Familial and sporadic hyperinsulinism: histopathologic findings and segregation analysis support a single autosomal recessive disorder

We evaluated the possible genetic contribution to hyperinsulinism in a series of patients seen during the past 15 years. Of 26 families, 5 (19%) had more than one child affected (multiplex family). There were no apparent differences between patients in the 5 multiplex and 21 simplex families, clinically, biochemically, or on histologic examination of the pancreatic specimens. The families studied had a total of 63 offspring; the 26 index patients had 37 siblings, 6 of whom were affected. After four patients with hyperinsulinism caused by adenoma were excluded from the study, segregation analysis was carried out to test the data for agreement with results expected if familial and isolated hyperinsulinism represented a single disease with recessive mode of inheritance and a segregation ratio of 0.25. Excellent agreement was found between the observed number of affected siblings (20) and the expected number (19.65), with a segregation ratio of 0.254. The results were consistent with the hypothesis that in most or all cases, hyperinsulinism is inherited as an autosomal recessive disease. There was no evidence of distinct familial and sporadic types.     

Placental teratoma.

The rare teratoma of the placenta has been compared to the fetus amorphus, two distinguishing characteristics being the teratoma's lack of structural organization and lack of large vessels entering the tumor. A case of placental teratoma and theories of origin are discussed.     

Alternative Treatments for Asthma: Assessing the Need

Alternative treatments such as troleandomycin methotrexate, gold, and intravenous gamma globulin are sometimes considered for severe asthmatics to minimize the need for systemic corticosteroids and reduce adverse effects. These alternative therapies may also be associated with significant toxicity and expense. The ability to reduce corticosteroid use and the need for alternative treatment interventions in 125 pediatric patients at our institution were reviewed. Because corticosteroid requirements were reduced significantly, only 23 of 125 children evaluated were considered for treatment alternatives with only 10 receiving such therapy. This study emphasizes the importance of a thorough and comprehensive review of corticosteroid requirements and usage prior to initiating alternative approaches to treatment in moderate to severe asthmatics as well as in patients thought to be “steroid-dependent.”     

Proton magnetic resonance spectroscopic imaging for discrimination of absence and complex partial seizures

We performed proton magnetic resonance spectroscopic imaging of the temporal lobes between, during, and soon after nonconvulsive seizures in 20 patients with documented temporal lobe epilepsy, 5 patients with primary generalized epilepsy, and 2 patients with secondary generalized epilepsy. Our objective was to determine whether there were metabolic changes observable by magnetic resonance spectroscopic imaging during seizures and whether these changes were specific for focal or generalized nonconvulsive seizures. We found a significant increase in lactate to creatine plus phosphocreatine (lactate/creatine) values, reflecting an imbalance in energy supply and demand or an adaptation in response to ictal neuronal discharges, during and soon after complex partial seizures, but not during or soon after absence seizures associated with generalized epilepsy. In patients with temporal lobe epilepsy, the N-acetylaspartate resonance relative to creatine plus phosphocreatine was low in one or both temporal lobes, indicating neuronal loss or damage. This was not observed in patients with primary generalized epilepsy. The regions with abnormal lactate/creatine and N-acetylaspartate/creatine values corresponded to the epileptogenic focus as defined by clinical-electroencephalographic investigation. There was no change in the N-acetylaspartate/creatine values in the temporal lobes between the interictal, ictal, or postictal states. We conclude that (1) partial seizures are associated with abnormally high lactate levels, but absence seizures are not, and (2) no short-term changes of N-acetylaspartate occur during or soon after complex partial seizures or absence seizures. These findings may be related to the lack of postictal confusion in patients with absence seizures, as well as with the more benign course of primary generalized epilepsy with nonconvulsive attacks.     

Cardiac Surgery in Nonagenarians

A bstract Objectives and Background : The purpose of this study was to document our initial experience with patients 90 years of age and older and to determine whether cardiac surgery is justified in this age group. Cardiac surgery in octogenarians has proven to be a successful and worthwhile procedure. A small group of nonagenarians with severe coronary artery disease (CAD) and aortic valve disease refractory to medical therapy have been considered for surgery. Methods : Fourteen patients aged 90 or more underwent cardiac surgery for symptomatic CAD or aortic valvular disease refractory to medical therapy. Eight patients underwent isolated coronary artery bypass grafting (CABG) and six patients underwent aortic valve replacement (AVR). All patients were in NYHA Class IV preoperatively. Results : Hospital mortality occurred in one patient (7%). Hospital morbidity occurred in 10 patients (71%) and included 7 cardiac, 5 neurological, 1 gastrointestinal, 1 infectious, and 1 pulmonary event. All survivors left the hospital symptomatically improved. The mean length of stay was 26 days. Four CABG patients went on to die at a mean of 2 years and 2 months, and 3 remain alive at a mean of 2 years and 4 months. Three AVR patients expired at a mean of 3 years and 4 months, and 3 remain alive at 4 years and 1 month. Conclusions : Cardiac surgery in carefully selected nonagenarians is justified and can be performed with acceptable results.     

Autologous blood transfusion for pediatric bone marrow donors.

Nine normal bone marrow donors aged 7-166 months (median 69 months) received autologous red cells which had been removed from their marrow harvest after collection. The median volume of marrow removed from the donors was 18.6 ml/kg which was equivalent to a median blood volume loss of 23.3%. Three infant donors were transfused with autologous red blood cells intraoperatively. These cells had been salvaged from the initial marrow aliquot and were transfused while bone marrow harvesting continued. No donors required homologous blood transfusion. This technique is useful for marrow donors in the pediatric age group when preharvest autologous blood collection is not feasible or available.     

Amyotrophic lateral sclerosis patient antibodies label Ca2+ channel α1 subunit

Sporadic amyotrophic lateral sclerosis is an idiopathic human degenerative disease of spinal cord and brain motor neurons. Prior studies demonstrated that most patients with amyotrophic lateral sclerosis posses immunoglobulins that bind to purified L-type voltage-gated calcium channels, that titers of anti–voltage-gated calcium channel antibodies correlate with disease progression rates, and that amyotrophic lateral sclerosis patient-derived antibodies (ALS IgG) produce electrophysiological changes in the function of voltage-gated calcium channels. Using Western transfer immunoblots and enzyme-linked immunosorbent assays, the calcium ionophore–forming α₁ subunig of the voltage-gated calcium channel is now identified as the major voltage-gated calcium channel antigen to which ALS IgG binds. Additionally, the binding of an L-type voltage-gated calcium channel α₁ subunit–directed monoclonal antibody, which itself mimics the effects of ALS IgG on skeletal muscle voltage-gated calcium channel currents, is selectively prevented by preaddition of ALS IgG. Voltage-gated calcium channel–binding IgG from patients with Lambert-Eaton myasthenic syndrome appears to be differentiated from ALS IgG by the reactivity of the former to both α₁ and β subunits of the calcium channel. These assays provide further evidence linking amyotrophic lateral sclerosis to an autoimmune process, and suggest one means to differentiate immunoglobulins from patients with amyotrophic lateral sclerosis from those of patients with another autoimmune disease expressing calcium channel antibodies.