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Biomedical subjects

D M Matthews

Publications and source records attributed to D M Matthews.

At least 19 recordsLinked to original sources

Post-traumatic hypothalamic-pituitary dysfunction presenting with biochemical features of primary hypothyroidism.

Two cases of post-traumatic hypothalamic-pituitary dysfunction are described where the primary pathology was shown to be understimulation of the pituitary by hypothalamic hormones. In each case, the biochemical presentation was a low serum thyroxine and elevated TSH concentration mimicking primary hypothyroidism. Treatment with thyroxine before cortisol replacement was not beneficial. In both cases, hydrocortisone therapy alone resulted in a rise in serum thyroxine and fall in serum TSH. Chronic cortisol deficiency may directly impair the thyroid response to TSH, whilst thyroxine appears to exert its feedback primarily at pituitary rather than hypothalamic level.

Adult

Kinetics of influx of peptides and amino acids into hamster jejunum in vitro: physiological and theoretical implications.

1. This paper reports a comparison of the kinetics of influx into hamster jejunum of a series of dipeptides of neutral, basic and acidic amino acids, and a tripeptide of neutral amino acids, with those of corresponding free amino acids. 2. Kt, the substrate concentration at which the transport rate is half the maximal transport rate, and Vmax, the maximal transport rate, were more similar from one peptide to another than among amino acids, with the result that, over a wide range of concentrations, rates of influx of individual peptides varied much less than those of amino acids. 3. It is suggested that this may account for the rates of absorption of amino acids being closely related to the amino acid composition of the protein fed, instead of being widely dissimilar as with corresponding mixtures of free amino acids. 4. With neutral amino acids, both Kt and Vmax. fell with increasing length of the side-chain, as observed on many previous occasions. This did not occur with the corresponding homologous dipeptides, which shows that the hypothesis that the apparent affinity for transport is related to the lipophilic properties of the side-chain cannot be applied to peptides.

Amino Acids

Relationship of skin thickness to duration of diabetes, glycemic control, and diabetic complications in male IDDM patients.

Skin thickness is primarily determined by collagen content and is increased in insulin-dependent diabetes mellitus (IDDM). We measured skin thickness in 66 IDDM patients aged 24-38 yr and investigated whether it correlated with long-term glycemic control and the presence of certain diabetic complications. With univariate analysis, skin thickness was increased and significantly related to duration of diabetes (P less than .001), previous glycemic control (P less than .001), retinopathy (P less than .001), cheiroarthropathy (P less than .001), and vibration-perception threshold (P less than .05). There was a negative correlation between forced expiratory volume at 1 s (P less than .05) and vital capacity (P less than .05) with duration of diabetes. Neither skin thickness nor ankle arteriomedial wall calcification correlated with abnormal autonomic function tests. When corrected for duration of diabetes, there was a weak correlation between skin thickness and glycemic control (P less than .05) but no correlation with retinopathy, cheiroarthropathy, and vibration-perception threshold. This study confirms that there are widespread connective tissue changes in diabetes mellitus, although the biochemistry needs further elucidation.

Adult

Neutrophil activation detected by increased neutrophil elastase activity in type 1 (insulin-dependent) diabetes mellitus.

Neutrophils have been implicated in the development of vascular disease, and increased plasma neutrophil elastase indicates increased neutrophil activation. The aim of this study was to determine whether neutrophil elastase levels, measured by radioimmunoassay, are altered in diabetes. One hundred Type 1 (insulin-dependent) diabetic patients and 35 comparably-aged control subjects were studied. There was no difference in the total white cell count, but the diabetic group had a higher neutrophil count (p less than 0.05). Plasma neutrophil elastase (p less than 0.001) and total neutrophil elastase (p less than 0.02) were increased in the diabetic group. The total neutrophil elastase levels reflected the neutrophil count, but plasma neutrophil elastase was independent of the number of neutrophils. The increased plasma neutrophil elastase level was not related to age, duration of diabetes, plasma glucose or HbA1. The results suggest an association between diabetes and neutrophil activation which may play a role in the development of vascular disease.

Adult

Photodynamic therapy: response of normal canine urethra using a cylindrical fiber.

Normal urethral response to photodynamic therapy (PDT) utilizing a cylindrical fiber was assessed in ten study and two control NIH fox-hounds. The canine urethras were treated 48 hours after intravenous injection of 3 mg/kg dihematoporphyrin ether (Photofrin II). A 1-mm fused silica optical fiber, with the distal 2-3 cm modified for cylindrical light distribution (660-microns diameter), was placed in the pendulous urethra. An argon-pumped dye laser delivered 100 mW of 630-nm light for 7 minutes (42 J) to the treatment area. Urethroscopy using either a 2.5-mm or a 2.8-mm flexible pediatric bronchoscope with video recording capability was performed immediately after PDT (12 animals) and 6 weeks later (nine animals); intravenous urography was performed 3 days and 6 weeks after PDT. There was no evidence of either urethral damage or stricture formation in any animal. Histopathology of the first three study specimens, obtained at 6 weeks, confirmed the absence of any pathology. Flexible instrumentation facilitates post-treatment assessment. This study demonstrates for the first time that, when a cylindrical fiber is used, photodynamic therapy may be applied to the urethra without damage to the normal urethral mucosa. This result has implications for potential treatment of initial or recurrent carcinoma in situ of the urethra using PDT.

Animals

The relationship between genetic deafness and fear-related behaviors in nervous pointer dogs.

Nervous pointer dogs have been extensively characterized as an animal model for some human pathological anxiety states. During our work with these animals suspicion developed that some of these dogs had a hearing deficit. We decided to systematically evaluate this observation and to study the relation between hearing status and fear-related behaviors in the nervous pointer dogs. Our results revealed that a majority of the nervous dogs in our colony (75%) suffer from bilateral deafness as demonstrated by complete absence of brain stem auditory evoked response. Furthermore, behavioral ratings revealed that hearing and deaf dogs do not differ in their pathological response to the characteristic fear-provoking stimuli (e.g., human interaction) and that both hearing and deaf nervous dogs markedly differ from normal dogs in that respect. The relation between these abnormalities and their implications for research involving breeding of animals for selected traits are further discussed in this report.

Animals

Response of normal canine ureter to photodynamic therapy using a cylindrical fiber.

Photodynamic therapy (PDT) was performed utilizing a cylindrical optical fiber to determine feasibility of distal ureteral treatment on 10 study and two control NIH foxhounds. The study animals were administered three mg./kg. dihematoporphyrin ether (Photofrin II) intravenously followed 48 hours later by open cystotomy. One ureter was irradiated with 42 joules of 630 nm. light delivered by a 660 micron diameter optical fiber modified for cylindrical light distribution. Intravenous urography was performed both at three days and six weeks post PDT. Hydroureteronephrosis was revealed in one treated ureter and one untreated ureter. Mild dilatation of the ureter was noted by urography in another treated ureter and in one ureter that did not undergo light irradiation; no distal obstruction was revealed in either case by proximal infusion of saline or by histopathology. Nine of the 10 treated ureters were found to have either no abnormal pathology or only minimal lymphocytic infiltration. In this study, the normal ureter was shown to tolerate photodynamic therapy at energy densities equivalent to those used to effect tumor regression and the feasibility of using a cylindrical optical fiber for treatment of ureteral malignancies was confirmed.

Animals

Increased urinary excretion of glycosaminoglycans in insulin-dependent diabetic patients with limited joint mobility.

Urinary excretion of glycosaminoglycans (GAG) was measured in 24-h specimens collected from 27 insulin-dependent male diabetic patients and 22 healthy males of similar ages. Excretion relative to creatinine was increased by 35% in the diabetic group as a whole (p less than 0.02). Twelve patients with limited joint mobility (cheiroarthropathy) formed a subgroup with high excretion (69% above controls), those without limited joint mobility being similar to controls. There was no correlation of retinopathy with GAG excretion.

Adult

The importance of the time interval between insulin injection and breakfast in determining postprandial glycaemic control--a comparison between human and porcine insulin.

This study assessed the effect of the time interval between insulin injection and breakfast in determining subsequent postprandial glycaemic control and also whether this differed between highly purified porcine insulin and human insulin (crb) in six diabetic patients (age range 24-36 years, duration of diabetes greater than 10 years) usually treated with twice daily Actrapid MC and Monotard MC and with stable insulin requirements and diabetic control. On separate mornings each patient was given, after an overnight fast, their usual dose of either Actrapid MC and Monotard MC or Humulin S and Humulin Zn injected 5, 20, or 40 min before a standard breakfast. The postprandial glycaemic profile was not significantly different at any of the three time intervals with Actrapid MC and Monotard MC. However, with the human insulin the profile was significantly better at the 40 min interval than at the 5 min interval (p less than 0.05) and this was also better than any of the profiles with the porcine insulin, there being a significant difference between the two types of insulin (p less than 0.05). These findings suggest that the time interval between insulin injection and breakfast may be more important with human insulin than with porcine insulin.

Adult

Are reduced lung volumes in IDDM due to defect in connective tissue?

Lung volumes were measured by spirometry and helium-dilution technique in 28 young adult men with insulin-dependent diabetes mellitus (IDDM) of long duration and compared with 16 age- and height-matched adult men without diabetes. Reduced values for forced expiratory volume at 1 s, vital capacity, functional residual capacity, total lung capacity, residual volume, and single-breath carbon monoxide transfer factor were found for the IDDM patients compared to the control subjects. The results are consistent with reduced lung volumes in IDDM patients and did not correlate with the presence or absence of mild cheiroarthropathy but may relate to duration of diabetes.

Adult

Impairment of monocyte "lectin-like" receptor activity in type 1 (insulin-dependent) diabetic patients.

In order to investigate whether the ability of peripheral blood monocytes to bind bacteria is impaired in diabetes, we studied carbohydrate-binding ("lectin-like") receptors and the receptor for the Fc portion of immunoglobulin on monocytes from 25 male Type 1 (insulin-dependent) diabetic patients and 10 age-matched healthy control subjects. Peripheral blood monocytes from the diabetic patients expressed lower levels of "lectin-like" receptors compared to the control subjects, whereas the expression of the receptor for the Fc portion of immunoglobulin was similar in both populations. There was no correlation between the degree of "lectin-like" binding activity and plasma glucose concentration or glycaemic control. Recognition of unopsonized bacteria by the "lectin-like" receptor is impaired in Type 1 diabetes; this may affect the efficient elimination of potential pathogens.

Adult

Nonrandom association of cellular antigens with HTLV-III virions.

Retroviruses are known to incorporate cellular antigens as they bud from infected cells. To identify the cellular antigens that associate with the AIDS-retrovirus, we evaluated a preparation of HTLV-III antigens with a panel of monoclonal antibodies reactive with a variety of antigens expressed on the H9 T-cell line used to produce the virus. Only monoclonal antibodies that identified HLA class-II antigens, beta-2 microglobulin, and a single anti-HLA class-I antibody were reactive in an ELISA of solubilized HTLV-III virus. No reactivity was seen with 11 monoclonal antibodies to T-cell antigens or with five antibodies to determinants on HLA class-I A or B molecules. These data suggest that on H9 cells the association of budding HTLV-III virions with cellular antigens may be a nonrandom process in which some HLA antigens, particularly class-II antigens, are selectively incorporated into the viral envelope. It is possible that a selective association of HLA class II antigens with budding HTLV-III virions may also occur for T cells infected in vivo, and could have relevance for the pathogenesis of this virus.

Antibodies, Monoclonal

Effects of sodium replacement on uptake of the dipeptide glycylsarcosine by hamster jejunum in vitro.

We report observations on transport of the hydrolysis-resistant dipeptide glycylsarcosine by rings of everted hamster jejunum in vitro in the presence and absence of Na+, using several substituents for Na+: Li+, K+, Cs+, Tris, choline and mannitol. At most concentrations, mediated influx of glycylsarcosine was depressed by Li+, K+, Cs+ and Tris, though not abolished. At high concentrations, it was moderately increased by choline and mannitol. Under conditions in which the tissue could concentrate the peptide in the presence of Na+, uptake was greatly depressed by all the substituents and the ability to concentrate was abolished. The Kt of mediated influx was affected in different ways according to the substituent used. Kt was reduced by Li+ replacement of Na+ and increased by choline replacement. Vmax was greatly reduced by all metallic substituents but not by non-metallic substituents. Though the results cannot yet be satisfactorily interpreted, they suggest possible reasons for previous conflicting results and show that it is impossible to make the unqualified statement that transport of glycylsarcosine is 'Na+-dependent'. It is now doubtful whether transport of this peptide into the intestinal cells is by co-transport with Na+, and the whole matter of Na+-dependence of intestinal peptide transport is in question.

Animals

Consequences of fluid loss in patients treated with ACE inhibitors.

Three patients are described in whom haemodynamic collapse and acute renal failure occurred following intercurrent gastrointestinal fluid loss during treatment with an angiotensin converting-enzyme inhibitor. The possible consequences of blockade of the formation of angiotensin II during fluid loss are discussed.

Acute Kidney Injury

Transient atrial fibrillation precipitated by hypoglycaemia: two case reports.

We describe two insulin-dependent diabetic females who presented with severe hypoglycaemia associated with atrial fibrillation which reverted to sinus rhythm after intravenous dextrose. Atrial fibrillation has not previously been reported as a complication of hypoglycaemia in insulin-dependent diabetic patients.

Adult

Changes in some aspects of platelet function with improvement of glycaemic control over 6 months.

Numerous platelet abnormalities, particularly hyperaggregation, have been described in diabetic patients, and it has been suggested that these may contribute towards the pathogenesis of microvascular complications. In the present study, the changes that occur in ADP-induced aggregation, sensitivity to a stable prostacyclin analogue (Iloprost), aggregation-induced thromboxane B2 production and platelet cyclic AMP levels were investigated in 9 young insulin-dependent diabetics, in which the glycaemic control significantly improved in one group (n = 5; HbA1 from 11.9-9.0%) over a 6 month period. With improvement of glycaemic control there was no significant change in the concentration of ADP required to produce 50 percent of the maximum aggregation wave response. However, there was a significant increase in the responsiveness of platelets to Iloprost and increased platelet thromboxane B2 production. There was no significant difference between the basal platelet cAMP levels before or after exposure to Iloprost. This study suggests that with improved short-term glycaemic control, although there are changes in platelet function, there may be no alteration in the homeostatic balance.

Adenosine Diphosphate

Mechanisms of peptide transport.

This review touches on the development of the concept of transmembrane transport of peptides, which originated more than 100 years ago, and discusses present knowledge of the phenomenon, with special reference to intestinal absorption of peptides. It deals with (1) Peptide transport in animal small intestine and its main features--active transport of di- and tripeptides into the absorptive cells, the question of sodium or proton dependence of peptide transport, the independence of peptide and amino acid transport, competition for transport between peptides, the number of transport systems involved, the influence of molecular structure on peptide transport, transport kinetics and relative rates of absorption of peptides and amino acids, nutritional and therapeutic aspects of peptide transport, mechanisms of absorption of small peptides of dietary origin and mechanisms of absorption of biologically active peptides (2) Peptide transport in other animal cells and tissues (3) Peptide transport in microorganisms (4) Peptide transport in higher plants and (5) Physiological advantages of peptide transport. The concluding remarks stress that though most of the salient features of peptide absorption may have been established by 1975, more investigators might usefully be engaged in studying the many remaining questions concerning peptide transport in the animal body, and point out the unfortunate effects of too narrow an approach to problems in the field.

Amino Acids