Historical vignette. The neurosurgeon's neurosurgeon: cushing operates on a Penfield

In his autobiography, Dr. Wilder Penfield relates the medical history of his sister, Mrs. Ruth Inglis, who developed a right frontal oligodendroglioma. Penfield performed the initial craniotomy on her, and after her death, reported the case in a paper on frontal lobe function in humans. Although Penfield has provided more than adequate information on certain aspects of his sister's illness, little has been published concerning her subsequent operation performed by Dr. Harvey Cushing at the Peter Bent Brigham Hospital. We feel this case is significant for several reasons. First, it sheds some light on Penfield's personal relationship with Cushing and his sister; it also shows the deep interest that Dr. Cushing took in his patients. Second, this case nicely illustrates how Cushing used his postoperative drawings to make his operative notes more precise. Finally, we see a sample of the work done by Dr. Louise Eisenhardt as pathologist at the Peter Bent Brigham Hospital.     

Omega-3 fatty acid treatment fails to alter alpha 1-adrenergic receptor mediated phosphoinositide turnover in streptozotocin-induced diabetic rats

1. The effect of omega-3 fatty acid supplementation on alpha 1-adrenergic receptor-mediated phosphoinositide turnover in the hearts of 6-week streptozotocin diabetic rats was studied. 2. The diabetic state was characterized by decreased body weight gain, hypoinsulinemia and hyperglycemia. Omega-3 fatty acid treatment did not have any significant effects on the above parameters. 3. Plasma triglyceride and cholesterol levels were significantly higher in diabetic rats compared with controls. 4. Omega-3 fatty acid treatment reduced the plasma triglyceride levels in the diabetic rats, whereas plasma cholesterol levels remained unaffected. 5. Norepinephrine (10 and 100 microM) stimulated inositol monophosphate (IP1) formation was significantly decreased in the diabetic rat heart compared with controls. Omega-3 fatty acid treatment had no significant effect on the norepinephrine-mediated IP1 formation in these rats. 6. Inositol bisphosphate (IP2) formation in response to 100 microM of norepinephrine was significantly lower in the diabetic rat heart; which was also not affected by omega-3 fatty acid treatment.     

An estimate of phylogenetic relationships among culicine mosquitoes using a restriction map of the rDNA cistron

Restriction maps of the rDNA cistron of twelve species of mosquitoes in six genera of the subfamily Culicinae were constructed using eight 6 bp recognition restriction enzymes. Anopheles albimanus was used as an outgroup. The size of the rDNA cistron ranged from 8.5 kb in Aedes katherinensis to 12.9 kb in Ae. polynesiensis. A total of twenty-six sites were scored; eighteen were polymorphic among ingroup taxa. The proportion of polymorphic nucleotide sites (Pnuc) was 0.059 and the heterozygosity per nucleotide site (Hnuc) was 0.028. Wagner and Fitch Parsimony, Dollo Parsimony and Nei-Li distance/neighbour-joining methods were used to construct phylogenetic trees. The rDNA RFLP dataset did not provide a well-supported phylogeny among culicine taxa. The RFLP phylogenies are incongruent with the morphology character based and molecular phylogenies and derived relationships did not correspond with current taxonomic classifications. The lack of resolution was due to homoplasy arising from frequent independent loss or gain of restriction sites among unrelated taxa.     

Risk factors for delayed immunization among children in an HMO.

OBJECTIVES. Improving the timely delivery of childhood immunizations has become a national imperative. This study aimed to identify nonfinancial predictors of delayed immunization among patients with good financial access to preventive care. METHODS. This prospective cohort study used telephone interviews and a computerized immunization tracking system to evaluate 13-month-old children (n = 530) in a regional group-model health maintenance organization. RESULTS. More than one third of parents interviewed did not know when the next immunization was due. Thirteen percent were late for the measles-mumps-rubella immunization, recommended at 15 months of age, by 90 days or more. Independent predictors of delayed immunization included having a larger number of children (odds ratio [OR] = 1.4, P < .01), not having a regular doctor (OR = 2.9, P < .05), not knowing when the shot was due (OR = 2.0, P < .01), and not worrying about the risks of shots (OR = 1.4, P < .05). CONCLUSIONS. Financial access alone does not guarantee timely childhood immunization. In managed care settings, which may cover increasing numbers of children under health care reform, interventions are needed to better inform parents of when immunizations are due.     

Malignant astrocytomas treated with iodine-125 labeled monoclonal antibody 425 against epidermal growth factor receptor: a phase II trial.

Twenty-five patients with primary presentation of malignant astrocytoma, astrocytoma with anaplastic foci, and glioblastoma multiforme were treated with surgical resection and definitive radiation therapy followed by intravenous or intra-arterial administration of Iodine-125 labeled monoclonal antibody-425, which binds specifically to human epidermal growth factor receptor. The patients presented with primary untreated disease, positive contrast enhanced computed tomography scans of the brain, and compatible clinical symptoms. In this Phase II clinical trial, the patients had surgical debulking or biopsy followed by definitively administered external beam radiation therapy and one or multiple doses (35 to 90 mCi per infusion) of radiolabeled antibody. The total cumulative doses ranged from 40 to 224 mCi. The administrations of the radiolabeled antibody were performed in most cases 4-6 weeks following completion of the primary surgery and radiation therapy. Ten patients had astrocytoma with anaplastic foci and 15 had glioblastoma multiforme. No significant life-threatening toxicities were observed during this trial. At 1 year 60% of the patients with astrocytoma with anaplastic foci or glioblastoma multiforme are alive. The median survival for both groups was 15.6 months.     

Partial tolerance in rat renal allograft recipients following multiple blood transfusions and concomitant cyclosporine

Multiple prior administrations of donor-strain blood while under limited cyclosporine cover, consistently induce extensive rat renal allograft survival and transplantation tolerance. Yet it was hypothesized that some chronic rejection mechanisms were nevertheless operative since consistent but nonprogressive minor renal dysfunction was observed long-term. A histopathologic study on these putative tolerant rats was undertaken to test this hypothesis. Twenty long-term LEW recipients of BN renal allografts receiving the blood-CsA regimen were examined histopathologically at day 100 post-transplant. Sixteen control LEW recipients receiving only a BN renal allograft were studied acutely at day 7 posttransplant. The control recipients demonstrated a range of lesions consistent with previous studies on acute renal allograft rejection in the rat. However, tolerant recipients demonstrated mild-to-moderate lesions consistent with chronic mechanisms of rejection including the following: moderate focal interstitial mononuclear inflammatory cellular infiltration, with periglomerular and perivascular accumulation; occasional arteriolar luminal obliteration and glomerular atrophy; focal areas of moderate interstitial fibrosis; mild interstitial hemorrhage; mild-to-moderate tubular atrophy; and focal tubular necrosis. Previously our laboratory has documented that tissue-specific renal basement membrane antigens may be responsible for inciting this pattern of focal chronic interstitial inflammation. However, from the present histopathologic studies, it would appear likely that chronic rejection mechanisms in these recipients, which were defined as tolerant by immunologic criteria, involve both tissue-specific and MHC determinants. Therefore, induction of transplantation tolerance in these indefinite survivors is partial or incomplete.     

Short-term hyperglycemia depresses immunity through nonenzymatic glycosylation of circulating immunoglobulin

Hyperglycemia accompanies a myriad of clinical conditions and causes an acceleration in the nonenzymatic glycosylation (NEG) of proteins. Since many proteins lose function when glycosylated, we assessed the effect of hyperglycemia on the function of immunoglobulin G. Twenty newborn Sprague-Dawley rats underwent splenectomy and 20, splenic mobilization alone. After 3 weeks, all animals received an intraperitoneal injection of Streptococcus pneumoniae. Twelve hours later, ten animals from each group received either control (CIG) or glycosylated (GIG) human immunoglobulin (0.3 gm/kg) intraperitoneally. Asplenic animals receiving GIG lived 28.5 hours vs. 49.6 hours for those receiving CIG (p less than 0.0001). Animals with spleens receiving GIG lived 48.2 hours vs. 51.7 hours for those receiving CIG (p = 0.03). Short-term glycosylation of immunoglobulin causes its inactivation. This may contribute to the increased risk of infection noted in hyperglycemic animals.