Murali Kolikonda

Depression and Anxiety Following Early Pregnancy Loss: Recommendations for Primary Care Providers

Early pregnancy loss is a shocking and traumatic event for women and their families. Miscarriage usually induces an intense period of emotional distress. This reaction tends to improve over the following several months, but some residual psychological concerns remain. It is important to screen for depression and anxiety in patients following a miscarriage. Most women in this circumstance do become pregnant again, yet mood disturbances can still coexist. When women are having difficulties at conception, worries may be magnified. Most women and physicians see post-miscarriage intervention as desired, and it is important to provide appropriate treatment. Management of depressive and anxiety symptoms after pregnancy loss can benefit future patient well-being.

RNA Polymerase 1 Is Transiently Regulated by Seizures and Plays a Role in a Pharmacological Kindling Model of Epilepsy

Ribosome biogenesis, including the RNA polymerase 1 (Pol1)-mediated transcription of rRNA, is regulated by the pro-epileptogenic mTOR pathway. Therefore, hippocampal Pol1 activity was examined in mouse models of epilepsy including kainic acid- and pilocarpine-induced status epilepticus (SE) as well as a single seizure in response to pentylenetetrazole (PTZ). Elevated 47S pre-rRNA levels were present acutely after induction of SE suggesting activation of Pol1. Conversely, after a single seizure, 47S pre-rRNA was transiently downregulated with increased levels of unprocessed 18S rRNA precursors in the cornu Ammonis (CA) region. At least in the dentate gyrus (DG), the pilocarpine SE-mediated transient activation of Pol1 did not translate into long-term changes of pre-rRNA levels or total ribosome content. Unaltered hippocampal ribosome content was also found after a 20-day PTZ kindling paradigm with increasing pro-convulsive effects of low dose PTZ that was injected every other day. However, after selectively deleting the essential Pol1 co-activator, transcription initiation factor-1A (Tif1a/Rrn3) from excitatory neurons, PTZ kindling was impaired while DG total ribosome content was moderately reduced and no major neurodegeneration was observed throughout the hippocampus. Therefore, Pol1 activity of excitatory neurons is required for PTZ kindling. As seizures affect ribosome biogenesis without long-term effects on the total ribosome content, such a requirement may be associated with a need to produce specialized ribosomes that promote pro-epileptic plasticity.

Kocuria kristinae infection during adalimumab treatment

ABSTRACT A common inhabitant of skin, the Kocuria kristinae of the Micrococcaceae family, has gained attention in recent years because it can induce pathology in humans. Reported is a Kocuria kristinae-caused abdominal abscess in a patient treated for rheumatoid arthritis with adalimumab. The tumor necrosis factor (TNF) inhibitor drugs are known to cause various bacterial, viral, and fungal infections. This is the first known case where an opportunistic infection with Kocuria has presented with an abdominal abscess in an immunocompromised individual who is on long term TNF inhibitors.

Prevention of Sudden Death in Patients With Epilepsy

To the Editor: Sudden unexpected death in epilepsy (SUDEP) occurs sometimes in people with ictal disorders.1 The diagnosis does not require evidence of a seizure and excludes status epilepticus as a cause of death. The postmortem examination must not reveal any toxic or anatomic pathology, and death must not be due to trauma or drowning. The prevalence of epilepsy in the United States is approximately 2.3 million in adults and 480,000 among children.1,2 One of 26 people in the United States and 1 of 103 people in Great Britain have epilepsy in their lifetime. The incidence of SUDEP is approximately 1–2 per 1,000 person years in patients with chronic epilepsy and 3–9 per 1,000 person years in severe, refractory seizures. There are more than 500 SUDEP deaths every year in Great Britain among the 600,000 individuals reported to have epilepsy.2 Postmortem studies indicate that up to 60% of all epilepsy-related deaths can be accounted for by SUDEP, making it the most common epilepsy-related cause of mortality.3 The risk of dying suddenly and unexpectedly for patients with epilepsy has been estimated to be more than 20 times greater than for the general population.1,2 The cause in two-thirds of the cases is unidentified. The most common risk factors for SUDEP are generalized tonic-clonic seizures, long-term epilepsy, male gender, polypharmacy, poor anticonvulsant drug compliance, and sleep deprivation.4 Case report. A 5-year-old girl, was treated in the pediatric neurology clinic. The diagnosis was severe, refractory seizures with a documented, recurrent myoclonic component of possible Dravet syndrome, according to ICD-9 diagnostic criteria. She had exhibited this convulsive disorder since the age of 3 years. Her epilepsy was managed with divalproex, temazepam, and a ketogenic diet. Despite pharmacotherapy, the child was never seizure free. One morning, the child was found dead in her bed. The family reported no new illnesses, change in ictal status, trauma, or other concerns recently. A postmortem examination revealed no toxic or anatomic pathology. The cause of death was considered to be SUDEP, noting a higher frequency of such occurrences in children with Dravet syndrome.5 Integration of different mechanisms is proposed to explain SUDEP: cardiac arrythmias, respiratory depression, and cerebral or autonomic dysfunction.6 Neuronal networks activated during a seizure inhibit the respiratory centers in the medulla, leading to hypoventilation with an acid-base imbalance, which can induce bradycardia, asystole, and death. Cardiorespiratory control by the brainstem is regulated via neurotransmitters like 5-hydroxytryptamine and adenosine.6 There is a rise in adenosine levels during convulsive activity that causes postictal hypoventilation, apnea, and arrhythmias. Serotonin decreases postictal hypoxemia, and reportedly in an animal experiment, selective serotonin reuptake inhibitor medications attenuated this influence.6 Talking about SUDEP with patients and family at the initial onset of seizures is controversial; rather, it is advised that it be discussed after patients are more established in the clinic.7 Utilizing a SUDEP safety checklist can help clinicians in assessing the risk of sudden death in patients with epilepsy.2 Discussion is for higher-risk individuals. A preventative plan is provided to patients and family, hopefully to improve patient compliance with medications and facilitate changes in lifestyle.7 Such a plan targets diminishing prominent risk factors (Table 1). Table 1. Prevention of Sudden Unexpected Death in Epilepsy1–7

Hyperactive Children Could They Have Sleep Disordered Breathing

To the Editor: Sleep disordered breathing (SDB) is underdiagnosed in children and difficult to differentiate from attention deficit hyperactivity disorder (ADHD). Both may present with similar symptoms of inattention, hyperactivity, irritability, and daytime sleepiness. Sleep disordered breathing includes primary snoring or obstructive sleep apnea, which are surprisingly common among children with hyperactivity. Adenotonsillar hypertrophy is the primary cause of obstructive sleep apnea between the ages of 2 and 8 years, coinciding with the age onset of ADHD, thus creating a difficult differential diagnosis. Sleep in these cases may be adequate in duration, but fragmented with frequent arousals that result in daytime dysfunction. Intermittent hypoxia during apnea causes inflammatory vascular changes in the brain, resulting in neurocognitive dysfunction, while sleep fragmentation causes inattentiveness. Approximately 25% of children with signs of ADHD also have evidence for SDB; about 28% of those scheduled for adenotonsillectomy exhibit criteria for ADHD (vs 7% for surgical controls). At 1 year post-adenotonsillectomy, 50% of them no longer meet the criteria for ADHD. Among adenotonsillectomy subjects with ADHD symptoms, 78% no longer evidenced ADHD after 6 months. Significant snoring is reported to be 2 times more common in children with ADHD than in other pediatric populations. It is important to screen for SDB in children who present with hyperactivity and/or inattention. Children with ADHD-like symptoms should be screened for signs of sleep disorders, such as snoring, apneas, and/or awakenings accompanied by gasping. When SDB is suspected, assessment includes a history, physical examination, X-ray of the neck, and fiberoptic endoscopy to rule out adenotonsillar hypertrophy. Polysomnography is the definitive means to diagnose SDB. Since SDB is rarely suspected in hyperactive children, detailed screening and diagnostic evaluation are critical. Psychostimulant treatment of a child with SDB may result in more sleep disturbance and dysfunctional behavior.

Guns in America: Defense or Danger?

Gun ownership in America is popular and has political support [1]. People often purchase guns for security, sometimes for sport or recreation, but also on occasion for nefarious considerations. The irony of this is that something obtained for safety or leisure purposes ends up killing or maiming people at an alarming rate, and with a high medical and social cost. Gun violence is an important health care issue [1]. The general public view about gun control and/or ownership is nearly evenly divided, with an increasing proportion favoring more built-in gun safety features and stricter laws, such as universal background checks.

A case of mouthwash as a source of ethanol poisoning: is there a need to limit alcohol content of mouthwash?

To the Editor: Mouthwash poisoning in adults is an infrequent presentation to the emergency service. It has been described in children and has led to tighter policies for safety packaging of the mouthwash bottles. We report a case of mouthwash poisoning in the context of a suicide attempt in an adult man. Case report. Mr A, a 53-year-old white man with a history of mouthwash ingestion as a suicide attempt, presented to the emergency department accompanied by police squad. He also had a history of DSM-IV bipolar disorder with psychosis. He reported consuming 2 large bottles of mouthwash about 12 hours before presenting to the emergency department. While in the emergency department, the patient continued to have suicidal ideation as well as visual and auditory hallucinations of a “pioneer and his family.” He verbalized that the voices were telling him to follow them and kill himself. He was positive for depression per screening questions and had no homicidal ideation or paranoid thoughts. His medication list included haloperidol, lithium carbonate, metoprolol, paliperidone palmitate, and temazepam. He had multiple suicide attempts in the past with mouthwash ingestion, the last one being 7 months ago. He had a history of alcohol abuse, but reported that he had not consumed any alcohol for the past 5 weeks. He smoked 1 pack of cigarettes per day for past 20 years. The patient lives in a group home and takes psychiatric medications as directed. Physical examination revealed him to be well-nourished. He was anxious but in no distress. Vital signs were as follows: blood pressure, 117/82 mm Hg; pulse, 80 beats/min; respirations, 16 breaths/min; temperature, 36.1°C (97°F). The pupils were 3 mm, equal, and reactive, and findings of the rest of his physical examination were within normal limits. Mr A was oriented to time, place, and person. His speech was fluent and non-dysarthric; cranial nerves were intact. Sensory and motor examination revealed no abnormalities. Cerebellar examination revealed a slightly unsteady gait and inability to do heel-toe walk, and there was finger-to-nose dysmetria. Deep tendon reflexes were within normal limits. Laboratory studies revealed complete blood cell count, thyroid-stimulating hormone levels, and free T4 levels to be within normal limits, and no abnormalities were found via electrocardiogram. No significant abnormalities in electrolytes were found. Serum chloride level was 114 mmol/L, serum carbon dioxide level was 19 mmol/L, the ratio of blood urea nitrogen to creatinine was 8.1; anion gap was 11 mmol/L, which is the upper limit of the normal range. Urinary ethanol level was 157 mg/dL. Computed tomography scan of the head revealed no abnormalities. During the course of hospitalization, Mr A was consulted by the psychiatry service. Besides being depressed and having some paranoid thoughts for the past few weeks, he did not report any other major mental health concerns. Ethanol is contained in a number of mouthwashes in a concentration typically between 5% and 27% of volume. Mouthwashes contain a variety of active and inactive ingredients. The ingredients of mouthwash include antibacterial agents, at least 50% water, stabilizers for non–water soluble ingredients, substances to improve palatability and stability, and preservatives to increase shelf-life. Ethanol is used in some mouthwash formulas as a solubilizer, stabilizer, preservative, and sensory cue with a distinctive taste as well as an antiplaque efficacy enhancer (adjuvant effect). Conflicting evidence exists regarding chronic mouthwash usage and its implication in causing oral cancers. A recent review article1 does not support the link between chronic mouthwash usage and oral cancers. There is also a concurrent rise in reports of ethanol abuse from household products such as mouthwashes, hand sanitizers, diphenhydramine syrup, aftershave lotions, and cosmetic products. Such abuse has been demonstrated in a case report2 of a female with acute ethanol ingestion whose blood ethanol levels remained persistently elevated due to secret ingestion of mouthwash in the hospital. There is a case report3 of fatal mouthwash poisoning in an adult that was believed to be due to the phenolic compound in the mouthwash. In 2009, McLay et al4 described mouthwash with alcohol content between 15% and 21% as a source of substance abuse in combat theaters. They described a case of psychosis due to mouthwash. A recent review5 demonstrated that ingestion of household products containing alcohol, especially mouthwashes and hand sanitizers, by children is still a major health concern. There is a relative decrease in incidence associated with child-resistant caps for the products. Even ethanol amounts as small as 1 ounce6 can produce deleterious effects such as hypoglycemia, seizures, and death in children. Children are more sensitive than adults to the effects of ethanol, and irritability might be the initial clue for the overdose; children are also more prone to hypoglycemic episodes. In children, tighter packaging has reduced the incidents of ingestion. In adults, however, there is increasing evidence that mouthwash is becoming a source of ethanol, with a preponderance of users being substance-dependent people. Hence, it is prudent to reduce the alcohol content of household nonbeverage ethanol products. Further research is mandated in the direction of contents of household products that can be potential sources of abuse and poisoning. It is also imperative for physicians to be vigilant about such sources of ethanol and advise their patients accordingly.