Phytotoxins from the pathogenic fungi Drechslera maydis and Drechslera sorghicola

Drechslera maydis, the causal agent of Southern corn leaf blight, and Drechslera sorghicola, the causal agent of leaf spot on Johnson grass, produce a series of phytotoxic sesterterpenoids. These sesterterpenoids belong to the ophiobolin family. One of them, ophiobolin I, was characterized by x-ray diffraction and served as a crucial reference compound for characterizing four other ophiobolins. All of the ophiobolins studied produce characteristic lesions on host plants at concentrations of 1 mM to 1 μM. The ophiobolin characterized as 6-epiophiobolin A is selectively toxic to corn bearing Texas-male-sterile (Tms) cytoplasm when assayed in a dark CO₂ fixation assay. It is plausible that these ophiobolins had a role in the 1970 corn-blight epidemic in North America.     

A double-blind study on the effect of discontinuation of gold therapy in patients with rheumatoid arthritis

Summary To assess the benefit of further gold treatment of rheumatoid arthritis (RA) patients who had already received more than 6 g of this metal, 24 such patients were included in a double-blind trial. Besides this gold group comprising 11 patients who received gold (Auromyose^®) in the same dosage schedule as before the study, the trial included a placebo group comprising 13 patients who received gold in a suspension diluted 1/100. In either group clinical, laboratory, and radiological data did not differ after 6 and 24 months in relation to the results at entry except for the serum gold concentrations, which were lower in the placebo group. We conclude that discontinuation of the treatment in RA patients who have received more than 6 g gold is not harmful to the patients for at least two years after withdrawal.     

Man-in-the-barrel syndrome

In a prospective study of 34 comatose patients who had an episode of systemic hypotension, 11 had the "man-in-the-barrel" syndrome (MIB). They moved both legs spontaneously or in response to pain, but did not move either arm. One of 11 patients (9%) with MIB survived to leave the hospital; 8 of the 23 patients (35%) without MIB recovered. Of patients who moved at least one limb to pain and had intact pupillary, corneal, and oculocephalic reflexes 24 hours after insult, one of nine (11%) patients with MIB survived, compared with six of nine patients (67%) without MIB. MIB is common after cerebral hypoperfusion and carries a poor prognosis.     

The definition of posttraumatic stress disorder in alcoholic Vietnam veterans. Are the DSM-III criteria necessary and sufficient?

The authors evaluated the validities of the DSM-III elements defining posttraumatic stress disorder (PTSD) in alcoholic Vietnam veterans by studying the relationships of each to qualification for a PTSD diagnosis under DSM-III standards, the history of a major stressor (3 or more months of combat), and the presence/absence of enough other problems to meet the symptomatic DSM-III requirements for this diagnosis. Elements dealing with the reexperiencing of traumas, diminished pleasure, detachment from others, hyperalertness, sleep disturbance, guilt over behaviors required for survival, and avoidance of stimuli reminiscent of traumas showed substantial correlations with eligibility for a PTSD diagnosis. However, items dealing with emotional expressiveness, response to intimacy, survival guilt, impaired memory, and trouble concentrating either failed to correlate with qualification for a PTSD diagnosis or yielded marginal results. One ("lacking direction") of 10 additional symptoms sometimes termed as "post-Vietnam syndrome" behaviors correlated with eligibility for a PTSD diagnosis as well. The present results and those described in earlier studies suggest that several modifications in the DSM-III definition of PTSD are desirable.     

A pharmacokinetic approach to the establishment of biopharmaceutic characteristics of different acetylsalicylic acid formulations in man

Eleven acetylsalicylic acid (ASA) formulations were administered to 26 healthy volunteers in a cross-over design. The properties of the preparations differed from conventional, effervescent, buffered to buccal. The objectives of this study were:

• 1 Consideration of the general aspects of a biopharmaceutical study: which parameter for which biopharmaceutic characteristic?
• 2 Measurement of the kinetic parameters of ASA: first-pass effect, mean residence time, mean appearance time, total body clearance, apparent volume of distribution, half-lives, etc.
• 3 Comparison of the formulations.

Most of the formulations yield mean residence times for ASA of 0.3–1.0h, which do not differ significantly (p > 0.05). For most of the products the first-pass effect is about 40 per cent; the average values of the apparent volume of distribution and whole body clearance, corrected for the first-pass effect, are about 201 and 650 ml min^?1, respectively. Peak levels are reached slowly for the buccal formulations, and rapidly for the buffered products. It is difficult, especially for ASA, to characterize the gastro-intestinal absorption with pharmacokinetic model parameters, because the first-pass effect is large and often elimination of ASA is faster than absorption. The model-independent approach has the special advantages of calculating reliable pharmacokinetic parameters, and creating theoretical possibilities to characterize the absorption patterns of the different formulations in a quantitative way. No significant differences in the values of the parameters are found between most of the formulations. The ASA first-pass effect is reasonably constant and buccal application has no advantage. Enteric coating of the outer layer of ASA formulations causes inconsistent absorption and may be categorized under ‘artificial mistakes’.     

Ab initio and PCILO investigations of local anaesthetic-model membrane interactions

A "double zeta" basis set ab initio method was used for investigation of the systems (trimethylamine-dimethylphosphate monoanion)H+, aniline-dimethylphosphate monoanion and formanilide-dimethylphosphate monoanion, which represent the models for associative sites of both local anaesthetics and the phospholipid part of the nerve membrane. According to the authors' calculations, complex I was found to be the most stable with a N+-H...O-hydrogen bond. Further, the PCILO method was used for investigation of the interactions of the polar groups of 1-[2-(2-methoxyphenylcarbamoyloxy)ethyl] piperidine (B) and its cation (BH) with N-methylacetamide, which represents a model of association sites of the lipoprotein part of membrane. The strongest hydrogen bond with the carbonyl group of N-methylacetamide forms a N+-H group of cationic form.     

Quantitation of carcinogen-induced DNA damage and repair in human cells with the UVR ABC excision nuclease from Escherichia coli

Recent studies by others have shown that the endonuclease complexcoded for by the uvrA, uvrB and uvrC genes of Escherichia coli(UVR ABC excision nuclease) can incise DNA containing a varietyof ‘bulky-type’ lesions, such as those resultingfrom u.v. light, (±)-7, 8ß-dihydroxy-9, 10-epoxy-7,8, 9, 10-tetrahydrobenzo[a]pyrene (anti-BPDE), and N-acetoxy-2-acetylaminofluorene.Using partially purified UVR ABC excision nuclease, we havequantitated the number of endonuclease sensitive sites (ESS)in purified DNA isolated from human fibroblasts treated withu.v. light or BPDE. The number of ESS/10⁸ daltons of DNA werecalculated from the number average mol. wt. of the DNA as determinedby sedimentation in alkaline sucrose gradients. The number ofendonuclease sites increased linearly with increasing dosesof either u.v. light or BPDE. The UVR ABC excision nucleasewas able to incise a majority of the BPDE-DNA adducts. Xerodermapigmentosum fibroblasts, complementation group A (XP12BE) had20–25% more ESS at each dose than the BPDE-treated normal(HSBP) cells. Cells treated with 4 µM BPDE and allowed12 h of incubation to perform excision repair showed removalof 60% of the initial number of ESS from HSBP DNA and 40% ofthe ESS from XP-A DNA. Beyond 12 h XP12BE cells lost no additionalESS while HSBP cells continued to lose ESS, athough at a slowerrate, until at 48 h only 22% of the initial ESS remained. Incells treated with 10 J/m² of u.v. light, the UVR ABC excisionnuclease detected 60% of the sites recognized by the pyridiminedimer specific Micrococcus luteus glycosylase/apyrimidinic endonuclease.These results demonstrate the potential use of the UVR ABC excisionnuclease in a quantitative assay for determining the numberof carcinogen-induced lesions in human DNA.     

Chronic lymphocytic leukemia and acquired disorders affecting the immune system: a case-control study

The relationship of a number of subacute or chronic infectious diseases, connective tissue or autoimmune disorders, allergic conditions, and surgical excision of lymphoid tissue with chronic lymphocytic leukemia (CLL) was examined in a case-control study involving 342 cases and 342 matched controls. In both analyses of all matched pairs and those pairs in which both subjects were respondents, no statistically significant association was found between a history of subacute viral infections or subacute and chronic bacterial infections and CLL. Connective tissue or autoimmune disorders also were found not to be associated with CLL. Examination of the association between several allergic conditions and CLL suggested a protective effect as did a "dose-response" analysis, although none of the individual disorders showed a statistically significant relationship; however, a test for linear trend was significant (P = .04). Similarly, examination of the relationship between surgical excision of lymphoid tissue in several anatomic locations and CLL showed a protective effect, statistically significant for tonsillectomy-adenoidectomy (odds ratio = 0.69; 95% confidence interval = 0.48, 0.98). A statistically significant negative dose-response relationship, substantiating the protectiveness of the effect, was found.     

Traumatic atlantooccipital dislocation

A young adult sustained a traumatic atlantooccipital dislocation together with fracture-dislocation at C.4/5 level and had total neurologic deficit below C4 segment. He retained full consciousness but required respiratory support. He developed a stress ulcer with hemorrhage and evidence of "shock lung." He responded to intensive care. Surgery on the 11th day secured reduction and internal fixation at both levels. Death due to respiratory and cardiac arrest followed on the 14th day. Postmortem examination revealed edema of the brain and brainstem.