By H. Uruk. Macalester College. 2018.
During the children’s growth and development purchase cardura 2 mg visa hypertension patho, the therapists pro- vide the best bridge between the education and medical systems order cardura 1mg online hypertension 33 years old. The final physical and emotional function and independence of these children depends on intervention by both the medical and educational systems; therefore, the bridging effect provided by the therapists is an important aspect. In addition to the standard therapy treatment in education, there are many treatment modalities that are promoted as beneficial for CP treatment. Some of these modalities may start as an alternative medicine approach, such as hippo- therapy, but then develop acceptance within traditional medicine. Others, such as hyperbaric oxygen therapy, develop a reputation of possible benefit but, upon careful investigation, their validity is discredited. The physician who treats the motor impairments of children with CP should understand the techniques, goals, and expected outcomes of therapies they order while also understanding the educational context in which these children function. Therapy In this discussion, the term therapy applies to physical, occupational, or speech therapy, all disciplines trained in the milieu of the medical system, although these individuals often work in the educational system. These dis- ciplines overlap significantly; however, each has a very defined area of ex- pertise. Physical therapy focuses on gross motor function, such as walking, running, jumping, and joint range of motion. There is some overlap with oc- cupational therapy, where the main focus is on fine motor skills, specifically upper extremity function and activities of daily living such as dressing, toi- leting, and bathing. This overlap between physical and occupational therapy occurs in the areas of seating and infant stimulation programs where both therapists perform the same function. Speech therapists focus on oral motor 152 Cerebral Palsy Management activities such as speech, chewing, and swallowing. A subspecialist speech therapist will do augmentative communication evaluations. Speech and oc- cupational therapy overlap in the area of teaching feeding skills to care- takers and self-feeding therapy for patients. The specific areas of practice of each of the therapy disciplines vary slightly among geographic regions and facilities. A major focus of all therapy is to maximize the individual’s in- dependence. The goal of this discussion on the therapy disciplines is not to promote a full review of each discipline, but to provide only the information that a physician who treats children concurrently with the therapist should possess. Also, most of this discussion is directed at the musculoskeletal mo- tor impairments because that is the focus of this text; however, it must be remembered that speech and communication are usually rated as more im- portant by individuals with disabilities. Physical Therapy Applying physical therapy to children with CP is common and has a large body of published data. Since 1990, there have been approximately 300 ci- tations in the National Library of Medicine reporting the use of physical therapy in children with CP. Most of these papers report physical therapy being used in conjunction with other treatments, such as surgical hip recon- structions or lower extremity reconstructions for gait improvement, or fol- lowing dorsal rhizotomy and Botox injections. Many of these reports are case series without controls to evaluate the index procedure, and most make no objective attempt to evaluate the impact of the therapy program sepa- rately from other modalities. The number of reports attempting to evaluate the impact of specific therapy programs is increasing; however, many con- tain few patients and no control groups. Many reports presume that physical therapy is like medication in that it can be evaluated by having a control group with no treatment. This research approach has some merit if no effect is found, such as the evaluation of therapy in infant stimulation programs. Recognizing these complex interactions has led to recommending more complex and global evaluations using multivariate analysis in research protocols. For example, a treat- ment protocol where physical therapy modalities along with casting and Botox are used to treat gait abnormality in young children cannot be rea- sonably evaluated by any other means. Recognizing the complex interaction of physical therapy in its own right will lead to improved research techniques for other treatments as well.
The assumption made by the authors was that PD patients developed tolerance generic cardura 2mg without a prescription blood pressure medication harmful. Despite these ﬁndings cardura 4 mg line heart attack zippo, the authors did not rule out the possibility that those receiving LD longer had a more progressive disease. Evidence indicates that conversion of dopa to dopamine can occur at sites other than dopaminergic terminals in the striatum (43,54,58). Thus, LD continues to be effective throughout the course of disease. Markham and Diamond (81,82) demonstrated this when they studied three groups of patients; those starting LD after 1–3 years of disease, 4–6 years, and 7–9 years. In this manner they could assess whether the apparent loss of efﬁcacy could relate to the disease duration or the duration of drug therapy. After 6 years of follow-up they noted the following: 1. The disability scores were different for the three groups at initiation of LD and remained different thereafter. Disability scores were the same for the three groups when they were matched for disease duration despite varied durations of therapy. There was no signiﬁcant difference with respect to the incidence of dyskinesias. In projecting the course of disease it was found that all three groups ultimately followed the same predictable course of progression independent of the duration of LD therapy. This was conﬁrmed after 12 years of follow- up of the ﬁrst group (81,82). The authors concluded that LD works at all stages of PD, does not result in tolerance over time, but does not stop progression of disease. In other words, changes in disability of PD are related to duration of disease and not duration of therapy or tolerance to LD. Aside from progression of disease, another cause of the apparent loss of efﬁcacy relates to narrowing of the therapeutic window—increased sensitivity to adverse effects such as dyskinesias and hallucinations (45,46). The worsening of disease also comes from the onset and progression of symptoms not attributable to dopamine systems, such as postural instability, freezing, and dementia (46). MORTALITY OF PD WITH LEVODOPA Several studies performed in the 1970s demonstrated that LD therapy improves mortality in PD. These studies compared the survival of LD- treated patients to the mortality rate demonstrated in the pre-levodopa Hoehn and Yahr study (2), which demonstrated that mortality was three Copyright 2003 by Marcel Dekker, Inc. Nearly all studies indicated that LD improved survival with rates of 1. Some investigators suggested that survival approached normal, while others indicated that the effect was only seen early in therapy and then disappeared. However, many of the studies have been criticized due to methodological ﬂaws, problems with patient selection, and possible biases. One study of particular interest (83) utilized a population-based study design (retrospective) to avoid many of these ﬂaws and examine the change in survival related to LD therapy. The study included patients treated from 1964 to 1978 to include patients treated early and late as well as untreated cases. Results indicated that survival for all patients was signiﬁcantly poorer than that of the general population but was better in treated than in untreated PD. Throughout the entire 17 years of follow-up there was reduced risk of death with LD therapy. One other area of interest relates to the timing of LD therapy. Does early or later intervention affect the survival rates? They divided patients into three groups: group one, 1–3 years of PD; group two, 4–6 years of PD; group three, 7–9 years of PD. They used observed-to-expected death rate (from a group of similar make-up in the general population) ratios as measures of survival. When duration of therapy is held constant at 15 years, the ratio was higher for patients with longer duration of disease. When duration of disease was held constant at 17 years, the patients in group one had a better mortality ratio than the other two groups. Thus, early initiation of LD therapy was beneﬁcial to life expectancy.
The DNA for exon 5 of the aldolase B gene was ampli- fied by polymerase chain reaction (PCR) buy discount cardura 2mg line blood pressure medication cialis, treated with AhaII order 4mg cardura free shipping arteria genus media, subjected to electrophoresis on an agarose gel, and stained with a dye that binds to DNA. On examining the gel himself, the husband became concerned that he might not be the biologic father of one or both of the children. From the pattern on the gel, you can reasonably conclude which of the following? An alcoholic is brought to the Emergency Room for a hypoglycemic coma. Because alcoholics are frequently malnourished, which of the following enzymes can be used to test for a thiamine deficiency? Intravenous fructose feeding can lead to lactic acidosis caused by which of the following? The polyol pathway of sorbitol production and the HMP shunt pathway are linked by which of the following? The pathways for oxidation of fatty acids, Krebs first formulated its reactions glucose, amino acids, acetate, and ketone bodies all generate acetyl CoA, into a cycle. It is also called the “citric acid which is the substrate for the TCA cycle. As the activated 2-carbon acetyl cycle” because citrate was one of the first group is oxidized to two molecules of CO2, energy is conserved as NADH, compounds known to participate. The most common name for this pathway, the tricar- FAD(2H), and GTP (Fig. NADH and FAD(2H) subsequently donate boxylic acid or TCA cycle, denotes the electrons to O2 via the electron transport chain, with the generation of ATP involvement of the tricarboxylates citrate from oxidative phosphorylation. Thus, the TCA cycle is central to energy gen- and isocitrate. Within the TCA cycle, the oxidative decarboxylation of -ketoglutarate is cat- The major pathways of fuel oxida- alyzed by the multisubunit -ketoglutarate dehydrogenase complex, which con- tion generate acetyl CoA, which is tains the coenzymes thiamine-pyrophosphate, lipoate, and FAD. In plex, the pyruvate dehydrogenase complex (PDC), catalyzes the oxidation of the first step of the TCA cycle, the acetyl por- pyruvate to acetyl CoA, thereby providing a link between the pathways of glycoly- tion of acetyl CoA combines with the 4- sis and the TCA cycle (see Fig. In the next two oxidative transferred to NAD and FAD and also the carbon in the two CO2 molecules that decarboxylation reactions, electrons are are produced. Oxaloacetate is used and regenerated in each turn of the cycle (see transferred to NAD to form NADH, and 2 Fig. However, when cells use intermediates of the TCA cycle for molecules of electron-depleted CO2 are released. Subsequently, a high- energy phosphate bond in GTP is generated from Glucose Fatty acids substrate level phosphorylation. In the Pyruvate remaining portion of the TCA cycle, succi- Ketone bodies nate is oxidized to oxaloacetate with the generation of one FAD(2H) and one NADH. CO2 The net reaction of the TCA cycle, which is the sum of the equations for individual Acetate Acetyl CoA Amino acids steps, shows that the two carbons of the CoASH acetyl group have been oxidized to two mol- OxaloacetateOxaloacetate + (4c)(4c) ecules of CO2, with conservation of energy NADH + H Citrate (6c)Citrate (6c) as three molecules of NADH, one of Malate (4c)Malate (4c) Isocitrate (6c)Isocitrate (6c) FAD(2H), and one of GTP. Fumarate (4c)Fumarate (4c) Tricarboxylic acid NADH + H+ FAD (2H) (TCA) cycle Succinate (4c)Succinate (4c) CO 2 αα-Ketoglutarate (5c)-Ketoglutarate (5c) GTP Succinyl-Succinyl- NADH + H+ GDP CoACoA (4c) CO2 Net reaction Acetyl CoA + 3NAD+ + FAD 2CO + CoASH + 3NADH + 3H+ 2 + GDP + P + 2Hi 2O + FAD (2H) + GTP Fig. The TCA cycle occurs in the mitochondrion, where its flux is tightly coordi- nated with the rate of the electron transport chain and oxidative phosphorylation through feedback regulation that reflects the demand for ATP. The rate of the TCA cycle is increased when ATP utilization in the cell is increased through the response of several enzymes to ADP levels, the NADH/ NAD ratio, the rate of FAD(2H) oxidation or the Ca2 concentration. For example, isocitrate dehydro- genase is allosterically activated by ADP. There are two general consequences to impaired functioning of the TCA cycle: (1) an inability to generate ATP from fuel oxidation, and (2) an accumulation of TCA cycle precursors. For example, inhibition of pyruvate oxidation in the TCA cycle results in its reduction to lactate, which can cause a lactic acidosis. The most common situation leading to an impaired function of the TCA cycle is a rela- tive lack of oxygen to accept electrons in the electron transport chain. THE WAITING ROOM Otto Shape, a 26-year-old medical student, has faithfully followed his diet and aerobic exercise program of daily tennis and jogging (see Chapter 19). He has lost a total of 33 lb and is just 23 lb from his college weight of 154 lb. His exercise capacity has markedly improved; he can run for a longer time at a Vitamins and minerals faster pace before noting shortness of breath or palpitations of his heart. Even his required for the TCA cycle test scores in his medical school classes have improved.
Methemoglobinemia can be acquired accumulates purchase cardura 1 mg visa blood pressure normal unit, leading to lysis of the erythrocyte cardura 2mg wide pulse pressure icd 9 code. When red blood cell lysis (hemoly- by ingestion of certain oxidants such as sis) substantially exceeds the normal rate of red blood cell production, the number of nitrites, quinones, aniline, and sulfon- erythrocytes in the blood drops below normal values, leading to a hemolytic anemia. Acquired methemoglobinemia can be treated by the administration of reducing B. The Erythrocyte Precursor Cells and Heme Synthesis agents, such as ascorbic acid or methylene blue. HEME STRUCTURE Heme consists of a porphyrin ring coordinated with an atom of iron (Fig. G6PD deficiency is the most com- Four pyrrole rings are joined by methionyl bridges (—CH—) to form the porphyrin mon enzyme deficiency known in ring (see Fig. Eight side chains serve as substituents on the porphyrin ring, humans, probably, in part, because two on each pyrrole. These side chains may be acetyl (A), propionyl (P), methyl individuals with G6PD deficiency are resist- (M), or vinyl (V) groups. In heme, the order of these groups is M V M V M P P M. The resistance to malaria This order, in which the position of the methyl group is reversed on the fourth ring, counterbalances the deleterious effects of the deficiency. G6PD-deficient red cells have is characteristic of the porphyrins of the type III series, the most abundant in nature. It is complexed with under conditions of oxidative stress. When proteins to form hemoglobin, myoglobin, and the cytochromes (see Chapters 7 and soldiers during the Korean War were given 21), including cytochrome P450 (see Chapter 24). SYNTHESIS OF HEME African ancestry developed a spontaneous anemia. Because the gene for G6PD is found Heme is synthesized from glycine and succinyl CoA (Fig. The enzyme one copy of a variant G6PD gene that catalyzes this reaction, -ALA synthase, requires the participation of pyridoxal All known G6PD variant genes contain phosphate, as the reaction is an amino acid decarboxylation reaction (glycine is small in-frame deletions or missense muta- decarboxylated; see Chapter 39). The corresponding proteins, therefore, The next reaction of heme synthesis is catalyzed by -ALA dehydratase, in have decreased stability or lowered activity, which two molecules of -ALA condense to form the pyrrole, porphobilinogen leading to a reduced half-life or lifespan for (Fig. Four of these pyrrole rings condense to form a linear chain and then a the red cell. No mutations have been found series of porphyrinogens. The side chains of these porphyrinogens initially contain that result in complete absence of G6PD. Based on studies with knockout mice, those mutations would be expected to result in CH2 embryonic lethality. CH3 CH Heme, which is red, is responsible for the color of red blood cells and HC CH of muscles that contain a large CH3 N CH 3 number of mitochondria. As a result of these structural dif- CH 2 ferences, chlorophyll is green. M = methyl (CH ); V = vinyl (—CH=CH ); P = propionyl (—CH —CH —COO ). Synthesis of -aminolevulinic acid Fe protoporphyria ( -ALA). To produce one molecule of heme, 8 molecules each of glycine and succinyl CoA are required. A series of porphyrinogens are generated in sequence. Heme regulates its own production by repressing the synthesis of -aminolevulinic acid ( -ALA) synthase (circled T) and by directly inhibiting the activity of this enzyme (circled –).