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Biomedical subjects

P J Milla

Publications and source records attributed to P J Milla.

At least 19 recordsLinked to original sources
PubMed1998

Gastroesophageal reflux in children and its relationship to erosion of primary and permanent teeth.

Gastroesophageal reflux (GOR) is often a self-limiting condition but nevertheless is a common cause of morbidity in childhood. Studies of adult patients with hiatus hernias and GOR have suggested that there is an increased incidence of dental erosion in these individuals. The aim of this study was to investigate the relationship between dental erosion and GOR in children. Fifty-three children aged 2 to 16 yr (mean 4.9 yr) with moderate to severe GOR, defined by pH monitoring, were examined for dental erosion. A questionnaire investigating dietary habits, other relevant medical conditions, and erosion risk factors was also completed. Results showed that the prevalence of dental erosion was low, when compared with the UK National Survey, with only 9 (17%) children showing any signs of erosion, and of these only one had erosion involving dentine. These results suggest that dental erosion may not be as great a problem in children with GOR as it is in adults. It may be that refluxing is limited to the oesophagus, and further work is needed to investigate those children that positively reflux into the mouth.

Adolescent↗
PubMed1998

Vomiting and gastroesophageal motor activity in children with disorders of the central nervous system.

BACKGROUND: Vomiting is common in children with disorders of the central nervous system (CNS) and is usually ascribed to gastroesophageal reflux (GER). However, recent acquisitions on the pathophysiology of vomiting suggest that the dysmotility of the foregut may be more widespread. METHODS: Fifty-five children with CNS disorders, 50 of whom suffered from retching and/or vomiting (18 following fundoplication) were studied. We assessed GER by 24 hour pH monitoring and endoscopy, gastric electrical activity by electrogastrography, and gastric half-emptying time (T1/2) of a milk meal be electrical impedance tomography. RESULTS: Of the 50 vomiting patients, 29 had GER (reflux index of 5.7%-87.4%; controls: < 5%), and 31 had gastric dysrhythmias (12 tachyarrhythmia at 5.5-11.2 cpm, 4 bradyarrhythmia at 1.7-1.9 cpm, 15 unstable electrical activity; controls; 2.2-4.0 cpm). Sixteen patients had GER and gastric dysrhythmias. Eleven of 18 patients with fundoplication had gastric dysrhythmias. Gastric T1/2 was delayed in 12 of 13 patients with gastric dysrhythmia (6 with GER), versus 2 of 5 with GER alone. No abnormalities were detected in the 5 patients who did not suffer from vomiting. CONCLUSIONS: Children with CNS disorders who vomit have abnormal gastric motility as often as GER. Following fundoplication, many patients continue to have symptoms possibly related to gastric dysrhythmias, the effects of which may be unmasked by fundoplication. Foregut dysmotility may be related to abnormal modulation of the enteric nervous system by the CNS or to involvement of the enteric nervous system by the same process affecting the brain.

Adolescent↗
PubMed1998

Rapadilino syndrome--a non-Finnish case.

We report on a boy with RAPADILINO syndrome. Including this report seven children with this syndrome have been described. The patient developed a poikilodermatous skin rash, suggesting overlap with the Rothmund-Thompson syndrome.

Abnormalities, Multiple↗
PubMed1998

Cystic fibrosis: present and future.

Cystic fibrosis (CF) is an inherited disorder of epithelial chloride transport affecting primarily pancreas, lungs, gut, liver and exocrine glands. The defect is caused by defects of the cystic fibrosis transmembrane regulation gene on chromosome 7. Genotyping has proved useful in identifying gene carriers, a definitive diagnosis, and in antenetal diagnosis. Genotype/phenotype relationships have shown that the commonest cause of pancreatic insufficiency is the D F508 mutation. Clinical trials are exploring the use of somatic gene therapy but this is not yet a viable treatment option. Liver, lung and intestinal disease result in malnutrition which causes further dysfunction of these organs. Aggressive nutritional and pancreatic enzyme therapy results in improved disease, normal growth and increased survival. However, high-dose enzyme therapy may in some individuals cause a fibrosing colonopathy. For those with end-stage liver and lung disease, transplantation holds out some hope.

Chromosome Aberrations↗
PubMed1997

Therapy for persistent hyperinsulinemic hypoglycemia of infancy. Understanding the responsiveness of beta cells to diazoxide and somatostatin.

The neonatal disorder persistent hyperinsulinemic hypoglycemia of infancy (PHHI) arises as the result of mutations in the subunits that form the ATP-sensitive potassium (KATP) channel in pancreatic beta cells, leading to insulin hypersecretion. Diazoxide (a specific KATP channel agonist in normal beta cells) and somatostatin (octreotide) are the mainstay of medical treatment for the condition. To investigate the mechanism of action of these agents in PHHI beta cells that lack KATP currents, we applied patch clamp techniques to insulin-secreting cells isolated from seven patients with PHHI. Five patients showed favorable responses to medical therapy, and two were refractory. Our data reveal, in drug-responsive patients, that a novel ion channel is modulated by diazoxide and somatostatin, leading to termination of the spontaneous electrical events that underlie insulin hypersecretion. The drug-resistant patients, both of whom carried a mutation in one of the genes that encode KATP channel subunits, also lacked this novel K+ channel. There were no effects of diazoxide and somatostatin on beta cell function in vitro. These findings elucidate for the first time the mechanisms of action of diazoxide and somatostatin in infants with PHHI in whom KATP channels are absent, and provide a rationale for development of new therapeutic opportunities by K+ channel manipulation in PHHI treatment.

Blood Glucose↗
PubMed1997

Tetrahydrobiopterin regulates cyclic GMP-dependent electrogenic Cl- secretion in mouse ileum in vitro.

1. Basal electrogenic Cl- secretion, measured as the short-circuit current (Isc), was variable in ileum removed from tetrahydrobiopterin (BH4)-deficient hph-1 mice and wild-type controls in vitro, although values were not significantly different. 2. The basal nitrite release and mucosal cyclic guanosine 3',5'-monophosphate (cyclic GMP) production were similar in control and BH4-deficient ileum. 3. Mucosally added Escherichia coli heat-stable toxin (STa, 55 ng ml-1) increased the nitrite release, cyclic GMP levels and the Isc in control ileum, but its secretory actions were reduced in BH4-deficient ileum. 4. L-Arginine (1 mM) increased the nitrite release, cyclic GMP production and the Isc in control ileum, but the actions were reduced in BH4-deficient ileum. 5. Serosal carbachol (1 mM) stimulated maximum short-circuit currents of similar magnitude in both control and BH4-deficient ileum, whilst nitrite release and cyclic GMP production were minimal. 6. E. coli STa and L-arginine increased electrogenic Cl- secretion across intact mouse ileum in vitro by releasing nitric oxide and elevating mucosal cyclic GMP. The inhibition of these processes in the hph-1 mouse ileum suggests that BH4 may be a target for the modulation of electrogenic transport, and highlight the complexity of the interactions between nitric oxide and cyclic GMP in the gut.

Animals↗
PubMed1997

Acquired intestinal aganglionosis and circulating autoantibodies without neoplasia or other neural involvement.

The clinical course, diagnosis, and treatment of 2 patients with acquired intestinal aganglionosis without other neurological involvement or neoplasia are described. They initially presented with constipation and abdominal pain in late childhood. They were found to have enteric ganglionitis with a loss of neurons together with vacuolated nerve cells surrounded by CD3- and CD4-positive T lymphocytes. This process initially affected only the colon but later the entire gastrointestinal tract was involved in 1 patient. Associated with this process there were circulating immunoglobulin G class enteric neuronal antibodies in high titer (1:5000-8000). The staining of central nervous system neuronal nuclei and Western blotting indicated the presence of antineuronal nuclear protein antibodies of the ANNA-1 (anti-Hu) type usually associated with paraneoplastic sensory neuropathy. However, the reaction pattern in enteric neurons was quite different with strong reaction to perikarya and only weak staining of nuclear antigens.

Adolescent↗
PubMed1997

Counting the cost: hospital versus home central venous catheter survival.

We compared catheter survival and sepsis rates in a tertiary paediatric gastroenterology centre with those at home in the same patients. We examined whether there were differences in the safety in the two locations, and estimated the financial and opportunity cost implications of any difference. We used survival analysis to analyse differences. Surgical records were audited to determine venous access workload, and to estimate cost implications. Twenty patients with chronic intestinal failure but stable parenteral nutrition requirements, ranging from 0.04-15.83 years of age were studied. The duration of line survival and sepsis-free intervals and rates of re-operation for venous access were determined to estimate morbidity and costs. The study encompassed 28 patient-years in hospital and 48 patient-years at home. There was a significant reduction in the rate of sepsis at home compared with hospital (Z = 4.30, P < 0.00001), and a similar improvement in line survival (Z = 4.36, P < 0.00001). Line insertions accounted for 21% of minor surgery in our hospital, one third being reinsertions. We conclude that central venous catheter sepsis rates are greatly improved at home. If home results could be achieved in the hospital setting, considerable cost savings would be made.

Adolescent↗
PubMed1997

Histological phenotypes of enteric smooth muscle disease causing functional intestinal obstruction in childhood.

AIMS: Functional intestinal obstruction or chronic idiopathic intestinal pseudo-obstruction is due to defects either in the enteric innervation or in intestinal smooth muscle. We have studied full-thickness intestinal biopsies from 27 patients with functional intestinal obstruction due to enteric smooth muscle disease by routine histology and electron microscopy together with histochemical and immunohistochemical techniques to detect changes in the intestinal smooth muscle. METHODS AND RESULTS: Two patients appeared to have an acquired intestinal myopathy as a result of an autoimmune process. In 25 the disorders were congenital, of these seven had segmental abnormalities limited to the rectum and distal colon and 18 had a diffuse disease affecting both the small and large bowel. We identified five apparent histological phenotypes of enteric muscle disease, three of which represent abnormalities in morphogenesis resulting in alterations in intestinal muscle layering and two exemplify intrinsic myocyte defects and/or changes in the extracellular matrix. CONCLUSIONS: Careful phenotyping of these patients is important in devising optimal treatment and in understanding the underlying defect as well as the possible genetic mechanisms resulting in these abnormalities. Recognition of autoimmune smooth muscle disease is helpful, since making the diagnosis influences the patient's management.

Child, Preschool↗
PubMed1997

An evaluation of the role of suction rectal biopsy in the diagnosis of intestinal neuronal dysplasia.

BACKGROUND: German pathologists have developed a consensus for histological features of intestinal neuronal dysplasia. METHODS: A blind reevaluation of ganglionic suction rectal biopsies from infants and children who initially presented with symptoms of intestinal dysmotility was made. RESULTS: 84 of 411 specimens had sufficient depth of submucosa for adequate assessment. Questionnaires or clinical interviews were employed 3-5 years after biopsy in these 84 patients to assess the relationship between histological changes and persistent symptomology. Eighteen children were lost to follow-up, 4 others had Hirschsprung's disease the study biopsy specimen having been taken from the pulled-through bowel after surgical resection of the aganglionic segment. The remaining 62 patients were divided into three groups. There were six patients in group A (both obligatory criteria) and 28 in group B (nonessential, or just one of the obligatory criteria), and 28 in group C (normal appearances). On follow-up, two of the 28 (7%) in group B, and six of the 28 (21%) in group C had persistent dysmotility symptoms. CONCLUSIONS: Histological criteria of the consensus of German Pathologists for intestinal neuronal dysplasia was unhelpful in predicting the clinical outcome and therefore, should not influence clinical management. As one of the obligatory criteria, hyperplasia of the submucosal plexus was significantly more common in neonates (< 4 weeks), it is concluded that this is an age-related variation.

Acetylcholinesterase↗
PubMed1997

Congenital chloride-losing diarrhoea: absence of the anion-exchange mechanism in the rectum.

BACKGROUND: Congenital chloride-losing diarrhoea is characterized by a defect in chloride/bicarbonate exchange, which is normally present in the ileum and colon. Whether the defect is an absence or a reversal of such an exchange is unclear, and we have investigated two young children with the disorder to answer this question. METHODS: We used a previously described nonequilibrium rectal dialysis method, using different dialysate anion concentrations, to investigate the movement of sodium, potassium, chloride, and bicarbonate in the rectum of the two children. RESULTS: The results showed that chloride and bicarbonate movements were not linked in any active way, and both ions appeared to move passively in response to the electrochemical gradients generated. CONCLUSIONS: In the two subjects studied, the defect in the rectum appears to be an absence of the normal anion exchange mechanism present in the bowel, rather than its reversal.

Bicarbonates↗
PubMed1997

The urological manifestations of hollow visceral myopathy in children.

PURPOSE: Hollow visceral myopathy is a rare clinical entity characterized by impaired intestinal function in the absence of mechanical occlusion. It can affect the smooth muscle of the whole or segments of the gastrointestinal tract and occasionally the urinary tract. We examined the urological manifestations of hollow visceral myopathy and management in the pediatric population. MATERIALS AND METHODS: We reviewed the records of 14 male patients 1 day to 2 years old (mean age 4.6 months) and 10 female patients 1 day to 5 years old (mean age 9.4 months) at presentation to our institution with hollow visceral myopathy. In all patients genitourinary tract ultrasound, voiding cystourethrography and serum creatinine measurement were done at presentation. RESULTS: All patients had gastrointestinal obstructive symptoms at presentation and 11 (46%) had urological symptoms, including urinary retention in 2, urinary tract infection in 3, and a prenatal diagnosis of megacystis and hydroureteronephrosis in 6. Overall 22 patients (92%) had urological abnormalities, all had poor bladder emptying and recurrent urinary tract infections, and 13 had megacystis associated with bilateral hydroureteronephrosis in 9 and unilateral hydroureteronephrosis in 2. There were 9 deaths from extensive gastrointestinal involvement and sepsis. Of the surviving 15 patients 13 have urological abnormalities, including 8 who perform and tolerate clean intermittent catheterization via the urethra and are well. Of the 4 male infants who did not tolerate clean intermittent catheterization appendicovesicostomy was done in 1, a Casale tube was placed in 1 and vesicostomy was performed in 2. The remaining female patient has day and night wetting. CONCLUSIONS: Urological abnormalities are common in hollow visceral myopathy and they can contribute to presenting symptoms. Clean intermittent catheterization via the urethra to aid in bladder emptying and decrease the frequency of urinary tract infections is the mainstay of treatment but surgery to construct an alternative catheterizable channel or vesicostomy may be required in intolerant patients.

Child, Preschool↗
PubMed1997

Non-infective colitis in infancy: evidence in favour of minor immunodeficiency in its pathogenesis.

Forty two infants below the age of 2 years presenting with chronic non-infective diarrhoea and shown to have histologically proved colitis were investigated over a five year period. Allergic colitis was the most common cause of colitis, accounting for 62% of the cases. Other colitides diagnosed included: non-specific colitis, autoimmune enterocolitis, and ulcerative colitis accounting for 10% each; severe combined immunodeficiency 7%, and Crohn's disease 3%. A positive family history and a personal history of atopy were obtained in 48% and 29% of the cases respectively. Serum immunoglobulin A, IgG2, and IgG4 were very low in over 50% of the entire cohort of infants with colitis; 66% of those with severe combined immunodeficiency, autoimmune enterocolitis, and ulcerative colitis (n = 11) had low CD3 and CD4 T lymphocytes with an accompanying increase in CD8 in two thirds of those with severe combined immunodeficiency. T lymphocytes were normal in those with allergic colitis. Thus infants with proved non-infective colitis as a group show a high prevalence of IgA, IgG2, and IgG4 deficiency. It is likely that this minor deficiency of mucosa associated immunoglobulin production has a role in the pathogenesis of the colitic process.

Autoimmune Diseases↗
PubMed1997

Non infective colitis in infancy: evidence in favour of minor immunodeficiency in its pathogenesis.

Forty two infants below the age of two years presenting with chronic non infective diarrhoea and shown to have histologically proven colitis were investigated over a five year period at this hospital. Allergic colitis was the most common cause of colitis accounting for sixty two percent of the cases. Other colitides diagnosed included: non specific colitis, autoimmune enterocolitis and ulcerative colitis accounting for 9.5% each, severe combined immunodeficiency 7.1% and Crohn's disease 2.8%. A positive family history and a personal history of atopy was obtained in 47.6% and 28.6% of the cases. Serum immunoglobulin A, IgG2 and IgG4 were very low in over 50% of the infants with colitis. Sixty six percent of those with severe combined immunodeficiency, autoimmune enterocolitis and ulcerative colitis (n = 11) had low CD3 and CD4 T lymphocytes with an accompanying elevated CD8 in 2/3 of those with severe combined immunodeficiency. T lymphocytes were normal in those with allergic colitis. We conclude that infants with proven non infective colitis show as a group a high prevalence of IgA, IgG2 and IgG4 deficiency. It is likely that this minor deficiency of mucosal associated immunoglobulin production have a role in the pathogenesis of the colitic process.

Autoimmune Diseases↗