Use of imprint cytology for assessment of surgical margins in lumpectomy specimens of breast cancer patients.

In the past several years, breast-conservation therapy has provided an alternative to mastectomy. In order to reduce the subsequent local tumor recurrence, it is critical that all the measures are in place to find the residual foci of occult microscopic tumor at the time of the initial lumpectomy procedure. An accepted method to evaluate the lumpectomy margins for presence of residual tumor is the use of imprint cytology (also called touch-prep), which is assessment of the presence or absence of the tumor cells by cytological preparation. This is a rapid, cost effective, and easy to use procedure with added advantage of saving tissue for permanent sectioning and rendering a definitive diagnosis. In this report, we present our experience using intraoperative imprint cytology for evaluation of the status of lumpectomy specimens in breast cancer patients. The objective of this study was to evaluate the diagnostic accuracy of intraoperative imprint cytology for assessment of surgical resection margins in lumpectomy margins of patients with breast carcinoma. This is a retrospective study of 100 cases of breast lumpectomy specimens, which had undergone intraoperative imprint cytology. The cases were retrieved from the archived files of the University of Florida, Department of Pathology at Shands Jacksonville. The results of intraoperative imprint cytology were compared with the histological findings of the corresponding permanent sections of the same cases as the gold standard. Overall, we reviewed 510 cytology imprint slides, which were obtained from 100 lumpectomy specimens. Among these cases, 37 slides from 22 cases were reported positive and the remaining were negative. Only eight slides from six cases of lumpectomy showed discrepancy between the result of intraoperative imprint cytology and the permanent sections of the same cases. In our study, intraoperative imprint cytology showed a sensitivity of 97%, specificity of 99%, with positive predictive value of 84%, and negative predictive value of 99%. This study demonstrates that intraoperative imprint cytology can be used as a reliable diagnostic procedure for the evaluation of the status of lumpectomy margins in breast cancer patients.

Immune thrombocytopenic purpura - current management practices.

The treatment of patients with immune thrombocytopenic purpura (ITP) is changing rapidly, as new agents demonstrate the capability of improving outcomes and decreasing toxicity. Prior to 1981, the only effective treatment options available to increase platelet counts in persons with ITP were corticosteroids and splenectomy. In recent years, intravenous immunoglobulin (IVIg) and intravenous Rh immunoglobulin (IV RhIg) have demonstrated efficacy comparable to that of corticosteroids for increasing platelet counts in ITP. In addition, IVIg and IV RhIg have demonstrated efficacy for maintaining corticosteroid-induced increased platelet counts by periodic infusion, causing a transient impairment of reticuloendothelial clearance function (medical splenectomy). Thus, the time-proven efficacy of corticosteroids for initial treatment of ITP (induction) may now be supplemented with IVIg or IV RhIg infusions for patients requiring ongoing treatment to support a timely and complete steroid taper, while sustaining the increased platelet count (maintenance) with less toxicity. Several investigators have reported that rituximab (anti-CD20) induced sustained remissions with minimal toxicity, in patients with chronic ITP. These reports are promising and, if confirmed, will provide another effective (spleen-sparing) option for managing acute ITP and a long-awaited option for patients who have had a splenectomy and are refractory to conventional agents. Other treatments, including danazol, azathioprine, cyclophosphamide, vinca alkaloids and cyclosporin A, have advocates, but evidence of their efficacy is limited to relatively small and mostly uncontrolled clinical trials. In our opinion, these agents should be reserved for symptomatic thrombocytopenia after refractoriness to corticosteroids, IVIg, IV RhIg, splenectomy and rituximab has been clearly established.

Molybdenum cofactor deficiency associated with Dandy-Walker complex.

Molybdenum cofactor deficiency is a rare and devastating disease leading to intractable seizures in the neonatal period. Severe loss of neocortical neurons, gliosis, and cystic necrosis of cerebral white matter resulting in significant cerebral volume loss are the neuropathological findings. The mechanism of cerebral injury is unknown, but sulphite excess, and sulphate or uric acid deficiencies are possible factors. We present here a new case of Molybdenum cofactor deficiency associated with Dandy-Walker complex with a history of three dead siblings, the latter also having Dandy-Walker malformation. We speculate that severe cerebral volume loss due to the above mentioned mechanisms may lead to an appearance resembling Dandy-Walker malformation.

Proinflammatory cytokines, prostaglandins and zinc in febrile convulsions.

BACKGROUND: Some changes in the levels of proinflammatory cytokines, prostaglandins and zinc (Zn) in peripheral blood and cerebrospinal fluid (CSF) have been suggested to occur for the pathogenesis of febrile convulsions (FC). METHODS: In order to test this hypothesis, the levels of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 alpha, IL-1 beta and prostaglandins (PGE(2), PGF(2 alpha), PGD(2)) in the CSF and plasma and the levels of Zn in serum and CSF were investigated in children during the acute and late phases of FC. Results were compared with control subjects with meningismus. RESULTS: During the acute phase of FC, children had significantly elevated plasma levels of IL-1 beta, CSF levels of TNF-alpha, plasma levels of PGE(2), PGF(2 alpha) and PGD(2) and CSF levels of PGD(2) (P<0.05). A positive correlation between the degree of fever and plasma IL-1 beta levels was observed in both patients and controls. Three months after the acute phase of FC, plasma levels of IL-1 beta had returned to levels seen in controls. Children with FC also had significantly decreased serum Zn levels during the acute phase (P<0.05). However, there was no significant difference between the groups with respect to CSF Zn levels (P>0.05). CONCLUSIONS: During the acute phase of FC, patients had significantly increased plasma IL-1 beta and prostaglandin levels and decreased serum Zn levels. These changes may be responsible for FC pathogenesis.

Progressive encephalopathy with edema, hypsarrhythmia, and optic atrophy (PEHO syndrome) in a Turkish child.

We report a Turkish boy with PEHO syndrome (progressive encephalopathy with edema, hypsarrhythmia, and optic atrophy). He had generalized hypotonia and abnormal eye movements during early infancy. Infantile spasms were seen in the second year of life. Arrest of psychomotor development and blindness were noticed early in childhood. Serial magnetic resonance imaging revealed progressive infratentorial atrophy with association of cortical atrophy and corpus callosum hypoplasia. This is an additional case of PEHO syndrome, to our knowledge the first such case from Turkey.

Possible mechanisms of late-life-onset allergic diseases and asthma in the senior citizen.

The clinical spectrum of allergic diseases and asthma changes over the life span of the individual and is influenced by a wide variety of anatomic, physiologic, and immunologic factors. Nowhere do these changes play a more important role than in the elderly patient with allergic disease or asthma where the culmination of these events contribute to disease expression, which at times can result in irreversible endstage disease. It is estimated that between 2010 and 2030 the elderly population will increase by 75% and will represent a significant proportion of consumers of total health care resources. This presentation will examine possible mechanism(s) that contribute to the development of late-onset allergic diseases and asthma in the elderly as a possible basis for identification of antecedents of endstage disease and interventive strategies for the prevention of the irreversible consequences in this population.

Persistent cough: differential diagnosis.

Cough may be defined as a physiologic response to foreign or noxious substances that enter or irritate the respiratory tract. It is the fifth most common symptom complex for which patients seek medical care and which results in more than 30 million office visits per year. When cough is present for more than three weeks it is referred to as chronic or persistent cough. This presentation will examine the differential diagnosis of persistent cough together with a description of the autonomic innervation of the human airways, mechanism(s) of cough, and approach to the patient.

Potential prophylactic use of benzodiazepines for hemodialysis-associated seizures.

Hemodialysis-associated seizure (HAS) is a common complication of hemodialysis. The efficiency of anticonvulsant drugs in treating or preventing seizures is poorly defined. In this study, children on long-term hemodialysis were examined for HAS and the effect of diazepam prophylaxis on HAS was investigated. Nine patients with a mean age of 14.1 + 2.8 years had HAS and 4 with a mean age of 13.0 +/- 4.4 years had never experienced HAS. The patients with HAS had tonic-clonic seizures. Four patients had focal slow-wave paroxysms, especially in the parieto-occipital regions; 2 had subcortical epileptiform discharges by electroencephalography. No correlation was observed between HAS and patient age, primary disease, prior history of seizures, type of dialysis, duration of hemodialysis, anemia, hyperparathyroidism, and administration of erythropoietin. Hypertension due to hypervolemia may also play a role in the development of HAS. Five patients with HAS first treated with phenobarbital (PB) had recurrence of seizures. As a dialyzable antiepileptic PB may be associated with an increased risk for HAS. In a preliminary study, we gave diazepam as a prophylactic therapy to 4 patients with HAS. During 6 months of follow-up, these patients had no seizures. The number of HAS was significantly different between the groups receiving PB and diazepam (z=-2,58, P=0.009). In conclusion, administration of diazepam per os to patients with HAS may be of value for preventing recurrence of HAS.

Effects of niacin-bound chromium and grape seed proanthocyanidin extract on the lipid profile of hypercholesterolemic subjects: a pilot study.

Hypercholesterolemia, a significant cardiovascular risk factor, is prevalent in the American population. Many drugs lower circulating cholesterol levels, but they are not infrequently associated with severe side effects. Accordingly, natural means to lower cholesterol levels safely would be welcomed. We examined 40 hypercholesterolemic subjects (total cholesterol 210-300 mg/dL) in a randomized, double-blind, placebo-controlled study. The four groups of ten subjects received either placebo bid, chromium polynicotinate (Cr) 200 microg bid, grape seed extract (GSE) 100 mg bid, or a combination of Cr and GSE at the same dosage bid. Over two months, the average percent change +/- SEM in the total cholesterol from baseline among groups was: placebo -3.5% +/- 4, GSE -2.5% +/- 2, Cr -10% +/- 5, and combination -16.5% +/- 3. The decrease in the last group was significantly different from placebo (p < 0.01). The major decrease in cholesterol concentration was in the LDL levels: placebo -3.0% +/- 4, GSE -1.0% +/- 2.0, Cr -14% +/- 4.0, and the combination -20% +/- 6.0. Again, the combination of Cr and GSE significantly decreased LDL when compared to placebo (p<0.01). HDL levels essentially did not change among the groups. Also, there was no significant difference in the triglyceride concentrations among the groups; and no statistically significant differences were seen in the levels of autoantibodies to oxidized LDL (Ox-LDL). However, the trend was for the two groups receiving GSE to have greater decreases in the latter parameter, i.e., -30.7% and -44.0% in the GSE and combined groups in contrast to -17.3% and -10.4% in the placebo and chromium groups. We determined the number of subjects in each group who decreased autoantibodies to oxidized LDL greater than 50% over eight weeks and found these ratios among groups: placebo = 2/9, Cr = 1/10, GSE = 6/10, and combined = 3/8. Thus, 50% of subjects (9/18) receiving GSE had a greater than 50% decrease in autoantibodies compared to 16% (3/19) in the two groups not receiving GSE. No significant changes occurred in the levels of circulating homocysteine and blood pressure among the four groups. We conclude that a combination of Cr and GSE can decrease total cholesterol and LDL levels significantly. Furthermore, there was a trend to decrease the circulating autoantibodies to oxidized LDL in the two groups receiving GSE.

Lymphocyte subsets and inflammatory mediators in patients with subacute sclerosing panencephalitis.

A defective cell-mediated immunity and inflammatory cytokines are suggested in the pathogenesis of subacute sclerosing panencephalitis. In this study we analyzed lymphocyte subsets in peripheral blood and concentrations of interleukin-1alpha (IL-1alpha), interleukin-2 (IL-2alpha), tumor necrosis factor-alpha (TNF-alpha), and platelet activating factor in plasma and cerebrospinal fluid before and after immunomodulatory therapy (interferon-alpha plus isoprinosine) in three patients with subacute sclerosing panencephalitis. Increased percentage of CD8+cells (T-suppressor/cytotoxic cell) and CD16+CD56+cells (NK cell) and reduced percentage of CD3+/HLA-DR+ (active T-cell) and CD3+ (total T-cell) cells were found before therapy. After immunomodulatory therapy, CD3+/HLA-DR+ (active T-cell) cells were markedly increased and there was a slight increase in the percentages of all lymphocyte subsets in the patients. The concentrations of platelet activating factor in plasma and cerebrospinal fluid were higher than the mean value in controls. Cerebrospinal fluid and plasma TNF-alpha and IL-2 levels were nondetectable in two patients who had a stationary course of disease and were markedly elevated in patient 3, who displayed a rapidly progressive course.

Infantile spasm: the effect of corticotropin (ACTH) on the free amino acid profile in cerebrospinal fluid.

Increased excitatory amino acid neurotransmission has been implicated in the pathogenesis of infantile spasm. In this study we studied the profile of free amino acids in cerebrospinal fluid (CSF) from 16 patients with infantile spasm before corticotropin (ACTH) treatment. After 10 weeks ACTH therapy the profile of amino acids in CSF was studied once more in eight of the patients. Eleven patients were in the symptomatic group, and five in the cryptogenic group. Increased aspartate levels were measured in CSF following ACTH therapy (P<0.05). It was concluded that aspartate might have an important role in hypothalamic-hypophyseal axis in patients with infantile spasm.

Associated brain abnormalities in patients with corpus callosum anomalies.

Forty-nine patients with corpus callosum (CC) anomalies were evaluated in terms of the clinical features and magnetic resonance imaging (MRI) findings. CC anomalies were classified as CC agenesis: 6 (12%), CC hypogenesis: 5 (10%), and CC hypoplasia: 38 (78%). In the CC hypoplasia group the mean value of the genu thickness of the CC was 0.29 +/- 0.1 cm, which was less than the normal value of the age-matched normal children (normal range: 0.6-1.2 cm). The associated brain abnormalities were in five distinct groups: gray matter abnormalities, white matter abnormalities, midline brain structure defects, cortical atrophy, and encephalomalacia. There was no uniformity for the clinical spectrum of CC anomalies. Microcephaly, developmental delay and seizures were the prominent findings in patients. The clinical features were more severe in cases with associated brain anomalies.

Pro-inflammatory cytokines, lymphocyte subsets and intravenous immunoglobulin therapy in Guillain-Barré syndrome.

Both cell-mediated immunity and humoral factors are involved in the pathogenesis of Guillain-Barré syndrome (GBS). Intravenous immunoglobulin (IVIG) has been reported to be a practical, effective and safe treatment in childhood GBS, although the mode of action of IVIG remains uncertain. We studied pro-inflammatory cytokines (interleukin-2, interleukin-1 alpha and tumor necrosis factor-alpha) in plasma and cerebrospinal fluid (CSF) and lymphocyte subsets in peripheral blood both in the acute phase and in the recovery period in six children with GBS treated with IVIG. Flow cytometry was used to determine the subsets of lymphocytes in peripheral blood, and cytokines analyses were performed by using ELISA technique. Results were compared with a control group of 20 healthy children. A standard protocol of IVIG (400 mg/kg/day for 5 days) was administered to all the patients. Plasma interleukin-2 concentrations and the number of HLA DR+ active T cells in peripheral blood were significantly higher in the acute phase of the disease than in the recovery period and in healthy controls. There was no significant difference in the other cytokine concentrations in plasma and CSF or in the other lymphocyte subsets in peripheral blood. Our data indicate that IVIG may provide its possible therapeutic effect by acting in the cell-mediated immunity in GBS patients.

Subcutaneous granuloma annulare and IgA-IgG2 deficiency.

Subcutaneous granuloma annulare (SGA) is a benign granulomatous disease occurring in childhood, with lesions most commonly located about the elbow, knee and scalp. the etiology of SGA remains obscure. We present a typical case with SGA also showing laboratory findings of IgA and IgG2 deficiency. Histologic findings of the lesions on the scalp were characterized by multiple large foci of complete collagen degeneration with a peripheral pallsade of histiocytes; the foci of degeneration was edematous basophilic. In contrast to current literature, an abnormality in the cellular immune system was not found. However, immune defects (IgA and IgG2 deficiency) related to the humoral immune system were observed.

Akinetic mutism due to diphenylhydantoin toxicity.

Akinetic mutism (AM) is a rare, specific, unconscious state. An AM patient seems to be awake, lacks mental activity, is unable to speak, and does not respond to any environmental stimulus. Cyclical sleep and awake states are maintained, and incontinence is present. Various factors such as tumor, vascular events, drug use and radiotherapy are responsible for the development of AM. A 12-year-old epileptic patient displayed AM and diphenylhydantoin toxicity (DPH). She seemed awake, was unable to speak or to understand, and had no movements with either spontaneous or noxious stimuli. Her serum DPH level was greater than 40 micrograms/ml. Magnetic resonance imaging (MRI) showed mild cerebellar atrophy. All known causes of AM were excluded. The AM state in this patient was considered to be due to toxic DPH levels. She regained her motor and mental activity within two months after carbamazepine was administered to replace DPH. She was symptom-free when examined at the two-year follow-up. No similar adverse effect of DPH has been reported to date.

Infantile polymyositis with normal serum creatine kinase level.

A 30-month-old boy who has been suffering progressive proximal muscle weakness and severe atrophy in shoulder and hip muscles from 11 months of age had prominent perivascular inflammatory cellular infiltration in his muscle biopsy and myopathic EMG changes. But his serum creatine kinase (CK) levels were repeatedly found to be within normal ranges. Oral prednisolone therapy (2 mg/kg/d) brought a complete recovery of muscle power and normalization of EMG and muscle biopsy findings. This report provides an additional support that the cases of infantile polymyositis with normal serum CK levels may respond well to steroid therapy.

Dysosteosclerosis: clinicoradiologic findings including brain MRI.

Dysosteosclerosis is a very rare bone dysplasia associated with sclerosis and platyspondyly. This paper reports the clinicoradiologic and MR imaging findings in this rare condition. The primary brain MR imaging finding was retarded white matter matter myelination.

Acute alternating hemiplegia. A case report.

Acute alternating hemiplegia in childhood is a rare disorder characterized by onset before 18 months of age and frequent attacks of alternating paralysis. In this case report, a 20-month-old boy having the diagnosis of acute alternating hemiplegia is presented. The diagnosis was based on clinical features. The frequency and severity of the hemiplegic attacks decreased following flunarizine therapy. In this case, cerebral perfusion was investigated during ictal and interictal periods. Tc-99m HMPAO-Brain single photon emission computed tomography (SPECT) revealed normal cerebral perfusion in ictal periods and hypoperfusion in interictal periods.