Fulminant Anti-GAD antibody encephalitis presenting with status epilepticus requiring aggressive immunosuppression.

Antibodies against glutamic acid decarboxylase (GAD) are reported in association with numerous neurological conditions including temporal lobe epilepsy and limbic encephalitis. We report a case of Anti-GAD-Antibody associated encephalitis presenting with epilepsia partialis continua (EPC) progressing to a fulminant encephalopathy preferentially affecting the frontal lobes associated with coma and refractory status epilepticus. The abnormalities identified on MRI included marked bilateral frontal lobe involvement which has not been reported in other auto-immune encephalitides and may be specific for Anti-GAD-Antibody associated encephalitis. Similar to the majority of cases of Anti-GAD associated neurological disturbance no underlying malignancy was identified. Treatment with high dose corticosteriods, IVIG and plasmapheresis had minimal response, but escalation of treatment with rituximab and cyclophosphamide was associated with clinical improvement, reducing antibody titers and resolution of MRI changes.

Transforming growth factor-beta receptor type I gene is frequently mutated in ovarian carcinomas.

Ovarian carcinomas (OCs), particularly recurrent OCs, are frequently resistant to transforming growth factor (TGF)-beta-mediated growth inhibition. Mutations in the TGF-beta receptor type II (TbetaR-II) gene are only evident in a minority of OCs, suggesting that other alterations of the TGF-beta signaling pathway may be involved in OC. Using PCR, cold single-strand conformation polymorphism, and DNA sequencing, we now show that 33% of primary OCs (10 of 30) harbor somatic changes in exons 2, 3, 4, and 6 of the TGF-beta receptor I (TbetaR-I) gene. Most of the changes are missense mutations and clustered largely in the catalytic domain of the receptor kinase. Interestingly, seven additional cases (23.3%) showed heterozygous carriers of an allelic variant [a 9-nucleotide deletion, del(GGC)(3)] in exon 1 of the TbetaR-I gene. This is in contrast with 10.6% of del(GGC)(3) heterozygous carriers in a recent report of a large normal population (n = 735; B. Pasche et al., Cancer Res., 59: 5678-5682, 1999). These results indicate that TbetaR-I is frequently mutated in OC and suggest that resistance to TGF-beta-mediated growth inhibition may frequently involve alterations of the TbetaR-I gene.

Challenges posed by non-random missing quality of life data in an advanced-stage colorectal cancer clinical trial.

Effects of variations in agent, dose, and route of treatment administration on patient reported quality of life (QOL) were examined for 279 patients enrolled on a seven-arm randomized clinical trial (S8905) of 5-FU and its modulation for advanced colorectal cancer. Patients completed QOL questionnaires at randomization and weeks 6, 11, and 21 post-randomization with five QOL endpoints considered primary: three treatment-specific symptoms (stomatitis, diarrhea, and hand/foot sensitivity); physical functioning; and emotional functioning. Patient compliance with the QOL assessment schedule was good, supporting the feasibility of including QOL measures in cooperative group trials. However, death and deteriorating health produced substantial missing data. Cross-sectional analyses indicated that the seven therapeutic arms did not differ in their impact on QOL. Unfortunately, longitudinal analyses of the QOL data were inappropriate given non-random missing data. Graphical presentation of non-random missing data identified the seriousness of this problem and its effect on potential conclusions about QOL during treatment. This problem appears to be particularly challenging in the context of advanced-stage disease. Failure to recognize the presence of non-random missing data can lead to serious overestimates of patient QOL over time.

Disease progression, adherence, and response to protease inhibitor therapy for HIV infection in an Urban Veterans Affairs Medical Center.

Indinavir therapy has demonstrated promise in the treatment of HIV-1 infection in clinical trials; however, its efficacy in a U.S. Veterans Affairs Medical Center, where access to therapy is generally unimpeded, is unknown. A review of the Miami cohort was conducted for the year beginning May 1996 to evaluate response to indinavir plus two nucleoside analogues. Of 483 HIV-1-positive patients (97% male; mean age, 46.7+/-9.7 years), 266 were offered indinavir based on their having CD4 counts <200 cells/microl or viral loads >10,000 copies/ml. Of these patients, 36% were adherent and experienced significant reductions in viral loads (-93,325+/-147,911 copies/ml) and elevations in CD4+ (111+/-103 cells/microl) and CD8+ (225+/-338 cells/microl) T cell counts. Adherent patients with baseline CD4 counts <100 cells/microl were 4.5 times more likely to have follow-up viral loads >10,000 copies/ml than those with CD4 >200 cells/microl. Adherent patients with CD4 counts <100 cells/microl did not show evidence of immune "exhaustion" because they were equal to those with CD4 counts >200 cells/microl in their capacity to replenish CD4 cells. Nonadherence to the regimen resulted in loss of therapeutic benefit and suggested that strategies to enhance adherence may become an essential component of treatment.

Epidemiology of diarrhoeal illness associated with coccidian-like organism among travellers and foreign residents in Nepal.

A newly described organism called CLB (coccidian-like or cyanobacterium-like body) has been identified in cases of prolonged diarrhoea. To confirm an association of CLB with disease and identify risk factors for transmission, we conducted a case-control study of travellers and foreign residents at two outpatient clinics in Kathmandu, Nepal. Patients without diarrhoea were matched to CLB cases by clinic and date of visit. For comparison, patients with other causes of diarrhoea were also studied. Stools were examined for enteric pathogens with standard microbiological and molecular genetic techniques. CLB was identified in 108 (11%) of 964 individuals with gastrointestinal symptoms compared with only 1 (1%) of 96 symptom-free controls (p = 0.003). 7% of residents in the US Embassy community acquired the infection. The diarrhoeal illness associated with CLB lasted a median of 7 weeks (interquartile range 4-9) compared with 9 days (4-19) for individuals with other causes of diarrhoea (p < 0.0001). The prevalence of other enteric pathogens was no higher among CLB cases than among symptom-free controls. Patients with CLB infection were more likely than controls to report consumption of untreated water (odds ratio 3.98; 95% CI 1.29-13.14); organisms of the same appearance were identified in an epidemiologically implicated water sample. The significant association of CLB with prolonged diarrhoea, and the low rate of other enteropathogens in CLB cases, strongly supports the hypothesis that CLB is a new pathogen. Epidemiological and environmental data suggest that the organism is waterborne.

Riding with Bucklebear: an automobile safety program for preschoolers.

Almost half of the accidental deaths of children are directly attributable to motor vehicle accidents, yet many children continue to ride unrestrained. This study was designed to determine if an educational program could increase preschool children's knowledge of car safety and improve their behavior when riding in cars. Knowledge scores increased significantly following the educational program, but the use of seat belts did not change markedly. Although young children can learn self-care skills in respect to seat belt use, they apparently need strong support and reinforcement from parents in their implementation.

Subdural empyema and epidural abscess: recent experience in a community hospital.

We treated 31 cases of localized central nervous system infection over a seven-year period in our community hospital. The causes included brain abscess in 18 cases (58%); cranial subdural empyema (CSE) in six cases (20%); spinal epidural abscess (SEA) in four cases (13%); cranial epidural abscess (CEA) in two cases (6%); and spinal subdural empyema (SSE) in one case (3%). Both CSE and CEA were often caused by sinusitis and manifested by fever, headache, altered sensorium, and focal neurologic signs. Treatment consisted of drainage by burr holes or craniotomy followed by long-term administration of parenteral antibiotics. Though all patients with CSE and CEA survived, half had severe residual neurologic deficits. Both SEA and SSE were manifested by fever, spinal pain, and loss of motor function, and both were treated by laminectomy drainage and antibiotic administration. One patient died and three of the other four had residual neurologic deficits or back pain. Diagnosis of CSE and CEA was facilitated by CT scanning, while clinical examination, CT scanning, and myelography were useful in diagnosing SEA; SSE was not suspected preoperatively.

Automobile seat belt practices of pregnant women.

Despite the fact that seat belts have been proved effective in reducing deaths and serious injuries, many pregnant women do not wear seat belts. A study was conducted to examine the seat belt practices of pregnant women. Of the 87 women who were interviewed, 40 reported using seat belts regularly during pregnancy. However, almost one-third of them did not adjust the belts properly for maximum protection. Older women and those with more education were more likely to use their seat belts routinely. Only 20 women recalled receiving information about seat belts during their pregnancies, but 48 women would have liked to receive more information.

Determination of gallium concentration in "blood-free" tissues using a radiolabeled blood marker.

Radioiodinated serum albumin has been used as a blood marker to define and quantitate physiological volumes for 12 organs and tissue types. The concentration of gallium-67 in "blood-free" tissues of rats was also determined at various times after intravenous administration. Tissues were divided into two kinetically distinguishable types based on reported nonuniform distribution of the blood marker and the gallium distribution observed in the present study. Gallium distribution into the liver and spleen was observed to be slow, with a discernable accumulation phase followed by monoexponential elimination. In contrast, gallium accumulation into the stomach, small and large intestines, heart, lung, skin/adipose tissue, and muscle was rapid and elimination was monophasic.

Enteral hyperthermia.

We have presented a previously unreported complication of enteral hyperalimentation, namely drug-induced fever due to tube feeding formula. Clinicians caring for patients receiving enteral hyperalimentation should be alert to this complication so that needless tests and medications can be avoided.

Brain abscess: recent experience at a community hospital.

Brain abscess is a formidable diagnostic and therapeutic problem with mortality ranging from 35% to 65%. It may occur at any age, and there is a male:female ratio of 2:1. Brain abscess arises from a contiguous focus of infection, direct implantation due to trauma, or hematogenous spread from a remote site. The commonest organisms isolated from brain abscess include streptococci, Staphylococcus aureus, Bacteroides species, and Enterobacteriaceae. Brain abscess frequently produces headache, vomiting, focal neurologic signs, and depressed level of consciousness. Fever and leukocytosis often are absent. Diagnosis is suggested by computerized tomography, but most cases require surgical confirmation. Optimal management consists of intensive antibiotic therapy. Aggressive surgical treatment is required in cases not responding to antimicrobial therapy. Long-term neurologic deficit occurs in up to 60% of cases.

Alteration of gallium distribution in the rat using periodically related elements: enhanced early imaging.

Complexes of carrier-gallium and indium were administered to normal rats and rats with tumors 2 to 6 hours after an injection of carrier-free 67Ga citrate in order to determine their effect on the distribution of 67Ga. Both Ga and In rapidly and significantly decreased the blood activity. Imaging with the same dosage schedule showed decreased activity in soft tissue and viscera, and increased activity in bone, kidney, and bladder. In animals with tumor high doses of carrier-Ga were shown to deplete tumor activity as well as activity in viscera and soft tissues. Moderate doses of carrier-Ga allowed blood and soft tissue clearing with no significant loss of tumor activity. When In citrate was administered to animals with tumors 2 hours after administration of 67Ga, tumor activity continued to increase while soft tissue and visceral activity decreased. Simultaneous injection of In citrate and 67Ga drastically altered the distribution of 67Ga. Two hours after the injection activity was present only in the tumor, kidney, bladder, and bone. This rapid clearance of non-productive Ga brings forth the potential for use of short lived, positron emitting 68Ga coupled with emission tomography.