Effects of different progestogens on human breast tumor cell growth.

OBJECTIVE: To examine the effect of progestogens currently used in hormone therapy on growth of human breast tumor cells. METHODS: MCF-7 cells were incubated in 10 nmol/l progestogens, including progesterone (P4), medroxyprogesterone acetate (MPA), norethisterone acetate (NETA), and cyproterone acetate (CPA), with or without 17ß-estradiol (E(2), 1 nmol/l and 10 nmol/l), as well as E(2) alone. Cell proliferation, apoptosis, and the expression of caspase-3 and proliferating cell nuclear antigen (PCNA) were evaluated. RESULTS: The ratios of apoptosis : proliferation significantly increased in cultures with progestogens alone, 1 nmol/l E(2) plus progestogens (except P4), and 10 nmol/l E(2) plus NETA. Caspase-3 significantly diminished in cultures with E(2) alone; this was completely reversed when progestogens were added. MPA alone or with 1 nmol/l E(2) and 10 nmol/l E(2) plus NETA significantly increased caspase-3. Using progestogens alone, except P4, significantly decreased PCNA expression. CONCLUSIONS: The results demonstrate that various progestogens have different effects on growth of breast tumor cells, especially with the combined usage of E(2). Progestogen-induced apoptosis may be partly inhibited with the presence of E(2), but less severe with lower E(2) concentrations. Therefore, the choice of progestogens, as well as the doses of E(2) and/or progestogen, may influence breast cancer risk.

A questionnaire survey on patients' willingness to pay with reference to the waiting time of public in-vitro fertilization treatment in Hong Kong.

OBJECTIVE: To evaluate patients' willingness to pay (WTP) with reference to the waiting time of public in-vitro fertilisation (IVF) treatment in order to improve the public IVF service in Hong Kong. STUDY DESIGN: A prospective multi-centred questionnaire survey. Infertile women attending infertility clinics of nine public hospitals in Hong Kong between October 2017 and August 2018 were asked to complete a questionnaire in their first clinic visit. RESULTS: Out of 1092 respondents, 10.4 % had private IVF cycles prior to their first visit at public hospitals. In general, patients were willing to pay more for a shorter waiting time for public IVF service. The proportion of respondents who were willing to pay more than HK$10,000 (US$1282) for one IVF cycle increased from 54.6% to 80.7% if the waiting time for public IVF service were hypothetically shortened from four years to one year. Likewise, 22.5 % versus 45.5 % were willing to pay more than HK$ 25,000 (US$3205) with a waiting time of four versus one year respectively. Assuming the cost per IVF cycle was HK$ 25,000 (US$3205), 23.4 % of respondents could afford one IVF cycle, 40.0 % of them could afford two IVF cycles and 31.5 % could afford three IVF cycles. A multivariate regression model demonstrated that only family income and presence of existing child(ren) were significant independent determinants of the maximum amount that an individual was willing to pay for IVF (p < 0.05). Those with family monthly income below HK$100,000 ($12,820) were less than half as likely, and those without existing child(ren) were more than double as likely, to be willing to pay higher for IVF. CONCLUSION: Patients were willing to pay more for a shorter waiting time for public IVF service. Those with family income below HK$100,000 (US$ 12,820) were less than half as likely, and those without existing children were more than double as likely, to be willing to pay higher for IVF.

Changing antiepileptic drug use for seizures in US neonatal intensive care units from 2005 to 2014.

OBJECTIVE: Neonatal seizures are a common problem in the neonatal intensive care unit and are frequently treated with antiepileptic drugs. Limited data exist on current or changing antiepileptic drug use for seizures in the neonatal intensive care unit.We sought to describe trends of antiepileptic drug exposure in a large volume of US neonatal intensive care unit from 2005 to 2014 and we hypothesized increasing levetiracetam exposure over the 10-year study period. STUDY DESIGN: Retrospective cohort study of infants from the Pediatrix Medical Group Clinical Data Warehouse, a large, multicenter, deidentified data set. Data were analyzed for trends in 2-year time periods. Our cohort included infants with a diagnosis of seizures who received an antiepileptic drug that were discharged from the neonatal intensive care unit from 1 January 2005 to 31 December 2014. RESULTS: Among 778 395 infants from 341 facilities, we identified 9134 infants with a seizure diagnosis who received an antiepileptic drug. Phenobarbital was used in 98% of the cohort. From 2005-2006 to 2013-2014 phenobarbital exposure declined from 99 to 96% (P<0.001), phenytoin exposure decreased from 15 to 11% (P<0.001) and levetiracetam exposure increased 10-fold from 1.4 to 14% (P<0.001). Overall, <1% of infants were exposed to carbamazepine, lidocaine or topiramate. CONCLUSIONS: Infants with seizures were overwhelmingly exposed to phenobarbital, despite a significant increase in levetiracetam exposure. The use of phenytoin declined and has been surpassed by levetiracetam as the second most widely used antiepileptic in the neonatal intensive care unit. These changes in antiepileptic drug usage patterns have occurred in the absence of novel efficacy data in neonates.

Sphenoid sinusitis masquerading as migraine headaches in children.

The sphenoid sinus is often referred to as the "neglected sinus." Isolated sphenoid sinusitis is a rare disease with potentially devastating complications. It occurs at an incidence of about 2.7% of all sinus infections. Although headache is the most common presenting symptom, there is no typical headache pattern. Three cases of children with isolated sphenoid sinusitis presenting with acute, subacute, and chronic headache symptoms are presented. The sensory innervation of the sphenoid sinus is derived from the ophthalmic and maxillary branches of the trigeminal nerve, which may explain the pathophysiology of the headache, similar to the trigeminovascular pain theory of migraine. There are few reports on sphenoid sinusitis and headache; however, modern neuroimaging has made this probably under-recognized disorder easier to diagnose and treat. Although the diagnosis can be difficult to differentiate from migraine headache, early and appropriate treatment usually results in an excellent outcome without morbidity.

Drug therapy in juvenile dermatomyositis: follow-up study.

A series of 33 patients with juvenile dermatomyositis was reviewed in terms of their prognosis in relation to their drug therapy. This retrospective study was intended to help clarify the use of various therapies in this rare, heterogeneous disease from our hospital's experience in the last 24 years. The results confirmed that oral corticosteroids should remain the undisputed first line of treatment. For more refractory, chronic patients, the results suggest that azathioprine should be the favored drug of first choice (in addition to corticosteroids). There may be a role for cyclosporine as a "rescue" treatment, but this needs to be further defined.

Encephalopathy associated with respiratory syncytial virus bronchiolitis.

Respiratory syncytial virus is an extremely common cause of childhood respiratory infections resulting in significant morbidity and mortality. Although apnea is a well-known complication in young infants with respiratory syncytial virus bronchiolitis, the encephalopathy associated with this infection is not well recognized. Our study reveals an incidence of encephalopathy of 1.8% in a total of 487 patients with respiratory syncytial virus bronchiolitis studied over a period of almost 4 years. Seizures were the presenting complication. Based on our study of a cohort of children with respiratory syncytial virus bronchiolitis, we believe that neurologic complications, although relatively uncommon, represent a significant component of this common childhood illness. Furthermore, respiratory syncytial virus has been shown to release several mediators that could directly or indirectly be neurotoxic and induce an encephalopathy associated with the respiratory illness.

Visual-evoked potentials in the assessment of optic gliomas.

The most effective method for the screening and monitoring of optic pathway gliomas in children with neurofibromatosis type 1 remains a dilemma. Children less than 6 years of age are the group at highest risk for the development of optic pathway gliomas. Although an annual ophthalmologic examination currently is recommended as the most efficient method to screen for optic pathway gliomas, this method is often unreliable and inaccurate in young children. Magnetic resonance imaging remains the most sensitive test; however, cost and the need for sedation or general anaesthetic preclude its use as a routine screening test. We previously have recommended visual-evoked potentials (VEPs) as a possible alternative or aid in the assessment of optic pathway gliomas in this group of patients. The aims of this study were to ascertain the sensitivity of VEPs in detecting optic pathway gliomas and to determine whether VEPs are useful in monitoring the progress of optic pathway gliomas. This study provides further evidence of the sensitivity of VEPs in detecting optic pathway gliomas. In addition, VEPs may provide additional useful information concerning the progression of optic pathway gliomas once they have been detected.

Anesthetic management of a parturient implanted with a permanent pacemaker--a case report.

At the present time, a patient with a pacemaker who undergoes an anesthesia for a surgical procedure is very common, but a parturient with a permanent pacemaker scheduled for elective cesarean section (c/s) is very rare. Complete heart block in pregnancy is not a common event and it may be congenital or acquired, particularly secondary to cardiac surgery. In normal women, the heart rate is physiologically increased commensurate with need, whereas in a parturient with installment of an implanted fixed rate pacemaker of VVI mode her heart rate cannot accelerate to cope with increased physiological demand because of the fixed pacing rate. For cesarean section, because of destabilized cardiovascular adaptation, an anesthesiologist must focus on detecting the early signs of compromised cardiac output in order to avoid maternal as well as fetal distress. He may run considerable risk to administer general or regional anesthesia to this kind of parturient. We present a case report in managing the parturient installed a with non-rate response type pacemaker undergoing C/S under epidural anesthesia.

Timing of gangrene tissue debridement after autologous bone marrow cell implantation in patients with superficial femoral arterial occlusion: preliminary experiences.

AIM: Although implantation of bone marrow mononuclear cells (BMI) was shown to improve outcomes in patients with severe peripheral arterial occlusive disease (PAOD), little experience has been reported in patients with an arterial occlusion level above the knee, ischemic gangrene, and high cardiovascular risk. This study sought to investigate the timing of gangrene tissue debridement and the safety of BMI in these patients. METHODS: Six "no-option" PAOD patients were enrolled with an arterial occlusion level above the knee, ischemic gangrene, and 3 systemic diseases related to a high cardiovascular risk. The ischemic status was evaluated by measuring the ankle-brachial index (ABI), transcutaneous oxygen pressure (TcPO2), and wound healing after BMI. RESULTS: All patients safely underwent the procedures with intravenous general anesthesia by titrating propofol. Major lower extremity amputation, minor debridement amputation, and debridement surgery were performed in 2 (33.3%), 1 (16.7%), and 2 (33.3%) patients, respectively, 3.1 2.8 months after BMI. Compared to the amputation group (N=3), the salvage group (N=3) had a significantly higher baseline ABI (P=0.02) and a shorter distance between the gangrene site and arterial occlusion site (P=0.01). In the 3 patients who underwent debridement, ABI and TcPO2 significantly improved 1 month after BMI, and gangrenous tissues were debrided 3.8 ± 3.6 (range, 1~8) months after BMI with complete healing within 1 month. CONCLUSION: Autologous BMI therapy is safe in patients at high cardiovascular risk with an arterial occlusion level above the knee and ischemic gangrene. Effective predictors of BMI include the baseline ABI and distance to the ischemia. Gangrene tissue should be debrided at least 1 month after BMI.

Randomized, phase III study results of clobazam in Lennox-Gastaut syndrome.

OBJECTIVE: To evaluate efficacy and safety of clobazam, a 1,5-benzodiazepine, as adjunctive therapy for Lennox-Gastaut syndrome (LGS). METHODS: Patients aged 2-60 years were randomized to placebo or clobazam 0.25, 0.5, or 1.0 mg/kg/day. Study consisted of 4-week baseline, 3-week titration, and 12-week maintenance phases, followed by a 2- or 3-week taper or continuation in an open-label extension. Primary endpoint was percentage decrease in mean weekly drop seizure rates during maintenance vs baseline phases for modified intention-to-treat (mITT) population. Secondary outcomes included other seizure types, responder rates, and physicians' and caregivers' global assessments. RESULTS: A total of 305 patients were screened, 238 were randomized, and 217 composed the mITT population. Of patients enrolled after a protocol amendment, 125/157 (79.6%) completed. Average weekly drop seizure rates decreased 12.1% for placebo vs 41.2% (p = 0.0120), 49.4% (p = 0.0015), and 68.3% (p < 0.0001) for the clobazam 0.25-, 0.5-, and 1.0-mg/kg/day groups. Responder rates (≥50%) were 31.6% (placebo) vs 43.4% (p = 0.3383), 58.6% (p = 0.0159), and 77.6% (p < 0.0001) for clobazam 0.25-, 0.5-, and 1.0-mg/kg/day groups. Physicians' and caregivers' assessments indicated clobazam significantly improved symptoms. Somnolence, pyrexia, upper respiratory infections, and lethargy were the most frequent adverse events reported for clobazam. CONCLUSIONS: Clobazam significantly decreased weekly drop seizure rates in LGS. No new safety signals were identified. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that clobazam as adjunctive therapy is efficacious, in a dosage-dependent manner, in reducing mean weekly drop seizure rates of patients with LGS over 12 weeks.

White matter density is increased in patients with hypothalamic hamartoma and multiple seizure types.

Many patients with hypothalamic hamartomas present in infancy with gelastic seizures of subcortical origin, but later develop additional seizure types, including complex partial, tonic, and generalized tonic-clonic seizures. The basic cellular mechanisms responsible for this evolution in seizure types are unknown. Using voxel-based morphometry of T1 weighted MRI scans we compared eight patients with only gelastic seizures with 16 age-matched patients with multiple seizure types and found significantly greater white matter density in the temporal lobes and cerebellum in those with multiple seizure types. This suggests that increased white matter density, perhaps resulting from maturational changes and resulting in increased brain connectivity, is associated with a higher likelihood of cortical involvement in epilepsy resulting from hypothalamic hamartoma.

Endoscopic resection of hypothalamic hamartomas for refractory symptomatic epilepsy.

BACKGROUND: Hypothalamic hamartomas (HHs), rare developmental abnormalities of the inferior hypothalamus, often cause refractory, symptomatic, mixed epilepsy, including gelastic seizures. We present 37 patients with HH who underwent transcortical transventricular endoscopic resection. METHODS: Between October 2003 and April 2005, 42 consecutive patients with refractory epilepsy who underwent endoscopic resection of HH were studied prospectively. The endoscope was held by an articulated pneumatic arm and tracked with a frameless stereotactic neuronavigation system. Data collection and follow-up were performed by personal interview. Five patients were excluded. The remaining 37 patients (22 males, 15 females; median age 11.8 years; range 8 months to 55 years) had frequent and usually multiple types of seizures. RESULTS: Postoperative MRI confirmed 100% resection of the HH from the hypothalamus in 12 patients. At last follow-up (median 21 months; range 13-28 months), 18 (48.6%) patients were seizure free. Seizures were reduced more than 90% in 26 patients (70.3%) and by 50% to 90% in 8 patients (21.6%). Overall, the mean postoperative stay was shorter in the endoscopic patients compared with our previously reported patients who underwent transcallosal resection (mean 4.1 days vs 7.7 days, respectively; p = 0.0006). The main complications were permanent short-term memory loss in 3 patients and small thalamic infarcts in 11 patients (asymptomatic in 9). CONCLUSIONS: Endoscopic resection of hypothalamic hamartoma (HH) is a safe and effective treatment for seizures. Its efficacy seems to be comparable to that of transcallosal resection of HH, but postoperative recovery time is significantly shorter.

Clinical rhabdomyolysis.

Although rhabdomyolysis is an uncommon disorder, especially in children, it can present as a severe, life-threatening event. Paediatricians need to be aware of this important, probably underdiagnosed disorder in order to implement appropriate early treatment. In this report, seven children with rhabdomyolysis of both forms, endogenous and exogenous, are presented. Despite comprehensive 'up-to-date' investigations being performed on paediatric patients with endogenous (often recurrent) rhabdomyolysis, the majority of these patients' underlying disorders will remain undiagnosed. Overall, these patients usually have a very good prognosis even if repeated, severe life-threatening episodes occur. It is recommended that a regimen of early therapy with fluids and sodium bicarbonate be instituted in all patients with rhabdomyolysis.

[Anesthesia for hepatoma resection].

Hepatocellular carcinoma is one of the leading cancers in Taiwan and is responsible for 20% of cancer deaths. Since long-term survival of hepatocellular carcinoma patients cannot be expected with any treatment other than surgery, the therapeutic value of hepatic resection has become more important than ever before. In Keelung Chang Gung Memorial Hospital, twenty-one patients with hepatoma received hepatic resection during the period of August 1985 to July 1989 were reviewed. These patients were induced for anesthesia with thiopental, succinylcholine and fentanyl; maintenance of anesthesia with isoflurane, N2O and O2. Four of them have abnormal coagulopathy preoperatively. Common intraoperative problems were metabolic acidosis and hypotension. Estimated blood loss showed great variety among these patients. Eighteen patients needed respiratory support and intensive care postoperatively. One patient was noted to have pulmonary edema. Otherwise, the overall procedure was smooth and satisfactory. In addition, there is no significantly difference in liver function test after a month of hepatoma resection. All the patients survived except one who died within two months after surgery.

Ilioinguinal nerve block with 0.375% marcaine for postoperative pain relief in cesarean section.

Bilateral ilioinguinal nerve block with local anesthetic drugs to treat postoperative pain in lower segment cesarean section (Pfannestiel incision) under general anesthesia had show profound effective by P. Bunting and I. McConachie. We used the same method but with lower concentration 0.375% marcaine 10 ml to each side in 12 patients. We compare the pain score and the requirement for pethidine intramuscular injection to 12 patients as control group. Pain score were less in the block patients within 8h after surgery, and total amount of pethidine given was 700 mg. In control group, the pain score were higher at the first 8 h than nerve block group during the study (p less than 0.05), and the total amount of pethidine requirement was 1250 mg. There were no observed adverse effect during the study.