Cervical Spinal Cord Stimulation for Failed Neck Surgery Syndrome.

PURPOSE OF REVIEW: Cervical spine pain with or without radicular symptoms is a common condition leading to high utilization of the healthcare system with over 10 million medical visits per year. Many patients undergo surgical interventions and unfortunately are still left with neck and upper extremity pain, sometimes referred to as "Failed Neck Surgery Syndrome." When these options fail, cervical spinal cord stimulation can be a useful tool to decrease pain and suffering as well as reduce prescription medication use. RECENT FINDINGS: Spinal cord stimulation is a well-established therapy for chronic back and leg pain and is becoming more popular for neck and upper extremity pain. Recent studies have explored cervical spinal cord stimulation with successful outcomes regarding improved pain scores, functional outcomes, and reduction of prescription medication use. Continued research into cervical spinal cord stimulation is essential for maximizing its therapeutic potential for patients with chronic neck and upper extremity pain. This review highlights the importance of cervical spinal cord stimulation as an option for patients with failed neck surgery syndrome.

Current Review of Regenerative Medicine Therapies for Spine-Related Pain.

PURPOSE OF REVIEW: Persistent spinal pain syndromes are pervasive and lead to functional impairment, increased healthcare utilization, potential disability, and high societal costs. Spinal (cervical, thoracic, lumbar, and sacroiliac joint) pain includes mechanical, degenerative, inflammatory, oncologic, and infectious etiologies. Regenerative medicine is a novel biotechnology targeting mechanical, degenerative, and inflammatory conditions believed to cause pain. Preparations including platelet-rich plasma, mesenchymal stem cells (adipose tissue and bone marrow aspirate concentrates), and growth factors are derived from an autologous donor. The goal of intervention through guided injection of the regenerative media is to reduce inflammation and reverse the degenerative cascade in hopes of restoring normal cellular composition (physiologic homeostasis) and anatomical function to improve pain and function. The authors review limited research supporting the use of platelet-rich plasma injections for facet joint arthropathy and sacroiliac joint pain compared to traditional steroid treatments, as well as the use of platelet rich plasma or mesenchymal stem cells for lumbar discogenic and radicular pain. RECENT FINDINGS: Current evidence to support regenerative medicine for spine-related pain is limited. Although several studies demonstrated a reduction in pain, many of these studies had a small number of participants and were case series or prospective trials. Regenerative medicine treatments lack evidence for the treatment of spine-related pain. Large randomized controlled trials are needed with consistent study protocols to make further recommendations.

Post-thoracotomy Pain Syndrome.

PURPOSE OF REVIEW: This article reviews PTPS demographics, diagnosis, pathophysiology, surgical and anesthetic techniques, and their role in preventing PTPS along with updated treatment options. RECENT FINDINGS: Post-thoracotomy pain syndrome (PTPS) can be incapacitating. The neuropathic type pain of PTPS is along the incision site and persists at least 2 months postoperatively. There is a wide reported range of prevalence of PTPS. There are several risk factors that have been identified including surgical technique and younger age. Several surgical and anesthetic techniques have been trialed to reduce pain after thoracotomy. Multimodal pain control is the suggested long-term treatment plan for patients with PTPS. There are several factors that can be modified to reduce pain and incidence of PTPS during the perioperative period and the use of multimodal analgesia is suggested for the treatment of PTPS.

Integrating APOL1 Gene Variants Into Renal Transplantation: Considerations Arising From the American Society of Transplantation Expert Conference.

Thirteen percent of individuals of African ancestry express two variant copies of the gene encoding apolipoprotein 1 (APOL1) that has been associated with an increased risk of end-stage renal disease (ESRD) in the general population. Limited studies suggest that the survival of transplanted kidneys from donors expressing two APOL1 risk alleles is inferior to that of kidneys from donors with zero or one risk allele. In living kidney donation, two case reports describe donors expressing two APOL1 risk alleles who developed ESRD. Given the potential impact of APOL1 variants on the utility and safety of kidney transplantation and living kidney donation, the American Society of Transplantation convened a meeting with the goals of summarizing the current state of knowledge with respect to transplantation and APOL1, identifying knowledge gaps and studies to address these gaps, and considering approaches to integrating APOL1 into clinical practice. The authors recognize that current data are not sufficient to support traditional evidence-based guidelines but also recognize that it may require several years to generate the necessary data. Thus, approaches as to how APOL1 might currently be integrated into the clinical decision-making process were considered. This report summarizes the group's deliberations.

Coccidioidomycosis Transmission Through Organ Transplantation: A Report of the OPTN Ad Hoc Disease Transmission Advisory Committee.

Donor-derived coccidioidomycosis has caused unexpected morbidity and mortality in transplant recipients. All proven or probable reports of donor-derived coccidioidomycosis to the Disease Transmission Advisory Committee between 2005 and August 2012 were reviewed. Six reports of proven or probable coccidioidomycosis were discovered. In four of six, the infection was first detected at autopsy in the recipient. In two cases it was first identified in the donor. Twenty-one recipients received organs from these six donors. Transmission occurred in 43% at a median of 30 days posttransplant with a mortality rate of 28.5%. Eleven recipients received preemptive antifungals, seven did not receive treatment, and treatment information was not reported for three recipients. Five of seven who did not receive prophylaxis/treatment died and all 11 who received early therapy survived. Six deaths occurred 14 to 55 days after transplant, with a median of 21 days. For exposed recipients, donor-derived coccidioidomycosis is a significant cause of morbidity and mortality. Evidence of infection in one recipient should prompt immediate evaluation for treatment of all other recipients from the same donor as preemptive treatment was effective. Further studies are needed to decide whether all donors from endemic areas should have routine serologic screening.

Hand-grip strength does not correlate with treatment-related weight loss in patients with head and neck cancer.

BACKGROUND: Hand-grip strength has been shown to be a reliable predictor of health outcomes. However, evidence supporting its use as an indicator of nutritional status is inconsistent. This study investigated its use in monitoring nutritional status in patients with head and neck cancer. METHODS: A prospective audit of patients treated for head and neck cancer was undertaken at four centres over a three-month period in 2009. Nutritional outcomes were collected at 3, 6 and 12 months, and the data were statistically analysed. RESULTS: Data from 114 patients showed that mean weight, but not hand-grip strength, fell significantly at 3, 6 and 12 months post-treatment (p < 0.003 vs p < 0.126). CONCLUSION: A fall in weight does not coincide with a drop in hand-grip strength in patients receiving treatment for head and neck cancer. Hand-grip strength may therefore not be of benefit in the nutritional assessment of these patients and should not be part of routine assessment.

Communication gaps associated with donor-derived infections.

The detection and management of potential donor-derived infections is challenging, in part due to the complexity of communications between diverse labs, organ procurement organizations (OPOs), and recipient transplant centers. We sought to determine if communication delays or errors occur in the reporting and management of donor-derived infections and if these are associated with preventable adverse events in recipients. All reported potential donor-derived transmission events reviewed by the Organ Procurement and Transplantation Network Ad Hoc Disease Transmission Advisory Committee from January 2008 to June 2010 were evaluated for communication gaps between the donor center, OPO and transplant centers. The impact on recipient outcomes was then determined. Fifty-six infection events (IEs; involving 168 recipients) were evaluated. Eighteen IEs (48 recipients) were associated with communication gaps, of which 12 resulted in adverse effects in 69% of recipients (20/29), including six deaths. When IEs and test results were reported without delay, appropriate interventions were taken, subsequently minimizing or averting recipient infection (23 IEs, 72 recipients). Communication gaps in reported IEs are frequent, occur at multiple levels in the communication process, and contribute to adverse outcomes among affected transplant recipients. Conversely, effective communication minimized or averted infection in transplant recipients.

Donor-transmitted malignancies in organ transplantation: assessment of clinical risk.

The continuing organ shortage requires evaluation of all potential donors, including those with malignant disease. In the United States, no organized approach to assessment of risk of donor tumor transmission exists, and organs from such donors are often discarded. The ad hoc Disease Transmission Advisory Committee (DTAC) of the Organ Procurement and Transplantation Network/United Network for Organ Sharing (OPTN/UNOS) formed an ad hoc Malignancy Subcommittee to advise on this subject. The Subcommittee reviewed the largely anecdotal literature and held discussions to generate a framework to approach risk evaluation in this circumstance. Six levels of risk developed by consensus. Suggested approach to donor utilization is given for each category, recognizing the primacy of individual clinical judgment and often emergent clinical circumstances. Categories are populated with specific tumors based on available data, including active or historical cancer. Benign tumors are considered in relation to risk of malignant transformation. Specific attention is paid to potential use of kidneys harboring small solitary renal cell carcinomas, and to patients with central nervous system tumors. This resource document is tailored to clinical practice in the United States and should aid clinical decision making in the difficult circumstance of an organ donor with potential or proven neoplasia.

Donor screening for human T-cell lymphotrophic virus 1/2: changing paradigms for changing testing capacity.

Organ Procurement and Transplant Network (OPTN) policy currently requires the testing of all potential organ donors for human T-cell lymphotrophic virus (HTLV)-1/2. Most Organ Procurement Organizations (OPO) use the Abbott HTLV-I/HTLV-II Enzyme Immunoassay (EIA). This assay will no longer be manufactured after December 31, 2009; the only commercially available FDA-licensed assay will be the Abbott PRISM HTLV-I/II assay which poses many challenges to OPO use for organ donor screening. As a result, screening donors for HTLV-1/2 in a timely manner pretransplant after December 31, 2009 will be challenging. The true incidence of HTLV-1 in United States (U.S.) organ donors is not well described but appears to be low ( approximately 0.03-0.5%). HTLV-1 is associated with malignancy and neurological disease; HTLV-2 has not been convincingly associated with disease in humans. Donors that are HTLV-1/2 seropositive are infrequently used despite most results being either false positive or resulting from HTLV-2 infection. There is urgent need to encourage the development of assays, instruments and platforms optimized for organ donors that can be used to screen for transmissible disease in donors; these must have appropriate sensitivity and specificity to identify all infections while minimizing organ loss through false positive testing.

Rat arylalkylamine N-acetyltransferase gene: upstream and intronic components of a bipartite promoter.

The daily rhythm in the activity of arylalkylamine N-acetyltransferase (AA-NAT) controls the rhythm in melatonin synthesis in the pineal gland. In the rat, transcriptional regulatory mechanisms play a major role in determining the observed pattern of AA-NAT gene expression. Remarkably, high levels of AA-NAT transcripts can only be detected in the night pineal; significant levels can also be found in the retina. To characterize the regulatory events that impinge upon the activity of the AA-NAT gene we embarked on the systematic analysis of the AA-NAT promoter. To this end we transfected several AA-NAT promoter derivative constructs to monitor reporter gene activity in both pineal and non-pineal primary cell cultures. Our studies revealed a cooperative arrangement between upstream promoter and downstream intronic regions which appear to contain most of the key elements necessary to ensure the proper spatio-temporal pattern of AA-NAT gene expression.

The rat arylalkylamine N-acetyltransferase gene promoter. cAMP activation via a cAMP-responsive element-CCAAT complex.

A 10-100-fold rhythm in the activity of arylalkylamine N-acetyltransferase (AA-NAT; EC 2.3.1.87) controls the rhythm in melatonin synthesis in the pineal gland. In some mammals, including the rat, the high nocturnal level of AA-NAT activity is preceded by an approximately 100-fold increase in AA-NAT mRNA. The increase in AA-NAT mRNA is generated by norepinephrine acting through a cAMP mechanism. Indirect evidence has suggested that cAMP enhances AA-NAT gene expression by stimulating phosphorylation of a DNA-binding protein (cAMP-responsive element (CRE)-binding protein) bound to a CRE. The nature of the sites involved in cAMP activation was investigated in this report by analyzing the AA-NAT promoter. An approximately 3700-base pair fragment of the 5'-flanking region of the rat AA-NAT gene was isolated, and the major transcription start points were mapped. The results of deletion analysis and site-directed mutagenesis indicate that cAMP activation requires a CRE.CCAAT complex consisting of a near-perfect CRE and an inverted CCAAT box located within two helical turns.

HWA-448 reduces gentamicin toxicity in LLC-PK1 cells.

An LLC-PK1 cell culture model was used to evaluate for a direct protective effect of the pentoxifylline analogue HWA-448 in gentamicin nephrotoxicity at the cellular level. Cells exposed to 2 mM gentamicin for 6 days displayed a significant decrease in specific activities of leucine aminopeptidase, NaK ATPase, and N-acetyl glucosaminidase, and an increase in total cellular phospholipids (P < .05). Concomitant exposure to 0.125 mM HWA-448, a dose that did not alter cellular enzymes or total phospholipids under physiologic conditions, prevented the alterations in marker enzymes and total phospholipids induced by gentamicin (P < .05). Gentamicin binding and uptake studies revealed 0.125 mM HWA-448 had no effect on LLC-PK1 cell plasma membrane binding or cellular gentamicin uptake. We conclude that HWA-448 ameliorates gentamicin-induced alterations in LLC-PK1 cell enzymes and phospholipids by a mechanism independent of plasma membrane binding or cellular uptake.

A legacy of violence in nonorganic failure to thrive.

It is often postulated that a mother's past experiences influence her ability to function as a parent. If those past experiences involve her as a victim of abuse, what lies ahead for her offspring? We studied 59 mothers of children referred for nonorganic failure to thrive (NOFTT) to the University of Colorado Health Sciences Center and compared their abuse history with a group of 131 mothers of children with normal growth. The mothers of NOFTT children were younger but of the same socioeconomic groups as the comparison mothers. Mothers of NOFTT children had a significantly higher history of abuse when compared to the comparison group p < 0.001. A surprising 80% of mothers of NOFTT children reported they were victims of abuse. We alert clinicians to the likelihood that mothers of children with NOFTT may be victims of abuse and that successful treatment of the child depends upon treatment of the mother-child dyad.

Reactions to perinatal loss: a qualitative analysis of the National Maternal and Infant Health Survey.

Women who had experienced an infant or fetal death responded to an open-ended question on the 1988 National Maternal and Infant Health Survey about their perinatal experience. A qualitative analysis of the 413 responses identified six major themes, including need for further information, problems with the mourning process, and unresolved questions about the cause of the death. Implications of the findings for health care practice are discussed.

Scrub typhus in Korea: importance of early clinical diagnosis in this newly recognized endemic area.

Scrub typhus became a well recognized infectious disease threat to military operations in the Pacific Theater during World War II. Early diagnosis and treatment with tetracycline or chloramphenicol dramatically reduces the mortality and morbidity of this disease. Korea is a newly recognized scrub typhus endemic country. We report our experience with 189 scrub typhus patients seen at a civilian outpatient clinic in Chinhae, Republic of Korea, from 1985 through 1990, and verify the accuracy of clinical diagnosis by serologic tests.

Virulence of wild-type E. coli uroisolates in experimental pyelonephritis.

This study was designed to analyze the colonizing and invasive properties of wild-type bacteriuric E. coli possessing a variety of phenotypic characteristics in experimental nonobstructive pyelonephritis (P and Type 1 [T] fimbriae, hemolysin [Hly], presence of K capsules, flagella [H], serotype, biotype, human and mouse serumcidal resistance). Special emphasis was on the role of Gal-Gal adhesin (P fimbriae) of non-genetically engineered uroisolates. It was shown that organisms that are P+ or T+ or Hly+ are more likely to colonize bladders than strains negative for those parameters (P less than 0.001). Additionally, P+ strains were more often associated with kidney histopathology than P- E. coli (P less than 0.05). However, the data also indicated that fimbriae (P and Type 1) were not sole determinants of virulence since two strains devoid of fimbriae, hemolysin, K capsules and sensitive to human serumcidal activity caused incipient and acute pyelonephritis. Even among identical serotypes and biotypes, the presence/absence of fimbriae did not appear to be the critical factor in urovirulence, nor did the presence of several positive characteristics (hemolysin, K capsule, flagella, serum resistance) in a given strain enhance uropathogenicity. Therefore, these properties do not need to work together to render an E. coli urovirulent. These phenotypic characters may simply represent associated or serologic markers with the host serving as the dominant determinant of susceptibility to urinary infection. The findings emphasize the inherent limitations in relating and extrapolating colonizing and invasive properties of genetically engineered strains to those of naturally occurring, wild-type E. coli human uroisolates causing pyelonephritis.

Alterations in cholinergic muscarinic and somatostatin binding sites in a patient with idiopathic intestinal pseudo-obstruction.

We present a comparative study of cholinergic muscarinic and somatostatin binding sites on isolated membranes from mucosa and tunica muscularis of normal and dilated parts of the proximal jejunum obtained at surgery from a patient with idiopathic intestinal pseudo-obstruction (IIP) syndrome. We found a statistically significant diminution of cholinergic muscarinic and somatostatin binding sites in mucosa taken from the dilated part of the jejunum, compared with those taken from the normal part. Tunica muscularis of the dilated part of the jejunum contained a significantly higher concentration of peripheral cholinergic muscarinic binding sites (M2) than the normal part did, whereas concentration of M1 cholinergic muscarinic and somatostatin binding sites was similar in both examined parts. These results indicate that IIP-syndrome may be related to alterations in cholinergic muscarinic binding sites in the tunica muscularis of the intestine.

Gastric, duodenal, and pancreatic somatostatin-like immunoreactivity during hypovolemic shock.

Because hypovolemic shock is known to cause gastric ulcers in animals and human beings, we investigated the tissue levels of somatostatin-like immunoreactivity (SLI) in the gastric corpus and antrum, duodenum, and pancreas during hypovolemic shock in rats. We studied male Wistar rats (N = 10 each) 15 min, 2 hr, and 12 hr after hypovolemic shock and compared results to a control group (N = 15). Two rats in both 2-hr and 12-hr groups showed gastric ulcers: three corporal and one antral. One animal developed multiple ulcers. In the gastric corpus and antrum and in the duodenum, tissue SLI showed significant decrease 15 min and 2 hr after shock. Gastric SLI remained low, whereas duodenal SLI recovered and rose above control level at 12 hr. Pancreatic SLI showed no significant changes during hypovolemic shock. Gastric tissue SLI levels that were significantly lower after shock than those of normal controls may have contributed to the peptic ulcer disease induced by hypovolemic shock in this experimental model.

Cochlear blood flow. The effect of six hours of noise exposure.

The effect of six hours of high-frequency, high-intensity noise exposure on cochlear blood flow (CoBF) was investigated in adult gerbils. The CoBF was measured by microsphere-surface preparation methods. Intracardiac injection of the microspheres (diameter, 11.1 microns; Dupont/New England Nuclear Research Products, Boston) was performed in the last few minutes of the sixth hour of continuous noise exposure, and reference blood was withdrawn from the iliac artery at a rate of 0.165 mL/min. The number of microspheres in the investigated tissue was assessed by direct counting under a microscope. The number of microspheres in the reference blood was counted by a Coulter counter. These experiments have shown that CoBF at the end of six hours of continuous noise exposure does not significantly differ from the CoBF in control animals.