James L Mills

Malformations in Infants of Diabetic Mothers Occur Before the Seventh Gestational Week: Implications for Treatment

In the present study we used a developmental morphologic approach to fix the latest time in development at which the malformations commonly reported in infants of diabetic mothers could occur. Developmental morphologic dating shows that the significantly more common congenital malformations in infants of diabetic mothers occur before the seventh week of gestation. This suggests that any therapeutic intervention aimed at decreasing the incidence of congenital malformations must be instituted during the critical early period.

The burden of gestational diabetes mellitus in Jamaican women with a family history of autosomal dominant type 2 diabetes

OBJECTIVES To determine if Jamaican women of African descent with a family history of early onset autosomal dominant type 2 diabetes have greater odds of developing gestational diabetes mellitus (GDM) than those without a family history of the disease. METHODS A comparative study was conducted of two groups of pregnant Jamaican women: the first with a family history of early onset autosomal dominant type 2 diabetes; the second with no history of the disease. Incidence, odds for developing GDM, and metabolic profiles in first and second trimesters were assessed using SPSS 11.5 (SPSS Inc., Chicago, Illinois, United States). RESULTS The incidence of GDM was 12.0% in women with a family history of early onset autosomal dominant type 2 diabetes and 1.5% in women without a family history of the disease (P<0.05). Women with a family history were nine times more likely to develop GDM than those without a family history of diabetes (95% confidence interval: 5.00-16.38, P<0.0001). CONCLUSION Family history of early onset autosomal dominant type 2 diabetes appears to increase susceptibility to GDM in Jamaican women. Pregnant women of any age with family history of early onset autosomal type 2 diabetes should be screened for GDM.

Multigenerational inheritance and clinical characteristics of three large pedigrees with early-onset type 2 diabetes in Jamaica

OBJECTIVE To document the existence and clinical characteristics of three large families with multigenerational inheritance of early-onset type 2 diabetes in Jamaica. METHODS Three probands from large families with multigenerational inheritance of early-onset type 2 diabetes in at least three generations were detected at the University Hospital of the West Indies in Jamaica. Each proband at the time of diagnosis was < 25 years of age, was lean, and did not require insulin therapy. Clinical, metabolic, and genetic assessments were undertaken to profile the diabetes in the three families. RESULTS Three pedigrees--BK, SU, and CA--consisting of 38, 48, and 113 members, respectively, with multigenerational inheritance of early-onset type 2 diabetes in at least three generations, were investigated. The mean age at diagnosis of the three pedigrees was 31.5 +/- 2.9 years, with 10 persons detected below 25 years of age. Findings suggestive of overweight, insulin resistance, low insulin secretion, dyslipidemia, and mild intra-abdominal obesity were present. Islet cell antibodies and sequence variants in MODY1 to -6 genes were absent. CONCLUSIONS Large families demonstrating multigenerational inheritance of diabetes and other characteristics consistent with early-onset type 2 diabetes are present in the Jamaican population.

Comparative Observations of Mucus Transport Velocity in Health and Disease

The present study evaluated mucus transport velocity (MTV) in different areas of the tracheobronchial tree in vitro in normal, acute and chronic bronchitic animals. The average MTV in normal animals ranged from 11.5 mm/min in the trachea to 0.64 mm/min in the pre-terminal bronchus. Chronic bronchitic animals showed mucus hypersecretion, areas of ciliary abnormality and mucus stagnation. The mean transport velocities ranged from 21.2 mm/min in the trachea to 4.1 mm/min in the pre-terminal bronchus. In the acutely ill animals, MTV ranged from 2.5 mm/min in the trachea to zero below the upper lobar bronchus. It is postulated that the higher than normal values in chronic bronchitis are due to altered mucus rheology, increased peristalsis and linear acceleration; whereas those in acute bronchitis were attributed to an early phase of viral or bacterial infection.

Diabetes and psychological co‐morbidity in children with a family history of early‐onset type 2 diabetes

The present study was conducted to evaluate for depressive symptoms and undiagnosed diabetes in children with familial history of early-onset type 2 diabetes. Studies have shown that diabetes doubles the risk for depression and that the duration of diabetes is related to the severity of the depression. Individuals with depression are also said to be at greater risk for developing diabetes. In many cases diabetes is detected whilst screening for depression. Fifty-three children aged between 6 and 17 years were screened for diabetes and assessed for depressive symptoms using the Children Depression Rating Scale, revised version (CDRS-R). Thirty-six (68.0 %) of the children with a family history of early-onset type 2 diabetes had CDRS-R scores consistent with likely or very likely major depressive disorders. Depressive symptoms score was predicted best by the number of generations of diabetes in the family, with an associated r = .65 and adjusted R(2) = .41. As the generations of diabetes increased, the more likely it was for a child to have diabetes (r = .38, p = .005). Four (7.5%) of the children were diagnosed with diabetes. The findings suggest that depressive symptoms are common in children with a family history of early onset type 2 diabetes and may co-exist with diabetes. The independent variable that reliably predicted the child depressive symptoms score was the number of generations of diabetes in the family.

Bronchomotor Tone in Protein-Energy Malnutrition

The study examined the reactivity of the tracheobronchial tree of rats maintained on low protein and tryptophan-deficient diets. It was found that: (1) Rats maintained on 5% protein or tryptophan-deficient diets showed little or no weight gain. A 15% protein diet was adequate for normal growth of female rats, but not of male rats. (2) Airways of malnourished rats showed significant bronchoconstriction when treated to an acetylcholine (AcCh) concentration of 10(-11) M. The threshold concentration of AcCh for normal rats was 10(-5) M. Airways of malnourished rats were also more sensitive to cold. (3) Rehabilitation of the malnourished rats attenuated the response to AcCh. Recovery, however, was not complete. (4) Prior application of phentolamine and atropine markedly reduced the sensitivity of the airways of malnourished rats to AcCh. The results seem to indicate that alpha-adrenoceptors and the vagus nerve may be involved in the observed increased reactivity of airways of malnourished rats.

Direct determination of luminal diameter changes in intrapulmonary airways.

A method is described for the direct measurement of changes in luminal diameter at all levels of the airway. Using this method it was found that (i) abrupt bronchiolar collapse occurred in the preterminal and terminal bronchioles once the luminal diameter was reduced to a critical level: (ii) decreased temperatures resulted in airway narrowing which was reversed by increasing the temperature to above 25 degrees C; as a rule, airway narrowing followed a cranial to caudal direction, and higher concentration of a drug being required to close the peripheral airways; (iii) bronchodilators except Carbuterol had no effect on resting bronchial tone or on acetylcholine-induced constriction in the absence of alpha-adrenoceptor blockade; (iv) at 35 degrees C rhythmic waves (frequency 6--20/min) were observed; these waves travelled from the periphery in a cranial direction.