Identification of the New Isotope

In an experiment performed at Lawrence Berkeley National Laboratory's 88-inch cyclotron, the isotope ^{244}Md was produced in the ^{209}Bi(^{40}Ar,5n) reaction. Decay properties of ^{244}Md were measured at the focal plane of the Berkeley Gas-filled Separator, and the mass number assignment of A=244 was confirmed with the apparatus for the identification of nuclide A. The isotope ^{244}Md is reported to have one, possibly two, α-decaying states with α energies of 8.66(2) and 8.31(2) MeV and half-lives of 0.4_{-0.1}^{+0.4} and ∼6 s, respectively. Additionally, first evidence of the α decay of ^{236}Bk was observed and is reported.

Regulation of neuronal plasticity and fear by a dynamic change in PAR1-G protein coupling in the amygdala.

Fear memories are acquired through neuronal plasticity, an orchestrated sequence of events regulated at circuit and cellular levels. The conventional model of fear acquisition assumes unimodal (for example, excitatory or inhibitory) roles of modulatory receptors in controlling neuronal activity and learning. Contrary to this view, we show that protease-activated receptor-1 (PAR1) promotes contrasting neuronal responses depending on the emotional status of an animal by a dynamic shift between distinct G protein-coupling partners. In the basolateral amygdala of fear-naive mice PAR1 couples to Gαq/11 and Gαo proteins, while after fear conditioning coupling to Gαo increases. Concurrently, stimulation of PAR1 before conditioning enhanced, but afterwards it inhibited firing of basal amygdala neurons. An initial impairment of the long-term potentiation (LTP) in PAR1-deficient mice was transformed into an increase in LTP and enhancement of fear after conditioning. These effects correlated with more frequent 2-amino-3-(5-methyl-3-oxo-1,2-oxazol-4-yl)propanoic acid (AMPA) receptor-mediated miniature post synaptic events and increased neuronal excitability. Our findings point to experience-specific shifts in PAR1-G protein coupling in the amygdala as a novel mechanism regulating neuronal excitability and fear.

Restless legs syndrome in sensory axonal neuropathy: A case-control study.

INTRODUCTION: The relation between neuropathy and restless legs syndrome (RLS) remains uncertain. Previous studies have analyzed heterogeneous neuropathic populations and findings have been to date inconsistent. MATERIALS AND METHODS: We studied a neuropathic population consisting of 59 patients with acquired, mixed, small and large fiber sensory axonal neuropathy. We compared our findings to those of 59 neurological controls with a similar age/gender distribution. International RLS Study Group criteria were used and severity assessed by International Restless Legs Syndrome Severity Scores (IRLSSS), by a single blinded telephone interviewer. Mimics were excluded as well as cases with infrequent (<5 days/month) symptoms. RESULTS: RLS was significantly more frequent in patients with neuropathy than in controls (28.8% versus 8.5%; P=0.008). Patients with neuropathy and RLS were significantly older (P=0.001), had later onset RLS (P=0.001), had more frequent RLS symptoms (P=0.009) and greater IRLSSS (P=0.019), than controls with RLS. There was no relation between presence of RLS in patients with sensory neuropathy and lower limb sensory electrophysiological findings. CONCLUSIONS: Our results suggest that acquired sensory axonal neuropathy may be associated with RLS. Further larger studies of homogeneous neuropathic populations are required in view of the potential therapeutic benefit specifically for RLS symptoms in patients with neuropathy.

Preemptive use of small dose fentanyl suppresses fentanyl induced cough.

BACKGROUND: Fentanyl, a synthetic opioid, is a popular choice amongst anaesthesiologists in the operating room. Pre induction intravenous fentanyl bolus is associated with coughing in 28-65% of patients. Fentanyl induced cough is not always benign and can be remarkably troublesome at the most critical moment of anaesthesia when airway reflex is lost. OBJECTIVES: To study the effect of pre emptive use of minimal dose fentanyl through the peripheral venous cannulae on the incidence of cough by a larger bolus of intravenous fentanyl. METHODS: One hundred and fifty patients aged 18-75 years undergoing elective surgical procedures were randomized into three groups of 50 each. The first group received 0.5 ml saline 0.9% intravenously one minute prior to the administration of fentanyl 150 µg (3 ml); the second group received pre emptive fentanyl 25 µg (0.5 ml) prior to the administration of fentanyl 125 µg (2.5 ml); and the third group received preemptive fentanyl 25 µg (0.5 ml), followed by the administration of fentanyl 150 µg (3 ml). Based on the number of coughs observed, cough severity was graded as mild (1-2), moderate (3-5), or severe (>5). RESULTS: The incidence of fentanyl induced cough was significantly lower in both pre emptive group 4 (8%) for 125 µg fentanyl and 7 (14%) for 150 µg than in the saline group 15 (30%). CONCLUSION: Pre-emptive use of minimal dose fentanyl 25 µg administered one minute before a larger bolus dose of fentanyl (125 or 150 µg) can effectively suppress cough.

Comparison of ketamine, fentanyl and clonidine as an adjuvant during bupivacaine caudal anaesthesia in paediatric patients.

BACKGROUND: Caudal epidural analgesia with bupivacaine is very popular in paediatric anaesthesia for providing intra- and postoperative analgesia. Several adjuvants have been used to prolong the action of bupivacaine. OBJECTIVES: To compare the efficacy of ketamine, fentanyl and clonidine in terms of quality and duration of analgesia they produce when added with caudal bupivacaine by single shot technique in children. METHODS: Eighty children, age one to ten years, undergoing sub-umbilical surgery, were prospectively randomized to one of four groups: caudal analgesia with 0.75 ml/ kg of 0.25% bupivacaine in normal saline (Group B) or caudal analgesia with 0.75 ml/kg of 0.25% bupivacaine with 1 µg/kg of clonidine in normal saline (Group BC) or caudal analgesia with 0.75 ml/kg of 0.25% bupivacaine with ketamine 0.5mg/kg (Group BK) or caudal analgesia with 0.75 ml/kg of 0.25% bupivacaine with fentanyl 1 mcg/kg (Group BF). Post-operative pain was assessed for 24 hours using the FLACC scale. RESULTS: The mean duration of analgesia was significantly longer in Group BC (629.06 ± 286.32 min) than other three groups P < 0.05. The pain score assessed using FLACC scale was compared between the four groups, and children in Group BC had lower pain scores, which was statistically significant. The requirement of rescue medicine was lesser in Group BC. Clonidine in a dose of 1 µg/kg added to 0.25% bupivacaine for caudal analgesia, during sub-umbilical surgeries, prolongs the duration of analgesia of bupivacaine, without any side effects in compare to fentanyl or ketamine. CONCLUSION: We conclude that clonidine in a dose of 1 µg/kg, added to 0.25% bupivacaine for caudal analgesia and administered as a 0.75 ml/kg mixture in children, for subumbilical surgery, significantly prolongs the duration of post-operative analgesia when compared to 0.75 ml/kg of 0.25% bupivacaine in normal saline than 0.75 ml/kg of 0.25% bupivacaine with ketamine 0.5 mg/kg or 0.75 ml/kg of 0.25% bupivacaine with fentanyl 1 mcg/kg or 0.75 ml/kg of 0.25% bupivacaine alone, without any side effects.

Breakage of fascial closure device during laparoscopic surgery.

Breakage of instruments during laparoscopic surgery is rare. However, when it does occur, locating and retrieving the broken part of the instrument can be cumbersome. Moreover, inability to do so may carry serious medicolegal implications. We report a patient in whom the tip of a fascial closure device broke during laparoscopic surgery. This was located by intraoperative fluoroscopy and retrieved from the extraperitoneal plane via a small incision. The paper discusses the probable factors responsible for breakage of the fascial closure device in our patient and reviews the previously reported cases of the rare complication of breakage of instruments during laparoscopic surgery.

Guanabenz effects on blood pressure and noninvasive parameters of cardiac performance in patients with hypertension.

Guanabenz (2,6 dichlorobenzylidene amino guanidine acetate) is a new antihypertensive whose mechanism of action appears to involve both central alpha adrenergic stimulation leading to suppression of sympathetic nervous system activity from bulbar vasoconstriction centers as well as peripheral adrenergic neuron blockade. In this study, the drug was shown to produce a statistically and clinically significant decrease in blood pressure during a 4-wk placebo-controlled double-blind study. For three additional months continued efficacy and safety were shown under open conditions in 17 hypertensive patients. Mild sedation occurred, but there were no postural hypotension, tachycardia, evidence of sodium retention, gastrointestinal disturbances, or electrocardiographic (ECB) abnormalities. Noninvasive parameters of cardiac performance in 10 patients after single doses of guanabenz showed no significant changes. Although the numbers of patients were relatively small, the data suggest that this new drug may be a useful antihypertensive agent that warrants further investigation.

Guanabenz and methyldopa on hypertension and cardiac performance.

In previous placebo-controlled studies, guanabenz was shown to be a safe and effective antihypertensive drug without acute effects on cardiac function. In view of its therapeutic advantages, a double-blind comparison of guanabenz with methyldopa was performed in a group of 36 patients over 6 mo. Both drugs produced statistically and clinically significant decreases in blood pressure with similar side effects. No laboratory or electrocardiographic abnormalities were found other than positive Coombs' tests which developed in 3 patients during methyldopa therapy. Cardiac performance in 26 of the patients, as measured by noninvasive techniques, showed no significant changes from either drug except for a progressive and statistically significant increase in systolic time interval (QS2) and the ratio of the pre-ejection period to left ventricular ejection time (PEP/LVET) during methyldopa therapy. For an additional 6 mo, continued efficacy and safety were shown under open conditions in those patients who had received guanabenz. The study suggests that guanabenz may be an important new antihypertensive drug because of effectiveness, absence of adverse cardiac effects, and paucity of side effects.

Vitamin A status of the newborn in relation to gestational age, body weight, and maternal nutritional status.

Studies were made of the vitamin A status of newborn as judged by cord serum vitamin A in relation to gestational age, birth weight, and maternal vitamin A status in 130 + 79 mother-infant pairs belonging to low and high income groups in urban Baroda. The mean values for maternal serum vitamin A (microgram/dl, mean +/- SE) in the two groups were 21.8 +/- 0.59 (n = 130) and 29.3 +/- 0.80 (n = 79), respectively. The corresponding values for cord serum vitamin A were 13.8 +/- 0.40 and 19.6 +/- 0.64 for full-term infants and 7.5 +/- 0.44 and 12.9 +/- 0.80 for premature infants. Even for comparable levels of maternal serum vitamin A, differences were found between income groups regarding birth weight and cord serum vitamin A. Mothers of premature infants had lower levels of serum vitamin A than those of full-term infants suggesting maternal vitamin A status to be one of the correlates of prematurity. Significant correlations were found between cord serum vitamin A, maternal serum vitamin A, gestational age, and growth status. These studies suggest that a poor vitamin A status is one of the features associated with a higher prevalence of prematurity and intrauterine growth retardation found in poorly nourished populations. These findings stress the importance of satisfactory vitamin A supplies to pregnant and nursing mothers to prevent vitamin A deficiency and growth retardation in the progeny.

Respiratory failure in pulmonary tuberculosis.

Of 852 patients admitted to Cook County Hospital with bacteriologically-proved pulmonary tuberculosis, 16 suffered respiratory failure. Of these 16, 5 died and 11 recovered. On follow-up, the survivors demonstrated significant improvement in oxygenation, but continued to show a severe restrictive ventilatory defect. Our patients, unlike those in previous reports, did not show airway obstruction. The principles of management are the same as for other pulmonary patients. Arterial blood gas analyses should be done on patients with advanced tuberculosis so that abnormalities of gas exchange will not be missed.

Bronchiectasis following heroin-induced pulmonary edema. Rapid clearing of pulmonary infiltrates.

We observed a patient who developed diffuse bronchiectasis subsequent to heroin-induced pulmonary edema. Unlike the previously reported cases, there was rapid clearing of pulmonary infiltrates and little evidence of severe aspiration. The development of bronchiectasis was attributed to a bronchial infection subsequent to clearing of the pulmonary edema. Physiologic dysfunction was characterized by marked obstruction, pulmonary hypertension, and mild hypoxemia.

Hospitalizations for severe complications of pregnancy, 1987-1992.

OBJECTIVE: To compute ratios of severe pregnancy complications (the number of hospitalizations for pregnancy complications per 100 deliveries) and to examine factors associated with their prevalence. METHODS: Using population-based California hospital discharge data to estimate hospitalization ratios of pregnancy complications during 1987-1992, we defined cases by preselected pregnancy complication codes from the International Classification of Diseases, Ninth Revision, Clinical Modification, excluding induced abortions and delivery-associated complications. All hospital deliveries of liveborn or stillborn infants were included in our denominator. We examined ratios by age, race-ethnicity, payment source, total hospitalization charges, and length of hospital stay. RESULTS: There were 833,264 hospitalizations for pregnancy complications in California (25 complications per 100 deliveries), which included admissions for preterm labor (33%), genitourinary infection (16%), and pregnancy-induced hypertension (15%). Age-specific ratios were highest for women 14 years old and younger (38 per 100 deliveries) and lowest for women 25-29 years old (23 per 100 deliveries). Ratios of complications varied by race-ethnicity; black women had the highest (42 per 100 deliveries), and Asian-Pacific Islander women had the lowest (21 per 100 deliveries). Ratios were unaffected by payment source. In 1987, Medicaid charges were $118 million for 33% of the number of total hospitalizations for complications. In 1992, such Medicaid hospitalizations accounted for $356 million (49%) of the $734 million in total charges and for 183,295 (45%) of the 409,000 total hospital days. CONCLUSION: Our results showed disparities in ratios of severe complications of pregnancy by age and race-ethnicity as well as a shift of financial burden to Medicaid. These findings suggest that such complications may be reduced by identifying risk factors and targeting high-risk groups.

Acute effect of substance P in immunologic vasculitis in the rat colon.

Substance P has been implicated as a neuronal mediator of inflammation in various inflammatory conditions. However, the exact role played by substance P in inflammatory bowel diseases or in experimental colonic vasculitis has not been clearly understood. In this study, we examined the effect of close superior mesenteric artery injection of substance P under prevailing inflammatory conditions induced by intravenous human albumin antialbumin immune complex followed by intracolonic perfusion of 2.5% formaldehyde in rats or intracolonic perfusion of 5% alcohol alone. The immune complex- and formaldehyde-treated rats showed severe microvascular changes such as microvascular plugging by red blood cells, endothelial breakage and extravasation of plasma proteins and red blood cells. The bolus injection of 10(-8) M substance P reduced extravasation of Evans blue dye by 50% and the tissue wet to dry ratio by 20% in immune complex- and formaldehyde-perfused rats. Myeloperoxidase activity was not changed. Substance P also significantly inhibited (44%) the extravasation in alcohol-perfused rats. Pretreatment of immune complex- and formaldehyde-treated rats with substance P antagonist reversed the effect of substance P. These findings suggest that the most immediate effect of substance P may be vasodilation and clearing of vascular plugs induced by immune complex and formaldehyde. This effect of substance P differs from its chronic effect, which causes vasodilation and extravasation.

Serum progesterone and norethisterone levels following injection of norethisterone enanthate in different sites and doses.

Serum progesterone (P) and norethisterone (NET) levels following injection of norethisterone enanthate (NETEN) were studied in 11 regularly menstruating women. In 6 subjects 200 mg NETEN was administered to the gluteal (IG) or deltoid (ID) region sequentially. The serum P levels remained anovulatory (less than 4 ng/mL) up to 12 weeks. Serum NET levels were similar whether injection was given IG or ID (paired t - test, NS). In 5 subjects given a 150-mg dose, serum P levels remained anovulatory up to 11 weeks. Serum NET levels declined faster than with the 200-mg dose, but the difference was not significant (Student's t - test, NS). Wide inter-subject variations were seen in both groups. NETEN therefore can effectively be administered in gluteal or deltoid regions. A lower dose of 150 mg may have contraceptive potential on an 8-week schedule.

Reproductive endocrine effects of intranasal administration of norethisterone (NET) to women.

Four consecutive menstrual cycles were studied in six healthy parous women. A solvent mixture comprising propylene glycol:ethanol:water (3:3:4) was sprayed intranasally daily using a glass atomizer between days 5 and 24 of the first (control) menstrual cycle. NET was dissolved in the solvent and similarly administered at a daily dose of 100 mcg during the second and third menstrual cycles. Nasal sprays were not administered during the fourth post-treatment cycle. Blood samples were taken during four consecutive cycles between days 8 and 15 and again between days 20 and 24 of the cycle to estimate levels of estradiol (E2), FSH, LH and progesterone (P). These studies revealed that nasal sprays of NET were well accepted and that no adverse clinical effects or menstrual disturbances occurred. NET inhibited ovulation in one cycle. The E2-induced mid-cycle rise in FSH and LH was either suppressed or inhibited in nine out of the 12 treated cycles. P levels in three treated cycles were indicative of luteal inadequacy. These endocrine effects of NET persisted into the post-treatment cycle in two cases.

Effects of intranasal administration of norethisterone on folliculogenesis, cervical mucus, vaginal cytology, endometrial morphology and reproductive-endocrine profile in women.

The effects of intranasal administration of norethisterone (NET) on menstrual cycle length, folliculogenesis, serum levels of estradiol, FSH, LH and progesterone, vaginal cytology, cervical mucus and endometrial morphology were studied in 8 volunteers (age 28 to 39 years, weighing between 46 and 54 kg). The study period comprised 4 consecutive menstrual cycles. In the first cycle (pretreatment cycle), only the vehicle (alcohol, propylene glycol, water; 3:3:4) was sprayed intranasally (100 microliters in each nostril), using a metered nebulizer, once daily from day 3 to the last day of menstrual cycle. In the next two cycles (treatment cycles), NET (300 micrograms/day) was administered once daily, starting from day one of menstrual cycle, between 9 and 10 a.m. The fourth cycle was a post-treatment cycle in which the volunteers were monitored for recovery. Blood samples (about 5 ml each) were collected once daily from day 8 to 24 and thereafter on alternate days until the last day of cycle during all the 4 cycles. Levels of estradiol, FSH, LH and progesterone were measured in the serum samples by radioimmunoassay methods. Cervical mucus samples and vaginal smears were collected once daily starting from day 7 or 8 of each cycle until the mucus was very scanty. Serial pelvic ultrasonography was performed starting from day 7 or 8 until the growing follicle disappeared or throughout the cycle in case a growing follicular cyst was observed. Endometrial aspirates were collected once around day 22 in each cycle and processed for routine histological examination.

Intrahepatic subcapsular hematoma complicating laparoscopic cholecystectomy.

A 64-year-old woman underwent endoscopic retrograde cholangiopancreatography for bile duct stones, followed 2 days later by an uneventful laparoscopic cholecystectomy. She presented after 10 days with upper abdominal discomfort, nausea, and pyrexia. Investigations revealed a decrease in hemoglobin, and computed tomography identified a large intrahepatic subcapsular hematoma in segments V and VI. There was no intraabdominal collection and the rest of the viscera were normal. The collection was drained percutaneously under ultrasound guidance and a wide-bore catheter placed. She was treated with intravenous antibiotics and the catheter was removed 14 days later upon cessation of drainage. Serial ultrasonographic examinations showed a reduction in the size of the hematoma and complete resolution at 4 months. She remained well and asymptomatic at follow-up 16 months later. We report this case due to its rarity and review the previously documented cases of this complication.

The role of laparoscopy in the management of common bile duct obstruction in children.

BACKGROUND: Laparoscopic common bile duct exploration is commonplace in adults; however, this procedure is not often performed in children. The goal of this study was to evaluate the results of laparoscopic common bile duct exploration in children. METHODS: Of 50 patients undergoing laparoscopic cholecystectomy, six patients (12%) had obstructing lesions of the common bile duct (CBD). Five children underwent laparoscopic common bile duct exploration, and one child had a preoperative endoscopic sphincterotomy and stone removal. RESULTS: The mean age at laparoscopic CBD exploration was 11.6 years (range, 5-16). The obstructing lesion was visualized by intraoperative cholangiography in all five patients. The mean operative time for laparoscopic cholecystectomy along with CBD exploration was 215 min (range, 160-282). The transcystic laparoscopic CBD exploration was performed using a 7-Fr, multichannel rigid, or 10-Fr flexible fiberoptic cystoscope. The stones were either pushed into the duodenum with the scope or extracted through the cystic duct using a 3-Fr Segura basket. In one patient, a candidial ball disintegrated during an attempt to remove it with the basket. A repeat cholangiogram at the end of each procedure showed an anatomically normal CBD with free flow of contrast into the duodenum. All patients enjoyed a quick recovery. They were started on a regular diet on the same day of surgery and discharged on the 1st or 2nd postoperative day. One patient with sickle cell disease developed a pulmonary infarction and required 5 additional days of hospitalization. One patient developed recurrent choledocholithiasis 6 months after laparoscopic exploration and was treated successfully with endoscopic sphincterotomy and stone extraction. CONCLUSIONS: Laparoscopic CBD exploration can be performed safely at the time of the cholecystectomy in children. Endoscopic sphincterotomy before cholecystectomy is not necessary. We recommend laparoscopic CBD exploration for obstructing lesions of the CBD. Endoscopic sphincterotomy should be reserved for recurrent lesions of the CBD after laparoscopic cholecystectomy.

Laparoscopically guided transperitoneal percutaneous nephrolithotomy for calculi in pelvic ectopic kidneys.

Although percutaneous nephrolithotomy is a well-established endourological modality for the management of calculi in the normally placed kidney, it is not easy to apply in the management of calculi in pelvic ectopic kidneys. We report the cases of three patients who were found to have large calculi in pelvic ectopic kidneys and subsequently underwent laparoscopically guided transperitoneal percutaneous nephrolithotomy, all with successful outcome. In all patients, complete stone clearance was achieved in a single operation with no intraoperative or postoperative morbidity. They remain asymptomatic and recurrence-free at a follow-up ranging from 2 to 38 months. Laparoscopic guidance allows the transperitoneal route to be used safely for percutaneous nephrolithotomy in patients with calculi in pelvic ectopic kidneys. We believe it to be a feasible, safe, and valid minimally invasive management option for this uncommon but challenging urological condition.