mm), suggesting that the distal movement of the tooth was a combination of rotation and translation (or tipping). The contribution of the molar rotation is more significant with a smaller total displacement of the tooth.