Reversed Holocene temperature-moisture relationship in the Horn of Africa.

Anthropogenic climate change is predicted to severely impact the global hydrological cycle1, particularly in tropical regions where agriculture-based economies depend on monsoon rainfall2. In the Horn of Africa, more frequent drought conditions in recent decades3,4 contrast with climate models projecting precipitation to increase with rising temperature5. Here we use organic geochemical climate-proxy data from the sediment record of Lake Chala (Kenya and Tanzania) to probe the stability of the link between hydroclimate and temperature over approximately the past 75,000 years, hence encompassing a sufficiently wide range of temperatures to test the 'dry gets drier, wet gets wetter' paradigm6 of anthropogenic climate change in the time domain. We show that the positive relationship between effective moisture and temperature in easternmost Africa during the cooler last glacial period shifted to negative around the onset of the Holocene 11,700 years ago, when the atmospheric carbon dioxide concentration exceeded 250 parts per million and mean annual temperature approached modern-day values. Thus, at that time, the budget between monsoonal precipitation and continental evaporation7 crossed a tipping point such that the positive influence of temperature on evaporation became greater than its positive influence on precipitation. Our results imply that under continued anthropogenic warming, the Horn of Africa will probably experience further drying, and they highlight the need for improved simulation of both dynamic and thermodynamic processes in the tropical hydrological cycle.

[Development and short-term effects of a standardized patient education program for in-patient cardiologic rehabilitation]. / Entwicklung und kurzfristige Effektivität eines standardisierten Schulungsprogramms für die Rehabilitation bei koronarer Herzkrankheit.

BACKGROUND: Patient education is an essential part in the treatment of coronary heart disease in medical rehabilitation. In the German-speaking area, no standardized and evaluated patient education program for coronary heart disease is available so far. In this paper, we demonstrate the development of a quality assured patient education program based on a health-education program of the German statutory pension insurance scheme. METHODS: In a multi-level approach, an existing program was modified concerning treatment evidence, practical guidelines, theories of health and illness behavior and quality criteria for patient education as well as clinical experience and thereafter manualized. In a formative evaluation, feasibility and patient acceptance of this modified program were assessed using evaluation questionnaires of patients and trainers. Afterwards, effects of the patient education program as compared to a traditional education program were assessed on a short-term (at discharge), medium-term (6-month follow-up) and long-term (12-month follow-up) basis in a multicenter quasi-experimental control group study of patients with coronary heart disease (n=434). RESULTS: Results of the formative evaluation demonstrate an overall good acceptance and a good feasibility of the manualized program. Short-term results show a significant small treatment effect in the primary outcome variable patients' knowledge (p=0.001, η2 =0.028). Furthermore, small effects were also observed among some secondary outcomes, such as attitude towards medication, planning of physical activity, psychological quality of life and satisfaction with the education program. CONCLUSION: A standardized education program for patients with coronary heart disease has been developed in a systematic process based on established quality standards. Depending on the outstanding medium and long-term effects, the program may be recommended for general use in medical rehabilitation. The manual provides the prerequisites allowing for a successful transfer into clinical practice.

Two modes of change in Southern Ocean productivity over the past million years.

Export of organic carbon from surface waters of the Antarctic Zone of the Southern Ocean decreased during the last ice age, coinciding with declining atmospheric carbon dioxide (CO(2)) concentrations, signaling reduced exchange of CO(2) between the ocean interior and the atmosphere. In contrast, in the Subantarctic Zone, export production increased into ice ages coinciding with rising dust fluxes, thus suggesting iron fertilization of subantarctic phytoplankton. Here, a new high-resolution productivity record from the Antarctic Zone is compiled with parallel subantarctic data over the past million years. Together, they fit the view that the combination of these two modes of Southern Ocean change determines the temporal structure of the glacial-interglacial atmospheric CO(2) record, including during the interval of "lukewarm" interglacials between 450 and 800 thousand years ago.

Deglacial pulses of deep-ocean silicate into the subtropical North Atlantic Ocean.

Growing evidence suggests that the low atmospheric CO2 concentration of the ice ages resulted from enhanced storage of CO2 in the ocean interior, largely as a result of changes in the Southern Ocean. Early in the most recent deglaciation, a reduction in North Atlantic overturning circulation seems to have driven CO2 release from the Southern Ocean, but the mechanism connecting the North Atlantic and the Southern Ocean remains unclear. Biogenic opal export in the low-latitude ocean relies on silicate from the underlying thermocline, the concentration of which is affected by the circulation of the ocean interior. Here we report a record of biogenic opal export from a coastal upwelling system off the coast of northwest Africa that shows pronounced opal maxima during each glacial termination over the past 550,000 years. These opal peaks are consistent with a strong deglacial reduction in the formation of silicate-poor glacial North Atlantic intermediate water (GNAIW). The loss of GNAIW allowed mixing with underlying silicate-rich deep water to increase the silicate supply to the surface ocean. An increase in westerly-wind-driven upwelling in the Southern Ocean in response to the North Atlantic change has been proposed to drive the deglacial rise in atmospheric CO2 (refs 3, 4). However, such a circulation change would have accelerated the formation of Antarctic intermediate water and sub-Antarctic mode water, which today have as little silicate as North Atlantic Deep Water and would have thus maintained low silicate concentrations in the Atlantic thermocline. The deglacial opal maxima reported here suggest an alternative mechanism for the deglacial CO2 release. Just as the reduction in GNAIW led to upward silicate transport, it should also have allowed the downward mixing of warm, low-density surface water to reach into the deep ocean. The resulting decrease in the density of the deep Atlantic relative to the Southern Ocean surface promoted Antarctic overturning, which released CO2 to the atmosphere.

Foraminiferal isotope evidence of reduced nitrogen fixation in the ice age Atlantic Ocean.

Fixed nitrogen (N) is a limiting nutrient for algae in the low-latitude ocean, and its oceanic inventory may have been higher during ice ages, thus helping to lower atmospheric CO2 during those intervals. In organic matter within planktonic foraminifera shells in Caribbean Sea sediments, we found that the 15N/14N ratio from the last ice age is higher than that from the current interglacial, indicating a higher nitrate 15N/14N ratio in the Caribbean thermocline. This change and other species-specific differences are best explained by less N fixation in the Atlantic during the last ice age. The fixation decrease was most likely a response to a known ice age reduction in ocean N loss, and it would have worked to balance the ocean N budget and to curb ice age-interglacial change in the N inventory.

Glacial/interglacial changes in subarctic north pacific stratification.

Since the first evidence of low algal productivity during ice ages in the Antarctic Zone of the Southern Ocean was discovered, there has been debate as to whether it was associated with increased polar ocean stratification or with sea-ice cover, shortening the productive season. The sediment concentration of biogenic barium at Ocean Drilling Program site 882 indicates low algal productivity during ice ages in the Subarctic North Pacific as well. Site 882 is located southeast of the summer sea-ice extent even during glacial maxima, ruling out sea-ice-driven light limitation and supporting stratification as the explanation, with implications for the glacial cycles of atmospheric carbon dioxide concentration.

Southward migration of the intertropical convergence zone through the Holocene.

Titanium and iron concentration data from the anoxic Cariaco Basin, off the Venezuelan coast, can be used to infer variations in the hydrological cycle over northern South America during the past 14,000 years with subdecadal resolution. Following a dry Younger Dryas, a period of increased precipitation and riverine discharge occurred during the Holocene "thermal maximum." Since approximately 5400 years ago, a trend toward drier conditions is evident from the data, with high-amplitude fluctuations and precipitation minima during the time interval 3800 to 2800 years ago and during the "Little Ice Age." These regional changes in precipitation are best explained by shifts in the mean latitude of the Atlantic Intertropical Convergence Zone (ITCZ), potentially driven by Pacific-based climate variability. The Cariaco Basin record exhibits strong correlations with climate records from distant regions, including the high-latitude Northern Hemisphere, providing evidence for global teleconnections among regional climates.

Life-threatening haemoptysis presenting as a late complication of an ovarian tumour.

Massive haemoptysis may arise as a result of lung malignancy. This case represents the first report of an ovarian granulosa cell tumour metastasising many years after initial tumour resection to the lung causing life-threatening haemoptysis. The management and subsequent clinical course of the patient are discussed as well as the natural history of granulosa-theca cell tumours.

Rapid changes in the hydrologic cycle of the tropical Atlantic during the last glacial.

Sedimentary time series of color reflectance and major element chemistry from the anoxic Cariaco Basin off the coast of northern Venezuela record large and abrupt shifts in the hydrologic cycle of the tropical Atlantic during the past 90,000 years. Marine productivity maxima and increased precipitation and riverine discharge from northern South America are closely linked to interstadial (warm) climate events of marine isotope stage 3, as recorded in Greenland ice cores. Increased precipitation at this latitude during interstadials suggests the potential for greater moisture export from the Atlantic to Pacific, which could have affected the salinity balance of the Atlantic and increased thermohaline heat transport to high northern latitudes. This supports the notion that tropical feedbacks played an important role in modulating global climate during the last glacial period.

[Influence of histopathological factors on dynamic MR mammography]. / Einfluss histopathologischer Faktoren auf die dynamische MR-Tomographie der Mamma.

AIM: To assess the histopathological background of enhancement mechanisms in dynamic MR mammography studies. METHODS: The dynamic MR mammography (MRM) examinations were done with a 1.5 T MR imager (Magnetom Vision, Siemens) using a double breast coil and a coronal FLASH-3D sequence. Enhancement data were acquired during 9 minutes post contrast medium injection (Gd-DTPA 0.2 mmol/kg). Acquisition time was 87 sec/slab. Early enhancement at the first post contrast measurement (E1) and slope of wash-out (SE2-L) were calculated. In immunohistology, proliferation was assessed by the monoclonal antibody Ki 67, capillaries were stained by a CD 31 antibody. Of a total of 48 operated patients, 58 lesions and 46 surrounding tissues were evaluated. RESULTS: Cellularity, capillary density and proliferation showed statistically significant correlations with E1 (p < 0.01). In multiple regression analysis, E1 was significantly associated only with high cellularity (p = 0.002) and the combination of high cellularity and high microvessel density (p = 0.002); a negative slope of wash out was significantly associated only with malignant histology (p = 0.027). CONCLUSIONS: Our findings indicate a direct influence of cellularity and microvessel density on early enhancement. The expression of the proliferation marker Ki 67 was not an independent predictor for contrast enhancement.

2-Amino-1-methyl-6-phenylimidazo [4,5-b]pyridine (PhIP) in human hair as biomarker for dietary exposure.

Heterocyclic aromatic amines (HAAs), formed during cooking of meat, are multipotent rodent carcinogens and are suspected to cause cancer in humans. In a search for suitable biomarkers for human dietary exposure to HAAs, we have investigated the concentration of a common fried food mutagen, 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine (PhIP), in human hair. Fourteen volunteers participated in the study, each contributing hair from a regular haircut, and completing a questionnaire about consumption of fried/grilled meat and smoking habits. Hair samples were treated with 1 N NaOH at 100 C, and the HAAs extracted under alkaline and acidic conditions, derivatized and analysed by gas chromatography-mass spectrometry. PhIP was found in 12 out of 14 hair samples, in amounts from approx. 50 to 5000 pg g(-1) hair, while two samples were below the detection limit (<50 pg g(-1) hair). Grey/white hair straws from subjects with a mixture of coloured and grey/white hair had about a 50% reduction in PhIP concentration as compared with the natural hair mixture from the same person. This demonstrates that melanin, responsible for hair colour and spectrophotometrically characterized in the samples, participates in PhIP binding. Thus, when HAA binding components of the hair are taken into account, hair seems like an interesting object of further investigation as a biomarker for human exposure to dietary PhIP.

Leptospirosis associated with severe pulmonary haemorrhage in Far North Queensland.

Pulmonary haemorrhage as a manifestation of leptospirosis is rarely diagnosed in developed countries. Five patients with proven leptospirosis associated with severe pulmonary haemorrhage presented to one hospital in Far North Queensland between January 1994 and June 1997. Four required admission to the intensive care unit and one patient died. Pulmonary haemorrhage is an uncommon but severe complication of leptospirosis and may be a source of diagnostic confusion in tropical areas of Australia.

Pharmacokinetics of naftopidil, a novel anti-hypertensive drug, in patients with hepatic dysfunction.

The pharmacokinetics of naftopidil, a novel alpha-1 adrenoceptor-blocking antihypertensive, were investigated in ten patients (9M/1F) with hepatic dysfunction after oral administration (50 mg, tablet) and after an intravenous infusion of 5.0 mg over 2 minutes. Results were compared to a control group of 12 healthy subjects (6M/6F) of a previous investigation, which was carried out according to the identical study protocol. The pharmacokinetic parameters obtained for the i.v. administration were comparable in both groups (half life 3.6 +/- 3.4 hours in liver-impaired subjects versus 3.3 +/- 2.1 hours in controls; clearance 11.9 +/- 4.7 ml/minute/kg versus 11.0 +/- 1.6 ml/minute/kg). Following oral administration the plasma levels and half-life times of naftopidil were significantly increased in liver impairment (t1/2 16.6 +/- 19.3 hours versus 5.4 +/- 3.2 hours in controls; P = 0.012). Mean values for the absolute bioavailability in patients with hepatic dysfunction were significantly higher (mean 75%, median 53%, range 13.4-211.0%) compared to healthy subjects (mean 17%, median 16%, range 6.7-29.6%, P = 0.001). Reduction of functional hepatic blood flow in chronic liver disease or, as evidenced in one case as a consequence of shunt surgery, is the probable cause of the observed alteration in naftopidil kinetics. This phenomenon occurred only following the oral 50 mg dose whereas the intravenous 5 mg dose obviously still could be normally handled. Naftopidil demethylation and hydroxylation were both less and non-uniformly affected. The pharmacokinetic findings suggest that in patients with severe hepatic impairment or evidence for marked changes in hepatic blood flow the dose of naftopidil may require adjustment to the lower end of the therapeutic range and/or may be limited to once daily. However, before definite conclusions can be drawn, further steady-state studies are required. Despite the pharmacokinetic discrepancies no difference in drug tolerability was seen between patients and healthy subjects.

Efficacy and tolerability of the renin inhibitor Ro 42-5892 in patients with hypertension.

The efficacy of multiple oral administration of the renin inhibitor Ro 42-5892 [(S)-alpha-](t-butylsulfonyl)-methyl]hydrocinnamamido]-N-[1S , 2R,3S)-1-(cyclohexylmethyl)-3-cyclopropyl-2,3-dihydroxypropyl]-imi dazole-4- propionamide] was studied. Forty-nine patients with moderate essential hypertension were randomly assigned to three groups that entered an 8-day double-blind oral treatment period: daily administration of placebo (group A), 300 mg Ro 42-5892 (group B), or 600 mg Ro 42-5892 (group C). Four hours after the last oral drug intake, placebo was administered intravenously to subjects in group A and 100 mg Ro 42-5892 was administered intravenously to subjects in groups B and C. Sitting systolic and diastolic blood pressures were measured on days 1 and 8 with a blood pressure device. On day 1, systolic blood pressure maximally decreased by 13.3 +/- 9.3, 20.2 +/- 11.2, and 24.1 +/- 11.3 mm Hg in groups A, B, and C, respectively (mean +/- SD; p < 0.01 for group A versus group C). Diastolic blood pressure maximally decreased 9.4 +/- 5.7, 13.9 +/- 8.7, and 11.8 +/- 5.7 mm Hg (difference not significant). On day 8, systolic blood pressure maximally decreased 19.5 +/- 16.5, 26.5 +/- 17.4, and 30.5 +/- 18.4 mm Hg and diastolic blood pressure maximally decreased 14.8 +/- 5.0, 16.2 +/- 9.0, and 17.9 +/- 12.7 mm Hg (difference not significant) compared with pretreatment values. Intravenous drug administration did not further reduce blood pressure, suggesting that the mode of action and not the low bioavailability was the limiting factor for the low efficacy.

Diabetic retinopathy. Assessment of severity and progression.

This study describes a classification of overall retinopathy severity based on the presence and severity of lesions graded in the Airlie House classification of diabetic retinopathy, and demonstrates its use in assessing progression of retinopathy over a 6-year period in a group of insulin-taking patients. One hundred and ninety-one insulin-taking patients with diabetes of at least 5 years' duration were identified from their doctors' records in 1970-1971. Patients were seen again in 1972-1973 and 1976-1977. Stereoscopic color fundus photographs of 7 fields in each eye were taken at each visit. All photos were graded using a modification of the Airlie House classification, which specified 6 levels of retinopathy for a given eye; when both eyes are considered an 11-step grading scheme results. Of all patients seen at the 2-year visit whose retinopathy was at risk of progressing, 41.2% showed progression of one level or more on the scale, 19.2% progression of two or more levels. At the 6-year examination comparable rates were 75.0% and 58.4%. Of patients whose retinopathy was level 4 in each eye (nonproliferative retinopathy of "moderate" severity) at the baseline visit, 13/21 (72%) had progressed to proliferative retinopathy in at least one eye at the 6-year examination. The classification scheme proposed appears useful for characterizing overall retinopathy severity of patients on the basis of gradings of fundus photographs. The data presented may be of help in planning trials of treatment aimed at slowing the development or progression of retinopathy.

Prognosis for life in patients with diabetes: relation to severity of retinopathy.

In a group of 709 individuals with diabetes diagnosed prior to age 50 and followed for five to thirteen years a strong inverse relationship was demonstrated between the severity of the retinopathy at the initial visit and survival. Survival in patients with no retinopathy or with microaneurysms only was little different from that of the general population (five-year rate .99, SE .01). The five-year survival rate for patients with more severe nonproliferative retinopathy, characterized by the presence of hemorrhages and/or exudates, but without new vessels or vitreous hemorrhage (B2), was .81 (SE .04), and that for patients with proliferative retinopathy (PDR) was .56 (SE .03). After adjustment for age at diagnosis of diabetes, duration of diabetes and sex, the differences in survival between these three groups were highly statistically significant. Impairment of visual acuity was also shown to be inversely related to survival. The five-year survival rate for patients with visual acuity of 20/200 or worse in each eye was .42 (SE .05). In patients with B2 retinopathy there was a weak but statistically significant trend towards decreasing survival with increasing duration of diabetes. In patients with PDR survival decreased with increasing duration up to 20 years, but then improved for patients with 20 years or more of diabetes.