Ten Years’ Follow-Up of a Family With Myokymia and Muscle Cramps Without Ataxia

Abstract Imatinib (IM) at 400 mg daily is the first line therapy for newly diagnosed CML patients (pts); however, less than 50% of major molecular responses (MMR) are obtained at 12 months. To improve these results, we designed a phase III, multicenter, open-label, prospective randomized trial. The reference arm was IM 400 mg daily (n=159). The 3 experimental arms were IM 600 mg daily (n=160), IM 400mg daily in combination with Ara-C, (20 mg/m2/day, days 15–28 of 28-day cycles)(n=158) and IM 400mg in combination with Peg-IFN alfa-2a (Peg-IFN2a, 90 μg weekly) (n=159). Treatment was delivered at least 12 months or until treatment failure (disease progression) or major toxicity. The primary endpoint is the overall survival. Other endpoints are: rate and duration of hematologic and cytogenetic responses, major (MCyR) and complete (CCyR), molecular response (major molecular response ie MMR) and the tolerability. Using treatment allocation ratio 1.1.1.1, randomization was stratified according to Sokal risk groups. The current interim analysis of the first 636 patients (α=0.85%, β=10%) at 1 year from randomization was planned in order to select the best experimental arm for further comparison with IM 400. The increased dose of IM or a combination regimen would be considered as promising if it increased the 4 log reduction response rate by at least 20 percentage points, e.g. from 15% to 35%, with an acceptable tolerability. Evaluation of molecular response up to 12 months was centralized, blinded and calculated according to International score (IS). Pts were recruited between 9/2003 and 10/2007.[median age 51 yrs (18–82), 62% of pts were male; Sokal distribution was low risk 33%, intermediate risk 41% and 27% high risk]. Median follow-up is 36 months (range 8–57) at the time of analysis. Overall, at 3 months 86 % of pts achieved complete hematologic response. The MCyR, CCyR and MMR rates at 6 and 12 months are: IM-400 IM-600 IM-Ara-c IM-PegIFN *p< 10−2 (overall); ** p<10−2 (overall) At 6 months (636 pts, ITT) MCyR 74% 79% 68% 74% CCyR * 48% 67% 55% 56% At 12months (562 evaluable pts) MCyR 64% 76% 77% 74% CCyR 57% 65% 66% 71% MMR at 6 months** 21% 33% 27% 39% MMR at 12 months 40% 52% 51% 61% Interestingly the rate of MMR at 6 months was significantly higher for IM-PegIFN as compared with IM-400 (p<10−3). The 4-log reduction rate in the BCR-ABL/ABL transcript were 18%, 21%, 22%, 34%, for the IM-400, IM-600, IM-Ara-c and IM-PegIFN arms respectively. The corresponding numbers of undetectable (complete molecular response) pts were 2%, 2%, 3% and 9% at 12 months respectively. Grade 3/4 neutropenia and/or thrombocytopenia occurred in 8% of IM-400 pts, in 14% of IM-600 pts, in 41% of IMAra- c pts and in 40% of IM-PegIFN pts respectively. Grade 3/4 non hematological events were reported in 19% of IM-400 pts, in 30% of IM-600 pts, in 27% of IM Ara-c pts and in 31% of IM-PegIFN pts. Among them a relationship between treatment and event was suspected for 21 pts (13%) with IM-400 (7 liver toxicity; 7 oedema+muscle cramps), for 31 pts (19%) with IM-600 (7 liver toxicity, 11 oedema+ muscle cramps) for 36 pts (23%) with IM-Ara-c (2 liver toxicity; 10 gut side effect) and for 47 pts (29%) with IM-PegIFN (6 liver toxicity, 13 skin rash). Discontinuation of experimental treatment occurred within the first 6 and 12 months in 26% and 18% of IM-Ara-c pts and in 35% and 11% pts of IM-PegIFN pts respectively. Within the first 12 months 36% of 600-IM pts reduced their dosage. Although a substantial number of pts stopped PegIFN, this first analysis indicates the usefulness of a combination of IM-PegIFN for the initial treatment of pts with CML CP with a significant molecular response rate improvement. Complete analysis of the 636 pts with a follow-up of 12 months will be presented.

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Famotidine induced hypomagnesemia leading to hypocalcemia

Oxford Medical Case Reports ◽

10.1093/omcr/omz133 ◽

2020 ◽

Vol 2020 (1) ◽

Author(s):

Rajesh Essrani ◽

Shehriyar Mehershahi ◽

Shri Jai Kirshan Ravi ◽

Rajesh Kumar Essrani ◽

Anuraj Sudhakaran ◽

...

Keyword(s):

Vitamin D ◽

Gastroesophageal Reflux Disease ◽

Gastroesophageal Reflux ◽

Past Medical History ◽

Dry Skin ◽

Urine Calcium ◽

Muscle Cramps ◽

History Of ◽

Calcium And Magnesium

Abstract Fifty-five-year-old female with a past medical history of gastroesophageal reflux disease was admitted to hospital due to increased confusion, and muscle cramps for last 15 days. She was taking famotidine 20 mg twice a day for the last 2 years. She was alert and oriented to person and place only. She had dry skin, positive Chvostek’s and Trousseau’s sign. Blood work showed 141 mmol/L of sodium, 0.7 mg/dl of creatinine, 5.7 mg/dl of calcium, 0.55 mg/dl of magnesium, low PTH but normal parathyroid related peptide PTHrP, vitamin D (25) and vitamin D (1.25). She was discharged home on electrolyte supplements. She was readmitted with very low calcium and magnesium. Extensive workup including 24 h of urine calcium and magnesium was unimpressive. She was treated with IV therapy and discharged to follow up with nephrology in the clinic, and famotidine was discontinued on second discharge. Her calcium and magnesium levels remained normal, and in a few weeks later, oral electrolyte supplements were discontinued.

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Treatment of fibrillary glomerulonephritis with rituximab: a 12-month pilot study

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa065 ◽

2020 ◽

Vol 36 (1) ◽

pp. 104-110 ◽

Cited By ~ 1

Author(s):

Stephen B Erickson ◽

Ladan Zand ◽

Samih H Nasr ◽

Mariam P Alexander ◽

Nelson Leung ◽

...

Keyword(s):

Creatinine Clearance ◽

Primary Outcome ◽

Nasal Congestion ◽

Common Adverse Event ◽

Secondary Outcome ◽

Efficacy And Safety ◽

Rare Type ◽

Fibrillary Glomerulonephritis ◽

Muscle Cramps

Abstract Background Fibrillary glomerulonephritis (FGN) is a rare type of glomerulonephritis with poor prognosis, with no known effective therapies available for treatment. The objective of the study was to evaluate the efficacy and safety of rituximab in treatment of patients with FGN and to investigate the effect of rituximab on DNAJB9 levels. Methods This was a pilot prospective clinical trial in which patients with idiopathic FGN were treated with two courses of rituximab (1 g each) 2 weeks apart at the beginning and then again at 6 months. Primary outcome was defined as preservation of kidney function at 12 months with stable or increased creatinine clearance. Secondary outcome was defined as achieving complete remission (CR) defined as proteinuria <300 mg/24 h or partial remission (PR) with proteinuria <3 g/24 h and at least 50% reduction in the proteinuria. DNAJB9 levels were also measured in the serum at baseline, 6 and 12 months. Results The creatinine clearance did not change significantly during this time, from 47.7 mL/min/1.73 m2 at baseline to 43.7 mL/min/1.73 m2 during follow-up (P = 0.15). Proteinuria declined from 4.43 (1.6–5.53) g/24 h at baseline to 1.9 (0.46–5.26) g/24 h at 12 months but did not reach significance (P = 0.06). None of the patients reached CR, and 3 of the 11 achieved PR. There was no change in the DNAJB9 levels following treatment with rituximab. The most common adverse event was nasal congestion, fatigue and muscle cramps. Conclusions Treatment of patients with two courses of rituximab over a span of 6 months was associated with stabilization of renal function but did not result in a significant change in proteinuria and with no change in the DNAJB9 levels.

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The symptomatology of fever: a step towards qualitative definition of fever

10.1101/2021.08.03.21261558 ◽

2021 ◽

Author(s):

Mayank Kapoor ◽

Nitin Kumar ◽

Prasan Kumar Panda

Keyword(s):

Cross Sectional ◽

Muscle Cramps ◽

General Weakness ◽

Associated Symptoms ◽

Higher Temperature ◽

Waking Up ◽

One Year ◽

Definition Of ◽

Loss Of Appetite

Background: The old definitions of fever are based on cross-sectional surveys of the population without analyzing the associated symptomatology. Objectives: To analyze associated symptoms with fever in a longitudinal follow-up study. Methods: In a longitudinal study over one year, 196 participants recorded three temperature readings daily, one after waking up, one between 12-3 PM, one before sleeping, and filled the symptomatology questionnaire in a thermometry diary. Results: Per protocol analysis was done for febrile participants (n=144). Fatigue (50.3%), warmth (47.3%), headache/head heaviness (47.0%), feeling malaise/general weakness (46.7%), loss of appetite (46.5%), muscle cramps/muscle aches (45.6%), chills/shivering (44.6%), increased sweating (43.0%), nausea (42.5%), irritability (38.9%), increased breathing rate (37.1%), and restlessness/anxiety/palpitations (36.5%) were the symptoms maximally seen during the febrile phase. A higher number of associated symptoms are associated with higher temperature readings. Dehydration suggested the numerically highest temperature values (100.86oF) but seen in few febrile patients. Conclusions: Incorporation of symptom analysis in febrile patients is the need of the hour. Fatigue and warmth are found to be most prevelent symptoms during febrile phase. Associated symptoms can help in predicting the intensity of fever also.

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Therapy and prevention for mental health: What if mental diseases are mostly not brain disorders?

Behavioral and Brain Sciences ◽

10.1017/s0140525x1800105x ◽

2019 ◽

Vol 42 ◽

Cited By ~ 2

Author(s):

John P. A. Ioannidis

Keyword(s):

Mental Health ◽

Mental Disease ◽

Brain Disorders ◽

Social Stressors ◽

Labor Education ◽

Mental Diseases ◽

Long Term Follow Up ◽

Political Decisions

AbstractNeurobiology-based interventions for mental diseases and searches for useful biomarkers of treatment response have largely failed. Clinical trials should assess interventions related to environmental and social stressors, with long-term follow-up; social rather than biological endpoints; personalized outcomes; and suitable cluster, adaptive, and n-of-1 designs. Labor, education, financial, and other social/political decisions should be evaluated for their impacts on mental disease.

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Brief summary of Kleť photographic search programme for minor planets

International Astronomical Union Colloquium ◽

10.1017/s0252921100031419 ◽

1999 ◽

Vol 173 ◽

pp. 189-192

Author(s):

J. Tichá ◽

M. Tichý ◽

Z. Moravec

Keyword(s):

Ccd Camera ◽

Minor Planet ◽

Minor Planets ◽

Main Belt

AbstractA long-term photographic search programme for minor planets was begun at the Kleť Observatory at the end of seventies using a 0.63-m Maksutov telescope, but with insufficient respect for long-arc follow-up astrometry. More than two thousand provisional designations were given to new Kleť discoveries. Since 1993 targeted follow-up astrometry of Kleť candidates has been performed with a 0.57-m reflector equipped with a CCD camera, and reliable orbits for many previous Kleť discoveries have been determined. The photographic programme results in more than 350 numbered minor planets credited to Kleť, one of the world's most prolific discovery sites. Nearly 50 per cent of them were numbered as a consequence of CCD follow-up observations since 1994.This brief summary describes the results of this Kleť photographic minor planet survey between 1977 and 1996. The majority of the Kleť photographic discoveries are main belt asteroids, but two Amor type asteroids and one Trojan have been found.

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Intranuclear Crystals in Regenerating Canine Kidneys

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100072502 ◽

1973 ◽

Vol 31 ◽

pp. 412-413

Author(s):

D.G. Osborne ◽

L.J. McCormack ◽

M.O. Magnusson ◽

W.S. Kiser

Keyword(s):

Epithelial Cell ◽

Epithelial Cells ◽

Tubular Epithelial Cell ◽

Tubular Epithelial Cells ◽

Cell Nuclei ◽

Crystalline Structures ◽

Small Crystals ◽

Membrane Bound

During a project in which regenerative changes were studied in autotransplanted canine kidneys, intranuclear crystals were seen in a small number of tubular epithelial cells. These crystalline structures were seen in the control specimens and also in regenerating specimens; the main differences being in size and number of them. The control specimens showed a few tubular epithelial cell nuclei almost completely occupied by large crystals that were not membrane bound. Subsequent follow-up biopsies of the same kidneys contained similar intranuclear crystals but of a much smaller size. Some of these nuclei contained several small crystals. The small crystals occurred at one week following transplantation and were seen even four weeks following transplantation. As time passed, the small crystals appeared to fuse to form larger crystals.

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Electron Microscopy of Human Gallstones

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100065523 ◽

1971 ◽

Vol 29 ◽

pp. 296-297

Author(s):

C. Wolpers ◽

R. Blaschke

Keyword(s):

Electron Microscopy ◽

Room Temperature ◽

Bile Pigment ◽

X Ray Diffraction ◽

Triclinic Crystal System ◽

X Ray ◽

Follow Up Study ◽

Infra Red ◽

Main Components

Scanning microscopy was used to study the surface of human gallstones and the surface of fractures. The specimens were obtained by operation, washed with water, dried at room temperature and shadowcasted with carbon and aluminum. Most of the specimens belong to patients from a series of X-ray follow-up study, examined during the last twenty years. So it was possible to evaluate approximately the age of these gallstones and to get information on the intensity of growing and solving.Cholesterol, a group of bile pigment substances and different salts of calcium, are the main components of human gallstones. By X-ray diffraction technique, infra-red spectroscopy and by chemical analysis it was demonstrated that all three components can be found in any gallstone. In the presence of water cholesterol crystallizes in pane-like plates of the triclinic crystal system.

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Articulatory Intervention for the Visually Impaired

Language Speech and Hearing Services in Schools ◽

10.1044/0161-1461.1003.139 ◽

1979 ◽

Vol 10 (3) ◽

pp. 139-144

Author(s):

Cheri L. Florance ◽

Judith O’Keefe

Keyword(s):

High School ◽

High School Students ◽

Behavior Change ◽

Visually Impaired ◽

School Students ◽

Handicapped Children ◽

Paired Stimuli ◽

Visually Handicapped ◽

Parent Program

A modification of the Paired-Stimuli Parent Program (Florance, 1977) was adapted for the treatment of articulatory errors of visually handicapped children. Blind high school students served as clinical aides. A discussion of treatment methodology, and the results of administrating the program to 32 children, including a two-year follow-up evaluation to measure permanence of behavior change, is presented.

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What Does Evidence-Based Practice Mean to You? A Follow-Up Study Examining School-Based Speech-Language Pathologists' Perspectives on Evidence-Based Practice

American Journal of Speech-Language Pathology ◽

10.1044/2019_ajslp-19-00171 ◽

2020 ◽

Vol 29 (2) ◽

pp. 688-704

Author(s):

Katrina Fulcher-Rood ◽

Anny Castilla-Earls ◽

Jeff Higginbotham

Keyword(s):

Clinical Practice ◽

Research Evidence ◽

Evidence Based Practice ◽

Evidence Based ◽

Clinical Expertise ◽

Speech Language Pathologists ◽

School Based ◽

Research Findings ◽

Ebp Implementation

Purpose The current investigation is a follow-up from a previous study examining child language diagnostic decision making in school-based speech-language pathologists (SLPs). The purpose of this study was to examine the SLPs' perspectives regarding the use of evidence-based practice (EBP) in their clinical work. Method Semistructured phone interviews were conducted with 25 school-based SLPs who previously participated in an earlier study by Fulcher-Rood et al. 2018). SLPs were asked questions regarding their definition of EBP, the value of research evidence, contexts in which they implement scientific literature in clinical practice, and the barriers to implementing EBP. Results SLPs' definitions of EBP differed from current definitions, in that SLPs only included the use of research findings. SLPs seem to discuss EBP as it relates to treatment and not assessment. Reported barriers to EBP implementation were insufficient time, limited funding, and restrictions from their employment setting. SLPs found it difficult to translate research findings to clinical practice. SLPs implemented external research evidence when they did not have enough clinical expertise regarding a specific client or when they needed scientific evidence to support a strategy they used. Conclusions SLPs appear to use EBP for specific reasons and not for every clinical decision they make. In addition, SLPs rely on EBP for treatment decisions and not for assessment decisions. Educational systems potentially present other challenges that need to be considered for EBP implementation. Considerations for implementation science and the research-to-practice gap are discussed.

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