Grant Gwinup

Relationship of Serum Glucose Concentration to Changes in Refraction

The effect of chronic changes in serum glucose concentration on refraction was studied by increasing the dose of insulin or chlorpropamide in 10 diabetic patients who initially had relatively high glucose concentrations. In every case when serum glucose concentration was reduced the vision became less myopic or more hyperopic. To assess acute changes, 10 diabetics (including four with aphakic eyes) were given an intravenous injection of glucose. In patients with intact lenses the vision became more myopic or less hyperopic following the administration of glucose, but in the aphakic eyes hyperopia increased. It is concluded from both the acute and chronic studies that higher levels of serum glucose concentration produce myopia and lower levels produce hyperopia. Furthermore, these changes are related to changes in the optical properties of the crystalline lens.

Oral Phentolamine in Nonspecific Erectile Insufficiency

Excerpt In patients with erectile insufficiency, it is often difficult to find a definite cause for the problem when clinical vascular disease, neurologic deficiency, obvious psychological problems...

Thyroid function studies in the nephrotic syndrome.

Total serum and urinary thyroxine (T4), triiodothyronine (T3), and thyroxine-binding globulin (TBG) as well as serum free T4, thyroid-stimulating hormone (TSH), and T3 resin uptake (T3RU) were measured in seven patients with the nephrotic syndrome. The nephrotic syndrome was defined by proteinuria exceeding 3 g/24 h. All patients were clinically euthyroid. Most values for total serum T4, free T4, T3, T3RU, TBG, and TSH were within normal limits. However, the mean serum T3 and TBG values were significantly lower in patients compared with the control group. The values (mean +/- 2 SD) for urinary T4 were 24.3 +/- 20.3 in the patient group and 1.5 +/- 0.7 microgram/24 h in the control group. Urinary T3 values for patients and the control group were 2100 +/- 856 and 848 +/- 253 ng/24 h respectively. Urinary TBG was 2.1 +/- 1.8 mg/24 h in the patients and undetectable in the control group. There was no correlation between daily urinary T3 and T4 and urinary TBG. There was a weak correlation between daily urinary protein excretion and urinary T4 (r = 0.5).

Thickness of Subcutaneous Fat and Activity of Underlying Muscles

Abstract In order to subject the concept of spot reduction to critical examination we have compared the circumference and the thickness of subcutaneous fat at specific sites over the right and le...

Cardiovascular changes in video-game players. Cause for concern?

Video games are one of the most popular recreational activities among Americans of all ages, especially teenaged boys and young men. Studies of the health hazards of video-game playing have linked seizures, psychologic disturbances, and other health problems with the games. The study reported here measured changes in blood pressure and heart rate that occurred in 23 young men when they played a video game. The mean systolic blood pressure for the entire group was considerably higher during play than before or after and was significantly higher in novice players than in more skilled players. Heart rate was also significantly higher during play. In view of these results, other cardiovascular changes might be expected to occur during video-game playing. Although the changes reported here were minor, even minor cardiovascular alterations could potentially prove serious in persons with cardiovascular disease.

Oral Administration of D-Ribose in Diabetes Mellitus

Thirty-four subjects were categorized on the basis of their glucose tolerance as normal (thirteen subjects), probable diabetics (six subjects), mild diabetics (five subjects), tolbutamide-responsive diabetics (five subjects) and insulin-dependent diabetics (five subjects). Fifteen grams of d-ribose dissolved in six ounces of water were administered orally to each of the subjects and the effect on serum glucose concentration was measured. The hypoglycemie effect of d-ribose varied in an orderly and progressive manner through the different categories of glucose intolerance. As their glucose intolerance increased in severity, the subjects were significantly less responsive to the blood glucose lowering effect of d-ribose. The serum immunoreactive insulin concentration in response to the oral administration of d-ribose was measured in the normal and mild diabetic subjects. The mild diabetics had a mean peak increase in immunoreactive insulin which was 2.6-fold greater than the normal subjects; however, the insulin concentrations attained were not significant in either group. Thus the insulinogenic response as determined in peripheral venous blood does not account for the differential hypoglycemie effect of d-ribose.

Effect of submaxillary gland extirpation on glucose and insulin tolerance in dogs.

Serum glucose and immunoreactive insulin (IRI) responses to oral glucose and intravenous insulin tolerance tests were determined in dogs before and after total bilateral extirpation of their submaxillary glands. A comparison was made with a control group of dogs before and after sham operations. Postoperative studies were performed at one, three and six months after surgery. No significant differences in glucose and IRI responses were observed between the two groups of dogs, nor upon comparison of the responses within each group at the various periods studied. A review of the literature which relates the salivary glands to diabetes mellitus in both experimental and clinical studies is presented. Our own experience of diabetes mellitus with apparent salivary gland involvement is briefly discussed. It is concluded that despite the relatively frequent association of salivary gland involvement and diabetes mellitus, the role of these glands in the pathogenesis and management of diabetes mellitus is obscure. At this time there is no apparent rationale to the performance of total submaxillary gland extirpation for the treatment of diabetes mellitus.

Cortisol, Valproic Acid, and ACTH Suppression

Excerpt To the editor: We read with interest the article by Koletsky and associates (1) on the cortisol suppression test in patients with elevated adrenocorticotropic hormone (ACTH) levels. In a pr...

A Light Lamentation

CheyneStokes respiration is a common and occasionally serious condition characterized by periodic breathing in which apneas or hypopneas alternate with hyperventilation in a crescendo-decrescendo pattern (1, 2). This respiratory pattern is frequently seen in severe heart failure, in which it may be associated with increased morbidity and mortality (3). CheyneStokes respiration is also seen in preterm infants (4) and may occur in normal persons during sleep and at high altitudes (5). Neurologic causes include stroke, tumors, meningitis, encephalitis, and trauma (6). Potential treatments include oxygen, carbon dioxide, and methylxanthines (3). One week of oral theophylline therapy attenuated nocturnal CheyneStokes respiration in patients with heart failure (7). We describe a patient with profound CheyneStokes respiration associated with several cardiac arrests requiring cardiopulmonary resuscitation. We describe effective, prompt, and sustained elimination of CheyneStokes respiration with intravenous and, subsequently, oral theophylline therapy. Case Report A 48-year-old woman with a 25-year history of diabetes mellitus and resulting retinopathy, neuropathy, and end-stage renal disease (for which she underwent dialysis) was noted to have CheyneStokes respiration. This condition was initially mild but worsened progressively over several years. The CheyneStokes respiration resulted in profound oxygen desaturation accompanied by three cardiopulmonary arrests. The cause of cardiopulmonary arrest was initially unknown and was suspected to be cardiogenic in nature. She experienced her first cardiopulmonary arrest requiring cardiopulmonary resuscitation when she was given midazolam, a benzodiazepine that sometimes causes respiratory depression, for placement of a gastric feeding tube. Her next cardiac arrest occurred 1 year later, toward the end of a hemodialysis session; a third cardiorespiratory arrest occurred the following day. The third episode was preceded by documented oxygen desaturation and ST-segment depression. At that time, her medications were oral acetaminophen (Tylenol, McNeil Consumer Products Co., Fort Washington, Pennsylvania), 650 mg every 4 hours as needed; aluminum hydroxide (Amphojel, Wyeth-Ayerst Laboratories, Philadelphia, Pennsylvania), 30 mL every 4 to 6 hours as needed; oral prochlorperazine (Compazine, SmithKline Beecham, Pittsburgh, Pennsylvania), 10 mg every 6 hours; sodium polystyrene sulfonate (Kayexalate, Sanofi Pharmaceuticals, New York, New York), 15 g/d by feeding tube; oral aspirin, 81 mg/d; oral levothyroxine (Synthroid, Knoll Pharmaceutical Co, Mount Olive, New Jersey), 0.1 mg/d; oral ferrous sulfate, 325 mg every night at bedtime; cisapride (Propulsid, Janssen Pharmaceutica, Titusville, New Jersey), 20 mg every night at bedtime; paroxetine hydrochloride (Paxil, SmithKline Beecham), 10 mg every night at bedtime; and trazodone, 400 mg every night at bedtime. Electrocardiographic changes resolved once the patients oxygenation improved, and myocardial infarction was ruled out. The patient was transferred to our tertiary care center. Her profound CheyneStokes respiration during wakefulness and sleep, which triggered repetitive oxygen desaturation to less than 40%, was noticed only after therapy with supplemental oxygen was discontinued. She was minimally conversant and markedly somnolent during the daytime. The patient weighed 60.2 kg, was 1.58 m tall, and had a body mass index of 24.1 kg/m2. The level of thyroid-stimulating hormone was normal (3.15 IU/mL). Transthoracic echocardiography revealed mild left ventricular hypertrophy with normal left ventricular function and right atrial enlargement. Magnetic resonance imaging of the patients brain revealed an old thalamic lacunar infarction. Cardiac catheterization revealed normal coronary arteries. Polysomnography showed an apneahypopnea index of 35 events/h with 219 total apneas (26 central apneas, 192 hypoventilatory hypopneas, and 1 obstructive apnea). A trial of continuous positive airway pressure was initiated but was not tolerated. The patient was dependent on 2 L of oxygen by nasal cannula, which was only partially effective. Thus, we evaluated the effect of intravenous theophylline on her CheyneStokes respiration. Methods and Results Baseline studies done before initiation of theophylline therapy and after discontinuation of oxygen therapy showed apneic episodes lasting from 20 to 50 seconds with oxygen desaturation to as low as 40% (Figure 1, top). During intravenous infusion of theophylline (0.6 mg/kg per hour, 400 mg in 100 mL of normal saline), CheyneStokes respiration resolved rapidly and completely. While breathing room air, the patient had no apneas or desaturation after approximately 3 mg of the theophylline was infused (theophylline level, 11.4 g/mL) (Figure 1, bottom). Figure 1. Recordings of oxygen saturation ( O Sat ), respiration ( Resp ), and blood pressure ( BP ) before and during intravenous theophylline therapy. Top. Bottom. The patient remained completely free of CheyneStokes respiration for the remainder of that day and night and had no nocturnal desaturation while receiving 1 L of oxygen by nasal cannula. Her daytime somnolence resolved and cognitive function improved, as reflected in part by her ability to initiate and maintain conversations; she could do neither before theophylline therapy. At 7:00 the following morning, her theophylline level was 2.2 g/mL. To determine the threshold for response to theophylline and to exclude any possible effects of the sleep state, we studied the patient at 11:00 the following morning. Supplemental oxygen therapy was discontinued. We obtained continuous measurements of heart rate (by electrocardiography), intra-arterial blood pressure, and central venous pressure. Oxygen saturation was monitored with a pulse oximeter (Nellcor Inc., Hayward, California). Chest wall movement was measured, and electromyography, electroencephalography, and electro-oculography were done. Minute ventilation was measured by using an S430 ventilation measuring system (KL Engineering, Vacumetrics, Inc., Ventura, California) with a precision, ultralight, unidirectional, inertia-compensated turbine flow transducer; during this measurement, the patient breathed through a mouthpiece with a nose clip to ensure exclusive mouth breathing. At baseline, the patients theophylline level was 1.1 g/mL (Figure 2 A). Measurement of arterial blood gases revealed a pH of 7.35, a Paco 2 of 60 mm Hg, and a Pao 2 of 55 mm Hg while breathing room air. Minute ventilation was 2.4 L/min. She manifested repetitive and progressively worsening CheyneStokes respiration with hypercapnia and oxygen desaturation as low as 29%; these symptoms were consistent with her initial clinical presentation. Measurements were not affected by a placebo infusion of saline. Polysomnography showed that desaturations to these levels occurred during both wakefulness and drowsiness, but the patient did not sleep. These desaturations were accompanied by ST-segment depression (Figure 2). No reflex bradycardia was evident during apnea. Figure 2. Recordings of oxygen saturation ( O Sat ), electrocardiography ( ECG ), respiration measurement ( Resp ), and intra-arterial blood pressure ( BP ) at baseline, early during intravenous theophylline administration, and at the end of theophylline ( Theo ) infusion. ABG co o A. o V E B. co o C. We then initiated therapy with theophylline, 0.6 mg/kg per hour. After intravenous infusion of 1.2 mg of theophylline, the patients CheyneStokes respiration began to decrease, with marked attenuation of oxygen desaturation. At this time, her theophylline level was 5.6 g/mL; her arterial blood gas measurements were a pH of 7.36, a Paco 2 of 58 mm Hg, and a Pao 2 of 64 mm Hg; and her minute ventilation was 5.2 L/min (Figure 2 B). When we further infused theophylline to a total dose of 2.4 mg, CheyneStokes respiration resolved completely. At this time, her theophylline level was 11.6 g/mL; her blood gas measurements were a pH of 7.57, a Paco 2 of 32 mm Hg, and a Pao 2 of 76 mm Hg; and her minute ventilation was 6.2 L/min (Figure 2 C). Both the decrease in somnolence and improvement in alertness were remarkable. The patient was discharged to home with orders to take oral theophylline in a sustained-release form (Theo-Dur, Key Pharmaceuticals, Inc., Kenilworth, New Jersey), 200 mg twice daily; this dosage was estimated to maintain a theophylline level of approximately 8 to 12 g/mL. At 18 months of follow-up, she continued to do very well while taking oral theophylline. Her serum theophylline levels were 8.0 g/mL at 3 months, 11.6 g/mL at 12 months, and 11.5 g/mL at 18 months. The patient and her husband reported marked subjective improvement in her quality of life. Discussion Our patient had an unusual presentation of severe CheyneStokes respiration during both wakefulness and sleep; it was not related to congestive heart failure but may have been due to autonomic neuropathy that affected her chemoreceptor function. Central apneas have been reported in patients with type 1 diabetes, particularly in those with autonomic neuropathy (8). These patients also have an absence of the usual bradycardia-tachycardia response to apnea. This combination of central sleep apnea and lack of appropriate autonomic response has been implicated in cardiorespiratory arrest (9). Hypoxic ventilatory depression as part of a generalized central nervous system depression probably contributed to the lack of ventilatory response to progressive hypoxia. CheyneStokes respiration occurred in our patient even during wakefulness and resulted in two spontaneous near-death episodes in 1 month. We cannot exclude the possibility that midazolam therapy, dialysis, and diabetic microangiopathy contributed to her cardiopulmonary arrests. Theophylline has been suggested as a possible therapy for CheyneStokes respiration. Although theophyllines mechanism of act