Effect of foot orthoses vs sham insoles on first metatarsophalangeal joint osteoarthritis symptoms: a randomized controlled trial.

OBJECTIVES: To compare contoured foot orthoses to sham flat insoles for first MTP joint OA walking pain. DESIGN: This was a participant- and assessor-blinded, sham-controlled, multi-centre randomized clinical trial set in community-based private practices. Eighty-eight adults aged ≥45 years with symptomatic radiographic first MTP joint OA were randomized to receive contoured foot orthoses (n = 47) or sham flat insoles (n = 41), worn at all times when wearing shoes for 12 weeks. Primary outcome was change in first MTP joint walking pain (11-point numerical rating scale (NRS), 0-10) over 12 weeks. Secondary outcomes included additional first MTP joint and foot pain measures, physical function, quality of life and physical activity. Separate linear regression models for primary and secondary outcomes on treatment group were fit, adjusting for the outcome at baseline and podiatrist. Other measures included adverse events. RESULTS: 88 participants were randomized and 87 (99%) completed the 12-week primary outcome. There was no evidence foot orthoses were superior to sham insoles for reducing pain (mean difference -0.3 NRS units (95% CI -1.2 to 0.6), p = 0.53). Similarly, foot orthoses were not superior to sham on any secondary outcomes. Sensitivity analyses yielded similar results. Adverse events were generally minor and transient. CONCLUSION: Contoured foot orthoses are no more effective than flat sham insoles for the clinical management of first MTP joint OA. Given the dearth of evidence on treatments for first MTP joint OA, further research is needed to identify effective management approaches for this common and debilitating condition.

Walking-related knee contact forces and associations with knee pain across people with mild, moderate and severe radiographic knee osteoarthritis: a cross-sectional study.

OBJECTIVE: To investigate knee contact forces (KCFs), and their relationships with knee pain, across grades of radiographic knee osteoarthritis (OA) severity. DESIGN: Cross-sectional exploratory analysis of 164 participants with medial knee OA. Radiographic severity was classified as mild (grade 2), moderate (grade 3) or severe (grade 4) using the Kellgren & Lawrence (KL) scale. Walking knee pain was assessed using an 11-point numerical rating scale. External knee adduction moment (external KAM) and internal muscle forces were used to calculate medial, lateral and total KCFs using a musculoskeletal computational model. Force-time series across stance phase of gait were compared across KL grades using Statistical Parametric Mapping. Associations between KCFs and pain across KL grades were assessed using linear models. RESULTS: Medial KCFs during early and middle stance were higher in participants with KL3 and KL4 compared to those with KL2. In contrast, lateral KCFs were higher in those with KL2 compared to KL3 and KL4 in middle to late stance. The external loading component (i.e., KAM) of the medial KCF during middle to late stance was also greater in participants with KL3 and KL4 compared to those with KL2, whereas the internal (i.e., muscle) component was greater in those with KL3 and KL4 compared to KL3 during early stance. There were no associations between medial KCF and knee pain in any KL grade. CONCLUSIONS: Medial and lateral KCFs differ between mild, moderate and severe radiographic knee OA but are not associated with knee pain severity for any radiographic OA grade.

International Foot and Ankle Osteoarthritis Consortium review and research agenda for diagnosis, epidemiology, burden, outcome assessment and treatment.

OBJECTIVE: To summarise the available evidence relating to the diagnosis, epidemiology, burden, outcome assessment and treatment of foot and ankle osteoarthritis (OA) and to develop an agenda to guide future research. METHOD: Members of the International Foot and Ankle Osteoarthritis Consortium compiled a narrative summary of the literature which formed the basis of an interactive discussion at the Osteoarthritis Research Society International World Congress in 2021, during which a list of 24 research agenda items were generated. Following the meeting, delegates were asked to rank the research agenda items on a 0 to 100 visual analogue rating scale (0 = not at all important to 100 = extremely important). Items scoring a mean of 70 or above were selected for inclusion. RESULTS: Of the 45 delegates who attended the meeting, 31 contributed to the agenda item scoring. Nineteen research agenda items met the required threshold: three related to diagnosis, four to epidemiology, four to burden, three to outcome assessment and five to treatment. CONCLUSIONS: Key knowledge gaps related to foot and ankle OA were identified, and a comprehensive agenda to guide future research planning was developed. Implementation of this agenda will assist in improving the understanding and clinical management of this common and disabling, yet relatively overlooked condition.

The influence of sex and pre-operative obesity on biomechanics two years after total knee arthroplasty: A longitudinal cohort study.

BACKGROUND: Sex and obesity may influence knee biomechanics associated with poor outcomes following primary total knee arthroplasty (TKA) however their long-term impact has not been investigated. RESEARCH QUESTION: Does sex and/or pre-operative obesity influence change in gait biomechanics from pre-TKA to two-years after TKA, and do knee biomechanics return to normal two-years after TKA? METHODS: In this longitudinal study, gait analysis was performed on 78 patients undergoing TKA for knee osteoarthritis prior to surgery (baseline), and on 66 (85 %) of these who returned at the two year follow-up. Gait biomechanics were also collected on a reference sample of 40 asymptomatic participants. Knee variables were analyzed according to time (pre- and post-TKA), sex (men and women), pre-operative obesity (obese vs non-obese), and group (TKA vs reference). Mixed linear regression models were used to examine the effects of TKA, obesity status, gender and all interactions. RESULTS: There were two-year reductions in peak knee frontal plane angle (mean difference -7.21°; 95% confidence intervals -9.37 to -5.05), peak knee adduction moment (KAM) (-17.64Nm; -23.04 to -12.24) and KAM impulse (-9.40Nm.s; -12.04 to -6.77) in males. These and other variables were unchanged in women. At two years, men exhibited a greater varus-valgus thrust excursion (4.9°; 2.7-7.2), and a lower peak knee frontal plane angle (-4.4°; -7.1 to -1.7) and peak KAM (-13.1Nm; -20.9 to -5.4), compared to the reference sample. Biomechanics at two years did not differ between pre-operative obesity subgroups, or between female TKA patients and the reference sample. SIGNIFICANCE: Changes in gait biomechanics two years after TKA are influenced by sex but not obesity. Men but not women showed altered knee biomechanics two years following TKR and compared to a reference sample. It is unknown whether these altered biomechanics in men impact longer term clinical outcomes and satisfaction following surgery.

Management of foot/ankle osteoarthritis by Australian general practitioners: an analysis of national patient-encounter records.

OBJECTIVE: To document the management of foot/ankle osteoarthritis/arthritis (OA) by general practitioners (GP) in Australia. DESIGN: We analysed data from the Bettering the Evaluation and Care of Health Program April 2010-March 2016 inclusive. Patient and GP encounter characteristics were extracted. Data were classified by the International Classification of Primary Care, Version 2, and summarised using descriptive statistics and 95% confidence intervals (95% CIs) around point estimates. RESULTS: The dataset included 583,900 patient-encounter records among which foot/ankle OA was managed 621 times, at a rate of 1.1 per 1000 encounters, with an annual estimated 152,000 GP encounters nationally. The management rate was most frequent among patients aged 65-74 years (2.25 per 1000 encounters). Comorbidities were managed at a rate of 105.8 per 100 encounters, the most common being hypertension, and few being other musculoskeletal problems. Foot/ankle OA was mostly managed using medication (64.6 per 100 problems), with prescription rates far exceeding non-pharmacological strategies such as counselling, advice or education (17.7 per 100), or allied health referral (10.1 per 100). When considering specific health/medical professionals, patients were referred to orthopaedic surgeons 8.4 times per 100 foot/ankle problems, podiatrists 6.3 times per 100 foot/ankle problems, and physiotherapists 2.6 times per 100 foot/ankle problems. CONCLUSIONS: Pharmacological management rates of foot/ankle OA were high and substantially exceeded non-pharmacological management such as lifestyle advice and allied health referral. Longitudinal studies are needed to determine the effectiveness of this care compared to self-management and conservative non-drug treatment in people with foot/ankle OA.

Effects of sex and obesity on gait biomechanics before and six months after total knee arthroplasty: A longitudinal cohort study.

BACKGROUND: Gait biomechanics, sex, and obesity can contribute to suboptimal outcomes from primary total knee arthroplasty. The aims of this study were to i) determine if sex and/or obesity influence the amount of change in gait biomechanics from pre-surgery to six months post-surgery and; ii) assess if gait returns to normal in men and women. METHODS: Three-dimensional gait analysis was performed on 43 patients undergoing primary total knee arthroplasty for knee osteoarthritis (pre- and six months post-operative) and 40 asymptomatic controls. Mixed linear regression models were fit to assess which factors influenced change in gait biomechanics within the arthroplasty cohort, and interaction terms were included to assess if biomechanics returned to normal following surgery. FINDINGS: Male peak knee adduction moment (p < 0.001) and impulse (p < 0.001) decreased six months following arthroplasty, whilst gait in women remained unchanged after surgery. Obesity did not influence gait changes in men or women. Gait of female arthroplasty participants did not differ from female controls after surgery except for sagittal plane knee range of motion (p = 0.003), whilst men differed from controls for peak knee adduction moment (p = 0.011), knee range of motion (p < 0.001), and peak knee flexion moment (p < 0.001). INTERPRETATION: Sex, but not obesity, influenced changes in gait biomechanics after arthroplasty. Men retained abnormal gait patterns after surgery, whilst women did not. Further research should determine the long-term implications of gait abnormalities seen in men after arthroplasty.

Moderators and mediators of effects of unloading shoes on knee pain in people with knee osteoarthritis: an exploratory analysis of the SHARK randomised controlled trial.

OBJECTIVE: To investigate moderators and biomechanical mediators of effects of unloading shoes on knee pain in people with knee osteoarthritis (OA). METHODS: Exploratory analysis from 164 participants in a clinical trial comparing unloading (ASICS GEL-Melbourne OA) to conventional walking shoes. The primary outcome was 6-month change in knee pain (11-point numerical rating scale (NRS)). Moderators included baseline peak knee adduction moment (KAM), radiographic severity (Kellgren & Lawrence (KL) scale), body mass, foot posture, neuropathic pain and diffuse knee pain. Mediators included change in peak KAM and KAM impulse. RESULTS: Radiographic severity was the only moderator to interact with footwear group (P = 0.02). Participants with KL = 2 experienced greater pain reductions with conventional compared to unloading shoes (mean difference in change in pain -1.64 units, 95% CI -3.07, -0.21), while unloading shoes tended to result in greater pain reductions than conventional shoes in KL = 3 (0.98, 95% CI -0.44, 2.39) and KL = 4 (0.64, 95% CI -0.64, 1.93). No variable showed any significant mediating effect in the entire cohort. However, there was some evidence that unloading shoes may reduce pain through reductions in peak KAM (indirect effect -0.31, 95% CIs -0.65, 0.03; P = 0.07) in people with KL ≥ 3, compared to conventional shoes. CONCLUSION: Unloading shoes conferred additional symptomatic benefits over conventional shoes in people with moderate to severe knee OA. There was some evidence effects may be mediated by a reduction in peak KAM. However, we were underpowered for subgroup analyses. These patients may represent a subgroup to which biomechanical interventions designed to reduce the KAM may be more effectively targeted.

The influence of sex and obesity on gait biomechanics in people with severe knee osteoarthritis scheduled for arthroplasty.

BACKGROUND: Sex and body mass may influence knee biomechanics associated with poor total knee arthroplasty (TKA) outcomes for knee osteoarthritis (OA). This study aimed to determine if gait differed between men and women, and overweight and class I obese patients with severe knee OA awaiting TKA. METHODS: 34 patients with severe knee OA (average age 70.0 (SD 7.2) years, body mass index 30.3 (4.1kg/m2)) were recruited from a TKA waiting list. Three-dimensional gait analysis was performed at self-selected walking speed. Comparisons were made between men and women, and overweight (body mass index (BMI) 25.0-29.9kg/m2) and class I obese (BMI 30.0-34.9kg/m2) participants. Biomechanical outcomes included absolute and body size-adjusted peak knee adduction moment (KAM), KAM impulse, peak knee flexion moment, as well as peak knee flexion and varus-valgus angles, peak varus-valgus thrust, and peak vertical ground reaction force (GRF). FINDINGS: Men had a higher absolute peak KAM, KAM impulse and peak GRF compared to women, and this sex-difference in frontal plane moments remained after adjusting for body size. However, when additionally adjusting for static knee alignment, differences disappeared. Knee biomechanics were similar between obesity groups after adjusting for the greater body weight of those with class I obesity. INTERPRETATION: Men had greater KAM and KAM impulse even after adjustment for body size; however adjustment for their more varus knees removed this difference. Obesity group did not influence knee joint kinematics or moments. This suggests sex- and obesity-differences in these variables may not be associated with TKA outcomes.

Longitudinal association between foot and ankle symptoms and worsening of symptomatic radiographic knee osteoarthritis: data from the osteoarthritis initiative.

OBJECTIVE: To assess whether foot and/or ankle symptoms are associated with an increased risk of worsening of knee pain and radiographic change in people with knee osteoarthritis (OA). METHODS: The presence and laterality of foot/ankle symptoms were recorded at baseline in 1368 participants from the Osteoarthritis Initiative (OAI) with symptomatic radiographic knee OA. Knee pain severity (measured using the Western Ontario and McMaster Universities Osteoarthritis Index pain subscale) and minimum medial tibiofemoral joint space (minJSW) width measured on X-ray were assessed yearly over the subsequent 4 years. Associations between foot/ankle symptoms and worsening of (1) knee pain, and (2) both knee pain and minJSW (i.e., symptomatic radiographic knee OA) were assessed using logistic regression. RESULTS: Foot/ankle symptoms in either foot/ankle significantly increased the odds of knee pain worsening (adjusted OR 1.54, 95% CI 1.25 to 1.91). Laterality analysis showed ipsilateral (adjusted OR 1.50, 95% CI 1.07 to 2.10), contralateral (adjusted OR 1.44, 95% CI 1.02 to 2.06) and bilateral foot/ankle symptoms (adjusted OR 1.61, 95% CI 1.22 to 2.13) were all associated with knee pain worsening in the follow up period. There was no association between foot/ankle symptoms and worsening of symptomatic radiographic knee OA. CONCLUSION: The presence of foot/ankle symptoms in people with symptomatic radiographic knee OA was associated with increased risk of knee pain worsening, but not worsening of symptomatic radiographic knee OA, over the subsequent 4 years. Future studies should investigate whether treatment of foot/ankle symptoms reduces the risk of knee pain worsening in people with knee OA.

The relationship between foot and ankle symptoms and risk of developing knee osteoarthritis: data from the osteoarthritis initiative.

OBJECTIVE: To investigate whether foot and/or ankle symptoms increase the risk of developing (1) knee symptoms and (2) symptomatic radiographic knee osteoarthritis (OA). DESIGN: 1020 Osteoarthritis Initiative (OAI) participants who were at-risk of knee OA, but were without knee symptoms or radiographic knee OA, were investigated. Participants indicated the presence and laterality of foot/ankle symptoms at baseline. The main outcome was development of knee symptoms (pain, aching or stiffness in and around the knee on most days of the month for at least 1 month in the past year). A secondary outcome was development of symptomatic radiographic knee OA (symptoms plus Kellgren and Lawrence [KL] grade ≥2), over the subsequent 4 years. Associations between foot/ankle symptoms and study outcomes were assessed by logistic regression models. RESULTS: Foot/ankle symptoms in either or both feet significantly increased the odds of developing knee symptoms (adjusted odds ratio (OR) 1.55, 95% confidence interval (CI) 1.10 to 2.19), and developing symptomatic radiographic knee OA (adjusted OR 3.28, 95% CI 1.69 to 6.37). Based on laterality, contralateral foot/ankle symptoms were associated with developing both knee symptoms (adjusted OR 1.68, 95% CI 1.05 to 2.68) and symptomatic radiographic knee OA (adjusted OR 3.08, 95% CI 1.06 to 8.98), whilst bilateral foot/ankle symptoms were associated with developing symptomatic radiographic knee OA (adjusted OR 4.02, 95% CI 1.76 to 9.17). CONCLUSION: In individuals at-risk of knee OA, the presence of contralateral foot/ankle symptoms in particular increases risk of developing both knee symptoms and symptomatic radiographic knee OA.

Effects of footwear on the knee adduction moment in medial knee osteoarthritis: classification criteria for flat flexible vs stable supportive shoes.

OBJECTIVE: To validate simple criteria that distinguish flat flexible from stable supportive walking shoes by comparing their effects on the knee adduction moment (KAM) in people with medial knee osteoarthritis (OA). DESIGN: This was a cross-sectional biomechanical study. We proposed five criteria to differentiate flat flexible from stable supportive shoes, and selected three pairs of shoes representing each class for biomechanical testing. 28 participants aged ≥50 years with symptomatic medial knee OA underwent gait analysis barefoot and wearing each of the six selected shoes, in random order. Differences in the peak KAM, KAM impulse and peak knee flexion moment (KFM) across test conditions were evaluated with a two-way repeated measures analysis of variance (ANOVA). Immediate changes in walking pain between conditions were also compared. RESULTS: Increases in KAM from barefoot were lower with each of the three flat flexible shoe styles (peak KAM: 6.1-8.9%; KAM impulse: 2.4-5.1%) compared to their stable supportive counterparts (peak KAM: 11.6-15.1%; KAM impulse 10.5-13.2%). There was a significant main effect for footwear class on peak KAM and KAM impulse, whereby stable supportive shoes increased the KAM significantly more than flat flexible shoes (P < 0.001). There were no differences in the KFM or immediate walking pain between footwear classes. CONCLUSIONS: Our proposed criteria can be used by researchers and clinicians to select flat flexible shoes for people with medial knee OA to minimise knee loading. Future research should evaluate whether wearing shoes based on these criteria translates to improvements in knee OA symptoms and/or slows structural disease progression.

The knee adduction moment and knee osteoarthritis symptoms: relationships according to radiographic disease severity.

OBJECTIVE: To investigate relationships between external knee adduction moment parameters (KAM) and osteoarthritis (OA) symptoms according to disease severity. DESIGN: 164 participants with symptomatic medial knee OA were included. Radiographic severity was graded by (1) Kellgren & Lawrence (KL) scale (Grade 2, n = 49; Grade, n = 52; Grade 4, n = 63) and; (2) medial tibiofemoral joint space narrowing (JSN) (Grade 1, n = 47; Grade 2, n = 50; Grade 3, n = 67). KAM-related parameters (peak KAM, KAM impulse and cumulative load) were determined from three-dimensional gait analysis and pedometry. Cumulative load was determined by multiplying KAM impulse by the average number of steps/day recorded over at least 5 days. Symptoms were assessed via numeric rating scale ((NRS), pain) and Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index (pain and physical function). Relationships between KAM parameters (independent variables) and symptoms (dependent variables) were evaluated by radiographic severity using linear models, adjusting for covariates. RESULTS: In mild disease (either KL Grade 2 or JSN Grade 1), there were no associations between KAM and symptoms. In moderate disease of KL Grade 3, higher KAM impulse was associated with greater WOMAC pain. In severe disease (KL Grade 4), higher KAM impulse was associated with less WOMAC pain (KL Grade 4), while higher peak KAM was associated with better function (KL Grade 4). Higher cumulative knee adduction load was associated with less pain on both NRS and WOMAC (JSN Grade 3) as well as better function (both JSN Grade 3 and KL Grade 4). CONCLUSIONS: Relationships between KAM-related parameters and symptoms differ according to underlying radiographic OA severity.

Quantifying varus and valgus thrust in individuals with severe knee osteoarthritis.

BACKGROUND: Varus-valgus thrust is a biomechanical characteristic linked to knee osteoarthritis disease progression. This study aimed to determine: i) direction of thrust in individuals awaiting total knee arthroplasty versus controls, ii) whether thrust and related parameters differed between groups, iii) differences between osteoarthritis patients awaiting surgery with varus and valgus thrust. METHODS: 44 patients scheduled for surgery and 40 asymptomatic participants were recruited. PRIMARY OUTCOME MEASURES: varus-valgus thrust excursion and absolute thrust magnitude, quantified by 3D gait analysis. FINDINGS: Few differences were found between the osteoarthritis group and controls. The osteoarthritis group as a whole had a more varus knee angle during early- (p<0.0001) and mid-stance (p=0.010) versus controls. The varus thrust osteoarthritis subgroup had a more varus knee angle in overall (p=0.012), early- (p<0.001), and mid- (p<0.001) stance, and a higher peak knee adduction moment (p=0.019) and impulse (p=0.001) when compared to varus thrust controls. No differences were found between the valgus thrust osteoarthritis and control groups. The varus thrust osteoarthritis group had a greater varus peak knee angle in overall (p<0.001), early- (p<0.001), and mid- (p<0.001) stance, higher peak knee adduction moment (p<0.001) and impulse (p=0.001), more varus static alignment (p=0.014), and lower quadriceps strength (p=0.035) than the valgus thrust osteoarthritis group. INTERPRETATION: Those with severe osteoarthritis and a varus thrust have poorer biomechanics, more varus static knee alignment, and lower quadriceps strength compared to those with osteoarthritis with a valgus thrust. Further work is needed to determine if these findings impact total knee arthroplasty outcome.

Acute salivary gland hypofunction in the duct ligation model in the absence of inflammation.

OBJECTIVE: The commonly associated aetiology of salivary gland inflammation and salivary hypofunction has led to the widely held belief that inflammation causes salivary gland hypofunction. Indeed, our own recent study seemed to support this contention. Here, we tested the hypothesis that, in an acute duct ligation model, eliminating inflammation the submandibular gland would recover normal function. MATERIALS AND METHODS: Ligation of the rat submandibular gland excretory duct for 24 h was used to induce inflammation and salivary gland hypofunction. A group of duct ligated rats was compared with a second group given dexamethasone, on the day of duct ligation. Twenty-four hours later salivary gland function was assessed and salivary glands were collected. RESULTS: Histology and myeloperoxidase activity assay revealed a profound decrease in inflammatory cell infiltration of ligated glands from rats given dexamethasone, compared with ligated glands in the absence of dexamethasone. Salivary flow rate evoked by methacholine was decreased (P < 0.01) by approximately 56% (ligated vs control, 79 +/- 9 microl min(-1) g(-1)vs 177 +/- 11 microl min(-1) g(-1)) and salivary flow from ligated dexamethasone-treated and ligated glands was similar. CONCLUSION: Despite eliminating the inflammatory reaction in the ligated gland, salivary hypofunction was not reversed, suggesting that other mechanisms must be at work in the ligation-induced salivary hypofunction.

Enzyme histochemistry of rat mast cell tryptase.

Fixation and staining conditions for rat mast cell tryptase and its histochemical distribution in different rat tissues were investigated. Prostate, skin, lung, gut, stomach and salivary glands were fixed in either aldehyde or Carnoy fixatives and then frozen or embedded in paraffin wax. Preservation of tryptase enzymic activity against peptide substrates required aldehyde fixation and frozen sectioning. Of the peptide substrates examined, z-Ala-Ala-Lys-4-methoxy-2-naphthylamide and z-Gly-Pro-Arg-4-methoxy-2-naphthylamide proved the most effective for the demonstration of tryptase. Double staining by enzyme cytochemistry followed by immunological detection of tryptase showed that, in all tryptase-containing mast cells, the enzyme is at least in part active. Conventional dye-binding histochemistry was used to confirm the identity of mast cells. Aldehyde-fixed mucosal mast cells required a much shorter staining time with Toluidine Blue if tissue sections were washed directly in t-butyl alcohol. Double staining by enzyme cytochemistry and dye binding showed that tryptase is absent from mucosal and subepidermal mast cells, which are also smaller in size and appear to contain fewer granules than connective tissue mast cells. This study demonstrates that rat mast cell tryptase, unlike tryptases in other species, is a soluble enzyme. It is stored in an active form and is absent from some mast cell subpopulations in mucosa, skin and lung.

Mucin histochemistry of submandibular and parotid salivary glands of man: light and electron microscopy.

Light-microscopy showed parotid serous acinar cells to contain neutral mucin, serous and mucous acinar cells of submandibular gland and intercalary ductal cells of both glands to contain acid and neutral mucins, and cells of striated ducts and excretory ducts to contain neutral mucin. Mucins were demonstrated ultrastructurally in a portion of the components of secretory granules of acinar cells and intercalary ductal cells, and in secretory granules of striated and excretory ductal cells. The mucins were all stained by techniques that reveal 1,2-glycols. Secretory granules of submandibular mucous and serous acinar cells and intercalary ductal cells were stained variably by the low iron-diamine technique for acid mucin, and those of mucous acinar cells by the high iron-diamine technique for sulphomucins mucin and possibly consisted of protein. The results suggest that one type of cell may be able to produce a range of secretory products and to package them variously into secretory granules.

Ultrastructural morphology of secretory granules of submandibular and parotid salivary glands of man.

Morphological variation among secretory granules of the same type of cell was found in the acini, intercalary and striated ducts, and collecting-ducts, and was greatest in serous and intercalary-duct cells. Secretory granules of monopartite and bipartite structure were seen in all these cell types; tripartite forms were seen in serous and intercalary-duct cells. A possible explanation for the variation is that one type of cell may be able to produce a range of secretory products and package them variously into secretory granules, thus creating different appearances.