Douglas A. Holt

Bilateral human fetal striatal transplantation in Huntington’s disease

BackgroundTransplanted striatal cells have been demonstrated to survive, grow, establish afferent and efferent connections, and improve behavioral signs in animal models of Huntington’s disease (HD). ObjectiveTo evaluate feasibility and safety and to provide preliminary information regarding the efficacy of bilateral human fetal striatal transplantation in HD. MethodsSeven symptomatic patients with genetically confirmed HD underwent bilateral stereotactic transplantation of two to eight fetal striata per side in two staged procedures. Tissue was dissected from the lateral half of the lateral ventricular eminence of donors 8 to 9 weeks postconception. Subjects received cyclosporine for 6 months. ResultsThree subjects developed subdural hemorrhages (SDHs) and two required surgical drainage. One subject died 18 months after surgery from probable cardiac arrhythmia secondary to severe atherosclerotic cardiac disease. Autopsy demonstrated clearly demarcated grafts of typical developing striatal morphology, with host-derived dopaminergic fibers extending into the grafts and no evidence of immune rejection. Other adverse events were generally mild and transient. Mean Unified HD Rating Scale (UHDRS) motor scores were 32.9 ± 6.2 at baseline and 29.7 ± 7.5 12 months after surgery (p = 0.24). Post-hoc analysis, excluding one subject who experienced cognitive and motor deterioration after the development of symptomatic bilateral SDHs, found that UHDRS motor scores were 33.8 ± 6.2 at baseline and 27.5 ± 5.2 at 12 months (p = 0.03). ConclusionsTransplantation of human fetal striatal cells is feasible and survival of transplanted cells was demonstrated. Patients with moderately advanced HD are at risk for SDH after transplantation surgery.

Congenital tuberculosis and management of exposures in a neonatal intensive care unit.

OBJECTIVES We report a case of congenital tuberculosis in a neonatal intensive care unit (NICU) and the management of exposure to other neonates in the hospital. We review the literature regarding congenital tuberculosis and management of exposures in the NICU. DESIGN Case report and a survey of exposures with a 3-month follow-up. SETTING Urban hospital. PATIENTS Neonates exposed to a case of congenital tuberculosis. INTERVENTIONS Exposure to tuberculosis was treated with isoniazid. Purified protein derivative tests were placed at baseline and 3 to 4 months after exposure. Chest radiographs were performed if clinically indicated. RESULTS Congenital tuberculosis was diagnosed in our patient at 21 days of age during a prolonged hospital course. After initiation of anti-tuberculous medications, the patient gradually recovered from his illness. While he was treated in the NICU, there were 37 potentially exposed infants. Of these, 36 were administered tuberculin skin tests (average age, 1.7 months), all of which were read as 0 mm of induration. Of those 37, 35 began prophylaxis with isoniazid, and 30 were able to complete treatment with a minimum of 3 months of isoniazid therapy. Of those 30, two infants received 6 months of therapy. Additionally, 29 of the 37 infants had chest radiographs, none of which showed suspicious infiltrates or adenopathy. Finally, 30 of the 36 infants had repeat tuberculin skin tests at 3 months, all of which were read as 0 mm of induration (average age, 3.7 months). CONCLUSION Congenital tuberculosis is an uncommon disease t hat requires early diagnosis for successful therapy and vigilant follow-up of potential exposures in the NICU.

Case report: toxic shock syndrome arising from cellulitis.

Toxic shock syndrome is a febrile, multiorgan illness related to toxins elaborated by staphylococcal or streptococcal infections. In the 1980s, most cases were associated with menstruation. More recently, many cases now are unrelated to menses. In this article, the authors describe a case of a nonmenstruating woman with toxic shock syndrome, associated with cellulitis of her arm. Cultures of the arm grew Staphylococcal aureus, which produced enterotoxin B.

Current views and challenges on clinical cholera

Cholera, an acute diarrheal infection has become a major global threat. Vibrio cholerae the causative agent of cholera has been responsible for six previous pandemics since 1817 that spanned four continents and Australia with the seventh pandemic ongoing since 1961. Two serogroups of V. cholerae O1 and O139 have the ability to secrete the enterotoxin with potential to cause epidemics. The prior six pandemics were caused by the classical biotype of the O1 serogroup. However, the emergence of the El Tor biotype and subsequent variants of El Tor with classical traits are the main isolates in the seventh pandemic. Cholera outbreaks have increased among vulnerable communities affected by war, earthquakes, conflicts and famines. Annually, 2.9 million cases of cholera occur globally in 69 endemic countries with 95,000 deaths. Early detection followed by prompt fluid and electrolyte replacement can reduce the case fatality ratio significantly. Improvements in water systems, sanitation and hygiene have effectively eliminated the transmission of cholera in high-income countries and reduced transmission in some developing nations. However, an estimated 1.8 billion are still at risk for cholera due to lack of potable water, inadequate sanitation and hygiene. Interventions focusing on hygiene in conjunction with proper disposal and treatment of sewage and provision of safe drinking water are likely to be effective in preventing the recurrence of cholera. Lastly, the use of current oral vaccines in endemic settings in combination with WASH interventions may be an effective approach to prevent and reduce the spread of cholera infection.

Human T-Cell Lymphotropic Virus-Type I

HTLV-I is a retrovirus now identified as the etiologic agent of two diverse disease processes: ATLL, an aggressive T-cell malignancy; and TSP/HAM, a chronic progressive myelopathy. Transmission can occur horizontally through blood transfusions, IV drug abuse and sexual intercourse. Vertical transmission may also occur. Available diagnostic modalities are serologic in nature and include the EIA and the more specific confirmatory assays WIB and RIPA. These studies are thus far suboptimal in terms of sensitivity and specificity, and await refinement. DNA amplification by the polymerase chain reaction seems to hold the most immediate diagnostic promise for the future. AZT apparently is not useful clinically, and current treatment is only palliative in nature. The diverse diseases caused by HTLV-I underscore the insidious nature of the Retroviridae family. These subtle cell-associated pathogens will undoubtedly be shown to play a significant role in other disease processes of uncertain etiology.

Central Nervous System Tuberculosis

Human immunodeficiency virus (HIV) and tuberculosis (TB) are, respectively, the number one and number two causes of infectious deaths worldwide. The relationship between these two microorganisms is unique, due to the synergistic ability of each disease to reactivate and accelerate the progression of the other. Through discussion of their general pathophysiology and the specific role of the human cellular immune response, four mechanisms will be delineated to further elaborate this challenging phenomenon.

The social determinants of health contextualized for the Zika virus

The social determinants of health are commonly understood as the milieu in which humans are born, live, work, reproduce, worship, and age that profoundly affect physical and mental health indicators and overall quality of life (US Department of Health and Human Services, 2017). These determinants are the proverbial deck of cards that a young infant is dealt; options for modification of one’s health are variable based on how one plays the hand. The World Health Organization considers health care one of the five pillars of the social determinants of health with economic stability, education, social context, and the built environment as equally important factors for a well-functioning personal and public health profile (World Health Organization, 2017). The determinants have modifiable policy levers at the global, national, and local levels of government and policy. Public health is best defined as the collective effort with which a society engages its population to encourage citizens to reach their utmost potential. An optimal public health system, and thus a healthy society, is dependent on a well-functioning network of government, medical centers and clinics, businesses, school systems, and infrastructure support of roads, utilities, and reliable transportation. The introduction of the Zika virus into the Western Hemisphere represents another somber step in the continuum of accelerated introduction of infectious disease vectors in recent times. The spread of Zika into Puerto Rico and the mainland United States represents the latest in a series of emerging infectious diseases that demanded a rapid public health emergency response. Public health task forces identified visible and invisible threats and mobilized for prevention, surveillance, monitoring, and response. In the context of the US territory of Puerto Rico, we remember that dengue and chikungunya virus already established an endemic foothold, with dengue virus making a limited debut into the Florida Keys in 2009. With devastating fetal effects, Zika unfortunately provides lasting visual stigmata of an already taxed social and public health infrastructure in endemic areas and naturally will elicit a rousing call to action for reform and improvement to prevent further sequelae. Puerto Rico, now ravaged by hurricane Maria, which made landfall on September 20, 2017 as the first Category 4 storm to impact the island since 1932, now has an intensified public health emergency as the population struggles for basic necessities with a delivery infrastructure in shambles.