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Biomedical subjects

M H Maxwell

Publications and source records attributed to M H Maxwell.

At least 55 records · Page 3Linked to original sources

Haematological and tissue abnormalities in chicks caused by acute and subclinical folate deficiency.

1. Haematological, histological and ultrastructural findings in young chicks fed on a purified diet severely deficient in folate are reported. 2. Growth of the birds was greatly depressed and they had a macrocytic anaemia. Other haematological changes included abnormal nuclear formations in erythrocytes, numerous mitoses and hypersegmented granulocytes. 3. Megaloblasts were observed in bone marrow and their fine structure is described for the first time in an avian species. 4. Morphological changes occurred also in the liver. The parenchyma had damaged sinusoidal endothelium, inflammatory cells and no glycogen. Mitochondria were damaged and many were associated with unusual crystalline structures. 5. Chickens fed on a semi-purified diet of low folate content showed no growth depression or clinical signs of deficiency but had abnormal haematological values and morphological changes that resembled those seen in birds fed on the purified diet. 6. These abnormalities responded to dietary supplements of pteroylmonoglutamic acid in a dose-related manner and may be useful in diagnosing subclinical folate deficiency.

Animals↗

The relation between degree of blood pressure reduction and mortality among hypertensives in the Hypertension Detection and Follow-Up Program.

The relation between degree of diastolic blood pressure reduction and mortality was examined among hypertensive persons in the Hypertension Detection and Follow-up Program. This program, conducted from 1973-1979, was a multicenter community-based trial, which followed 10,940 hypertensive participants for five years. The one-year annual visit was the first occasion on which change in blood pressure could be measured on all participants. During the subsequent four years of follow-up on 10,053 participants, 568 deaths occurred. With time-dependent life tables and time-dependent Cox life table regression analyses, the existence of a quadratic function which modeled the relation between diastolic blood pressure reduction and mortality was supported, even after adjusting for other risk factors. The minimum mortality hazard ratio, based on a particular model, occurred at a diastolic blood pressure reduction of 26.2 mmHg (standard error = 13.4) in the whole population and 10.0 mmHg (standard error = 5.3) in the baseline diastolic blood pressure stratum 90-104 mmHg. After this reduction, there was a small increase in the risk of death. There was no evidence of the quadratic function after fitting the same model with systolic blood pressure. Methodological issues involved in studying a particular degree of blood pressure reduction were considered. The confidence interval around the change corresponding to the minimum hazard ratio was wide, and the obtained blood pressure level should not be interpreted as a goal for treatment. Blood pressure reduction was attributed not only to pharmacologic therapy but also to regression to the mean, and to other factors unrelated to treatment.

Actuarial Analysis↗

Beyond blood pressure control. Effect of antihypertensive therapy on cardiovascular risk factors.

Mild hypertension accounts for approximately 60% of the mortality associated with high blood pressure. In addition to hypertension, other major cardiovascular risk factors include left ventricular hypertrophy (LVH), dyslipoproteinemia, and glucose intolerance. Thus, the effects of agents used to treat hypertension on these risk factors are of considerable importance. Large therapeutic intervention trials have shown that while adequate treatment of mild hypertension significantly and consistently reduces all-cause mortality as well as the risk of stroke and congestive heart failure, an anticipated reduction in coronary heart disease (CHD) has not been demonstrated. It is possible adverse metabolic side effects (hypercholesterolemia, hyperglycemia, hypokalemia) of widely used agents, such as diuretics and beta-blockers may be partially offsetting the beneficial effects of blood pressure reduction, with the net result being a failure of these agents to reduce the risk of CHD. Angiotensin-converting enzyme inhibitors (ACEIs) and calcium channel blockers do not produce these adverse metabolic derangements. The use of antihypertensive agents that have favorable or neutral metabolic effects should further reduce the risk of cardiovascular morbidity and mortality attributable to high blood pressure, including CHD.

Antihypertensive Agents↗

Cations in essential hypertension.

Sodium intake has been linked to the development and perpetuation of hypertension for almost a century. Nevertheless, considerable controversy over this relationship remain. More recently, the other major body cations, potassium, calcium and magnesium, have also been implicated. The evidence relating dietary sodium, potassium, calcium and magnesium intake to hypertension is summarized, and the present evidence for dietary modification of cation intake in the treatment of mild essential hypertension is evaluated.

Calcium↗

Cations and hypertension: sodium, potassium, calcium, and magnesium.

The association between sodium intake and hypertension has been studied for almost a century. More recently, it has been suggested that abnormalities in dietary intake of potassium, calcium, and magnesium may play a major role in the pathogenesis of hypertension. A critical analysis of selected data from animal and human studies is discussed.

Animals↗

Controlled multicenter study of the antihypertensive effects of lisinopril, hydrochlorothiazide, and lisinopril plus hydrochlorothiazide in the treatment of 394 patients with mild to moderate essential hypertension.

Lisinopril (LIS) is a lysine analog of enalaprilat, the active metabolite of enalapril, an angiotensin-converting enzyme inhibitor (ACEI). Unlike enalapril, the precursor of enalaprilat, LIS is not a prodrug but has equal ACEI efficacy and potency and a slightly longer duration of action after oral administration. Short-term (12 weeks) and long-term (24 weeks) blood pressure control has been studied with LIS, hydrochlorothiazide (HCTZ), and LIS + HCTZ when given once a day. Drug treatment had three phases: (i) 2-4 weeks of single-blind placebo washout; (ii) 12 weeks of double-blind comparison therapy with LIS 20, 40, and 80 mg vs. HCTZ 12.5, 25, and 50 mg, vs. LIS + HCTZ 20 + 12.5, 40 + 25, and 80 + 50 mg; (iii) 13-24 weeks single-blind LIS vs. LIS + HCTZ. Starting double-blind therapy at the lowest dose, all three groups doubled the dose at weeks 4 and 8 if BP was not controlled with sitting diastolic BP (SDBP) less than 90 mm Hg. At the end of 12 weeks of double-blind therapy, uncontrolled HCTZ-only and LIS-only treatment groups were advanced to combination LIS + HCTZ therapy but uncontrolled LIS + HCTZ patients were dropped. Mean BP reductions (systolic/diastolic, mm Hg) for all three groups after 12 weeks of double-blind comparison therapy were: (i) LIS (n = 162), -16.6/-12.5; (ii) HCTZ (n = 155), -10.4/-6.8; (iii) LIS + HCTZ (n = 74), -23.9/-18.2 with p less than 0.01 for all groups compared to baseline.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Evaluation of antihypertensive efficacy of lisinopril compared to metoprolol in moderate to severe hypertension.

A double-blind controlled, randomized, parallel, multicenter 12-week study was conducted to compare the antihypertensive efficacy of lisinopril with that of metoprolol in treatment of moderate to severe hypertension. Initially, 118 patients were recruited on lisinopril and 61 on metoprolol; and for the purpose of efficacy analysis at week 8, 115 patients on lisinopril and 60 on metoprolol were included. The doses of lisinopril or metoprolol were 40-80 mg/day and 100-200 mg/day, respectively. At week 4, the pretreatment diastolic blood pressure of 111 mm Hg was decreased to 97 mm Hg (p less than 0.01) with lisinopril: metoprolol decreased the diastolic blood pressure from 110 to 99 mm Hg (p less than 0.01). Similar decreases were noted at week 8; however, the drop in blood pressure with lisinopril was not significantly different from that with metoprolol. Systolic blood pressure also demonstrated a decrease of about 18 mm Hg with lisinopril and 12 mm Hg with metoprolol (p less than 0.01). This larger decrease in systolic blood pressure with lisinopril was statistically significant at week 4 (p less than 0.05). These decreases in systolic blood pressures were maintained at week 8, again with statistical significance (p less than 0.01). Of the 118 lisinopril-treated patients, four were discontinued from lisinopril therapy because of headache, dizziness, rash, flushing, or lymphadenopathy. Four patients out of 61 (9.8%) were discontinued from metoprolol therapy because of fatigue, somnolence, asthenia, weight gain, flatulence, tremor, or bronchospasm. In conclusion, lisinopril 40-80 mg once daily is as effective as metoprolol 100-200 mg once daily in reducing diastolic blood pressure in patients with moderate to severe hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

Ochratoxicosis A in young Khaki Campbell ducklings.

Ochratoxin A (OA), a potent nephrotoxic mycotoxin, was fed at 2 ppm in the diet to Khaki Campbell ducklings from hatch to 18 days old. It caused retarded growth, enlargement of the kidneys and liver and regression of the thymus. Light and electron microscopical changes seen in the liver included an accumulation of glycogen and the presence of mis-shapen mitochondria in the hepatocytes. OA caused thickening of the glomerular basement membrane and in infiltration of lymphoid cells into the kidney. There was an increased deposition of IgG in the glomeruli. OA-fed ducklings had normal levels of circulating IgG in their sera and there was a subepithelial migration of IgG-positive cells in the bursa of Fabricius. In general, OA-induced changes seen in ducklings, both with the light and electron microscopes, were similar to, but less pronounced than those seen in the fowl and turkey.

Animals↗

Mechanisms of hypertension in obesity.

We conclude that the following may explain the rise in blood pressure with obesity and the subsequent fall in blood pressure (Fig. 2): (1) An increase in calories, protein, or carbohydrate leads to an increase in plasma catecholamines, sympathetic nervous system activity, and insulin secretion. (2) These factors, in turn, lead to increased renal sodium retention and stimulation of the renin-aldosterone system which, in turn, leads to: (3) An increased cardiac output with an inability to appropriately adjust the peripheral resistance to maintain normotension with resultant hypertension. Conversely, the fall in blood pressure with weight reduction can be explained by (Fig. 3): (1) A decrease in calorie, carbohydrate, or protein intake which leads to: (2) A decrease in circulating plasma catecholamines, sympathetic nervous system activity, and insulin secretion which results in: (3) A natriuresis and decrease in the renin-aldosterone system, which causes a decrease in circulating blood volume and in cardiac output. This, in turn, lowers blood pressure towards normal. The unanswered question still remains: why do some obese patients become hypertensive and others remain normotensive? Perhaps there are weight-sensitive individuals and weight-resistant individuals just as there appear to be salt-sensitive and salt-resistant hypertensive patients. Perhaps the answer is genetic. These questions also remain to be answered.

Adrenal Glands↗

Haematology and morphological changes in young broiler chicks with experimentally induced hypoxia.

The haematology, histology and ultrastructure of day-old broiler chicks subject to experimentally induced hypoxia during incubation were examined. Some birds were allowed to reach five weeks old before examination. All the red blood cell parameters, namely, haemoglobin, packed cell volume and red cell counts were raised significantly in hypoxic birds compared with control material and the results closely resembled the haematological profile of young broilers with an ascitic syndrome. By week 5 these parameters had returned to normal. Morphological changes were seen in all the organs examined from day-old hypoxic chicks. The lungs showed much congestion and large numbers of granulocytes were present in hearts, and testes. In the livers, hepatocytes contained enlarged mitochondria together with a reduction in glycogen content. Congested lungs were seen at five weeks old but recovery to normal morphology was observed in all other organs.

Animals↗

Ultrastructural study of ochratoxicosis in quail (Coturnix coturnix japonica).

Ultrathin sections of liver and kidney from 11-week-old quail fed, from day-old, ochratoxin A (OA) (mixed in the diet at levels of 4 and 8 ppm) were examined in the electron microscope. Pathological changes in the kidneys were limited to the proximal convoluted tubules (PCT) and glomeruli. In the PCTs, abnormal mitochondria and excessive numbers of lipid droplets were the principal findings with glomeruli showing thickened basement membranes. Swollen mitochondria and variable glycogen deposition were the chief features present in the livers. It is suggested that OA is more hepatotoxic in quail than in broilers, as well as being nephrotoxic.

Animals↗

Postmarketing survey of the effects of an atenolol/chlorthalidone combination in the treatment of hypertension.

A large-scale postmarketing survey was conducted in the United States to evaluate the antihypertensive efficacy and safety of a combination of 50 mg of the long-acting cardioselective beta-blocker atenolol and 25 mg of the monosulfonamyl diuretic chlorthalidone. The program included 28,585 patients (of whom 26,892 provided sufficient information by questionnaire for an assessment of efficacy and race), and the participation of 7,009 primary-care physicians. After four weeks of treatment, patients had a mean reduction in systolic blood pressure of 21 mmHg and in diastolic blood pressure of 13 mmHg. The magnitude of these reductions did not differ appreciably with respect to age, sex, race, or previous therapy. Diastolic blood pressure was reduced by at least 11 mmHg in 55% of patients and systolic blood pressure was reduced by at least 16 mmHg in 59% of patients. Physicians' assessments indicated that 86% of patients achieved satisfactory control of blood pressure by the end of the study. The physicians' global assessment of the effectiveness of treatment indicated that the combination was better than previous therapy in 82% of patients; 91% of physicians planned to continue treatment with the fixed combination. There were no adverse experiences that had not been reported previously, and only dizziness exceeded an incidence of 1%. It was concluded that the fixed combination provides added blood pressure control and the convenience of a simplified once-daily regimen without added side effects, regardless of age, sex, race, or prior antihypertensive therapy.

Adolescent↗

Fine structural and cytochemical studies of eosinophils from fowls and ducks with eosinophilia.

The ultrastructure and cytochemistry of eosinophils from adult fowl and ducks with either spontaneous or experimentally induced eosinophilia were examined. The results showed that a high proportion of the eosinophils in the peripheral blood of eosinophilic birds had ultrastructural features different from those of normal eosinophils. In both species, there was a reduction in cell size. Fowl eosinophil granules showed similar morphological changes to those seen in the quail with many crescentic and vacuolated forms being present. In eosinophilic ducks, the crystalline interna of the specific granules were often fragmented or were either partially or completely lysed. Cytochemically, peroxidase activity in both species was generally unaltered in abnormal eosinophils compared with those from normal birds. This correlates with the findings in man. However, amounts of acid phosphatase and trimetaphosphatase were reduced in many cells, with a large proportion of granules being non-reactive. The latter observation corresponds with that in quail but differs from man, in which stimulated eosinophils have increased enzymatic activity.

Acid Anhydride Hydrolases↗

Ultrastructural and cytochemical studies in normal Japanese quail (Coturnix coturnix japonica) eosinophils and in those from birds with experimentally induced eosinophilia.

Normal eosinophil development in the Japanese quail (Coturnix coturnix japonica) was similar to that described in the fowl and the duck, with granulogenesis occurring in the Golgi apparatus. The characteristic lipid droplets were small in the immature eosinophils, and after staining specifically for lipid, small moieties were also traced to the Golgi apparatus. In mature eosinophils the lipid droplets measured between 1.0 and 1.5 micron in diameter and they were surrounded by profiles of smooth endoplasmic reticulum. Eosinophilia was difficult to induce in quails; injections of either horse serum or bovine serum albumin (BSA)/aluminium hydroxide produced a poor response. In some quails in which eosinophilia was produced, however, eosinophil granules showed many crescentic and vacuolated forms. The lipid droplets in the activated eosinophils were fused in many cells to form large intracellular aggregates of lipid. Quail eosinophils, which hitherto have been regarded as peroxidase-negative, had strong activity in the lipid droplets of cells from stimulated birds. It is postulated that this peroxidase-positive reaction may represent a form of ceroid or lipofuscin pigment resulting from lipid peroxidation. Acid phosphatase and trimetaphosphatase reactions were reduced in many activated cells, with a large proportion of granules being non-reactive. The results of dietary manipulations in quails appear to suggest that in stressful situations the eosinophil metabolism is altered and there is a reduction in the number of lipid droplets in the cell.

Acid Anhydride Hydrolases↗

Ultrastructure of Peyer's patches in the domestic fowl and turkey.

Peyer's patches in the fowl and turkey were indistinguishable at the ultrastructural level and were similar in many respects to those found in mammals. They were overlaid by a lymphoepithelium containing undifferentiated intestinal epithelial cells with a well developed microvillous border, follicle associated epithelial (FAE) or M cells with short blunt microvilli, lymphocytes and plasma cells. FAE cells had a lightly stained cytoplasm with vacuoles and vesicles. They were similar to mammalian FAE cells. The lymphoid aggregates of Peyer's patches consisted of small and large lymphocytes, lymphoblasts and plasma cells. Macrophages and globule leucocytes were seen among the lymphoid cells.

Animals↗

A fine structural study of the turkey harderian gland.

The ultrastructure of the turkey Harderian gland is described and the findings support previous histological descriptions of the gland. The gland is a compound tubulo-acinar structure composed of characteristic bipolar epithelial cells providing a predominantly merocrine secretion to the lumina. In the basal aspect of the cell, aggregations of non-secretory lipid-like droplets were evident and apically, the secretion was mucoid. The cells had abundant mitochondria, granular endoplasmic reticulum, ribosomes and a complex network of Golgi elements. In the subepithelial regions, myoepithelial cells and large numbers of plasma cells were seen. Within the granular endoplasmic reticulum cisternae of the epithelial cells, fibrillary or crystalline rods in some instances measuring up to 10 micron in length, with a 7.0 nm repeat pattern, were frequently seen.

Animals↗

Experimental stimulation of eosinophil production in the domestic fowl (Gallus gallus domesticus).

A method has been devised to produce eosinophilia in birds experimentally. Multiple intraperitoneal injections of bovine serum albumin (BSA) produced a greater response than horse serum in young adult fowls, and injections of 2 ml BSA were more effective than injections of 0.2 ml. The highest eosinophilic responses were obtained with injections of BSA together with aluminium hydroxide. Thymectomy had little effect on eosinophil numbers following horse serum injections but irradiation produced a depressed response. Horse serum that had been heated to 56 degrees C for 30 minutes to inactivate complement and to denature proteins, including possible horse IgE, induced an eosinophilic response in 50 per cent of birds compared with only 14 per cent with unheated horse serum. Furthermore, when the former birds were reinjected after a rest period of 13 weeks, the eosinophilic response followed a similar curve as before but a higher proportion of birds responded. Birds aged over two years did not give a good eosinophilic response after horse serum stimulation. There was no consistent correlation between raised IgE levels and eosinophil numbers. Tolerance to horse serum was detected in some birds using a radial immunodiffusion technique. Analyses of blood plasma from birds with eosinophilia showed a significant increase in total amino acids compared with normal birds.

Agar↗