Th1/Th2 predominance and proinflammatory cytokines determine the clinicopathological severity of IgA nephropathy.

BACKGROUND: IgA nephropathy is one of the most common forms of primary glomerulonephritis in adults. Its pathogenesis is complex. The nature of infiltrating and proliferating cells and of cellular mediators could contribute to the progression of IgA nephropathy towards end-stage renal failure. METHODS: To evaluate this hypothesis, we attempted to quantify the magnitude of intrarenal gene expression of various cytokines (IL-1 beta, TNF-alpha, IL-6, IL-15, IL-2, IFN-gamma, IL-10) and chemokines (IL-8, RANTES, MCP-1) in 48 renal core biopsy specimens, diagnosed as IgA nephropathy by immunofluorescence microscopy. Semi-quantitative reverse-transcriptase polymerase chain reaction using internal competitors was used for the quantification of gene transcripts. RESULTS: The expression of intrarenal gene transcripts of various cytokines and chemokines was closely interrelated, but not associated with the pathological grading system. The IFN-gamma/IL-10 ratio was higher in patients with renal dysfunction than in those with normal renal function (P=0.0483). Gene transcript levels of proinflammatory cytokines were related to the amount of proteinuria. In patients with severe glomerular sclerosis, the ratio of IFN-gamma/IL-10 gene transcripts was high (P=0.04). IL-10 gene transcript level was related to the severity of tubulointerstitial damage. The levels of gene expression of IL-10 (P=0.009), IFN-gamma (P=0.03), and TNF-alpha (P=0.005) were related to the degree of mesangial matrix expansion and the extent of intrarenal arteriolar changes correlated with the expression of the IL-8 gene transcript (r=0.43, P=0.004). CONCLUSIONS: We propose that Th1/Th2 predominance and the level of proinflammatory cytokines could determine the pathogenetic processes and the severity of the clinical manifestations of IgA nephropathy.

The relationship between plasma leptin and nutritional status in chronic hemodialysis patients.

Leptin serves an important role in suppressing appetite in mice and is known to be elevated in chronic renal failure (CRF) patients. But clinical significance of leptin as an appetite-reducing uremic toxin, remains to be determined. So we studied the relationship between plasma leptin and nutritional status in 46 chronic hemodialysis (HD) patients. Pre HD leptin was measured and divided by body mass index (BMI) to give adjusted leptin levels. KT/Vurea (K, dialyzer urea clearance; T, duration of HD; V, volume of distribution of urea), C-reactive protein (CRP), plasma insulin and nutritional parameters such as serum albumin, normalized protein catabolic rate (nPCR), subjective global assessment (SGA), BMI and mid-arm muscle circumference (MAMC) were also measured. Mean plasma leptin levels were 8.13+/-2.91 ng/mL (male 3.15+/-0.70; female 14.07+/-6.14, p<0.05). Adjusted leptin levels were positively correlated with nPCR (male r=0.47, p<0.05; female r=0.46, p<0.05), SGA (male r=0.43, p<0.05; female r=0.51, p<0.05) and MAMC (male r=0.60, p<0.005; female r=0.61, p<0.05). They did not correlate with KT/Vurea, serum albumin, hematocrit, bicarbonate, insulin and CRP. Presence of DM and erythropoietin therapy had no effect on leptin levels. These results suggest that leptin is a marker of good nutritional status rather than a cause of protein energy malnutrition in chronic HD patients.

La Crosse and other forms of California encephalitis.

The California serogroup viruses are mosquito viruses that cause human infections on five continents. They are maintained and amplified in nature by a wide variety of mosquito vectors and mammalian hosts; they thrive in a remarkably wide variety of microclimates (eg, tropical, coastal temperate marshland, lowland river valleys, alpine valleys and highlands, high boreal deserts, and arctic steppes). In 1993, California serogroup viruses caused 71% of all cases of arboviral illness in the United States, principally La Crosse encephalitis. The 30 to 180 annual cases of La Crosse encephalitis represent 8% to 30% of all cases of encephalitis, rendering this illness the most common and important endemic mosquito-borne illness in the USA. Subclinical or mild infections are much more common. Methods and results acquired from intense study of California serogroup viruses have been applied, with benefit, to the study of the ecology and pathogenesis of many more serious human arboviral illnesses. The evolutionary potential of viruses, with particular reference to the development of more virulent strains, has been studied more closely in the California serogroup viruses than in almost any other agent of human disease.

Osmiophilic deposits in cytosomes in Hallervorden-Spatz syndrome.

A young child with Hallervorden-Spatz syndrome is presented. She was well until 8 years of age when she lost interest in activities and her school performance declined. At age 11 years, she began having episodes of blepharospasm, accompanied by bilateral ptosis and occasional episodes of oculogyric crisis. By age 12 years, her motor coordination had declined and she began to exhibit evidence of dementia, dystonia, dysarthria, and tremor. Motor incoordination, dystonia, and tremor progressed until the patient was wheel-chair-bound. Multiple tests were performed, including metabolic studies, magnetic resonance imaging, bone marrow biopsy, and electron microscopy of the buffy coat. Both bone marrow and buffy coat revealed inclusions in the cytosomes which were granular and osmiophilic. To our knowledge, this is the third case report of inclusion bodies found in patients with manifestations of Hallervorden-Spatz syndrome. These findings suggest that obtaining a buffy coat and bone marrow biopsy may aid in the diagnosis of Hallervorden-Spatz syndrome and ultimately provide information regarding etiology.

Infantile olivopontocerebellar atrophy with spinal muscular atrophy (infantile OPCA + SMA).

We report three siblings (two boys and girl) with familial (autosomal recessive) infantile olivopontocerebellar atrophy (OPCA) associated with lower motoneuron involvement. Brain autopsy findings in two of the children revealed a multisystem degeneration characterized by marked hypoplasia of phylogenetically new parts of the brain stem (basis pontis and inferior olivary nuclei) associated with hypoplasia of the neocerebellum, both cerebellar and cerebral peduncle. All three infants died before six months of age. The clinical features are characterized by severe hypotonia, areflexia, failure to thrive, respiratory insufficiency in all cases, cardiomyopathy and dislocated hips at birth in two of the three siblings. Extensive serum, urinary and leukocyte enzyme assays in the second infant failed to disclose a specific metabolic abnormality. The diagnosis of OPCA was established prior to death by Magnetic Resonance Imaging (MRI) in the youngest infant. Since OPCA represents a heterogeneous group of diseases, correlation of neuropathologic, clinical, genetic and MRI findings at early stages of evolution becomes crucial in the understanding of the nosology of OPCA and its variants.

Acquired paroxysmal movement disorders.

Acquired paroxysmal movement disorders are reported less frequently than the familial forms of paroxysmal dyskinesias. Three children, with the acquired form of the disorder which followed an early childhood encephalopathic event, are described. Three similarly affected children have been reported previously. Movement disorders developing after perinatal encephalopathy appear to be a distinct entity. Patients with this condition demonstrated clinical improvement following the initiation of antiepileptic medications.

Optic glioma associated with Beckwith-Wiedemann syndrome.

A 6-year-old boy with decreased vision was found to have Beckwith-Wiedemann syndrome with an associated glioma involving the intracranial optic nerves, chiasm, and optic tracts. The association of this syndrome with visceral and central nervous system neoplasms is discussed.

Phenytoin-induced thrombocytopenia.

A 15-year-old boy developed thrombocytopenia and purpura two weeks after starting phenytoin therapy. The blood phenytoin level was in the toxic range. There was an increase in immature neutrophils but no abnormalities were present in other cell lines. Recovery was complete after drug therapy was discontinued. Thrombocytopenia is a rare isolated complication of phenytoin therapy. The probable autoimmune etiology distinguishes this syndrome from other phenytoin-induced blood dyscrasias.

Reenactment of the triggering situation for the diagnosis of epilepsy.

When a fixed set of ambient circumstances is associated with convulsive or nonconvulsive paroxysmal attacks, reenactment of the situation should be considered as a possible shortcut for reaching a diagnosis. Reenactment determined the diagnosis in 30 of 32 patients with paroxysmal disorders. The referral diagnosis was correct in only 13 of the 32 patients. To be appropriately executed, the reenactment should entail polygraphic recording of at least EEG, ECG, and respiration. Vertex electrodes should be included to avoid overlooking of cortical electrodecremental event. If unsuccessful at the first attempt, reenactment should be repeated.

Clinical aspects of La Crosse encephalitis: neurological and psychological sequelae.

Only rarely will a child continue to have focal neurologic findings, such as paresis, for as long as 8 years after LAC encephalitis. Most of the other focal neurologic findings, such as Babinski reflexes, pathologic reflexes, aphasias, choreas, dysarthrias and ataxias, resolve completely. Abnormal electroencephalographic findings during the acute period were note in 86-100% of the cases. On 1-8 year follow-up, EEG abnormalities were noted in approximately 33% of the subjects tested. Seizures are present at high frequency during acute illness and recurrent seizures may occur in 6-13% of the cases 1-8 years after infection. The cognitive and intellectual functioning of children following LAC encephalitis is not significantly different from that of the normal population. As a group, LAC encephalitis victims also function in the normal range in terms of their academic performances. There are individuals, however, who will have suffered permanent destructive lesions resulting in lowered IQ and lowered school performance. Behavioral abnormalities are difficult to measure and when present, difficult to ascribe to a definitive cause.

Hypomelanosis of Ito (incontinentia pigmenti achromians)--a clinicopathologic study: macrocephaly and gray matter heterotopias.

We studied a boy with macrocephaly, hypotonia, pigmentary retinopathy, unilateral whorled hypopigmented skin lesions, and seizures. Skin biopsy confirmed the clinical diagnosis of hypomelanosis of Ito. Postmortem examination at age 22 months revealed a severe neuronal migrational defect that altered the cerebral cortex architecture of white matter. There were many gray matter heterotopias characterized by altered neurons and giant cells. Electronmicroscopy revealed the astrocytic nature of the giant cells. Embryologic migration of both melanoblasts from neural crest and cortical neurons occurs in the second trimester, suggesting a common mechanism for the developmental pathology of skin and brain.

Lateral cervical meningocele.

Although lateral meningoceles have been described in the thorax, they have not been previously reported in the neck. We describe an infant who was born with a lateral meningocele in the cervical posterior triangle that was felt clinically to be cystic hygroma. Surgical excision was complicated by a cerebral spinal fluid fistula and subsequent meningitis. Problems that this patient presented and potential complications in management are discussed. Although the clinical manifestations of lateral meningoceles and extradural cysts are quite different, there are many anatomic similarities between these entities and other cervical masses that confuse diagnosis and nosology. Their differential diagnosis is reviewed.

Familial infantile myasthenia.

Familial infantile myasthenia is a rare type of myasthenia that usually occurs in connection with respiratory depression. The condition is characterized by (1) absence of myasthenia in the mother, (2) occurrence of a similar disorder among siblings, (3) respiratory depression at birth, (4) episodic weakness and apnea during the first two years of life, and (5) improvement with age. Since the condition responds to anticholinesterase medication, early diagnosis is important. Familial infantile myasthenia is a potential cause of sudden infant death and should be considered in infants with unexplained respiratory distress.

The Dubowitz syndrome: further observations.

An autosomal recessive disorder characterized by intrauterine growth retardation, postnatal retardation, microcephaly, sparse hair, toe syndactyly, and characteristic facial appearance is now recognized as the Dubowitz syndrome. Five addition additional cases of the Dubowitz syndrome are reported, including 2 with documented vascular abnormalities.

Brainstem auditory evoked response in adrenoleukodystrophy.

Clinical, laboratory, and electrophysiological data, including brainstem auditory evoked responses, are reported in a case of adrenoleukodystrophy. A striking asymmetry was noted in wave VI of the brainstem auditory evoked potential, followed by absence of any recognizable wave on the abnormal side. The presumed site of origin of wave VI is the medical geniculate body, a structure severely involved in adrenoleukodystrophy. It is suggested that the brainstem auditory evoked response may promise noninvasive diagnostic aid in this disorder and that absence of wave VI may emerge as a clinically useful finding in diseases of the central nervous system.

Benign subdural collections of infancy.

During the past two years we studied six infants with subdural collections of fluid. All patients had macrocrania and excessive transillumination of the head. Rapid head growth was common but five patients were otherwise asymptomatic. Subdural taps performed on five children confirmed the presence of abnormal fluid over the cerebral convexities. Subdural fluid in four patients was compatible with effusion and in another with a hematoma. Computerized tomographic evaluation of all infants showed ventricular enlargement, wide cerebral sulci, decreased density in the anterior temporal regions, large sylvian cisterns, prominent interhemispheric fissures, and decreased density over the cerebral convexities. The CT findings resembled cerebral atrophy but psychomotor development and neurologic examinations have been norma.