The Genetic Structure of Populations of the Douglas-Fir Swiss Needle Cast Fungus Nothophaeocryptopus gaeumannii in New Zealand.

Swiss needle cast is a foliar disease of Douglas-fir (Pseudotsuga menziesii) that results in premature foliage loss and reduced growth. The causal fungus, Nothophaeocryptopus gaeumannii, was first detected in New Zealand in 1959 and spread throughout the North and South Islands over the following decades. The contemporary genetic structure of the N. gaeumannii population in New Zealand was assessed by analyzing 468 multilocus SSR genotypes (MLGs) from 2,085 N. gaeumannii isolates collected from 32 sites in the North and South Islands. Overall diversity was lower than that reported from native N. gaeumannii populations in the northwestern United States, which was expected given that N. gaeumannii is introduced in New Zealand. Linkage disequilibrium was significantly higher than expected under random mating, suggesting that population structure is clonal. Populations of N. gaeumannii in the North and South Islands were weakly differentiated, and the isolates collected from sites within the islands were moderately differentiated. This suggests that gene flow has occurred between the N. gaeumannii populations in the North and South Islands, and between the local N. gaeumannii populations within each island. Eighteen isolates of N. gaeumannii Lineage 2, which has previously been reported only from western Oregon, were recovered from two sites in the North Island and four sites in the South Island. The most likely explanation for the contemporary distribution of N. gaeumannii in New Zealand is that it was introduced on infected live seedlings through the forestry or ornamental nursery trade, as the fungus is neither seed borne nor saprobic, and the observed population structure is not consistent with a stochastic intercontinental dispersal event.

Impact of Swiss needle-cast on growth of Douglas-fir.

Phaeocryptopus gaeumannii, the cause of Swiss needle-cast, is widely distributed in plantations of Douglas-fir in many parts of the world. Nevertheless, information remains limited on its precise effect on stand growth, particularly in relation to regional climate, and on its consequent economic cost. In New Zealand, the spread of P. gaeumannii over a period of ≈30 years following its discovery in 1959 was closely monitored, and the timing of its arrival in different forests is known. This information was coupled with data from permanent sample plots in order to quantify the associated historical growth increment loss. Analyses revealed a steady decline in growth rate over the period from the first appearance of P. gaeumannii to a point when it stabilized at a lower increment level 14 to 20 years later. The cumulative mean reduction was 25% for mean top height, 27% for basal area, and 32% for stem volume. Volume growth rate decline was greater in the North Island (35%) than the South Island (23%) of New Zealand. These reductions in volume growth are estimated to equate to a loss in net present value of $NZ2,620 ha(-1) and $NZ1,470 ha(-1) for the North and South Islands, respectively, using a discount rate of 6%. Mortality did not increase as a result of infection by P. gaeumannii. The disease had less effect on cooler sites, especially those with low spring minimum temperatures (P < 0.001). Negligible growth decline occurred on sites with daily minimum October temperatures averaging <3.2°C.

Stock-Type Susceptibility and Delineation of Treatment Areas for a Cryptic Pinus radiata Root Disease.

ABSTRACT Planting material with superior resistance to Armillaria root disease was identified in a field trial established to investigate variation in Armillaria infection among different Pinus radiata nursery stock types. At stand age 6.4 years, total infection incidence, mortality, and degree of root collar girdling by Armillaria spp. were all significantly lower among trees derived from both rooted stool bed cuttings (physiological age 1 to 3 years) and rooted field cuttings (physiological age 3 to 6 years) than among those grown from seedlings. Cutting types did not differ significantly from one another. No significant differences were found between stock types in stem diameter, but trees from stool bed cuttings were significantly taller than seedling trees. Whether these differences remain detectable later in the rotation, initial results suggest that it may be advantageous to plant robust stock, of either cuttings or seedlings, on Armillaria-infested sites. The incidence of infection in living, green-crowned trees was unevenly distributed across the trial site, and was greater nearer to trees killed by Armillaria spp. than further away (significant within a radius of 10 m). By mapping visible Armillaria-caused mortality prior to thinning, it may be possible to delineate areas with a higher incidence of concealed chronic infection, thus defining infested sites for postharvest treatment.

Hodgkin's disease after cardiac transplant: a report of two cases.

Non-Hodgkin's lymphoma is a well recognized sequela of transplant related immunosuppression. Hodgkin's disease has only rarely been described in this context. We describe two cases of Hodgkin's disease after heart and heart/lung transplants respectively. Both patients continued to receive immunosuppressive therapy with cyclosporin and prednisolone, and received combination chemotherapy. One died of Aspergillus infection following the second course of chemotherapy. The other patient completed his chemotherapy and remains in remission. We discuss the possible aetiology and management of post-transplant Hodgkin's disease.

High-dose therapy and autologous stem cell rescue for poor risk and refractory lymphoma: a single centre experience of 123 patients.

Over an 8-year period we autografted 123 patient with poor-risk lymphoma. Sixty-three patients had Hodgkin's disease (HD) and 60 non-Hodgkin's lymphoma (NHL). Of the patients with HD, 45 had responsive and 18 resistant disease prior to high-dose therapy. Fifty-three patients with NHL had responsive and seven had resistant disease at the time of transplantation. Seventy-seven patients received autologous bone marrow (BM) rescue, 39 autologous peripheral blood progenitor cell (PBPC) rescue, and seven combined BM and PBPC rescue. High-dose chemotherapy was BEM in 67, BEAM in 39, TBI and cyclophosphamide or etoposide or BCNU in 10, etoposide/mitozantrone in six and etoposide/melphalan in one. There was eight (6.5%) deaths due to treatment-related toxicity, within the first 100 days post-transplantation. Of the patients with HD 41 (65%) are alive at a median follow-up of 39 months (range 2-94). Thirty-three (52%) patients remain in CR. The median DFS of the 63 patients with HD is 34 months (95% CI 7-61). The median DFS for patients transplanted with responsive disease was significantly better than for those transplanted with refractory disease (61 vs 21 months P < 0001). Thirty-five (58%) of the patients with NHL are alive, and 20 (33%) remain in CR. The median DFS for patients transplanted with responsive and refractory disease was 11 months (95% CI 3-19) and 4 months (95% CI 0-9; P = NS) respectively. The median DFS for patients transplanted with HD was significantly better than for patients transplanted with NHL (34 vs 8 months, P < 0.002). In both groups there was no significant difference in DFS in patients receiving one, two, three or more lines of therapy prior to transplantation. In summary, in patients with poor-risk lymphoma who have responsive disease high-dose therapy may result in durable CRs. Conversely, only a small proportion of patients with HD or NHL with resistant disease achieve CR after autologous stem cell rescue.

Heat-related deaths in Philadelphia--1993.

A study of heat-related deaths associated with the 1993 heat wave in Philadelphia, Pennsylvania, was conducted. Most of these deaths were in the susceptible elderly with preexisting natural diseases who lived alone without air conditioning in upstairs bedrooms with windows shut, thus creating an even hotter environment. These excessive deaths under such conditions did not meet the standard clinical criteria for hyperthermia because of varying postmortem intervals. Therefore, the authors stress the utility of a postmortem definition of heat-related death to better define the magnitude of health risk posed by hot weather and warn public health and other agencies to take preventative measures.

Peripheral blood progenitor cell transplantation: a single centre experience comparing two mobilisation regimens in 67 patients.

Between June 1991 and January 1995 we performed 67 peripheral blood progenitor cell transplants (PBPCT). Ten patients (group 1) were mobilised with 7 gm/m2 of cyclophosphamide followed by daily G-CSF injections (5 micrograms/kg, subcutaneously). When the white cell count reached 1 x 10(9)/1 they were leukapheresed for 5 days. After stem cell infusion they received G-CSF (10 micrograms/kg/day) until the neutrophil count reached 1.5 x 10(9)/1. Fifty-six patients had PBPCs mobilised with 3 gm/m2 of cyclophosphamide followed by daily subcutaneous G-CSF (5 micrograms/kg) and PBPCs were harvested on 2 consecutive days, when the white cell count rose to 4 x 10(9)/1. After stem cell infusion this group did not receive G-CSF. In 47 of the 56 patients (group 2) adequate MNC (> or = 4 x 10(8)/kg) and/or CFU-GM (> or = 10 x 10(4)/kg) were obtained. Insufficient MNC and/or CFU-GM were obtained in 10 patients. They were therefore transplanted using a combination of bone marrow and peripheral blood progenitor cells (group 3). Overall 64 patients successfully engrafted. Median days to neutrophils > or = 0.5 x 10(9)/1 were 9 (range 8-13), 12 (range 8-25) and 11 (range 9-16) and to platelets > or = 50 x 10(9)/1 were 11 (range 9-23), 13 (range 9-90) and 16 (range 13-99) in groups 1, 2 and 3 respectively. Patients in group 1 had a faster neutrophil recovery than patients in group 2 (P = 0.0002). The three patients who failed to engraft all received a combination of autologous peripheral blood and bone marrow cells.

Severe hemosiderosis post allogenic bone marrow transplantation.

Abnormal liver function persisting late after allogeneic BMT is usually attributed to chronic GvHD, viral hepatitis or drug toxicity. We describe a patient who had negative hepatitis serology, was on no hepatotoxic medication, had no evidence of GvHD but had abnormal liver function 15 months post MBT. She was diagnosed as having grade IV hemosiderosis of the liver. Her total red cell support had only been 52 units. We therefore postulate that in a proportion of patients receiving allogeneic BMT impaired intestinal iron absorption may be an important cause of hemosiderosis.

Fatal thromboembolism in acute promyelocytic leukaemia treated with a combination of all-trans retinoic acid and aprotonin.

We describe a case of acute promyelocytic leukaemia where the combined use of all-trans retinoic acid and an antifibrinolytic (aprotinin) may have contributed to worsening of coagulopathy.

Interstitial pneumonitis as a late complication of high dose therapy with cyclophosphamide/thiotepa and peripheral blood progenitor cell rescue for carcinoma of the breast.

The incurability of metastatic breast cancer with conventional chemotherapy has prompted many units to investigate the role of high dose chemotherapy and autologous stem cell rescue in patients with advanced or poor risk primary disease. Although preliminary data from centres treating patients with these modalities are encouraging, both in terms of rapidity of haemopoietic recovery and progression free survival, there is nonetheless a procedure related toxicity. We describe a patient with inflammatory carcinoma of the breast who received high dose cyclophosphamide and thiotepa prior to peripheral blood progenitor cell rescue, and developed a steroid responsive interstitial pneumonitis 10 weeks after stem cell infusion.

Autografting for multiple myeloma: a 5-year experience at a single institution.

Over a 5-year period, we have performed 33 autologous bone marrow or PBPC transplantations for multiple myeloma. Nine patients were in complete remission and 24 in partial remission at time of transplantation. Conditioning regimens were BEM (BCNU, etoposide and melphalan) in 29, busulphan and cyclophosphamide in three and melphalan alone in one. Two patients (6%), died within 3 months of transplant-related mortality, seven (21.3%), died of disease progression at a median follow-up of 11 months (range 4-24). Twenty-four patients (72.7%) are alive at a median follow-up of 15 months (range 4-61). Of nine patients transplanted in CR, four have relapsed and are alive and five remain in CR. Of 24 patients transplanted in PR, nine have died, six remain in PR, eight achieved CR and one has progressive disease. The overall median progression-free survival (PFS) is 31 months (95% CI = 20-42). For patients transplanted in PR the median PFS is 24 months (95% CI = 22-26), the median PFS for patients transplanted in CR has not yet been reached. The median PFS for patients achieving CR pre- or post-transplantation was better than for patients neither achieving CR pre- nor post-transplantation (P = 0.05). The median PFS was also significantly improved for patients requiring only primary therapy, compared to patients needing second-line therapy to achieve CR or stable PR prior to transplantation (31 vs 11 months, P = 0.02).

Isolation and structure determination of two novel phenazines from a Streptomyces with inhibitory activity against metallo-enzymes, including metallo-beta-lactamase.

Two novel metabolites, SB 212021 and SB 212305, have been isolated from a Streptomyces and shown to have molecular formulae of C15H10N2O5 and C20H17N3O8S, respectively. The structures were deduced by a combination of NMR techniques and mass spectral fragmentation patterns and shown to be novel members of the phenazine group of antibiotics. In the absence of added zinc, both compounds had IC50's of 1-75 microM for the Bacteroides fragilis 262 CfiA and Xanthomonas maltophilia L-1 metallo-beta-lactamases. The compounds also inhibited ACE with IC50's of 55 and 68 microM, respectively. Mode of action studies illustrate that the compounds inhibit some metalloenzymes by chelation of the active site metal ion. They exhibit poor antibacterial activity.

Ruptured vascular malformation masquerading as battered/shaken baby syndrome: a nearly tragic mistake.

Battered/shaken baby syndrome is a clinical and pathologic diagnosis based on clinical examination, central nervous system dysfunction, and intracranial, optic nerve sheath, and retinal hemorrhages in infants under the age of three years. This report describes a case in which the battered/shaken baby syndrome was suspected because of an unusual parental reaction to an acute, mortal illness in their seven-week-old baby, as well as an acute intracranial hemorrhage coupled with the discovery of optic nerve sheath hemorrhages at necropsy. Thorough microscopic study, however, uncovered an unusual subarachnoid vascular malformation, the rupture of which led to the death of the infant. This case underscores the importance of complete postmortem examinations in cases of suspected child abuse, and teaches caution in jumping to hasty conclusions.

Cocaine-induced agitated delirium, forceful struggle, and minor head injury. A further definition of sudden death during restraint.

Four cases from the Philadelphia Medical Examiner's Office are presented and the literature is reviewed to define further the syndrome of sudden death occurring during cocaine-induced agitated delirium and struggle during restraint in individuals who also sustain minor head injury. The mechanism of death involves a terminal arrhythmia, most likely due to sympathetic sensitization of the myocardium by cocaine and the stress of struggle sometimes juxtaposed upon the stratum of minimal natural disease. In the cases described, the head injury in itself was insufficient to be a cause of death. Recognition of the role of the pharmacologic effect of cocaine and the lethal effects of its use in this setting is crucial.

Comparison of post-mortem urinary and vitreous humour organic acids.

We have analysed organic acid profiles in 74 samples of post-mortem vitreous humour from the sudden infant death syndrome and compared the profiles to those obtained from the corresponding urine or bladder wall swab. There was a high degree of correlation indicating that vitreous humour analysis in high-risk infants is an appropriate analytical strategy when urine is not available. In our patient sample two infants had evidence of abnormal methylmalonic acid metabolism, one had glyceric aciduria (and elevated levels of vitreous humour glyceric acid), one had evidence of pre-existing liver damage as judged by the presence of 4-hydroxyphenyllactic acid, one had a non-ketotic dicarboxylic aciduria indicating inhibited fatty acid oxidation and two patients had significant long-chain 3-hydroxydicarboxylic acids and evidence of paracetamol ingestion.

Azelaic and pimelic acids: metabolic intermediates or artefacts?

Azelaic and pimelic acids are excreted in elevated amounts in urine in disorders of mitochondrial beta-oxidation and disorders of peroxisomal beta-oxidation, for which they are of significant diagnostic value. We have detected the presence of azelaic, pimelic and even-chain-length dicarboxylic acids (adipic, suberic and sebacic acids) arising artefactually as a result of storage of small sample volumes in plastic containers. Storage of samples for organic acid analysis in glass containers is recommended.

Cocaine in decomposed human remains.

From March 1988 through March 1990, at the Philadelphia Medical Examiner's Office toxicology laboratory, samples from 77 decomposed human bodies were tested for the presence of cocaine, employing gas chromatography/mass spectrometry (GC-MS). The material analyzed included decomposed soft tissue, bloody decomposition fluid, mummified tissue, maggots, and beetle feces. Twenty-two cases (28.6%) were positive for cocaine, many of these cases in states of advanced decomposition. These findings indicate the usefulness of testing decomposed tissue for cocaine in all cases where its presence is suspected. This is contrary to what might be expected, since cocaine is generally labile and rapidly broken down by both enzymatic and nonenzymatic mechanisms.

Atherosclerotic cardiovascular disease and sudden deaths among young adults in Wayne County.

Based on postmortem records at the Wayne County Medical Examiners' Office from 1982 to 1986, autopsy results indicated that the deaths of 129 persons aged 20-34 resulted from heart disease: 51 of these deaths were attributed to atherosclerotic cardiovascular disease (ASCVD), 29 to hypertensive cardiovascular disease, 28 to cardiomyopathy, and 21 to other cardiac causes. The majority of the deaths due to ASCVD occurred among men, both black and white, followed by black women, and the incidence increased with age. All of these deaths due to ASCVD were sudden and accounted for all deaths due to ischemic heart disease in this age group among Wayne County residents. Diabetes mellitus, left ventricular hypertrophy, a history of seizures, and the recent ingestion of alcohol were all found to be associated with sudden death from ASCVD in this group. Obesity did not seem to be a significant factor. These data suggest that ASCVD is not rare as a cause of death in young adults and some of the risk factors identified in older subjects also operate in this age group.

Cocaine in Wayne County Medical Examiner's cases.

We determined the incidence of detection of cocaine or its metabolites in Wayne County (Michigan) Medical Examiner's cases from 1984 to 1987. Over this four-year period there was a significant (P less than 0.01) increase each year in evidence of recent cocaine use in this population, reaching 38.3% of all tested cases in 1987. Much of this increase was accounted for by homicide victims, especially those in their third or fourth decade of life, of whom 58.6 and 56.3%, respectively, tested positive in 1987. There was a large increase in recent cocaine use in teenage homicide victims in 1987, having previously changed little from 1984 to 1986. In victims of drug abuse, recent cocaine use also increased significantly (p less than 0.01) each year, reaching 47.6% in 1987, generally in combination with heroin. Although deaths attributed solely to cocaine were not as common, they also increased significantly each year from 4 in 1984 to 25 in 1987. Compared with the general population, those who use cocaine in Wayne County are more likely than those who do not to die prematurely, often as a result of violence.