Putting the public (back) into public health: leadership, evidence and action.

There is a strong evidence-based rationale for community capacity building and community empowerment as part of a strategic response to reduce health inequalities. Within the current UK policy context, there are calls for increased public engagement in prevention and local decision-making in order to give people greater control over the conditions that determine health. With reference to the challenges and opportunities within the English public health system, this essay seeks to open debate about what is required to mainstream community-centred approaches and ensure that the public is central to public health. The essay sets out the case for a reorientation of public health practice in order to build impactful action with communities at scale leading to a reduction in the health gap. National frameworks that support local practice are described. Four areas of challenge that could potentially drive an implementation gap are discussed: (i) achieving integration and scale, (ii) effective community mobilization, (iii) evidencing impact and (iv) achieving a shift in power. The essay concludes with a call to action for developing a contemporary public health practice that is rooted in communities and offers local leadership to strengthen local assets, increase community control and reduce health inequalities.

Gaining children's perspectives: a multiple method approach to explore environmental influences on healthy eating and physical activity.

In order to inform local action for health improvement, this pilot study used multiple methods to explore children's perspectives of environmental influences on their eating and physical activity. Thirty-nine children aged 9-11 years from a North London local authority took photos, drew maps, and attended focus groups. We found that the approach engaged children and that each of the methods returned useful, complementary information. The results highlighted a number of areas for local policymakers and practitioners to consider when developing work to prevent childhood obesity. We conclude that these methods of gaining children's views should be further developed and tested.

Occult cardiac contractile dysfunction in dystrophin-deficient children revealed by cardiac magnetic resonance strain imaging.

BACKGROUND: Duchenne muscular dystrophy (DMD) is an inherited disease characterized by early onset of skeletal muscle degeneration and progressive weakness. Although dilated cardiomyopathy may occur during adolescence, it is often undetected early in its course because of physical inactivity and generalized debilitation. The purpose of this study was to apply the technique of cardiac magnetic resonance (CMR) tagging to detect occult cardiac dysfunction in young subjects with DMD by measuring myocardial strain and torsion. METHODS AND RESULTS: Thirteen DMD pediatric subjects without clinically apparent heart disease and 9 age-matched healthy males were recruited. Each was scanned on a 1.5-T clinical scanner to acquire contiguous short-axis planes from the apex to the mitral valve plane and then 3 tagged images at base, midventricle, and apex. Global and segmental myocardial net twist and circumferential strain were computed with the use of 2D homogeneous strain analysis. Ventricular torsion was computed by normalizing net twist by the distance from apex to mitral valve plane. DMD patients exhibited normal left ventricular volumes and ejection fractions but manifested reduced midventricular and basal cross-sectional global circumferential strain compared with the reference group (P<0.005). These alterations also appeared in segmental analyses in the septal, anterior, lateral, and inferior walls (P<0.05). CONCLUSIONS: In patients predisposed to cardiomyopathies because of dystrophinopathy, occult regional cardiac dysfunction can be diagnosed with CMR tagging. This method of strain imaging analysis may offer a sensitive approach for delineating the presence and progression of cardiovascular disease and for assessing therapies designed to modulate the onset and course of heart failure.

Improving quality of sexually transmitted disease case management in rural South Africa.

OBJECTIVE: To measure quality of sexually transmitted disease (STD) syndromic case management and aspects of health-seeking behaviour at baseline in an intervention trial. SETTING: Ten rural primary care clinics, Hlabisa district, South Africa. DESIGN: Simulated patients (fieldworkers trained to present with STD syndromes) made a total of 44 clinic visits; 49 STD patients were interviewed when exiting clinics; facilities were assessed for availability of necessary equipment and drugs; 10 focus group discussions were held with staff; and STD syndrome surveillance was performed in all 10 clinics. RESULTS: A total of 9% of simulated patients were correctly managed (given correct drugs, plus condoms and partner notification cards), recommended drug treatment was given in only 41% of visits, and appropriate counselling was given in 48% of visits. Among patients leaving the clinic, although 39% waited over an hour to be seen and only 37% were consulted in private, all reported staff attitudes as satisfactory or good. Only six clinics had syndromic management protocols available, three reported intermittent drug shortages, and seven lacked partner notification cards. Focus group discussions revealed good staff knowledge about STD, but showed lack of training in syndromic management and low morale. Surveillance data showed that while 75% of those presenting for care did so within 1 week of symptom onset, 27% had been treated for an STD in the preceding 3 months, and only 6% of those treated were contacts. CONCLUSIONS: Quality of STD case management was poor despite good staff knowledge and availability of most essential resources. An intervention comprising staff training and STD syndrome packets has been designed to improve quality of case management.

PIP: The effectiveness of syndromic management of sexually transmitted disease (STD) patients--a strategy that has been proposed for introduction to South Africa's public health sector--depends on both the quality of case management and health-seeking behavior patterns. These issues were assessed in 10 rural primary care clinics in South Africa's Hlabisa district. Field workers trained to present with STD syndromes (simulation patients) made a total of 44 clinic visits. In addition, 49 actual STD patients were interviewed when exiting clinics, facilities were checked for availability of essential drugs and equipment, 10 focus group discussions were held with staff, and STD syndrome surveillance was performed. Among simulated patients, only 9% were correctly managed (i.e., given correct drugs, condoms, and partner notification cards); appropriate counseling was provided in just 48% of visits. All clients interviewed as they left the clinic reported satisfactory or good staff attitudes, even though 39% waited over 1 hour to be seen and only 37% were seen in privacy. Only 6 clinics had syndromic management cards available, 3 reported intermittent drug shortages, and 7 lacked partner notification cards. In focus groups, staff demonstrated adequate knowledge of STDs, but poor morale and a lack of training in syndromic management. Finally, surveillance data revealed that, although 75% of patients presented within 1 week of symptom onset, 27% had been treated for an STD in the past 3 months and only 6% of those treated were contacts. An intervention comprised of staff training and STD syndrome packets has been designed to improve the quality of STD case management in South Africa.

Congenital muscular dystrophy syndromes distinguished by alkaline and acid phosphatase, merosin, and dystrophin staining.

Congenital muscular dystrophy syndromes are characterized by congenital weakness, contractures, and dystrophic features on muscle biopsy. However, these syndromes are often difficult to diagnose precisely because their clinical and pathologic characteristics are not specific and resemble changes in other myopathies. We examined muscle biopsies from 20 children with a congenital muscular dystrophy syndrome. Disease controls with dystrophies or other myopathies (n=19) and normal individuals (n=15) were studied for comparison. In each biopsy we determined (1) numbers of muscle fibers with alkaline phosphatase (AlkP) staining, (2) numbers of acid phosphatase-(AcP) positive cells, (3) dystrophin levels by immunocytochemistry, and (4) the distribution of merosin and laminin-A staining. A ratio of AcP:AlkP staining was calculated for each biopsy. In nine patients with congenital muscular dystrophy (younger than 4 years of age) with normal dystrophin, the AcP:AlkP ratio was low (0.09 +/- 0.03). In contrast, in Duchenne muscular dystrophy, the AcP:AlkP ratio was 15 times higher (1.6 +/- 0.04, p=0.001). The three children with congetial muscular dystrophy syndromes and reduced dystrophin and one child with facioscapulohumeral dystrophy had AcP:AlkP ratios in the range of Duchenne muscular dystrophy patients (2.4 +/- 1.4). Low Ac:AlkP ratios were related to relative absence of AcP-positive cells. Merosin staining was absent in 5 of the 17 congenital muscular dystrophy biopsies tested. None of the 5 children with merosin-negative but all 12 with merosin-positive stains walked (p=0.0002). We conclude that a pattern of few AcP-positive cells in the setting of numerous AlkP staining muscle fibers has specificity for congenital muscular dystrophy syndromes and provides histopathologic support for the diagnosis. Reduced merosin in muscle predicts more severe weakness and long-term disability.

High-titer selective serum anti-beta-tubulin antibodies in chronic inflammatory demyelinating polyneuropathy.

Although chronic inflammatory demyelinating polyneuropathy (CIDP) is presumed to be an autoimmune disorder, no neural antigen has been recognized as an immune target. We found that serum IgM from a patient with CIDP and an IgM paraprotein reacted with a 53-kd protein by Western blot analysis. Amino acid sequence analysis identified this protein as beta-tubulin. We then studied sera from 70 CIDP patients, 35 Guillain-Barré syndrome (GBS) patients, and 483 disease (amyotrophic lateral sclerosis, Alzheimer's disease, multiple sclerosis, diabetes, and other polyneuropathies) and normal controls for selective high-titer anti-beta-tubulin using ELISA methodology. Forty-two percent (30/70) of patients with CIDP had selective high titer IgM reactivity against beta-tubulin; 23% (16/70) had selective high-titer IgG reactivity against beta-tubulin. Overall, 57% of CIDP patients, 20% of GBS patients, and 2% of control patients had selective, high serum IgM or IgG anti-beta-tubulin reactivity. Selective high-titer serum anti-beta-tubulin antibodies occur in a majority of patients with CIDP but are rare in other chronic neuropathies or CNS disorders.

Mutations in the human skeletal muscle chloride channel gene (CLCN1) associated with dominant and recessive myotonia congenita.

Myotonia, defined as delayed relaxation of muscle after contraction, is seen in a group of genetic disorders that includes autosomal dominant myotonia congenita (Thomsen's disease) and autosomal recessive myotonia congenita (Becker's disease). Both disorders are characterized electrophysiologically by increased excitability of muscle fibers, reflected in clinical myotonia. These diseases are similar except that transient weakness is seen in patients with Becker's, but not Thomsen's disease. Becker's and Thomsen's diseases are caused by mutations in the skeletal muscle voltage-gated chloride channel gene (CLCN1). Genetic screening of a panel of 18 consecutive myotonia congenita (MC) probands for mutation in CLCN1 revealed that a novel Gln-68-Stop nonsense mutation predicts premature truncation of the chloride channel protein. Four previously reported mutations, Arg-894-stop, Arg-338-Gln, Gly-230-Glu, and del 1437-1450, were also noted in our sample set. The Arg-338-Gln and Gly-230-Glu mutations were found in patients with different phenotypes from those of previous reports. Further study of the Arg-338-Gln and Gln-230-Glu alleles may shed light on variable modes of transmission (dominant versus recessive) in different families. Physiologic study of these mutations may lead to better understanding of the pathophysiology of myotonia in these patients and of voltage-gated chloride channel structure/function relationships in skeletal muscles.

Serum IgM monoclonal autoantibody binding to the 301 to 314 amino acid epitope of beta-tubulin: clinical association with slowly progressive demyelinating polyneuropathy.

We identified five patients with IgM monoclonal autoantibodies that bound to human brain tubulin. In a companion study, we found that IgM in these sera selectively recognized one of three epitopes on tubulin. IgM from three patients bound selectively to a small epitope on human beta-tubulin comprising amino acids 301 to 314. The other two sera recognized tubulin amino acids 215 to 235 and 315 to 336. In this study, we compared the clinical syndromes in these patients with the tubulin epitope recognized by their serum IgM. The three patients with IgM binding to tubulin amino acids 301 to 314 all had chronic inflammatory demyelinating polyneuropathy (CIDP) syndromes with slowly progressive weakness, hyporeflexia, and electrophysiologic studies consistent with demyelination. Two of these patients had significant asymmetry to their weakness. The two other patients had diagnoses of polyradiculopathy and amyotrophic lateral sclerosis with no evidence of peripheral nerve demyelination. We conclude that IgM monoclonal anti-tubulin antibodies have some association with demyelinating polyneuropathy syndromes, but may occur in patients with other clinical syndromes as well. A stronger association with demyelinating polyneuropathies may occur if the anti-tubulin antibodies recognize the 301 to 314 amino acid epitope on tubulin. This tubulin epitope, or a similar one on another molecule, could play an important antigenic role in the development of demyelinating polyneuropathies with features of CIDP.

Childhood chronic inflammatory demyelinating neuropathies: clinical course and long-term follow-up.

Chronic inflammatory demyelinating neuropathy (CIDP) is a rare disease in childhood. We reviewed the clinical characteristics, response to therapy, and long-term prognosis in 13 children (1.5 to 16 years of age) diagnosed with CIDP at Washington University Medical Center, St. Louis, and the Royal Children's Hospital, Melbourne, Australia, between 1979 and 1994. The most common presenting symptom (in 11/13 [85%]) was lower extremity weakness associated with difficulty in walking. Preceding events within 1 months of onset, mostly intercurrent infections or vaccinations, occurred in seven children (54%). The disease was monophasic in three children (23%). One relapse occurred in four (30%) and multiple relapses in six (46%). All patients had at least short-term response to steroids. Three children (23%) recovered completely during the first year. Ten children (77%) had residual weakness after an average follow-up of 6 years. There seems to be two populations of children with CIDP. One subgroup, with a favorable prognosis, progressed to peak disability over less than 3 months; these children often have a monophasic course with complete resolution of symptoms and signs and withdrawal from all medications by 1 year after onset. A second subgroup progressed for 3 months or longer; these children all required substantial does of prednisone for prolonged periods and had considerable long-term morbidity with persistent weakness.

Laminin alpha2 muscular dystrophy: genotype/phenotype studies of 22 patients.

OBJECTIVE: To determine the number of primary laminin alpha2 gene mutations and to conduct genotype/phenotype correlation in a cohort of laminin alpha2-deficient congenital muscular dystrophy patients. BACKGROUND: Congenital muscular dystrophies (CMD) are a heterogeneous group of muscle disorders characterized by early onset muscular dystrophy and a variable involvement of the CNS. Laminin alpha2 deficiency has been reported in about 40 to 50% of cases of the occidental, classic type of CMD. Laminin alpha2 is a muscle specific isoform of laminin localized to the basal lamina of muscle fibers, where it is thought to interact with myofiber membrane receptor, such as integrins, and possibly dystrophin-associated glycoproteins. METHODS: Seventy-five CMD patients were tested for laminin alpha2 expression by immunofluorescence and immunoblot. The entire 10 kb laminin alpha2 coding sequence of 22 completely laminin alpha2-deficient patients was screened for causative mutations by reverse transcription (RT)-PCR/single strand conformational polymorphisms (SSCP) analysis and protein truncation test (PTT) analysis followed by automatic sequencing of patient cDNA. Clinical data from the laminin alpha2-deficient patients were collected. RESULTS: Thirty laminin alpha2-negative patients were identified (40% of CMD patients tested) and 22 of them were screened for laminin alpha2 mutations. Clinical features of laminin alpha2-deficient patients were similar, with severe floppiness at birth, delay in achievement of motor milestones, and MRI findings of white matter changes with normal intelligence. Loss-of-function mutations were identified in 95% (21/22) of the patients studied. SSCP analysis detected laminin alpha2 gene mutations in about 50% of the mutant chromosomes; PTT successfully identified 75% of the mutations. A two base pair deletion mutation at position 2,096-2,097 bp was present in 23% of the patients analyzed. CONCLUSIONS: Our data suggest that the large majority of laminin alpha2-deficient patients show laminin alpha2 gene mutations.

Three mouse models of muscular dystrophy: the natural history of strength and fatigue in dystrophin-, dystrophin/utrophin-, and laminin alpha2-deficient mice.

To optimize and evaluate treatments for muscular dystrophy, it is important to know the natural history of the disease in the absence of therapeutic intervention. Here we characterized disease progression of three mutant mouse strains of muscular dystrophy: mdx mice, which lack dystrophin; mdx:utrn-/- mice, which also lack utrophin; and dy/dy mice, which are deficient in laminin alpha2. Normal mice show a marked increase in forelimb strength over the first 10 weeks of life and little fatigue (<5%) over five consecutive strength trials. Mdx and mdx:utrn-/- mice demonstrate less strength then normal mice and approximately 40% fatigue at each age. Mdx mice become obese but mdx:utrn-/- mice do not. Dy/dy mice remain small and are much weaker than mdx and mdx:utrn-/- mice at all ages even when normalized to weight; however, they show only minimal fatigue (10%). This work demonstrates a distinct pattern of disease progression in each model and provides a foundation for assessing strategies for improving strength in each model.

Assessment of body composition in heart transplant patients.

Orthotopic heart transplantation (OHT) recipients often experience increased body weight (BW) following surgery. Using hydrostatic weighing (HW), this study assessed the body density (BD) and body composition of 17 white and seven black male OHT patients. It examined the cross-validity of the Jackson and Pollock seven and three site skinfold (SF) regression equations for predicting BD in these patients. We hypothesized that both prednisone (P) dose and months post-operative (MPO) would be inversely related to BD. The average of the last five of ten HW trials was used in computing BD. BW and % body fat (BF) were 88.5 +/- 17.8 kg (mean +/- SD) and 33.5 +/- 9.4%, respectively. The correlation coefficient between hydrostatically determined BD and BD determined via two of the three intercept revised Jackson and Pollock SF equations was r = 0.89, SE = 0.009. A polynomial regression model for BD using P dose and MPO provided a correlation coefficient of r = 0.71, SE = 0.015. Partial correlation techniques incorporating SF, age, MPO, and P dose indicated that neither P dose or MPO provided any significant additive effect, above SF and age, when predicting BD. We conclude that in OHT patients receiving glucocorticoids, the intercept revised Jackson and Pollock SF regression equations are generally applicable and associated with a SE of +/- 4 BF percentage points. Up to 49 months after OHT, both P dose and MPO are inversely related to BD but provide no additive value above SF for predicting BD.

Progressive infantile axonal polyneuropathy.

Polyneuropathies are relatively uncommon in early infancy and the majority of affected children are found to have hypomyelinating neuropathies. Axonal sensorimotor neuropathies have been described in childhood but the majority of affected children present at or after 6 months of age, have nonprogressive courses, and achieve the ability to walk, albeit late. Here we present three infants with infantile progressive axonal polyneuropathy from two families with nonconsanguineous parents. Each child presented shortly after the neonatal period and with rapid progression to quadriplegia. Involvement of the lower cranial nerves, phrenic nerves, or both was present in each child. Electrophysiology was diagnostic in each child. While the diagnosis of spinal muscular atrophy was considered in each case, clinical presentation, biopsies, and genetic testing were inconsistent with this diagnosis. Recognition of this early form of progressive axonal neuropathy is important as respiratory compromise occurred early and the condition showed familial inheritance in two of our patients.

Long-term survival in a child with arthrogryposis multiplex congenita and spinal muscular atrophy.

Spinal muscular atrophy type 0 is a severe form of spinal muscular atrophy that is usually fatal in the first months of life. These children present with arthrogryposis multiplex congenita and respiratory compromise. We describe a child with spinal muscular atrophy and arthrogryposis multiplex congenita who has had a much better course and is alive without ventilator support at age 6 years. This case illustrates that the prognosis for spinal muscular atrophy and arthrogryposis multiplex congenita cannot always be predicted with certainty.

Chronic inflammatory demyelinating polyneuropathy in childhood.

Chronic inflammatory demyelinating polyneuropathy (CIDP) in children is relatively rare. However, it has been recognized for many years. In patients presenting with this disease, subacute onset of weakness usually develops over at least 2 months and often progresses to a loss of ambulation. Some children's initial presentations may mimic Guillain-Barré syndrome. Dysasthesias are common. Males are affected more than females, and antecedent illnesses or vaccinations occur in approximately half of patients. Physical examination reveals diffuse, proximal greater than distal weakness, with an absence or depression of muscle stretch reflexes. Electrophysiology confirms demyelination, and spinal fluid examination demonstrates albuminocytologic dissociation. The clinical presentation, diagnosis, and prognosis of childhood CIDP are reviewed. Treatment and immunologic features are also discussed in this article.

Poliomyelitis-like syndrome associated with Epstein-Barr virus infection.

A 20-month-old male presented with an acute clinical syndrome resembling poliomyelitis, characterized by a flaccid monoplegia, areflexia of the involved limb, and preserved sensation. Electrophysiologic studies supported a neuronopathic localization involving the anterior horn cells. Although laboratory evidence for a poliovirus infection was absent, serologic and polymerase chain reaction studies documented an active central nervous system infection with Epstein-Barr virus, indicating that a poliomyelitis-like syndrome may be produced by infectious agents other than enteroviruses.

Mutation analysis in Emery-Dreifuss muscular dystrophy.

The purpose of this study was to search for STA gene defects in three families with clinically typical Emery-Dreifuss muscular dystrophy. Emery-Dreifuss is an X-linked muscular dystrophy with humeroperoneal weakness and life-threatening, but treatable, cardiac abnormalities in male patients and in female carriers. The defect is in the gene coding for emerin, a 254 amino acid protein of unknown function. Complementary and genomic DNA from T lymphocytes from the reported patients and their family members were amplified, cloned, and sequenced. A novel mutation, a 26 base-pair deletion in three brothers and a carrier mother, was detected in one family. A splicing mutation with one base pair insertion and a five base-pair deletion, which have been described previously, were found in the second and third families, respectively. The additional novel mutation detected and the findings of three different mutations in these three families support the idea of genetic heterogeneity of Emery-Dreifuss muscular dystrophy with different mutations in different families.

Inadequate treatment for sexually transmitted diseases in the South African private health sector.

Correct management of sexually transmitted diseases (STDs) is important for their control, and to reduce HIV transmission. Guidelines on syndromic management of STDs were introduced by the provincial Department of Health in KwaZulu/Natal (KZN) in South Africa in 1995. The drug treatment provided for STDs by the 11 private general practitioners in one rural district was assessed and compared with provincial guidelines. Information was gathered through semistructured interviews which asked the 11 doctors, who all dispense prescribed drugs as part of the consultation fee, how they would treat 3 hypothetical cases of STD syndromes. In all 33 prescriptions, the treatment did not correspond exactly with provincial recommendations and only 3 (9%) were adequate. All other prescriptions were inadequate because dose or duration was incorrect in 6 (18%), or because incorrect drugs were prescribed in 24 (73%) of cases. Eight of the 11 doctors did not provide adequate treatment for any of their cases. A continuing medical education programme for the doctors and their staff was devised to improve the STD treatment in the private sector in this South African district.

PIP: The correct management of sexually transmitted diseases (STD) can help to control and reduce the spread of HIV infection. To that end, guidelines upon the syndromic management of STDs were introduced by the provincial Department of Health in KwaZulu/Natal (KZN) in South Africa in 1995. Drug treatment provided for STDs by 11 private general practitioners in 1 rural district was investigated and compared with provincial guidelines. Study data were collected through semi-structured interviews in which the doctors were asked how they would treat 3 hypothetical cases of STD. In all of the 33 prescriptions written by the physicians, the treatment failed to correspond exactly with provincial recommendations and only 3 were adequate. The other prescriptions were inadequate because either the dose or regimen duration was incorrect in 6 cases, and because the wrong drugs were prescribed in 24 cases. 8 of the physicians did not provide adequate treatment for any of their cases. A continuing medical education program for the doctors and their staff was subsequently created to improve the private sector treatment of STDs in KZN.