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Mutations in GBA1, which encode for the protein glucocerebrosidase (GCase), are the most common genetic risk factor for Parkinson's disease and dementia with Lewy bodies. In addition, growing evidence now suggests that the loss of GCase activity is also involved in onset of all forms of Parkinson's disease, dementia with Lewy bodies, and other dementias, such as progranulin-linked frontal temporal dementia. As a result, there is significant interest in developing GCase-targeted therapies that have the potential to stop or slow progression of these diseases. Despite this interest in GCase as a therapeutic target, there is significant inconsistency in the methodology for measuring GCase enzymatic activity in disease-modeling systems and patient populations, which could hinder progress in developing GCase therapies. In this review, we discuss the different strategies that have been developed to assess GCase activity and highlight the specific strengths and weaknesses of these approaches as well as the gaps that remain. We also discuss the current and potential role of these different methodologies in preclinical and clinical development of GCase-targeted therapies. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Anatomy is an early researched discipline of natural science. Ancient civilizations (e.g., Greece, Egypt, Mesopotamia, and China) made significant contributions to our current understanding of medicine, including human anatomy. However, in modern China (from 1912 to the present), some contemporary scholars prefer to overlook the fact that anatomy was studied before modern China. Therefore, the author chronologically lists typical hallmark events and publications related to human anatomy before modern China, summarizes the influences of anatomy on traditional Chinese medicine, and analyzes the reasons for the slow progression of anatomy before modern China. The purpose is to better understand the history and culture of anatomy before modern China, serving as the first step of anatomical education for medical students in mainland China.

This clinical trial (ChiCTR1800019185) is designed to be an open‐label, prospective, single‐center, single arm exploratory research study. The study will recruit non‐small cell lung cancer patients (NSCLC) with slow progression after first‐line treatment with EGFR‐TKI drugs. Slow progression will be confirmed by the presence of serum carcinoembryonic antigen or imaging evaluation. The primary aim is to assess progression‐free survival after EGFR‐TKIs treatment combined with apatinib 250 mg once daily. The secondary objectives are to evaluate objective efficacy, disease control rates, quality of life, overall survival, and safety. From September 2018 to September 2020, under specific entry and discharge standards, we plan to enroll 38 eligible patients until the end of the study. We hope that our study will help to explore a new way of combining the small molecular inhibitors of antiangiogenesis with EGFR‐TKIs to overcome acquired drug resistance.

To assess the effect of clinical factors on the development and progression of atrophy and fibrosis in patients with neovascular age-related macular degeneration (nAMD) receiving long-term treatment in the real world.An ambispective 36-month multicentre study, involving 359 nAMD patients from 17 Spanish hospitals treated according to the Spanish Vitreoretinal Society guidelines, was designed. The influence of demographic and clinical factors, including the presence and location of retinal fluid, on best-corrected visual acuity (BCVA) and progression to atrophy and/or fibrosis were analysed.After 36 months of follow-up and an average of 13.8 anti-VEGF intravitreal injections, the average BCVA gain was +1.5 letters, and atrophy and/or fibrosis were present in 54.8% of nAMD patients (OR = 8.54, 95% CI = 5.85-12.47, compared to baseline). Atrophy was associated with basal intraretinal fluid (IRF) (OR = 1.87, 95% CI = 1.09-3.20), whereas basal subretinal fluid (SRF) was associated with a lower rate of atrophy (OR = 0.40, 95% CI = 0.23-0.71) and its progression (OR = 0.44, 95% CI = 0.26-0.75), leading to a slow progression rate (OR = 0.34, 95% CI = 0.14-0.83). Fibrosis development and progression were related to IRF at any visit (p 0.001). In contrast, 36-month SRF was related to a lower rate of fibrosis (OR = 0.49, 95% CI = 0.29-0.81) and its progression (OR = 0.50, 95% CI = 0.31-0.81).Atrophy and/or fibrosis were present in 1 of 2 nAMD patients treated for 3 years. Both, especially fibrosis, lead to vision loss. Subretinal fluid (SRF) was associated with good visual outcomes and lower rates of atrophy and fibrosis, whereas IRF yields worse visual results and a higher risk of atrophy and especially fibrosis in routine clinical practice.

BACKGROUND: Nearsightedness (myopia) causes blurry vision when one is looking at distant objects. Interventions to slow the progression of myopia in children include multifocal spectacles, contact lenses, and pharmaceutical agents. OBJECTIVES: To assess the effects of interventions, including spectacles, contact lenses, and pharmaceutical agents in slowing myopia progression in children. SEARCH METHODS: We searched CENTRAL; Ovid MEDLINE; Embase.com; PubMed; the LILACS Database; and two trial registrations up to February 2018. A top up search was done in February 2019. SELECTION CRITERIA: We included randomized controlled trials (RCTs). We excluded studies when most participants were older than 18 years at baseline. We also excluded studies when participants had less than ‐0.25 diopters (D) spherical equivalent myopia. DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methods. MAIN RESULTS: We included 41 studies (6772 participants). Twenty‐one studies contributed data to at least one meta‐analysis. Interventions included spectacles, contact lenses, pharmaceutical agents, and combination treatments. Most studies were conducted in Asia or in the United States. Except one, all studies included children 18 years or younger. Many studies were at high risk of performance and attrition bias. Spectacle lenses: undercorrection of myopia increased myopia progression slightly in two studies; children whose vision was undercorrected progressed on average ‐0.15 D (95% confidence interval [CI] ‐0.29 to 0.00; n = 142; low‐certainty evidence) more than those wearing fully corrected single vision lenses (SVLs). In one study, axial length increased 0.05 mm (95% CI ‐0.01 to 0.11) more in the undercorrected group than in the fully corrected group (n = 94; low‐certainty evidence). Multifocal lenses (bifocal spectacles or progressive addition lenses) yielded small effect in slowing myopia progression; children wearing multifocal lenses progressed on average 0.14 D (95% CI 0.08 to 0.21; n = 1463; moderate‐certainty evidence) less than children wearing SVLs. In four studies, axial elongation was less for multifocal lens wearers than for SVL wearers (‐0.06 mm, 95% CI ‐0.09 to ‐0.04; n = 896; moderate‐certainty evidence). Three studies evaluating different peripheral plus spectacle lenses versus SVLs reported inconsistent results for refractive error and axial length outcomes (n = 597; low‐certainty evidence). Contact lenses: there may be little or no difference between vision of children wearing bifocal soft contact lenses (SCLs) and children wearing single vision SCLs (mean difference (MD) 0.20D, 95% CI ‐0.06 to 0.47; n = 300; low‐certainty evidence). Axial elongation was less for bifocal SCL wearers than for single vision SCL wearers (MD ‐0.11 mm, 95% CI ‐0.14 to ‐0.08; n = 300; low‐certainty evidence). Two studies investigating rigid gas permeable contact lenses (RGPCLs) showed inconsistent results in myopia progression; these two studies also found no evidence of difference in axial elongation (MD 0.02mm, 95% CI ‐0.05 to 0.10; n = 415; very low‐certainty evidence). Orthokeratology contact lenses were more effective than SVLs in slowing axial elongation (MD ‐0.28 mm, 95% CI ‐0.38 to ‐0.19; n = 106; moderate‐certainty evidence). Two studies comparing spherical aberration SCLs with single vision SCLs reported no difference in myopia progression nor in axial length (n = 209; low‐certainty evidence). Pharmaceutical agents: at one year, children receiving atropine eye drops (3 studies; n = 629), pirenzepine gel (2 studies; n = 326), or cyclopentolate eye drops (1 study; n = 64) showed significantly less myopic progression compared with children receiving placebo: MD 1.00 D (95% CI 0.93 to 1.07), 0.31 D (95% CI 0.17 to 0.44), and 0.34 (95% CI 0.08 to 0.60), respectively (moderate‐certainty evidence). Axial elongation was less for children treated with atropine (MD ‐0.35 mm, 95% CI ‐0.38 to ‐0.31; n = 502) and pirenzepine (MD ‐0.13 mm, 95% CI ‐0.14 to ‐0.12; n = 326) than for those treated with placebo (moderate‐certainty evidence) in two studies. Another study showed favorable results for three different doses of atropine eye drops compared with tropicamide eye drops (MD 0.78 D, 95% CI 0.49 to 1.07 for 0.1% atropine; MD 0.81 D, 95% CI 0.57 to 1.05 for 0.25% atropine; and MD 1.01 D, 95% CI 0.74 to 1.28 for 0.5% atropine; n = 196; low‐certainty evidence) but did not report axial length. Systemic 7‐methylxanthine had little to no effect on myopic progression (MD 0.07 D, 95% CI ‐0.09 to 0.24) nor on axial elongation (MD ‐0.03 mm, 95% CI ‐0.10 to 0.03) compared with placebo in one study (n = 77; moderate‐certainty evidence). One study did not find slowed myopia progression when comparing timolol eye drops with no drops (MD ‐0.05 D, 95% CI ‐0.21 to 0.11; n = 95; low‐certainty evidence). Combinations of interventions: two studies found that children treated with atropine plus multifocal spectacles progressed 0.78 D (95% CI 0.54 to 1.02) less than children treated with placebo plus SVLs (n = 191; moderate‐certainty evidence). One study reported ‐0.37 mm (95% CI ‐0.47 to ‐0.27) axial elongation for atropine and multifocal spectacles when compared with placebo plus SVLs (n = 127; moderate‐certainty evidence). Compared with children treated with cyclopentolate plus SVLs, those treated with atropine plus multifocal spectacles progressed 0.36 D less (95% CI 0.11 to 0.61; n = 64; moderate‐certainty evidence). Bifocal spectacles showed small or negligible effect compared with SVLs plus timolol drops in one study (MD 0.19 D, 95% CI 0.06 to 0.32; n = 97; moderate‐certainty evidence). One study comparing tropicamide plus bifocal spectacles versus SVLs reported no statistically significant differences between groups without quantitative results. No serious adverse events were reported across all interventions. Participants receiving antimuscarinic topical medications were more likely to experience accommodation difficulties (Risk Ratio [RR] 9.05, 95% CI 4.09 to 20.01) and papillae and follicles (RR 3.22, 95% CI 2.11 to 4.90) than participants receiving placebo (n=387; moderate‐certainty evidence). AUTHORS' CONCLUSIONS: Antimuscarinic topical medication is effective in slowing myopia progression in children. Multifocal lenses, either spectacles or contact lenses, may also confer a small benefit. Orthokeratology contact lenses, although not intended to modify refractive error, were more effective than SVLs in slowing axial elongation. We found only low or very low‐certainty evidence to support RGPCLs and sperical aberration SCLs.

Dominant mutations in MFN2 cause a range of phenotypes, including severe, early-onset axonal neuropathy, "classical CMT2," and late-onset axonal neuropathies. We report a large family with an axonal polyneuropathy, with clinical onset in the 20s, followed by slow progression.

Key Clinical Message Giant condyloma acuminatum is a rare variant of genital warts also known as Buschke‐Löwenstein tumor. It is characterized by a slow progression of exophytic, ulcerative, and cauliflower‐shaped tumor with benign histological features. Verrucous carcinoma however is a rare variant of well‐differentiated squamous cell carcinoma with limited metastatic potential.

Migration behaviour and estuarine mortality of cultivated Atlantic salmon Salmo salar smolts in a 16 km long estuary were studied using two methods: (1) acoustic telemetry and (2) group tagging in combination with trap nets. Progression rates of surviving individuals through the estuary were relatively slow using both methods [0·38 LT (total length) s-1 v. 0·25 LT s-1 ]. In 2012, the progression rate was slow from the river to the estuary (0·55 LT s-1 ) and the first part of the estuary (0·31 LT s-1 ), but increased thereafter (1·45-2·21 LT s-1 ). In 2013, the progression rate was fast from the river to the estuary (4·31 LT s-1 ) but was slower thereafter (0·18-0·91 LT s-1 ). Survival to the fjord was higher in 2012 (47%) compared to 2013 (6%). Fast moving individuals were more likely to migrate successfully through the estuary compared to slower moving individuals. Adult recapture of coded-wire-tagged S. salar was generally low (0·00-0·04%). Mortality hot spots were related to topographically distinct areas such as the river outlet (in 2012) or the sill separating the estuary and the fjord (in 2013). At the sill, an aggregation of cod Gadus morhua predating on cultivated smolts was identified. The results indicate that slow progression rates through the estuary decreases the likelihood of smolts being detected outside the estuary. The highly stochastic and site-specific mortality patterns observed in this study highlight the complexity in extrapolating mortality patterns of single release groups to the entire smolt run of wild S. salar.

A 72‐year‐old woman presented with acute onset of shortness of breath and fatigue over several days, and was found to be in acute respiratory failure. Computed tomography of the chest revealed diffuse ground‐glass opacities, crazy‐paving, multiple nodules, and a large mass in the right lower lobe. She was diagnosed with B‐cell lymphoma and a pulmonary lymphoproliferative disorder (PLD). PLD is known to present with a variety of radiographic patterns. The course of PLD is usually one of slow progression, and acute respiratory failure is a rare presentation. Physicians should be aware that acute respiratory failure can be caused by PLD.

We determined prospectively the clinical and electrophysiological progression of idiopathic, diabetic, paraproteinemic, alcoholic, and B12 deficiency neuropathy in 606 subjects over 3 years. We hypothesized that idiopathic peripheral neuropathy would demonstrate slower progression when compared with other etiologies. Laboratory assessments were used to determine the etiology of peripheral neuropathy at baseline and after 3 years. When compared with peripheral neuropathy related to type 1 or type 2 diabetes mellitus, subjects with idiopathic peripheral neuropathy progressed much slower, but demonstrated similar rates of progression to that of the other groups. Overall, detectable progression was minimal over 3 years. After 3 years, only 3% of cases of idiopathic peripheral neuropathy had any potentially identifiable causes discovered. Clinical and electrophysiological detection of very slow progression for these five types of peripheral neuropathy is possible using currently established clinical scales and standard electrophysiological techniques.

Objective Little is known about the natural history of knee osteoarthritis (OA). We sought to identify common patterns of joint space narrowing (JSN) in well-characterized knee OA patients in the placebo arm of a 2-year international study. Methods We performed secondary data analyses of 622 adults ages 39–80 years in North America (n = 310) and Europe (n = 312) with symptomatic knee OA. Fluoroscopically positioned semiflexed anteroposterior radiographs were obtained at 0, 12, and 24 months. Group-based trajectory modeling was used to identify distinctive groups of individuals with similar trajectories of JSN, taking into account sex, age, and body mass index. Results Seven groups were identified. Four exhibited joint space width (JSW) stability over 2 years representing the most common trajectory (71%), which was unrelated to initial JSW. Atypical courses included slow, rapid, and moderate progressors; most had significant JSN at study entry. Slow progressors (20%) had a mean JSN of 0.2 mm over 2 years. Only 2% of the sample demonstrated rapid JSN (2.1 mm), while 7% had JSN of 0.7 mm. Rapid progressors tended to be men, while slow and moderate progressors were older and heavier. Conclusion Most (70%) people with OA demonstrated no significant JSN over 2 years; 20% showed slow progression, 7% had moderate, and 2% had rapid JSN. Progressors tended to have less JSW at study entry and were older and heavier; rapid progressors were more likely to be men. Understanding common patterns of the course of knee OA may offer new opportunities to target those at greatest risk of disability.

We report an investigation of the validity of teachers' ratings of children's progress in 'phonics' as a screener for dyslexia. Seventy-three 6-year-olds from a whole school population were identified as 'at risk' of dyslexia according to teacher judgements of slow progression through phonic phases. Six months later, children's attainments in literacy and phonological skills were compared with those of their typically developing peers matched on age and gender. Teacher assessments of risk were related to individual differences in performance on a standardised test of reading ability. Teacher assessments overestimated 'risk of dyslexia', defined as below-average reading performance. However, teacher judgements, supplemented by tests of phoneme awareness and rapid naming, allowed a sensitive and specific identification of children who subsequently experienced reading difficulties. These findings show teachers can identify risk of dyslexia; the accuracy of this process can be improved by administering two tests of phonological skills. © 2011 UKLA.

Material requirements planning (MRP) systems became a prominent approach to managing the flow of raw material and components on the factory floor in the late 20th century. Its adoption was not an over night phenomenon, but was a slow progression over many decades. This article chronicles many developments and events during the formative years of MRP, highlighting changes in computer technology and contributions by key early proponents of this approach for managing the flow of material on the factory floor.

Human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS) have been very serious problems since the 1980s. The progression of HIV infection into AIDS can be suppressed to some extent with reverse transcriptase inhibitors (RTIs) and protease inhibitors (PIs); however, there are some serious problems with treatments using the anti-HIV drugs (e.g. very high expense, complicated administration, and drug resistance). Hence, more studies on HIV and the development of more effective anti-HIV treatments are required. We consider it important to understand the complex dynamics involved in HIV infection, and we therefore propose new mathematical models of HIV infection. In the modeling, we have paid attention to the nonlinear relations between stimuli and responses (i.e., when responses are plotted against the logarithm of stimuli, a sigmoid curve is obtained), and to lymphoid organs which seem more important than the blood compartment (i.e., lymphoid organs are major reservoirs of HIV virions and contain most of the lymphocytes). Using the models, we have found that viral antigenic mutation plays an important role in the slow progression in the chronic phase of HIV infection. We have also found that viral antigenic mutation can cause relapse of HIV infection when the inhibition rate of anti-HIV drugs is low and that viral antigenic mutation cannot cause relapse when the inhibition rate is high.

Although there are no proven ways to delay onset or slow progression of Alzheimer's disease (AD), studies suggest that diet can affect risk. Dates palm fruit are good sources of minerals (Se, Cu, K and Mg), vitamins (C, A, B6, B9, B2, B3), dietary fiber and total phenolics and natural antioxidants (anthocyanins & ferulic acid). Polyphenols have been shown to be neuroprotective in different model systems. We asked whether dietary supplementation with 2% dates or 4% dates would influence behavior and AD like pathology in a transgenic mouse model. The four month old mice with double Swedish APP mutation (APPsw/Tg2576) were purchased from Taconic Farm, NY, USA. The experimental groups of APP-transgenic mice from the age of 4 months were fed custom-mix diets (pellets) containing 2% dates or 4% dates. The control groups, i.e. tg mice and wild-type mice were fed diet without dates. Animals from all groups were undergone behavioral assessments at the age of 4-5 months and 14-15 months by Morris water maze tes...

We examined a large Turkmen family with 'pseudo-dominant' inheritance of Friedreich's ataxia resulting from consanguineous marriage of a Friedreich's ataxia patient to a heterozygote carrying an ancestral mutated allele. Two distinct phenotypes of the disease co-segregated within this genealogy. Two brothers from the younger generation exhibited 'classical' Friedreich's ataxia with onset of symptoms before 10 years and a rapidly progressive course. In contrast, three patients (two sisters from the younger generation and their father) had a more benign phenotype of late-onset Friedreich's ataxia with the onset at 26, 45 and 48 years and slow progression over decades. The patients with 'classical' Friedreich's ataxia were homozygous for a common ancestral expanded allele of the X25 gene containing 700-800 GAA repeats, while the patients with late-onset Friedreich's ataxia had two different mutated alleles, the shorter 250-repeat expansion of paternal origin and the longer 700-repeat expansion of maternal origin. One may conclude that clinical variability of Friedreich's ataxia in our patients is accounted for predominantly by a modifying effect of one of the two (shorter or longer) expanded alleles inherited from their affected father. Our observation clearly demonstrates the significance of variable-sized alleles for the phenotypic expression of the disease.

Summary Fusarium species may cause localised skin infections in immunocompetent individuals. At least half of these infections are preceded by skin breakdown. The lesions are characterised by slow progression and good response to therapy. Here we present a 60-year-old non-diabetic man with stasis ulcers showing Fusarium oxysporum growth in culture of both pus swabs and skin biopsy specimens. The patient was confined to wheelchair because of recurrent sacral chordoma of 15 years duration, which was not under treatment for the last 3 years. Leg ulcers were resistant to antifungal therapy, and healed rapidly after improving of stasis with local and systemic measures.

Objective To investigate the relation between the rise in intrauterine pressure and rise in fetal head to cervix force in normal, slow and induced labour. Design Prospective observational study. Setting The labour ward of a London teaching hospital. Participants Forty patients were recruited from the antenatal clinic and labour ward of a West London Hospital. Five had normal onset and progression of labour, 14 had slow progression of labour and 21 had induced onset of labour. Method Intrauterine pressure and head-to-cervix force was measured simultaneously using an intrauterine pressure catheter and a specially designed four sensor head-to-cervix force probe. Results For each contraction of each labour, scattergrams of force by pressure were plotted. Three patterns were observed. When the rise in pressure preceded the rise in force, a positive 'loop' was generated. When the rise in pressure and force occurred simultaneously a linear pattern was generated (a neutral 'loop'). When the rise in pressure lags the rise in force, a negative 'loop' was generated. In normally progressive labour the distribution of loops was 29.1 %, 22.6 % and 48.3 %, respectively, in slow labour the distribution was 26.1 %, 14.1 % and 59.8 % and in induced labour the distribution was 33.8 %, 14.4 % and 51.8 %. These distributions were not statistically different. However, a higher proportion of negative loops was observed in labours augmented with oxytocin compared to those receiving no oxytocin (MW-U = 87, P = 0.036). No differences were observed comparing parity, use of PGE 2 , epidural analgesia, or mode of delivery. Contraction frequency (number/10 minutes) was inversely correlated to the percentage of negative loops (r s = - 0.34, P = 0.033) and positively correlated with percentage of positive loops (r s = 0.36, P = 0.027). Conclusions This is the first report of the temporal relation between intrauterine pressure and head-to-cervix force in labour. The most common pattern is that the rise in pressure lags the rise in force, suggesting that a seal has to be created between the fetal head and cervix before a rise in pressure can occur. When oxytocin is given in labour, a higher proportion of loops are negative indicating that there is poor application of the fetal head and cervix in a greater proportion of contractions.

Hypertrophic obstructive cardiomyopathy (HOCM) is a primary myocardial disease with typical echocardiography features of asymmetric septal hypertrophy and evidence of left ventricular outflow tract obstruction. The natural history of HOCM is characterized by a slow progression of symptoms and a significant annual mortality rate. We report an unusual case of transient HOCM during pregnancy with evidence of total resolution postpartum. hypertrophic cardiomyopathy, pregnancy, idiopathic hypertrophic subaortic stenosis, two-dimensional echocardiography, Doppler echocardiography

A young man presenting with a Tourette syndrome-like disorder that was the main clinical manifestation of Hallervorden-Spatz syndrome is described. It is recommended that, even in the case of slow progression, HSS should be considered in the differential diagnosis of TS-like disorders.

Two families with Emery-Dreifuss muscular dystrophy (EMD) are described. Several unusual features for EMD are emphasized. One of the patients had severe neuromuscular disability with inability to walk during early childhood. This patient also had mild bifacial paresis. His brothers had the typical slow progression of EMD. In some of the patients, muscle weakness distribution was more widespread than has usually been reported, with prominent involvement of finger extensors. It is suggested that there is a wide phenotypic spectrum in EMD. In both families, the disease segregated with markers spanning the EMD locus in Xq28. © 1993 John Wiley & Sons, Inc.

We thank Prof. Filik for his interest in our recent article. 2 He points to the fact that the interpretation of our results could be affected by lack of data on physical activity and diet. In response to this issue, we are aware that both physical activity and diet are able to affect not only anthropometric and metabolic parameters of visceral adiposity index (VAI) but also the severity of liver disease. Unfortunately, data on both physical activity and diet in our patients with biopsy-proven non-alcoholic fatty liver disease (NAFLD) are not available, even if we are confident that their variations should not significantly affect our results. In fact, in our study, we evaluated histological liver damage and metabolic features of NAFLD patients who had not yet undergone lifestyle intervention. In any case, we found useful a further prospective evaluation of the impact of baseline diet and physical activity on both VAI and liver disease severity. These data, in fact, together with follow-up data, could help validate VAI as a surrogate marker of metabolic and liver disease improvement after therapeutic approaches in NAFLD patients.

This report compares the progression of renal failure in type-I diabetic patients fed either a low or a normal protein diet. In a prospective, randomized, controlled fashion, 47 adult patients were placed either on a 0.6 g/ kg daily protein intake (study) or a greater than 1.0 g/ kg (control) daily protein intake. Dietary phosphorus was maintained between 0.5 and 1.0 g for study patients and greater than 1.0 g for control patients. Renal function was monitored by iothalamate and creatinine clearance measurements at 3- to 6-month intervals. Patients were studied for periods up to 46 months (mean 34.7 months). Study patients had a slower deterioration of renal function with clearance decreasing at 25 to 40% the rate observed in control patients. Proteinuria was reduced by 45% in the study group when compared to the control group (2.9 g/dL vs 5.4 g/dL). The authors conclude that a protein-phosphorus-restricted diet can slow progression of renal failure in diabetic patients.

Eleven new cases of adenoid cystic carcinoma of the breast are added to the 95 previously reported. They were studied for their biological behavior, and an attempt was made to correlate histologic features with prognosis. A comparison was made with analogous tumors in extramammary sites, and possible relationship with carcinoid tumors of the breast explored. The patients in the study followed a biological course very similar to that described by previous studies, i.e., slow progression, local recurrence if inadequately resected, and absence of lymph node metastases. Only one patient developed distant metastases after an interval of ten years following radical mastectomy. If the diagnosis of adenoid cystic carcinoma is reserved for those lesions displaying the distinctive appearance and typical epithelial-stromal relationships which have been described, the authors feel that simple mastectomy with careful follow-up surveillance is the treatment of choice.

We report on 3 brothers with a myopathy that also affected their maternal grandfather and great-uncle. Characteristic features are onset in early childhood, very slow progression, normal life expectancy, weakness of proximal limb muscles, especially in the legs, elevation of serum creatine kinase, and no cardiac or intellectual involvement. In biopsy material muscle fibers are almost never necrotic but show excessive autophagic activity and exocytosis of the phagocytosed material. We suggest that this family has an undescribed type of congenital myopathy, for which we propose the name X-linked myopathy with excessive autophagy.

Factors influencing survival were reviewed in 464 patients with recurrent breast cancer. Site of first recurrence and rate of tumor progression governed prognosis more than choice of initial therapy. Overall median survival was 22--26 months for bone/soft-tissue disease, 10--12 months for pleura/lung, and 4--6 months for liver/brain recurrence. Patients with slow rates of tumor progression at each site had longer survival terms than did rapid progressors. About 50% of patients with bone or soft-tissue recurrence had slow progression and long survival, regardless of whether initial treatment was local or systemic. In visceral recurrence, the number of patients with slow progression was doubled with systemic therapy in comparison to local treatment (from 16--20% for the latter to 37--38% for the former). In addition, long-term survival in patients with similar progression rates was best using initial systemic therapy.

Summary 1 Six patients who gave a history of gastric symptoms of long duration associated with consistant pain have been submitted to partial gastrectomy with no mortality. 2 Medical treatment under hospital regime gave only partial or temporary relief. 3 The gross pathological condition found at operation confirmed the long-standing nature of the disease with no evidence of complete healing, but showed evidence of slow progression towards deep penetration and perforation. 4 In four cases hiyperchlorhydria was transformed into achlorhydria. 5 Partial gastrectomy gave immediate relief in all cases, with no return of symptoms up to a period of twelve months. 6 Partial gastrectomy removes the “ulcer-bearing” and “acid-secreting” areas, and eliminates the possibility of malignant change. 7 Partial gastrertomy was attended by comparatively little Shock, both operative and post-operative. 8 In view of the gross pathological change found, nothing less than partial gastrectoniy was indicated or held out any hope of permanent cure.

The gaits of 19 species of Macropodinae were studied from 360 m of movie film taken in zoos. Four gaits were identified: (1) the slow progression involving all the limbs plus the tail which was similar in all the species and used mainly while grazing; (2) the walk, the only gait in which the pairs of limbs were not used synchronously and confined to the sole arboreal species of Dendrolagus; (3) the quadrupedal bound involving the use of the hindfeet and then the forefeet in sequence and believed to be a primitive gait because it is only found in the relatively primitive species of Setonix and Dendrolagus; and (4) the bipedal hop, the fastest gait, which is often correlated with the habitat of a species. The probable phylogeny of the Macropodinae is presented, based on gaits and other available taxonomic criteria.

Chronic edema can be debilitating in Noonan's syndrome. Transient childhood lymphedema may be followed by elephantiasis as early as adolescence. Recurrent streptococcal cellulitis exacerbates this problem. Hygenic measures and prophylactic antiobiotic therapy may slow progression of lymphedema of the legs in Noonan's syndrome.