Improvement Of Muscle Weakness Research Articles

Divergent Phenotypes with Same CHRNE Mutation in Two Siblings with Congenital Myasthenic Syndrome

Background: Congenital myasthenic syndrome is a rare inherited neuromuscular disorder resulting in abnormal weakness and fatigue on exertion with onset at or shortly after birth or in early childhood. Clinical Description: A 2-year-old boy presented to us with respiratory failure, having a history of recurrent respiratory tract infections and underlying isolated motor delay. His 7-year-old elder sister had undiagnosed generalized weakness. Management and Outcome: While the index case was being stabilized with mechanical ventilation, his elder sibling was evaluated. Ptosis was noted in her, which improved with neostigmine. Examination and laboratory investigations ruled out other differentials. Clinical exome sequencing was sent which showed homozygous CHRNE ENST00000649488.2.c.1367_1369del. (p.Asn456del) resulting in acetylcholine receptor deficiency. Both siblings were started on oral pyridostigmine and salbutamol, resulting in improvement in muscle weakness over 3 months and 4 months in younger and older sibling, respectively. Conclusion: Recurrent respiratory insufficiency when associated with motor delay may be suggestive of a neuromuscular disorder. Even siblings with the same mutation may have different levels of severity of clinical manifestation.

A Review of The Evidence for the Utility of Physical Activity Monitor Use in Patients with Idiopathic Inflammatory Myopathies.

Few proven therapies exist for patients with idiopathic inflammatory myopathies (IIM), partly due to the lack of reliable and valid outcome measures for assessing treatment responses. The current core set measures developed by the International Myositis Assessment and Clinical Studies group were developed to standardize assessments of disease activity and treatment effect. None of the current measures address functional improvement in muscle weakness. Therefore, supplemental measures for more objectively assessing physical activity levels and fatiguability in free-living settings are needed to assess disease activity more comprehensively. Validated physical activity monitors (PAMs) have the potential to serve as an objective functional outcome measure in clinical trials and observational studies. This review examines the current evidence for using body-worn PAMs in clinical settings with IIM patients. A practical overview of methods for PAM use in clinical patient populations (including measurement details and data processing) that focuses on IIM patients is also presented.

Abstract 16715: Rare or Disregarded; A Case of Autoimmune Myopathy

Introduction: Statin-induced myopathy can present with symptoms ranging from mild myalgia to significant muscle weakness. This case report highlights how statin-induced autoimmune myopathy often goes undiagnosed. Case Presentation: We present a 69 year old male with a past medical history of coronary artery disease who presented with myalgia and progressive proximal muscle weakness for 2 months. On admission, creatinine kinase (CK) level was noted to be elevated at 8323 u/L. Atorvastatin was held on admission and the patient received intravenous (IV) fluid as treatment for presumed rhabdomyolysis. Although CK was trending down, the patient did not show any significant improvement in muscle weakness or myalgia. At this point, myositis was suspected, so a myositis panel including anti-HMG Co-A Reductase antibody was ordered and the patient was started on IV steroids. Anti-HMG Co-A Reductase antibody was positive and the rest of myopathy workup was negative; meanwhile, the patient's muscle weakness significantly improved. The patient was discharged on a methylprednisolone with close outpatient rheumatology follow-up. Discussion: Drug-induced rhabdomyolysis is one of many causes of myalgia. It is crucial to review a patient’s medication list and discontinue any possible medications that are possible offenders. Statin-induced myopathy should also be suspected when typical treatment for rhabdomyolysis is failing. Statin induced autoimmune myopathy is associated with muscle weakness, elevated CK and a positive anti-HMG Co-A Reductase antibody, which requires discontinuation of Statin and initiation of immunosuppressive therapy. Conclusions: This case report highlights the importance of early identification and management of statin-induced autoimmune myopathy as a possible differential diagnosis in patients with muscle weakness, elevated CK levels while on statin therapy who do not respond to IV fluid alone.

Thyrotoxic Periodic Paralysis Precipitated by Viral Hepatitis

Thyrotoxic hypokalaemic Periodic Paralysis (TPP) is a medical emergency usually seen in Grave’s disease, commonly in persons of oriental descent. The present case is a rare first time presentation of TPP in association with acute viral hepatitis A. A 46-yearold female presented with weakness, vomiting, fever, altered sensorium and yellow discolouration for 20 days. She was diagnosed to have hepatic failure due to viral hepatitis A. Her serum potassium level was 1.79 mmol/L. Treatment for hepatic failure and i.v. potassium chloride replacement was started. Sensorium improved but severe hypokalaemia and flaccid paralysis persisted. Thyroid functions were assessed and thyrotoxicosis due to Grave’s disease was diagnosed. Carbimazole and systemic corticosteroids were also started and potassium infusion was continued. Serum potassium became normal only after thyroid hormones reached normal limits followed by improvement in muscle weakness. TPP can be precipitated in conditions of stress, thyroid functions should be assessed in cases of hypokalaemic periodic paralysis even in absence of overt thyroid disease.

A STUDY TO ASSESS THE EFFECTIVENESS OF INTRADIALYTIC EXERCISE ON MUSCLE STRENGTHENING OF HEMODIALYTIC PATIENTS IN SELECTED HOSPITALS OF GANDHINAGAR

A Quasi-experimental study was conducted to assess the effectiveness of intradialytic exercise on haemodialytic patients in selected areas of Gandhinagar. The study was conducted among the haemodialytic patients group in selected areas of Gandhinagar. The main aim of our study is to evaluate the effectiveness of intradialytic exercise on haemodialytic patients in selected areas of Gandhinagar. The general system model was used as conceptual framework. A quantitative approach with Quasi experimental study design was used to achieve the objective of the study. The study samples considered of 50 haemodialytic patients in selected hospitals of Gandhinagar. The observational checklist was used to assist the effectiveness of intradialytic on haemodialytic patients in selected areas of Gandhi The result shows that intradialytic exercise given to the haemodialytic patients in experimental group, the muscle strengthening improved which was assessed by observational checklist. In the experimental group, the pretest mean is 8.08 and posttest is 10.6, the mean difference was 2.52, standard deviation of pre-test was 1.87 and of posttest was 3.05 which showing that level of muscle strengthening was improved. In control group, the pre-test mean is 7.4 and the post-test is 7.12, the mean difference is 0.28, standard deviation of pre-test is 1.83 and of post-test is 1.94. Calculated value is 3.83 which is more than table value at level of 0.05 level of significance which showing effectiveness of intradialytic exercise. This study therefore, offers an encouraging solution towards improvement of muscle weakness and level of muscle strengthening score after administration of intradialytic exercise.nagar. The study intends to assess the effectiveness of intradialytic exercise on haemodialytic patients in selected areas of Gandhinagar. The study reveals that the post-testscore of haemodialytic patients on muscle strengthening is higher in the experimental group than the control group. It shows that Intradialytic exercise is more effective in experimental group so Null hypotheses is rejected and research hypotheses is accepted.

Improvement of muscle weakness by nalfurafine hydrochloride (TRK-820), a kappa opioid receptor agonist

Improvement of muscle weakness by nalfurafine hydrochloride (TRK-820), a kappa opioid receptor agonist

EFFICACY OF SHASTIKA SHALI PINDA SWEDA IN MUSCULAR DYSTROPHY: A CASE STUDY

Muscular dystrophy is a group of diseases that make muscles weaker and less flexible over time. This disease comes under Beeja dosha and Mamsavaha Srotodushti which leads to Mamsavaha Kshaya and impairment of Mamsagni and can be treated as Mamsagat vata which is explained in Ayurvedic text. This is a single case study was conducted to evaluate the efficacy of Shastika Shali Pinda Sweda in muscular dystrophy. The case report is A female patient aged 14 years was admitted in IPD of Kayachikitsa and Panchakarma with complains of both lower limb weakness, loss of muscle strength. It was a diagnosed case of muscular dystrophy. The patient was unable to walk, sit and stand properly due to the weakness in lower limbs and other associated symptoms loss of appetite, weakness. Diagnosis done by the examination of muscle power and tone. During the examination, Muscle tone and power diminished in the lower limbs of the patient. Materials and methods are Shastika Shali, Bala mool (decoction), Milk, Ksheer bala tail (for Abhyanga). Triphala churna 1 gram at bedtime and Shunthi churna 0.5 gram two times before meal given to enhancing the appetite. Shastika Shali Pinda Sweda was done for 14 days regularly and then follow-up after 1 month. The patient showed significant improvement in muscle weakness, and she can be able to do her work without any support. This single case study shows the efficacy of Panchakarma procedure and minimize the severity of disease and improving quality of life of patients.

Abstract 14604: Flecainide Induced Myalgias. A Rare but Important Adverse Reaction

Introduction: Flecainide is an anti-arrhythmic used in patients with symptomatic arrhythmias without structural heart anomalies. It is known to cause several non-cardiac adverse reactions, most commonly headaches, dizziness, fatigue and nausea. We report a case of symmetric polymyalgia, a rare side effect of flecainide. Case Report: A 62 year-old woman with history of atrial fibrillation presented with chest heaviness and generalized myalgias. Just 5 days prior to her presentation, she underwent a cardiac ablation and was started on flecainide 150 mg twice daily. Her other home medications included furosemide, carvedilol, dabigatran, losartan and aspirin, all of which were unchanged. Vital signs were stable. Pertinent exam findings included tenderness to palpation over bilateral calf muscles, muscle strength testing with 3/5 in bilateral flexor and extensor muscles of hip and knee joints, and absent bilateral knee and ankle reflexes. EKG showed normal rate and rhythm. ESR and CRP were elevated with a normal ANA and creatinine kinase. The Naranjo score of 7 suggested a probable cause for flecainide-induced myalgias. Flecainide was discontinued leading to improvement in muscle weakness and reflexes at the time of discharge, and at follow-up visits, her symptoms completely resolved. Discussion: Antiarrhythmics are commonly used medications with cardiac and non-cardiac adverse effects. Flecainide-induced adverse effects are dose dependent. In dose ranging studies, increasing flecainide dosages caused significant myalgias, especially in patient taking 300 mg/day. In the appropriate clinical context, healthcare providers should be aware of this rare, reversible adverse effect, to prevent extensive inflammatory or neuromuscular disease workup. As our case illustrates, early discontinuation of flecainide can resolve myalgias and prevent long-term sequelae.

Recovery from hypoxemia and Hypercapnia following noninvasive pressure support ventilation in a patient with statin-associated necrotizing myopathy: a case report

BackgroundStatin-associated necrotizing myopathy (SANM) is a rare autoimmune disorder caused by administration of statins. SANM is characterized by weakness due to necrosis and regeneration of myofibers. Here we report the first case of SANM with acute respiratory failure treated with noninvasive pressure support ventilation in addition to immunosuppressants.Case presentationA 59-year-old woman who had been treated with 2.5 mg/day of rosuvastatin calcium for 5 years stopped taking the drug 4 months before admission to our hospital due to elevation of creatine kinase (CK). Withdrawal of rosuvastatin for 1 month did not decrease the level of CK, and she was admitted to our hospital due to the development of muscle weakness of her neck and bilateral upper extremities. Anti-3-hydroxy-3-methylglutaryl coenzyme A reductase antibodies were positive. Magnetic resonance imaging showed myositis, and muscle biopsy from the right biceps brachii muscle showed muscle fiber necrosis and regeneration without inflammatory cell infiltration, suggesting SANM. After the diagnosis, she received methylprednisolone pulse therapy (mPSL, 1 g/day × 3 days, twice) and subsequent oral prednisolone therapy (PSL, 30 mg/day for 1 month, 25 mg/day for 1 month and 22.5 mg/day for 1 month), leading to improvement of her muscle weakness. One month after the PSL tapering to 20 mg/day, her muscle weakness deteriorated with oxygen desaturation (SpO2: 93% at room air) due to hypoventilation caused by weakness of respiratory muscles. BIPAP was used for the management of acute respiratory failure in combination with IVIG (20 g/day × 5 days) followed by mPSL pulse therapy (1 g/day × 3 days), oral PSL (30 mg/day × 3 weeks, then tapered to 25 mg/day) and tacrolimus (3 mg/day). Twenty-seven days after the start of BIPAP, she was weaned from BIPAP with improvement of muscle weakness, hypoxemia and hypercapnia. After she achieved remission with improvement of muscle weakness and reduction of serum CK level to a normal level, the dose of oral prednisolone was gradually tapered to 12.5 mg/day without relapse for 3 months.ConclusionsOur report provides new insights into the role of immunosuppressants and biphasic positive airway pressure for induction of remission in patients with SANM.

Effect of dry needling on submaximal strength and pain in patients with active myofascial trigger points in the rectus femoris: A case series

AbstractA myofascial trigger point (MTrP) is a hyperirritable area of a skeletal muscle, of nodular appearance on palpation and located in a taut band. One of the techniques for the treatment of MTrP is dry needling (DN). The aim of the present work was to determine whether treatment with DN is effective in terms of pain relief and improvement of muscle weakness. For this purpose, differences in the Visual Analog Scale (VAS) and the Brzycki Test were observed before and after treatment of an active MTrP of the rectus femoris. In total, 5 patients received the treatment, of which 80% showed an improvement in pain and an increase in submaximal strength. Although it is not possible to establish a causal relationship, the results appear consistent with our hypothesis that DN is able to generally improve the symptoms of pain and weakness that appeared in patients.

SUN-604 Dermatomiositis in a Patient with Papillary Thyroid Cancer: Simple Association or Paraneoplastic Syndrome?

The presentation of Dermatomyositis as a paraneoplastic syndrome is known. It is associated with malignancy of lung, pancreas, ovary, gastrointestinal and lymphoma not hodking. In thyroid neoplasias, the evidence is almost nil, with 8 cases published to date. Remission of Dermatomyositis does not always occur after thyroidectomy.A 24-year-old woman with hypothyroidism in treatment. In 6 months progressive hyperpigmentation is added in front, malar, nasogeniana, axillary, lumbar and popliteal region; asthenia and proximal muscle weakness that intensifies until hospitalization. On examination: 3N goiter, right thyroid nodule palpable, TSH: 4.9, T4L: 1.1, total CPK: 6579, LDH: 2791, popliteal and lumbosacral hyperpigmentation biopsy: Acanthosis Nigricans. Electromyography: Inflammatory Myopathy, Muscle Biopsy: Dermatomyositis. ANA: speckled pattern 1: 320, other exams: normal. With these findings and fulfilling the criteria of Bohan and Peter is diagnosed Dermatomyositis. We proceed to the search for hidden neoplasms discarding those commonly associated. Thyroid ultrasound: hypoechoic image in left lobe, vascularized, ill-defined edges of 11x10 mm. BAAF: Bethesda VI. Thyroglobulin: 6.84 ng / m, Anti-thyroglobulin: 67.68 IU / mL. Total thyroidectomy was performed with group VI dissection. AP: Classic type Papillary Carcinoma pT3N1a. Dermatomyositis was managed with pulses of methylprednisolone leaving the hospital with oral corticotherapy, there was moderate improvement in muscle weakness, with persistence of hyperpigmentation.Although there is controversy between the association of these two entities, we consider it important to include thyroid cancer in the search for hidden neoplasms. The corresponding permission was requested to the patient to use his information for academic purposes.

Acute Myocarditis and Myositis Associated With Nivolumab Therapy

SESSION TITLE: Student/Resident Case Report Poster - Cardiovascular Disease I SESSION TYPE: Student/Resident Case Report Poster PRESENTED ON: Tuesday, October 25, 2016 at 01:30 PM - 02:30 PM INTRODUCTION: Nivolumab a monoclonal antibody which selectively inhibits programmed cell death-1(PD-1) receptor is FDA approved for the treatment of solid cancers.1 We present a case of a 79 year old male with history of metastatic non small cell lung cancer (NSCLC) on nivolumab who presented with muscle pain, weakness and dyspnea. His presentation was consistent with nivolumab induced auto-immune myositis and myocarditis. CASE PRESENTATION: A 79 year old male presents with complaints of acute onset back pain and generalized weakness causing gait instability for 2 weeks and dyspnea for 3 days. He was diagnosed with metastatic adenocarcinoma of the lung and on treatment with nivolumab, last dose was 1 week before presentation. On presentation he was hypotensive (80/45mmHg), HR was 76 beats/min irregular rhythm. On exam S3 gallop was present and lungs were clear. There was evidence of neck flexor weakness and symmetric pure motor proximal hip flexor weakness. Hemoglobin of 10.6 g/dl, AST:1083 IU/ml, ALT:497 IU/ml. Creatine kinase 14014 U/L and aldolase of 71 U/L. Auto immune work up was negative. MRI of the proximal leg muscles showed diffuse edema in the quadriceps, adductors and gluteus muscles. Troponin T peaked at 3.66 ng/ml, and pro BNP was elevated at 9532 pg/ml. Patient developed worsening ventricular arrhythmias. His LV function was markedly reduced (LVEF15%). He was started on inotropes and amiodarone. Myocardial and muscle biopsies were planned but patient refused both the procedures.He was started on amiodarone and lidocaine for frequent multifocal ventricular tachyarrhythmias. Supportive inotropic therapy was used. After the MRI results corticosteroid therapy was initiated. On clinical examination mild improvement in muscle weakness was noted. DISCUSSION: Cancer immunotherapy is a double edged sword. Monoclonal antibodies against T cells enhance the immune response not only to cancer cells but also to normal host tissue1. The presentation of patients who present with adverse effects of these agents often mimics autoimmune diseases.In our patient the differential diagnosis of polymyositis was entertained. However the recent administration of nivolumab and negative muscle antibodies made nivolumab the likely culprit. Myositis and myocarditis have been separately reported as adverse effects of PD1 therapy.2,3 CONCLUSIONS: Immune related adverse effects of monoclonal antibodies must be identified early in the clinical course as discontinuation of the offending agent may hasten recovery. Reference #1: Brahmer JR, Tykodi SS, et al. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med. 2012;366:2455-65. Reference #2: Läubli H, Balmelli C, et al. Acute heart failure due to autoimmune myocarditis under pembrolizumab treatment for metastatic melanoma. J Immunother Cancer. 2015 Apr 21;3:11. Reference #3: Yoshioka M, Kambe N, et al. Case of respiratory discomfort due to myositis after administration of nivolumab. J Dermatol. 2015 Oct;42(10):1008-9. DISCLOSURE: The following authors have nothing to disclose: Anita Mehta, Nayan Desai, Fredric Ginsberg No Product/Research Disclosure Information

AB0649 Clinical Features of Spontaneous Pneumomediastinum in Dermatomyositis

BackgroundSpontaneous pneumomediastinum is a rare complication and a poor prognostic factor of dermatomyositis (DM). But the mechanisms, outcome, and prognostic factors of DM associated pneumomediastinum have not yet been evaluated.ObjectivesTo...

FRI0499 Retrospective CASE Series of Refractory Antisynthetase Syndrome Successfully Treated with Rituximab (3 CASES)

BackgroundAntisynthetase syndrome (ASS) is an idiopathic inflammatory myopathy characterised by the presence of anti-Jo-1 antibodies. Patients usually present with myositis, interstitial lung diseases, and arthritis. Corticosteroid therapy is the first...

Paraneoplastic dermatomyositis with carcinoma cervix: a rare clinical association.

Dermatomyositis is an uncommon inflammatory myopathy associated with cutaneous manifestations. It may also occur as paraneoplastic syndrome associated with various malignancies, most common of which being lung, breast, stomach, rectum, kidney, or testicular cancer. A postmenopausal woman presented to us with generalized itching along with skin rash and proximal muscle weakness of 2 years' duration. Examination revealed heliotrope rash and mechanic hands and muscle power 2/5 in proximal muscle groups of both upper and lower limbs. A clinical diagnosis of dermatomyositis was made which was supported by raised lactate dehydrogenase levels and skin biopsy findings. Past history was significant for vaginal discharge and bleeding per vagina. Further work-up revealed carcinoma cervix and she was referred to oncology department for further management. Temporal relationship and improvement of muscle weakness with treatment of underlying neoplasm supported its paraneoplastic nature. So, final diagnosis of keratinizing squamous cell carcinoma of cervix with paraneoplastic dermatomyositis was made. A nationwide cohort study of 1,012 patients with dermatomyositis in Taiwan revealed only 3 patients with cervical cancer. So this case is being reported for its rare association with carcinoma cervix and to highlight the need of detailed evaluation for underlying malignancies in patients with dermatomyositis.

Expression of vascular endothelial growth factor by plasma cells in the sclerotic bone lesion of a patient with POEMS syndrome

Sirs: Bone lesions are frequently present in patients with POEMS syndrome [1, 2]. Since solitary bone lesions are often plasmacytomas, they must be aggressively treated with surgery or radiotherapy. We report a case of POEMS syndrome with a solitary bone lesion. In this patient, plasma cells in the osteosclerotic lesion were the source of vascular endothelial growth factor (VEGF). A 42–year-old man developed distal dominant polyneuropathy two months after myocardial infarction. Following the onset of neurological symptoms, he exhibited edema, bristly skin, and swelling of the liver in the abdominal CT. Platelet counts were 822,000/mm, and immunoelectrophoresis demonstrated Mprotein of IgA k. Serum IL-6 and VEGF were measured using standardized ELISA (SRL, Inc., Tokyo, Japan). Although the IL-6 level was normal (2.1 pg/ml. Normal value; <4.0 pg/ml), the serum VEGF level was significantly elevated (18,500 pg/ml). He was diagnosed with POEMS syndrome. However, bone marrow aspiration from the ileum exhibited a normal appearance, and CT of the chest and the abdomen revealed no abnormal lesions, suggesting solitary or extramedullary plasmacytoma. Following steroid pulse therapy, treatment with prednisolone reduced the serum VEGF to 860 pg/ ml with marked improvement of muscle weakness and skin lesions. Although the neuropathy remained clinically stable, he again exhibited edema and bristly skin 9 months after the pulse therapy, and the serum VEGF was increased to 5,120 pg/ml. Bone scintigraphy demonstrated a spot

Quantitative evaluation of improvement in muscle weakness in a patient receiving extracorporeal photopheresis for scleroderma: Magnetic resonance imaging and magnetic resonance spectroscopy

1. Griffiths CEM, Voorhees JJ. Immunological mechanisms involved in psoriasis. Semin Immunopaihol 1992; 13:44154. Voorhees JJ. Leukotrienes and other lipoxygenase products in the pathogenesis and therapy of psoriasis and other dermatoses. Arch Dermatol 1983;119:541-7. Baker BS, Friy L. The immunology of psoriasis. Br J Dermatol 1992;126:1-9. Stichlerling M, Bomscheuer E, Schroder JM, et al. Localization of neutrophil-activating peptide-l/interleukin-8 immunoxeactivity in normal and psoriatic skin. J Invest Dermatol 1991;96:26-30. Gillitzer R, Berger R, Mielke V, et al. Upper keratinocytes of psoriatic skin lesions express high levels of NAP-l/IL-8 mRNA in situ. J Invest Dermatol 1991;97:73-9. 6.

REMISSION OF MYASTHENIA GRAVIS FOLLOWING PLASMA-EXCHANGE

A course of daily plasma-exchange was undertaken in 3 patients with severe myasthenia gravis (M.G.) who had failed to respond to anticholinesterases, thymectomy, and steroids. In the 2 cases with acquired M.G., exchange was associated with an unequivocal improvement in muscle weakness and fatiguability, indicating that a humoral factor in plasma is directly concerned in causing the disorder of neuromuscular transmission. The improvement began within a few days of initiating exchange and continued for several days after exchange ceased. Preliminary evidence suggests that the beneficial effect can be maintained with subsequent immunosuppressive therapy. The patient with congenital M.G. failed to improve, suggesting that its pathogenesis may differ from that of the acquired disease.

Myopathy in Chronic Renal Failure

A group of eleven patients in end-stage renal failure who developed proximal weakness is described. The muscle weakness in all cases was shown to be myopathic in nature by quantitative electromyography. Four of the patients presented with muscle dysfunction and were found to have severe osteomalacia secondary to renal disease. In these patients vitamin D in high doses produced some improvement in muscle weakness. In the other patients who were on maintenance dialysis, muscle weakness improved dramatically after renal transplantation or dialysis with deionized water. There were no quantitative differences between the two groups as far as muscle weakness was concerned. However it is suggested that metabolic bone disease may be one pathogenic factor in the first group and that some aspect of renal failure per se (or its treatment by dialysis) may predominate in the second and contribute to the first.

EFFECTS OF 1,25-DIHYDROXYCHOLECALCIFEROL ON CALCIUM ABSORPTION, MUSCLE WEAKNESS, AND BONE DISEASE IN CHRONIC RENAL FAILURE

Small amounts (0.35-2.7 μg.) of 1,25 dihydroxycholecalciferol (1,25-D.H.C.C.), the hormonally active metabolite of vitamin D 3, were given to eleven patients with chronic renal failure for 4-150 days. 1,25-D.H.C.C. given for 4-8 days increased intestinal 47Ca absorption without causing large changes in plasma calcium or phosphate, or in plasma or urine hydroxyproline measurements. 1,25-D.H.C.C. was given for a longer period (58 and 150 days) to two of the patients. In one, a 14-year-old girl, plasma alkaline phosphatase and non-protein bound hydroxyproline fell and there was healing of radiological rickets and secondary hyperparathyroidism; and in the other, a man of 58 years, there was striking improvement in muscle weakness. The resistance to treatment with vitamin D in chronic renal failure is probably related to impaired metabolic conversation to active derivatives, the most important of which may be 1,25–D.H.C.C. 1,25–D.H.C.C. seems capable of correcting some, if not all, of the disturbances in calcium metabolism in this disorder.