Third Year Of Treatment Research Articles

Three‐year data from a comparative study with recombinant human growth hormone in the treatment of short stature in young children with intrauterine growth retardation

Growth acceleration and bone maturation were studied for 3 y in 69 children with severe short stature and a history of intrauterine growth retardation (IUGR), to determine the effect of treatment with recombinant human growth hormone (r‐hGH). The patients were enrolled in an open, multicentre trial and were randomly allocated to either the treated group (Group 1) or the control group (Group 2). The children in Group 1 were treated daily with 0.2 IU/kg/body weight (0.067 mg/kg) s.c, during 3 y and the children in Group 2 started the study with a 1‐y observation period followed by a 3‐y treatment period. At birth, their mean weight standard deviation score (SDS) was ‐2.5 and their mean length SDS ‐3.5. At baseline, the patients were prepubertal, non‐GHdeficient, with no known dysmorphic features. Mean age was 4.5 y, bone age was 3.3 y, height SDS was ‐3.4, height velocity (HV) SDS was ‐1.6, and body mass index SDS was ‐1.4. After 1 y of treatment, linear HV in Group 1 increased in comparison with the pre‐treatment period (from 5.7 ± 2.0 to 10.1 ± 1.7cm/y;p < 0:001)and with the firstyear of observation in Group2(p < 0:001). Increased HV was sustained during the second and third year of treatment and was significantly higher than at baseline. A similar growth pattern was seen during the 3y of GH treatment in Group 2. Mean height SDS for chronological age increased by 2.0 ± 0.7 in the two groups after 3 y of treatment. HV after 1 y of treatment was negatively correlated with growth velocity at baseline. Bone age remained retarded but increased with a mean of almost 4 y after 3y of treatment in both groups. Even at a dose that is three times the replacement dose treatment with r‐hGH was well tolerated. From these results, we conclude that r‐hGH treatment over 3 y can induce sustained catch‐up growth in young children with severe short stature and a history of IUGR. Long‐term studies are needed to assess ultimate effects on final height.

Effects of elevated atmospheric CO2 on soil microbiota in calcareous grassland

AbstractMicrobial responses to three years of CO2 enrichment (600 μL L–1) in the field were investigated in calcareous grassland. Microbial biomass carbon (C) and soil organic C and nitrogen (N) were not significantly influenced by elevated CO2. Microbial C:N ratios significantly decreased under elevated CO2 (– 15%, P = 0.01) and microbial N increased by + 18% (P = 0.04). Soil basal respiration was significantly increased on one out of 7 sampling dates (+ 14%, P = 0.03; December of the third year of treatment), whereas the metabolic quotient for CO2 (qCO2 = basal respiration/microbial C) did not exhibit any significant differences between CO2 treatments. Also no responses of microbial activity and biomass were found in a complementary greenhouse study where intact grassland turfs taken from the field site were factorially treated with elevated CO2 and phosphorus (P) fertilizer (1 g P m–2 y–1). Previously reported C balance calculations showed that in the ecosystem investigated growing season soil C inputs were strongly enhanced under elevated CO2. It is hypothesized that the absence of microbial responses to these enhanced soil C fluxes originated from mineral nutrient limitations of microbial processes. Laboratory incubations showed that short‐term microbial growth (one week) was strongly limited by N availability, whereas P was not limiting in this soil. The absence of large effects of elevated CO2 on microbial activity or biomass in such nutrient‐poor natural ecosystems is in marked contrast to previously published large and short‐term microbial responses to CO2 enrichment which were found in fertilized or disturbed systems. It is speculated that the absence of such responses in undisturbed natural ecosystems in which mineral nutrient cycles have equilibrated over longer periods of time is caused by mineral nutrient limitations which are ineffective in disturbed or fertilized systems and that therefore microbial responses to elevated CO2 must be studied in natural, undisturbed systems.

Growth hormone treatment of short children born small‐for‐gestational‐age: the Nordic Multicentre Trial

The aims of this study were to evaluate the efficacy and safety of different doses of growth hormone (GH) treatment in prepubertal short children born small‐for‐gestational‐age (SGA). Forty‐eight children born SGA from Sweden, Finland, Denmark and Norway were randomly allocated to three groups: a control group of 12 children received no treatment for 2 y, one group was treated with GH at 0.1 IU/kg/d (n= 16), and one group was treated with GH at 0.2 IU/kg/d (n= 20). In total 42 children completed 2 y of follow‐up, and 24 children from the treated groups completed 3 y of treatment. Their mean (SD) age at the start of the study was 4.69 (1.61) y and their mean (SD) height was ‐3.16 (0.70) standard deviation scores (SDS). The children remained prepubertal during the course of the study. No catch‐up growth was observed in the untreated group, but a clear dose‐dependent growth response was found in the treated children. After the third year of treatment, the group receiving the higher dose of GH, achieved their target height. The major determinants of the growth response were the dose of GH used, the age at the start of treatment (the younger the child, the better the growth response) and the family‐corrected individual height deficit (the higher the deficit, the better the growth response). Concentration of insulin‐like growth factor‐I (IGF‐I) and IGF‐binding protein‐3 increased during treatment. An increase in insulin levels was found without negative effects on fasting glucose levels or glycosylated haemoglobin levels. GH treatment was well tolerated. In conclusion, short prepubertal children born SGA show a dose‐dependent growth response to GH therapy, and their target height SDS can be achieved within 3 y of treatment given GH at 0.2 IU/kg/d. However, the long‐term benefit of different regimens of GH treatment in children born SGA remains to be established.

Effects of enhanced nitrogen deposition in a spruce forest at Klosterhede, Denmark, examined by moderate NH 4NO 3 addition

The fate and effects of increased N deposition were investigated by experimental manipulation in a mature Norway spruce plantation at Klosterhede, western Denmark. The ambient N deposition was 15–20 kg N ha −1 yr −1. Addition of 35 kg N ha −1 yr −1 as ammonium nitrate to a 500-m 2 plot was carried out by handspraying monthly for 4 years. During the first year the spray was labeled with 15N. Tree growth was depressed by 4 successive spring or summer droughts throughout the treatment years. The nitrogen concentration in needles increased in the third year of treatment and critical low P concentrations (0.6–1 mg P g −1) developed possibly as a combined effect of drought and N stress on roots and mycorrhizae. Reduced retranslocation of N was indicated by increased concentration and flux of N in needle litterfall. Increased uptake of N was observed in all parts of the trees and the fraction of the input N taken up was increased from 32 to 43%, whereas the fraction immobilized in the soil was decreased from 40 to 33% of the input N. The decomposition remained unchanged, whereas the net N mineralization was increased 85% over the control. The effect on net mineralization may have resulted from saturation of the immobilization process rather than from an increase in gross mineralization. Soil respiration was not affected, indicating that microbial activity did not respond. Nitrification and denitrification were not important in either control or treated soils. Soil solution chemistry responded promptly to nitrogen applications. Nitrate concentrations increased at all depths, and nitrate leaching increased from < 0.3 to 4.2 kg N ha −1 yr −1 by the third year. Reduced biological control on nitrate leaching was indicated by increased nitrate concentration in soil water at the end of the growing season. Ammonium concentrations increased down to 15 cm depth, but all ammonium was retained in the system. Despite the increased nitrate leaching, 92% of the total inputs were retained. No changes in concentrations of other major ions due to the N additions were detectable. The effects of the successive droughts on growth and nutrient cycling caused significant interaction on the response to N addition. Continuation of the N addition treatment will be necessary to observe the full response of the simulated deposition increase in this forest.

Effects of weekly nitrogen additions on N cycling in a coniferous forest catchment, Gårdsjön, Sweden

In spite of nitrogen being a major limiting factor for forest growth in most parts of Scandinavia, increased nitrate levels in surface waters and soil water have been coupled to questions of increased inputs and decreasing immobilization of nitrogen in watersheds. To study an ecosystem response to elevated nitrogen deposition, NH 4NO 3 was added to a 0.52 ha forested headwater catchment in weekly portions by means of sprinklers below the canopy. Total nitrogen input as throughfall increased from the ambient 11 kg N ha −1 yr −1 to approximately 51 kg ha −1 yr −1 in the treatment years. The catchment, situated in Gårdsjön, Sweden, is dominated by naturally generated Norway spruce with Scots pine in drier areas. The mean age of the forest is 104 yr. N concentrations in foliage, weight and N concentrations in litterfall, in situ net N mineralization and nitrate transformation (resin core technique), and leaching of N below the organic LFH horizon were studied on a catchment (NITREX) or plot (NITREX, CONTROL) level. This was coupled with input-output budgets to estimate fluxes and cycling of N during the pre-treatment year and the third year of treatment. There was a significant increase in net N mineralization in the NITREX plots the 3rd year of treatment, and a significant interaction between plot and year indicating a response to N addition for both net mineralization and nitrate transformation. The increased flux of nitrate from incubated soil cores, as well as the increased concentration in soil water and runoff indicated that the increased nitrification was possibly coupled with a preferential uptake of NH 4N by the microflora. The spatial variability of the nitrogen transformation rates was generally large and increased with treatment. The N concentration in needle litter showed an increase the 5th year of treatment, but no effect of nitrogen addition was found on the total weight of litterfall or on the N concentration of foliage. The key processes that determine the ecosystem response to increased inputs of nitrogen seem to be net mineralization and nitrogen transformation rates, together with the mechanism and capacity of N assimilation into the soil pool. The major sink for both externally added and internally produced inorganic N was calculated to be the soil organic pool. N assimilation into the upper organic LF horizon dominated, and this assimilation is the first of three suggested ways for coniferous ecosystems to respond to increased chronic N input. Over time, the system is hypothesized to change towards a system with a reduced assimilation capacity, a possible decreased decomposition rate, and an increased export of nitrate through leaching. The time-span of these changes is still uncertain.

Effects of long-term antihypertensive treatment with lisinopril on resistance arteries in hypertensive patients with left ventricular hypertrophy.

To evaluate the effects of long-term antihypertensive therapy with the angiotensin converting enzyme inhibitor lisinopril on structural alterations and the endothelial function of small resistance arteries in hypertensive patients with left ventricular hypertrophy. Fourteen patients with left ventricular hypertrophy were treated for 3 years with a lisinopril-based regimen. Patients underwent an echocardiographic evaluation of left ventricular mass index at baseline, during the first and third years of treatment. At the end of the treatment period, subcutaneous small resistance arteries (obtained by biopsy of the subcutaneous fat from the gluteal region) were dissected and mounted on a micromyograph (Mulvany's technique); the media : lumen ratio was then calculated. Data obtained were compared with those observed for 14 untreated essential hypertensive patients and 14 normotensive subjects, age- and sex-matched. In the present study, a significantly lower media : lumen ratio was observed in treated compared with untreated hypertensive patients, although it remained significantly higher than that in normotensive subjects. In treated hypertensive patients a significant reduction in clinic blood pressure was observed. However, their blood pressure remained significantly higher than that in normotensive subjects. Significant correlations between the media : lumen ratio and blood pressure, left ventricular mass index or changes in left ventricular mass index during treatment were observed. The response to acetylcholine administration was reduced in untreated hypertensives compared with that in normotensives. In patients treated with lisinopril, the vasodilatation obtained with the two higher doses of acetylcholine was greater than that in untreated hypertensives, thus suggesting an improvement of endothelial function. Long-term therapy based on lisinopril was associated with a smaller media : lumen ratio in the subcutaneous small resistance arteries of hypertensive patients with left ventricular hypertrophy. Our retrospective study confirms previous findings obtained in prospective studies with other angiotensin converting enzyme inhibitors. Endothelial function was probably improved by lisinopril therapy.

Haloperidol plasma ‘threshold’ levels for relapse prevention in schizophrenia: a study with haloperidol decanoate

Forty-eight schizophrenic outpatients treated with flexible doses of haloperidol decanoate were followed up in a naturalistic fashion for 3 years with periodic monitoring of clinical symptoms, side effects and haloperidol plasma concentrations. There was no relationship between plasma level and clinical response, however categorical data analysis showed that patients with plasma levels over 4 ng/ml had a significantly reduced relapse rate compared with patients with plasma levels below this plasma ‘threshold’ level. This effect could be observed during the first, second as well as third year of treatment. The relapse rate did not change significantly in relation to time (during years 1, 2, 3), when patients with haloperidol plasma levels below and equal to or over 4 ng/ml were considered separately. In patients with haloperidol equal to or over 4 ng/ml, the variability (measured as coefficient of variation %) in the total scores of SAPS and SANS was lower, indicating a better clinical stability. These data are in fairly good agreement with other literature findings showing that an indiscriminate dose reduction strategy during long-term treatment of schizophrenic disorders with haloperidol decanoate should be discouraged, since it leads to an increase in the relapse rate. Before deciding about a dose reduction, clinicians should take into careful consideration some clinically relevant variables (i.e. frequency of previous relapses, severity of symptoms, iatrogenic depression, risk for development of extrapyramidal side effects) for each patient. A better clinical stability during treatment with haloperidol decanoate can be obtained when plasma ‘threshold’ levels for response are reached.

CAN COST EFFECTIVENESS OF GROWTH HORMONE BE IMPROVED?

Top of pageAbstract We report the growth velocities of all growth hormone-deficient, pre-pubertal patients treated since onset of therapy with a daily dose of recombinant hGH in our clinic. As illustrated in the table below, our patients attained adequate growth velocities while treated with approximately 60% of the dose most widely used. The study population consisted of 20 pre-pubertal patients, 9 of whom had “organic” and 11 of whom had idiopaihic etiologies of their growth hormone deficiency. Average age at onset of treatment was 6.6 years. Average bone age maturation during treatment was 1.2 years for each year of chronological age. The growth velocities in the second and third year of treatment did not decline from those of the first year. Of note, Ranke and Guilbaud (Acta Paedtr. Scand [Suppl] 379: 109-115, 1991) have found that high first year doses of hGH have a negative influence on second year growth. Since both cost and metabolic side effects increase with the magnitude of the hGH dose, current recommended dosages may need to be reviewed.

Adverse reactions to ivermectin treatment for onchocerciasis. Results of a placebo-controlled, double-blind trial in Malawi

A three-year placebo-controlled, double-blind trial involving 7148 persons was conducted to determine adverse reactions to ivermectin given annually for treatment of onchocerciasis by mass distribution. Musculoskeletal pains, oedema of the face or extremities, itching and papular rash were statistically associated with ivermectin treatment in the first year. In the second year of treatment these reactions were less frequently reported, although still more prevalent in ivermectin recipients. During the third year of treatment all persons received ivermectin. Persons who had missed ivermectin treatment in the second year did not have significantly more adverse reactions after treatment in the third year. Those who had received placebo during the first 2 years reported some adverse reactions more frequently following ivermectin than did those who had received ivermectin from the beginning of the study. Oedema was the adverse reaction of greatest concern to patients and this involved the face most commonly. A single episode of bullous skin lesions developed in 5 persons who had received ivermectin. These lesions did not reoccur with subsequent treatment. No episode of hypotension after treatment was observed.

Third-year evaluation of host-targeted permethrin for the control of Ixodes dammini (Acari: Ixodidae) in southeastern Connecticut.

The impact of commercially available permethrin-treated cotton balls targeted at Ixodes dammini Spielman, Clifford, Piesman & Corwin on white-footed mice, Peromyscus leucopus, was evaluated for a third year at five residential sites in south-central Connecticut. Each site had been treated twice each year from 1989 through 1991 with sufficient product to treat 0.4 ha of mouse habitat, and results were compared with five untreated sites. There were no significant differences in the number of host-seeking nymphs or adults of I. dammini, the vector of the Lyme disease spirochete, Borrelia burgdorferi, in 1991 between the treated and untreated sites. The rate of infection in host-seeking nymphs by B. burgdorferi at the treated sites (15.3% of 600) was comparable with that at the untreated sites (16.5% of 454). Only 16.3% of 86 P. leucopus captured at the treated sites were infested with I. dammini subadults compared with 66.9% of 118 from the mice at the untreated sites. The impact of permethrin-treated cotton during the third year of treatment was similar to that observed for the first 2 yr and did not reduce the risk of exposure to spirochete-infected, host-seeking nymphs and adults of I. dammini.

When the going gets rough ... difficult points in treatment: Identification, exploration and working through (panel)

This paper is a summarized report of a panel presentation made by three analysts on the topic of resolving difficult points in the treatment of three of their patients through the understanding of countertransference and transference issues. The first analyst presented a case in which a stalemate was broken by addressing three different kinds of countertransference. The second presenter addressed an impasse in the treatment of her drug addicted male patient which was caused by positive transference and countertransference. The third analyst discussed the resolution of a critical point in the third year of treatment of a female patient which was uncovered by addressing the parameter of appointment scheduling. The candor and honesty of these presentations takes the reader into the heart of practice issues and illustrates how stalemates are resolved and treatment deepened. Audience reaction indicated that more such presentations which illustrate how analysts really work would be welcome.

Treatment of Postmenopausal Osteoporosis with Calcitriol or Calcium

Osteoporosis is a common problem whose management is controversial. To evaluate the efficacy and safety of calcitriol (1,25-dihydroxyvitamin D3) in the treatment of postmenopausal osteoporosis, we conducted a three-year prospective, multicenter, single-blind study in 622 women who had one or more vertebral compression fractures. The women were randomly assigned to receive treatment with calcitriol (0.25 micrograms twice a day) or supplemental calcium (1 g of elemental calcium daily) for three years. New vertebral fractures were detected by means of lateral roentgenography of the spine each year, and calcium absorption was measured in 392 of the women. The women who received calcitriol had a significant reduction in the rate of new vertebral fractures during the second and third years of treatment, as compared with the women who received calcium (second year, 9.3 vs. 25.0 fractures per 100 patient-years; third year, 9.9 vs. 31.5 fractures per 100 patient-years; P less than 0.001). This effect was evident only in women who had had five or fewer vertebral fractures at base line (second year, 5.2 vs. 25.3 fractures per 100 patient-years; third year, 4.2 vs. 31.0 fractures per 100 patient-years; P less than 0.0001). The groups also differed significantly in the number of peripheral fractures; 11 such fractures occurred in 11 women in the calcitriol group, whereas 24 occurred in 22 women in the calcium group (P less than 0.05). There was no significant difference between the groups in the incidence of side effects requiring withdrawal of treatment (8.6 percent in the calcitriol group vs. 6.5 percent in the calcium group). Continuous treatment of postmenopausal osteoporosis with calcitriol for three years is safe and significantly reduces the rate of new vertebral fractures in women with this disorder.

Growth hormone treatment of growth failure secondary to total body irradiation and bone marrow transplantation.

Growth hormone was given to 13 children (nine boys, four girls) with acute leukaemia who had undergone treatment with cyclophosphamide and total body irradiation before bone marrow transplantation. Mean age at total body irradiation and bone marrow transplantation was 9.0 years (range 3.7-15.8). Endocrinological investigation was carried out at a mean of 2.0 years (range 0.4-4.0) after bone marrow transplantation. Peak serum growth hormone responses to hypoglycaemia were less than 10.0 micrograms/l (less than 20.0 mU/l) in 10, 10.5 micrograms/l (21.0 mU/l) in one, greater than 16.0 micrograms/l (greater than 32.0 mU/l) in two patients. Mean age of the patients at the start of growth hormone treatment was 12.2 years (range 5.8-18.2). The mean time between total body irradiation and bone marrow transplantation and the start of growth hormone treatment was 3.2 years (range, 1.1-5.0). Height velocity SD score (SD) increased from a mean pretreatment value of -1.27 (0.65) to + 0.22 (0.81) in the first year, +0.16 (1.11) in the second year, and +0.42 (0.71) in the third year of treatment. Height SD score (SD) changed only slightly from -1.52 (0.42) to -1.50 (0.47) in the first year, to -1.50 (0.46) in the second year, and -1.74 (0.92) in the third year. Measurement of segmental proportions showed no significant increase in subischial leg length from -0.87 (0.67) to -0.63 (0.65) in the first year, to -0.58 (0.70) in the second year, and -0.80 (1.14) in the third year of treatment. Our data indicate that children who have undergone total body irradiation and bone marrow transplantation respond to treatment with growth hormone in either of two dose regimens, with an increase in height velocity that is adequate to restore a normal growth rate but not to 'catch up', and that total body irradiation impairs not only spinal but also leg growth, possibly by a direct effect of irradiation on the epiphyses and soft tissues.

Influence of Repeated Applications of 2,4-D on Yield and Juice Quality of Concord Grapes (Vitis labruscana)

In two field experiments over a 4-yr period, 2,4-D amine applied up to four times per year from late April to early June at 2.5, 10, and 25 ppmw produced a wide range of symptoms on ‘Concord’ grapes. When 2,4-D symptoms in July were severe, yields were reduced by as much as 85%. However, when 2,4-D symptoms in July were slight (less than 2 on a 0 to 6 visual scale), grape yields were not reduced. A second-order polynomial described well (R2= 0.92) the relationship between symptoms and grape yield. Symptoms of 2,4-D on grape leaves did not persist beyond the year of treatment, although grape yields did not recover fully until the second year after the last 2,4-D treatment In the first year of 2,4-D treatments, low grape yields were correlated with reduced weight and number of berries per cluster. In the second and third year of treatment, low grape yields were correlated with fewer clusters per shoot in addition to lower cluster weight and fewer berries per cluster. When 2,4-D was applied one year only, soluble solids in the grape juice were reduced as much as 9%, although reductions were not related to severity of foliar symptoms. When 2,4-D was applied for three consecutive years, soluble solids in the juice were consistently higher in grapes with moderate to severe 2,4-D symptoms. There were no consistent effects of 2,4-D on juice color or titratable acidity. The pH of fresh juice was increased slightly by 2,4-D with the maximum being 10% after 3 yr of consecutive treatments. In the first subsequent non-treatment year after 3 yr of 2,4-D treatments, juice quality was similar to the quality of nontreated grapes. At a detection limit of 0.05 ppmw, 2,4-D was not detected in the harvested grapes. Based on the results of these experiments, grapes with slight 2,4-D symptoms would not be expected to have reduced yields or reduced juice quality.

Recombinant Human Growth Hormone Treatment of Children with Chronic Renal Failure: Update 1990

Nine children with growth retardation due to chronic renal failure were treated with recombinant human growth hormone (rhGH) for 12-36 months. Results demonstrated a significant increase in height velocity at each 12-month interval compared with that achieved during the year prior to treatment. However, the increase in bone age was no greater than the increase in chronological age during the period of treatment. The mean calculated creatinine clearance did not decrease significantly during the 36 months of treatment; however, two patients required institution of dialysis at 18 and 30 months following initiation of rhGH treatment. There was no exacerbation of the glucose intolerance of uraemia following treatment. Currently, 6 of 7 patients who have been treated for more than 24 months have achieved sufficient acceleration in height velocity to attain an SDS of less than -2.00 and are above the 5th centile for chronological age on the growth curve. These updated data indicate that rhGH treatment of growth retarded children with chronic renal failure continues to result in accelerated height velocity during the second and third year of treatment, and demonstrate the potential for such children to achieve normal stature (+/- 2 SD) for chronological age despite the continued presence of chronic renal failure.

Effects of 3 Years of Growth Hormone Therapy in Short Normal Children

The effect of 3 years of growth hormone (GH) treatment on growth rate, predicted height, carbohydrate and metabolic status, and thyroid function was studied in 16 short prepubertal children growing with a normal pretreatment growth rate. The height velocity SDS increased from a pretreatment value of -0.44 +/- 0.33 (mean +/- SD) to a value of +2.20 +/- 1.03 during the first year of treatment. It was maintained at a value above zero over the subsequent 2 years. By the end of the third year of treatment, the predicted final height had increased by 6.8 cm in the boys and by 4.2 cm in the girls (p less than 0.001 and p less than 0.01, respectively). Increasing the dose of GH on a body surface area basis reduced the deceleration of growth observed during the second year of treatment, leading to an improvement in height prognosis over that year. Glucose homoeostasis was achieved initially at the expense of an elevation in fasting serum insulin concentration, but this had returned to pretreatment values by the end of the second year of therapy.

Traitement des pubertes precoces par un agoniste du LH-RH (D-Trp6-LH-RH)

Chronic administration of luteinizing hormone-releasing hormone (LH-RH) is currently considered as the most appropriate therapy of precocious puberty. A delayed release preparation of D-Trp-6-LH-RH (Décapeptyl ® in microcapsules) designed to release the agonist for 28 days after intramuscular injection of 60 μg/kg body wt was given to 12 boys and 26 girls with precocious puberty. Plasma levels of gonadotropins and sex steroids were suppressed to prepubertal levels within 3 weeks, whilst pituitary responses to LH-RH test were almost abolished within 7 weeks. A significant improvement of secondary sex characteristics, as well as gonadal size, was observed within 6 months. Growth velocity (cm/yr, mean ± SD) was reduced in boys and girls from 9.9 ± 3.4 and 9.6 ± 3.3 respectively before treatment to 5.2 ± 1.0 and 5.3 ± 1.3 respectively during the third year of treatment. The mean ratio height age/bone age was just before treatment 0.91 in boys and 0.88 in girls and increased to 1 after 3 yr of treatment. This study shows that Decapeptyl in microcapsules induced a prolonged suppression of gonadal function and a relative blockade of bone maturation. A significant improvement of adult height relative to the effect of conventional treatments should be expected.

Seasonal Soil Waterlogging Influences Water Relations and Leaf Nutrient Content of Bearing Apple Trees

Abstract Bearing ‘Macspur’/M.26 apple trees (Malus domestica Borkh.) were grown in plastic-lined basins under orchard conditions. Four treatments were imposed in each of 3 years consisting of controls and 6-week periods of soil waterlogging in the spring, summer, or fall. Stomatal conductance (gs), transpiration rate (E), leaf water content (LWC), and stem water potential (ψstem) were measured at the end of each waterlogging period. Stomatal conductance was significantly reduced by spring and summer waterlogging, but not by fall waterlogging. Reduction in g, and E generally increased over years. Stem water potential after spring and fall waterlogging averaged 8% less negative than controls in all 3 years, with no trend over the 3 years. In contrast, of summer-waterlogged trees was unaffected, 45% was more negative, and 31% less negative than controls in the first, second, and third year of treatment, respectively. Annual reductions in growth and yield due to the waterlogging treatments were related to decreased gs and to both negative and postive changes in ψstem. Leaf levels of N, P, K, and Cu measured in July were reduced only by summer waterlogging, with no trend in reponse over years.

Treated blood pressure, rather than pretreatment, predicts survival in hypertensive patients. A report from the DHSS Hypertension Care Computing Project (DHCCP).

A group of hypertensive patients (n = 2855) with an untreated diastolic blood pressure greater than or equal to 90 mmHg were followed in the Department of Health and Social Security (DHSS) Hypertension Care Computing Project (DHCCP) for periods of up to 10 years. During this period 191 of these patients died. Survival was assessed in relation to pretreatment blood pressure levels and blood pressure achieved during treatment. The blood pressure during treatment was a useful predictor of mortality, but the pretreatment pressure was not. After adjusting for age, mortality was particularly related to the height of the systolic and diastolic blood pressure during the second and third years of treatment. In men, age-standardized 5-year mortality was greater than 10% in those with a first year treated systolic pressure greater than 150 mmHg or a diastolic pressure greater than 95 mmHg. In women, age standardized 5-year mortality was greater than 5% with the same levels of treated blood pressure. The longest survival occurred with the lowest bands of treated pressure, i.e. systolic pressure less than 140 and diastolic pressure less than 90 mmHg; the 5-year mortality being less than 7% in men and less than 3% in women. Treated systolic and diastolic pressures were useful in predicting death from ischaemic heart disease (IHD).

Dose-response relationship in the treatment of hypopituitary children with human growth hormone: a retrospective survey.

During the past 15 years, dose-response studies of hGH have been limited to prepubertal patients with complete somatotrophic deficiency, who have usually been treated with hGH three times/week within a dose range of 10-40 IU/kg/year. In such studies a weak positive correlation has been found (r = 0.429, p less than 0.001) with marked important individual variations. Very few or no data have been published regarding the dose-response relationship after the first year of hGH treatment, or when the dose is increased because the growth rate is waning, or during puberty. The present paper reports some data on these issues. A group of 32 young hGH deficient children, whose bone age was 0-4 years, was followed up for at least 3 years with hGH given intramuscularly three times weekly at doses of 12-48 IU/kg/year (mean, 25 +/- 9 IU/kg/year - i.e. approximately 0.15 IU/kg/injection). A dose-response relationship existed during the first year but not during the following 2 years nor for the height gain obtained at the end of the third year of treatment. The results of an increase of the dose of hGH by 33-66% in 13 prepubertal hGH deficient children whose growth rate had decreased after 2-5 years of treatment were fair in 6, limited in 4 and absent in 3, and did not relate to the extent of dose increase. However, this series is too small to allow definite conclusions. The growth rate of 67 adolescents with complete hGH deficiency and normal spontaneous puberty was close to the normal mean in the 45 males but much less in the 22 females. Although the least favourable results came from cases with post-radiotherapy hypopituitarism, the mean total pubertal growth spurt in patients with idiopathic hGH deficiency was also below the average, mainly in the girls, and with a large range of individual variation. An important fact was that bone age increased more than height age or chronological age in these hypopituitary pubertal patients. No dose-response relationship was found in this group, within a limited range of doses (40 patients receiving 16-20 IU/kg/year injected three times weekly, 19 receiving less than 16 IU/kg/year and 8 receiving more than 20 IU/kg/year). It may be concluded that in prepubertal hypopituitary children, hGH at a dose of approximately 20 IU/kg/year at the onset of treatment is probably appropriate. The lack of a dose-response relationship after the first year of treatment suggests that higher initial doses should be avoided.(ABSTRACT TRUNCATED AT 400 WORDS)