A 90-Day Inhalation Toxicity Study with Benomyl in Rats

A 90-Day Inhalation Toxiaty Study with Benomyl in Rats. WARHEIT,D. B., KELLY, D. P., CARAKOSTAS, M. C., AND SINGER, A. W. (1989).Fundam Appl Toxicol./ 12, 333-345. Benomyl [methyl 1-(butylcarbamoyl)-2-benzimidazolecarbamate,CAS Registry No. 17804-35-2] is a fungicide and the possibilityfor inhalation exposure exists for field workers. To assessthe toxicity of benomyl, groups of 20 male and 20 female CDrats were exposed nose-only 6 hr a day, 5 days a week, to concentrationsof 0, 10, 50 or 200 mg/m³ of a benomyl atmosphere. At the midpoint(approximately 45 days on test) and at the end of the exposureperiod, blood and urine samples for clinical evaluation werecollected from 10 rats/group/sex, and these animals were sacrificedfor pathological examination. Similar evaluations were performadon all remaining rats at the end of the 90-day test period.After approximately 45 days on test, compoundrelated degenerationof the olfactory epithelium was observed in all males and in8 of 10 female rats exposed to 200 mg/m³ benomyl. Two male ratsexposed to 50 mg/m³ had similar, although less severe, areasof olfactory epithelial degeneration. After approximately 90days of exposure, the remaining 10 rats/group/sex were sacrificedand examined. Of these rats, all of the males and females exposedto 200 mg/m³ had olfactory degeneration, along with 3 malesexposed to 50 mg/m³ of benomyl. No other observed lesions wereinterpreted to have been caused by the benomyl exposure. Inaddition, male rats exposed to 200 mg/m³ benomyl had depressedmean body weights compared to controls and this finding correlatedwith a reduction in food consumption. Based on pathologicalobservations, 10 mg/m³ represents the no-observable-effect level(NOEL) for the male rats, and 50 mg/m³ is the NOEL for the femalerats.     

Decreased incidence of headache after accidental dural puncture in caesarean delivery patients receiving continuous postoperative intrathecal analgesia

To examine the effects of prolonged (> 24 h) intrathecal catheterization with the use of postoperative analgesia on the incidence of post–dural puncture headache (PDPH), charts of 45 obstetric patients who had accidental dural puncture following attempts at epidural block were reviewed retrospectively. Three groups were identified: Group I (n = 15) patients had a dural puncture on the first attempt at epidural block, but successful epidural block on a repeated attempt; Group II (n=17) patients had a dural puncture with immediate conversion to continuous spinal anaesthesia with catheterization lasting only for the duration of caesarean delivery; Group III (n= 13) patients had an immediate conversion to spinal anaesthesia and received post–caesarean section continuous intrathecal patient–controlled analgesia consisting of fentanyl 5 (ig'ml^-1 with bupivacaine 0.25 mg·ml^-1 and epinephrine 2 μg·ml^-1 with catheterization lasting >24 h. No parturient in group III developed a PDPH. This was substantially lower ( P < 0.009) than the 33% incidence for group I and the 47% incidence for group II. The incidence of a PDPH did not differ between group I and II. Similarly, there was no difference between group I and II with regard to requests for a blood patch. Patients receiving continuous intrathecal analgesia had excellent pain relief, could easily ambulate and none complained of pruritus, nausea, vomiting, sensory loss or weakness. In conclusion, indwelling spinal catheterization > 24 h with continuous intrathecal analgesia following accidental dural puncture in parturients may for some patients be a suitable method for providing PDPH prophylaxis and postoperative analgesia.     

An improved low-formaldehyde embalming fluid to preserve cadavers for anatomy teaching

The desired properties required for successful embalming of cadavers for gross anatomy teaching include: (1) good long-term structural preservation of organs and tissues with minimal shrinkage or distortion; (2) prevention of over-hardening, while maintaining flexibility and suppleness of internal organs; (3) prevention of desiccation; (4) prevention of fungal or bacterial growth and spread within a specific cadaver and to other cadavers in the dissection room; (5) reduction of potential biohazards (spread of infection to dissection personnel and students); (6) reduction of environmental chemical hazards (especially from formaldehyde and phenol) in order to comply with increasingly severe health and safety regulations and a new awareness of possible dangers of these chemicals in the workplace; and (7) retention of colour of tissues and organs while minimising oxidation effects that result in 'browning'.     

Myocardial infarction in an adult resulting from coronary ancurysms previously documented in childhood after an acute episode of Kawasaki's disease

Coronary aneurysms resulting from a previous episode of Kawasaki'sdisease are considered an important cause of myocardial infarctionin children. A case of a 19-year-old man presenting with anacute myocardial infarction associated with coronary aneurysmsis described. These coronary lesions were previously evaluatedangiographically and echocardiographically at the age of 13years, 5 months after the acute episode of a Kawasaki's disease.     

First 24 Hours of Acute Pancreatitis

Differences in metabolic Iiomeostasis in 12 patients with initial vs. eight patients with repeated attacks of acute pancreatitis have been compared during the acute phase of the disease. As a group, subjects vvitli a previous history of pancreatitis had significantly lower glucagon concfiitrations (P < 0.002) for the over all 24-hour study period. Conversely, the serum concentrations of blood sugar, insulin. growth hormone, gastrin, cortisol. nonesterified fatty acids, triglycerides and cholesterol failed to distinguish between the two patient groups. Likewise, immunoreactive plasma parathyroid hormone and calcitonin levels were comparable in both patient populations. Of the measurements considered. it would appear therefore that plasma immunoreactive glucagon is the best indicator of previous pancreatic inflanunation. Evaluation of parenchymal integrity during an episode of acute pancreatitis would he ol prognostic therapeutic value in this disease.     

Canine Exocrine Pancreatic Secretory Changes Induced by an Intragastric Ethanol Test Meal

In five dogs with chronic gastric fistulas (Thomas cannula) and a new type of chronic pancreatic fistula which permits collection of pure nonactivated pancreatic juice after ingestion of a test meal, the following series of experiments were performed: In the first series, a test meal (400 gm. canned dog meat) was given with 200 ml. saline simultaneously infused through the gastric cannula. In response to this stimulus, the 20-minute peak pancreatic flow rate and bicarbonate output were respectively 33% and 34%, of the maximal secretion of the pancreatic gland obtained with secretin in six control dogs provided with gastric and the classical Thomas duodenal fistula. The 20-minute peak protein output represented 84% of the maximal secretory capacity attained with dose-response curves to CCK in the same group of control animals.
In the second series either 1.5 or 2.0 gm./kg. ethanol were given instead of saline. Intragastric ethanol induced a dissociation of pancreatic secretion: a significant inhibition of flow rate, of bicarbonate concentration and output and a significant rise of protein concentration; protein output remaining unchanged.
It is postulated that ethanol, acting on the stomach and duodenojejunum, evokes, independently of its gastrin-releasing capacity', an unknown humoral or nervous mechanism that counteracts the ethanol-elicited cholinergic-mediated inhibition of pancreatic protein secretion which has been previously described.     

Studies on abnormal hemoglobins. III. The interrelationship of type S (sickle cell) hemoglobin and type F (alkali resistant) hemoglobin in sickle cell anemia

1. It could be demonstrated that of the three tested types of human hemoglobin—N (normal adult), S (sickle cell) and F (fetal)—only the reduced S compound shows tactoid and gel formation in sufficiently concentrated solutions.These physico-chemical phenomena may be used for the qualitative identificationof S hemoglobin.

2. The alkali resistant hemoglobin fraction, present in sickle cell anemiaerythrocytes (but not in trait red cells), was concentrated in purified form. Notactoid or gel formation could be elicited. Therefore, this alkali resistant pigment does not appear to be a variant of S hemoglobin. It seems probable thatsickle cell anemia erythrocytes contain two separate types of pathologic hemoglobin (S and F) which are not directly related to each other.

Submitted on June 21, 1951 Accepted on July 23, 1951     

Psychosexual trauma of an abnormal cervical smear

Summary. The psychosexual sequelae of diagnosis and treatment of pre-invasive cervical atypia were assessed in three groups of women. The first group included 30 women referred to a colposcopy clinic with an abnormal cervical smear indicating cervical intraepithelial neoplasia (CIN), the second comprised 50 women who were traced as sexual partners of men with penile human papillomavirus (HPV) infection; 26 of them had histologically proven cervical atypia and 24 had no such evidence. The third group included 25 women traced as partners of men with non-specific urethritis and who did not have cervical disease. Before and after questionnaires assessed six aspects of sexual behaviour and responses before diagnosis and 6 months after treatment in women with cervical atypia. These were compared with answers given by women investigated and treated, if necessary, as partners of men with sexually transmitted disease (control group). There were statistically significant adverse psychosexual sequelae associated with diagnosis and treatment of pre-invasive cervical epithelial disease.     

Tissue macrophage response in human papillomavirus infection and cervical intraepithelial neoplasia

Summary. Tissue macrophages in the uterine cervix were studied immunocytochemically with monoclonal antibody (MoAb) 3.9 which reacts with the majority of macrophages, and Ell which is specific for the C3b receptor, CR1. Samples from five normal women, six with human papillomavirus (HPV) infection and 10 with cervical intraepithelial neoplasia (CIN) were tested. A small population of MoAb 3.9 positive and only occasional MoAb Ell positive macrophages were found in the normal cervix. In HPV infection and CIN there was a significant infiltration of MoAb 3.9 positive and MoAb Ell positive macrophages in both the epithelium and the stroma. The pattern of infiltration in these groups of women suggests that these macrophages were most likely to be functioning as the first line of defence against the spread of the virus infection, either through a direct anti-virus mechanism or non-specific phagocytosis.