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Biomedical subjects

W J Riley

Publications and source records attributed to W J Riley.

At least 109 records · Page 6Linked to original sources

The diabetogenic effects of streptozotocin in mice are prolonged and inversely related to age.

Single "subdiabetogenic" doses of streptozotocin (SZ), when given to young male CD-1 mice, produced a delayed onset of hyperglycemia dependent on the dose of SZ and on the age of the mice. The effect was markedly reduced or absent in older mice given the same dose of SZ per kg of body weight. Histologic examination of the pancreas of these animals revealed that SZ induced greater damage to the islets of the young mice compared with older mice. In addition to the characteristic findings of a decrease in insulin-containing cells and an increase in glucagon- and pancreatic polypeptide-containing cells there was evidence of new islet formation. Delayed-onset hyperglycemia was also induced in young inbred DBA/2J, C57BL/KsJ, and SWR/J mice with single SZ doses as well as with alloxan in young CD-1 mice, indicating that the effect was not specific for CD-1 mice not for SZ as the agent inducing beta-cell injury. The induction of beta-cell autoimmunity did not appear to be important in the delayed diabetogenic effect of SZ, since insulitis was rare and followed the onset of hyperglycemia when seen, and islet cell autoantibodies were not found. Rather, SZ induced more beta-cell destruction in young animals than in older mice, and the continued somatic growth of the former suggests that the delayed hyperglycemia was due to an out-growing of a reduced insulin supply. That mild to severe diabetes could be induced by the same dose of SZ/kg, depending only on the age of the mice when SZ was given, may have implications for understanding the apparent heterogeneity of human diabetes mellitus.

Aging↗

Adrenal autoantibodies and Addison disease in insulin-dependent diabetes mellitus.

Stored sera from 466 patients with insulin-dependent diabetes mellitus and from 144 controls were examined for organ-specific antibodies to human adrenal cortex. Adrenal antibodies were found in seven of the patients with IDDM (1.5%) and in one control (0.7%). None of 91 black patients with IDDM had adrenal antibodies. All of the seven patients with adrenal antibodies had other organ-specific antibodies. Three had clinical hypothyroidism and one was thyrotoxic. All of these seven patients had a HLA-B8-bearing haplotype, suggesting that the B8-bearing haplotype confers an extremely high "relative risk" for adrenal autoimmunity in IDDM. Organ-specific autoimmune disease and/or organ-specific antibodies were found in 30% of the first-degree relatives of these eight probands with the adrenal antibodies (seven with IDDM and one control). We conclude that screening patients with IDDM for adrenal antibodies of low yield (1.9% among white patients). Further, adrenal antibodies may be present for at least two years without the development of Addison disease. Antibodies reactive only to the zona glomerulosa of the adrenal cortex may be benign. Patients with IDDM and thyroid microsomal antibodies are more likely to have adrenal antibodies (6.5%), as are patients with IDDM and a B8-bearing haplotype and those with IDDM and family histories of organ-specific autoimmunity.

Addison Disease↗

Cerebral edema complicating diabetic ketoacidosis in childhood.

Three patients who developed fatal cerebral edema in the diabetes camp setting were reviewed with 14 previously reported instances in persons under 21 years of age. Seven occurred in the initial episode of diabetic ketoacidosis. Minimal blood glucose levels less than 250 mg/dl were recorded in 8/17. Rate of fluid administration, rate of Na or K infusion, and hyponatremia or hypokalemia were not consistent factors. Two of the 17 patients received oral fluids only. An etiologic role for rate of blood glucose correction or speed of hydration was not substantiated by this experience and review.

Adolescent↗

Ambulatory diabetes management with pulsed subcutaneous insulin using a portable pump.

A portable pump, programmed to administer intermittent pulses of insulin subcutaneously, supplemented by premeal boluses, was used by 8 patients for periods up to 12 months. Two boys, 11 and 16 years of age, sought improved growth; four young adults age 19 to 26 years desired normalization of metabolism to forestall microvascular complications already manifest; a 14-year-old girl had been incapacitated by unstable diabetes and a 26-year-old woman had been unable to attain sufficient control to gain weight without developing hypoglycemia. Maximal possible control with conventional insulin administration was attempted prior to pump use and such control was measured by glycohemoglobin (HgbA1) percentage and urine and blood sugar levels during a 24-hour period and compared with control with pump use. All initially had marked reduction in 24-hour urine volume (mean 3.3 L +/- .4 SEM to 1.4 +/- 0.2), urine glucose (mean 198 g +/- 81 to 14 +/- 4) and glycemia (mean 258 mg/dl +/- 29 to 133 +/- 12). HgbA1% declined markedly in all but the 14-year-old girl over the first weeks and reached normal or near normal levels in three patients. Four patients continued to use the pump after 3.5 to 12 months because of improved sense of well being, weight control, and in one, marked reduction in proteinuria. Both boys had a doubling of growth pace. Four patients are no longer using the pump after 3 to 8 months because of inconvenience, manipulation with intermittent usage, intolerance of normoglycemia, or overzealous control attempts with dangerous hypoglycemia. Pump use may permit the attainment of levels of control previously not possible, but is extremely demanding for patients and health personnel and must remain an experimental method in carefully selected and monitored patients.

Adolescent↗

Islet cell and other organ-specific antibodies in U.S. Caucasians and Blacks with insulin-dependent diabetes mellitus.

Islet cell antibodies (ICA) were detected in 168 (33%) of 504 patients with insulin-dependent diabetes mellitus (IDDM). Mean age of onset of IDDM was 8.6 +/- 0.2 yr and mean age at testing was 13.4 +/- 0.3 yr. None of 162 controls without diabetes (mean age 21.8 +/- 0.9 yr) had ICA. Caucasian patients (404) had a 74% frequency of ICA within 3 mo of diagnosis and an overall ICA frequency of 36%. These results were similar to those reported from Europe. Black patients (100) had lower frequencies of ICA (P < 0.01) and thyroid antibodies (P < 0.05). Caucasian patients with onset of IDDM before 5 yr of age (107) had a lower frequency (P < 0.01) of ICA (21%) than those (297) with a later age of onset (42%). Patients with persistent ICA beyond 5 yr of IDDM had increased frequencies of gastric parietal and adrenal cortex cell antibodies. Thyroid microsomal antibodies were less frequent (P < 0.05) in blacks (4%) than in Caucasians (20%). The former did not have adrenal antibodies. Similar ICA frequencies among Caucasians with IDDM in the U.S. and in Europe suggest that etiologic factors are similar in the two geographic regions. The lower frequencies of ICA in patients with IDDM onset before 5 yr of age suggest that some of these patients may have a different etiology and/or a more rapid disappearance of islet cell antigens than patients with a later onset.l The lower ICA frequencies in black patients can be explained by heterogeneity of IDDM in this group and by admixture of IDDM susceptibility genes from the Caucasian genome to the black genome.

Adolescent↗

Low dose single weekly injections of growth hormone: response during first year of therapy of hypopituitarism.

Initial year growth responses to single weekly injections of 2.5 units human growth hormone (hGH) in 29 patients with hypopituitarism (130 units/yr/patient) were compared to responses in a series using smaller doses in conjunction with androgen (48 to 112 units/yr); the US collaborative study experience with the standard dose (2 units 3 times/wk = 312 units/yr), and with two size-adjusted doses (0.06 units/kg 3 times/wk = 212 +/- 94 SD units/yr, 0.03 units/kg 3 times/wk = 116 +/- 33 units/yr); and to the British experience with much larger doses (1,040 units/yr). During the first year of hGH treatment our patients grew an average 13% faster than the androgen-supplemented and collaborative study-0.03 units/kg/dose groups. They had a similar pace to the collaborative study-312 units/yr and 0.06 units/kg/dose patients, but grew 15% more slowly than did the British patients. Growth response correlated positively with age and negatively with hGH dose per kilogram of body weight. Of 17 patients with isolated growth hormone deficiency ten developed hypothyroidism with hGH therapy, leading to a policy of routine adjunctive thyroxine replacement.

Adolescent↗

The effect of long-distance running on some biochemical variables.

Biochemical variables have been measured in a group of volunteers during and after a long-distance run. Plasma glucose levels remained relatively constant and a significant decrease in plasma bicarbonate was noted. Plasma sodium, chloride, total protein, albumin and calcium showed significant increased of an order compatible with water losses occurring during the run. Plasma potassium, urea, creatinine, uric acid, phosphate and bilirubin all show much more marked and variable increases. The plasma enzymes alkaline phosphatase, lactate dehydrogenase, aspartate aminotransferase and creatine kinase likewise increased significantly throughout the run. Whilst most constituents showed a tendency to return to normal at 20-30 hours after the run, gross increases were observed for aspartate aminotransferase and creatine kinase.

Adipose Tissue↗