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Biomedical subjects

M M Jones

Publications and source records attributed to M M Jones.

At least 163 records · Page 9Linked to original sources

The fibrous flexor sheaths of the fingers.

The structure of the digital fibrous flexor sheath was examined by dissection and histology. The presence of a specific system of named fibrous tissue bands, forming annular and cruciate pulleys, was noted confirming details which are well established in the surgical literature although not detailed by the anatomical texts. These pulleys were linked by thin parts of the sheath. When the inner aspect of the sheath was examined, it was found that it was not a continuous smooth surface, as depicted in both anatomical and surgical texts. The thin parts of the sheath often overlapped the free edges of the pulleys before attaching to their superficial aspects, so that the pulleys possessed free edges within the sheath. Forty eight cadaveric fingers were examined in order to determine the frequency of occurrence and sizes of these overlaps. The largest and most frequent overlap was found at the distal end of the A2 pulley (which attaches to the proximal phalanx).

Cadaver↗

Evaluation of preserved bovine tendon xenografts: a histological, biomechanical and clinical study.

Glutaraldehyde treated bovine tendon xenografts have been introduced into clinical trials as human knee ligament replacements recently, following animal experiments. This paper reports a further clinical study in which complications arose from implant debris. A laboratory study showed that the implants were not absorbed or integrated into the tissues of the host animals, as had been claimed by the originators. Mechanical tests of tendon reconstructions showed that the implants were not functional. It was concluded that this material is not suitable for clinical use within the knee joint as a cruciate ligament prosthesis.

Animals↗

Chelating-agent suppression of cadmium-induced hepatotoxicity.

The administration of sodium N-methyl-N-dithiocarboxy-D-glucamine (NaG) at 500 mg/kg, i.p., or sodium calcium diethylenetriaminepentaacetic acid (DTPA) at 632.5 mg/kg, i.p., reduces the serum enzyme levels characteristic of hepatic damage following the intravenous administration of cadmium chloride (3.5 mg CdCl2.2.5H2O/kg). Some effect on serum enzyme levels was found even when the interval between administration of cadmium chloride and that of the antagonist was as great as 4 h. The enzymes examined included aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), alanine aminotransferase (SGPT), and alkaline phosphatase (AP). A histopathological examination of the livers of such animals also reveals the presence of a significant protective action.

Alanine Transaminase↗

Effects of diethyldithiocarbamate and structural analogs in mice with systemic candidal infections.

Three different substituted dithiocarbamates: sodium diethyldithiocarbamate (DDTC), sodium dimethyldithiocarbamate (DmDTC), and sodium N-methyl-D-glucamine dithiocarbamate (NMG-DTC) were evaluated for their ability to combat the growth and development of three human pathogenic strains of Candida albicans, in vitro and in vivo, in mice. DDTC and DmDTC produced marked growth inhibition on agar plates, in vitro, of three different strains of Candida albicans, while NMG-DTC displayed little inhibitory effect. Low, nontoxic doses of each compound administered to immunosuppressed mice exhibited impressive therapeutic effects in treating candidiasis. NMG-DTC showed the best consistent therapeutic antifungal effect against Candida albicans in mice immunosuppressed with Solu-Medrol. Combinations of low doses of DDTC and Amphotericin-B appeared to be effective in treating systemic candidal infections, and the results suggested that these combinations may offer therapeutic advantages over those produced by the use of either agent alone.

Amphotericin B↗

Dithiocarbamate inhibition of cadmium-induced changes in spermatozoan acetyltransferases.

The administration of sodium N-methyl-N-dithiocarboxy-D-glucamine (NaG) subsequent to the administration of CdCl2.2.5H2O to male rats, inhibits the cadmium-induced decreases in spermatozoan acetyltransferase (AT) levels and provides marked protection against the cadmium-induced morphologic testicular changes in the cauda and corpus and partial protection against the changes in the caput.

Acetyltransferases↗

Amphipathic dithiocarbamates as cadmium antagonists: N-cyclohexyl-N-sulfonatoalkyl derivatives.

Disodium salts of the substituted dithiocarbamates (DTCs) N-cyclohexyl-N-(2-sulfonatoethyl) DTC, N-cyclohexyl-N-(3-sulfonatopropyl) DTC, and N-cyclohexyl-N-(2-hydroxy-3-sulfonatopropyl) DTC were synthesized and assessed as complexing agents for reducing organ concentrations of cadmium (Cd) in mice. At least one week after mice were given 0.03 mg of CdCl2.2.5 H2O containing 1.0 microCi of 109CdCl2 ip they were treated ip with various doses of each DTC. Administration of 4.44 mmoles/kg of each analog q2dx4 produced about a 60% reduction in the whole-body Cd burdens. There was approximately a 50% reduction of renal Cd concentrations and a greater than 90% reduction of hepatic Cd. There was no significant effect on the Cd levels in pancreas, spleen, testes, or brain. Mobilization of organ Cd stores led to excretion of Cd principally in the feces; treatment with 2.22 mmoles/kg of each analog qdx3 promoted a cumulative excretion of 32-40% of the administered metal. Rational design of potential Cd complexing agents is discussed with reference to the relative aqueous and lipid solubilities of the N,N-substituents on DTC congeners.

Animals↗

The effect of some chelating agents on the biliary and urinary excretion of manganese in rats.

The biliary excretion of manganese, in rats which have been loaded with manganese via their drinking water, can be significantly enhanced by the administration of the chelating agents: desferrioxamine (DSF), sodium bis(hydroxyethyl) dithiocarbamate (DEDTC), and sodium isonipecotamidedithiocarbamate (INADTC). The effect of these chelating agents on the urinary excretion of manganese was more complex and was found to be dependent upon the level of loading of manganese as well as the individual chelating agent. For animals with drinking water containing 400 mg/liter of manganese, the administration of the chelating agents led to a decrease in the sum of the biliary plus urinary manganese excretion. The results are of special interest in that they show that under some conditions the administration of chelating agents can lead to changes other than those expected.

Animals↗

Multiple primary malignancies in head and neck cancer.

Multiple primary (MP) malignancies were found in 9.7% of 1961 patients with primary head and neck cancer diagnosed at The Johns Hopkins Hospital, Baltimore, during the years 1975 to 1985. The index tumors were divided into six main groups. Out of the 190 MP malignancies, 46.9% were synchronous and 53.1% were metachronous. Seventy-four percent of MP lesions were noted during the first year after diagnosis of the index primary tumor. Patients with an index tumor in the upper aerodigestive tract had a significantly increased risk of developing a second cancer in the head and neck area. This risk was 5.94 for the oral cavity, 6.98 for the pharynx, 3.57 for the larynx, and 7.02 for the esophagus. Patients with an index tumor in the salivary gland or the thyroid gland had, respectively, a 3.59 and a 7.38 higher risk than the general population of developing a second tumor. Efforts aimed at improving the survival of patients with head and neck cancer must incorporate strategies for the prevention, early detection, and treatment of MP neoplasms.

Adult↗

Congenital cytomegalovirus infection and maternal systemic lupus erythematosus: a case report.

We describe an infant with symptomatic congenital cytomegalovirus infection, who was born to a mother with active systemic lupus erythematosus. Infection in the child resulted from reactivation of maternal cytomegalovirus infection. The mother's use of prednisone may have contributed to the reactivation. The role of maternal immunosuppression in the acquisition of congenital viral infection by the neonate is discussed.

Adult↗

Inhibition of cis-diamminedichloroplatinum (II)--induced renal toxicity in the rat.

The hydroxyl-containing dithiocarbamates, sodium (di(hydroxyethl)-dithiocarbamate (NaY) and sodium N-methyl, N-dithiocarboxy-D-glucamine (NaG), appear to possess definite advantages over sodium diethyldithiocarbamate (DDTC) in reducing the cis-dichlorodiammineplatinum (Cis-Pt)-induced renal damage in rats given Cis-Pt as an IV bolus of 7.5 mg/kg 1 h before the IP administration of the dithiocarbamate. Renal damage, as estimated by blood urea nitrogen (BUN) values and serum creatinine levels, was less at all times up until sacrifice in animals given NaY or NaG than in those given DDTC. An even more effective method for suppression of Cis-Pt renal toxicity is to use a combination of procedures. The most efficacious combination involves a 24-h pretreatment with DDTC or NaG plus acetazolamide and normal saline hydration 30 min before administration of Cis-Pt, followed by post-treatment with NaG. With this combination therapy renal function can be almost completely spared. Although DDTC or NaG pretreatment is highly effective when used in conjunction with NaG post-treatment, DDTC or NaG pretreatment alone has no renal sparing effect on renal function or renal platinum accumulation. In experiments in which antidotes were given 1 h after Cis-Pt and the animals were followed up for 75 days, a chronic interstitial nephritis at 75 days, suggesting a persistent cell-mediated immune response to Cis-Pt-induced renal damage, may be the basis for chronically abnormal renal function resulting from Cis-Pt. Treatment with all three dithiocarbamates, NaY, NaG, and DDTC, reduced the intensity of this cellular reaction and also reduced platinum levels in the kidneys. Although NaY and NaG are effective heavy metal chelators and renal function is spared and kidney platinum levels are substantially reduced by the dithiocarbamates, no parallel loss of antineoplastic activity by Cis-Pt on the rat Walker carcinoma was observed. Since the dithiocarbamates have no known human toxicity that would disqualify their clinical use, phase 1 clinical trials are indicated.

Animals↗

Control of some aspects of cis-platinum nephrotoxicity.

The elevations of blood urea nitrogen and serum creatinine caused by cis-platinum in rats can be prevented by a combination of procedures centered around the administration of sodium N-methyl-N-dithiocarboxyglucamine (NaG), before and very soon after the cis-platinum is administered in hypertonic (4.5%) saline. Elevations in-blood urea nitrogen and serum creatinine levels subsequent to such treatment are largely eliminated. These same procedures appear to have no effect on the anti-tumor action of the cis-platinum, as measured by tumor size and mass and by survival times, in female Sprague-Dawley rats inoculated with the Walker 256 carcinoma. The degree of myelosuppression, as measured by the white blood cell count is also slightly reduced. White blood cell counts returned to normal values more rapidly in animals treated with NaG than in those treated with cis-platinum alone. An examination of the dose-response curve for the suppression of cis-platinum nephrotoxicity by NaG shows that this can be achieved with mole ratios of NaG: cis-platinum as low as 1:1 given after appropriate pretreatment. A preliminary structure-activity study on the suppression of cis-platinum induced elevations in blood urea nitrogen and serum creatinine by four closely related dithiocarbamates shows that this can also be achieved effectively by several dithiocarbamates in which the nitrogen atom bears polar substituents.

Animals↗

Role of intravenous nitroglycerin in the treatment of severe pregnancy-induced hypertension complicated by pulmonary edema.

Intravenous nitroglycerin would appear to be an ideal agent for the treatment of severe pregnancy-induced hypertension complicated by cardiogenic pulmonary edema. Nitroglycerin infusion effectively reduces preload by venous dilatation and, at higher doses, results in arterial vasodilatation. Because of these pharmacologic properties, the effects of intravenous nitroglycerin were studied in three patients with severe pregnancy-induced hypertension complicated by pulmonary edema. The major cardiovascular effects of nitroglycerin were to reduce the mean pulmonary capillary wedge pressure from 27 +/- 4 to 14 +/- 6 mm Hg, which result in a change in the colloid osmotic pressure to pulmonary capillary wedge pressure gradient from -10 to 2 mm Hg. No significant changes occurred in heart rate, central venous pressure, or cardiac index. Analysis of oxygen-related parameters revealed a significant (p less than 0.05) increase in oxygen delivery and extraction accompanied by a 53% increase in oxygen consumption. The changes in oxygen-related variables appeared to be secondary to a fall in mixed venous oxygen tension from 39 +/- 4 to 33 +/- 1 torr. These changes occurred without any significant improvement in arterial oxygen tension. We conclude that while intravenous nitroglycerin expeditiously corrects the hydrostatic derangements of pulmonary edema seen in pregnancy-induced hypertension, a rapid improvement in arterial oxygenation does not occur.

Female↗

Cardiovascular alterations in severe pregnancy-induced hypertension: effects of intravenous nitroglycerin coupled with blood volume expansion.

Control of blood pressure in severe pregnancy-induced hypertension has often relied on agents with an unpredictable onset and duration of action. Because intravenous nitroglycerin is a potent, rapidly acting agent with a hemodynamic half-life measured in minutes, we evaluated its cardiovascular effects with and without volume expansion in six patients with severe pregnancy-induced hypertension. Nitroglycerin alone reduced mean arterial pressure by 27.5% without any significant changes in heart rate, central venous pressure, or stroke volume. The pulmonary capillary wedge pressure fell from 9 +/- 3 to 4 +/- 2 mm Hg (p less than 0.05) while the cardiac index decreased from 3.51 +/- 0.67 to 2.87 +/- 0.76 L/min X m2. Oxygen delivery fell significantly (p less than 0.05), from 617 +/- 78 to 491 +/- 106 ml/min X m2. While volume expansion alone had no effect on mean arterial pressure, the combination of blood volume expansion and nitroglycerin resulted in a marked resistance to the hypotensive effect of nitroglycerin. Cardiac index, pulmonary capillary wedge pressure, and oxygen utilization were not significantly different from baseline values when volume expansion preceded nitroglycerin. We conclude that the ease with which nitroglycerin reduces blood pressure is dependent on the individual patient's volume status. Although volume expansion allows one to maintain cardiac index, pulmonary capillary wedge pressure, and oxygen utilization when used in combination with nitroglycerin, this benefit may be offset by a concomitant reduction in hypotensive capability.

Adolescent↗

Effects of monoalkyl dithiocarabamates on mobilization of cadmium in the mouse.

Monoalkyl dithiocarbamates are capable of mobilizing cadmium from aged intracellular deposits in which the cadmium is largely present in metallothionein. The sodium salts of monomethyl, ethyl, n-propyl, and n-butyl dithiocarbamates have been prepared, characterized, and examined for their relative ability to mobilize cadmium from such aged deposits in the kidneys, liver, spleen, testes, brain, and pancreas as well as from the whole body, using sodium diethyl dithiocarbamate as the positive control. Alterations in the structure of the dithiocarbamates can be correlated with alterations in organ cadmium levels. The acute toxicity of these compounds is sufficiently greater than disubstituted dithiocarbamates that their use would appear to possess few advantages, although they do seem to be more effective in reducing testicular cadmium levels.

Animals↗

Effects of dithiocarbamates on cadmium distribution and excretion in chronically exposed rats.

One month after termination of a 3-mo exposure of rats to cadmium (Cd in drinking water at a concentration of 50 mg/l), the effects of dithiocarbamate analogs on the excretion and distribution of the cadmium were determined. Sodium salts of three dithiocarbamates [sodium bis(hydroxyethyl) dithiocarbamate, DEDTC; sodium N-methyl-D-glucamine dithiocarbamate, MGDTC; and sodium 4-carboxamidopiperidine dithiocarbamate, INADTC] were given to rats ip 2 times at 2.46 mmol/kg. In the following administration of the first injection of DEDTC, cadmium excretion via the urine amounted to 15.8 micrograms and via bile amounted to 124.4 micrograms Cd. Following administration of MGDTC, the urinary and biliary excretions of cadmium were 14.5 and 47 micrograms, respectively, while in the case of INADTC the corresponding values were 23.6 and 7.9 micrograms cadmium. In control animals the urinary and biliary excretion per 12 h reached 0.09 and 0.12 micrograms Cd. Gel permeation chromatography (GPC) analysis of bile revealed differences in the distribution of Cd in the elution fractions after the first injections of the individual dithiocarbamates. For all three dithiocarbamates, significant decreases of the concentrations of cadmium in the liver and kidney were found. DEDTC (but neither of the other compounds) increased the concentration of cadmium in the brain from control levels of 49 +/- 5 ppb to 105 +/- 16 ppb.

Administration, Oral↗

Structural effects in the dithiocarbamate-enhanced biliary excretion of cadmium.

The dithiocarbamate enhancement of the biliary excretion of cadmium in rats loaded with cadmium (by either the oral or sc route) was found to be strongly dependent on the structure of the groups attached to the nitrogen atom of the dithiocarbamate moiety. Those dithiocarbamates containing hydroxyl-bearing attached groups were found to be capable of causing the greatest enhancement of the cadmium content of the bile. For the compounds of this type that were examined, this enhancement of biliary cadmium content varied from 30-fold to over 2000-fold. No enhancement of the biliary excretion of cadmium was found subsequent to the administration of sodium diethyldithiocarbamate, though this compound is known to cause a significant increase in the fecal excretion of cadmium.

Administration, Oral↗