The Role of Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers in Postangioplasty Restenosis.

Postangioplasty restenosis remains a clinical problem, and various strategies have been used to minimize or eliminate this complication. Stimulation of the renin-angiotensin system has been shown to cause vascular smooth muscle migration, matrix deposition, and endothelial dysfunction, which are possible causes of postangioplasty restenosis, suggesting that the use of angiotensin-converting enzyme (ACE) inhibitors and/or angiotensin receptor blockers might ameliorate or prevent restenosis. However, data obtained to date in both animal and human studies of various designs show conflicting results regarding the benefit or lack of benefit of angiotensin inhibition strategies. It has also been shown that the type of ACE genotype may influence the effects of drugs on restenosis, suggesting that in the future, a pharmacogenetic approach might be of use for augmenting the benefit in patients from inhibitors of the angiotensin system. As of now, there are no supportive data to suggest a benefit of using routine ACE inhibitors or angiotensin receptor blockers to prevent postangioplasty restenosis in the general population.

A 32-year-old male with recurrent hypothermia and hypotension of unknown cause.

OBJECTIVE: To report a rare case with hypothermia, hypotension and thrombocytopenia. CLINICAL PRESENTATION AND INTERVENTION: A 32-year-old male presented with recurrent hypothermia, hypotension and thrombocytopenia. He had reduced sensitivity to the environmental temperature, but had no structural brain abnormalities on MRI. The patient recovered completely with warming and supportive treatments. CONCLUSION: This case showed that rare cases of idiopathic hypothermia, hypotension and thrombocytopenia should be managed clinically and warming and supportive treatments were successful.

Importance of Regular and Maintenance Therapy Adherence in Neuromyelitis Optica (NMO): Lessons from a Repeating Relapse Case.

BACKGROUND Neuromyelitis optica (NMO) is a rare demyelinating disease of the central nervous system; NMO predominantly affects the spinal cord and optic nerves. The diagnosis is based on history, clinical presentation, seropositive NMO-IgG antibody, and notably, exclusion of other diseases. Despite the absence of definitive therapeutic strategies for NMO, methylprednisolone pulse therapy and plasma exchange are used for acute phase treatment, while immunosuppressive agent(s) are recommended to prevent relapses and improve prognosis. Here, we report a repeating relapse NMO case due to lack of regular and maintenance therapy. CASE REPORT A 58-year-old female with chronic NMO presented with a three-day history of new-onset right leg weakness and pain. The patient was diagnosed with NMO three years ago and presented with her fourth attacks. During her initial diagnosis, she was initiated on steroids. One year later, she developed the first relapse and was treated with steroids and rituximab, leading to 1.5-year remission. After the second relapse, steroids and rituximab was still given as maintenance therapy, but was not followed. Thus, the third relapse occurred in five months. During this hospitalization, she received initially high-dose solumedrol (1 g daily for five days) in addition to gabapentin 100 mg (gradually increased to 300 mg) three times a day for muscle spasms. Due to worsening of paresthesia and hemiparesis, it was decided to place her on plasma exchange treatment. After two plasma exchanges, the patient's condition was improved and she regained strength in her lower extremity. She completed five more cycles of plasma exchange, and was then discharged on steroid therapy (prednisone 20 mg daily for 10 days then taper) as maintenance therapy and with follow-up in neurology clinic. CONCLUSIONS Over the span of three years, the patient has had three relapses since her NMO diagnosis where her symptoms have worsened. Steroid therapy alone seemed not insufficient in managing her more recent relapses. Nonadherence to NMO treatment likely increased her risk for recurrence, thus regular and long-term maintenance therapy is imperative to delay the progression and prevent relapse in NMO.

An Uncommon Case of Lower Limb Deep Vein Thrombosis with Multiple Etiological Causes.

BACKGROUND Deep vein thrombosis (DVT) is a type of venous thromboembolism with diverse clinical and environmental risk factors. Very few cases of DVT with multiple high risk factors have been reported. Here, we report an uncommon DVT case with multiple etiological causes, including appendicitis/appendectomy, morbid obesity, immobilization, positive phosphatidylserine IgG, and heterozygous factor V Leiden mutation. CASE REPORT A 43-year-old female was brought to the emergency room because of 2-week history of pain and swelling and ultrasound revealing evidence of DVT in the right leg. One month ago, she underwent an exploratory laparotomy because of subacute appendicitis. After surgery, the patient stayed at home in bed with very limited activity. She did not have a cough, hemoptysis, chest pain, or shortness of breath. She was morbidly obese, and had a past medical history of diabetes, hypertension, and hyperlipidemia. A full coagulation workup was completed, including Protein C, Protein S, and antiphospholipid antibody, as well as factor V and prothrombin gene mutation screen. Her D-dimer was positive. Computed tomography (CT) angiography of the lungs ruled out major emboli but was unable to rule out minor emboli. A heterozygous factor V Leiden R506Q mutation was detected. Of interest was a significantly positive phosphatidylserine IgG with a value of over 42. She was started with enoxaparin (120 mg, twice a day), and warfarin was added on day 2 when pulmonary embolism was ruled out by CT angiography. The International Normalized Ratio (INR) was monitored daily to adjust warfarin dose. CONCLUSIONS Multiple etiological factors present in this patient may have contributed to her lower-limb DVT, including appendicitis/appendectomy, morbid obesity, immobilization, positive phosphatidylserine IgG, and factor V Leiden mutation. Therefore, it is important to follow the complete workup for hypercoagulable states. This can help with diagnosis and therapy, and also give insight into the pathogenicity, which can help with prevention of recurrence and severe complications of DVT.

Hyperbaric oxygen and lymphoid system function: a review supporting possible intervention in tissue transplantation.

This review addresses the many ways that hyperbaric oxygen (HBO2) has been found to mitigate immune reactions, many of which are involved in rejection of allograft transplants, and thus offers a rationale for its possible use as an adjunct to help preserve and protect transplanted tissues. Rejection may involve both immunological reactions of the lymphoid system, or lymphoid-independent damage from trauma or other factors, including reperfusion injury. Lymphoid-induced damage involves cellular elements such as CD4 and macrophage cell types, as well as both proinflammatory and inhibitory cytokines. Cytokines such as TNFs and interleukins activate T-cells and macrophages, resulting in endothelial damage and its consequences. The immunosuppressive effects of HBO2 include suppression of autoimmune symptoms, decreased production of IL-1 and CD4 cells, and increased percentage and absolute number of CD8 cells. HBO2 normalizes cell-bound immunity and decreases the serum concentration of immune complexes. Studies have shown MHC class I expression to be altered when cultures were exposed to HBO2, so as to become undetectable by monoclonal antibodies or cytotoxic T lymphocytes. HBO2 has been used in support of replanted rabbit ear grafts, spinal cord tissue transplants, dislocated young permanent teeth in children, replanting of fingers, free fibula reconstruction of segmental mandibular resections, autogenous free bone grafts, transplantations of the cornea, and liver transplants. In addition to its specific effects on the immune system, HBO2 improves tissue oxygenation, reduces free radical damage during reperfusion, maintains marginally ischemic tissue, and accelerates wound healing. These properties make HBO2 a promising intervention to be tested in transplantation recipients.

Hyperhomocysteinemia-induced upper extremity deep vein thrombosis and pulmonary embolism in a patient with methyltetrahydrofolate reductase mutation: a case report and literature review.

The study highlights pulmonary embolism and deep vein thrombosis by methylene tetrahydrofolate reductase (MTHFR) deficiency-related hyperhomocysteinemia occurring in rare locations of left veins superior to the heart extensively. A 59-year-old white man with history of leg pain, smoking, weight loss, benign prostatic hyperplasia, lipoma and panic attack presented with shortness of breath and chest pain for 2 days precipitated by not feeling well for months. The diagnostic workup revealed pulmonary embolism and deep vein thrombosis in the left subclavian vein which extended throughout the left brachiocephalic vein to the superior vena cava and left jugular vein. Further workup showed moderate hyperhomocysteinemia with normal levels of vitamin B6, B12 and folic acid. Methylene tetrahydrofolate reductase genetic study found the patient to be homozygous for G677T variant. He was started on low-molecular-weight heparin and was discharged on oral anticoagulant. No recurrent thrombotic episodes were witnessed after 4 months of follow-up after discharge.

Hyperbaric oxygen in the treatment of patients with cerebral stroke, brain trauma, and neurologic disease.

Hyperbaric oxygen (HBO) therapy has been used to treat patients with numerous disorders, including stroke. This treatment has been shown to decrease cerebral edema, normalize water content in the brain, decrease the severity of brain infarction, and maintain blood-brain barrier integrity. In addition, HBO therapy attenuates motor deficits, decreases the risks of sequelae, and prevents recurrent cerebral circulatory disorders, thereby leading to improved outcomes and survival. Hyperbaric oxygen also accelerates the regression of atherosclerotic lesions, promotes antioxidant defenses, and suppresses the proliferation of macrophages and foam cells in atherosclerotic lesions. Although no medical treatment is available for patients with cerebral palsy, in some studies, HBO therapy has improved the function of damaged cells, attenuated the effects of hypoxia on the neonatal brain, enhanced gross motor function and fine motor control, and alleviated spasticity. In the treatment of patients with migraine, HBO therapy has been shown to reduce intracranial pressure significantly and abort acute attacks of migraine, reduce migraine headache pain, and prevent cluster headache. In studies that investigated the effects of HBO therapy on the damaged brain, the treatment was found to inhibit neuronal death, arrest the progression of radiation-induced neurologic necrosis, improve blood flow in regions affected by chronic neurologic disease as well as aerobic metabolism in brain injury, and accelerate the resolution of clinical symptoms. Hyperbaric oxygen has also been reported to accelerate neurologic recovery after spinal cord injury by ameliorating mitochondrial dysfunction in the motor cortex and spinal cord, arresting the spread of hemorrhage, reversing hypoxia, and reducing edema. HBO has enhanced wound healing in patients with chronic osteomyelitis. The results of HBO therapy in the treatment of patients with stroke, atherosclerosis, cerebral palsy, intracranial pressure, headache, and brain and spinal cord injury are promising and warrant further investigation.

Skin squamous cell carcinoma presenting as cellulitis.

In general, skin squamous cell carcinoma (SCC) presents as papules or plaques with erythematous or pigmented appearance that may ulcerate the skin. Cellulitis caused by metastatic deposit from a known primary skin SCC has been reported once.1 We describe a patient who presented with cellulitis on the face that did not respond well to full course of antibiotics treatment, and turned out to be a newly diagnosed SCC after biopsy. Other differential diagnoses, such as malignancy, should be suspected in all unusual presentations and biopsy should be taken if patients do not show an optimal and desired improvement after receiving a full-course of antibiotic therapy for cellulitis.

Novel histone deacetylase inhibitors in clinical trials as anti-cancer agents.

Histone deacetylases (HDACs) can regulate expression of tumor suppressor genes and activities of transcriptional factors involved in both cancer initiation and progression through alteration of either DNA or the structural components of chromatin. Recently, the role of gene repression through modulation such as acetylation in cancer patients has been clinically validated with several inhibitors of HDACs. One of the HDAC inhibitors, vorinostat, has been approved by FDA for treating cutaneous T-cell lymphoma (CTCL) for patients with progressive, persistent, or recurrent disease on or following two systemic therapies. Other inhibitors, for example, FK228, PXD101, PCI-24781, ITF2357, MGCD0103, MS-275, valproic acid and LBH589 have also demonstrated therapeutic potential as monotherapy or combination with other anti-tumor drugs in CTCL and other malignancies. At least 80 clinical trials are underway, testing more than eleven different HDAC inhibitory agents including both hematological and solid malignancies. This review focuses on recent development in clinical trials testing HDAC inhibitors as anti-tumor agents.