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A case of 5α-reductase deficiency is described who presented clinically as primary amenorrhoea. Plasma levels of the two isomers resulting from the 5α-reduction of testosterone provide a simple method for diagnosing this condition. An intermediate abnormality was found in other family members consistent with the heterozygous state.

Summary Isometric exercise causes a substantial rise in BP in normotensive and untreated hypertensives. The authors studied the isometric hand-grip test in 5 groups of treated hypertensives, namely β-blockers, β-blockers + diuretics, β-blockers + diuretics + vasodilators, alpha-methyldopa alone and labetalol. All groups showed a substantial rise in both systolic and diastolic BP, and the increments in BP differed little from that in normotensives. Some patients, despite multiple therapy, achieved increments of up to 60 mmHg from rest. Treated hypertensives with cardiac and cerebro-vascular disease are at risk performance isometric exercise.

1. In 10 normal subjects water immersion to the neck at 35°C produced a highly significant natriuresis and diuresis. 2. Urinary prostaglandin E levels did not change significantly throughout immersion. 3. During the diuresis of water immersion a suppression of urinary antidiuretic hormone occurred.

1. We studied 12 normotensive non-ketotic diabetic patients during poor metabolic control, with sustained hyperglycaemia, and again, after an interval of 3 weeks, when metabolic control was improved. On each occasion we measured blood pressure, total exchangeable sodium, plasma volume, transcapillary escape rate of albumin, and plasma concentrations of angiotensin II and aldosterone. 2. With improved diabetic control there was a small but significant fall in arterial pressure. Total exchangeable sodium was normal when control was poor but rose significantly to above normal with improved control. 3. Plasma volume also rose significantly with improved control, and the transcapillary escape rate of albumin fell and the intravascular mass of albumin rose. 4. Plasma angiotensin II and aldosterone concentrations were significantly above normal during poor metabolic control, but fell to normal with improved control. 5. These findings indicate a resetting of the relationship between blood pressure and exchangeable sodium when diabetic control improves. The association between exchangeable sodium and concentrations of angiotensin II and aldosterone also appears altered in diabetic patients. These changes associated with varying metabolic control must be considered when studying cardiovascular disease in diabetic patients.

1. Thermoneutral water immersion produces a physiological increase of thoracic blood volume, raises central venous pressure and increases urinary sodium excretion by a hitherto ill-understood mechanism. We have investigated whether this enhanced sodium excretion could be mediated by the recently discovered natriuretic factor, atrial natriuretic peptide (ANP). 2. During water immersion there was a highly significant (P < 0.001) twofold increase of the mean plasma ANP concentration and a doubling of the mean urinary sodium excretion. Both were unchanged during the control experiments. 3. These results are consistent with the hypotheses (a) that ANP is released into plasma in response to central blood volume expansion and (b) that it functions as a natriuretic hormone in normal man under physiological conditions.

The optical spectra of the alkaline‐earth fluorides doped with Ge3+ (MeF2:Gd3+, where Me represents Ca, Sr, or Ba) at octahedral sites are analyzed to determine the effect of lattice size on the cubic crystal‐field parameters. The point‐charge model predicts a linear dependence of the first‐order crystal‐field splitting on B04 which in turn varies inversely with the Gd3+–F− separation to the fifth power (R−5). The slopes of plots of log b40 vs logR yield values of − 2.1, − 2.7, and 0 for the 8S7 / 2, 6P7 / 2, and 6P5 / 2 multiplets, respectively. This apparent discrepancy is resolved by the inclusion of crystal‐field interactions in all orders between the 8S and 6(P, I, D) multiplets. The log(A40〈r4〉) vs logR plot is found to be − 1.8 which agrees with the EPR result to within experimental error. The disagreement with the point‐charge model is examined.

The energy E of a polar diatomic molecule in a uniform external electric field F is expressible as E=E0−piFi−(2 !)−1αijFiFj−(3 !)−1βijkFiFjFk−···, where E0 is the energy of the molecule out of the field, pi is the permanent dipole moment, αij is the dipole polarizability tensor, and βijk is the first hyperpolarizability tensor. In this work, theoretical results are presented for αij and βijk for some diatomic molecules. The zero‐order wavefunctions used in these calculations are extended basis Hartree—Fock functions of the Roothaan type. The values of αij and βijk are obtained via an uncoupled Hartree—Fock scheme. The results for αij are compared with previous uncoupled and coupled self‐consistent‐field calculations. The present scheme improves upon the previous uncoupled calculations and compares favorably with the results obtained in self‐consistent‐field calculations. Finally, these polarizabilites and hyperpolarizabilites are found to be quite sensitive to the quality of the zero‐order wavefunctions.

The existence of a separate cubic phase RF3:3(MeF2), which provides a cubic symmetry site with local charge compensation for a tripositive rare earth ion in a fluorite lattice, is examined in order to explain the increase in cubic sites with increasing rare earth impurity concentration. An expression for the minimum concentration at which such a phase would be stable is presented. For the case of SrF2:Ge3+ or SrF2: (Gd3+, Ce3+) a calculation estimates that such a phase could form at 0.36% total rare earth impurity concentration.

The energy levels of ${\mathrm{Gd}}^{3+}$ in the cubic crystal field of Ca${\mathrm{F}}_{2}$ are calculated using free-ion vectors computed with spin-other-orbit and spin-spin interactions included. The ${{B}_{0}}^{4}$ and ${{B}_{0}}^{6}$ coefficients are fitted to the experimental $^{6}P_{\frac{7}{2}}$ and $^{6}P_{\frac{5}{2}}$ splittings. Using only the 18 ${M}_{J}$ components of the $^{6}P$ free-ion levels as a basis, values of ${{B}_{0}}^{4}=\ensuremath{-}2270.79$ ${\mathrm{cm}}^{\ensuremath{-}1}$ and ${{B}_{0}}^{6}=730.65$ ${\mathrm{cm}}^{\ensuremath{-}1}$ are obtained. This calculation gives a mean error of 8 ${\mathrm{cm}}^{\ensuremath{-}1}$ between calculated and experimental levels. To improve the quality of the fit, the basis was extended to the 134 ${M}_{J}$ components of the $^{8}S$ and $^{6}(P, I, D)$ free-ion levels. For this calculation, ${{B}_{0}}^{4}=\ensuremath{-}2160.0$ ${\mathrm{cm}}^{\ensuremath{-}1}$ and ${{B}_{0}}^{6}=792.85$ ${\mathrm{cm}}^{\ensuremath{-}1}$, and the mean error is reduced to about 0.5 ${\mathrm{cm}}^{\ensuremath{-}1}$. This calculation predicts the correct order of the ground-state levels and gives an over-all ground-state splitting of about one-half the experimental splitting. The calculated ground-state splitting does not change when the basis is further extended to include all higher free-ion levels containing $^{6}G$ character. We conclude that a good crystal-field calculation for ${\mathrm{Gd}}^{3+}$ is possible and depends strongly on the quality of the free-ion states.

In this report we describe a patient who produced the clinical and laboratory features of Cushing's syndrome by injecting himself for many months with hydrocortisone. Factitious Cushing's syndrome is a variant of the Münchausen syndrome and should be considered if tests used to establish the diagnosis of Cushing's syndrome appear incongruous particularly in subjects with access to medical intelligence and drugs.

The hormonal and renal response to volume expansion, produced by water immersion for 4 h, was studied in 14 insulin-dependent diabetic subjects (seven without complications, seven with autonomic neuropathy) and in 14 age-and-sex-matched normal control subjects. The diabetic subjects showed an impaired natriuretic response to volume expansion (total amount of sodium excreted 21 mmol compared to 39 mmol in normals, P less than 0.01) but the response did not differ in those with and without autonomic neuropathy. There was no significant difference in the suppression of plasma renin or aldosterone during immersion in either group. Plasma catecholamines suppressed on immersion in all groups. Basal values were lowest in the group with autonomic involvement. Atrial natriuretic peptide levels showed a twofold rise (from 4.8 to 9.6 pmol/l, P less than 0.01) on immersion. There was no significant difference in the levels of this hormone between diabetic patients and normal subjects or between those diabetics with and those without autonomic neuropathy. The present study confirms that diabetic subjects retain sodium avidly during volume expansion. This enhancement cannot be ascribed to any measurable difference in the levels of circulating hormones known to be involved in natriuresis and is not influenced by the presence of autonomic neuropathy.

Twenty-seven diabetic patients with clinical evidence of neuropathy were investigated by foot radiography, two-phase bone scintigraphy, biothesiometry and cardiovascular autonomic function testing. Typical signs of diabetic osteopathy on radiography were found in 10 subjects (37%), the degree of radiographic abnormality correlating with the severity of neurological impairment. Furthermore, all diabetics with evidence of severe neuropathy showed some evidence of osteopathy on foot radiographs. In all 10 cases of diabetic osteopathy diagnosed radiographically, abnormalities were shown on scintigraphy. In addition, five other patients showed scintigraphic abnormalities, without corresponding changes on radiography, and in this group the neurological impairment was less severe. Although confirmatory longitudinal studies are necessary, it seems likely that the earliest changes of diabetic neuropathic osteopathy may thus be recognized on bone scintigraphy, at a time when conventional radiographs are normal. This stage of diabetic osteopathy is associated with a lesser degree of neurological impairment.

Available evidence indicates that poor metabolic control and raised blood pressure each accelerate the development of diabetic microangiopathy. Microangiopathy is associated with excess albumin deposition in capillary basement membranes and it has been suggested that increased extravasation of plasma constituents may lead to basement membrane thickening. We measured the transcapillary escape rate of albumin, an indicator of the rate of extravasation of intravascular albumin from the circulation per unit time, following intravenous injection of 125I-human serum albumin. We examined the independent effects on the transcapillary escape rate of albumin of non-ketotic poor metabolic control, hypertension and microangiopathy. We studied non-diabetic control subjects and diabetic patients, initially when in non-ketotic poor metabolic control and again when control had been improved. We also studied normotensive well-controlled diabetic patients without microangiopathy, normotensive well-controlled diabetic patients with microangiopathy, hypertensive well-controlled diabetic patients without microangiopathy and hypertensive well-controlled diabetic patients with microangiopathy. The transcapillary escape rate of albumin was similar in non-diabetic control subjects (5.5 +/- 0.7%/h) and in both Type 1 (5.3 +/- 1.2%/h) and Type 2 (5.1 +/- 0.6%/h) normotensive diabetic patients without long-term complications. During poor metabolic control the transcapillary escape rate of albumin was significantly higher than in non-diabetic subjects (8.8 +/- 0.8%/h and 5.5 +/- 0.7%/h respectively, p less than 0.01). With improved control values fell significantly to 6.3 +/- 0.9%/h (p less than 0.02), not significantly different from control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Observations demontrant chez certains patients diabetiques une balance hydrique et sodee positive avant l'apparition de ces complications, en rapport avec une alteration de la permeabilite capillaire et des anomalies nephrologiques

The epidemiologic link between obesity and hypertension is more clearly emerging to be one between insulin resistance and hypertension. Relative insulin resistance occurs not only in obese hypertensive patients but also in non-obese lean essential hypertensive patients. Although insulin has complex actions on the circulation, plausible mechanisms by which insulin might raise blood pressure include renal sodium retention and stimulation of the sympathetic nervous system. However, the evidence that insulin can actually raise blood pressure in the long-term is lacking. Since hypertension does not develop in all obese or insulin-resistant subjects, the relationship must be modulated by other genetic or environmental factors. Obesity, diminished physical conditioning, aging, and diabetes are ubiquitous contributors to relative insulin resistance and all are associated with a tendency for blood pressure to rise. Conditions and agents associated with acquired insulin resistance and secondary forms of hypertension include pregnancy, oral contraceptives, acromegaly, and glucocorticoids. Although type 2 non-insulin-dependent diabetes is a state of increased insulin resistance, hypertension is partly sustained by secondary renal mechanisms. Future research should identify the genetic and environmental determinants of insulin resistance in hypertension and utilize these in therapy.

Autonomic function was investigated by tests of heart rate variation in 506 unselected insulin-dependent diabetics aged 12 to 85 years. Heart rate variability was measured by a computerised technique during rest and in response to a single deep breath, the Valsalva manoeuvre and standing. Changes in heart rate were compared with age-related normal ranges derived from 310 non-diabetic control subjects aged 18 to 87 years. Heart rate responses were found to be below the 5th centile control value in 13 to 23 per cent of diabetics. Impaired heart rate variability occurred more frequently in response to a single deep breath than to the other procedures. Results from all four procedures were combined in each subject to give an 'autonomic score', varying from 0 to 4. This score was greater than 1 in only five of 310 (1.6 per cent) non-diabetic control subjects. A score of 2 or more was therefore defined as abnormal and indicative of cardiac autonomic denervation. Abnormal autonomic scores were found in 84 diabetics (16.6 per cent). In diabetic subjects the autonomic score correlated most closely with heart rate variability at rest and in response to a single deep breath. Abnormal autonomic scores correlated significantly with duration of diabetes (p less than 0.0001) but not with age (p = 0.06). The frequency of abnormal autonomic scores was greatest in diabetics aged 40 to 49 years (24.5 per cent) and those with diabetes of 20 or more years duration (30.7 per cent).

Diabetic ketoacidosis is usually associated with marked secondary hyperaldosteronism. Plasma levels of renin, angiotensin II, and aldosterone are markedly raised before treatment in most patients, with values falling rapidly toward normal as metabolic control is restored. In a few patients, mostly those with long-term complications of diabetes, plasma levels of renin, angiotensin II, and aldosterone before treatment remain within the normal range. In moderately hyperglycemic patients who have glycosuria but not ketonuria, plasma levels of all three substances are significantly higher than when control is improved. Occasionally, moderately hyperglycemic patients have mild secondary hyperaldosteronism. Improved metabolic control in such patients causes a rise in plasma volume and a rise in total exchangeable sodium, the latter to levels significantly above normal. Plasma catecholamine levels are markedly elevated in diabetic ketoacidosis, probably as a consequence of the ketoacidotic state. In nonketotic patients with moderate hyperglycemia, basal plasma norepinephrine levels are normal; catecholamine responses to exercise may be exaggerated, however. Epidemiological and animal studies suggest a relationship between blood pressure and blood glucose levels. There are few clinical studies of the effects of altering metabolic control of diabetes on blood pressure, and this is an important area for further study.

Autonomic function was investigated by tests of heart rate variation in 506 unselected insulindependent diabetics aged 12 to 85 years. Heart rate variability was measured by a computerised technique during rest and in response to a single deep breath, the Valsalva manoeuvre and standing. Changes in heart rate were compared with age-related normal ranges derived from 310 non-diabetic control subjects aged 18 to 87 years. Heart rate responses were found to be below the 5th centile control value in 13 to 23 per cent of diabetics. Impaired heart rate variability occurred more frequently in response to a single deep breath than to the other procedures. Results from all four procedures were combined in each subject to give an ‘autonomic score’, varying from 0 to 4. This score was greater than 1 in only five of 310 (1.6 per cent) non-diabetic control subjects. A score of 2 or more was therefore defined as abnormal and indicative of cardiac autonomic denervation. Abnormal autonomic scores were found in 84 diabetics (16.6 per cent). In diabetic subjects the autonomic score correlated most closely with heart rate variability at rest and in response to a single deep breath. Abnormal autonomic scores correlated significantly with duration of diabetes ( p

Immersion in water in spas has been practised for centuries and has many proponents. Despite fierce debate about its efficacy there has been little scientific evaluation of the effect of immersion in mineral waters. Eight normal subjects were immersed in Bath spa water for two hours and the renal, haematological, and cardiovascular responses were compared with those in the control periods before and after immersion. Significant, twofold diuresis and natriuresis, 5% haemodilution, and a 50% increase in cardiac index were observed in subjects immersed, sitting, in Bath spa water at 35 degrees C. These changes may constitute part of the scientific rationale for spa treatment in many states of disease.

Five diabetic patients had acute visual impairment due to papilloedema, which was bilateral in two patients. The clinical features and subsequent course were compatible with ischaemic optic mononeuropathy presumed to result from ischaemia in a posterior ciliary artery. This cause should always be considered in the differential diagnosis of papilloedema in a diabetic patient to avoid the instigation of inappropriate and invasive investigations. In general the condition has a good prognosis.

The purpose of this report was to examine the influence of nephropathy and sodium balance on the orthostatic blood pressure and renin (PRA) responses of diabetic patients with orthostatic hypotension (OH). Four groups of similar age were studied: non-diabetic controls (n = 7), diabetics free of OH and other diabetic complications (n = 7), diabetics with OH but no nephropathy (n = 6), and diabetics with OH and nephropathy (24-hr urine protein greater than 400 mg, n = 6). In the diabetics with OH, mean systolic BP fell 49 and 47 mmHg on standing in the groups without and with nephropathy respectively. NaE (expressed as % predicted by leanness index) differed significantly between the groups and was 100 +/- 2 in the controls, 109 +/- 3 in the diabetics free of complications, 102 +/- 2 in the diabetics with OH free of nephropathy, and 121 +/- 6 in diabetics with OH and nephropathy (p less than 0.05 compared to diabetics with OH and no nephropathy). Both supine (r = 0.68, p less than 0.02) and upright (r = 0.78, p less than 0.005) mean arterial pressure correlated with NaE in diabetics with OH but not in the other groups. Upright PRA was greatest in diabetics with OH but no nephropathy and lowest in diabetics with OH and nephropathy. These findings suggest that the presence of nephropathy markedly influences sodium balance in diabetics with OH and has a substantial influence on orthostatic BP and PRA responses.

We report a patient with long standing untreated ankylosing spondylitis, who presented with a malignant lymphoma and simultaneously developed systemic sclerosis. We are unaware of previous reports associating these conditions.

In ten normal subjects thermoneutral neck-out water immersion produced a highly significant natriuresis and diuresis mediated via an induced central hypervolaemia. During immersion suppression of plasma noradrenaline and adrenaline was observed but no change occurred in plasma dopamine levels. No correlation was found between the suppression of noradrenaline and the diuresis and natriuresis. The reduction in plasma noradrenaline observed may reflect a widespread diminution of sympatho-adrenal activity during water immersion. This reduction could be a consequence of the cardiovascular changes of immersion and may not be directly involved in the mechanism of the renal response.

This report summarizes the progress achieved in the von Karman Gas Dynamics Facility (VKF) of the Arnold Engineering Development Center (AEDC), Air Force Systems Command (AFSC) to (1) improve the reconstruction process of holographic results, (2) develop diffuse, three-dimensional holography for use in the wind tunnel, and (3) prepare a data reduction program for converting interferometric results into meaningful static density distributions of a nonsymmetrical flow field. The report also contains some recommendations to make holography a more practical technique for recording optical results in the adverse environment existing around large supersonic and hypersonic wind tunnels.

In a double-blind placebo-controlled trial the effect of Sorbinil (250 mg daily) on diabetic neuropathy was examined. After a 2-month run-in placebo period (with three major assessments) 21 patients were randomized to Sorbinil and 10 to placebo, and all were studied for a further 12 months with neurophysiological measurements at 3-month intervals of nerve conduction velocity in multiple nerves, autonomic function tests, vibration thresholds as well as clinical examination and an extensive self-assessment of symptoms. Two subjects on Sorbinil treatment developed a hypersensitivity reaction and were withdrawn. Metabolic control and severity of neuropathy was not significantly different between groups. There were no changes in symptoms as judged by self-assessment scores. No patient entered the trial with neuropathic ulcers but ulceration developed in 4 patients during Sorbinil treatment and in 1 of the placebo group. No beneficial effect of Sorbinil was demonstrated on either the clinical manifestation or on the neurophysiological measurements made in these neuropathic diabetic patients over 12 months of treatment.

Atrial natriuretic peptide (ANP) and the renin-angiotensin-aldosterone system are important regulatory hormones in sodium homeostasis. We have measured these hormones during volume expansion produced by water immersion in diabetic subjects without and with microalbuminuria or frank proteinuria and compared the response with normal controls. Diabetic subjects excreted about half the amount of sodium that was excreted by the normal subjects (39 vs 21 mmol) over 4 h. Diabetic subjects and normal ones showed a twofold rise in ANP during immersion and a marked suppression of both plasma renin activity and aldosterone. There was no difference in the hormonal response between diabetic and normal subjects or between those diabetic subjects with and those without incipient (microalbuminurics) or established nephropathy.

A laser interferometer technique is being applied to the characterization of boundary-layer conditions on models in supersonic and hypersonic wind tunnels in the von Kaman Facility at Arnold Engineering Development Center (AEDC). The Boundary-Layer Transition Detector (BLTD), based on lateral interferometry, is applicable for determining the turbulence frequency spectrum of boundary layers in compressible flow. The turbulence, in terms of air density fluctuations, is detected by monitoring interferometric fringe phase shifts (in real time) formed by one beam which passes through the boundary layer and a reference beam which is outside the boundary layer. This technique is nonintrusive to the flow field unlike other commonly used methods such as pitot tube probing and hot-wire anemometry. Model boundary-layer data are presented at Mach 8 and compared with data recorded using other methods during boundary-layer transition from laminar to turbulent flow. Spectra from the BLTD reveal the presence of a high-frequency peak during transition, which is characteristic of spectra obtained with hot wires. The BLTD is described along with operational requirements and limitations.