Author Archives: Richard

About Richard

Inventor, entrepreneur, father, medical device manager.

Breathing Problems

Posted on by
Reply
Mechanism of CO2    Retention in Patients With Neuromuscular Disease*
[Clinical    Investigations: Control Of Breathing]
Misuri, Gianni MD; Lanini, Barbara MD; Gigliotti, Francesco MD; Iandelli, Iacopo MD; Pizzi, Assunta MD; Bertolini, Maria Grazia RT; Scano, Giorgio MD, FCCP
*From the Fondazione Don C. Gnocchi, ONLUS, Pozzolatico (Firenze), Italy.
Manuscript received February 26, 1999; revision accepted September 21, 1999.
This study was supported by a grant from MPI of Italy.
Correspondence to: Giorgio Scano, MD, FCCP, Section of Respiratory Disease, Fondazione Don C. Gnocchi, ONLUS, Pozzolatico, Via Imprunetana, Pozzolatico (Firenze), CAP 50020 Italy; e-mail: riabrfi@tin.it
Abstract

Background: In many studies of patients with muscle weakness, chronic hypercapnia has appeared to be out of proportion to the severity of muscle disease, indicating that factors other than muscle weakness are involved in CO2 retention. In patients with COPD, the unbalanced inspiratory muscle loading-to-strength ratio is thought to trigger the signal for the integrated response that leads to rapid and shallow breathing and eventually to chronic hypercapnia. This mechanism, although postulated, has not yet been assessed in patients with muscular dystrophy.
Abbreviations: Eldyn = dynamic lung elastance; Eldyn (%Pplsn) = elastic load per unit of inspiratory muscle force; FRC = functional residual capacity; LGD = limb-girdle dystrophy; MD = myotonic dystrophy; MEP = maximal expiratory pressure; MIP = maximal inspiratory pressure; NMD = neuromuscular disease; NS = not significant; Pi = mean inspiratory driving pressure; P0.1 = mouth occlusion pressure; Ppl = pleural pressure; Pplsn = pleural pressure during a sniff maneuver; Rf = respiratory frequency; RL = lung resistance; RSB = rapid and shallow breathing; TE = expiratory time; TI = inspiratory time; TTOT = total time of respiratory cycle; VC = vital capacity; [latin capital V with dot above]E = minute ventilation; VT = tidal volume; Zrs = impedance of the respiratory system
sdfsdafsdafd
Materials and Methods
Subjects
Twenty consecutive patients (10 men) with a mean age of 47.6 years (range, 23 to 67 years) were studied: 11 patients with limb-girdle dystrophy (LGD), 3 with Duchenne muscular dystrophy, 2 with amyotrophic lateral sclerosis, 1 with Charcot-Marie-Tooth syndrome, 1 with Becker muscular dystrophy, 1 with MD, 1 with facioscapulohumeral dystrophy, and no respiratory complaints. Nine were ambulatory, and 11 were wheelchair bound. The standard criteria were used to select patients. 20,21

None of the patients had a scoliosis nor any abnormalities on chest radiograph nor obvious abnormalities in diaphragm placement. Five patients were current mild smokers (<=5 pack-years).

Seventeen normal subjects matched for age (range, 26 to 62 years; mean, 41.5 years) and sex (8 men) were studied as a control group. The study was approved by the local ethics committee, and the subjects gave their informed consent.

The anthropometric characteristics of the patients are shown in Table 1.
Functional Evaluation

Routine spirometry, obtained with the patients seated in a comfortable armchair, was measured as previously described. 13,16,22 Functional residual capacity (FRC) was measured by the helium dilution technique. The normal values for lung volumes were those of the European Community for Coal and Steel. 23 Arterial blood gas tensions were measured with a blood gas analyzer (IL-1304; Instrumentation Laboratory; Milan, Italy).
sdfsdafsdafd
Protocol All subjects were tested in the morning. Before the experiment, the subjects were well acquainted with the laboratory and equipment. An arterial blood sample and lung function tests were performed, and then changes in volume, flow, and Ppl were recorded. Finally, the respiratory muscle strength tests were performed in each patient.

Data Analysis
Volume and time components of the respiratory cycle, RL, and Eldyn were averaged in each patient over 30 consecutive breaths. Eldyn was expressed both as an actual value and as a percent of Pplsn, an index of the balance between the elastic load of the lung relative to the maximal inspiratory force available. Single and stepwise multiple regression analyses were performed to assess relationships between variables. The statistical analysis we carried out considers the dependency of a variable (eg, the level of PaCO2) on a series of independent variables. The effect of each variable on PaCO2 was evaluated independent of the effect of all other variables. In a multivariate analysis, a rule of thumb is to limit the number of variables as a function of the number of patients.28 Thus, multiple regression analysis with stepwise selection of the independent variables was carried out relating PaCO2 to functional variables. The proportion of total variance in the dependent variable accounted for by the predicted variables is reported as the square of the correlation coefficient (r2). Single regression analysis was performed using Pearson’s single correlation coefficient. Comparisons between groups were made using the Mann-Whitney U test. A value of p < 0.05 was considered as the threshold of statistical significance. Data are presented as mean ± SD unless otherwise specified. .
Results

Clinical, anthropometric, and respiratory function characteristics of the patients (and control subjects) are shown in Table 1. As shown in Table 1, vital capacity (VC) was reduced in 11 patients, as was total lung capacity in 9. The means of MIP (47.8 ± 28.3 cm H2O; range, 11 to 127 cm H2O; p = 0.00001) and MEP (49.5 ± 26.2 cm H2O; range, 15 to 104 cm H2O; p = 0.00002) were significantly lower than in control subjects. In 11 patients and 10 patients, the values of MIP and MEP, respectively, were lower than the mean – 2 SD of the value calculated for the control subjects. Arterial blood gases were normal in all but eight patients in whom PaCO2 was considered to be high (>= 45 mm Hg) and in three patients in whom PaCO2 was low (< 80 mm Hg). In some of the patients, and particularly in patients 12 and 14, in whom PaCO2 was normal, a high level of ventilation was found.
sdfsdafsdafd
Discussion
We have found that in patients with NMD, Eldyn (%Pplsn) is the strongest predictor of the variance in PaCO2. Increased Eldyn (%Pplsn) was associated with a decreased TI, which truncates VT, thereby leading to chronic CO2 retention (PaCO2).
sdfsdafsdafd
References
1 Begin R, Bureau MA, Lupien L, et al. Control of breathing in Duchenne’s muscular dystrophy. Am J Med 1980; 69:227-234
2 Kilburn KH, Eagen JT, Sieker HO, et al. Cardiopulmonary insufficiency in myotonic and progressive muscular dystrophy. N Engl J Med 1959; 261:1089-1096

Cataracts

Posted on by
Reply

CATARACTS

Cataracts are a common problem with Myotonic dystrophy. Often it will be the first symptom of the disease. These are easy treatable with replacements often at a low-cost.

Cataract Brochure Myotonic Dystrophy (PDF)
Information on eyes and Dry eyes

Yichieh Shiuey, MD and Theresa C. Chen, MD
Massachusetts Eye and Ear Infirmary, Harvard Medical
School, Boston, MA
This is a high magnification view of a cataract in a middle-aged woman. (Photograph courtesy of Teresa C. Chen, MD)

What type of cataract is this?
Answer: Christmas tree cataract.

What systemic medical condition is classically associated with these lens findings?
Answer: Myotonic dystrophy

What other ocular findings may this patient have?
Answer: Ptosis, orbicularis weakness, progressive external ophthalmoplegia, and pigmentary retinopathy similar to that of Kearn’s Sayre syndrome. Aside from Christmas tree cataracts which contain multicolored iridescent crystals, patients with myotonic dystrophy may also have spokelike cortical opacities along the suture line.

What general physical examination findings may this patient have?
Answer: Myotonia is the often the first detectable physical exam finding. This may be strikingly demonstrated by shaking hands with the patient. The patient may not be able to release his or her grip. Patients with myotonic dystrophy may also have weakness of the limb muscles, particularly the leg extensors. Atrophy of limb muscles may also be apparent on inspection. Men in this condition often have early onset of frontal baldness.

What is the inheritance pattern of this systemic medical condition?
Answer: autosomal dominant

A Call for Cataract Samples
The early appearance of cataracts is an important feature of Myotonic Dystrophy and is often the only obvious symptom in those only mildly affected. This suggests that the lens of the eye is particularly sensitive to Myotonic Dystrophy making it an important target for research.The Norwich Eye Research Groupheaded by Professor George Duncan is one of the foremost centres for lens research in the world. The causes of cataract as well as the development of improved treatments are the central themes of our work. As a member of the group I am heading the Cataract in Myotonic Dystrophy Project.To carry out our research we would like to obtain tissue samples from people with Myotonic Dystrophy. During a normal cataract operation a small piece of tissue is removed from the front of the lens and discarded by the surgeon. At no inconvenience to the patient this small piece of tissue, can be preserved and would be sufficient for us to carry out some extremely valuable work. Not only will it help us to understand how Myotonic Dystrophy causes cataract in the lens but it could give us more fundamental information about the disease as a whole.

Without your support this type of research would not be possible. So can I ask that if you are considering having a cataract operation you contact us either directly here in Norwich (j.rhodes@uea.ac.uk) or via the Myotonic Dystrophy Foundation in Palo Alto , CA and we will arrange with your Ophthalmic consultant for collection of the samples.

Thank you.

Dr. Jeremy D. Rhodes.
e-mail: j.rhodes@uea.ac.uk
Tel: 44 1603 592252

The Norwich Eye Group, School of Biological Sciences, University of East Anglia, Norwich, NR4 7TJ, UK

Dental Needs

Posted on by
Reply

Dental Needs of Patients with DM

Because of the nature of Myotonic Dystrophy, patients need increased dental care. This can come in several forms but the decreased amount of muscle strength can affect the person with DM. They may have more plaque and need more frequnet brushing and dental hygiene. We have found a few articles and stories that focus on dental care that you may wish to review. Print out the first one and take it to your dentist.

Diabetes

Posted on by
Reply

DIABETES

This page will try and summarize information on myotonic dystrophy and diabetes.

Study:

Pathogenesis of Diabetics in Myotonic Dystrophy.

Myotonic dystrophy (MD) is the most common adult form of muscular dystrophy with an estimated prevalence of 1 in 8000 and is often complicated by diabetes. MD is dominantly inherited and is due to heterozygosity for a tri-nucleotide repeat expansion mutation in a protein kinase gene and it was suggested that this induces derangement of RNA metabolism also able to reduce insulin receptor expression. To test whether the abnormal RNA metabolism or a specific malfunction of protein kinase gene may induce insulin resistance prior to the onset of diabetes, we studied 5 glucose-tolerant MD patients (3F/2M, 41 [+ or -] 8yrs, 59 [+ or -] 7 kg, BMI21 [+ or -] 2 kg/[m.sup.2]) and 5 matched healthy subjects, by means of a) dual x-ray energy absorption b) euglycemic-hyperinsulinemic clamp (1 mU/kg/min) c) primed-continuous infusion of 6,6-[d.sup.2]-glucose and I-[sup.13]C-leucine d) indirect calorimetry. Fasting plasma insulin were similar, but proinsulin concentrations were increased in M!

D patients (p=0.01) and the ratio intact proinsulin/insulin (20 [+ or -] 4% vs 5 [+ or -] 1%; p=0.01) was 4-fold higher in MD. MD showed increased body fat mass (35 [+ or -] 5 vs 26 [+ or -] 2%; p=0.05) but lipid oxidation and FFA concentration in the post absorptive and clamp conditions were comparable between the two groups. Glucose metabolism (oxidative and non-oxidative) during insulin stimulation was comparable to normals (6.9 [+ or -] 1.4 vs 8.2 [+ or -] 1.1 mg/]kg FFM.min]; p=0.49). Leucine flux in the post absorptive condition was slightly increased and its sensitivity to insulin was impaired in MD (suppression =8[+ or -]2 vs 19 [+ or -] 2%; p=0.05); also suppression of plasma glutamine (8 [+ or -] 5%) and phenylalanine (8 [+ or -] 2%) concentrations during the clamp were similar than in normals (33 [+ or -] 7 and 15 [+ or] 3% respectively; p=0.05). In summary, MD showed alterations of protein metabolism in both post absorptive and insulin stimulated conditions resulti!

ng in increased proteolysis and muscle wasting. Insulin dependent glucose metabolism is preserved; therefore insulin resistance for glucose is not a major factor in the pathogenesis of diabetes in MD. On the contrary, abnormal insulin cleavage leading to increased proinsulin levels, probably related to specific protein kinase gene malfunction, represents a marker of secretory dysfunction capable to induce diabetes mellitus.

GIANLUCA PERSEGHIN, MAURO COMOLA, CINZIA ARCELLONI, EMANUELA PAGLIATO, ROBERTO LANZI, ALBERTO BATTEZZATI(*), LIVIO LUZI(*), Milan, Italy

(*) ADA Professional Section Member. See Duality of Interest Information.