X-ray irradiation effects on nuclear and membrane regions of single SH-SY5Y human neuroblastoma cells investigated by Raman micro-spectroscopy.

Raman micro-spectroscopy was performed in vitro on nuclear and membrane regions of single SH-SY5Y human neuroblastoma cells after irradiation by graded X-ray doses (2, 4, 6, 8 Gy). The acquired spectra were analyzed by principal component analysis (PCA) and interval-PCA (i-PCA) methods. Biochemical changes occurring in the different regions of single cells as a consequence of the radiation exposure were observed in cells fixed immediately after the irradiation. The most relevant effects arose from the analysis of the spectra from the cell nucleus region. The observed changes were discussed in terms of the modifications in the cell cycle, resulting in an increase in the DNA-related signal, a protein rearrangement and changes in lipid and carbohydrates profiles within the nucleus. Potential markers of an apoptotic process in cell population irradiated with 6 and 8-Gy X-ray doses could have been singled out. No significant effects were found in spectra from cells fixed 24 h after the irradiation, thus suggesting the occurrence of repairing processes of the X-ray induced damage.

Forensic sciences and forensic odontology: issues for dental hygienists and therapists.

The scientific literature contains very little about the role of the dental hygienist/therapist in the specific areas of forensic investigations and collection of evidence. The authors examine how the contribution of a highly qualified dental hygienist can be particularly helpful during human forensic identification operations and non-accidental traumas like domestic violence, child abuse, neglect and bitemarks. Forensic dental identification of human remains is a highly complex multidisciplinary challenge. It requires the involvement of several professionals who are expert in forensic science. Among these, one or more adequately trained dental hygienists could be involved. Dental hygienists/therapists may also be asked to record cutaneous lesions in two different situations. The first may be the dental office where she/he may detect oval, elliptic, or semicircular lesions on the skin of the uncovered neck, shoulder and arms of a patient. The second is the crime scene or the morgue (if one is involved), which may require a visit by the forensic odontologist called by the medical examiner or the coroner to perform an odontological autopsy. The purpose of our study is to highlight procedures that should be followed by the dental hygienist/therapist in collecting forensic information in the above-mentioned scenarios. As a valuable resource, the authors recommend training of dental hygienists in the area of forensic sciences, with particular attention to information technology and photography.

Liver X receptor activation controls intracellular cholesterol trafficking and esterification in human macrophages.

Liver X receptors (LXRs) are nuclear receptors that regulate macrophage cholesterol efflux by inducing ATP-binding cassette transporter A1 (ABCA1) and ABCG1/ABCG4 gene expression. The Niemann-Pick C (NPC) proteins NPC1 and NPC2 are located in the late endosome, where they control cholesterol trafficking to the plasma membrane. The mobilization of cholesterol from intracellular pools to the plasma membrane is a determinant governing its availability for efflux to extracellular acceptors. Here we investigated the influence of LXR activation on intracellular cholesterol trafficking in primary human macrophages. Synthetic LXR activators increase the amount of free cholesterol in the plasma membrane by inducing NPC1 and NPC2 gene expression. Moreover, ABCA1-dependent cholesterol efflux induced by LXR activators was drastically decreased in the presence of progesterone, which blocks postlysosomal cholesterol trafficking, and reduced when NPC1 and NPC2 mRNA expression was depleted using small interfering RNA. The stimulation of cholesterol mobilization to the plasma membrane by LXRs led to a decrease in cholesteryl ester formation and Acyl-coenzyme A cholesterol acyltransferase-1 activity. These data indicate that LXR activation enhances cholesterol trafficking to the plasma membrane, where it becomes available for efflux, at the expense of esterification, thus contributing to the overall effects of LXR agonists in the control of macrophage cholesterol homeostasis.

Effects of recent, short-term hyperglycemia on responses to hypoglycemia in humans. Relevance to the pathogenesis of hypoglycemia unawareness and hyperglycemia-induced insulin resistance.

A single episode of recent hypoglycemia increases, whereas long-term hyperglycemia decreases, the glycemic thresholds of responses of counterregulatory hormone and symptoms to subsequent hypoglycemia in humans. To assess whether short-term, antecedent hyperglycemia exerts effects opposite to those observed after acute hypoglycemia, seven normal, nondiabetic subjects and eight insulin-dependent diabetes mellitus (IDDM) patients were studied during hyperinsulinemic-hypoglycemic clamp (sequential, 90-min plateaus of plasma glucose [PG] of 4.3, 3.7, 3.0, and 2.4 mmol/l). Nondiabetic subjects were studied the morning after either 6-h clamped hyperglycemia (PG approximately 13.5 mmol/l) or euglycemia (PG approximately 5 mmol/l) between 1600 and 2200 the previous day (glucose and insulin infused on both occasions), as well as after nocturnal hyperglycemia (PG approximately 13.5 mmol/l) or euglycemia between 2300 and 0500. The IDDM patients were studied after 15 h of euglycemia or hyperglycemia (approximately 17 mmol/l) but identical hyperinsulinemia (approximately 225 pmol/l) between 1600 and 0700. Neither PG thresholds of counterregulatory hormone, symptoms, onset of cognitive dysfunction to hypoglycemia, nor maximal responses were affected by antecedent, short-term hyperglycemia in normal nondiabetic subjects and IDDM patients (NS). However, the rate of glucose infusion required to maintain hypoglycemic plateaus during hypoglycemia was lower after hyperglycemia (nondiabetic subjects 31.2 +/- 3.4 vs. 36.7 +/- 4 mumol.kg-1.min-1, IDDM patients 33 +/- 3.1 vs. 42.5 +/- 3.9 mumol.kg-1.min-1; P < 0.05) indicating greater insulin resistance induced by antecedent hyperglycemia. In conclusion, in contrast to acute hypoglycemia and long-term hyperglycemia, recent, short-term hyperglycemia does not affect physiological responses to hypoglycemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Pharmacokinetics and pharmacodynamics of subcutaneous injection of long-acting human insulin analog glargine, NPH insulin, and ultralente human insulin and continuous subcutaneous infusion of insulin lispro.

To compare the pharmacokinetics/dynamics of the long-acting insulin analog glargine with NPH, ultralente, and continuous subcutaneous (SC) infusion of insulin lispro (continuous subcutaneous insulin infusion [CSII]), 20 C-peptide-negative type 1 diabetic patients were studied on four occasions during an isoglycemic 24-h clamp. Patients received SC injection of either 0.3 U/kg glargine or NPH insulin (random sequence, crossover design). On two subsequent occasions, they received either an SC injection of ultralente (0.3 U/kg) or CSII (0.3 U x kg(-1) x 24 h(-1)) (random sequence, crossover design). After SC insulin injection or CSII, intravenous (IV) insulin was tapered, and glucose was infused to clamp plasma glucose at 130 mg/dl for 24 h. Onset of action (defined as reduction of IV insulin >50%) was earlier with NPH (0.8 +/- 0.2 h), CSII (0.5 +/- 0.1 h), and ultralente (1 +/- 0.2 h) versus glargine (1.5 +/- 0.3 h) (P < 0.05) (mean +/- SE). End of action (defined as an increase in plasma glucose >150 mg/dl) occurred later with glargine (22 +/- 4 h) than with NPH (14 +/- 3 h) (P < 0.05) but was similar with ultralente (20 +/- 6 h). NPH and ultralente exhibited a peak concentration and action (at 4.5 +/- 0.5 and 10.1 +/- 1 h, respectively) followed by waning, whereas glargine had no peak but had a flat concentration/action profile mimicking CSII. Interindividual variability (calculated as differences in SD of plasma insulin concentrations and glucose infusion rates in different treatments) was lower with glargine than with NPH and ultralente (P < 0.05) but was similar with glargine and CSII (NS). In conclusion, NPH and ultralente are both peak insulins. Duration of action of ultralente is greater, but intersubject variability is also greater than that of NPH. Glargine is a peakless insulin, it lasts nearly 24 h, it has lower intersubject variability than NPH and ultralente, and it closely mimics CSII, the gold standard of basal insulin replacement.

Meticulous prevention of hypoglycemia normalizes the glycemic thresholds and magnitude of most of neuroendocrine responses to, symptoms of, and cognitive function during hypoglycemia in intensively treated patients with short-term IDDM.

To test the hypothesis that hypoglycemia unawareness is largely secondary to recurrent therapeutic hypoglycemia in IDDM, we assessed neuroendocrine and symptom responses and cognitive function in 8 patients with short-term IDDM (7 yr) and hypoglycemia unawareness. Patients were assessed during a stepped hypoglycemic clamp, before and after 2 wk and 3 mo of meticulous prevention of hypoglycemia, which resulted in a decreased frequency of hypoglycemia (0.49 +/- 0.05 to 0.045 +/- 0.03 episodes/patient-day) and an increase in HbA1c (5.8 +/- 0.3 to 6.9 +/- 0.2%) (P < 0.05). We also studied 12 nondiabetic volunteer subjects. At baseline, lower than normal symptom and neuroendocrine responses occurred at lower than normal plasma glucose, and cognitive function deteriorated only marginally during hypoglycemia. After 2 wk of hypoglycemia prevention, the magnitude of symptom and neuroendocrine responses (with the exception of glucagon and norepinephrine) nearly normalized, and cognitive function deteriorated at the same glycemic threshold and to the same extent as in nondiabetic volunteer subjects. At 3 mo, the glycemic thresholds of symptom and neuroendocrine responses normalized, and surprisingly, some of the responses of glucagon recovered. We concluded that hypoglycemia unawareness in IDDM is largely reversible and that intensive insulin therapy and a program of intensive education may substantially prevent hypoglycemia and at the same time maintain the glycemic targets of intensive insulin therapy, at least in patients with IDDM of short duration.

Long-term intensive therapy of IDDM patients with clinically overt autonomic neuropathy: effects on hypoglycemia awareness and counterregulation.

To test the hypothesis that hypoglycemia unawareness and impaired counterregulation are reversible after meticulous prevention of hypoglycemia in IDDM patients with diabetic autonomic neuropathy (DAN), 21 patients (8 without DAN [DAN-]; 13 with DAN [DAN+]; of the latter, 7 had orthostatic hypotension [DAN+PH+] and 6 did not [DAN+PH-]) and 15 nondiabetic subjects were studied during stepped hypoglycemia (plateau plasma glucose decrements from 5.0 to 2.2 mmol/l) before and 6 months after prevention of hypoglycemia (intensive therapy). After 6 months, frequency of mild hypoglycemia decreased from approximately 20 to approximately 2 episodes/patient-month while HbA1c increased from 6.2 +/- 0.3 to 6.9 +/- 0.2% (P < 0.05). Responses of adrenaline improved more in DAN- patients (from 1.17 +/- 0.12 to 2.4 +/- 0.22 nmol/l) than in DAN+PH- (from 0.75 +/- 0.25 to 1.56 +/- 0.23 nmol/l) and DAN+PH+ patients (from 0.80 +/- 0.24 to 1.15 +/- 0.27 nmol/l, P < 0.05) but remained lower than in nondiabetic subjects (4.9 +/- 0.37 nmol/l, P < 0.05), whereas glycemic thresholds normalized only in DAN-, not DAN+. Autonomic symptoms of hypoglycemia improved but remained lower in DAN- (6.2 +/- 0.6) than in nondiabetic subjects (8.1 +/- 1.1) and lower in DAN+PH+ (4 +/- 0.8) than in DAN+PH- subjects (5.1 +/- 0.8, P < 0.05), whereas neuroglycopenic symptoms normalized (NS). Cognitive function deteriorated less before than after prevention of hypoglycemia (P < 0.05). Thus, intensive therapy with emphasis on preventing hypoglycemia reverses hypoglycemia unawareness in DAN+ patients despite marginal improvement of adrenaline responses, results in low frequency of hypoglycemia despite impaired counterregulation, and maintains HbA1c in the range of intensive therapy. We conclude that DAN, long IDDM duration per se, and antecedent recent hypoglycemia contribute to different extents to impaired adrenaline responses and hypoglycemia unawareness.

Alcohol abuse and dependence in Latinos living in the United States: validation of the CAGE (4M) questions.

BACKGROUND: Brief alcoholism screening questionnaires have not been adequately studied in the rapidly growing Latino population living in the United States. OBJECTIVE: To assess (1) the prevalence of alcoholism and (2) the performance of 2 alcohol screening instruments in Latinos. SUBJECTS AND METHODS: We performed a cross-sectional interview study in an urban teaching hospital-based primary care practice. Consecutive self-identified Latino subjects provided informed consent. All subjects were interviewed in English or Spanish using 2 alcoholism screening tools, the CAGE (or the Spanish version, the 4M), and the Alcohol Use Disorders Identification Test, and a criterion standard for the diagnosis of alcohol abuse and dependence, the Composite International Diagnostic Interview. RESULTS: Of 210 subjects interviewed, 36% had a lifetime diagnosis of alcohol abuse or dependence by the criterion standard. Thirty-one percent were currently drinking hazardous amounts of alcohol. A CAGE (4M) score of 1 or more was 92% sensitive and 74% specific, and a score of 2 or more was 80% sensitive and 93% specific for a lifetime diagnosis of alcohol abuse or dependency. CAGE (4M) scores of 0, 2, 3, and 4 were associated with likelihood ratios (0.1, 4.8, 18.5, and 36.8, respectively) that resulted in substantial changes from pretest (36%) to posttest probability (to 6%, 73%, 91%, and 95%, respectively) of a diagnosis of alcohol abuse or dependency. At the standard cutoff point, the Alcohol Use Disorders Identification Test detected only 51% of subjects with alcohol disorders. CONCLUSIONS: In Latinos in primary care settings, alcohol abuse and dependence are common and the CAGE (4M) is a brief, valid, screening tool for detecting alcohol use disorders.

Improved postprandial metabolic control after subcutaneous injection of a short-acting insulin analog in IDDM of short duration with residual pancreatic beta-cell function.

OBJECTIVE: To compare postprandial metabolic control after subcutaneous injection of a short-acting insulin analog [Lys(B289),Pro(B29)] (Lispro) or human regular insulin (Humulin R U-100 [Hum-R]) in insulin-dependent diabetes mellitus (IDDM) of short duration with residual beta-cell function. RESEARCH DESIGN AND METHODS: Six IDDM patients (age 25 +/- 2 years, diabetes duration 14 +/- 2 months, HbA1c 6.4 +/- 0.5%) with residual pancreatic beta-cell function (fasting plasma C-peptide 0.19 +/- 0.02 nmol/l) were studied on three different occasions. Postbreakfast plasma glucose was maintained at approximately 7.1 mmol/l by means of intravenous insulin until either 1200 when 0.1 U/kg Hum-R was injected or until 1225 when 0.1 U/kg of either Hum-R or Lispro was injected subcutaneously. Lunch (mixed meal, 692 Kcal) was served at 1230 (0 min). Six nondiabetic control subjects were also studied. RESULTS: After Lispro administration, the 120-min plasma glucose decreased more (6.1 +/- 0.3 mmol/l) than after injection of Hum-R at -30 min (7.7 +/- 0.3 mmol/l) or -5 min (9.9 +/- 0.2 mmol/l). By the end of the study, plasma glucose was still lower after Lispro was injected (6.7 +/- 0.3 mmol/l) than after Hum-R was injected at -30 min (7.6 +/- 0.3 mmol/l) or -5 min (7.3 +/- 0.2 mmol/l) (P < 0.05). Two IDDM patients required glucose to prevent hypoglycemia after being injected with Lispro, but four required glucose after being injected with Hum-R at -5 min (Lispro approximately 27 mmol glucose infused between 90 and 240 min; Hum-R approximately 80 mmol between 240 and 390 min). After Lispro, plasma insulin peaked earlier (at 30 min, 342 +/- 29 pmol/l) than after Hum-R injection at -30 min (at 90 min, 198 +/- 28 pmol/l) and was superimposable on that of nondiabetic subjects. In Hum-R injected at -5 min, plasma insulin peaked later (at 120 min) and subsequently remained greater than in the two other studies. CONCLUSIONS: Despite the lack of a time interval between injection and meal, Lispro controls postprandial plasma glucose concentration better than Hum-R given 30 min before meals and, to an even greater extent, better than Hum-R given 5 min before meals. In addition, Lispro minimizes the risk of postprandial hypoglycemia, thus closely mimicking the postprandial glucose homeostasis of nondiabetic subjects. IDDM patients with residual pancreatic beta-cell function are the ideal candidates for prandial use of Lispro because they can maintain near-normoglycemia longer after subcutaneous analog injection because of residual endogenous insulin secretion.

Neglect-associated constructional disorders: a paradoxical phenomenon?

Five neglect patients without diffuse cognitive impairment or overt constructional disabilities were asked to bisect lines and rectangles and to copy rectangles bisected in their midplane. As a group, patients showed the usual rightward bias in bisecting lines and a milder deviation in bisecting horizontally-aligned rectangles, but showed a leftward deviation of the subjective midline in the copying task. This was due to drawing the left half shorter with respect to normal controls but three patients also drew the right half longer (the total length was the same as that of controls). A possible interpretation of rectangle copying results in these three patients is that they could create a representation of the stimulus to be copied accurately enough to reproduce its total length correctly but the subjective distribution of right and left space within that representation was unbalanced. However, specific experimental work is needed to verify why our patients with mild to moderate unilateral spatial neglect overrepresented the left side in a line bisection task and underrepresented it in a copying task.

N-methyl-D-aspartate lesions of the pedunculopontine nucleus block acquisition and impair maintenance of responding reinforced with brain stimulation.

Excitotoxin lesions of the pedunculopontine tegmental nucleus have been found to block the acquisition of a conditioned place preference induced by morphine or amphetamine, and it has been suggested that such lesions may attenuate the primary reinforcing effects of these drugs and, possibly, other reinforcers. The present study examined the effects of pedunculopontine lesions on the reinforcing effects of brain stimulation. N-methyl-D-aspartate-induced lesions of the pedunculopontine nucleus prevented spontaneous acquisition of lever pressing for brain stimulation reinforcement during five daily 1 h sessions of training. The effective lesions damaged the retrorubral fields in addition to the pedunculopontine tegmental nucleus. N-methyl-D-aspartate (25 or 50 nmol) lesions of the retrorubral fields did not block acquisition of self-stimulation, however, controls reached their maximum rate of responding in the first session, responding of rats with retrorubral field lesions gradually increased over five days. When excitotoxin-induced lesions of the pedunculopontine nucleus were made after acquisition of self-stimulation, lesioned rats continued to respond to brain stimulation, but at a lower rate than controls. The results show that pedunculopontine lesions interfere with the learning and expression of a response reinforced by brain stimulation just as they block learning motivated by drugs and natural rewards. They also suggest that collateral damage to the retrorubral fields may contribute to the effects of pedunculopontine lesions on reinforced behaviour. These data support the view that the pedunculopontine tegmental nucleus is involved in the process by which reinforcers control purposive behaviour.

Depth dependence of the analytical expression for the width of the point spread function (spatial resolution) in time-resolved transillumination.

Simple analytical expressions for the point spread function (PSF) at different depths can save computation time and improve the performance of inverse algorithms for optical imaging. In particular, application of such formulas simplifies quantification of the optical characteristics of tissue abnormalities inside highly scattering media. Earlier it was shown within the random walk theory framework that the PSF for time-resolved transillumination imaging through a highly scattering slab is well represented by a Gaussian. We have experimentally validated a simple formula of the random walk model for the effective width of this Gaussian, as a function of time delay, at different depths of the target. Presented analysis of published experimental data, concerning effective width of the PSF, for a slab of considerably smaller thickness also demonstrates good agreement between the data and predictions of our model. This PSF width determines spatial resolution of the time-resolved imaging and is widely discussed in the literature.

Conditioned place preference induced by delta 9-tetrahydrocannabinol: comparison with cocaine, morphine, and food reward.

The rewarding property of delta 9-tetrahydrocannabinol (THC), the psychoactive constituent of marijuana and hashish, was studied using the conditioned place preference paradigm, and compared to that of cocaine, morphine, and food reward. The results of Experiment 1 demonstrated that 2.0 and 4.0 mg/kg doses produced a reliable shift in preference for the THC-paired compartment. The THC place preference observed at 2.0 and 4.0 mg/kg was nearly equivalent to that produced by low doses of cocaine (5.0 mg/kg), morphine (4.0 mg/kg), and food in non food-deprived animals. The second experiment used a different conditioning procedure that included a washout period for THC. The results of Experiment 2 demonstrated that a THC place preference could be obtained using a lower dose of THC (1.0 mg/kg), and that this THC place preference was equivalent to that produced by 10 mg/kg cocaine. At higher doses (2.0 and 4.0 mg/kg), THC produced a dose-dependent place aversion. These results suggest that THC's action on brain reward substrates, previously demonstrated by electrical brain stimulation reward, in vivo brain microdialysis, and in vivo brain electrochemistry studies, reflects itself behaviorally in increased appetitive motivational value for environmental stimuli associated with ingestion of marijuana and hashish.

Genetic differences in delta 9-tetrahydrocannabinol-induced facilitation of brain stimulation reward as measured by a rate-frequency curve-shift electrical brain stimulation paradigm in three different rat strains.

Lewis, Fischer 344, and Sprague-Dawley rats were implanted with electrodes in the medial forebrain bundle and trained to lever press for brain stimulation reward using a rate-frequency curve-shift electrical brain stimulation paradigm based on a series of 16 pulse frequencies ranging from 25 to 141 Hz in descending order. Once reward thresholds were stable, rats were given 1.0 mg/kg delta 9-tetrahydrocannabinol (delta 9-THC), the psychoactive constituent in marijuana and hashish, or vehicle, by intraperitoneal injection. Lewis rats showed the most pronounced delta 9-THC-induced enhancement of brain reward functions. Sprague-Dawley rats showed an enhancement of brain reward functions that was approximately half that seen in Lewis rats. Brain reward functions in Fischer 344 rats were unaffected by delta 9-THC at the dose tested. These results are consistent with previous work showing Lewis rats to be highly sensitive to the rewarding properties of a variety of drugs of abuse, including opiates, cocaine, and alcohol, while Fischer 344 rats are relatively less sensitive. They extend such previous findings to cannabinoids, and further suggest that genetic variations to other cannabinoid effects may also exist.

Bell's palsy: the steroid controversy revisited.

The treatment of Bell's palsy with steroids is controversial. Several series of patients have shown steroids to be beneficial to a statistically significant degree; however, their experimental design was of poor quality and made this data less clinically valuable. The negative trials showing no benefit with steroids did not examine enough patients to have a chance to show a clinically important difference. These series must be considered as partially completed studies and not as conclusive negative trials. A Type I error analysis is the accepted method of statistically analyzing the data of these trials. After reviewing the evidence, it becomes clear that further scientific research is needed.

Luetic hearing loss.

Luetic hearing loss has been noted with increasing frequency in recent years. Four cases of luetic hearing loss seen at Walter Reed General Hospital from 1974 to 1975 are presented and discussed. Symptoms and pathology of luetic involvement of the inner ear are also presented. Serum FTA-ABS and TPI, in addition to VDRL, must be routinely obtained during the workup of hearing loss. CSF FTA-ABS should be obtained if serum FTA-ABS and TPI are positive. Reversibility may be dependent on early detection of luetic hearing loss and treatment with high doses of antibiotics and steroids.

Modelling drug kinetics with brain stimulation: dopamine antagonists increase self-stimulation.

The rewarding effects of brain stimulation and drugs are believed to depend on a common neural system. However, the pattern of responding produced by drug reinforcers is different from the pattern produced by conventional brain stimulation. Furthermore, pharmacological antagonists of reinforcement increase the rate of drug self-administration but depress self-stimulation. To test the hypothesis that the differences in the characteristics of brain stimulation and drugs as reinforcers are due to differences in the kinetics of drugs and brain stimulation, we modelled drug kinetics with frequency-modulated trains of brain stimulation. We report that animals will self-administer such brain stimulation in a manner that resembles drug self-administration and that, under these conditions, dopamine antagonists can increase the rate of self-stimulation.

Congenital multiple fibromatosis (infantile myofibromatosis).

A female newborn had a rare case of congenital multiple fibromatosis, consisting of multiple fibrous lesions that histologically resemble myofibromas. Bony and soft-tissue lesions usually undergo spontaneous resolution, but excision may be required if vital structures are compromised as was the case in this patient. When the lesions involve the viscera in a generalized form of the disease, the result is often fatal.

Complications of the external (combination) rhinoplasty approach.

More rhinoplastic surgeons are using the external (combination) rhinoplasty approach for selected patients. Although several large series report few complications, the initial experience of newcomers may be different. A series of 26 external rhinoplasty approaches was examined, representing the initial experience of supervised residents. The most common complication was incising the anterior margin of the lower lateral cartilage at the juncture of the lateral and medial crura. To prevent this problem, it is recommended that the skin be elevated off the lower lateral cartilages from both a medial direction up over the domes and a lateral direction downward. To repair this complication, a figure-of-eight suture is used to reapproximate the incision.

Perturbation model to predict the effect of spatially varying absorptive inhomogeneities in diffusing media.

We develop a perturbation model to predict the effect of a spatially varying absorptive inhomogeneities in a diffusing slab. The model is based on a perturbation solution of diffusion equation derived for a refractive index mismatch between the scattering slab and the surrounding medium, through the use of the extrapolated boundary conditions. We show that the model allows to compute the time-dependent relative change in the transmitted signal resulting from the presence of the inclusion. We derive simplified expressions for the perturbed time-resolved transmittance that allows to implement an efficient fitting procedure for obtaining the optical properties of the absorptive inclusion. The accuracy of the predictions of the model was investigated through comparison with the results of the Finite Element Method to solve the time-dependent diffusion equation numerically. The procedure is used to obtain the absorption perturbation parameter of an absorptive inclusion characterized by spatially dependent Gaussian distribution of its absorption coefficient located at the midplane of a scattering slab.