BACKGROUND: In humans, after fertilization, the zygote divides into two 2n diploid daughter blastomeres. During this division, DNA is replicated, and the remaining mutually exclusive genetic mutations in the genome of each cell are called post-zygotic variants. Using these somatic mutations, developmental lineages can be reconstructed. How these two blastomeres are contributing to the entire body is not yet identified. This study aims to evaluate the cellular contribution of two blastomeres of 2-cell embryos to the entire body in humans using post-zygotic variants based on whole genome sequencing. METHODS: Tissues from different anatomical areas were obtained from five donated cadavers for use in single-cell clonal expansion and bulk target sequencing. After conducting whole genome sequencing, computational analysis was applied to find the early embryonic mutations of each clone. We developed our in-house bioinformatics pipeline, and filtered variants using strict criteria, composed of mapping quality, base quality scores, depth, soft-clipped reads, and manual inspection, resulting in the construction of embryological phylogenetic cellular trees. RESULTS: Using our in-house pipeline for variant filtering, we could extract accurate true positive variants, and construct the embryological phylogenetic trees for each cadaver. We found that two daughter blastomeres, L1 and L2 (lineage 1 and 2, respectively), derived from the zygote, distribute unequally to the whole body at the clonal level. From bulk target sequencing data, we validated asymmetric contribution by means of the variant allele frequency of L1 and L2. The asymmetric contribution of L1 and L2 varied from person to person. CONCLUSION We confirmed that there is asymmetric contribution of two daughter blastomeres from the first division of the zygote across the whole human body.

Radical trachelectomy is a fertility-preserving alternative to radical hysterectomy in carefully selected young women with early-stage cervical cancer. However, in cases with subsequent severe cervical stenosis, assisted reproductive techniques can be difficult. This is a case report of a 34-year-old patient who underwent robot-assisted radical trachelectomy and cerclage for early-stage (IB2) adenosquamous carcinoma. Three months after surgery, the patient underwent ovarian stimulation using a gonadotropin-releasing hormone antagonist protocol. As it was impossible to perform transcervical embryo transfer due to the almost complete absence of the cervical opening, transmyometrial embryo transfer under ultrasound guidance was performed. This resulted in a successful singleton pregnancy. This is the first case of successful pregnancy conceived by in vitro fertilization with transmyometrial embryo transfer in a patient who had previously undergone robot-assisted radical trachelectomy.

Radical trachelectomy is a fertility-preserving alternative to radical hysterectomy in carefully selected young women with early-stage cervical cancer. However, in cases with subsequent severe cervical stenosis, assisted reproductive techniques can be difficult. This is a case report of a 34-year-old patient who underwent robot-assisted radical trachelectomy and cerclage for early-stage (IB2) adenosquamous carcinoma. Three months after surgery, the patient underwent ovarian stimulation using a gonadotropin-releasing hormone antagonist protocol. As it was impossible to perform transcervical embryo transfer due to the almost complete absence of the cervical opening, transmyometrial embryo transfer under ultrasound guidance was performed. This resulted in a successful singleton pregnancy. This is the first case of successful pregnancy conceived by in vitro fertilization with transmyometrial embryo transfer in a patient who had previously undergone robot-assisted radical trachelectomy.

Pudendal neuralgia is characterized by severe sharp pain along the innervation area of pudendal nerve, which may be worsened when sitting position. Successful pudendal nerve block is crucial to the diagnosis of pudendal neuralgia. Although fluoroscopy-guided pudendal nerve blocks have traditionally been performed, recently ultrasound-guided pudendal nerve blocks were reported. For the long term effect of nerve block, pulsed radiofrequency was performed under fluoroscopic guidance in some reports. We report our successful experiences of three cases using ultrasound-guided pulsed radiofrequency.
Diagnosis ; Humans ; Nerve Block ; Pudendal Nerve* ; Pudendal Neuralgia*

PURPOSE: Levodopa is the most effective anti-Parkinsonian agent. It has also been known to exhibit analgesic properties in laboratory and clinical settings. However, studies evaluating its effects on neuropathic pain are limited. The aim of the present study was to examine the anti-allodynic effects of levodopa in neuropathic rats. MATERIALS AND METHODS: Sprague-Dawley male rats underwent the surgical procedure for L5 and L6 spinal nerves ligation. Sixty neuropathic rats were randomly divided into 6 groups for the oral administration of distilled water and levodopa at 10, 30, 50, 70, and 100 mg/kg, respectively. We co-administered carbidopa with levodopa to prevent peripheral synthesis of dopamine from levodopa, and observed tactile, cold, and heat allodynia pre-administration, and at 15, 30, 60, 90, 120, 150, 180, and 240 min after drug administration. We also measured locomotor function of neuropathic rats using rotarod test to examine whether levodopa caused side effects or not. RESULTS: Distilled water group didn't show any difference in all allodynia. For the levodopa groups (10-100 mg/kg), tactile and heat withdrawal thresholds were increased, and cold withdrawal frequency was decreased dose-dependently (p<0.01). In addition, levodopa induced biphasic analgesia. Different dosage of levodopa did not impact on the rotarod time (p>0.05). CONCLUSION: Levodopa reversed tactile, cold and heat allodynia in neuropathic rat without any side effects.
Animals ; Carbidopa/administration & dosage/adverse effects/therapeutic use ; Dopamine Agents/administration & dosage/adverse effects/*therapeutic use ; Hyperalgesia/*drug therapy ; Levodopa/administration & dosage/adverse effects/*therapeutic use ; Male ; Neuralgia/*drug therapy ; Rats ; Rats, Sprague-Dawley ; Rotarod Performance Test

Dexmedetomidine, which is a selective alpha2-adrenoceptor agonist, was recently introduced into clinical practice for its analgesic properties. The purpose of this study was to evaluate the effects of dexmedetomidine in a vincristine-evoked neuropathic rat models. Sprague-Dawley rats were injected intraperitoneally with vincristine or saline (0.1 mg/kg/day) using a 5-day-on, 2-day-off schedule for 2 weeks. Saline and dexmedetomidine (12.5, 25, 50, and 100 microg/kg) were injected to rats developed allodynia 14 days after vincristine injection, respectively. We evaluated allodynia at before, 15, 30, 60, 90, 120, 180, and 240 min, and 24 hr after intraperitoneal drug (normal saline or dexmedetomidine) injection. Saline treatment did not show any differences for all the allodynia. Maximal paw withdrawal thresholds to mechanical stimuli were 3.0 +/- 0.4, 9.1 +/- 1.9, 13.0 +/- 3.6, 16.6 +/- 2.4, and 24.4 +/- 1.6 g at saline, 12.5, 25, 50, and 100 microg/kg dexmedetomidine injection, respectively. Minimal withdrawal frequency to cold stimuli were 73.3 +/- 4.2, 57.1 +/- 6.8, 34.3 +/- 5.7, 20.0 +/- 6.2, and 14.3 +/- 9.5 g at saline, 12.5, 25, 50, and 100 microg/kg dexmedetomidine injection, respectively. Dexmedetomidine shows a dose-dependent antiallodynic effect on mechanical and cold stimuli in vincristine-evoked neuropathic rat models (P < 0.05).
Analgesics/*therapeutic use ; Animals ; Behavior, Animal/drug effects ; Dexmedetomidine/*therapeutic use ; Disease Models, Animal ; Hyperalgesia/chemically induced/*drug therapy ; Injections, Intraperitoneal ; Male ; Pain Threshold ; Rats ; Rats, Sprague-Dawley ; Vincristine/toxicity

Dexmedetomidine, which is a selective alpha2-adrenoceptor agonist, was recently introduced into clinical practice for its analgesic properties. The purpose of this study was to evaluate the effects of dexmedetomidine in a vincristine-evoked neuropathic rat models. Sprague-Dawley rats were injected intraperitoneally with vincristine or saline (0.1 mg/kg/day) using a 5-day-on, 2-day-off schedule for 2 weeks. Saline and dexmedetomidine (12.5, 25, 50, and 100 microg/kg) were injected to rats developed allodynia 14 days after vincristine injection, respectively. We evaluated allodynia at before, 15, 30, 60, 90, 120, 180, and 240 min, and 24 hr after intraperitoneal drug (normal saline or dexmedetomidine) injection. Saline treatment did not show any differences for all the allodynia. Maximal paw withdrawal thresholds to mechanical stimuli were 3.0 +/- 0.4, 9.1 +/- 1.9, 13.0 +/- 3.6, 16.6 +/- 2.4, and 24.4 +/- 1.6 g at saline, 12.5, 25, 50, and 100 microg/kg dexmedetomidine injection, respectively. Minimal withdrawal frequency to cold stimuli were 73.3 +/- 4.2, 57.1 +/- 6.8, 34.3 +/- 5.7, 20.0 +/- 6.2, and 14.3 +/- 9.5 g at saline, 12.5, 25, 50, and 100 microg/kg dexmedetomidine injection, respectively. Dexmedetomidine shows a dose-dependent antiallodynic effect on mechanical and cold stimuli in vincristine-evoked neuropathic rat models (P < 0.05).
Analgesics/*therapeutic use ; Animals ; Behavior, Animal/drug effects ; Dexmedetomidine/*therapeutic use ; Disease Models, Animal ; Hyperalgesia/chemically induced/*drug therapy ; Injections, Intraperitoneal ; Male ; Pain Threshold ; Rats ; Rats, Sprague-Dawley ; Vincristine/toxicity

Chronic perineal pain is an often encountered problem, which produces a great degree of functional impairment and frustration to the patient and a challenge to the treating physician. The reason for this problem is that the region contains diverse anatomic structures with mixed somatic, visceral and autonomic innervations affecting bladder and bowel control and sexual function. A blockade of nociceptive and sympathetic supply to the perineal region, supplied through the ganglion impar has been shown to benefit patients with chronic perineal pain. Several options to this block have been described that chemical neurolysis, radiofrequency ablation etc. Although the analgesic effect of Botulinum toxin type A (BoNT-A) has long been considered secondary to its action for muscle relaxation, BoNT-A also affects the release of the neurotransmitters that are involved in pain perception. We describe a patient who was successfully given ganglion impar block with BoNT-A.
Botulinum Toxins ; Botulinum Toxins, Type A ; Frustration ; Ganglion Cysts ; Humans ; Muscle Relaxation ; Nerve Block ; Neurotransmitter Agents ; Pain Perception ; Urinary Bladder

Despite recent methodological advancement of the practical pain medicine, many cases of the chronic anorectal pain have been intractable. A 54-year-old female patient who had a month history of a constant severe anorectal pain was referred to our clinic for further management. No organic or functional pathology was found. In spite of several modalities of management, such as medications and nerve blocks had been applied, the efficacy of such treatments was not long-lasting. Eventually, she underwent temporary then subsequent permanent sacral nerve stimulation. Her sequential numerical rating scale for pain and pain disability index were markedly improved. We report a successful management of the chronic intractable anorectal pain via permanent sacral nerve stimulation. But further controlled studies may be needed.
Female ; Humans ; Middle Aged ; Nerve Block

Chronic pain is a multifactorial condition with both physical and psychological symptoms, and it affects around 20% of the population in the developed world. In spite of outstanding advances in pain management over the past decades, chronic pain remains a significant problem. This article provides a mechanism- and evidence-based approach to improve the outcome for pharmacologic management of chronic pain. The usual approach to treat mild to moderate pain is to start with a nonopioid analgesic. If this is inadequate, and if there is an element of sleep deprivation, then it is reasonable to add an antidepressant with analgesic qualities. If there is a component of neuropathic pain or fibromyalgia, then a trial with one of the gabapentinoids is appropriate. If these steps are inadequate, then an opioid analgesic may be added. For moderate to severe pain, one would initiate an earlier trial of a long term opioid. Skeletal muscle relaxants and topicals may also be appropriate as single agents or in combination. Meanwhile, the steps of pharmacologic treatments for neuropathic pain include (1) certain antidepressants (tricyclic antidepressants, serotonin and norepinephrine reuptake inhibitors), calcium channel alpha2-delta ligands (gabapentin and pregabalin) and topical lidocaine, (2) opioid analgesics and tramadol (for first-line use in selected clinical circumstances) and (3) certain other antidepressant and antiepileptic medications (topical capsaicin, mexiletine, and N-methyl-d-aspartate receptor antagonists). It is essential to have a thorough understanding about the different pain mechanisms of chronic pain and evidence-based multi-mechanistic treatment. It is also essential to increase the individualization of treatment.
Analgesics, Opioid ; Antidepressive Agents ; Calcium Channels ; Capsaicin ; Chronic Pain ; Fibromyalgia ; Lidocaine ; Ligands ; Mexiletine ; N-Methylaspartate ; Neuralgia ; Neuromuscular Agents ; Norepinephrine ; Pain Management ; Serotonin ; Sleep Deprivation ; Tramadol