Paternal occupational lead exposure and congenital malformations.

STUDY OBJECTIVE--The aim was to investigate whether occupational exposure to lead in fathers is associated with congenital malformation in their children. DESIGN--The study was a retrospective case-control study, nested within the wives of men biologically monitored for inorganic lead. Information on pregnancy outcome was obtained from medical registers. SUBJECTS--Cases were defined as wives with malformed child during 1973-82. Three age matched controls were selected for each case from the wives who had given birth during 1973-1983. The final study population was 27 cases and 57 controls. MEASUREMENTS AND MAIN RESULTS--Paternal lead exposure was assessed with blood lead measurements and data obtained from a questionnaire. The response rate was 67% among the cases and 76% among the controls. The odds ratio (OR) of congenital malformation for paternal lead exposure was increased (OR 2.4, 95% confidence interval 0.9-6.5), although not reaching statistical significance. The odds ratios varied from 1.9 to 3.2, when adjusted for one potential confounding variable at a time. CONCLUSIONS--Because of the small numbers and low participation, this study offers limited support for the hypothesis that paternal lead exposure is associated with congenital malformation. Further epidemiological studies on the reproductive hazards of paternal lead exposure are needed.     

Bromine-76 and carbon-11 labelled NNC 13-8199, metabolically stable benzodiazepine receptor agonists as radioligands for positron emission tomography (PET)

NNC 13-8241 has recently been labelled with iodine-123 and developed as a metabolically stable benzodiazepine receptor ligand for single-photon emission computed tomography (SPECT) in monkeys and man. NNC 13-8199 is a bromo-analogue of NNC 13-8241. This partial agonist binds selectively and with subnanomolar affinity to the benzodiazepine receptors. We prepared ⁷⁶Br labelled NNC 13-8199 from the trimethyltin precursor by the chloramine-T method. Carbon-11 labelled NNC 13-8199 was synthesised by N-alkylation of the nitrogen of the amide group with [¹¹C]methyl iodide. Positron emission tomography (PET) examination with the two radioligands in monkeys demonstrated a high uptake of radioactivity in the occipital, temporal and frontal cortex. In the study with [⁷⁶Br]NNC 13-8199, the monkey brain uptake continued to increase until the time of displacement with flumazenil at 215 min after injection. For both radioligands the radioactivity in the cortical brain regions was markedly reduced after displacement with flumazenil. More than 98% of the radioactivity in monkey plasma represented unchanged radioligand 40 min after injection. The low degree of metabolism indicates that NNC 13-8199 is metabolically much more stable than hitherto developed PET radioligands for imaging of benzodiazepine receptors in the primate brain. [⁷⁶Br]NNC 13-8199 has potential as a radioligand in human PET studies using models where a slow metabolism is an advantage. Received 19 April and in revised form 10 June 1997     

Iron absorption from bread in humans: inhibiting effects of cereal fiber, phytate and inositol phosphates with different numbers of phosphate groups.

Iron absorption was measured from five kinds of bread made from various types of flour and fermented in different ways in order to obtain a wide variation in the content of fiber, phytate (inositol hexaphosphate) and its degradation products, inorganic phosphate and inositol phosphates with fewer numbers of phosphate groups (inositol pentaphosphate through monophosphate). Each experiment had 9-10 subjects and, in each subject, iron absorption was measured from control rolls made from low extraction wheat flour and one kind of test roll using two different radioiron tracers: 55Fe and 59Fe. The inhibition of iron absorption was closely related to the content of phytate-phosphorous as determined using the AOAC method, and to the sum of the tri- through hexaphosphate groups as determined using the HPLC method. As an example, prolonged fermentation of whole-rye bread reduced total inositol phosphates to the same amount as in the control rolls and increased fractional iron absorption to the same high level, in spite of a fiber content five times as great. The results strongly suggest that the inhibitory effect of bran on iron absorption is due to its content of phytate and other inositol phosphates present after fermentation, rather than to its content of fiber or other constituents. Thus, effective fermentation will increase the bioavailability of iron in whole-meal bread.     

Digitalis poisoning from medicinal herbs. Two different mechanisms of production]

Two cases of digitalis toxicity due to uncontrolled ingestion of medicinal herbs are presented. The first of them was caused by oleander (Nerium oleander); digoxinemia levels were very high in this patient (4.44 ng/l), who presented many brady- and tachyarrhythmias. These arrhythmias disappeared when digoxinemia returned to normal values. The second patient had atrial fibrillation with slow ventricular rate, severe hypokalemia (2.1 mEq/l) and normal digoxinemia levels. He was taking medicinal herbs for a cold, with sorbitol between its components. Sorbitol may be similar to mannitol and glycerol (osmotic diuretic drugs) when taken at high doses. Uncontrolled ingestion of medicinal herbs is not safe, and severe poisoning can occur.     

Is there a role for laparoscopic appendectomy in pediatric surgery?

Although laparoscopic procedures are currently in vogue in general surgery, the role of this approach in children has not been prospectively evaluated in the United States using the new instrumentation now available to us. To assess the value of laparoscopic appendectomy (LA) in childhood, we prospectively compared 14 LAs with 50 open appendectomies (OA) over 6 months in a single children's hospital. Antibiotic usage was at the discretion of the surgeon regardless of the procedure performed and was not different between groups. LA was performed under the direction of a single laparoscopy-trained surgeon and patient selection was based on parental consent. A three-puncture LA technique was used; children from this group were allowed to return to full activities as soon as they were comfortable. There were no significant differences between groups for severity of disease, age, weight, hospital cost, or complications. The types of complications that developed were comparable in both groups. The percent of complicated appendicitis (gangrene or perforation) was 32% in the OA group and 36% in the LA group. Patients in the LA group spent significantly fewer days in the hospital and returned to unrestricted activities (school, athletics, etc) faster than patients in the OA group. LA is approximately $1,000 more expensive than OA, the differences being easily explainable by the cost of the disposable supplies necessary for the procedure (laser fibers, trocars, etc), but because of the shorter hospital stay in the LA group the mean total cost for each group was comparable. These data suggest that although there appears to be no cost advantage, LA shortens the hospital stay and allows children to return to unrestricted activity sooner than OA.(ABSTRACT TRUNCATED AT 250 WORDS)     

Acute psychotropic effects of bilateral subthalamic nucleus stimulation and levodopa in Parkinson's disease.

High-frequency deep brain stimulation (DBS) of the subthalamic nucleus (STN) improves the motor symptoms of Parkinson's disease (PD). Opposite changes in mood, such as mania or depression, have been reported after surgery, but it is not known whether these side effects are specifically related to STN DBS. To learn whether STN DBS also influences the limbic loop, we investigated acute subjective psychotropic effects related to levodopa or bilateral STN DBS. After a median postoperative follow-up of 12 months, 50 PD patients completed the Addiction Research Center Inventory (ARCI), assessing subjective psychotropic effects in four conditions: off-drug/on-stimulation; off-drug/off-stimulation; on-drug/off-stimulation; and on-drug/on-stimulation. Both levodopa and STN DBS improved all the ARCI subscales, indicating subjective feelings of well being, euphoria, increase in motivation, and decrease in fatigue, anxiety, and tension. A suprathreshold dose of levodopa was significantly more effective than STN DBS, using the same electrical parameters as for chronic stimulation, on four of the five ARCI subscales. We concluded that 1) both STN DBS and levodopa have synergistic acute beneficial psychotropic effects in PD, 2) the psychotropic effects of both treatments need to be considered in the long-term management of chronic STN DBS, and 3) the results indicate an involvement of the limbic STN in mood disorders of PD.     

Remifentanil-induced Postoperative Hyperalgesia and Its Prevention with Small-dose Ketamine

Background: Remifentanil-induced secondary hyperalgesia has been documented experimentally in both animals and healthy human volunteers, but never clinically. This study tested the hypotheses that increased pain sensitivity assessed by periincisional allodynia and hyperalgesia can occur after relatively large-dose intraoperative remifentanil and that small-dose ketamine prevents this hyperalgesia.

Methods: Seventy-five patients undergoing major abdominal surgery were randomly assigned to receive (1) intraoperative remifentanil at 0.05 [mu]g [middle dot]kg-1 [middle dot]min-1 (small-dose remifentanil); (2) intraoperative remifentanil at 0.40 [mu]g [middle dot]kg-1 [middle dot]min-1 (large-dose remifentanil); or (3) intraoperative remifentanil at 0.40 [mu]g [middle dot]kg-1 [middle dot]min-1 and 0.5 mg/kg ketamine just after the induction, followed by an intraoperative infusion of 5 [mu]g [middle dot] kg-1 [middle dot] min-1 until skin closure and then 2 [mu]g [middle dot]kg-1 [middle dot]min-1 for 48 h (large-dose remifentanil-ketamine). Pain scores and morphine consumption were recorded for 48 postoperative hours. Quantitative sensory tests, peak expiratory flow measures, and cognitive tests were performed at 24 and 48 h.

Results: Hyperalgesia to von Frey hair stimulation adjacent to the surgical wound and morphine requirements were larger (P < 0.05) and allodynia to von Frey hair stimulation was greater (P < 0.01) in the large-dose remifentanil group compared with the other two groups, which were comparable. There were no significant differences in pain, pressure pain detection threshold with an algometer, peak flow, cognitive tests, or side effects.