Obstetric Outcomes of an Afro-Caribbean Cohort Following Universal Screening and Treatment of Subclinical Hypothyroidism.

OBJECTIVE: Restoration of euthyroidism with l-thyroxine reportedly reduces obstetric complications associated with subclinical hypothyroidism (SCH). The objective was to determine if obstetric outcomes of treated subjects were equivalent to euthyroid subjects. METHODS: This was a prospective cohort study. Subjects were considered euthyroid if serum thyroidstimulating hormone (TSH) was 0.4-3 mIU/L and free thyroxine (FT4) 10.29-17.05 pmol/L with negative thyroid peroxidase antibodies (TPOAb). Subclinical hypothyroidism was diagnosed if FT4 was 10.29-24.45 pmol/L and TSH 2.5-3 mU/L with positive TPOAb, or TSH > 3.0 mU/L regardless of antibody status. Subclinical hypothyroidism subjects were treated with l-thyroxine until TSH < 2.5 mIU/L. Data were analysed with Stata (StataCorp, USA). RESULTS: Seven hundred and sixty-nine singleton pregnancies were screened; 96% at 14 weeks gestation. Five hundred and eleven (66%) were euthyroid by study definition. Prevalence of SCH was 1.9% (15/769); 26% (4/15) were TPOAb positive. Eighty-one per cent were treated according to protocol; compliance was 54%. Mean gestational age (GA) at first endocrinologist visit was 22.7 ± 2.7 weeks. Normal TSH was documented in 36% at GA 33 ± 2.94 weeks. Subjects with SCH had significantly greater pre-existing history of preterm premature rupture of membranes (PPROM) and preterm labour, Caesarean sections for non-reassuring fetal heart rate and neonatal necrotizing enterocolitis. CONCLUSION: L-thyroxine appeared to reduce obstetric complications. However, prevalence of SCH was low and compliance was < 50%.

Antiphospholipid and other autoantibodies in a cohort of habitual aborters and healthy multiparous women in Jamaica.

Blood samples from 50~women who had had recurrent spontaneous abortions and 135 healthy multiparous women were investigated for anticardiolipin (aCL) antibodies and anti-ß2 Glycoprotein 1 (anti-ß2 GP1) dependent aCL antibodies by enzyme-linked immunosorbent assays (ELISA), lupus anticoagulant activity was measured by activated partial thromboplastin time, antinuclear antibodies, rheumatoid factors and thyroid antibodies using standard techniques. Serological tests for syphilis were performed on all sera and thyroid function was evaluated. There was no significant difference in the prevalence of autoantibodies in habitual aborters and control subjects (60% and 44%, respectively). Habitual aborters differed from controls only in the prevalence of positive aCL antibody tests (15/50, 30% vs. 15/135, 11%; χ² = 8.5, P= 0.01); medium/high concentrations of aCL antibodies (9/50, 18% vs. 9/135, 7%; χ² 4.3, P= 0.05); aCL antibodies of the IgM isotype (8/50, 16% vs. 7/135, 5%; χ² = 4.5, P= 0.05) and anti-ß2- GPI antibodies (7/50, 14% vs. 3/135, 2%; χ² 6.1, P= 0.05). We recommend aCL antibody screening in habitual aborters and the performance of the anti-ß2 GP1 antibody tests to identify those most at risk.

Clinical and laboratory features of youth onset type 2 diabetes in Jamaica.

OBJECTIVES: To assess the frequency of youth onset Type 2 diabetes mellitus (T2D) in Jamaica and the characteristics of youth with this form of diabetes. METHODS: Patients from two major referral hospitals, diagnosed with diabetes before age 25 years and < 6 years prior to the study, were evaluated. Classification was based on the presence of GAD-65 and IA-2 diabetes autoantibodies (AB), fasting (FCP) and stimulated C-peptide (SCP) measurements, serum leptin and clinical phenotype as follows: (i) Type IA diabetes--AB+, (ii) Type lB diabetes--AB- and FCP < 230 pmol/l and/or SCP < 660pmol/l, (iii) Type 2 diabetes - AB- and FCP > 500 pmol/L and or SCP 2 1160 pmol/l (iv) Untypeable diabetes--AB- and FCP 230-500 pmol/l and or SCP 660-1160 pmol/l and (v) Lipoatrophic diabetes--clinical phenotype and serum leptin. RESULTS: Fifty-eight participants (21M, 37F, age 20-8 years, duration of diabetes 2.6-2 years) were enrolled in the study. Using the classification criteria, Type 1 diabetes was the most common form of diabetes: 18 (31%) Type 1A, 18 (31%) Type IB. Overall 22% (13 patients) had T2D. Patients with T2D were more likely to be female, older at diagnosis, obese and have a higher blood pressure when compared to those with Type 1 diabetes. In logistic regression analysis, age of diabetes onset, gender BMI, systolic and diastolic blood pressure were significantly associated with T2D. Obesity measured by BMI was the strongest predictor of T2D. CONCLUSIONS: While Type 1 diabetes was the predominant form of diabetes in this study, a significant proportion of Jamaicans with youth onset diabetes may have T2D. Obesity is the strongest clinical predictor of Type 2 diabetes in the young diabetic patient.

Cardiovascular risk profile in Caribbean youth with diabetes mellitus.

OBJECTIVE: To assess the effect of diabetes mellitus type on conventional and novel cardiovascular risk factors in patients, diagnosed with diabetes from two major referral hospitals in Jamaica, before age 25 years and with diabetes duration < 6 years. METHODS: Participants were classified based on the presence of GAD-65 and IA-2 autoantibodies, C-peptide, leptin and clinical phenotype. Trained observers obtained anthropometric measurements and sitting blood pressure. Fasting blood was taken for glucose, A1c, lipids, high sensitivity C-reactive protein and lipoprotein profile. RESULTS: Fifty-eight participants (21M; 37F age 20 +/- 8 [Mean +/- SD] years, diabetes duration 2.6 +/- 2 years) were enrolled. Thirty-six had Type 1 diabetes (T1D), thirteen Type 2 diabetes (T2D), six were not typed and three had lipoatrophic diabetes. Patients with Type 2 diabetes (T2D) were more obese with a higher systolic blood pressure but a lower A1c than those with Type 1 diabetes (T1D). Total cholesterol, LDL-cholesterol, triglycerides, VLDL, LDL and HDL particle numbers were similar in patients with T1D and T2D. HDL-cholesterol and LDL and HDL particle sizes were lower in patients with T2D but differences were no longer significant after adjusting for BMI. CONCLUSIONS: Risk factors for cardiovascular disease are common in patients with all forms of youth onset diabetes. Clinicians should therefore investigate these risk factors in their patients regardless of diabetes type.

Autoantibodies in Caribbean youth with diabetes mellitus.

The prevalence of diabetes and other autoantibodies in patients with recently diagnosed youth onset diabetes was evaluated. Fifty-seven patients (95% black, age 19 +/- 5 years, 36% male, diabetes duration 2.6 +/- 2.2 years) were clinically diagnosed as having type 1 (n = 35), type 2 (n = 13) and lipoatrophic diabetes (n = 3) while 6 remained untyped. GAD65 was the most common diabetes-associated autoantibody in patients with type 1A diabetes (12/17; 71%). The prevalence of any diabetes-associated autoantibodies decreased with diabetes duration (OR[95%CI]/yr after diagnosis 0.50[0.31,0.82]) and was not associated with age of onset, duration or gender. Rheumatoid factor (13/57; 23%), smooth muscle (6/57; 11%), gastric-parietal cell (5/57; 9%) and thyroid microsomal antibodies (5/57; 9%) were the most frequent non-diabetes associated autoantibodies and were more common in patients with type 1A diabetes. Only one patient had clinical autoimmune disease (hypothyroidism). Type 1A diabetes may constitute up to half the cases of newly diagnosed type 1 diabetes in Jamaican youth and is associated with a higher prevalence of other organ-specific autoantibodies.

Chemical composition of urinary tract stones at the University Hospital of the West Indies / Composición química de las piedras del tracto urinario en el Hospital Universitario de West Indies

Urinary tract stones occur frequently with the incidence being about one to fifteen per cent worldwide. Patients may be asymptomatic or sometimes they may present with haematuria. Severe lumbar pain radiating to the loin requiring immediate analgesic treatment may occur. Stones generally consist of organic and inorganic material. The organic material may be present in the nidus and can contribute up to about 2.5% of the total weight. Inorganic minerals make up the bulk of the stone. Data are presented for the inorganic minerals present in the stones seen at the University Hospital of the West Indies over a 25-year period. Six hundred and forty-one (445 males and 196 females) stones were analyzed by routine chemical methods. Calcium was the main constituent, being seen in 93.9% of the stones. This was followed by oxalate 60.1%, urate 37.0%, bicarbonate 16.5% and magnesium 8.6%. There were four cystine containing stones. Treatment includes medical management for the underlying cause and surgical methods for the removal of the stones. Chemical methods of analysis of the stones has its limitations and should be replaced by more sophisticated methods eg X-ray diffraction crystallography which would give more accurate details of the structure of the stones.

Las piedras del tracto urinario se presentan frecuentemente con una incidencia de aproximadamente uno a quince por ciento a nivel mundial. Los pacientes pueden ser asintomáticos o presentarse con hematuria. Puede producirse dolor lumbar severo que se irradia a toda la región lumbar y que requiere tratamiento analgésico inmediato. Las piedras generalmente están formadas por material orgánico e inorgánico. El material orgánico puede estar presente en el nido y puede contribuir hasta aproximadamente 2.5% del peso total. Los minerales inorgánicos constituyen la mayor parte de las piedras. Se presentan datos de los minerales inorgánicos presentes en las piedras vistas en el Hospital Universitario de West Indies en un periodo de 25 años. Seiscientos cuarenta y una (445 varones y 196 hembras) piedras fueron analizadas mediante métodos químicos de rutina. El calcio fue el constituyente principal, observándosele en el 93.9% de las piedras. El mismo fue seguido por el oxalato (60.1%), el urato (37.0%), el bicarbonato (16.5%) y el magnesio (8.6%). Había cuatro cistinas que contenían piedras. El tratamiento incluye el manejo médico de la causa subyacente y los métodos quirúrgicos para la eliminación de las piedras. Los métodos químicos de análisis de las piedras tienen sus limitaciones y deben reemplazarse por métodos más sofisticados, tales como la cristalografía por difracción de rayos X. que daría detalles más exactos de la estructura de las piedras.

Chemical composition of urinary tract stones at the University Hospital of the West Indies.

Urinary tract stones occur frequently with the incidence being about one to fifteen per cent worldwide. Patients may be asymptomatic or sometimes they may present with haematuria. Severe lumbar pain radiating to the loin requiring immediate analgesic treatment may occur Stones generally consist of organic and inorganic material. The organic material may be present in the nidus and can contribute up to about 2.5% of the total weight. Inorganic minerals make up the bulk of the stone. Data are presented for the inorganic minerals present in the stones seen at the University Hospital of the West Indies over a 25-year period. Six hundred and forty-one (445 males and 196females) stones were analyzed by routine chemical methods. Calcium was the main constituent, being seen in 93.9% of the stones. This was followed by oxalate 60.1%, urate 37.0%, bicarbonate 16.5% and magnesium 8.6%. There were four cystine containing stones. Treatment includes medical management for the underlying cause and surgical methods for the removal of the stones. Chemical methods of analysis of the stones has its limitations and should be replaced by more sophisticated methods eg X-ray diffraction crystallography which would give more accurate details of the structure of the stones.

Autoantibodies, human T lymphotropic virus type 1 and type 1 diabetes mellitus in Jamaicans.

The clinical characteristics, autoantibody profiles and seroprevalence of human T lymphotropic virus Type 1 (HTLV-1) were assessed in 30 Jamaican patients with Type 1 diabetes mellitus. Two hundred and fifty-two blood donors and 108 patients with Graves' disease were included as controls for the HTLV-1 component of the study. The mean age of onset of diabetes mellitus was 20.5 +/- 9.2 years and the mean duration of diabetes mellitus was 10.5 +/- 6.1 years. The remarkable clinical data included an absence of other associated organ-specific autoimmune diseases, and clinical evidence and history of congenital rubella in one patient. Islet cell cytoplasmic antibodies (ICA) were absent but 17% (5/30) of the diabetic patients tested positive for glutamic acid decarboxylase (GAD) antibodies. No other organ-specific autoantibodies were detected but non-organ-specific autoantibodies were present in 9 (30%) of the sera of diabetic patients. The seroprevalence of HTLV-1 in the patients with diabetes mellitus was significantly higher than that in the healthy controls (17% (5/30) versus 4% (11/252), p = 0.05). Autoantibodies were found in the sera of 4/5 (80%) of the diabetic patients who were positive for HTLV-1. None of the patients with onset of diabetes mellitus below age 15 years was HTLV-1 positive. The likely polyaetiological nature of Type 1 diabetes mellitus in Jamaicans is being further investigated at the molecular level.

Autoantibodies, human T lymphotropic virus type 1 and type 1 diabetes mellitus in Jamaicans

The clinical characteristics, autoantibody profiles and seroprevalence of human T lymphotropic virus Type 1 (HTLV-1) were assessed in 30 Jamaican patients with Type 1 diabetes mellitus. Two hundred and fifty-two blood donors and 108 patients with Graves' disease were included as controls for the HTLV-1 component of the study. The mean age of onset of diabetes mellitus was 20.5 +/- 9.2 years and the mean duration of diabetes mellitus was 10.5 +/- 6.1 years. The remarkable clinical data included an absence of other associated organ-specific autoimmune diseases, and clinical evidence and history of congenital rubella in one patient. Islet cell cytoplasmic antibodies (ICA) were absent but 17 (5/30) of the diabetic patients tested positive for glutamic acid decarboxylase (GAD) antibodies. No other organ-specific autoantibodies were detected but non-organ-specific autoantibodies were present in 9 (30) of the sera of diabetic patients. The seroprevalence of HTLV-1 in the patients with diabetes mellitus was significantly higher than that in the healthy controls (17 (5/30) versus 4 (11/252), p = 0.05). Autoantibodies were found in the sera of 4/5 (80) of the diabetic patients who were positive for HTLV-1. None of the patients with onset of diabetes mellitus below age 15 years was HTLV-1 positive. The likely polyaetiological nature of Type 1 diabetes mellitus in Jamaicans is being further investigated at the molecular level.

The influence of persistent hyperglycaemia on hyperfibrinogenaemia and hyperviscosity in diabetes mellitus

The effect of hyperglycaemia on hyperfibrinogenaemia and its consequence on plasma viscosity was investigated in 69 diabetic patients during the course of hypoglycaemic treatment. Glycaemic control was assessed by measurement of glycosylated haemoglobin (HbA1). Plasma fibrinogen concentration (PFC) was determined by a clot-weight method. The relative plasma viscosity (RPV) was measured by capillary viscometry. The mean PFC and RPV were significantly (p < 0.001) elevated in the diabetic patients as compared with a non-diabetic control group. Both PFC and RPV showed a distinct, step-wise increase with progressively poorer glycaemic control. The data strongly indicate that persistent hyperglycaemia is associated with a frank hyperfibrinogenaemia and hyperviscous plasma in most of the diabetic patients studied. These abnormal haemorrheological changes could impact adversely on both the haemostatic process and circulation in diabetic patients.

The role of C-peptide in the classification of diabetes mellitus.

We investigated twenty-one insulin-using patients, who had all been labelled as having insulin dependent diabetes mellitus (IDDM) or type 1 diabetes. Physicians have been erroneously using the term IDDM loosely to include all diabetics on insulin. The clinical criteria of the National Diabetes Data Group/WHO were used to reclassify these patients. Only thirteen were found to have IDDM and eight non-insulin dependent diabetes mellitus (NIDDM). Using fasting C-peptide values, only five of the thirteen with clinical IDDM truly had IDDM, the others might have maturity onset diabetes of the young (MODY) or diabetes in the young. Of the eight with clinical NIDDM seven had normal to high C-peptide values; the lone patient with low C-peptide values had diabetes diagnosed at age 64 years. We conclude that the clinical classification of diabetes mellitus may be inaccurate and that C-peptide evaluation improves the accuracy of the classification.

The influence of persistent hyperglycaemia on hyperfibrinogenaemia and hyperviscosity in diabetes mellitus.

The effect of hyperglycaemia on hyperfibrinogenaemia and its consequence on plasma viscosity was investigated in 69 diabetic patients during the course of hypoglycaemic treatment. Glycaemic control was assessed by measurement of glycosylated haemoglobin (HbA1). Plasma fibrinogen concentration (PFC) was determined by a clot-weight method. The relative plasma viscosity (RPV) was measured by capillary viscometry. The mean PFC and RPV were significantly (p < 0.001) elevated in the diabetic patients as compared with a non-diabetic control group. Both PFC and RPV showed a distinct, step-wise increase with progressively poorer glycaemic control. The data strongly indicate that persistent hyperglycaemia is associated with a frank hyperfibrinogenaemia and hyperviscous plasma in most of the diabetic patients studied. These abnormal haemorrheological changes could impact adversely on both the haemostatic process and circulation in diabetic patients.

Some clinical factors contributing to the development of the diabetic foot.

Clinical neurological studies, blood pressure measurements and some haematological investigations were performed on a random sample of forty-four patients, at the Diabetes Out-Patient Clinic of the University Hospital of the West Indies (UHWI), to examine some of the factors that predispose to the development of the diabetic foot. Our results revealed that 86% of the patients had elevated glycosylated haemoglobin (HbA1 > 9.0%), 82% had clinical signs of peripheral sensory neuropathy, 29% had signs of autonomic neuropathy in addition to peripheral sensory neuropathy. Sixty-one per cent (61%) of the patients had ankle/arm systolic blood pressure ratio less than 1.0 and were diagnosed as having peripheral vascular disease (PVD). The group with neuropathy was found to have a significantly lower diastolic blood pressure (p < 0.0005) than the group without neuropathy. We believe that hyperglycaemia-induced vasodilation (indicated by a lower diastolic blood pressure) in a significant number of diabetics resulted in compensatory shunting of blood from the deeper tissues, including nerves, to the periphery. The resulting endoneural hypoxia could be responsible for the unusually high incidence of peripheral sensory neuropathy detected in this sample of diabetic patients. Metabolic factors may also play a role.

Prevalence of antibodies to hepatitis C virus and other markers in Jamaica.

Three population groups, 1500 blood donors, 513 antenatal women representing a normal population group and 250 sicklers representing a multiply transfused group were studied to determine the prevalence of hepatitis C viral (HCV) infection in Jamaica. The relationship to liver enzyme levels, hepatitis B infection, syphilis and HIV infection was also investigated. Sera were screened by enzyme-linked immunoassay (EIA) for anti-HCV C100-3 and subsequently tested by a supplementary second generation recombinant immunoblot assay (RIBA). In the blood donors, the prevalence of anti-HCV was low, 0.3%-0.4%, the same level as that reported by several European countries. In the multiply transfused sicklers, the prevalence was more than seven times higher. No HCV infection was detected in the antenatal group. There was little correlation between HCV infection and surrogate markers alanine aminotransferase (ALT) and antibody to hepatitis B core antigen (anti-HBc) and no correlation with sexually transmitted diseases.

Effect of aqueous neem (Azadirachta indica) extract on testosterone and other blood constituents in male rats. A pilot study.

Effect of oral administration of crude aqueous neem extract on serum testosterone and other blood constituents was studied in the male Wistar rats for 10 weeks. The neem treatment resulted in significant decreases (p < 0.01) in total testosterone, total bilirubin and K+ in serum. There were also increases (p < 0.05) in packed cell volume, mean corpuscular haemoglobin concentration, red blood cell, white blood cell and lymphocyte counts without showing any cytotoxic effects in the body.

Toxic effects of ackee oil (Blighia sapida L) following subacute administration to rats.

Subacute intraperitoneal administration of the lipid portion of the unripe ackee arillus, referred to as "ackee oil", resulted in marked neutropenia (p less than 0.001) and increase in platelets (p less than 0.01) without anaemia, in rats. Blood urea, sodium and aspartate aminotransferase levels were significantly decreased but glucose and bilirubin levels were similar to those of controls. The lungs showed areas of petechial haemorrhages and a dose-related perivascular and peribronchial mononuclear cell infiltration. The pulmonary toxicity may be interpreted as a hypersensitive reaction to ackee oil. Further research is in progress on the neutropenic effects of ackee oil.

Toxic effects of ackee oil (Blighia sapida L) following subacute administration to rats

Subacute intraperitoneal administration of the lipid portion of the unripe ackee arillus, referred to as "ackee oil", resulted in marked neutropenia (p<0.001) and increase in platelets (p<0.01) without anaemia, in rats. Blood urea, sodium amd aspartate aminotransferase levels were significantly decreased but glucose and bilirubin levels were similar to those of controls. The lungs showed areas of petechial haemorrhaghes and a dose-related perivascular and peribronchial mononuclear cell infiltration. The pulmonary toxicity may be interpreted as a hypersensitive reaction to ackee oil. Further research is in progress on the neutropenic effects of ackee oil.

Biochemical abnormalities in multiple myeloma.

Monoclonal gammopathies can either be benign or more commonly malignant. The commonest disease associated with it is multiple myeloma. Over the seven-year period 1984-1990, two hundred and thirty-four monoclonal gammopathies were seen at the University Hospital, Jamaica. Multiple myeloma was diagnosed in one hundred and fifty-six cases (84 males and 72 females). The diagnoses of most of the others were not known as the samples came from other institutions. Of the patients with myeloma, the most common immunoglobulin type was IgG followed by IgA and then pure light chain disease. Only in about half of the cases where urine was analysed was Bence-Jones protein found. The majority of the cases had abnormal total serum protein, albumin and total globulin concentrations. Most of the cases also were in renal failure. Hypercalcaemia, hyperphosphataemia, elevated alkaline phosphatase, gammaglutamyl transferase and aspartate aminotransferase occurred in about one-third of them. These results were not much different from those reported in other countries.

Biochemical abnormalities in multiple myeloma

Monoclonial gammopathies can either be benign or more commonly malignant. The commonest disease associated with it is multiple myeloma. Over the seven-year period 1984-1990, two hundred and thirty-four monoclonal gammopathies were seen at the University Hospital, Jamaica. Multiple myeloma was diagnosed in one hundred and fifty-six cases (84 males and 72 females). The diagnosis of most of the others were not known as the samples came from other institution. Of the patients with myeloma, the most common immunoglobulin type was IgG followed by IgA and then pure light chain disease. Only in about half of the cases where urine was analysed was Bence-Jones protien found. The majority of the cases had abnormal total serum protein, albumin and total globulin concentrations. Most of the cases also were in renal failure. Hypercalcaemia, hyperphoshataemia, elevated alkaline phosphate, gammaglutamyl transferase and aspartate aminotransferase occured in about one-third of them. These results were not much different from those reported in other countries